@article {pmid42185262, year = {2026}, author = {Cossa, A and Dalmasso, A and Campani, G and Bugani, E and Caprioli, C and Bulla, N and Tirelli, A and Zhan, Y and Pelicci, PG}, title = {MiTo: tracing the phenotypic evolution of somatic cell lineages via mitochondrial single-cell multi-omics.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {}, pmid = {42185262}, issn = {2041-1723}, support = {PALM//Fondazione Umberto Veronesi (Umberto Veronesi Foundation)/ ; }, mesh = {*Single-Cell Analysis/methods ; *Cell Lineage/genetics ; *Mitochondria/genetics/metabolism ; Multiomics ; Humans ; *Breast Neoplasms/genetics/pathology ; Phenotype ; Female ; Phylogeny ; Gene Regulatory Networks ; }, abstract = {Mitochondrial single-cell lineage tracing has recently emerged as a scalable and non-invasive tool to trace somatic cell lineages. However, the reliability and resolution of this technology remains highly debated. Here, we present MiTo, a novel end-to-end framework for robust mitochondrial single-cell lineage tracing data analysis. Benchmarked against real-world datasets, MiTo outperforms state-of-the-art methods and baselines in data pre-processing and clonal inference. Applied to a time-resolved dataset of breast cancer evolution (>2,500 cells), MiTo accurately infers ground-truth cell lineages (ARI = 0.94) and cell state transitions, detects clonal fitness markers, and quantifies heritability of gene regulatory networks. Comparing alternative lineage markers, MiTo quantifies the resolution limit of existing mitochondrial single-cell lineage tracing systems, which currently enable reliable inference of coarse-grained cellular ancestries, but not high-resolution phylogenetic inference. In conclusion, this work provides robust tools and practical guidelines to dissect somatic evolution with single-cell multi-omics.}, } @article {pmid42475569, year = {2026}, author = {Chitnis, M and Kaub, L and Vďačný, P and Beiers, LM and Sturm, S and Coskun, ÖK and Mills, DB and Gomez-Saez, GV and Mengue, L and Gottschaldt, KD and Gilder, SA and Obert, T and Rurik, I and Sturm, EV and Orsi, WD}, title = {Magnetotaxis in an anaerobic ciliate via tripartite syntrophy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {30}, pages = {e2609513123}, doi = {10.1073/pnas.2609513123}, pmid = {42475569}, issn = {1091-6490}, support = {OR417/9-1//Deutsche Forschungsgemeinschaft (DFG)/ ; }, mesh = {*Magnetosomes/metabolism/genetics ; *Ciliophora/physiology/microbiology/genetics ; *Deltaproteobacteria/genetics/physiology ; Anaerobiosis ; Phylogeny ; Ferrosoferric Oxide/metabolism ; }, abstract = {Magnetotaxis has evolved independently numerous times in bacteria, whereby genetically controlled biomineralization of nano-crystalline magnets results in swimming along Earth's magnetic field lines. Compared to magnetotactic bacteria (MTB), evolutionary mechanisms of magnetotaxis as a trait in eukaryotes remain poorly understood. Here, we report a magnetotactic ciliate, Tropidoatractus magnetotacticus sp. nov., that acquires magnetotaxis via syntrophy. T. magnetotacticus exhibits magnetotaxis due to the magnetic moment of internal ferrimagnetic magnetite (Fe3O4) nanoparticles forming ellipsoidal "necklace-shaped" parallel chains. Electron microscopy revealed T. magnetotacticus hosts numerous internal rod-shaped bacteria containing these magnetosome chains. Consistent with this, a genomic population of MTB (Thermodesulfobacteriota) in magnetically sorted T. magnetotacticus cells was found that encoded and expressed a magnetosome gene cluster responsible for magnetosome Fe3O4 biomineralization closely related to that of the ectosymbiont "Candidatus Desulfarcum epimagneticum." T. magnetotacticus also housed a second genomic population affiliated with the endosymbiotic methanogen Methanoregula. Metatranscriptomes of sorted T. magnetotacticus cells show eukaryotic hydrogenosomal Fe-hydrogenase gene expression, and expression of genes encoding proteins in an electron transport chain indicative of H2-producing mitochondria-related organelles. Active gene expression of energy metabolism pathways indicates a tripartite syntrophic network whereby anaerobic fermentation products from T. magnetotacticus are consumed by two syntrophic partners: MTB producing the magnetosome chains and hydrogenotrophic methanogens. Our findings show how magnetotaxis can emerge as a trait in eukaryotes via syntrophic cooperation.}, } @article {pmid42476231, year = {2026}, author = {Carlström, A and Vazquez-Calvo, C and Ott, M}, title = {Orchestration of OXPHOS biogenesis through regulation of mitochondrial translation.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {}, number = {}, pages = {120194}, doi = {10.1016/j.bbamcr.2026.120194}, pmid = {42476231}, issn = {1879-2596}, abstract = {Mitochondrial gene expression is a remnant of the endosymbiotic origin of the organelle, which contains a complete gene expression system that contributes only a handful of subunits to the complexes driving oxidative phosphorylation (OXPHOS). During evolution, many processes of gene expression in mitochondria have diverged from the bacterial ancestor. A central problem to assemble oxidative phosphorylation complexes is that they contain subunits from two genetic sources. Hence, mechanisms have evolved to synchronize expression of nuclear and mitochondrial genes to avoid problems with stoichiometry, which could hamper their assembly. Here, we will summarize recent insights into how gene expression operates with a focus on the mechanisms related to the control of mitochondrial translation in yeast and human cells.}, } @article {pmid42464925, year = {2026}, author = {Záhonová, K and Doležal, P and Tachezy, J and Lukeš, J and Speijer, D and Hampl, V}, title = {Phylogenetic ancestry of Metamonada proteins points to a common origin of mitochondria in all eukaryotes.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msag175}, pmid = {42464925}, issn = {1537-1719}, abstract = {Hypotheses concerning eukaryogenesis, the evolution of eukaryotic cells, differ in the relative timing of mitochondrial acquisition. Recently, a serial endosymbiotic hypothesis proposed that hydrogenosomes and mitosomes (MROs) in Metamonada originated from an independent endosymbiosis, later replaced by Alphaproteobacteria-related mitochondria, contradicting the paradigm of mitochondrial presence in the last eukaryotic common ancestor. This serial endosymbiotic hypothesis implicitly predicts the scarcity of alphaproteobacterial genes from Metamonada genomes, because they never contained this endosymbiont. We tested this prediction using a set of 1,399 and 97 proteins inferred for the Metamonada ancestor and confined to their MROs, respectively. We detected five and 14 orthologous groups (OGs) with alphaproteobacterial affiliation in the respective datasets. None of these OGs was present in oxymonads, a Metamonada subgroup lacking MROs, thus serving as blank references. Our data are therefore consistent with the ruling paradigm that mitochondria and MROs originated from an Alphaproteobacterium during a single common endosymbiosis.}, } @article {pmid42467109, year = {2026}, author = {Sadeesh, EM and Lahamge, MS and Ampadi, AN and Mohiddin, R}, title = {The Unique Mitochondrial Architecture of the Buffalo Brain: A Comparative Transcriptomic Analysis of Transport, Signaling, and Detoxification.}, journal = {Neurochemical research}, volume = {51}, number = {4}, pages = {}, pmid = {42467109}, issn = {1573-6903}, mesh = {Animals ; *Mitochondria/metabolism/genetics ; *Brain/metabolism ; *Signal Transduction/physiology ; Buffaloes ; *Gene Expression Profiling/methods ; *Transcriptome/physiology ; Female ; Humans ; Biological Transport/physiology ; }, abstract = {The brain is uniquely vulnerable to mitochondrial dysfunction, a primary hallmark of neurodegenerative diseases. While mitochondria are universally recognized as cellular powerhouses, their organ-specific functional architectures remain poorly defined. In this study, we present a high-resolution transcriptomic analysis compared across cerebellar tissue (used as the neural reference) and peripheral tissues (heart, kidney, and ovary) to map the coordination of transport, signaling, and detoxification. Using ovarian tissue as a stable physiological baseline, our findings demonstrate that neural mitochondria are fundamentally architected for metabolic surveillance and repair rather than sheer bioenergetic throughput. To safely meet the extreme metabolic demands of synaptic transmission, the brain exhibits reduced transcriptional emphasis on bulk bioenergetic exchange pathways relative to signaling and repair modules in favor of three highly specialized functional pillars: tightly regulated transport (e.g., SFXN4, SLC25A14, and SLC25A22, SLC25A25), highly responsive metabolic signaling (anchored by EFHD1 and retrograde communication), and targeted detoxification and protein repair (e.g., MSRA and MSRB2). Furthermore, phylogenetic conservation analysis comparing the bovine lineage to the human transcriptomic reference data across 90 million years of mammalian evolution confirms that these neural-specific adaptations exhibit highly conserved expression hierarchies. This evolutionary rigidity proves that this specific neurochemical architecture is a deeply conserved, essential requirement for protecting the central nervous system. Consequently, defining this baseline establishes a critical molecular framework for identifying precise therapeutic targets to combat oxidative stress, excitotoxicity, and age-related neurodegeneration.}, } @article {pmid42459323, year = {2026}, author = {Wang, C and Lv, J and Wu, J and Wang, S and Song, S}, title = {Androgen receptor signaling organizes ferroptosis escape in castration-resistant prostate cancer: a threshold-based model for therapeutic timing.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1884640}, pmid = {42459323}, issn = {2234-943X}, abstract = {Castration-resistant prostate cancer (CRPC) remains the lethal endpoint of prostate cancer progression, driven by the persistence and adaptive reprogramming of androgen receptor (AR) signaling under therapeutic pressure. Although AR-ferroptosis crosstalk has been increasingly recognized, current models are largely descriptive and fail to explain why ferroptosis escape becomes a stable feature of resistant disease. Here, we propose that in CRPC, AR signaling functions not merely as a molecular regulator, but as the dominant state organizer of ferroptosis resistance, whereas ferroptosis influences AR primarily through a special feedback modulation rather than as an initiating driver of resistance evolution. We further suggest that this state can be understood through the concept of a ferroptosis threshold, which is shaped by AR across four interconnected axes: anti-ferroptotic defense, membrane lipid substrate ecology, edox buffering and iron toxicity boundary. Within this framework, mitochondria emerge not as passive effectors, but as central integrative hubs that couple metabolic rewiring, iron handling, reactive oxygen species control, and organelle communication to consolidate ferroptosis resistance. Building on this view, we propose a temporal model of AR-driven ferroptosis escape in CRPC, spanning an early vulnerability window after AR pathway inhibition, a phase of adaptive anti-ferroptotic reconstruction, and the eventual establishment of a resistant steady state. This model provides a theoretical basis for stage-specific therapeutic intervention. It supports both "early interception" during the vulnerability window and "late-state destabilization" after resistant homeostasis has been established. In addition, it provides a rationale for biomarker-guided dynamic monitoring and temporally informed combination therapeutic strategies.}, } @article {pmid42098088, year = {2026}, author = {Baierna, B and Rahman, T and Latimer, S and Basset, GJ and Moreno, SNJ}, title = {Evolutionary remodeling of ubiquinone biosynthesis in Toxoplasma gondii reveals an essential bi-functional monooxygenase.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {}, pmid = {42098088}, issn = {2041-1723}, support = {AI169846//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; 24PRE1192541//American Heart Association (American Heart Association, Inc.)/ ; MCB-2216747//National Science Foundation (NSF)/ ; }, mesh = {*Toxoplasma/metabolism/genetics/enzymology/growth & development/drug effects ; *Protozoan Proteins/metabolism/genetics/chemistry ; *Mixed Function Oxygenases/metabolism/genetics/chemistry/antagonists & inhibitors ; *Ubiquinone/biosynthesis ; Molecular Docking Simulation ; Mitochondria/metabolism ; Animals ; Evolution, Molecular ; }, abstract = {Apicomplexan parasites like Toxoplasma gondii harbor a divergent mitochondrial proteome, much of which remains uncharacterized despite its essentiality for parasite survival. One such essential pathway is ubiquinone (UQ) biosynthesis. Here, we characterize the UQ synthesis machinery in T. gondii and show that conserved enzymes, TgCoq3 and TgCoq5, are essential for growth and mitochondrial function, and associate in a multi-protein complex. Using proximity labeling and subcellular fractionation, approaches suited to detect low-abundance proteins, we identify TgCoqFMO, a FAD-dependent monooxygenase required for UQ synthesis. Unlike canonical eukaryotic systems that employ multiple monooxygenases to modify specific carbons on the UQ aromatic ring, TgCoqFMO catalyzes two distinct hydroxylation steps, an activity not previously reported in eukaryotes. Molecular docking and chemical screening identified TgCoqFMO inhibitors that impair tachyzoite growth and reduce bradyzoite viability. These findings reveal a divergent UQ biosynthesis pathway with fewer components in apicomplexans and establish TgCoqFMO as a promising antiparasitic target.}, } @article {pmid42298057, year = {2026}, author = {Diao, S and Zou, JY and Wang, S and Chan, JE and Kortlever, RM and Poulain, N and Ghaddar, N and Kim, H and Evan, GI and Koumenis, C and Hatzoglou, M and Walter, P and Sonenberg, N and Le Quesne, J and Tammela, T and Koromilas, AE}, title = {Integrated stress response couples mitochondrial fitness with lineage reprogramming to drive cancer evolution.}, journal = {Nature cell biology}, volume = {28}, number = {7}, pages = {1529-1544}, pmid = {42298057}, issn = {1476-4679}, support = {PJT-178173//Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)/ ; PJT-168864//Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)/ ; C4750/A12077//Cancer Research UK (CRUK)/ ; R01-CA268597//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; DK060569//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01-CA270116//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; }, mesh = {Animals ; Humans ; *Integrated Stress Response ; *Mitochondria/metabolism/pathology/genetics ; *Lung Neoplasms/pathology/genetics/metabolism ; Activating Transcription Factor 4/metabolism/genetics ; Epithelial-Mesenchymal Transition ; Adenocarcinoma of Lung/pathology/genetics/metabolism ; *Cell Lineage ; Eukaryotic Initiation Factor-2/metabolism/genetics ; Proto-Oncogene Proteins c-myc/metabolism/genetics ; Mice ; Cell Line, Tumor ; Metabolic Reprogramming ; *Cellular Reprogramming ; Transcription Factors/metabolism/genetics ; Gene Expression Regulation, Neoplastic ; Phosphorylation ; *Adenocarcinoma/pathology/genetics/metabolism ; Signal Transduction ; Cell Dedifferentiation ; Thyroid Nuclear Factor 1 ; }, abstract = {Tumour progression towards dedifferentiated cell clusters plays a critical role in intratumour heterogeneity and therapy resistance. While tumour microenvironmental stress has been implicated, the underlying mechanisms remain poorly defined. Using mouse models of lung adenocarcinoma, we demonstrate that activation of the integrated stress response (ISR)-marked by phosphorylation of eIF2 (p-eIF2) and ATF4 induction-drives tumour heterogeneity. ISR activation facilitates the emergence of high-plasticity, undifferentiated and pre-epithelial-to-mesenchymal transition clusters characterized by elevated ATF4 and MYC activity. This process is MYC dependent and involves ISR-mediated repression of NKX2-1, a key determinant of alveolar identity, and induction of CHCHD10, a regulator of mitochondrial integrity and metabolic fitness. Disruption of the p-eIF2-ATF4 axis induces mitochondrial dysfunction, limits dedifferentiation and suppresses tumour growth. In human lung adenocarcinoma, ISR-driven dedifferentiation correlates with advanced disease and poor prognosis, identifying the ISR as a central driver of lineage reprogramming and metabolic fitness in tumour progression.}, } @article {pmid42445829, year = {2026}, author = {Shi, Y and Lu, Y and Zhou, Y and Chen, R and Li, Z and Liu, H and Cao, J}, title = {Precision Nanomedicine for Renal Tubular Injury: From Passive Accumulation to Subcellular Targeting.}, journal = {International journal of nanomedicine}, volume = {21}, number = {}, pages = {616742}, pmid = {42445829}, issn = {1178-2013}, mesh = {Humans ; Animals ; *Nanomedicine/methods ; *Kidney Tubules/injuries/metabolism/drug effects ; Drug Delivery Systems ; *Precision Medicine/methods ; *Kidney Diseases/drug therapy/metabolism ; }, abstract = {Renal tubular epithelial cell injury is a central pathogenic feature of kidney diseases, yet precise therapeutic interventions remain elusive. Conventional nanomedicines relying on passive accumulation lack the specificity required to treat complex tubular pathologies. This review elucidates the evolution of renal nanotherapeutics from non-specific organ accumulation to active, biologically informed targeting. We examine strategies utilizing specific surface receptors and injury-associated microenvironmental signals to engineer ligand-directed and stimuli-responsive nanocarriers. Furthermore, we highlight biomimetic platforms, such as engineered extracellular vesicles. Crucially, to achieve the ultimate goal of precision intervention, we emphasize the necessity of subcellular targeting. With a primary focus on mitochondria, we delineate hierarchical delivery strategies designed to restore cellular bioenergetics and metabolic homeostasis. Finally, we provide a forward-looking perspective on overcoming translational barriers by integrating DNA barcoding and artificial intelligence to accelerate the discovery of clinically translatable, precision nanomedicines.}, } @article {pmid42447183, year = {2026}, author = {Crino, OL and Friesen, CR and Hill, GE and Leibold, DC and Recio, P and Salin, K and Wild, KH and Noble, DWA}, title = {How developmental stressors affect mitochondrial respiratory function: a systematic review and meta-analysis.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1002/brv.70199}, pmid = {42447183}, issn = {1469-185X}, support = {DP210101152//Australian Research Council/ ; FT220100276//Australian Research Council Future Fellowship/ ; }, abstract = {The environmental conditions organisms experience during early development can have powerful and sustained effects on morphology, physiology, behaviour, and performance. Such developmental effects can influence reproductive success, survival, and life-history strategies and can be transmitted across generations (i.e. trans and intergenerational effects). In this way, developmental effects can be powerful drivers of evolutionary change. Given the developmental environment affects a range of phenotypic traits, it has been proposed that physiological responses to developmental conditions are modulated through cellular mechanisms that are shared across cell and tissue types, such as mitochondrial function. Mitochondrial respiratory function is highly sensitive to environmental conditions and exposure to adverse conditions during development can have sustained effects on different aspects of aerobic respiration in mitochondria. However, it is currently unknown if these effects are widespread across taxonomic groups and which components of mitochondrial respiratory function are most likely to be affected by the environment during development. We compiled data from 86 studies to examine the effects of developmental stressors (nutritional imbalance, glucocorticoid hormone exposure, parental care deprivation, and psychological disturbance) on mitochondrial respiratory function using meta-analysis. We sought to uncover whether there are general effects of developmental stressors on different aspects of mitochondrial respiratory function (antioxidants, metabolic capacity, oxidative damage, oxidative stress, and aerobic respiration). We tested how the type of developmental stressor, together with timing of exposure (prenatal versus postnatal), and sex and taxon of the test subjects influenced the magnitude, direction, and duration of effects on mitochondrial respiratory function. Finally, we tested which aspects of mitochondrial respiratory function were most impacted by developmental stressors. We found that exposure to glucocorticoids, parental care deprivation, and psychological disturbances during development generally decreased mitochondrial respiratory function. Generally, these developmental stressors increased the production of reactive oxygen species and oxidative damage and reduced aerobic respiration, metabolic capacity, and antioxidant levels. Nutritional imbalances during development (including both restricted and excessive nutrition) had a slight negative effect on mitochondrial respiratory function, but this effect may be influenced by publication bias. Overall, our results show that exposure to stressors during development negatively affects mitochondrial respiratory function, suggesting that changes in cellular metabolism may link developmental stressors to variation in whole animal traits and individual fitness.}, } @article {pmid42430363, year = {2026}, author = {Capera, MO and Medina, NS and Montaña-Lozano, P and Moreno-Carmona, M and Baeza, A and Prada-Quiroga, C}, title = {Evolutionary patterns of the mitochondrial control region in vertebrates: A large-scale comparative analysis.}, journal = {PloS one}, volume = {21}, number = {7}, pages = {e0353555}, doi = {10.1371/journal.pone.0353555}, pmid = {42430363}, issn = {1932-6203}, mesh = {Animals ; *Evolution, Molecular ; *Vertebrates/genetics ; Phylogeny ; *DNA, Mitochondrial/genetics ; *Genome, Mitochondrial ; Conserved Sequence ; *Mitochondria/genetics ; Base Composition ; }, abstract = {The mitochondrial control region (CR) is the largest non-coding region in the vertebrate mitogenome and contains essential elements for replication and transcription. Despite its functional relevance, its evolutionary dynamics remain poorly understood. Here, we analyzed 5,235 complete vertebrate CRs spanning 11 classes to investigate how conserved sequences blocks (CSBs) and Extended Termination-Associated sequences (ETAS) shaped CR evolution. We hypothesized that CR length is positively associated with repeat accumulation, with tetrapods exhibiting longer and more complex CRs than fishes, while core elements remain conserved. Our analyses revealed marked inter- and intra-class variability, with longer CRs in tetrapods (1,283.27 ± 489.6 bp) than in fishes (969.25 ± 239.5 bp). Duplication events were restricted to tetrapods, especially birds and reptiles. Nucleotide composition was heterogeneous among orders, and structural divergence of CSBs was inferred across lineages. Repetitive elements were present in ~43% of CRs, with their abundance strongly correlated with CR length. Importantly, longer CRs were associated with higher GC content and greater variation in copy number of ETAS and CSBs. These results demonstrate that mitogenome CR expansion in vertebrates is largely driven by repeat proliferation, whereas key motifs required for replication and transcription are retained. We further identify lineage-specific trends, including pronounced CR elongation in amphibians and reptiles, contrasted with progressive reduction and simplification in birds and mammals. Our study provides the first comprehensive comparative framework of vertebrate CR evolution, highlighting how repetitive elements, conserved motifs, and nucleotide composition jointly contribute to both functional regulation and lineage-specific diversification.}, } @article {pmid42423042, year = {2026}, author = {Chen, M and Qu, Q and Zhang, Z}, title = {Kingdom-wide evolutionary characterization of RNA editing factors in Archaeplastida.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msag168}, pmid = {42423042}, issn = {1537-1719}, abstract = {RNA editing, a post-transcriptional modification in plant mitochondria and plastids, is essential for environmental adaptation and diverse physiological processes. Despite extensive identification of RNA editing factors, primarily including pentatricopeptide repeat (PPR), multiple organelle RNA editing factor (MORF), organelle RNA recognition motif-containing (ORRM), and organelle zinc finger (OZ) proteins, their evolutionary history remains poorly understood. Here, we perform kingdom-wide evolutionary analyses across 364 high-quality Archaeplastida genomes and find massive PPR gene expansions in early-diverging land plants, predominantly driven by dispersed duplication associated with retroposition. Furthermore, integrative analyses imply that DYW subgroup PPR genes have been horizontally transferred from plants to bdelloid rotifers. MORF proteins, accessory partners of PPRs, possess MORF hallmark domains structurally similar to protein-folding peptidase S8 propeptide/proteinase inhibitor I9 domains, suggesting a role in protein folding during RNA editing. Considering diverse domain compositions, we reclassify MORF, ORRM, and OZ proteins and uncover prevalent hallmark domain fusions. Together, these findings illuminate the kingdom-wide evolution of plant RNA editing machinery.}, } @article {pmid42423244, year = {2026}, author = {Fahimi, P and Lynch, M and Matta, CF}, title = {Decoding the Hot-Mitochondrion Paradox.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {48}, number = {7}, pages = {e70159}, doi = {10.1002/bies.70159}, pmid = {42423244}, issn = {1521-1878}, support = {//Dalhousie University/ ; //Natural Sciences and Engineering Research Council of Canada/ ; //Canada Foundation for Innovation/ ; //Saint Mary's University/ ; //Mount Saint Vincent University/ ; //Digital Research Alliance of Canada/ ; /NH/NIH HHS/United States ; //National Science Foundation/ ; //Simons Foundation/ ; //Moore Foundation/ ; }, mesh = {*Mitochondria/metabolism/physiology ; *Mitochondrial Membranes/metabolism/physiology ; Animals ; *Hot Temperature ; Humans ; Membrane Proteins/metabolism ; }, abstract = {In a 2018 paper and a subsequent article published in 2023, researchers reported that mitochondria maintain temperatures 10°C-15°C higher than the surrounding cytoplasm-a finding that deviates by five to six orders of magnitude from theoretical predictions based on Fourier's law of heat conduction. In 2022, we proposed a solution to this apparent paradox. In the present perspective, we build upon that framework and introduce new ideas to further unravel how a biological membrane-whether of an organelle or a whole cell-can become significantly warmer than its environment. We propose that ion-translocating proteins embedded in the inner mitochondrial membrane (IMM) can be modeled as ratchet engines, introducing a novel, previously overlooked mode of heat transfer. This mechanism, coupled with localized heat release during the cyclical dehydration-translocation-hydration of ions through membrane proteins, may generate transient but substantial temperature spikes. The cumulative thermal occupancy of these microscopic events across the three-dimensional surface of the IMM can account for the elevated temperatures detected by molecular probes.}, } @article {pmid42411493, year = {2026}, author = {Stefano, GB}, title = {Beyond Amyloid: Evolutionary and Immune-Metabolic Perspectives on Alzheimer's Disease.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {31}, number = {6}, pages = {53859}, doi = {10.31083/FBL53859}, pmid = {42411493}, issn = {2768-6698}, mesh = {Humans ; *Alzheimer Disease/metabolism/immunology/pathology ; Animals ; *Amyloid beta-Peptides/metabolism/immunology ; Immunity, Innate ; Brain/metabolism/immunology/pathology ; Mitochondria/metabolism ; Biological Evolution ; Gastrointestinal Microbiome ; }, abstract = {Alzheimer's disease (AD) is increasingly recognized as a multifactorial and systems-level disorder that extends beyond the classical amyloid cascade hypothesis. Rather than dismissing established concepts such as tau pathology, synaptic dysfunction, vascular compromise, mitochondrial abnormalities, and impaired proteostasis, emerging evidence suggests that these processes may interact dynamically with chronic immune activation, microbial signaling, and systemic metabolic stress. Recent studies examining the microbiome-gut-brain axis, chronic infection, innate immunity, and systemic immune-metabolic dysfunction have broadened the conceptual framework of AD pathogenesis. Importantly, amyloid-β (Aβ) is now understood to possess evolutionarily conserved antimicrobial and immunomodulatory properties, suggesting that amyloid deposition may initially represent a protective host-defense response rather than solely a toxic pathological event. This perspective does not overturn the amyloid cascade model but instead reframes amyloid biology within a broader adaptive evolutionary context in which chronic or dysregulated activation becomes maladaptive during aging. The present opinion article integrates these converging concepts into a unified framework in which AD emerges from the prolonged interaction among immune responses, microbial exposures, metabolic disturbances, mitochondrial dysfunction, vascular injury, and age-associated failures in proteostatic resilience. This integrative interpretation seeks to humanize the disease process by viewing neurodegeneration not simply as isolated protein accumulation, but as the gradual exhaustion of ancient host-defense and energy-regulatory systems that were originally evolutionarily advantageous for survival.}, } @article {pmid42412246, year = {2026}, author = {Salminen, A and Kaarniranta, K and Kauppinen, A}, title = {Endosymbiotic theory of aging revisited: Age-related leakage of mitochondrial dsDNA/RNA stimulates cytosolic nucleic acid sensors which remodel the immune network and promote the aging process.}, journal = {Biogerontology}, volume = {27}, number = {4}, pages = {}, pmid = {42412246}, issn = {1573-6768}, support = {KK333302//Research Council of Finland/ ; }, mesh = {*Aging/immunology ; *DNA, Mitochondrial/metabolism/immunology ; Humans ; Animals ; *Symbiosis ; Cytosol/metabolism ; *Mitochondria/metabolism ; Innate Immunity Recognition ; cGAS-STING Signaling Pathway ; RNA, Double-Stranded/metabolism ; Immunity, Innate ; }, abstract = {About 1.5-2 billion years ago, an endosymbiosis between aerobic α-proteobacteria and anaerobic archaeal cells generated mitochondria, i.e., organelles capable of producing oxidative energy. The bacterial genome was fundamentally reduced and a circular mitochondrial genome evolved containing mainly the genes coding for the subunits of the electron transport chain. Before the symbiotic event, there existed a virus-host co-evolution which involved the development of sensors for detecting dangerous viral DNA/RNA molecules. Endosymbiosis supplied eukaryotic cells not only with an oxidative powerhouse to allow the evolution of more complex multicellular organisms but it also meant that cells now housed an organelle which was able to generate reactive oxygen species (ROS) and to leak mitochondrial DNA (mtDNA) and double-stranded RNA (dsRNA) into the cytoplasm. There is now abundant evidence that during aging and age-related diseases mitochondria are prone to release both mtDNA and dsRNA. In the cytoplasm, mtDNA/dsRNA molecules activate a number of cytosolic nucleic acid sensors leading to the secretion of type-1 interferons (IFN) and many other cytokines which promote an age-related proinflammatory state. Currently, it is known that mtDNA can activate the cGAS-STING pathway, AIM2 inflammasomes, IFI16 receptors, and ZBP1 sensors and in addition mitochondrial dsRNA stimulates RIG-1/MDA5 signaling. Interestingly, there is abundant evidence that all these receptors are drivers of cellular senescence and inflammaging. For decades, there has been mounting evidence that mitochondria have a crucial role in the aging process. We will examine this question from the perspective of evolution and propose that mitochondrial evolution created an endogenic source for the leakage of dangerous mtDNA/dsRNA which subsequently stimulated cytosolic DNA/RNA sensors, an evolutionarily conserved viral defence mechanism. It seems that these two evolutionary events provided not only the basis for the inevitable process of aging but also ensuring the death of parental organisms.}, } @article {pmid42412929, year = {2026}, author = {Bettinazzi, S and Chakraborty, A and Grover-Thomas, F and Dowling, DK and Camus, MF}, title = {Mitonuclear discordance modulates mitochondrial ageing dynamics in natural Drosophila populations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {28}, pages = {e2529208123}, doi = {10.1073/pnas.2529208123}, pmid = {42412929}, issn = {1091-6490}, support = {101030803//EC | Horizon Europe | Excellent Science | HORIZON EUROPE Marie Sklodowska-Curie Actions (MSCA)/ ; NE/V014307/1//UKRI | Natural Environment Research Council (NERC)/ ; DP200100892//Australian Research Council/ ; RPG-2023-198//Leverhulme Trust (The Leverhulme Trust)/ ; RG\R1\251294//Royal Society (The Royal Society)/ ; }, mesh = {Animals ; *Mitochondria/metabolism/genetics ; *Aging/genetics/physiology ; Reactive Oxygen Species/metabolism ; Longevity ; *Drosophila melanogaster/genetics/physiology ; *Cell Nucleus/metabolism/genetics ; Oxidative Stress ; *Drosophila/genetics ; }, abstract = {Mitochondrial decline is a hallmark of ageing, yet the role of intergenomic compatibility in shaping ageing trajectories remains poorly understood, particularly in an ecologically relevant framework. Hormetic interventions have been proposed as strategies to modulate metabolism and lifespan, but it is unknown how this operates in the context of mitonuclear discordance. Here, we demonstrate that mitonuclear mismatch accelerates age-related mitochondrial decline, elevates reactive oxygen species production, and shortens lifespan. Strikingly, early-life mitochondrial stress induced by dietary modulation counteracts these effects, promoting mitochondrial homeostasis and longevity. Our findings reveal mitonuclear interactions shaping ageing trajectories in natural populations and provide unique evidence that targeted interventions can act as a buffer against the detrimental impact of genetic discordance.}, } @article {pmid42308148, year = {2026}, author = {Nováková, Z and Bartošová-Sojková, P and Kudláčová, J and Baselious, F and Kutilová, Z and Jaklová, P and Meleshin, M and Motlová, L and Schenkmayerova, A and Vrkoslav, V and Strnad, Š and Horáček, N and Gruber, A and Žáček, P and Kroll, S and Havlínová, B and Ondráková, M and Tučková, R and Krunclová, T and Cvačka, J and Oborník, M and Schutkowski, M and Sippl, W and Bařinka, C}, title = {Functional divergence and structural changes of Class IV histone deacetylases (HDACs) across the tree of life.}, journal = {Molecular biology and evolution}, volume = {43}, number = {7}, pages = {}, pmid = {42308148}, issn = {1537-1719}, support = {86652036//CAS/ ; 24-12155S//Czech Science Foundation/ ; 25-15611S//Czech Science Foundation/ ; LUAUS23247//MEYS CR/ ; //Helmholtz-Zentrum Berlin für Materialien und Energie/ ; //CMS-Biocev/ ; //CIISB/ ; //Instruct-CZ Centre/ ; LM2023042//MEYS CR/ ; CZ.02.01.01/00/23_015/0008175//MEYS CR/ ; //BIOCEV/ ; LM2023050//MEYS CR/ ; }, mesh = {*Histone Deacetylases/genetics/chemistry/metabolism ; Phylogeny ; Evolution, Molecular ; Bacteria/enzymology/genetics ; Archaea/enzymology/genetics ; Substrate Specificity ; Models, Molecular ; Eukaryota/enzymology/genetics ; Catalytic Domain ; }, abstract = {Class IV histone deacetylases (HDACs) are the least understood branch of the classical zinc-dependent HDAC family with HDAC11 standing out as the sole member of Class IV HDACs. Using a broad phylogenetic dataset spanning bacteria, archaea, and eukaryotes, we identified two deeply conserved HDAC11 lineages, clades A and B, that differ in evolutionary origin, predicted subcellular localization, and enzymatic properties. Clade A is enriched in phototrophic eukaryotes and targeted to mitochondria or plastids, whereas clade B predominates in heterotrophs and localizes mainly to the cytoplasm or nucleus. High-resolution crystal structures of selected representatives from each clade revealed a conserved catalytic core but distinct structural features-including electrostatic surface profiles, loop architectures, and foot pocket geometries-that clearly separate the two lineages and act as sequential "selectivity filters" shaping substrate specificity. Biochemical assays show robust long-chain fatty acid deacylase activity in clade B enzymes, but no detectable activity for any of clade A representatives against peptide substrates, suggesting adaptation to alternative, nonpeptidic targets. Together, these findings define a revised evolutionary framework for HDAC11 and provide structural and functional insights into the diversification of this ancient enzyme family.}, } @article {pmid42409184, year = {2026}, author = {McEwan, F and Santo, JD and Kambara, C and Tarrat-Castells, M and Woods, RM and Harte, M and Glazier, JD and Hager, R}, title = {Maternal immune activation induces sex-dependent metabolic, epigenetic and GABAergic trajectories in the hippocampus.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {106895}, doi = {10.1016/j.bbi.2026.106895}, pmid = {42409184}, issn = {1090-2139}, abstract = {Maternal immune activation (MIA) is associated with increased risk of neurodevelopmental disorders, including schizophrenia. Research demonstrates sex-specific responses to MIA, yet how MIA interacts with intrinsic sex differences during brain development remains unclear. Here, we investigated how poly(I:C)-induced MIA alters metabolic, epigenetic and inhibitory developmental trajectories. Female, but not male, poly(I:C) offspring exhibited an object location memory deficit, implicating the hippocampus as a vulnerable region. Using RNA sequencing of the prenatal hippocampus, we identified a pronounced female-specific transcriptional response to MIA, with enrichment of mitochondrial and chromatin-related pathways. Concurrently, intrinsic sex differences indicated divergent metabolic/mitochondrial maturation, such as increased expression of Ppargc1a (encoding peroxisome proliferator-activated receptor gamma coactivator 1-α) and increased antioxidant activity in females compared to males, consistent with greater metabolic capacity. MIA interacted with these trajectories, producing sex-dependent effects on mitochondrial dynamics which coincided with signatures of a more permissive chromatin state, including reduced histone deacetylase activity, increased histone acetylation and reduced H3K27 methylation. In adulthood, MIA offspring showed altered chloride transporter expression, with a shift toward NKCC1 (a molecular driver of the GABAergic switch) and evidence of promoter-level epigenetic regulation, most evident in females. This coincided with reduced clusters of the scaffolding protein gephyrin in adolescent poly(I:C) females, consistent with altered inhibitory synapse maturation. Together, these findings indicate that sex-specific metabolic programming shapes the neurodevelopmental response to MIA and contributes to the observed sex differences in brain and behavioural response. Understanding typical sex differences in mitochondrial development is critical for predicting vulnerability and informing therapeutic treatment.}, } @article {pmid42377538, year = {2026}, author = {Wang, X and Li, J and Li, S and Zhang, X and Wang, J and Hou, T and He, J}, title = {Identification of the R2R3-MYB transcription factor family in goji and LbaR2R3-MYB3 mediated wax biosynthesis enhancing powdery mildew resistance in tobacco.}, journal = {Plant cell reports}, volume = {45}, number = {7}, pages = {}, pmid = {42377538}, issn = {1432-203X}, support = {24JRRA650//Gansu Province Natural Science Foundation/ ; 2026A-063//Gansu Provincial Education Science and Technology Innovation Project/ ; 32060341//National Natural Science Foundation of China/ ; }, mesh = {*Transcription Factors/metabolism/genetics ; *Plant Proteins/genetics/metabolism ; *Nicotiana/genetics/microbiology/metabolism/immunology ; *Disease Resistance/genetics ; *Plant Diseases/microbiology/immunology/genetics ; Gene Expression Regulation, Plant ; *Ascomycota/physiology/pathogenicity ; *Waxes/metabolism ; Plants, Genetically Modified ; Phylogeny ; Plant Leaves/genetics/microbiology/metabolism ; Amino Acid Sequence ; Multigene Family ; }, abstract = {The transcription factor LbaR2R3-MYB3 of goji promotes the biosynthesis of wax components including alkanes, alcohols, fatty acids, and ketones, increases total leaf cuticular wax load, and consequently enhances tobacco resistance to powdery mildew. Goji (Lycium barbarum) is one of the important economic forest species in northwest China. Powdery mildew is a common disease of goji plants that significantly reduces yield and quality, causing substantial economic losses for growers. Cuticular wax serves as the first physical barrier protecting plants against both biotic and abiotic stresses. Members of the R2R3-MYB transcription factor family in goji have not been previously reported, and the relationship between the key member LbaR2R3-MYB3 and cuticular wax biosynthesis and powdery mildew resistance remains unclear. Therefore, this study employed "Ningqi I" goji as the experimental material and identified 75 R2R3-MYB transcription factor family members distributed across 11 chromosomes in the genome. The goji LbaR2R3-MYB proteins mainly localized in the nucleus, mitochondria, cytoplasm, and chloroplasts. Ten conserved motifs were identified in LbaR2R3-MYB3 proteins, with Motif1, Motif2, and Motif3 being the most widely distributed. The promoters of these family members contain multiple cis-acting elements responsive to hormones and abiotic stress. Members of the LbaR2R3-MYB transcription factor family exhibited evolutionary instability. The LbaR2R3-MYB3 gene was cloned from goji leaves yielding a 756 bp fragment. Heterologous expression vectors were successfully constructed, and transgenic tobacco lines overexpressing LbaR2R3-MYB3 (LbaR2R3-MYB3-OE) were obtained. Compared with wild-type tobacco, the cuticular wax load in transgenic tobacco leaves was significantly increased by 1.82-fold, with significant increases in alkanes, alcohols, fatty acids, and ketones. The transgenic tobacco lines showed a 38.2% reduction in powdery mildew incidence and a 59.8% decrease in disease index compared to WT, indicating significantly enhanced resistance to powdery mildew. These results demonstrate that the transcription factor LbaR2R3-MYB3 promotes the biosynthesis of wax components including alkanes, alcohols, fatty acids, and ketones, increases total leaf cuticular wax load, and consequently enhances tobacco resistance to powdery mildew.}, } @article {pmid42368458, year = {2026}, author = {Román-Carraro, FC and Gutiérrez-Kobeh, L}, title = {Apoptosis as an evolutionary battleground: pathogen pressure and the shaping of programmed cell death pathways.}, journal = {Frontiers in cell and developmental biology}, volume = {14}, number = {}, pages = {1800300}, pmid = {42368458}, issn = {2296-634X}, abstract = {Apoptosis is a tightly regulated form of programmed cell death that enables the controlled elimination of damaged or infected cells without eliciting deleterious inflammatory responses. Beyond its fundamental roles in embryogenesis, tissue homeostasis, and cellular turnover, the molecular architecture of apoptosis reflects deep evolutionary origins shaped by mitochondrial quality control, the emergence of intercellular communication, and immune surveillance mechanisms. Apoptotic signaling is initiated through three principal pathways, the extrinsic (death receptor-mediated), perforin/granzyme-mediated, and intrinsic (mitochondrial) pathways, which converge on caspase activation as the final execution step. Accumulating evidence indicates that persistent interactions with intracellular pathogens have profoundly influenced the evolution and diversification of these pathways. Viruses, bacteria, fungi, and protozoan parasites have independently evolved convergent strategies to suppress, delay, redirect, or exploit apoptosis by targeting conserved regulatory nodes, including mitochondrial outer membrane permeabilization, Bcl-2 family proteins, Bid-mediated pathway integration, Apaf-1-dependent caspase activation, and inhibitors of apoptosis proteins. These pathogen-driven pressures have not only shaped infection outcomes but have also contributed to the expansion, redundancy, and regulatory complexity of host apoptotic machinery. Here, we synthesize recent advances in the understanding of pathogen-mediated modulation of apoptosis and propose that programmed cell death operates as part of an integrated, evolutionarily conserved network of host defense. In this framework, apoptosis emerges as a central battleground in host-pathogen coevolution, linking cellular homeostasis to immune protection.}, } @article {pmid42370847, year = {2026}, author = {Keuper, M and Jastroch, M}, title = {Evolution of Adaptive Non-Shivering Thermogenesis in Mammals.}, journal = {Physiology (Bethesda, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1152/physiol.00020.2026}, pmid = {42370847}, issn = {1548-9221}, support = {CTS 25:3971//Carl Tryggers Stiftelse för Vetenskaplig Forskning (Carl Trygger Foundation)/ ; 2022-03136//Vetenskapsrådet (VR)/ ; 101201284//EC | European Research Council (ERC)/ ; }, abstract = {Endothermy depends on the ability to generate heat beyond basal metabolic output. The transition from incidental metabolic heat production to regulated adaptive thermogenesis represents a critical, yet poorly understood milestone in vertebrate evolution. In vertebrates, adaptive thermogenesis includes shivering thermogenesis and non-shivering thermogenesis (NST), the latter involving molecular mechanisms that release energy in the form of heat independently of muscle contraction. This review synthesizes physiological, comparative, and evolutionary findings on adaptive NST, with a focus on adipose-based thermogenesis mediated by its unique mitochondrial uncoupling protein 1 (UCP1). We highlight a two-stage evolutionary model in which a pre-thermogenic adipose program governing UCP1 expression preceded the emergence of efficient UCP1-mediated thermogenesis in eutherian mammals. The source of NST and underlying mechanisms in other tissues and in non-eutherian endothermic vertebrates are less well understood. We discuss proposed UCP1-independent sources of cellular heat production in adipose tissue and muscle. Although these pathways can increase cellular energy expenditure, evidence supporting their role as dedicated and regulated thermogenic mechanisms remains limited to date. Collectively, these findings suggest that adaptive NST is not a singular conserved mechanism but a diverse and context dependent evolutionary strategy with important implications for understanding human physiology and disease.}, } @article {pmid41957773, year = {2026}, author = {Ferrer, M and Pedrón, M and Soriano, O and Martínez-Julvez, M and Marín-Baquero, M and García-Villanueva, R and Velázquez-Campoy, A and Marco-Brualla, J and Ripollés-Yuba, C and Fernández-Silva, P and Medina, M and Miramar, MD and Bestué, M and Moreno-Loshuertos, R and Ferreira, P}, title = {Clinical and molecular characterization of a novel pathogenic AIFM1 E336K mutation connecting mitochondrial dysfunction and neurodegeneration.}, journal = {Cell communication and signaling : CCS}, volume = {24}, number = {1}, pages = {}, pmid = {41957773}, issn = {1478-811X}, support = {PID2022-136369NB-I00//Ministerio de Ciencia e Innovación/ ; }, mesh = {Humans ; *Apoptosis Inducing Factor/genetics/metabolism/chemistry ; Male ; *Mitochondria/metabolism/pathology/genetics ; Fibroblasts/metabolism ; *Mutation ; Protein Stability ; Mitochondrial Proteins/metabolism ; Transcription Factors/metabolism ; Mitochondrial Precursor Protein Import Complex Proteins ; }, abstract = {Mutations in the AIFM1 gene, encoding the apoptosis-inducing factor (AIF), have been associated with a spectrum of neurometabolic disorders. However, the mechanistic basis underlying their pathogenicity remains poorly understood. In this work, we identified and comprehensively characterized a novel hemizygous AIFM1 mutation c.1006G > A (E336K) in a male patient presenting with a progressive hereditary axonal sensorimotor polyneuropathy with childhood onset, inherited in an X-linked recessive pattern, associated with sensorineural hearing loss and without cognitive impairment. The clinical phenotype was consistent with Charcot-Marie-Tooth disease type 4 (CMTX4). Patient-derived fibroblasts exhibited reduced AIF protein stability despite preserved mRNA expression, impaired growth in OXPHOS-dependent conditions, decreased basal respiration, and altered assembly of mitochondrial respiratory supercomplexes. These defects were accompanied by reduced CHCHD4 protein levels and mitochondrial content. The purified E336K protein exhibited compromised FAD retention, decreased thermal stability, impaired NADH affinity, destabilization of the charge-transfer complex crucial for sustaining the AIF: CHCHD4 interaction, and a shift in coenzyme preference toward NADPH. Structurally, the substitution of Glu336 with Lys remodels the electrostatic environment of the NADH-binding cleft, thereby compromising redox function and weakening CHCHD4 binding. Despite these defects, the protein with the E336K mutation retained DNA binding, nuclease activity, and binding to nuclear partners, although parthanatos induction was attenuated in patient fibroblasts. Collectively, these molecular alterations converge on defective mitochondrial bioenergetics and dynamics, providing a direct mechanistic link to the patient’s clinical evolution.These findings provide a framework for understanding AIFM1-related disorders and pave the way for the development of future personalized molecular therapies.}, } @article {pmid42252140, year = {2026}, author = {Muñoz-Gómez, SA and Sørensen, MES and Shazib, SUA and Shin, MK and Bauer, T and Kreutz, M and Hess, S}, title = {Evolutionary assembly of a unique purple-green photosymbiosis revealed by expanded ciliate diversity.}, journal = {The ISME journal}, volume = {20}, number = {1}, pages = {}, pmid = {42252140}, issn = {1751-7370}, support = {417585753//Emmy Noether Programme of the German Research Foundation/ ; 80NSSC24K1875//NASA Exobiology Program/ ; }, mesh = {*Symbiosis ; Phylogeny ; *Ciliophora/classification/physiology/genetics ; Germany ; Republic of Korea ; *Biological Evolution ; Evolution, Molecular ; Sequence Analysis, DNA ; }, abstract = {Symbioses are widespread in nature and have been the source of much evolutionary innovation. While some types of symbioses evolved multiple times, others are extremely rare. Only two purple photosymbioses between heterotrophic eukaryotes and intracellular purple bacteria have been documented. What factors prevent the more frequent establishment of purple photosymbioses? To shed light on this question, we investigated the evolutionary history of the purple-green ciliate Pseudoblepharisma tenue (Spirostomidae) using a phylogenetic and comparative approach and newly discovered species. We sampled about 30 new isolates of spirostomid ciliates from Germany and South Korea, inferred a comprehensive and robust phylogeny based on >200 proteins, and resolved the sister relationship between Pseudoblepharisma and Spirostomum. Furthermore, we characterized P. tenue's sister species, here renamed Pseudoblepharisma chlorelligerum, and revealed that it constitutes a quadripartite symbiosis between a ciliate, a green alga, and two non-photosynthetic bacteria. This oxygenic photosymbiosis is presumed to be supplemented with amino acids by its bacterial symbionts. In addition, we discovered three colorless, non-photosymbiotic Pseudoblepharisma species, which branch as sister to the photosymbiotic P. tenue and P. chlorelligerum. Our phylogenetic and comparative genomic analyses suggest that the green algal symbionts of P. tenue predated the acquisition of purple bacterial symbionts, and that the ancestor of the extant Pseudoblepharisma species was non-photosymbiotic and facultatively anaerobic. These data allowed us to hypothesize on the evolutionary steps that led to the origin of P. tenue and thus bring us closer to explaining the conditions that led to the evolutionary emergence of a unique purple-green symbiosis.}, } @article {pmid41618126, year = {2026}, author = {Usmani, SF and Saddique, MAB and Fiaz, S and Tahir, MHN and Waheed, U and Abdalla, MA and Ahmed, UAH and Alharthi, B and Farid, HN and Pan, R and Yang, SH}, title = {Genome-wide identification of ADK gene family associated with heat stress tolerance in chili (Capsicum annuum L.).}, journal = {BMC genomic data}, volume = {27}, number = {1}, pages = {}, pmid = {41618126}, issn = {2730-6844}, mesh = {*Capsicum/genetics/physiology ; Phylogeny ; *Thermotolerance/genetics ; Multigene Family ; *Plant Proteins/genetics/metabolism ; *Heat-Shock Response/genetics ; Genome, Plant ; Gene Expression Regulation, Plant ; }, abstract = {Chili (Capsicum annuum), also known as hot pepper, is a major vegetable crop in the Solanaceae family. It originated from C. annuum var. minimum, native to Mexico, Southern Peru, and Bolivia. High temperatures negatively affect all key development stages of chili, including fruit set, pollen viability, floral aberration, and the number of seeds per fruit. Heat stress tolerance is a crucial trait in chili and may be regulated by the Adenylate Kinase (ADK) gene family. Although ADK genes have been studied in Arabidopsis thaliana, Oryza sativa, Glycine max, Solanum lycopersicum, and Solanum tuberosum, they remain uncharacterized in C. annuum. This study presents the first genome-wide analysis of the ADK gene family in chili, including gene identification, phylogenetics, motif analysis, expression profiling, and stress-related interaction networks. This study identified nine ADK genes in C. annuum and 70 orthologs from four other species using BLASTp. Phylogenetic analysis grouped the genes into four clades, while gene structure analysis revealed gene lengths ranging from 1,204 to 13,304 bp, with 4 to 17 exons. Conserved motifs and ADK domains were identified. Chromosomal mapping placed the genes across nine chromosomes, with segmental duplications aiding expansion. Predicted subcellular localization suggested that most CaADK proteins localize to chloroplasts and mitochondria. In silico expression profiling showed that CaADK1 and CaADK8 had the highest expression under heat stress, indicating their potential role in thermotolerance. These findings provide novel insights into the CDK gene family in chili and offer molecular targets for enhancing heat stress tolerance in C. annuum.}, } @article {pmid41654727, year = {2026}, author = {Yuan, L and Wang, X and Lin, H and Yu, LJ and Chi, W}, title = {Lineage-specific expansion and functional diversification of mTERF proteins sculpt organellar regulation in plants.}, journal = {BMC plant biology}, volume = {26}, number = {1}, pages = {}, pmid = {41654727}, issn = {1471-2229}, support = {2025M782662//China Postdoctoral Science Foundation/ ; 2021YFA1300400, 2022YFF1001700//National Key Research and Development Program/ ; BK20250004//Natural Science Foundation of Jiangsu Province/ ; }, mesh = {Phylogeny ; *Plant Proteins/genetics/metabolism ; Evolution, Molecular ; *Mitochondrial Proteins/genetics/metabolism ; *Magnoliopsida/genetics/metabolism ; Mitochondria/metabolism/genetics ; Arabidopsis/genetics ; Gene Expression Regulation, Plant ; Chloroplasts/metabolism/genetics ; }, abstract = {The endosymbiotic origin of mitochondria and chloroplasts necessitated the transfer of thousands of genes to the host nucleus, yet the evolutionary paths leading to their functional specialization in organelles remain largely unexplored. Here, we investigate this fundamental question through a comprehensive analysis of the mitochondrial transcription termination factor (mTERF) family, nucleic acid-binding proteins critical for organellar gene regulation. We find that plant mTERFs underwent substantial lineage-specific expansion, diversifying into four major clades in angiosperms. Phylogenetic reconstruction reveals a complex evolutionary history: while chloroplast-targeted mTERFs and a subset of mitochondrial ones share a red algal origin, a novel clade of mitochondrial mTERFs emerged later in seed plants. This diversification underpins functional specialization in developmental transitions, such as the shift from vegetative to reproductive growth, and in environmental adaptation. Genetic analysis in Arabidopsis demonstrates that mTERF10, a positive regulator of salt tolerance, acts as a negative regulator of thermotolerance, illustrating how neofunctionalization facilitates adaptation to disparate stresses. Our study elucidates the evolutionary dynamics of nuclear-encoded organellar proteins and the regulatory networks they govern.}, } @article {pmid41654759, year = {2026}, author = {Ran, Z and Li, Z and Xiao, X and Gu, W and An, M and Xu, J and Guo, Z}, title = {Organellar genome evolution in Camellia tianeensis (Theaceae): comparative insights into RNA editing, codon usage, and DNA transfer between chloroplast and mitochondrion.}, journal = {BMC genomics}, volume = {27}, number = {1}, pages = {}, pmid = {41654759}, issn = {1471-2164}, support = {32400179//National Natural Science Foundation of China/ ; Qian ke he ren cai CXTD [2025] 053//2024 Guizhou Science and Technology Innovation Talent Team Construction Project: Wildlife Innovation Team of the Forestry college of Guizhou University/ ; }, mesh = {*RNA Editing ; *Camellia/genetics/classification ; *Evolution, Molecular ; *Genome, Mitochondrial ; *Codon Usage ; *Genome, Chloroplast ; Phylogeny ; *Chloroplasts/genetics ; *Mitochondria/genetics ; Genome, Plant ; }, abstract = {Camellia tianeensis, a rare member of sect. Chrysantha Chang of the family Theaceae, is widely known for its ornamental and medicinal importance and is often referred to “Queen of the Tea Family”. Despite its biological and economic value, little is known about the structure and evolution of its organellar genomes. In this study, we assembled and compared the complete chloroplast and mitochondrial genomes of C. tianeensis using combined short- and long-read sequencing. The chloroplast genome was 156,865 bp in length and encoded 131 genes, whereas the mitochondrial genome measured 1,098,121 bp and contained 51 genes. Four protein-coding genes—rps12, rps14, rps16, and rps7—were shared by both organelles. The mitochondrial genome exhibited 404 RNA-editing sites, about 6.2 times more than the chloroplast genome (65 sites), primarily resulting in conversions from hydrophilic to hydrophobic amino acids. The mitochondrial genome contained more simple sequence repeats (SSRs) and dispersed repeats than the chloroplast genome, with complementary repeats absent in both. Codon-usage analysis revealed a strong bias toward A/U-ending codons in both genomes, with ten optimal codons shared, suggesting the action of translational selection. Phylogenetic analysis confirmed that C. tianeensis belongs to sect. Chrysantha and showed close affinity to C. nitidissima. Moreover, nine chloroplast-derived fragments totaling 42.9 kb were identified within the mitochondrial genome, indicating active inter-organelle DNA transfer. These results provide the first comprehensive organellar genomic resources for sect. Chrysantha and offer valuable insights into organelle evolution, RNA-editing diversity, and horizontal DNA exchange in higher plants.}, } @article {pmid41772694, year = {2026}, author = {Olkowicz, M and Jedrzejewska, A and Tyrankiewicz, U and Fedak, FA and Berkowicz, P and Kwiatkowski, G and Rosales-Solano, H and Roy, KS and Karas, A and Krol, O and Tomczyk, M and Smolenski, RT and Pawliszyn, J and Chlopicki, S}, title = {Defects in auxiliary fuel oxidation and mitochondrial pyruvate transport mark transition to overt heart failure in Tgαq*44 mice.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41772694}, issn = {1479-5876}, support = {PSP U1U/P03/NO/03.18//BioS Priority Research Area under the program "Excellence Initiative - Research University" at the Jagiellonian University in Krakow/ ; 2021/42/A/NZ4/00273//National Science Centre/ ; 2023/49/N/NZ4/04120//National Science Centre/ ; IRCPJ 184412-15//Natural Sciences and Engineering Research Council (NSERC) of Canada/ ; }, mesh = {Animals ; *Heart Failure/metabolism/pathology/blood ; Oxidation-Reduction ; *Pyruvic Acid/metabolism ; *Mitochondria/metabolism ; Mice, Transgenic ; Biological Transport ; Fatty Acids/metabolism ; Glucose/metabolism ; Male ; Energy Metabolism ; Mice ; }, abstract = {BACKGROUND: Defective catabolism of alternative and glucose-sparing fuel sources has recently been implicated in the development of cardiovascular and metabolic diseases, including heart failure (HF), but the molecular mechanisms and a causal relationship linking them to altered glucose metabolism are unknown. METHODS: Herein, alterations in cardiac protein expression in an established HF model (Tgαq*44 mice) were explored at different ages (4−14 months) in relation to changes in energy substrate preference, high-energy phosphate metabolism, and a snapshot of plasma metabolites. A small cohort of HF cases (n = 20) and non-failing controls (n = 18) was also used to confirm translational value of the findings. RESULTS: The progression of HF in Tgαq*44 mice was characterised by an increased reliance on glucose along with reduced mitochondrial oxidative metabolism that was associated with impaired MPC (mitochondrial pyruvate carrier)−mediated pyruvate utilisation and redirection of glycolytic intermediates into the hexose monophosphate shunt, glycogenesis, and serine biosynthetic pathway. Defects in fatty acid (FA), pyruvate, branched-chain amino acid (BCAA), and ketone body (KB) oxidation, alongside prominent elevation of lactate, represented major features of altered cardiac metabolism in end-stage HF. Chronic accumulation of BCAAs next to suppressed KB and disrupted glucose oxidation were also found in patients with advanced HF, underlying the clinical relevance of the observed alterations. CONCLUSION: This study provides the comprehensive pattern of metabolic evolution of HF, highlighting several possible avenues to rescue from the HF-prone phenotype, such as promoting BCAA and KB catabolism, or normalising glucose utilisation by overexpressing MPC.}, } @article {pmid41776219, year = {2026}, author = {Panahi, B and Hamid, R and Ghorbanzadeh, Z and Jacob, F}, title = {Genome-wide identification and functional characterisation of the EDS1 gene family reveals evolutionary conservation and stress-responsive regulatory roles in barley.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {41776219}, issn = {2045-2322}, mesh = {*Hordeum/genetics ; Phylogeny ; *Plant Proteins/genetics/metabolism/chemistry ; *Stress, Physiological/genetics ; *Evolution, Molecular ; Gene Expression Regulation, Plant ; *Multigene Family ; Genome, Plant ; MicroRNAs/genetics ; Gene Duplication ; Conserved Sequence ; *DNA-Binding Proteins/genetics ; Promoter Regions, Genetic ; }, abstract = {Enhanced Disease Susceptibility 1 (EDS1) genes are central regulators of plant innate immunity and have emerging roles in biotic stress adaptation. Although extensively characterized in dicots, a genome-wide investigation of the EDS1 gene family in barley (Hordeum vulgare L.) remains unavailable. Thirteen HvEDS1 genes were systematically identified by integrated HMM and BLASTP approaches. These genes encode structurally distinct proteins that differ in length, charge, stability and subcellular localization, with several of them reported to occur in the nucleus, chloroplasts, mitochondria and cytoskeleton. Phylogenetic analyses subdivided the HvEDS1 proteins into three major clades, revealing both a diversification of monocots and conserved ancestors. Analyses of gene structure and conserved motifs revealed clade-specific exon–intron architectures and domain configurations, suggesting functional specialization. Analysis of the genome distribution showed that the spread of HvEDS1 is primarily due to scattered duplications, with purifying selection acting on the duplicated pairs. Analysis of the promoters identified numerous cis-regulatory elements that respond to hormones (ABA, JA), light (G-box) and abiotic influences (MBS), suggesting multi-layered transcriptional regulation. The predicted miRNA–mRNA interactions revealed that hvu-miR6192, a stress-responsive microRNA, targets receptor-like kinases involved in abiotic stress signaling, suggesting a post-transcriptional regulatory role in HvEDS1-mediated stress responses. KEGG enrichment linked HvEDS1 genes to lipid signaling pathways, including glycerophospholipid and α-linolenic acid metabolism, as well as ubiquitin-mediated proteolysis. Structural modelling indicated conservation of key EDS1 domains, but showed protein-specific variations in loop flexibility and secondary structure content, suggesting different functional dynamics. The overall transition from a specialized, low-redundancy network under normal conditions to a highly coordinated and overlapping network under fungal stress condition reflects the versatility of the HvEDS1 family in rewiring of signaling cascades stress responsive pathways during different physiological conditions. This first genome-wide characterization of the HvEDS1 gene family reveals its structural diversity, evolutionary development and potential role in immunity and abiotic stress signaling. The identified candidates provide valuable targets for functional validation and molecular breeding of stress-resistant barley cultivars.}, } @article {pmid41781574, year = {2026}, author = {Bhardwaj, P and Prajapati, MR and Gupta, N and Majumder, S and Baranwal, VK and Sharma, SK}, title = {Identification of a novel mitovirus in Colocasia esculenta through high‑throughput sequencing and in-silico miRNA prediction for sequence-specific gene silencing.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {29}, number = {4}, pages = {423-431}, pmid = {41781574}, issn = {1618-1905}, mesh = {*Colocasia/virology ; *MicroRNAs/genetics ; High-Throughput Nucleotide Sequencing ; Phylogeny ; *RNA Viruses/genetics/classification/isolation & purification ; RNA-Dependent RNA Polymerase/genetics ; *Gene Silencing ; Plant Diseases/virology ; Genome, Viral ; RNA, Viral/genetics ; Open Reading Frames ; Plant Leaves/virology ; }, abstract = {Mitoviruses are simple RNA viruses typically associated with fungal mitochondria, although recent studies suggest their presence in plant transcriptomes. In this study, we report the identification and molecular characterization of a novel mitovirus from Colocasia esculenta using high-throughput sequencing (HTS). Analysis of symptomatic leaf tissues revealed a 2,644 nucleotide-long viral genome encoding a single open reading frame (ORF) for an RNA-dependent RNA polymerase (RdRp) of 544 amino acids. The viral sequence, tentatively named Colocasia esculenta associated mitovirus 2 (CeaMV2), showed 60.76% amino acid identity with known mitoviruses, supporting its classification as a novel species within the family Mitoviridae. Phylogenetic analysis showed that CeaMV2 clustered within the family Mitoviridae, grouped with other plant-associated mitoviruses, supporting its placement within the family Mitoviridae. The conserved domain searches confirmed the presence of the mitovirus-specific RdRp domain (Pfam: PF05919). RT-PCR and Sanger sequencing further validated the presence of CeaMV2 in C. esculenta leaf samples. The relatively short RdRp and its expression in plant transcriptome suggest possible association with plant mitochondria. Furthermore, in-silico analysis identified several plant-derived mature miRNAs, such as sbi-miR6231-3p, with high binding affinity to the CeaMV2 RdRp gene, suggesting a potential role for RNA interference in the host-virus interaction. This finding expands the known diversity of mitoviruses and highlights the utility of HTS in uncovering cryptic viral infections and potential RNAi-based defense mechanisms in economically important crops.}, } @article {pmid41931186, year = {2026}, author = {Akhilesh, K and Naik, VCB and Chandrakar, G and Sindhura, KAV and Rao, VP and Prabhulinga, T and Sundaram, RM}, title = {MtCOI-based genetic diversity and population structure of the White-Backed Planthopper, Sogatella furcifera Horváth across major rice ecosystems of India.}, journal = {Molecular biology reports}, volume = {53}, number = {1}, pages = {}, pmid = {41931186}, issn = {1573-4978}, support = {IF230039//Department of Science and Technology, Ministry of Science and Technology, India/ ; }, mesh = {Animals ; *Hemiptera/genetics ; India ; Genetic Variation/genetics ; Phylogeny ; Haplotypes/genetics ; *Electron Transport Complex IV/genetics ; *Oryza/parasitology ; Ecosystem ; Genetics, Population/methods ; Bayes Theorem ; Gene Flow ; Mitochondria/genetics ; }, abstract = {BACKGROUND: The white-backed planthopper, Sogatella furcifera Horváth is a major rice pest in Asia, causing direct phloem-feeding damage and transmitting Southern rice black-streaked dwarf virus (SRBSDV). Despite its economic importance in India, information on its genetic diversity, population connectivity and demographic history remains limited. METHODS AND RESULTS: Mitochondrial cytochrome oxidase I (mtCOI) sequences (710 bp) from 44 individuals representing 16 populations across nine Indian states were analysed to assess genetic structure. Phylogenetic analyses using Maximum Likelihood and Bayesian inference recovered a single monophyletic cluster with shallow divergence and no region-specific lineages. Three closely related haplotypes were detected, differing by a single mutation, with one dominant haplotype (H1) comprising 88.63% of individuals. Overall haplotype and nucleotide diversity were low (Hd = 0.342; π = 0.00057) and southern populations showed mitochondrial monomorphism under current sampling. AMOVA indicated that most genetic variation occurred within populations (92.68%), with only 7.32% among populations. Pairwise FST and gene flow analyses indicated heterogeneous connectivity, while isolation-by-distance analysis detected a significant positive correlation between genetic and geographic distances (r ≈ 0.50, P < 0.05). Neutrality tests (Tajima’s D; Fu and Li’s D and F) were negative but non-significant. Bayesian Skyline Plot analysis indicated moderate historical fluctuations in effective population size without evidence of recent rapid expansion or severe bottlenecks. CONCLUSIONS: Indian populations of S. furcifera exhibit low mitochondrial genetic differentiation, shallow spatial structuring and moderate isolation by distance. The overall pattern suggests demographic stability and substantial dispersal potential; however, inference is limited by the resolution of a single mitochondrial marker. These findings provide a baseline for understanding WBPH population dynamics in India and highlight the need for high-resolution nuclear markers to better resolve fine-scale structure relevant to migration monitoring and pest management.}, } @article {pmid41963795, year = {2026}, author = {Stuehler, DS and Cano, LM and Heck, M}, title = {Rapid and reproducible haplotyping of complete mitochondrial genomes using split k-mers.}, journal = {BMC genomics}, volume = {27}, number = {1}, pages = {}, pmid = {41963795}, issn = {1471-2164}, support = {2022-70029-038503//National Institute of Food and Agriculture/ ; 8062-22410-007-000-D//Agricultural Research Service/ ; 2020-70029-33176//Emergency Citrus Disease Research and Extension Program/ ; }, mesh = {*Genome, Mitochondrial ; *Haplotypes ; Animals ; Phylogeny ; Hemiptera/genetics ; Reproducibility of Results ; }, abstract = {Accurate phylogenetic analysis of mitochondrial haplotypes underpins a wide spectrum of biological inquiry. While multilocus sequence-based phylogenies are standard, inconsistent gene selection and removal of terminal overhangs during alignment trimming disregard non-coding sequence as well as limit the reproducibility of haplotyping methods. To examine alternative approaches, we tested split k-mer analysis (SKA) to reassess published mitogenome datasets of one mammalian and two insect species. SKA accurately haplotyped each dataset, improved polymorphism detection in the hemipteran Diaphorina citri and aided in the identification of D. citri haplotypes associated with the titer of “Candidatus Liberibacter asiaticus”, the bacterium associated with citrus greening disease. We present a new mitogenome haplotyping method and script, ska-mtdna.py.}, } @article {pmid41326992, year = {2025}, author = {Radwan, NS and Lamlom, SF and Emwas, AH and Jaremko, M and Abdelsalam, NR}, title = {Genome-wide identification, characterization, and evolutionary analysis of the HSP70 gene family in rice (Oryza sativa L.).}, journal = {BMC plant biology}, volume = {25}, number = {1}, pages = {1671}, pmid = {41326992}, issn = {1471-2229}, mesh = {*Oryza/genetics/metabolism ; *HSP70 Heat-Shock Proteins/genetics/metabolism ; *Evolution, Molecular ; Phylogeny ; *Plant Proteins/genetics/metabolism ; Multigene Family ; *Genome, Plant ; Chromosome Mapping ; Genes, Plant ; Stress, Physiological/genetics ; Gene Duplication ; }, abstract = {Heat shock proteins 70 (HSP70s) are highly conserved molecular chaperones essential for maintaining protein homeostasis under environmental stress conditions. Despite rice being a staple crop for over half the world population and facing increasing climate-related stresses, comprehensive characterization of its OsHSP70 gene family has remained incomplete. We identified and characterized 32 OsHSP70 genes in the rice genome through integrated bioinformatics and experimental approaches. Phylogenetic analysis classified these genes into five distinct subfamilies (A-E), with subfamily D predominating (15 members, 46.9%). Chromosome mapping revealed non-random distribution across 9 chromosomes, with notable gene clusters on chromosomes 3 (7 genes) and 11 (10 genes), indicating tandem duplication as a major expansion mechanism. Evolutionary analysis through Ka/Ks ratios demonstrated that 83% of duplicated gene pairs evolved under purifying selection (Ka/Ks < 1), with divergence times spanning from 0.98 to 64.75 million years ago. Subcellular localization predictions identified diverse targeting patterns: 34.9% chloroplast, 32.6% cytoplasm, and 14.0% mitochondria, reflecting functional compartmentalization. Quantitative RT-PCR analysis under five abiotic stress conditions (heat, cold, drought, salt, and submergence) identified seven highly stress-responsive genes (Os01g62290, Os03g02260, Os03g11910, Os03g16860, Os03g16920, Os03g50250, Os05g35400, and Os05g38530) with maximum fold changes exceeding eightfold, particularly under heat stress. Os03g50250 (OsHSP70-13) emerged as the strongest responder across multiple stresses. Protein–protein interaction networks revealed integration with key metabolic and stress response pathways. These findings establish a comprehensive framework for understanding OsHSP70-mediated stress tolerance mechanisms in rice and identify priority candidates for developing climate-resilient varieties through targeted breeding or genome editing approaches.}, } @article {pmid42244571, year = {2026}, author = {Tressel, LG and Havird, JC and Choi, IS and Ruhlman, TA and Cardoso, D and Wojciechowski, MF and Jansen, RK}, title = {Coordinated Evolutionary Rates in Oxidative Phosphorylation Complexes of Papilionoid Legumes: Cytonuclear Coevolution and Relaxed Selection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {42244571}, issn = {2692-8205}, abstract = {Across eukaryotes, mitochondrial (mt) and nuclear genomes coordinate the expression and interaction of gene products to maintain cellular functions. While mitonuclear coevolution has been widely explored in animals, it remains understudied in plants, despite their utility as model systems due to relatively slow mitochondrial evolutionary rates and the presence of plastids. Plants rely on oxidative phosphorylation (OXPHOS) for ATP conversion, which requires cofunctionality and likely coevolution of mitochondrial and nuclear gene products. Here, we investigated evolutionary rate covariation (ERC) between mitochondrial- and nuclear-encoded OXPHOS genes in papilionoid legumes, where plastid-nuclear coevolution and an inversion in plastid DNA have been documented previously. Using 50 legume species spanning 15 papilionoid clades, we estimated evolutionary rates for five gene sets: mt-encoded OXPHOS genes, nuclear-encoded mitochondrial-targeted (N-mt) OXPHOS genes, and three control nuclear gene sets that lack mitochondrial interactions (glycolysis, cell cycle, and cytosolic ribosomal genes). Both mt and N-mt OXPHOS genes exhibited significantly elevated nonsynonymous (d N) and synonymous substitution rates (d S) in the 50-kb inversion clade relative to other legumes, suggesting accelerated mitochondrial substitution rates. Moreover, elevated d N /d S ratios in mt and N-mt OXPHOS genes in this clade were driven by relaxed purifying, not intensified positive selection. ERCs were highest for OXPHOS complexes and genes with physical mitonuclear interactions, as predicted under mitonuclear coevolution. We discuss how these results compare to other cases of cytonuclear coevolution in plants, including plastid-nuclear coevolution in papilionoids, and why dual-targeted, nuclear-encoded genes that repair mt and plastid DNA may underly patterns of molecular evolution in both organelles.}, } @article {pmid42353411, year = {2026}, author = {Fu, YT and Gao, WZ and Shi, L}, title = {Comparative Retinal Morphology of Two Sympatric Lizard Species from Distinct Microhabitats.}, journal = {Animals : an open access journal from MDPI}, volume = {16}, number = {12}, pages = {}, doi = {10.3390/ani16121799}, pmid = {42353411}, issn = {2076-2615}, support = {32260257//National Natural Science Foundation of China/ ; }, abstract = {This study investigated retinal interspecific differences between two sympatric lizards from the Turpan Basin of Xinjiang that occupy distinct microhabitats. Eremias roborowskii inhabits shrublands, while Phrynocephalus axillaris lives in open sandy areas. We adopted retinal whole-mounting, paraffin sectioning, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) to compare retinal structure, oil droplet traits, photoreceptor arrangement, and ultrastructural characteristics between the two species. Both species exhibited five types of colored oil droplets, a temporal fovea, and a highly vascularized conus papillaris, confirming cone-dominant retinas. P. axillaris had larger oil droplets with an average diameter of 3.719 ± 1.100 μm. In contrast, E. roborowskii showed a higher oil droplet density of 1473 ± 1203 ind/mm[2]. The inner plexiform layer (IPL) was significantly thicker in E. roborowskii (56.01 ± 14.76 μm) relative to P. axillaris (50.76 ± 15.25 μm). The two species also differed markedly in photoreceptor ultrastructure. E. roborowskii contained mitochondria-rich ellipsoids, while P. axillaris possessed glycogen-enriched paraboloids. These structural variations reflect compatibility with local ambient light conditions. E. roborowskii is predisposed to suit diffuse shrubland light through high droplet density and mitochondrial-dominant ellipsoids, whereas P. axillaris tends to accommodate intense open-field sunlight via larger oil droplets and well-developed paraboloids. This study provides key morphological evidence to reveal how microhabitat divergence drives retinal specialization among desert reptiles.}, } @article {pmid42353767, year = {2026}, author = {Lin, B and Zhang, X and Yu, Z and Zhao, W and Ma, G and Song, S and Li, X and Zhuang, Y and Zhang, J and Zhang, D and Chen, B}, title = {Genome-Wide Identification and Expression Analysis of the Soybean GmHSP100 Gene Family in Response to Heat and Salt Stresses.}, journal = {Genes}, volume = {17}, number = {6}, pages = {}, doi = {10.3390/genes17060608}, pmid = {42353767}, issn = {2073-4425}, support = {2023LZGC006, 32572365, 32322062, 32441057, SRICSPYF-BS2025109, ZR2023JQ009, SDARS-28-01, and SDARS-28-06//Shandong Agricultural University/ ; }, mesh = {*Glycine max/genetics/metabolism ; Gene Expression Regulation, Plant ; *Salt Stress/genetics ; Multigene Family ; *Plant Proteins/genetics/metabolism ; *Heat-Shock Proteins/genetics/metabolism ; *Heat-Shock Response/genetics ; Phylogeny ; Gene Expression Profiling ; Promoter Regions, Genetic ; Genome-Wide Association Study ; *Soybean Proteins/genetics ; Genome, Plant ; }, abstract = {BACKGROUND: Heat shock protein 100 (HSP100) is a key molecular chaperone that maintains intracellular proteostasis and enhances plant tolerance. However, the HSP100 gene family in soybean (Glycine max) has not been systematically characterized.

METHODS: In this study, we performed genome-wide identification and comprehensive analysis of the GmHSP100 gene family and analyzed their phylogeny, genomic distribution, synteny, protein structures, subcellular localization, promoter cis-elements, and expression patterns under heat and salt stresses via bioinformatics approaches and quantitative real-time PCR (qRT-PCR) validation.

RESULTS: Thirteen GmHSP100 members were identified, which were classified into CLPB, CLPC and CLPD subfamilies. Segmental and whole-genome duplications primarily drove the expansion of this gene family. All encoded proteins possessed conserved AAA+ ATPase domains, with distinct motifs across subfamilies. Most proteins localized to the cytoplasm, while CLPC and CLPD targeted chloroplasts and GmCLPB4 localized to mitochondria. Promoter analysis identified numerous elements associated with light, hormone and stress responses. Expression profiling showed strong tissue specificity and time-dependent stress-treatment induction. Heat stress triggered rapid and strong upregulation of the GmHSP100s, whereas salt stress salt stress induced their relatively delayed and sustained expression.

CONCLUSIONS: These findings reveal the evolutionary conservation and diversification of the GmHSP100 gene family in soybean, providing a foundational framework for understanding the functions of GmHSP100 in stress adaptation.}, } @article {pmid42339914, year = {2026}, author = {Rothera, EY and Horam, S and Hu, Y and Lin, SA and David, AJ and Xiao, TS}, title = {Theme and variations: activation and regulation of gasdermin-mediated inflammation.}, journal = {Biochemical Society transactions}, volume = {54}, number = {7}, pages = {831-843}, doi = {10.1042/BST20250185}, pmid = {42339914}, issn = {1470-8752}, support = {R35GM152080//HHS | National Institutes of Health (NIH)/ ; R01AA030699//HHS | National Institutes of Health (NIH)/ ; }, mesh = {Humans ; Gasdermins ; Animals ; *Inflammation/metabolism ; Pyroptosis ; Signal Transduction ; *Neoplasm Proteins/metabolism ; Protein Processing, Post-Translational ; Intracellular Signaling Peptides and Proteins/metabolism ; }, abstract = {Gasdermins are effectors for pyroptosis, a highly inflammatory form of cell death. Mammalian gasdermin (GSDM) family members harbor N-terminal domains (NTDs) that bind membrane phospholipids and assemble oligomeric pores. Their C-terminal domains are regulatory modules, which suppress the cytolytic function of the NTDs under homeostatic conditions, and in several cases mediate the recruitment of proteases that cleave GSDMs following upstream signaling. The initial model for gasdermin activation was that upon protease processing their NTDs localize to the plasma membrane to assemble oligomeric pores and mediate pyroptosis. Emerging evidence suggests fascinating variations of this paradigm. For example, cleavage-independent pyroptotic activities have been reported for several family members that undergo post-translational modifications such as S-acylation, PARylation, oxidation, or phosphorylation. Furthermore, some gasdermins associate with membranes from organelles such as mitochondria, and often play non-pyroptotic roles in cellular physiology. In the present mini-review, we briefly summarize the molecular mechanisms governing the activation of different gasdermin family members, focusing on protease processing as the most well-studied mechanism. This is followed by discussion of two aspects of gasdermin biology. Namely, cleavage-independent pyroptotic activities and the localization of gasdermins at mitochondria and nucleus implicated in pyroptotic and non-pyroptotic functions. The diverse mechanisms of gasdermin activation and regulation in response to different upstream signaling pathways demonstrate the versatility of this conserved family of pore-forming proteins in various aspects of cellular physiology throughout evolution. The pleiotropic functions of gasdermins in inflammatory disorders, antimicrobial defense, antitumor immunity, neurodegenerative disorders etc., suggest fertile ground for exploration of therapeutic avenues.}, } @article {pmid42342450, year = {2026}, author = {Chowdhury, S and Kruger, AJ and Roger, LM}, title = {Conserved HSP60 structure with lineage- and context-specific regulation in cnidarians.}, journal = {Life science alliance}, volume = {9}, number = {9}, pages = {}, doi = {10.26508/lsa.202503592}, pmid = {42342450}, issn = {2575-1077}, mesh = {Animals ; *Chaperonin 60/genetics/metabolism/chemistry ; Phylogeny ; Heat-Shock Response ; *Cnidaria/metabolism/genetics ; Sea Anemones/metabolism/genetics ; Mitochondria/metabolism ; Stress, Physiological ; }, abstract = {Heat shock proteins safeguard proteostasis under stress. We examined mitochondrial chaperonin HSP60 in three cnidarians to assess stress responses. We evaluated HSP60 expression in Pocillopora acuta (hard coral), Exaiptasia diaphana (sea anemone), and Cassiopea xamachana (upside-down jellyfish) using immunoblotting. In P. acuta, HSP60 was not detected at the fragment level under either control (25°C) or heat-stress (30°C). In contrast, isolated cells showed transient HSP60 expression under both temperature conditions, indicating context-dependent regulation in coral. E. diaphana and C. xamachana showed elevated HSP60 expression over 24 h when stressed (+5°C above laboratory optima). These patterns indicate lineage-specific regulatory mechanisms underlying chaperone-mediated stress response pathways. Thus, thermal sensitivity varies among species and across biological contexts. Consistent antibody cross-reactivity prompted evolutionary analysis. Phylogenetic analyses confirmed cnidarian HSP60 proteins are orthologous to vertebrate HSP60, demonstrating deep conservation across Metazoa. Although HSP60 is ancient and highly conserved, its role in regulating mitochondrial proteostasis varies across early-diverging metazoans. This study underlines the role of chaperone plasticity in cnidarian thermotolerance and diverging bleaching susceptibility of symbiotic cnidarians.}, } @article {pmid42333737, year = {2026}, author = {Edgeloe, JM and Starko, S and Wood, GV and Pessarrodona, A and Minne, AJP and Wernberg, T}, title = {Complete organellar genomes of Cystophora brownii: Insights into mitochondrial and plastid structure and evolution in brown algae.}, journal = {Journal of phycology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jpy.70187}, pmid = {42333737}, issn = {1529-8817}, support = {DE25010015//Australian Research Council Discovery Early Career Research Award/ ; //Forrest Research Foundation/ ; 2022GR001626-3076//Revive and Restore Grant/ ; IE230100464//Australian Research Council Industry Fellowship/ ; //Winnifred Violet Scott Grant/ ; DP240100230//Australian Research Council Discovery Project/ ; }, abstract = {Cystophora (order Fucales) is one of the most diverse genera of habitat-forming brown algae and is endemic to temperate reefs of Australia and New Zealand. Species in this genus form complex habitat structures that support diverse marine communities and contribute to coastal productivity. However, Cystophora spp. are highly sensitive to environmental stress, and recent declines across parts of their historical range highlight their vulnerability to ocean warming. Despite their ecological importance, genomic resources for Cystophora remain scarce, limiting insight into their evolutionary history, adaptive capacity, and resilience to environmental change. Here, we sequenced, assembled, and annotated the complete plastid and mitochondrial genomes of the widespread species Cystophora brownii using PacBio HiFi long-read sequencing. We characterized organellar genome architecture and gene content, conducted comparative analyses with other Fucalean taxa, and reconstructed phylogenetic relationships within the Fucales. The mitochondrial genome is 36,047 bp and contains 66 conserved genes (GenBank accession PZ196221). The plastid genome is 124,536 bp and contains 171 conserved genes, including two inverted repeat regions (GenBank accession PX975689). Comparative analyses indicate conserved gene content, order, and structure relative to other Fucalean organellar genomes. Maximum likelihood phylogenetic analyses robustly place C. brownii within the Fucales with strong support, resolving it as sister to the remaining Sargassaceae, suggesting an early divergence within the family that may date to the Miocene. These genomic resources provide a foundation for resolving the evolutionary placement of Cystophora and advancing studies of organellar genome evolution in brown algae.}, } @article {pmid42330929, year = {2026}, author = {Boscaro, V and Keeling, PJ}, title = {Evolution: An endogenous energy-metabolizing organelle.}, journal = {Current biology : CB}, volume = {36}, number = {12}, pages = {R708-R710}, doi = {10.1016/j.cub.2026.05.010}, pmid = {42330929}, issn = {1879-0445}, abstract = {Mitochondria originated from endosymbiotic bacteria, and in some eukaryotes they further evolved into anaerobic hydrogenosomes. The 'hydrogenosomes' of rumen-dwelling ciliates, however, appear instead to have evolved endogenously from the endomembrane system, making them unique among organelles involved in energy metabolism.}, } @article {pmid42332066, year = {2026}, author = {Valdivieso-Rivera, F and Furino, VO and Leher, CE and Zanesco, AM and Cruz, MK and Gan, FC and Santoro, AL and Regina-Ferreira, L and Santos, GL and Gonçalves, T and Leiria, LO and Moraes-Vieira, PM and Castilho, RF and Kajimura, S and Mori, MA and Velloso, LA and Sponton, CH}, title = {E4BP4 safeguards brown fat mitochondria from obesity-induced fragmentation via ceramide repression.}, journal = {EMBO reports}, volume = {}, number = {}, pages = {}, pmid = {42332066}, issn = {1469-3178}, support = {2019/15025-5,2020/14725-0,2020/06057-8,2021/08354-2,2013/07607-8,2021/12964-0//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; }, abstract = {Brown adipose tissue (BAT) counteracts obesity-related metabolic dysfunction through both thermogenic and non-thermogenic means. However, substantial evidence indicates that obesity negatively affects BAT mitochondrial morphology and oxidative capacity, impairing systemic energy homeostasis. Motivated by this apparent contradiction, we investigate the relationship between obesity and mitochondrial dynamics, as the underlying mechanisms remain incompletely understood. Here, we identify E4BP4 as a transcriptional repressor that prevents obesity-induced mitochondrial fragmentation and oxidative dysfunction by inhibiting ceramide synthesis in brown fat. Specifically, E4BP4 interacts with PRDM16 to repress Cers6 mRNA expression and consequently reduces C16:0 ceramide levels by binding to a 65 kb upstream enhancer region of the Cers6 gene. Notably, the preservation of mitochondrial integrity in BAT by E4BP4 gain-of-function improves systemic glucose homeostasis, independent of weight loss. Collectively, our findings establish E4BP4 as a molecular safeguard against obesity-induced mitochondrial fragmentation and oxidative dysfunction, primarily by suppressing ceramide synthesis in brown fat.}, } @article {pmid37221926, year = {2023}, author = {Dong, X and Zhang, H and Zhu, X and Wang, K and Xue, H and Ye, Z and Zheng, C and Bu, W}, title = {Mitochondrial introgression and mito-nuclear discordance obscured the closely related species boundaries in Cletus Stål from China (Heteroptera: Coreidae).}, journal = {Molecular phylogenetics and evolution}, volume = {184}, number = {}, pages = {107802}, doi = {10.1016/j.ympev.2023.107802}, pmid = {37221926}, issn = {1095-9513}, mesh = {Animals ; *Heteroptera ; Phylogeny ; China ; *Genome, Mitochondrial ; Mitochondria ; Mitomycin ; }, abstract = {Accurate taxonomy and delimitation are of great importance for pest control strategies and management programs. Here, we focus on Cletus (Insecta: Hemiptera: Coreidae), which includes many crop pests. The species boundaries still conflict and only cytochrome c oxidase subunit I (COI) barcoding has been previously used for molecular studies. We generated new mitochondrial genome and nuclear genome-wide SNPs to explore the species boundaries of 46 Cletus samples from China using multiple species delimitation approaches. All results recovered a monophyly with high support, except for two closely related species in clade I - C. punctiger and C. graminis. Mitochondrial data demonstrated admixture in clade I, while genome-wide SNPs unambiguously identified two separate species, which were confirmed by morphological classification. Inconsistent nuclear and mitochondrial data indicated mito-nuclear discordance. Mitochondrial introgression is the most likely explanation, and more extensive sampling and more comprehensive data are needed to ascertain a pattern. Accurate species delimitation will shed light on species status; thus, an accurate taxonomy is of particular concern, as there is a pressing need to implement precise control of agricultural pests and to perform further research on diversification.}, } @article {pmid37231782, year = {2023}, author = {Shi, J and Yan, S and Li, W and Yang, X and Cui, Z and Li, J and Li, G and Li, Y and Hu, Y and Gao, S}, title = {PacBio full-length transcriptome analysis provides new insights into transcription of chloroplast genomes.}, journal = {RNA biology}, volume = {20}, number = {1}, pages = {248-256}, pmid = {37231782}, issn = {1555-8584}, mesh = {Animals ; *Genome, Chloroplast ; Gene Expression Profiling ; Molecular Sequence Annotation ; Transcriptome ; DNA, Mitochondrial/genetics ; Chloroplasts/genetics ; *Arabidopsis/genetics ; }, abstract = {Chloroplast and mitochondrial DNA (cpDNA and mtDNA) are apart from nuclear DNA (nuDNA) in a eukaryotic cell. The transcription system of chloroplasts differs from those of mitochondria and eukaryotes. In contrast to nuDNA and animal mtDNA, the transcription of cpDNA is still not well understood, primarily due to the unresolved identification of transcription initiation sites (TISs) and transcription termination sites (TTSs) on the genome scale. In the present study, we characterized the transcription of chloroplast (cp) genes with greater accuracy and comprehensive information using PacBio full-length transcriptome data from Arabidopsis thaliana. The major findings included the discovery of four types of artifacts, the validation and correction of cp gene annotations, the exact identification of TISs that start with G, and the discovery of polyA-like sites as TTSs. Notably, we proposed a new model to explain cp transcription initiation and termination at the whole-genome level. Four types of artifacts, degraded RNAs and splicing intermediates deserve the attention from researchers working with PacBio full-length transcriptome data, as these contaminant sequences can lead to incorrect downstream analysis. Cp transcription initiates at multiple promoters and terminates at polyA-like sites. Our study provides new insights into cp transcription and new clues to study the evolution of promoters, TISs, TTSs and polyA tails of eukaryotic genes.}, } @article {pmid37239339, year = {2023}, author = {Wu, Z and Yang, T and Qin, R and Liu, H}, title = {Complete Mitogenome and Phylogenetic Analysis of the Carthamus tinctorius L.}, journal = {Genes}, volume = {14}, number = {5}, pages = {}, pmid = {37239339}, issn = {2073-4425}, mesh = {Phylogeny ; *Carthamus tinctorius/genetics ; *Genome, Mitochondrial/genetics ; Repetitive Sequences, Nucleic Acid ; }, abstract = {Carthamus tinctorius L. 1753 (Asteraceae), also called safflower, is a cash crop with both edible and medical properties. We analyzed and reported the safflower mitogenome based on combined short and long reads obtained from Illumina and Pacbio platforms, respectively. This safflower mitogenome mainly contained two circular chromosomes, with a total length of 321,872 bp, and encoded 55 unique genes, including 34 protein-coding genes (PCGs), 3 rRNA genes, and 18 tRNA genes. The total length of repeat sequences greater than 30 bp was 24,953 bp, accounting for 7.75% of the whole mitogenome. Furthermore, we characterized the RNA editing sites of protein-coding genes located in the safflower mitogenome, and the total number of RNA editing sites was 504. Then, we revealed partial sequence transfer events between plastid and mitochondria, in which one plastid-derived gene (psaB) remained intact in the mitogenome. Despite extensive arrangement events among the three mitogenomes of C. tinctorius, Arctium lappa, and Saussurea costus, the constructed phylogenetic tree based on mitogenome PCGs showed that C. tinctorius has a closer relationship with three Cardueae species, A. lappa, A. tomentosum, and S. costus, which is similar to the phylogeny constructed from the PCGs of plastid genomes. This mitogenome not only enriches the genetic information of safflower but also will be useful in the phylogeny and evolution study of the Asteraceae.}, } @article {pmid37239358, year = {2023}, author = {Ran, B and Zhu, W and Zhao, X and Li, L and Yi, Z and Li, M and Wang, T and Li, D}, title = {Studying Genetic Diversity and Relationships between Mountainous Meihua Chickens Using Mitochondrial DNA Control Region.}, journal = {Genes}, volume = {14}, number = {5}, pages = {}, pmid = {37239358}, issn = {2073-4425}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; *Chickens/genetics ; Genetic Variation/genetics ; Phylogeny ; Mitochondria/genetics ; }, abstract = {The Mountainous Meihua chicken is a unique regional germplasm resource from Tongjiang County, Bazhong City, China, but its genetic structure and evolutionary relationships with other native chicken breeds in the Sichuan region remain unclear. Here, we analyzed a total of 469 sequences, including 199 Mountainous Meihua chicken sequences generated in this study, together with 30 sequences representing 13 clades and 240 sequences from seven different Sichuan local chicken breeds downloaded from NCBI. These sequences were further used to analyze genetic diversity, patterns of population differentiation, and phylogenetic relationships between groups. We show that Mountainous Meihua chicken mtDNA sequences have high haplotypic and nucleotide diversity (0.876 and 0.012, respectively) and with a T bias that is suggestive of good breeding potential. Phylogenetic analysis showed that Mountainous Meihua chickens belong to clades A, B, E, and G and have a low affinity to other chicken breeds, with a moderate degree of differentiation. A non-significant Tajima's D indicates that no demographic expansions occurred in the past. Finally, the four maternal lineages identified in Mountainous Meihua chicken showed unique genetic characteristics.}, } @article {pmid37239904, year = {2023}, author = {Rossi, F and Picone, G and Cappadone, C and Sorrentino, A and Columbaro, M and Farruggia, G and Catelli, E and Sciutto, G and Prati, S and Oliete, R and Pasini, A and Pereiro, E and Iotti, S and Malucelli, E}, title = {Shedding Light on Osteosarcoma Cell Differentiation: Impact on Biomineralization and Mitochondria Morphology.}, journal = {International journal of molecular sciences}, volume = {24}, number = {10}, pages = {}, pmid = {37239904}, issn = {1422-0067}, mesh = {Humans ; Osteogenesis ; Biomineralization ; Cell Line, Tumor ; *Osteosarcoma/metabolism ; Cell Differentiation/physiology ; Mitochondria/metabolism ; *Bone Neoplasms/metabolism ; Cell Proliferation/physiology ; }, abstract = {Osteosarcoma (OS) is the most common primary malignant bone tumor and its etiology has recently been associated with osteogenic differentiation dysfunctions. OS cells keep a capacity for uncontrolled proliferation showing a phenotype similar to undifferentiated osteoprogenitors with abnormal biomineralization. Within this context, both conventional and X-ray synchrotron-based techniques have been exploited to deeply characterize the genesis and evolution of mineral depositions in a human OS cell line (SaOS-2) exposed to an osteogenic cocktail for 4 and 10 days. A partial restoration of the physiological biomineralization, culminating with the formation of hydroxyapatite, was observed at 10 days after treatment together with a mitochondria-driven mechanism for calcium transportation within the cell. Interestingly, during differentiation, mitochondria showed a change in morphology from elongated to rounded, indicating a metabolic reprogramming of OS cells possibly linked to an increase in glycolysis contribution to energy metabolism. These findings add a dowel to the genesis of OS giving new insights on the development of therapeutic strategies able to restore the physiological mineralization in OS cells.}, } @article {pmid37249052, year = {2023}, author = {Chen, Y and Guo, Y and Xie, X and Wang, Z and Miao, L and Yang, Z and Jiao, Y and Xie, C and Liu, J and Hu, Z and Xin, M and Yao, Y and Ni, Z and Sun, Q and Peng, H and Guo, W}, title = {Pangenome-based trajectories of intracellular gene transfers in Poaceae unveil high cumulation in Triticeae.}, journal = {Plant physiology}, volume = {193}, number = {1}, pages = {578-594}, pmid = {37249052}, issn = {1532-2548}, mesh = {*Poaceae/genetics ; Triticum/genetics ; Genome, Plant/genetics ; *Oryza/genetics ; Zea mays/genetics ; Evolution, Molecular ; }, abstract = {Intracellular gene transfers (IGTs) between the nucleus and organelles, including plastids and mitochondria, constantly reshape the nuclear genome during evolution. Despite the substantial contribution of IGTs to genome variation, the dynamic trajectories of IGTs at the pangenomic level remain elusive. Here, we developed an approach, IGTminer, that maps the evolutionary trajectories of IGTs using collinearity and gene reannotation across multiple genome assemblies. We applied IGTminer to create a nuclear organellar gene (NOG) map across 67 genomes covering 15 Poaceae species, including important crops. The resulting NOGs were verified by experiments and sequencing data sets. Our analysis revealed that most NOGs were recently transferred and lineage specific and that Triticeae species tended to have more NOGs than other Poaceae species. Wheat (Triticum aestivum) had a higher retention rate of NOGs than maize (Zea mays) and rice (Oryza sativa), and the retained NOGs were likely involved in photosynthesis and translation pathways. Large numbers of NOG clusters were aggregated in hexaploid wheat during 2 rounds of polyploidization, contributing to the genetic diversity among modern wheat accessions. We implemented an interactive web server to facilitate the exploration of NOGs in Poaceae. In summary, this study provides resources and insights into the roles of IGTs in shaping interspecies and intraspecies genome variation and driving plant genome evolution.}, } @article {pmid37254790, year = {2023}, author = {López-García, P and Moreira, D}, title = {The symbiotic origin of the eukaryotic cell.}, journal = {Comptes rendus biologies}, volume = {346}, number = {}, pages = {55-73}, doi = {10.5802/crbiol.118}, pmid = {37254790}, issn = {1768-3238}, mesh = {*Eukaryotic Cells ; *Symbiosis ; Phylogeny ; Archaea/genetics ; Eukaryota/genetics ; Biological Evolution ; }, abstract = {Eukaryogenesis represented a major evolutionary transition that led to the emergence of complex cells from simpler ancestors. For several decades, the most accepted scenario involved the evolution of an independent lineage of proto-eukaryotes endowed with an endomembrane system, including a nuclear compartment, a developed cytoskeleton and phagocytosis, which engulfed the alphaproteobacterial ancestor of mitochondria. However, the recent discovery by metagenomic and cultural approaches of Asgard archaea, which harbour many genes in common with eukaryotes and are their closest relatives in phylogenomic trees, rather supports scenarios based on the symbiosis of one Asgard-like archaeon and one or more bacteria at the origin of the eukaryotic cell. Here, we review the recent discoveries that led to this conceptual shift, briefly evoking current models of eukaryogenesis and the challenges ahead to discriminate between them and to establish a detailed, plausible scenario that accounts for the evolution of eukaryotic traits from those of their prokaryotic ancestors.}, } @article {pmid37262983, year = {2023}, author = {Camus, MF and Dhawanjewar, AS}, title = {Multilevel selection on mitochondrial genomes.}, journal = {Current opinion in genetics & development}, volume = {80}, number = {}, pages = {102050}, doi = {10.1016/j.gde.2023.102050}, pmid = {37262983}, issn = {1879-0380}, mesh = {*Genome, Mitochondrial/genetics ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Biological Evolution ; Eukaryota/genetics ; Evolution, Molecular ; }, abstract = {Mitochondria are vital organelles for life in eukaryotes, taking centre stage in the process of cellular respiration. This process is regulated via a series of finely coordinated obligate interactions of molecules encoded by two genomes: nuclear DNA and mitochondrial DNA. Both genomes are required to work harmoniously to provide cellular energy, with detrimental consequences occurring when there is miscommunication between them. Whilst the need for cooperation is strong, vast differences between genomes (ploidy, size, and inheritance) create an arena for conflict. Here, we examine the varying levels of selection operating on the mitochondrial genome and the consequences they have on all these levels. We conclude by highlighting the potential for conflict when selection at different levels is driven by different evolutionary forces.}, } @article {pmid37267944, year = {2023}, author = {Záhonová, K and Low, RS and Warren, CJ and Cantoni, D and Herman, EK and Yiangou, L and Ribeiro, CA and Phanprasert, Y and Brown, IR and Rueckert, S and Baker, NL and Tachezy, J and Betts, EL and Gentekaki, E and van der Giezen, M and Clark, CG and Jackson, AP and Dacks, JB and Tsaousis, AD}, title = {Evolutionary analysis of cellular reduction and anaerobicity in the hyper-prevalent gut microbe Blastocystis.}, journal = {Current biology : CB}, volume = {33}, number = {12}, pages = {2449-2464.e8}, doi = {10.1016/j.cub.2023.05.025}, pmid = {37267944}, issn = {1879-0445}, mesh = {Animals ; Humans ; *Blastocystis/genetics ; *Gastrointestinal Microbiome/genetics ; Mitochondria/genetics/metabolism ; Organelles/metabolism ; Eukaryota ; }, abstract = {Blastocystis is the most prevalent microbial eukaryote in the human and animal gut, yet its role as commensal or parasite is still under debate. Blastocystis has clearly undergone evolutionary adaptation to the gut environment and possesses minimal cellular compartmentalization, reduced anaerobic mitochondria, no flagella, and no reported peroxisomes. To address this poorly understood evolutionary transition, we have taken a multi-disciplinary approach to characterize Proteromonas lacertae, the closest canonical stramenopile relative of Blastocystis. Genomic data reveal an abundance of unique genes in P. lacertae but also reductive evolution of the genomic complement in Blastocystis. Comparative genomic analysis sheds light on flagellar evolution, including 37 new candidate components implicated with mastigonemes, the stramenopile morphological hallmark. The P. lacertae membrane-trafficking system (MTS) complement is only slightly more canonical than that of Blastocystis, but notably, we identified that both organisms encode the complete enigmatic endocytic TSET complex, a first for the entire stramenopile lineage. Investigation also details the modulation of mitochondrial composition and metabolism in both P. lacertae and Blastocystis. Unexpectedly, we identify in P. lacertae the most reduced peroxisome-derived organelle reported to date, which leads us to speculate on a mechanism of constraint guiding the dynamics of peroxisome-mitochondrion reductive evolution on the path to anaerobiosis. Overall, these analyses provide a launching point to investigate organellar evolution and reveal in detail the evolutionary path that Blastocystis has taken from a canonical flagellated protist to the hyper-divergent and hyper-prevalent animal and human gut microbe.}, } @article {pmid37268349, year = {2023}, author = {Pellielo, G and Agyapong, ED and Pinton, P and Rimessi, A}, title = {Control of mitochondrial functions by Pseudomonas aeruginosa in cystic fibrosis.}, journal = {International review of cell and molecular biology}, volume = {377}, number = {}, pages = {19-43}, doi = {10.1016/bs.ircmb.2023.03.008}, pmid = {37268349}, issn = {1937-6448}, mesh = {Humans ; *Cystic Fibrosis ; Pseudomonas aeruginosa/physiology ; Persistent Infection ; Inflammation/genetics ; Mitochondria ; }, abstract = {Cystic fibrosis (CF) is a genetic disease characterized by mutations of cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to a dysfunctional chloride and bicarbonate channel. Abnormal mucus viscosity, persistent infections and hyperinflammation that preferentially affect the airways, referred to the pathogenesis of CF lung disease. It has largely demonstrated that Pseudomonas aeruginosa (P. aeruginosa) represents the most important pathogen that affect CF patients, leading to worsen inflammation by stimulating pro-inflammatory mediators release and tissue destruction. The conversion to mucoid phenotype and formation of biofilms, together with the increased frequency of mutations, are only few changes that characterize the P. aeruginosa's evolution during CF lung chronic infection. Recently, mitochondria received increasing attention due to their involvement in inflammatory-related diseases, including in CF. Alteration of mitochondrial homeostasis is sufficient to stimulate immune response. Exogenous or endogenous stimuli that perturb mitochondrial activity are used by cells, which, through the mitochondrial stress, potentiate immunity programs. Studies show the relationship between mitochondria and CF, supporting the idea that mitochondrial dysfunction endorses the exacerbation of inflammatory responses in CF lung. In particular, evidences suggest that mitochondria in CF airway cells are more susceptible to P. aeruginosa infection, with consequent detrimental effects that lead to amplify the inflammatory signals. This review discusses the evolution of P. aeruginosa in relationship with the pathogenesis of CF, a fundamental step to establish chronic infection in CF lung disease. Specifically, we focus on the role of P. aeruginosa in the exacerbation of inflammatory response, by triggering mitochondria in CF.}, } @article {pmid37269314, year = {2023}, author = {Patriarcheas, D and Momtareen, T and Gallagher, JEG}, title = {Yeast of Eden: microbial resistance to glyphosate from a yeast perspective.}, journal = {Current genetics}, volume = {69}, number = {4-6}, pages = {203-212}, pmid = {37269314}, issn = {1432-0983}, support = {R03 ES034881/ES/NIEHS NIH HHS/United States ; NIH NIEHS R03 ES034881/NH/NIH HHS/United States ; NIH NIEHS R03 ES034881/NH/NIH HHS/United States ; }, mesh = {Saccharomyces cerevisiae/genetics/metabolism ; *Herbicides/pharmacology ; Glycine/pharmacology/metabolism ; Plants ; Amino Acids, Aromatic ; }, abstract = {First marketed as RoundUp, glyphosate is history's most popular herbicide because of its low acute toxicity to metazoans and broad-spectrum effectiveness across plant species. The development of glyphosate-resistant crops has led to increased glyphosate use and consequences from the use of glyphosate-based herbicides (GBH). Glyphosate has entered the food supply, spurred glyphosate-resistant weeds, and exposed non-target organisms to glyphosate. Glyphosate targets EPSPS/AroA/Aro1 (orthologs across plants, bacteria, and fungi), the rate-limiting step in the production of aromatic amino acids from the shikimate pathway. Metazoans lacking this pathway are spared from acute toxicity and acquire their aromatic amino acids from their diet. However, glyphosate resistance is increasing in non-target organisms. Mutations and natural genetic variation discovered in Saccharomyces cerevisiae illustrate similar types of glyphosate resistance mechanisms in fungi, plants, and bacteria, in addition to known resistance mechanisms such as mutations in Aro1 that block glyphosate binding (target-site resistance (TSR)) and mutations in efflux drug transporters non-target-site resistance (NTSR). Recently, genetic variation and mutations in an amino transporter affecting glyphosate resistance have uncovered potential off-target effects of glyphosate in fungi and bacteria. While glyphosate is a glycine analog, it is transported into cells using an aspartic/glutamic acid (D/E) transporter. The size, shape, and charge distribution of glyphosate closely resembles D/E, and, therefore, glyphosate is a D/E amino acid mimic. The mitochondria use D/E in several pathways and mRNA-encoding mitochondrial proteins are differentially expressed during glyphosate exposure. Mutants downstream of Aro1 are not only sensitive to glyphosate but also a broad range of other chemicals that cannot be rescued by exogenous supplementation of aromatic amino acids. Glyphosate also decreases the pH when unbuffered and many studies do not consider the differences in pH that affect toxicity and resistance mechanisms.}, } @article {pmid37275157, year = {2023}, author = {Himmelstrand, K and Brandström Durling, M and Karlsson, M and Stenlid, J and Olson, Å}, title = {Multiple rearrangements and low inter- and intra-species mitogenome sequence variation in the Heterobasidion annosum s.l. species complex.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1159811}, pmid = {37275157}, issn = {1664-302X}, abstract = {INTRODUCTION: Mitochondria are essential organelles in the eukaryotic cells and responsible for the energy production but are also involved in many other functions including virulence of some fungal species. Although the evolution of fungal mitogenomes have been studied at some taxonomic levels there are still many things to be learned from studies of closely related species.

METHODS: In this study, we have analyzed 60 mitogenomes in the five species of the Heterobasidion annosum sensu lato complex that all are necrotrophic pathogens on conifers.

RESULTS AND DISCUSSION: Compared to other fungal genera the genomic and genetic variation between and within species in the complex was low except for multiple rearrangements. Several translocations of large blocks with core genes have occurred between the five species and rearrangements were frequent in intergenic areas. Mitogenome lengths ranged between 108 878 to 116 176 bp, mostly as a result of intron variation. There was a high degree of homology of introns, homing endonuclease genes, and intergenic ORFs among the five Heterobasidion species. Three intergenic ORFs with unknown function (uORF6, uORF8 and uORF9) were found in all five species and was located in conserved synteny blocks. A 13 bp long GC-containing self-complementary palindrome was discovered in many places in the five species that were optional in presence/absence. The within species variation is very low, among 48 H. parviporum mitogenomes, there was only one single intron exchange, and SNP frequency was 0.28% and indel frequency 0.043%. The overall low variation in the Heterobasidion annosum sensu lato complex suggests a slow evolution of the mitogenome.}, } @article {pmid37276405, year = {2023}, author = {Kumar, P and Babu, KSD and Singh, AK and Singh, DK and Nalli, A and Mukul, SJ and Roy, A and Mazeed, M and Raman, B and Kruparani, SP and Siddiqi, I and Sankaranarayanan, R}, title = {Distinct localization of chiral proofreaders resolves organellar translation conflict in plants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {24}, pages = {e2219292120}, pmid = {37276405}, issn = {1091-6490}, mesh = {*Organelles/metabolism ; Mitochondria/metabolism ; RNA, Transfer, Amino Acyl/metabolism ; Chloroplasts/metabolism ; RNA, Transfer/metabolism ; *Arabidopsis/genetics ; }, abstract = {Plants have two endosymbiotic organelles originated from two bacterial ancestors. The transition from an independent bacterium to a successful organelle would have required extensive rewiring of biochemical networks for its integration with archaeal host. Here, using Arabidopsis as a model system, we show that plant D-aminoacyl-tRNA deacylase 1 (DTD1), of bacterial origin, is detrimental to organellar protein synthesis owing to its changed tRNA recognition code. Plants survive this conflict by spatially restricting the conflicted DTD1 to the cytosol. In addition, plants have targeted archaeal DTD2 to both the organelles as it is compatible with their translation machinery due to its strict D-chiral specificity and lack of tRNA determinants. Intriguingly, plants have confined bacterial-derived DTD1 to work in archaeal-derived cytosolic compartment whereas archaeal DTD2 is targeted to bacterial-derived organelles. Overall, the study provides a remarkable example of the criticality of optimization of biochemical networks for survival and evolution of plant mitochondria and chloroplast.}, } @article {pmid37277654, year = {2023}, author = {Devant, P and Kagan, JC}, title = {Molecular mechanisms of gasdermin D pore-forming activity.}, journal = {Nature immunology}, volume = {24}, number = {7}, pages = {1064-1075}, pmid = {37277654}, issn = {1529-2916}, support = {P30 DK034854/DK/NIDDK NIH HHS/United States ; R01 AI116550/AI/NIAID NIH HHS/United States ; R01 AI167993/AI/NIAID NIH HHS/United States ; R37 AI116550/AI/NIAID NIH HHS/United States ; }, mesh = {*Intracellular Signaling Peptides and Proteins/genetics/metabolism ; *Gasdermins ; Pyroptosis ; Interleukin-1/metabolism ; Cell Membrane/metabolism ; Inflammasomes/metabolism ; }, abstract = {The regulated disruption of the plasma membrane, which can promote cell death, cytokine secretion or both is central to organismal health. The protein gasdermin D (GSDMD) is a key player in this process. GSDMD forms membrane pores that can promote cytolysis and the release of interleukin-1 family cytokines into the extracellular space. Recent discoveries have revealed biochemical and cell biological mechanisms that control GSDMD pore-forming activity and its diverse downstream immunological effects. Here, we review these multifaceted regulatory activities, including mechanisms of GSDMD activation by proteolytic cleavage, dynamics of pore assembly, regulation of GSDMD activities by posttranslational modifications, membrane repair and the interplay of GSDMD and mitochondria. We also address recent insights into the evolution of the gasdermin family and their activities in species across the kingdoms of life. In doing so, we hope to condense recent progress and inform future studies in this rapidly moving field in immunology.}, } @article {pmid37278219, year = {2023}, author = {Markaki, M and Tsagkari, D and Tavernarakis, N}, title = {Mitophagy and long-term neuronal homeostasis.}, journal = {Journal of cell science}, volume = {136}, number = {11}, pages = {}, doi = {10.1242/jcs.260638}, pmid = {37278219}, issn = {1477-9137}, support = {ERC-GA695190-MANNA/ERC_/European Research Council/International ; }, mesh = {Humans ; *Mitophagy/physiology ; Autophagy/physiology ; Neurons/metabolism ; *Neurodegenerative Diseases/metabolism ; Homeostasis ; }, abstract = {Neurons are highly polarized, post-mitotic cells that are characterized by unique morphological diversity and complexity. As highly differentiated cells that need to survive throughout organismal lifespan, neurons face exceptional energy challenges in time and space. Therefore, neurons are heavily dependent on a healthy mitochondrial network for their proper function and maintenance under both physiological and stress conditions. Multiple quality control systems have evolved to fine-tune mitochondrial number and quality, thus preserving neuronal energy homeostasis. Here, we review the contribution of mitophagy, a selective form of autophagy that targets dysfunctional or superfluous mitochondria for degradation, in maintaining nervous system homeostasis. In addition, we discuss recent evidence implicating defective or dysregulated mitophagy in the pathogenesis of neurodegenerative diseases.}, } @article {pmid37279941, year = {2023}, author = {Sheikh, S and Pánek, T and Gahura, O and Týč, J and Záhonová, K and Lukeš, J and Eliáš, M and Hashimi, H}, title = {A Novel Group of Dynamin-Related Proteins Shared by Eukaryotes and Giant Viruses Is Able to Remodel Mitochondria From Within the Matrix.}, journal = {Molecular biology and evolution}, volume = {40}, number = {6}, pages = {}, pmid = {37279941}, issn = {1537-1719}, mesh = {*Giant Viruses/genetics/metabolism ; Phylogeny ; Mitochondrial Proteins/genetics/metabolism ; Mitochondria/genetics/metabolism ; Dynamins/genetics/metabolism ; Saccharomyces cerevisiae/genetics ; }, abstract = {The diverse GTPases of the dynamin superfamily play various roles in the cell, as exemplified by the dynamin-related proteins (DRPs) Mgm1 and Opa1, which remodel the mitochondrial inner membrane in fungi and metazoans, respectively. Via an exhaustive search of genomic and metagenomic databases, we found previously unknown DRP types occurring in diverse eukaryotes and giant viruses (phylum Nucleocytoviricota). One novel DRP clade, termed MidX, combined hitherto uncharacterized proteins from giant viruses and six distantly related eukaryote taxa (Stramenopiles, Telonemia, Picozoa, Amoebozoa, Apusomonadida, and Choanoflagellata). MidX stood out because it was not only predicted to be mitochondria-targeted but also to assume a tertiary structure not observed in other DRPs before. To understand how MidX affects mitochondria, we exogenously expressed MidX from Hyperionvirus in the kinetoplastid Trypanosoma brucei, which lacks Mgm1 or Opa1 orthologs. MidX massively affected mitochondrial morphology from inside the matrix, where it closely associates with the inner membrane. This unprecedented mode of action contrasts to those of Mgm1 and Opa1, which mediate inner membrane remodeling in the intermembrane space. We speculate that MidX was acquired in Nucleocytoviricota evolution by horizontal gene transfer from eukaryotes and is used by giant viruses to remodel host mitochondria during infection. MidX's unique structure may be an adaptation for reshaping mitochondria from the inside. Finally, Mgm1 forms a sister group to MidX and not Opa1 in our phylogenetic analysis, throwing into question the long-presumed homology of these DRPs with similar roles in sister lineages.}, } @article {pmid37282330, year = {1989}, author = {Andreuccetti, P}, title = {Ultrastructural Observations on the Germ Plasm in the Lizard Podarcis sicula: (germ plasm/germ cells/ultrastructure/reptiles).}, journal = {Development, growth & differentiation}, volume = {31}, number = {3}, pages = {269-273}, doi = {10.1111/j.1440-169X.1989.00269.x}, pmid = {37282330}, issn = {1440-169X}, abstract = {Ultrastructural studies on embryos and adult females of Podarcis sicula revealed fibrogranular electron-dense aggregates in the cytoplasm of primordial germ cells, oogonia, and oocytes. The ultrastructural similarities of these aggregates to fibrogranular aggregates in germ cells of some animal species and their relationship with mitochondria, free ribosomes, as well as cisternae of the rough endoplasmic reticulum strongly suggest that they correspond to the germ plasm.}, } @article {pmid37286063, year = {2023}, author = {Abalde, S and Crocetta, F and Tenorio, MJ and D'Aniello, S and Fassio, G and Rodríguez-Flores, PC and Uribe, JE and Afonso, CML and Oliverio, M and Zardoya, R}, title = {Hidden species diversity and mito-nuclear discordance within the Mediterranean cone snail, Lautoconus ventricosus.}, journal = {Molecular phylogenetics and evolution}, volume = {186}, number = {}, pages = {107838}, doi = {10.1016/j.ympev.2023.107838}, pmid = {37286063}, issn = {1095-9513}, mesh = {Humans ; Animals ; Phylogeny ; *Mitochondria/genetics ; Genetic Speciation ; *Genome, Mitochondrial ; Snails/genetics ; DNA, Mitochondrial/genetics ; }, abstract = {The Mediterranean cone snail, Lautoconus ventricosus, is currently considered a single species inhabiting the whole Mediterranean basin and the adjacent Atlantic coasts. Yet, no population genetic study has assessed its taxonomic status. Here, we collected 245 individuals from 75 localities throughout the Mediterranean Sea and used cox1 barcodes, complete mitochondrial genomes, and genome skims to test whether L. ventricosus represents a complex of cryptic species. The maximum likelihood phylogeny based on complete mitochondrial genomes recovered six main clades (hereby named blue, brown, green, orange, red, and violet) with sufficient sequence divergence to be considered putative species. On the other hand, phylogenomic analyses based on 437 nuclear genes only recovered four out of the six clades: blue and orange clades were thoroughly mixed and the brown one was not recovered. This mito-nuclear discordance revealed instances of incomplete lineage sorting and introgression, and may have caused important differences in the dating of main cladogenetic events. Species delimitation tests proposed the existence of at least three species: green, violet, and red + blue + orange (i.e., cyan). Green plus cyan (with sympatric distributions) and violet, had West and East Mediterranean distributions, respectively, mostly separated by the Siculo-Tunisian biogeographical barrier. Morphometric analyses of the shell using species hypotheses as factor and shell length as covariate showed that the discrimination power of the studied parameters was only 70.2%, reinforcing the cryptic nature of the uncovered species, and the importance of integrative taxonomic approaches considering morphology, ecology, biogeography, and mitochondrial and nuclear population genetic variation.}, } @article {pmid37289794, year = {2023}, author = {Hebert, PDN and Bock, DG and Prosser, SWJ}, title = {Interrogating 1000 insect genomes for NUMTs: A risk assessment for estimates of species richness.}, journal = {PloS one}, volume = {18}, number = {6}, pages = {e0286620}, pmid = {37289794}, issn = {1932-6203}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; *Genome, Insect ; Mitochondria/genetics ; Insecta/genetics ; Risk Assessment ; Cell Nucleus/genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {The nuclear genomes of most animal species include NUMTs, segments of the mitogenome incorporated into their chromosomes. Although NUMT counts are known to vary greatly among species, there has been no comprehensive study of their frequency/attributes in the most diverse group of terrestrial organisms, insects. This study examines NUMTs derived from a 658 bp 5' segment of the cytochrome c oxidase I (COI) gene, the barcode region for the animal kingdom. This assessment is important because unrecognized NUMTs can elevate estimates of species richness obtained through DNA barcoding and derived approaches (eDNA, metabarcoding). This investigation detected nearly 10,000 COI NUMTs ≥ 100 bp in the genomes of 1,002 insect species (range = 0-443). Variation in nuclear genome size explained 56% of the mitogenome-wide variation in NUMT counts. Although insect orders with the largest genome sizes possessed the highest NUMT counts, there was considerable variation among their component lineages. Two thirds of COI NUMTs possessed an IPSC (indel and/or premature stop codon) allowing their recognition and exclusion from downstream analyses. The remainder can elevate species richness as they showed 10.1% mean divergence from their mitochondrial homologue. The extent of exposure to "ghost species" is strongly impacted by the target amplicon's length. NUMTs can raise apparent species richness by up to 22% when a 658 bp COI amplicon is examined versus a doubling of apparent richness when 150 bp amplicons are targeted. Given these impacts, metabarcoding and eDNA studies should target the longest possible amplicons while also avoiding use of 12S/16S rDNA as they triple NUMT exposure because IPSC screens cannot be employed.}, } @article {pmid37291154, year = {2023}, author = {Lee, Y and Cho, CH and Noh, C and Yang, JH and Park, SI and Lee, YM and West, JA and Bhattacharya, D and Jo, K and Yoon, HS}, title = {Origin of minicircular mitochondrial genomes in red algae.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3363}, pmid = {37291154}, issn = {2041-1723}, mesh = {Phylogeny ; *Genome, Mitochondrial/genetics ; Eukaryotic Cells ; Mitochondria/genetics ; *Rhodophyta/genetics ; Evolution, Molecular ; }, abstract = {Eukaryotic organelle genomes are generally of conserved size and gene content within phylogenetic groups. However, significant variation in genome structure may occur. Here, we report that the Stylonematophyceae red algae contain multipartite circular mitochondrial genomes (i.e., minicircles) which encode one or two genes bounded by a specific cassette and a conserved constant region. These minicircles are visualized using fluorescence microscope and scanning electron microscope, proving the circularity. Mitochondrial gene sets are reduced in these highly divergent mitogenomes. Newly generated chromosome-level nuclear genome assembly of Rhodosorus marinus reveals that most mitochondrial ribosomal subunit genes are transferred to the nuclear genome. Hetero-concatemers that resulted from recombination between minicircles and unique gene inventory that is responsible for mitochondrial genome stability may explain how the transition from typical mitochondrial genome to minicircles occurs. Our results offer inspiration on minicircular organelle genome formation and highlight an extreme case of mitochondrial gene inventory reduction.}, } @article {pmid37295735, year = {2023}, author = {Gul, I and Abbas, MN and Kausar, S and Luo, J and Gao, X and Mu, Y and Fan, W and Cui, H}, title = {Insight into crustacean cathepsins: Structure-evolutionary relationships and functional roles in physiological processes.}, journal = {Fish & shellfish immunology}, volume = {139}, number = {}, pages = {108852}, doi = {10.1016/j.fsi.2023.108852}, pmid = {37295735}, issn = {1095-9947}, mesh = {Animals ; *Cathepsins/genetics/chemistry ; Proteins ; Biological Evolution ; *Physiological Phenomena ; }, abstract = {Cathepsins belong to a group of proteins that are present in both prokaryotic and eukaryotic organisms and have an extremely high degree of evolutionary conservation. These proteins are functionally active in extracellular environments as soluble enzymatic proteins or attached to plasma membrane receptors. In addition, they occur in cellular secretory vesicles, mitochondria, the cytosol, and within the nuclei of eukaryotic cells. Cathepsins are classified into various groups based on their sequence variations, leading to their structural and functional diversification. The molecular understanding of the physiology of crustaceans has shown that proteases, including cathepsins, are expressed ubiquitously. They also contain one of the central regulatory systems for crustacean reproduction, growth, and immune responses. This review focuses on various aspects of the crustaceans cathepsins and emphasizes their biological roles in different physiological processes such as reproduction, growth, development, and immune responses. We also describe the bioactivity of crustaceans cathepsins. Because of the vital biological roles that cathepsins play as cellular proteases in physiological processes, they have been proposed as potential novel targets for the development of management strategies for the aquaculture industries.}, } @article {pmid37299482, year = {2023}, author = {Manilla, V and Santopaolo, F and Gasbarrini, A and Ponziani, FR}, title = {Type 2 Diabetes Mellitus and Liver Disease: Across the Gut-Liver Axis from Fibrosis to Cancer.}, journal = {Nutrients}, volume = {15}, number = {11}, pages = {}, pmid = {37299482}, issn = {2072-6643}, mesh = {Humans ; *Non-alcoholic Fatty Liver Disease/metabolism ; *Diabetes Mellitus, Type 2/complications/pathology ; *Carcinoma, Hepatocellular/metabolism ; Dysbiosis/complications/pathology ; *Liver Neoplasms/metabolism ; Liver/metabolism ; Liver Cirrhosis ; Fibrosis ; }, abstract = {Type 2 diabetes mellitus is a widespread disease worldwide, and is one of the cornerstones of metabolic syndrome. The existence of a strong relationship between diabetes and the progression of liver fibrosis has been demonstrated by several studies, using invasive and noninvasive techniques. Patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) show faster progression of fibrosis than patients without diabetes. Many confounding factors make it difficult to determine the exact mechanisms involved. What we know so far is that both liver fibrosis and T2DM are expressions of metabolic dysfunction, and we recognize similar risk factors. Interestingly, both are promoted by metabolic endotoxemia, a low-grade inflammatory condition caused by increased endotoxin levels and linked to intestinal dysbiosis and increased intestinal permeability. There is broad evidence on the role of the gut microbiota in the progression of liver disease, through both metabolic and inflammatory mechanisms. Therefore, dysbiosis that is associated with diabetes can act as a modifier of the natural evolution of NAFLD. In addition to diet, hypoglycemic drugs play an important role in this scenario, and their benefit is also the result of effects exerted in the gut. Here, we provide an overview of the mechanisms that explain why diabetic patients show a more rapid progression of liver disease up to hepatocellular carcinoma (HCC), focusing especially on those involving the gut-liver axis.}, } @article {pmid37303610, year = {2023}, author = {Liang, Y and Fang, X and Zheng, L and Wu, H and He, Z and Xiong, Z and Hong, J and Ai, X and Liang, G}, title = {The complete mitochondrial genome of Choristoneura metasequoiacola Liu,1983 (Lepidoptera: Tortricidae).}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {8}, number = {6}, pages = {653-657}, pmid = {37303610}, issn = {2380-2359}, abstract = {Choristoneura metasequoiacola Liu, 1983 is an important caterpillar species that specifically infests the leaves and branches of Metasequoia glyptostroboides Hu & W. C. Cheng 1948 with short larval infestations, long-term dormancy, and has a limited distribution in Lichuan, Hubei, China. The complete mitochondria genome of C. metasequoiacola was determined by using Illumina NovaSeq, and analyzed based on previously annotated sibling species. In total, we obtained mitochondria genome with 15,128 bp in length, circular in shape with a double-stranded closed ring structure, including 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and an AT-rich region. Of which the nucleotide composition was highly A + T biased, accounting for 81.98% of the whole mitogenome. Thirteen protein-coding genes (PCGs) were 11,142 bp; Twenty-two tRNA genes and AT-rich region were 1,472 and 199 bp, respectively. Phylogenetically, the relationship between Choristoneura spp. (containing C. metasequoiacola) and Adoxophyes spp. was closer than any other two genera from Tortricidae, and the relationship between C. metasequoiacola and C.murinana was the closest among nine sibling species from that genus, which helps to explain species evolution within the family Tortricidae.}, } @article {pmid37305924, year = {2023}, author = {Floriano, AM and Batisti Biffignandi, G and Castelli, M and Olivieri, E and Clementi, E and Comandatore, F and Rinaldi, L and Opara, M and Plantard, O and Palomar, AM and Noël, V and Vijay, A and Lo, N and Makepeace, BL and Duron, O and Jex, A and Guy, L and Sassera, D}, title = {The evolution of intramitochondriality in Midichloria bacteria.}, journal = {Environmental microbiology}, volume = {25}, number = {11}, pages = {2102-2117}, doi = {10.1111/1462-2920.16446}, pmid = {37305924}, issn = {1462-2920}, mesh = {Animals ; *Ixodes/microbiology ; Bacteria/genetics ; Mitochondria/genetics ; Phylogeny ; Symbiosis ; }, abstract = {Midichloria spp. are intracellular bacterial symbionts of ticks. Representatives of this genus colonise mitochondria in the cells of their hosts. To shed light on this unique interaction we evaluated the presence of an intramitochondrial localization for three Midichloria in the respective tick host species and generated eight high-quality draft genomes and one closed genome, showing that this trait is non-monophyletic, either due to losses or multiple acquisitions. Comparative genomics supports the first hypothesis, as the genomes of non-mitochondrial symbionts are reduced subsets of those capable of colonising the organelles. We detect genomic signatures of mitochondrial tropism, including the differential presence of type IV secretion system and flagellum, which could allow the secretion of unique effectors and/or direct interaction with mitochondria. Other genes, including adhesion molecules, proteins involved in actin polymerisation, cell wall and outer membrane proteins, are only present in mitochondrial symbionts. The bacteria could use these to manipulate host structures, including mitochondrial membranes, to fuse with the organelles or manipulate the mitochondrial network.}, } @article {pmid37309528, year = {2021}, author = {Yang, W and Zou, J and Yu, Y and Long, W and Li, S}, title = {Repeats in mitochondrial and chloroplast genomes characterize the ecotypes of the Oryza.}, journal = {Molecular breeding : new strategies in plant improvement}, volume = {41}, number = {1}, pages = {7}, pmid = {37309528}, issn = {1572-9788}, abstract = {UNLABELLED: Mitochondria and chloroplast are very important organelles for organism, participating in basic life activity. Their genomes contain many repeats which can lead to a variation of genome structure. Oryza is an important genus for human beings' nutrition. Several mitochondrial and chloroplast genomes of Oryza have been sequenced, which help us to insight the distribution and evolution of the repeats in Oryza species. In this paper, we compared six mitochondrial and 13 chloroplast genomes of Oryza and found that the structures of mitochondrial genomes were more diverse than chloroplast genomes. Since repeats can change the structure of the genome, resulting in the structural diversity of the genome, we analyzed all repeats and found 31 repeats in mitochondrial and 13 repeats in chloroplast genomes. Further, we developed 21 pairs of MRS molecular markers and 12 pairs of CRS molecular markers based on mitochondrial repeats and chloroplast repeats, respectively. These molecular markers can be used to detect the repeat-mediated recombination in Oryza mitochondrial and chloroplast genomes by PCR or fluorescence quantification.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11032-020-01198-6.}, } @article {pmid37311262, year = {2023}, author = {Annes, K and Ferreira, CR and Valente, RS and Marsico, TV and Tannura, JH and da Silveira, JC and Silva, FH and Landim-Alvarenga, FDC and Mesquista, FS and Sudano, MJ}, title = {Contribution of lipids to the organelle differential profile of in vitro-produced bovine embryos.}, journal = {Theriogenology}, volume = {208}, number = {}, pages = {109-118}, doi = {10.1016/j.theriogenology.2023.06.005}, pmid = {37311262}, issn = {1879-3231}, mesh = {Female ; Pregnancy ; Cattle ; Animals ; *Endoplasmic Reticulum ; *Mitochondria ; Lipid Droplets ; Blastocyst ; Ceramides ; }, abstract = {Each living organism is unique because of the lipid identity of its organelles. The diverse distribution of these molecules also contributes to the role of each organelle in cellular activity. The lipid profiles of whole embryos are well documented in the literature. However, this approach can often lead to the loss of relevant information at the subcellular and consequently, metabolic levels, hindering a deeper understanding of key physiological processes during preimplantation development. Therefore, we aimed to characterize four organelles in vitro-produced bovine embryos: lipid droplets (LD), endoplasmic reticulum (ER), mitochondria (MIT), and nuclear membrane (NUC), and evaluate the contribution of the lipid species to each organelle evaluated. Expanded blastocysts were subjected to cell organelle isolation. Thereafter, lipid extraction from cell organelles and lipid analysis using the Multiple Reaction Monitoring (MRM) profiling method were performed. The LD and ER displayed a greater number of lipids (Phosphatidylcholine - PC, Ceramide - Cer, and Sphingomielin - SM) with high signal-to-noise intensities. This result is due to the high rate of biosynthesis, lipid distribution, and ability to store and recycle lipid species of these organelles. The NUC had a more distinct lipid profile than the other three organelles, with high relative intensities of PC, SM, and triacylglycerols (TG), which is consistent with its high nuclear activity. MIT had an intermediate profile that was close to that of LD and ER, which aligns with its autonomous metabolism for some classes of phospholipids (PL). Our study revealed the lipid composition of each organelle studied, and the roles of these lipids could be associated with the characteristic organellar activity. Our findings highlight the lipid species and classes that are relevant for the homeostasis and function of each associated organelle and provide tentative biomarkers for the determination of in vitro embryonic development and quality.}, } @article {pmid37325898, year = {2023}, author = {Sabbah, HN and Taylor, C and Vernon, HJ}, title = {Temporal evolution of the heart failure phenotype in Barth syndrome and treatment with elamipretide.}, journal = {Future cardiology}, volume = {19}, number = {4}, pages = {211-225}, doi = {10.2217/fca-2023-0008}, pmid = {37325898}, issn = {1744-8298}, mesh = {Humans ; *Barth Syndrome/genetics/pathology ; *Heart Failure/drug therapy ; Stroke Volume ; Phenotype ; Cardiolipins ; Oligopeptides ; }, abstract = {Barth syndrome (BTHS) is a rare genetic disorder caused by pathogenic variants in TAFAZZIN leading to reduced remodeled cardiolipin (CL), a phospholipid essential to mitochondrial function and structure. Cardiomyopathy presents in most patients with BTHS, typically appearing as dilated cardiomyopathy (DCM) in infancy and evolving to hypertrophic cardiomyopathy (HCM) resembling heart failure (HF) with preserved ejection fraction (HFpEF) in some patients ≥12 years. Elamipretide localizes to the inner mitochondrial membrane where it associates with CL, improving mitochondrial function, structure and bioenergetics, including ATP synthesis. Numerous preclinical and clinical studies in BTHS and other forms of HF have demonstrated that elamipretide improves left ventricular relaxation by ameliorating mitochondrial dysfunction, making it well suited for therapeutic use in adolescent and adult patients with BTHS.}, } @article {pmid37327832, year = {2023}, author = {Thacker, CE and Tyler McCraney, W and Harrington, RC and Near, TJ and Shelley, JJ and Adams, M and Hammer, MP and Unmack, PJ}, title = {Diversification of the sleepers (Gobiiformes: Gobioidei: Eleotridae) and evolution of the root gobioid families.}, journal = {Molecular phylogenetics and evolution}, volume = {186}, number = {}, pages = {107841}, doi = {10.1016/j.ympev.2023.107841}, pmid = {37327832}, issn = {1095-9513}, mesh = {Humans ; Animals ; Phylogeny ; *Fishes/genetics ; *Perciformes/genetics ; Mitochondria ; Fossils ; }, abstract = {Eleotridae (sleepers) and five smaller families are the earliest diverging lineages within Gobioidei. Most inhabit freshwaters in and around the Indo-Pacific, but Eleotridae also includes species that have invaded the Neotropics as well as several inland radiations in the freshwaters of Australia, New Zealand, and New Guinea. Previous efforts to infer phylogeny of these families have been based on sets of mitochondrial or nuclear loci and have yielded uncertain resolution of clades within Eleotridae. We expand the taxon sampling of previous studies and use genomic data from nuclear ultraconserved elements (UCEs) to infer phylogeny, then calibrate the hypothesis with recently discovered fossils. Our hypothesis clarifies ambiguously resolved relationships, provides a timescale for divergences, and indicates the core crown Eleotridae diverged over a short period 24.3-26.3 Ma in the late Oligocene. Within Eleotridae, we evaluate diversification dynamics with BAMM and find evidence for an overall slowdown in diversification over the past 35 Ma, but with a sharp increase 3.5 Ma in the genus Mogurnda, a clade of brightly colored species found in the freshwaters of Australia and New Guinea.}, } @article {pmid37330026, year = {2023}, author = {Nguyen, TP and Nguyen, BT and Dao, TNL and Ho, TH and Lee, PT}, title = {Investigation of the functional role of UNC93B1 in Nile tilapia (Oreochromis niloticus): mRNA expression, subcellular localization, and physical interaction with fish-specific TLRs.}, journal = {Fish & shellfish immunology}, volume = {139}, number = {}, pages = {108902}, doi = {10.1016/j.fsi.2023.108902}, pmid = {37330026}, issn = {1095-9947}, mesh = {Humans ; Animals ; Mice ; *Cichlids ; Phylogeny ; Fish Proteins/chemistry ; Toll-Like Receptors/genetics/metabolism ; Phagocytosis ; Streptococcus agalactiae/physiology ; *Fish Diseases ; *Streptococcal Infections/veterinary ; Gene Expression Regulation ; Immunity, Innate/genetics ; Membrane Transport Proteins/genetics ; }, abstract = {Nile tilapia (Oreochromis niloticus) is one of the major food fish worldwide. The farming business, on the other hand, has faced considerable obstacles, such as disease infestations. Toll-like receptors (TLRs) play an important function in the activation of the innate immune system in response to infections. Unc-93 homolog B1 (UNC93B1) is a key regulator of nucleic acid (NA)-sensing TLRs. Here the UNC93B1 gene, which was cloned from Nile tilapia tissue for this investigation, had the same genetic structure as a homologous gene in humans and mice. Phylogenetic analysis revealed that Nile tilapia UNC93B1 clustered with UNC93B1 from other species and separately from the UNC93A clade. The gene structure of the Nile tilapia UNC93B1 was found to be identical to that of human UNC93B1. Our gene expression studies revealed that Nile tilapia UNC93B1 was highly expressed in the spleen, followed by other immune-related tissues such as the head kidney, gills, and intestine. Moreover, Nile tilapia UNC93B1 mRNA transcripts were up-regulated in vivo in the head kidney and spleen tissues from poly I:C and Streptococcus agalactiae injected Nile tilapia, as well as in vitro in LPS stimulated Tilapia head kidney (THK) cells. The Nile tilapia UNC93B1-GFP protein signal was detected in the cytosol of THK cells and was co-localized with endoplasmic reticulum and lysosome but not with mitochondria. Moreover, the results of a co-immunoprecipitation and immunostaining analysis showed that Nile tilapia UNC93B1 can be pulled down with fish-specific TLRs such as TLR18 and TLR25 from Nile tilapia, and was found to be co-localized with these fish-specific TLRs in the THK cells. Overall, our findings highlight the potential role of UNC93B1 as an accessory protein in fish-specific TLR signaling.}, } @article {pmid37333265, year = {2023}, author = {Hanson, SE and Doyle, MT and Bernstein, HD}, title = {The patatin-like protein PlpD forms novel structurally dynamic homodimers in the Pseudomonas aeruginosa outer membrane.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37333265}, issn = {2692-8205}, abstract = {Members of the Omp85 superfamily of outer membrane proteins (OMPs) found in Gram-negative bacteria, mitochondria and chloroplasts are characterized by a distinctive 16-stranded β-barrel transmembrane domain and at least one periplasmic POTRA domain. All previously studied Omp85 proteins promote critical OMP assembly and/or protein translocation reactions. Pseudomonas aeruginosa PlpD is the prototype of an Omp85 protein family that contains an N-terminal patatin-like (PL) domain that is thought to be translocated across the OM by a C-terminal β-barrel domain. Challenging the current dogma, we found that the PlpD PL-domain resides exclusively in the periplasm and, unlike previously studied Omp85 proteins, PlpD forms a homodimer. Remarkably, the PL-domain contains a segment that exhibits unprecedented dynamicity by undergoing transient strand-swapping with the neighboring β-barrel domain. Our results show that the Omp85 superfamily is more structurally diverse than currently believed and suggest that the Omp85 scaffold was utilized during evolution to generate novel functions.}, } @article {pmid37336341, year = {2023}, author = {Liu, S and Xu, S and Liu, S and Chen, H}, title = {Importance of DJ-1 in autophagy regulation and disease.}, journal = {Archives of biochemistry and biophysics}, volume = {743}, number = {}, pages = {109672}, doi = {10.1016/j.abb.2023.109672}, pmid = {37336341}, issn = {1096-0384}, mesh = {Humans ; Reactive Oxygen Species/metabolism ; *Oxidative Stress/physiology ; Hypoxia/metabolism ; *Neoplasms ; Autophagy/physiology ; Protein Deglycase DJ-1/metabolism ; }, abstract = {Autophagy is a highly conserved biological process that has evolved across evolution. It can be activated by various external stimuli including oxidative stress, amino acid starvation, infection, and hypoxia. Autophagy is the primary mechanism for preserving cellular homeostasis and is implicated in the regulation of metabolism, cell differentiation, tolerance to starvation conditions, and resistance to aging. As a multifunctional protein, DJ-1 is commonly expressed in vivo and is associated with a variety of biological processes. Its most widely studied role is its function as an oxidative stress sensor that inhibits the production of excessive reactive oxygen species (ROS) in the mitochondria and subsequently the cellular damage caused by oxidative stress. In recent years, many studies have identified DJ-1 as another important factor regulating autophagy; it regulates autophagy in various ways, most commonly by regulating the oxidative stress response. In particular, DJ-1-regulated autophagy is involved in cancer progression and plays a key role in alleviating neurodegenerative diseases(NDS) and defective reperfusion diseases. It could serve as a potential target for the regulation of autophagy and participate in disease treatment as a meaningful modality. Therefore, exploring DJ-1-regulated autophagy could provide new avenues for future disease treatment.}, } @article {pmid37338543, year = {2023}, author = {Wong, JE and Zíková, A and Gahura, O}, title = {The Ancestral Shape of the Access Proton Path of Mitochondrial ATP Synthases Revealed by a Split Subunit-a.}, journal = {Molecular biology and evolution}, volume = {40}, number = {6}, pages = {}, pmid = {37338543}, issn = {1537-1719}, mesh = {*Mitochondrial Proton-Translocating ATPases/genetics/chemistry/metabolism ; *Proton-Translocating ATPases/metabolism ; Protons ; Eukaryota/metabolism ; Escherichia coli/genetics/metabolism ; Adenosine Triphosphate/metabolism ; }, abstract = {The passage of protons across membranes through F1Fo-ATP synthases spins their rotors and drives the synthesis of ATP. While the principle of torque generation by proton transfer is known, the mechanisms and routes of proton access and release and their evolution are not fully understood. Here, we show that the entry site and path of protons in the lumenal half channel of mitochondrial ATP synthases are largely defined by a short N-terminal α-helix of subunit-a. In Trypanosoma brucei and other Euglenozoa, the α-helix is part of another polypeptide chain that is a product of subunit-a gene fragmentation. This α-helix and other elements forming the proton pathway are widely conserved across eukaryotes and in Alphaproteobacteria, the closest extant relatives of mitochondria, but not in other bacteria. The α-helix blocks one of two proton routes found in Escherichia coli, resulting in a single proton entry site in mitochondrial and alphaproteobacterial ATP synthases. Thus, the shape of the access half channel predates eukaryotes and originated in the lineage from which mitochondria evolved by endosymbiosis.}, } @article {pmid37364099, year = {2023}, author = {Lynch, M}, title = {Mutation pressure, drift, and the pace of molecular coevolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {27}, pages = {e2306741120}, pmid = {37364099}, issn = {1091-6490}, support = {R35 GM122566/GM/NIGMS NIH HHS/United States ; R35-GM122566-01/NH/NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; Mutation ; *Mutation Rate ; Genome ; Genetic Drift ; }, abstract = {Most aspects of the molecular biology of cells involve tightly coordinated intermolecular interactions requiring specific recognition at the nucleotide and/or amino acid levels. This has led to long-standing interest in the degree to which constraints on interacting molecules result in conserved vs. accelerated rates of sequence evolution, with arguments commonly being made that molecular coevolution can proceed at rates exceeding the neutral expectation. Here, a fairly general model is introduced to evaluate the degree to which the rate of evolution at functionally interacting sites is influenced by effective population sizes (Ne), mutation rates, strength of selection, and the magnitude of recombination between sites. This theory is of particular relevance to matters associated with interactions between organelle- and nuclear-encoded proteins, as the two genomic environments often exhibit dramatic differences in the power of mutation and drift. Although genes within low Ne environments can drive the rate of evolution of partner genes experiencing higher Ne, rates exceeding the neutral expectation require that the former also have an elevated mutation rate. Testable predictions, some counterintuitive, are presented on how patterns of coevolutionary rates should depend on the relative intensities of drift, selection, and mutation.}, } @article {pmid37364695, year = {2023}, author = {Barrera, CA and Ortega, J and Gutierrez-Guerrero, YT and Baeza, JA}, title = {Comparative mitochondrial genomics of American nectar-feeding long-nosed bats Leptonycteris spp. with insights into the phylogeny of the family Phyllostomidae.}, journal = {Gene}, volume = {879}, number = {}, pages = {147588}, doi = {10.1016/j.gene.2023.147588}, pmid = {37364695}, issn = {1879-0038}, mesh = {Animals ; Phylogeny ; *Chiroptera/genetics ; Plant Nectar ; Genomics ; Mitochondria/genetics ; *Genome, Mitochondrial/genetics ; RNA, Transfer/genetics ; }, abstract = {Among leaf-nosed bats (family Phyllostomidae), the genus Leptonycteris (subfamily Glossophaginae), contains three migratory and obligate nectar-dwelling species of great ecological and economic importance; the greater long-nosed bat L. nivalis, the lesser long-nosed bat L. yerbabuenae, and the southern long-nosed bat L. curasoae. According to the IUCN, the three species are categorized as 'vulnerable', 'endangered', and 'near threatened', respectively. In this study, we assembled and characterized in detail the mitochondrial genome of Leptonycteris spp. and examined the phylogenetic position of this genus in the family Phyllostomidae based on protein coding genes (PCGs). The mitogenomes of L. nivalis, L. curasoae, and L. yerbabuenae are 16,708, 16,758, and 16,729 bp in length and each encode 13 PCGs, 22 transfer RNA genes, 2 rRNA genes, and a putative control region (CR). Mitochondrial gene order is identical to that reported before for the family Phyllostomidae. All tRNAs exhibit a 'cloverleaf' secondary structure, except tRNA-Serine-1 that is missing the DHU arm in the three species. All PCGs are exposed to purifying selection with atp8 experiencing the most relaxed purifying selection as the ω ratio was higher for this gene compared to the other PCGs in each species. The CR of each species contains three functional domains: extended termination associated sequence (ETAS), Central, and conserved sequence block domain (CSB). A phylomitogenomic analysis revealed that Leptonycteris is monophyletic and most closely related to the genus Glossophaga. The analysis also supported the monophyly of the family Glossophaginae in the speciose family Phyllostomidae. The mitochondria characterization of these species provides relevant information to develop molecular markers for conservation purposes.}, } @article {pmid37367622, year = {2023}, author = {van der Walt, D and Steenkamp, ET and Wingfield, BD and Wilken, PM}, title = {Evidence of Biparental Mitochondrial Inheritance from Self-Fertile Crosses between Closely Related Species of Ceratocystis.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {9}, number = {6}, pages = {}, pmid = {37367622}, issn = {2309-608X}, abstract = {Hybridization is recognized as a notable driver of evolution and adaptation, which closely related species may exploit in the form of incomplete reproductive barriers. Three closely related species of Ceratocystis (i.e., C. fimbriata, C. manginecans and C. eucalypticola) have previously been shown to hybridize. In such studies, naturally occurring self-sterile strains were mated with an unusual laboratory-generated sterile isolate type, which could have impacted conclusions regarding the prevalence of hybridization and inheritance of mitochondria. In the current study, we investigated whether interspecific crosses between fertile isolates of these three species are possible and, if so, how mitochondria are inherited by the progeny. For this purpose, a PCR-RFLP method and a mitochondrial DNA-specific PCR technique were custom-made. These were applied in a novel approach of typing complete ascospore drops collected from the fruiting bodies in each cross to distinguish between self-fertilizations and potential hybridization. These markers showed hybridization between C. fimbriata and C. eucalypticola and between C. fimbriata and C. manginecans, while no hybridization was detected in the crosses involving C. manginecans and C. eucalypticola. In both sets of hybrid progeny, we detected biparental inheritance of mitochondria. This study was the first to successfully produce hybrids from a cross involving self-fertile isolates of Ceratocystis and also provided the first direct evidence of biparental mitochondrial inheritance in the Ceratocystidaceae. This work lays the foundation for further research focused on investigating the role of hybridization in the speciation of Ceratocystis species and if mitochondrial conflict could have influenced the process.}, } @article {pmid37368881, year = {2023}, author = {Tanabe, TS and Grosser, M and Hahn, L and Kümpel, C and Hartenfels, H and Vtulkin, E and Flegler, W and Dahl, C}, title = {Identification of a novel lipoic acid biosynthesis pathway reveals the complex evolution of lipoate assembly in prokaryotes.}, journal = {PLoS biology}, volume = {21}, number = {6}, pages = {e3002177}, pmid = {37368881}, issn = {1545-7885}, mesh = {*Thioctic Acid/genetics/metabolism ; Peptide Synthases/genetics/metabolism ; Phylogeny ; Bacterial Proteins/metabolism ; Sulfur ; }, abstract = {Lipoic acid is an essential biomolecule found in all domains of life and is involved in central carbon metabolism and dissimilatory sulfur oxidation. The machineries for lipoate assembly in mitochondria and chloroplasts of higher eukaryotes, as well as in the apicoplasts of some protozoa, are all of prokaryotic origin. Here, we provide experimental evidence for a novel lipoate assembly pathway in bacteria based on a sLpl(AB) lipoate:protein ligase, which attaches octanoate or lipoate to apo-proteins, and 2 radical SAM proteins, LipS1 and LipS2, which work together as lipoyl synthase and insert 2 sulfur atoms. Extensive homology searches combined with genomic context analyses allowed us to precisely distinguish between the new and established pathways and map them on the tree of life. This not only revealed a much wider distribution of lipoate biogenesis systems than expected, in particular, the novel sLpl(AB)-LipS1/S2 pathway, and indicated a highly modular nature of the enzymes involved, with unforeseen combinations, but also provided a new framework for the evolution of lipoate assembly. Our results show that dedicated machineries for both de novo lipoate biogenesis and scavenging from the environment were implemented early in evolution and that their distribution in the 2 prokaryotic domains was shaped by a complex network of horizontal gene transfers, acquisition of additional genes, fusions, and losses. Our large-scale phylogenetic analyses identify the bipartite archaeal LplAB ligase as the ancestor of the bacterial sLpl(AB) proteins, which were obtained by horizontal gene transfer. LipS1/S2 have a more complex evolutionary history with multiple of such events but probably also originated in the domain archaea.}, } @article {pmid37371486, year = {2023}, author = {Ding, Y and Zhang, S and Guo, Q and Leng, J}, title = {Mitochondrial Diabetes Is Associated with the ND4 G11696A Mutation.}, journal = {Biomolecules}, volume = {13}, number = {6}, pages = {}, pmid = {37371486}, issn = {2218-273X}, mesh = {Adult ; Phylogeny ; *NADH Dehydrogenase/genetics ; *DNA, Mitochondrial/genetics ; *Mitochondria/genetics ; East Asian People ; Mutation ; Humans ; Aged ; *Diabetes Mellitus, Type 2/genetics ; Middle Aged ; }, abstract = {Type 2 diabetes mellitus (T2DM) is a common endocrine disorder which remains a large challenge for clinicians. Previous studies have suggested that mitochondrial dysfunction plays an active role in T2DM progression, but a detailed mechanism is still elusive. In the current study, two Han Chinese families with maternally inherited T2DM were evaluated using clinical, genetic, molecular, and biochemical analyses. The mitochondrial genomes were PCR amplified and sequenced. Phylogenetic and bioinformatic analyses were used to assess the potential pathogenicity of mitochondrial DNA (mtDNA) mutations. Interestingly, the matrilineal relatives of these pedigrees exhibited variable severity of T2DM, in particular, the age at onset of T2DM varied from 26 to 65 years, with an average of 49 years. Sequence analysis revealed the presence of ND4 G11696A mutation, which resulted in the substitution of an isoleucine for valine at amino acid (AA) position 312. Indeed, this mutation was present in homoplasmy only in the maternal lineage, not in other members of these families, as well as 200 controls. Furthermore, the m.C5601T in the tRNA[Ala] and novel m.T5813C in the tRNA[Cys], showing high evolutional conservation, may contribute to the phenotypic expression of ND4 G11696A mutation. In addition, biochemical analysis revealed that cells with ND4 G11696A mutation exhibited higher levels of reactive oxygen species (ROS) productions than the controls. In contrast, the levels of mitochondrial membrane potential (MMP), ATP, mtDNA copy number (mtDNA-CN), Complex I activity, and NAD[+]/NADH ratio significantly decreased in cell lines carrying the m.G11696A and tRNA mutations, suggesting that these mutations affected the respiratory chain function and led to mitochondrial dysfunction that was involved in T2DM. Thus, our study broadened the clinical phenotypes of m.G11696A mutation.}, } @article {pmid37381996, year = {2023}, author = {Zhao, JH and Chen, YC and Hua, ZY and Liu, TR and Zhao, YY and Huang, LQ and Yuan, Y}, title = {[Cloning and gene function of dicarboxylate-tricarboxylate carrier protein in Gastrodia elata].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {48}, number = {12}, pages = {3140-3148}, doi = {10.19540/j.cnki.cjcmm.20230310.102}, pmid = {37381996}, issn = {1001-5302}, mesh = {*Gastrodia/genetics ; Phylogeny ; Amino Acids ; Cloning, Molecular ; Carrier Proteins ; }, abstract = {The gene GeDTC encoding the dicarboxylate-tricarboxylate carrier protein in Gastrodia elata was cloned by specific primers which were designed based on the transcriptome data of G. elata. Bioinformatics analysis on GeDTC gene was carried out by using ExPASY, ClustalW, MEGA, etc. Positive transgenic plants and potato minituber were obtained by virtue of the potato genetic transformation system. Agronomic characters, such as size, weight, organic acid content, and starch content, of potato minituber were tested and analyzed and GeDTC gene function was preliminarily investigated. The results showed that the open reading frame of GeDTC gene was 981 bp in length and 326 amino acid residues were encoded, with a relative molecular weight of 35.01 kDa. It was predicted that the theoretical isoelectric point of GeDTC protein was 9.83, the instability coefficient was 27.88, and the average index of hydrophilicity was 0.104, which was indicative of a stable hydrophilic protein. GeDTC protein had a transmembrane structure and no signal peptide and was located in the inner membrane of mitochondria. The phylogenetic tree showed that GeDTC was highly homologous with DTC proteins of other plant species, among which GeDTC had the highest homology with DcDTC(XP_020675804.1) in Dendrobium candidum, reaching 85.89%. GeDTC overexpression vector pCambia1300-35Spro-GeDTC was constructed by double digests, and transgenic potato plants were obtained by Agrobacterium-mediated gene transformation. Compared with the wild-type plants, transgenic potato minituber harvested by transplanting had smaller size, lighter weight, lower organic acid content, and no significant difference in starch content. It is preliminarily induced that GeDTC is the efflux channel of tricarboxylate and related to the tuber development, which lays a foundation for further elucidating the molecular mechanism of G. elata tuber development.}, } @article {pmid37386734, year = {2023}, author = {Arnqvist, G and Rowe, L}, title = {Ecology, the pace-of-life, epistatic selection and the maintenance of genetic variation in life-history genes.}, journal = {Molecular ecology}, volume = {32}, number = {17}, pages = {4713-4724}, doi = {10.1111/mec.17062}, pmid = {37386734}, issn = {1365-294X}, mesh = {*Polymorphism, Genetic ; Selection, Genetic ; Biological Evolution ; Alleles ; *Life History Traits ; Models, Genetic ; Genetic Variation ; Epistasis, Genetic ; }, abstract = {Evolutionary genetics has long struggled with understanding how functional genes under selection remain polymorphic in natural populations. Taking as a starting point that natural selection is ultimately a manifestation of ecological processes, we spotlight an underemphasized and potentially ubiquitous ecological effect that may have fundamental effects on the maintenance of genetic variation. Negative frequency dependency is a well-established emergent property of density dependence in ecology, because the relative profitability of different modes of exploiting or utilizing limiting resources tends to be inversely proportional to their frequency in a population. We suggest that this may often generate negative frequency-dependent selection (NFDS) on major effect loci that affect rate-dependent physiological processes, such as metabolic rate, that are phenotypically manifested as polymorphism in pace-of-life syndromes. When such a locus under NFDS shows stable intermediate frequency polymorphism, this should generate epistatic selection potentially involving large numbers of loci with more minor effects on life-history (LH) traits. When alternative alleles at such loci show sign epistasis with a major effect locus, this associative NFDS will promote the maintenance of polygenic variation in LH genes. We provide examples of the kind of major effect loci that could be involved and suggest empirical avenues that may better inform us on the importance and reach of this process.}, } @article {pmid37389212, year = {2023}, author = {Stefano, GB and Büttiker, P and Weissenberger, S and Esch, T and Anders, M and Raboch, J and Kream, RM and Ptacek, R}, title = {Independent and sensory human mitochondrial functions reflecting symbiotic evolution.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1130197}, pmid = {37389212}, issn = {2235-2988}, mesh = {Humans ; *Mitochondria ; *Genes, Bacterial ; Quorum Sensing ; Virion ; }, abstract = {The bacterial origin of mitochondria has been a widely accepted as an event that occurred about 1.45 billion years ago and endowed cells with internal energy producing organelle. Thus, mitochondria have traditionally been viewed as subcellular organelle as any other - fully functionally dependent on the cell it is a part of. However, recent studies have given us evidence that mitochondria are more functionally independent than other organelles, as they can function outside the cells, engage in complex "social" interactions, and communicate with each other as well as other cellular components, bacteria and viruses. Furthermore, mitochondria move, assemble and organize upon sensing different environmental cues, using a process akin to bacterial quorum sensing. Therefore, taking all these lines of evidence into account we hypothesize that mitochondria need to be viewed and studied from a perspective of a more functionally independent entity. This view of mitochondria may lead to new insights into their biological function, and inform new strategies for treatment of disease associated with mitochondrial dysfunction.}, } @article {pmid37406344, year = {2023}, author = {Lamb, IM and Okoye, IC and Mather, MW and Vaidya, AB}, title = {Unique Properties of Apicomplexan Mitochondria.}, journal = {Annual review of microbiology}, volume = {77}, number = {}, pages = {541-560}, pmid = {37406344}, issn = {1545-3251}, support = {R01 AI028398/AI/NIAID NIH HHS/United States ; R01 AI100569/AI/NIAID NIH HHS/United States ; R01 AI132508/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Mitochondria/genetics/metabolism ; *Toxoplasma/metabolism ; Biological Evolution ; *Malaria ; }, abstract = {Apicomplexan parasites constitute more than 6,000 species infecting a wide range of hosts. These include important pathogens such as those causing malaria and toxoplasmosis. Their evolutionary emergence coincided with the dawn of animals. Mitochondrial genomes of apicomplexan parasites have undergone dramatic reduction in their coding capacity, with genes for only three proteins and ribosomal RNA genes present in scrambled fragments originating from both strands. Different branches of the apicomplexans have undergone rearrangements of these genes, with Toxoplasma having massive variations in gene arrangements spread over multiple copies. The vast evolutionary distance between the parasite and the host mitochondria has been exploited for the development of antiparasitic drugs, especially those used to treat malaria, wherein inhibition of the parasite mitochondrial respiratory chain is selectively targeted with little toxicity to the host mitochondria. We describe additional unique characteristics of the parasite mitochondria that are being investigated and provide greater insights into these deep-branching eukaryotic pathogens.}, } @article {pmid37407024, year = {2023}, author = {Healy, TM and Burton, RS}, title = {Genetic incompatibilities in reciprocal hybrids between populations of Tigriopus californicus with low to moderate mitochondrial sequence divergence.}, journal = {Evolution; international journal of organic evolution}, volume = {77}, number = {9}, pages = {2100-2108}, doi = {10.1093/evolut/qpad122}, pmid = {37407024}, issn = {1558-5646}, mesh = {Animals ; *Copepoda/genetics ; Mitochondria/genetics/metabolism ; Chromosomes ; Genome ; Genotype ; DNA, Mitochondrial/genetics ; }, abstract = {All mitochondrial-encoded proteins and RNAs function through interactions with nuclear-encoded proteins, which are critical for mitochondrial performance and eukaryotic fitness. Coevolution maintains inter-genomic (i.e., mitonuclear) compatibility within a taxon, but hybridization can disrupt coevolved interactions, resulting in hybrid breakdown. Thus, mitonuclear incompatibilities may be important mechanisms underlying reproductive isolation and, potentially, speciation. Here we utilize Pool-seq to assess the effects of mitochondrial genotype on nuclear allele frequencies in fast- and slow-developing reciprocal inter-population F2 hybrids between relatively low-divergence populations of the intertidal copepod Tigriopus californicus. We show that mitonuclear interactions lead to elevated frequencies of coevolved (i.e., maternal) nuclear alleles on two chromosomes in crosses between populations with 1.5% or 9.6% fixed differences in mitochondrial DNA nucleotide sequence. However, we also find evidence of excess mismatched (i.e., noncoevolved) alleles on three or four chromosomes per cross, respectively, and of allele frequency differences consistent with effects involving only nuclear loci (i.e., unaffected by mitochondrial genotype). Thus, our results for low-divergence crosses suggest an underlying role for mitonuclear interactions in variation in hybrid developmental rate, but despite substantial effects of mitonuclear coevolution on individual chromosomes, no clear bias favoring coevolved interactions overall.}, } @article {pmid37408243, year = {2023}, author = {Frigo, E and Tommasin, L and Lippe, G and Carraro, M and Bernardi, P}, title = {The Haves and Have-Nots: The Mitochondrial Permeability Transition Pore across Species.}, journal = {Cells}, volume = {12}, number = {10}, pages = {}, pmid = {37408243}, issn = {2073-4409}, mesh = {Animals ; *Mitochondrial Permeability Transition Pore/metabolism ; *Mitochondrial Membrane Transport Proteins/metabolism ; Drosophila melanogaster/metabolism ; Mitochondria/metabolism ; Saccharomyces cerevisiae/metabolism ; Adenosine Triphosphate/metabolism ; Mammals/metabolism ; }, abstract = {The demonstration that F1FO (F)-ATP synthase and adenine nucleotide translocase (ANT) can form Ca[2+]-activated, high-conductance channels in the inner membrane of mitochondria from a variety of eukaryotes led to renewed interest in the permeability transition (PT), a permeability increase mediated by the PT pore (PTP). The PT is a Ca[2+]-dependent permeability increase in the inner mitochondrial membrane whose function and underlying molecular mechanisms have challenged scientists for the last 70 years. Although most of our knowledge about the PTP comes from studies in mammals, recent data obtained in other species highlighted substantial differences that could be perhaps attributed to specific features of F-ATP synthase and/or ANT. Strikingly, the anoxia and salt-tolerant brine shrimp Artemia franciscana does not undergo a PT in spite of its ability to take up and store Ca[2+] in mitochondria, and the anoxia-resistant Drosophila melanogaster displays a low-conductance, selective Ca[2+]-induced Ca[2+] release channel rather than a PTP. In mammals, the PT provides a mechanism for the release of cytochrome c and other proapoptotic proteins and mediates various forms of cell death. In this review, we cover the features of the PT (or lack thereof) in mammals, yeast, Drosophila melanogaster, Artemia franciscana and Caenorhabditis elegans, and we discuss the presence of the intrinsic pathway of apoptosis and of other forms of cell death. We hope that this exercise may help elucidate the function(s) of the PT and its possible role in evolution and inspire further tests to define its molecular nature.}, } @article {pmid37408307, year = {2023}, author = {Yang, C and Li, X and Yang, L and Chen, S and Liao, J and Li, K and Zhou, J and Shen, W and Zhuang, X and Bai, M and Bassham, DC and Gao, C}, title = {A positive feedback regulation of SnRK1 signaling by autophagy in plants.}, journal = {Molecular plant}, volume = {16}, number = {7}, pages = {1192-1211}, doi = {10.1016/j.molp.2023.07.001}, pmid = {37408307}, issn = {1752-9867}, mesh = {Protein Serine-Threonine Kinases/genetics/metabolism ; *Arabidopsis Proteins/genetics/metabolism ; *Arabidopsis/metabolism ; Feedback ; Autophagy/genetics ; Gene Expression Regulation, Plant ; }, abstract = {SnRK1, an evolutionarily conserved heterotrimeric kinase complex that acts as a key metabolic sensor in maintaining energy homeostasis in plants, is an important upstream activator of autophagy that serves as a cellular degradation mechanism for the healthy growth of plants. However, whether and how the autophagy pathway is involved in regulating SnRK1 activity remains unknown. In this study, we identified a clade of plant-specific and mitochondria-localized FCS-like zinc finger (FLZ) proteins as currently unknown ATG8-interacting partners that actively inhibit SnRK1 signaling by repressing the T-loop phosphorylation of the catalytic α subunits of SnRK1, thereby negatively modulating autophagy and plant tolerance to energy deprivation caused by long-term carbon starvation. Interestingly, these AtFLZs are transcriptionally repressed by low-energy stress, and AtFLZ proteins undergo a selective autophagy-dependent pathway to be delivered to the vacuole for degradation, thereby constituting a positive feedback regulation to relieve their repression of SnRK1 signaling. Bioinformatic analyses show that the ATG8-FLZ-SnRK1 regulatory axis first appears in gymnosperms and seems to be highly conserved during the evolution of seed plants. Consistent with this, depletion of ATG8-interacting ZmFLZ14 confers enhanced tolerance, whereas overexpression of ZmFLZ14 leads to reduced tolerance to energy deprivation in maize. Collectively, our study reveals a previously unknown mechanism by which autophagy contributes to the positive feedback regulation of SnRK1 signaling, thereby enabling plants to better adapt to stressful environments.}, } @article {pmid37419430, year = {2023}, author = {Françoso, E and Zuntini, AR and Ricardo, PC and Araujo, NS and Silva, JPN and Brown, MJF and Arias, MC}, title = {The complete mitochondrial genome of Trigonisca nataliae (Hymenoptera, Apidae) assemblage reveals heteroplasmy in the control region.}, journal = {Gene}, volume = {881}, number = {}, pages = {147621}, doi = {10.1016/j.gene.2023.147621}, pmid = {37419430}, issn = {1879-0038}, mesh = {Bees/genetics ; Animals ; *Hymenoptera/genetics ; *Genome, Mitochondrial ; Heteroplasmy ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Phylogeny ; }, abstract = {The evolution of mitochondrial genomes in the stingless bees is surprisingly dynamic, making them a model system to understand mitogenome structure, function, and evolution. Out of the seven mitogenomes available in this group, five exhibit atypical characteristics, including extreme rearrangements, rapid evolution and complete mitogenome duplication. To further explore the mitogenome diversity in these bees, we utilized isolated mtDNA and Illumina sequencing to assemble the complete mitogenome of Trigonisca nataliae, a species found in Northern Brazil. The mitogenome of T. nataliae was highly conserved in gene content and structure when compared to Melipona species but diverged in the control region (CR). Using PCR amplification, cloning and Sanger sequencing, six different CR haplotypes, varying in size and content, were recovery. These findings indicate that heteroplasmy, where different mitochondrial haplotypes coexist within individuals, occurs in T. nataliae. Consequently, we argue that heteroplasmy might indeed be a common phenomenon in bees that could be associated with variations in mitogenome size and challenges encountered during the assembly process.}, } @article {pmid37424728, year = {2023}, author = {Gospodaryov, DV and Ballard, JWO and Camus, MF and DeSalle, R and Garvin, MR and Richter, U}, title = {Editorial: Energy-producing organelles and the nucleus: a phenomenal genomic friendship.}, journal = {Frontiers in genetics}, volume = {14}, number = {}, pages = {1230032}, pmid = {37424728}, issn = {1664-8021}, } @article {pmid37424790, year = {2023}, author = {Margenat, M and Betancour, G and Irving, V and Costábile, A and García-Cedrés, T and Portela, MM and Carrión, F and Herrera, FE and Villarino, A}, title = {Characteristics of Mycobacterium tuberculosis PtpA interaction and activity on the alpha subunit of human mitochondrial trifunctional protein, a key enzyme of lipid metabolism.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1095060}, pmid = {37424790}, issn = {2235-2988}, mesh = {Humans ; Lipid Metabolism ; *Mycobacterium tuberculosis ; Phylogeny ; Ubiquitins ; *Mitochondrial Trifunctional Protein/metabolism ; *Bacterial Proteins/metabolism ; }, abstract = {During Mycobacterium tuberculosis (Mtb) infection, the virulence factor PtpA belonging to the protein tyrosine phosphatase family is delivered into the cytosol of the macrophage. PtpA interacts with numerous eukaryotic proteins modulating phagosome maturation, innate immune response, apoptosis, and potentially host-lipid metabolism, as previously reported by our group. In vitro, the human trifunctional protein enzyme (hTFP) is a bona fide PtpA substrate, a key enzyme of mitochondrial β-oxidation of long-chain fatty acids, containing two alpha and two beta subunits arranged in a tetramer structure. Interestingly, it has been described that the alpha subunit of hTFP (ECHA, hTFPα) is no longer detected in mitochondria during macrophage infection with the virulent Mtb H37Rv. To better understand if PtpA could be the bacterial factor responsible for this effect, in the present work, we studied in-depth the PtpA activity and interaction with hTFPα. With this aim, we performed docking and in vitro dephosphorylation assays defining the P-Tyr-271 as the potential target of mycobacterial PtpA, a residue located in the helix-10 of hTFPα, previously described as relevant for its mitochondrial membrane localization and activity. Phylogenetic analysis showed that Tyr-271 is absent in TFPα of bacteria and is present in more complex eukaryotic organisms. These results suggest that this residue is a specific PtpA target, and its phosphorylation state is a way of regulating its subcellular localization. We also showed that phosphorylation of Tyr-271 can be catalyzed by Jak kinase. In addition, we found by molecular dynamics that PtpA and hTFPα form a stable protein complex through the PtpA active site, and we determined the dissociation equilibrium constant. Finally, a detailed study of PtpA interaction with ubiquitin, a reported PtpA activator, showed that additional factors are required to explain a ubiquitin-mediated activation of PtpA. Altogether, our results provide further evidence supporting that PtpA could be the bacterial factor that dephosphorylates hTFPα during infection, potentially affecting its mitochondrial localization or β-oxidation activity.}, } @article {pmid37429000, year = {2023}, author = {Wan, H and Zhang, Y and Wu, L and Zhou, G and Pan, L and Fernie, AR and Ruan, YL}, title = {Evolution of cytosolic and organellar invertases empowered the colonization and thriving of land plants.}, journal = {Plant physiology}, volume = {193}, number = {2}, pages = {1227-1243}, pmid = {37429000}, issn = {1532-2548}, mesh = {Humans ; Cytosol/metabolism ; *beta-Fructofuranosidase/metabolism ; Plants/genetics/metabolism ; *Embryophyta/metabolism ; Carbon/metabolism ; Evolution, Molecular ; }, abstract = {The molecular innovation underpinning efficient carbon and energy metabolism during evolution of land plants remains largely unknown. Invertase-mediated sucrose cleavage into hexoses is central to fuel growth. Why some cytoplasmic invertases (CINs) function in the cytosol, whereas others operate in chloroplasts and mitochondria, is puzzling. We attempted to shed light on this question from an evolutionary perspective. Our analyses indicated that plant CINs originated from a putatively orthologous ancestral gene in cyanobacteria and formed the plastidic CIN (α1 clade) through endosymbiotic gene transfer, while its duplication in algae with a loss of its signal peptide produced the β clade CINs in the cytosol. The mitochondrial CINs (α2) were derived from duplication of the plastidic CINs and coevolved with vascular plants. Importantly, the copy number of mitochondrial and plastidic CINs increased upon the emergence of seed plants, corresponding with the rise of respiratory, photosynthetic, and growth rates. The cytosolic CIN (β subfamily) kept expanding from algae to gymnosperm, indicating its role in supporting the increase in carbon use efficiency during evolution. Affinity purification mass spectrometry identified a cohort of proteins interacting with α1 and 2 CINs, which points to their roles in plastid and mitochondrial glycolysis, oxidative stress tolerance, and the maintenance of subcellular sugar homeostasis. Collectively, the findings indicate evolutionary roles of α1 and α2 CINs in chloroplasts and mitochondria for achieving high photosynthetic and respiratory rates, respectively, which, together with the expanding of cytosolic CINs, likely underpin the colonization of land plants through fueling rapid growth and biomass production.}, } @article {pmid37429369, year = {2023}, author = {Ahlawat, S and Sharma, U and Arora, R and Sharma, R and Chhabra, P and Veer Singh, K and Vijh, RK}, title = {Mitogenomic phylogeny reveals the predominance of the Nubian lineage of African wild ass in Indian donkeys.}, journal = {Gene}, volume = {880}, number = {}, pages = {147627}, doi = {10.1016/j.gene.2023.147627}, pmid = {37429369}, issn = {1879-0038}, mesh = {Animals ; Humans ; *Equidae/genetics ; Phylogeny ; *DNA, Mitochondrial/genetics ; Africa ; Domestication ; Haplotypes ; Genetic Variation ; }, abstract = {To contribute to the knowledge of maternal genetic diversity in domestic donkeys, this study investigated the mitochondrial DNA variations and analyzed the genetic structure in Indian donkeys based on 31 mitogenome sequences representing four breeds/populations (Agra, Halari, Kachchhi and Spiti). A total of 27 haplotypes with a haplotype diversity value of 0.989 were evident in the donkey genetic resources of India. The genetic differentiation between the investigated populations was evaluated using population pairwise FST values, which showed maximum differentiation between Kachchhi and Halari donkeys. The Neighbor-Joining (NJ) tree based on the whole mitogenome sequence and the Median-Joining (MJ) network for partial D-loop fragment showed clear demarcation of Indian donkeys into Nubian and Somali clades, substantiating African maternal origin of Indian domestic donkeys. The topology of the MJ network excluded the Asian wild asses as the possible progenitors of Indian donkeys. Halari and Agra donkeys showed conformity exclusively to the Nubian lineage of the African wild asses. However, representation of both the Nubian and Somali lineages was observed in Kachchhi and Spiti donkeys. Comprehensive analysis carried out by retrieving D-loop sequences from different countries representing Asia, Africa, Europe and South America revealed existence of shared haplotypes across geographically isolated regions of the globe. This observation is indicative of utility of donkeys as pack animals across inter-continental trading routes during development of human civilizations. Our results represent a valuable contribution to maternal genetic diversity of Indian donkeys and provide insights into the worldwide spread of the species following initial domestication in Africa.}, } @article {pmid37437976, year = {2023}, author = {Atayik, MC and Çakatay, U}, title = {Mitochondria-associated cellular senescence mechanisms: Biochemical and pharmacological perspectives.}, journal = {Advances in protein chemistry and structural biology}, volume = {136}, number = {}, pages = {117-155}, doi = {10.1016/bs.apcsb.2023.03.003}, pmid = {37437976}, issn = {1876-1631}, mesh = {*Mitochondria ; *Cellular Senescence ; Signal Transduction ; }, abstract = {Initially, endosymbiotic relation of mitochondria and other cellular compartments had been continued mutually. However, that evolutionary adaptation impaired because of the deterioration of endosymbiotic crosstalk due to aging and several pathological consequences in cellular redox status are seen, such as deterioration in redox integrity of mitochondria, interfered inter-organelle redox signaling and inefficient antioxidant response element mediated gene expression. Although the dysfunction of mitochondria is known to be a classical pattern of senescence, it is unresolved that why dysfunctional mitochondria is the core of senescence-associated secretory phenotype (SASP). Redox impairment and SASP-related disease development are generally together with weaken immunity. Impaired mitochondrial redox integrity and its ineffectiveness in immunity control render elders to be more prone to age-related diseases. As senotherapeutic agents, senolytics remove senescent cells whilst senomorphics/senostatics inhibits the secretion of SASP. Senotherapeutics and the novel approaches for ameliorating SASP-related unfavorable effects are recently thought to be promising ways as mitochondria-targeted gerotherapeutic options.}, } @article {pmid37451476, year = {2023}, author = {Záhonová, K and Valach, M and Tripathi, P and Benz, C and Opperdoes, FR and Barath, P and Lukáčová, V and Danchenko, M and Faktorová, D and Horváth, A and Burger, G and Lukeš, J and Škodová-Sveráková, I}, title = {Subunit composition of mitochondrial dehydrogenase complexes in diplonemid flagellates.}, journal = {Biochimica et biophysica acta. General subjects}, volume = {1867}, number = {9}, pages = {130419}, doi = {10.1016/j.bbagen.2023.130419}, pmid = {37451476}, issn = {1872-8006}, mesh = {*Mitochondria/metabolism ; *Pyruvate Dehydrogenase Complex/metabolism ; Multienzyme Complexes/metabolism ; Ketoglutarate Dehydrogenase Complex/metabolism ; Pyruvates/metabolism ; }, abstract = {In eukaryotes, pyruvate, a key metabolite produced by glycolysis, is converted by a tripartite mitochondrial pyruvate dehydrogenase (PDH) complex to acetyl-coenzyme A, which is fed into the tricarboxylic acid cycle. Two additional enzyme complexes with analogous composition catalyze similar oxidative decarboxylation reactions albeit using different substrates, the branched-chain ketoacid dehydrogenase (BCKDH) complex and the 2-oxoglutarate dehydrogenase (OGDH) complex. Comparative transcriptome analyses of diplonemids, one of the most abundant and diverse groups of oceanic protists, indicate that the conventional E1, E2, and E3 subunits of the PDH complex are lacking. E1 was apparently replaced in the euglenozoan ancestor of diplonemids by an AceE protein of archaeal type, a substitution that we also document in dinoflagellates. Here, we demonstrate that the mitochondrion of the model diplonemid Paradiplonema papillatum displays pyruvate and 2-oxoglutarate dehydrogenase activities. Protein mass spectrometry of mitochondria reveal that the AceE protein is as abundant as the E1 subunit of BCKDH. This corroborates the view that the AceE subunit is a functional component of the PDH complex. We hypothesize that by acquiring AceE, the diplonemid ancestor not only lost the eukaryotic-type E1, but also the E2 and E3 subunits of the PDH complex, which are present in other euglenozoans. We posit that the PDH activity in diplonemids seems to be carried out by a complex, in which the AceE protein partners with the E2 and E3 subunits from BCKDH and/or OGDH.}, } @article {pmid37453661, year = {2023}, author = {Dreishpoon, MB and Bick, NR and Petrova, B and Warui, DM and Cameron, A and Booker, SJ and Kanarek, N and Golub, TR and Tsvetkov, P}, title = {FDX1 regulates cellular protein lipoylation through direct binding to LIAS.}, journal = {The Journal of biological chemistry}, volume = {299}, number = {9}, pages = {105046}, pmid = {37453661}, issn = {1083-351X}, support = {R01 CA279550/CA/NCI NIH HHS/United States ; R35 CA242457/CA/NCI NIH HHS/United States ; R35 GM122595/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Humans ; Cell Proliferation/genetics ; Cell Respiration/genetics ; *Ferredoxins/genetics/metabolism ; *Lipoylation/genetics ; Metabolome ; Protein Binding ; *Sulfurtransferases/metabolism ; }, abstract = {Ferredoxins are a family of iron-sulfur (Fe-S) cluster proteins that serve as essential electron donors in numerous cellular processes that are conserved through evolution. The promiscuous nature of ferredoxins as electron donors enables them to participate in many metabolic processes including steroid, heme, vitamin D, and Fe-S cluster biosynthesis in different organisms. However, the unique natural function(s) of each of the two human ferredoxins (FDX1 and FDX2) are still poorly characterized. We recently reported that FDX1 is both a crucial regulator of copper ionophore-induced cell death and serves as an upstream regulator of cellular protein lipoylation, a mitochondrial lipid-based post-translational modification naturally occurring on four mitochondrial enzymes that are crucial for TCA cycle function. Here we show that FDX1 directly regulates protein lipoylation by binding the lipoyl synthase (LIAS) enzyme promoting its functional binding to the lipoyl carrier protein GCSH and not through indirect regulation of cellular Fe-S cluster biosynthesis. Metabolite profiling revealed that the predominant cellular metabolic outcome of FDX1 loss of function is manifested through the regulation of the four lipoylation-dependent enzymes ultimately resulting in loss of cellular respiration and sensitivity to mild glucose starvation. Transcriptional profiling established that FDX1 loss-of-function results in the induction of both compensatory metabolism-related genes and the integrated stress response, consistent with our findings that FDX1 loss-of-function is conditionally lethal. Together, our findings establish that FDX1 directly engages with LIAS, promoting its role in cellular protein lipoylation, a process essential in maintaining cell viability under low glucose conditions.}, } @article {pmid37453725, year = {2023}, author = {Shively, CA and Frye, BM and Negrey, JD and Johnson, CSC and Sutphen, CL and Molina, AJA and Yadav, H and Snyder-Mackler, N and Register, TC}, title = {The interactive effects of psychosocial stress and diet composition on health in primates.}, journal = {Neuroscience and biobehavioral reviews}, volume = {152}, number = {}, pages = {105320}, pmid = {37453725}, issn = {1873-7528}, support = {R01 AG054523/AG/NIA NIH HHS/United States ; R01 AG061805/AG/NIA NIH HHS/United States ; R01 HL122393/HL/NHLBI NIH HHS/United States ; T32 AG033534/AG/NIA NIH HHS/United States ; RF1 AG058829/AG/NIA NIH HHS/United States ; T32 AG052354/AG/NIA NIH HHS/United States ; R01 HL087103/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Primates ; Stress, Psychological ; Anxiety ; *Diet, Mediterranean ; Social Isolation ; }, abstract = {Social disadvantage and diet composition independently impact myriad dimensions of health. They are closely entwined, as social disadvantage often yields poor diet quality, and may interact to fuel differential health outcomes. This paper reviews effects of psychosocial stress and diet composition on health in nonhuman primates and their implications for aging and human health. We examined the effects of social subordination stress and Mediterranean versus Western diet on multiple systems. We report that psychosocial stress and Western diet have independent and additive adverse effects on hypothalamic-pituitary-adrenal and autonomic nervous system reactivity to psychological stressors, brain structure, and ovarian function. Compared to the Mediterranean diet, the Western diet resulted in accelerated aging, nonalcoholic fatty liver disease, insulin resistance, gut microbial changes associated with increased disease risk, neuroinflammation, neuroanatomical perturbations, anxiety, and social isolation. This comprehensive, multisystem investigation lays the foundation for future investigations of the mechanistic underpinnings of psychosocial stress and diet effects on health, and advances the promise of the Mediterranean diet as a therapeutic intervention on psychosocial stress.}, } @article {pmid37463427, year = {2023}, author = {Warren, JM and Broz, AK and Martinez-Hottovy, A and Elowsky, C and Christensen, AC and Sloan, DB}, title = {Rewiring of Aminoacyl-tRNA Synthetase Localization and Interactions in Plants With Extensive Mitochondrial tRNA Gene Loss.}, journal = {Molecular biology and evolution}, volume = {40}, number = {7}, pages = {}, pmid = {37463427}, issn = {1537-1719}, mesh = {*Amino Acyl-tRNA Synthetases/genetics ; RNA, Transfer/genetics ; Cell Nucleus/genetics ; Mitochondria/genetics ; Genome, Plant ; }, abstract = {The number of tRNAs encoded in plant mitochondrial genomes varies considerably. Ongoing loss of bacterial-like mitochondrial tRNA genes in many lineages necessitates the import of nuclear-encoded counterparts that share little sequence similarity. Because tRNAs are involved in highly specific molecular interactions, this replacement process raises questions about the identity and trafficking of enzymes necessary for the maturation and function of newly imported tRNAs. In particular, the aminoacyl-tRNA synthetases (aaRSs) that charge tRNAs are usually divided into distinct classes that specialize on either organellar (mitochondrial and plastid) or nuclear-encoded (cytosolic) tRNAs. Here, we investigate the evolution of aaRS subcellular localization in a plant lineage (Sileneae) that has experienced extensive and rapid mitochondrial tRNA loss. By analyzing full-length mRNA transcripts (PacBio Iso-Seq), we found predicted retargeting of many ancestrally cytosolic aaRSs to the mitochondrion and confirmed these results with colocalization microscopy assays. However, we also found cases where aaRS localization does not appear to change despite functional tRNA replacement, suggesting evolution of novel interactions and charging relationships. Therefore, the history of repeated tRNA replacement in Sileneae mitochondria reveals that differing constraints on tRNA/aaRS interactions may determine which of these alternative coevolutionary paths is used to maintain organellar translation in plant cells.}, } @article {pmid37464732, year = {2023}, author = {Wang, F and Zhang, N and Zhao, C and Song, Z and Caiyan, X}, title = {Codon usage bias analysis of mitochondrial protein-coding genes in 12 species of Candida.}, journal = {Journal of genetics}, volume = {102}, number = {}, pages = {}, pmid = {37464732}, issn = {0973-7731}, mesh = {Humans ; *Codon Usage ; *Candida/genetics ; Codon/genetics ; Mitochondrial Proteins/genetics ; Mitochondria/genetics ; Nucleotides/genetics ; }, abstract = {The incidence of diseases that are caused by fungal infection is gradually increasing, together with antibiotic abuse and the number of patients with hypoimmunity. The many challenges in clinical anti-fungi treatment include serious adverse effects and drug resistance. The mitochondria of fungi have been found to be closely associated with pathopoiesia and drug resistance. Hence, we investigated patterns in Candida mitochondrial genes codon usage bias to provide new information to guide anti-fungal research. According to the nucleotide composition results, most mitochondrial genes of the analysed Candida tended to use A/T bases rather than G/C bases. The relative synonymous codon usage values demonstrated that UUA, AGU, CCU, GCU, UGA, AGA and GGU were the common preferential codons of mitochondrial genes in 12 Candida species. Codon adaptation index (CAI) analysis indicated that the ATP9 of Candida parapsilosis had the highest value, and the ND6 of C. auris had the lowest value. The CAI clearly correlated with the codon bias index, except in C. maltose and C. viswanathii, and was significantly positively correlated with the average GC content. Together, our results suggested that the codon usage pattern is affected by multiple factors, among which GC content is critical. Nucleotide composition, selection pressure and mutation pressure influence codon bias in Candida mitochondrial genes, with dominant status to mutation pressure. Codon usage bias analyses of Candida mitochondrial genes may provide new insight into its evolution.}, } @article {pmid37479023, year = {2023}, author = {Boël, M and Voituron, Y and Roussel, D}, title = {Body mass dependence of oxidative phosphorylation efficiency in liver mitochondria from mammals.}, journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology}, volume = {284}, number = {}, pages = {111490}, doi = {10.1016/j.cbpa.2023.111490}, pmid = {37479023}, issn = {1531-4332}, mesh = {Animals ; *Oxidative Phosphorylation ; *Mitochondria, Liver/metabolism ; Adenosine Triphosphate/metabolism ; Mitochondria/metabolism ; Mammals/metabolism ; Oxygen Consumption/physiology ; }, abstract = {In eukaryotes, the performances of an organism are dependent on body mass and chemically supported by the mitochondrial production of ATP. Although the relationship between body mass and mitochondrial oxygen consumption is well described, the allometry of the transduction efficiency from oxygen to ATP production (ATP/O) is still poorly understood. Using a comparative approach, we investigated the oxygen consumption and ATP production of liver mitochondria from twelve species of mammals ranging from 5 g to 600 kg. We found that both oxygen consumption and ATP production are mass dependent but not the ATP/O at the maximal phosphorylating state. The results also showed that for sub-maximal phosphorylating states the ATP/O value positively correlated with body mass, irrespective of the metabolic intensity. This result contrasts with previous data obtained in mammalian muscles, suggesting a tissue-dependence of the body mass effect on mitochondrial efficiency.}, } @article {pmid37479726, year = {2023}, author = {Falchi, FA and Forti, F and Carnelli, C and Genco, A and Pizzoccheri, R and Manzari, C and Pavesi, G and Briani, F}, title = {Human PNPase causes RNA stabilization and accumulation of R-loops in the Escherichia coli model system.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {11771}, pmid = {37479726}, issn = {2045-2322}, mesh = {Humans ; *Escherichia coli/genetics ; *R-Loop Structures ; Causality ; Gene Expression Regulation ; RNA/genetics ; }, abstract = {Polyribonucleotide phosphorylase (PNPase) is a phosphorolytic RNA exonuclease highly conserved throughout evolution. In Escherichia coli, PNPase controls complex phenotypic traits like biofilm formation and growth at low temperature. In human cells, PNPase is located in mitochondria, where it is implicated in the RNA import from the cytoplasm, the mitochondrial RNA degradation and the processing of R-loops, namely stable RNA-DNA hybrids displacing a DNA strand. In this work, we show that the human PNPase (hPNPase) expressed in E. coli causes oxidative stress, SOS response activation and R-loops accumulation. Hundreds of E. coli RNAs are stabilized in presence of hPNPase, whereas only few transcripts are destabilized. Moreover, phenotypic traits typical of E. coli strains lacking PNPase are strengthened in presence of the human enzyme. We discuss the hypothesis that hPNPase expressed in E. coli may bind, but not degrade, the RNA, in agreement with previous in vitro data showing that phosphate concentrations in the range of those found in the bacterial cytoplasm and, more relevant, in the mitochondria, inhibit its activity.}, } @article {pmid37481145, year = {2023}, author = {DeCicco, LH and DeRaad, DA and Ostrow, EN and Moyle, RG}, title = {A complete species-level phylogeny of the Erythrura parrotfinches (Aves: Estrildidae).}, journal = {Molecular phylogenetics and evolution}, volume = {187}, number = {}, pages = {107883}, doi = {10.1016/j.ympev.2023.107883}, pmid = {37481145}, issn = {1095-9513}, mesh = {Animals ; Phylogeny ; *Passeriformes/genetics ; DNA ; Genes, Mitochondrial ; Mitochondria/genetics ; DNA, Mitochondrial/genetics ; Sequence Analysis, DNA ; }, abstract = {Identifying species boundaries and phylogenetic relationships among groups of closely related species provides a necessary framework for understanding how biodiversity evolves in natural systems. Here we present a complete phylogeny of the avian genus Erythrura (family Estrildidae) commonly known as parrotfinches, which includes species threatened by habitat loss and the pet trade. Using both mitogenome and reduced-representation genome-wide nuclear DNA sequence data, we reconstructed the evolutionary history of the group by sampling all 12 recognized species, four of which had not previously been studied in a phylogenetic context. We included intra-species geographic sampling that allowed us to comment on species limits in some taxa. We recovered the Gouldian Finch (Chloebia gouldiae) of Australia which has often been placed in the monotypic genus Chloebia, as being sister to a clade comprising all Erythrura species. In addition, we recovered a well-supported clade comprising eight species distributed throughout the Pacific Island eco-region, whereas those species occurring in continental southeast Asia, the Greater Sundas, and the Philippines, were recovered as earlier branching lineages. Of note was the early branching of the Fiji-endemic E. kleinschmidti which corroborates its unique phenotype. We also found a deep phylogenetic split (8.59% corrected, 7.89% uncorrected divergence in the mitochondrial gene ND2) between the Java and Philippine populations of E. hyperythra, indicating unrecognized species-level diversity within this taxon. In contrast, genome-wide nuclear data suggested that the New Guinea endemic species E. papuana is embedded within the widespread species E. trichroa in all phylogenetic reconstructions, corroborating previously published mitochondrial data that suggested a similar pattern. By generating a phylogenetic hypothesis for the relationships among all species of Erythrura parrotfinches, we provide a framework for better understanding the extant diversity and evolutionary history of this group.}, } @article {pmid37481257, year = {2023}, author = {Collington, E and Lobb, B and Mazen, NA and Doxey, AC and Glerum, DM}, title = {Phylogenomic Analysis of 155 Helminth Species Reveals Widespread Absence of Oxygen Metabolic Capacity.}, journal = {Genome biology and evolution}, volume = {15}, number = {8}, pages = {}, pmid = {37481257}, issn = {1759-6653}, mesh = {Animals ; Phylogeny ; Reactive Oxygen Species/metabolism ; *Parasites ; Electron Transport Complex IV/genetics ; Caenorhabditis elegans/genetics/metabolism ; Oxygen/metabolism ; }, abstract = {The terminal electron acceptor of most aerobic respiratory chains, cytochrome c oxidase (COX), has been highly conserved throughout evolution, from aerobic prokaryotes to complex eukaryotes. Oxygen metabolism in parasitic helminths differs significantly from that of most aerobic eukaryotes, as these organisms can switch between aerobic and anaerobic metabolisms throughout their life cycles. Early studies suggested a lack of COX activity in certain parasitic helminths, and the role of COX in helminth mitochondria remains unclear. To determine whether a functional COX is widely present in helminths, we analyzed the phylogenetic distribution of oxygen metabolism systems across 155 helminth genomes, investigating three distinct sets of protein-coding genes involved in different aspects of oxygen metabolism: COX and its assembly factors, peroxisomes, and the most abundant reactive oxygen species (ROS)-metabolizing proteins. While glycolytic and citric acid cycle enzymes are highly conserved in helminthic species, we observed an apparent widespread absence of essential COX genes across 52% of helminth species investigated. While the most common proteins involved in the defense against ROS are highly maintained across virtually all lineages, we also observed an apparent absence of essential peroxisomal protein-coding genes in 42% of species investigated. Our results suggest that a subset of parasitic helminths utilize oxygen differently from related, nonparasitic species such as Caenorhabditis elegans, with significant differences in their mitochondrial electron transport chains and peroxisomes. The identification of substantive differences between parasite and host metabolism offers a new avenue for the development of anthelmintic agents that could target these divergent pathways.}, } @article {pmid37489100, year = {2023}, author = {Yordanov, G and Palova, N and Mehandjyiski, I and Hristov, P}, title = {Mitochondrial DNA sequencing illuminates genetic diversity and origin of Hunagrian Nonius horse breed and his relatives - Danubian horse and Serbian Nonius.}, journal = {Animal biotechnology}, volume = {34}, number = {8}, pages = {3897-3907}, doi = {10.1080/10495398.2023.2237533}, pmid = {37489100}, issn = {1532-2378}, mesh = {Animals ; Horses/genetics ; Female ; *DNA, Mitochondrial/genetics ; Serbia ; *Genetic Variation/genetics ; Mitochondria/genetics ; Sequence Analysis, DNA ; Haplotypes/genetics ; Phylogeny ; }, abstract = {From a historical perspective, horse breeding in Bulgaria has been very well developed since the time of the Thracians (early Bronze Age c. 3000 BCE). Archaeological discoveries from this era present us with an extremely rich type diversity, including wild and local primitive horses, the prototype of heavy draft horses, and fine riding horses.The objective of this study was to investigate the genetic structure of unexamined populations of three closely related horse breeds - the Danubian Nonius Hungarian Nonius and Serbian Nonius horses. A 608 bp long fragment of the mtDNA D-loop region was amplified and sequenced. The obtained results showed completely different genetic profiles between the investigated breeds. We identified nine of the 17 haplogroups described in modern horses. Most of the obtained sequences fell into M, L, G, and O'P lineages, which reflects the genetic profiles of the ancestral mares that were probably used at the initial stages of formation of the breeds. The population of the Danubian horse was characterized by a high prevalence of Central Asian specific haplogroup G (45%), followed by Western Eurasian specific haplogroups L and M (both about 21%). In contrast to the Danubian horse, in the Nonius breed the highest frequency of Western Eurasian haplogroup M (43.5%) was found, followed by Middle Eastern haplogroups O'P (26.1%) Central Asian specific E (13.0%) and G (13.1%). The Serbian Nonius horse showed a completely different genetic profile with a prevalence of the rare for Europe haplogroup D (66.7%), followed by Central Asian specific G (16.7%). The high mitochondrial haplotype diversity (Hd = 0.886) found in the investigated samples is evidence for multiple maternal origins in all populations.In conclusion, the obtained results demonstrated a high percentage of haplogroup sharing especially in the Danubian and Hungarian Nonius horse breeds, which reflects the possible common origins of the two breeds. In contrast to these breeds, the Serbian Nonius, despite the small number of investigated animals, showed a specific genetic profile, which could be explained by different and independent origins.}, } @article {pmid37491310, year = {2023}, author = {Costa, RD and Thomaz Neto, FJ and Moustafa, MT and Atilano, SR and Chwa, M and Cáceres-Del-Carpi, J and Mohamed, MH and Kenney, MC and Kuppermann, BD}, title = {The role of mitochondrial genes on nuclear gene expression in neovascular age related macular degeneration: analysis of nuclear VEGF gene expression after ranibizumab treatment in cytoplasmic hybrid retinal pigment epithelial cell lines correlated with clinical evolution.}, journal = {International journal of retina and vitreous}, volume = {9}, number = {1}, pages = {44}, pmid = {37491310}, issn = {2056-9920}, support = {P30 EY034070/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: The present study tests the hypothesis that mitochondrial genes have retrograde signaling capacity that influences the expression of nuclear genes related to angiogenesis pathways. Cytoplasmic hybrid (cybrid) in vitro cell lines with patient specific mitochondria inserted into an immortalized retinal pigment epithelial cell line (ARPE-19) were used to test this hypothesis. This type of analysis can provide important information to identify the optimal regimen of anti-VEGF treatment, personalizing age-related macular degeneration (AMD) therapies.

METHODS: Mitochondria deficient ARPE-19 cells (Rho0) were fused with AMD donor's platelets to create individual cybrid cell lines containing mitochondria from patients with phenotypic AMD disease and nuclear DNA from the immortalized RPE cell line. The cybrids were treated with Ranibizumab (Lucentis, Genentech, San Francisco, CA), at 4 different concentrations for 24 h, and subsequently the levels of reactive oxygen species (ROS), gene expression for VEGF-A, hypoxia-inducible factor 1-alpha (HIF1-a) and manganese superoxide dismutase (SOD2) were measured. The clinical evolution of the two AMD-donors were correlated with the molecular findings found in their 'personalized' cybrids.

RESULTS: Cybrids from Patient-01 showed down-regulation of gene expression of VEGF-A and HIF-1a at both 1X and 4X Ranibizumab concentrations. Patient-01 AMD cybrid cultures had an increase in the ROS levels at 1X (P = 0.0317), no changes at 2X (P = 0.8350) and a decrease at 4X (P = 0.0015) and 10X (P = 0.0011) of Ranibizumab. Clinically, Patient-01 responded to anti-VEGF therapy but eventually developed geographic atrophy. Patient-02 cybrids demonstrated up-regulation of gene expression of VEGF-A and HIF-1a at Ranibizumab 1X and 4X concentrations. There was decreased ROS levels with Ranibizumab 1X (P = 0.1606), 2X (P = 0.0388), 4X (P = 0.0010) and 10X (P =  < 0.0001). Clinically, Patient-02 presented with a neovascular lesion associated with a prominent production of intraretinal fluid in clinical follow-up requiring regular and repeated intravitreal injections of Ranibizumab with recurrent subretinal fluid.

CONCLUSIONS: Our cybrid model has the potential to help personalize the treatment regimen with anti-VEGF drugs in patients with neovascular AMD. Further investigation is needed to better understand the role that the mitochondria play in the cellular response to anti-VEGF drugs. Future studies that focus on this model have the potential to help personalize anti-VEGF treatment.}, } @article {pmid37491455, year = {2023}, author = {von der Dunk, SHA and Hogeweg, P and Snel, B}, title = {Obligate endosymbiosis enables genome expansion during eukaryogenesis.}, journal = {Communications biology}, volume = {6}, number = {1}, pages = {777}, pmid = {37491455}, issn = {2399-3642}, mesh = {Phylogeny ; *Eukaryotic Cells/metabolism ; *Symbiosis/genetics ; Biological Evolution ; Mitochondria/genetics ; }, abstract = {The endosymbiosis of an alpha-proteobacterium that gave rise to mitochondria was one of the key events in eukaryogenesis. One striking outcome of eukaryogenesis was a much more complex cell with a large genome. Despite the existence of many alternative hypotheses for this and other patterns potentially related to endosymbiosis, a constructive evolutionary model in which these hypotheses can be studied is still lacking. Here, we present a theoretical approach in which we focus on the consequences rather than the causes of mitochondrial endosymbiosis. Using a constructive evolutionary model of cell-cycle regulation, we find that genome expansion and genome size asymmetry arise from emergent host-symbiont cell-cycle coordination. We also find that holobionts with large host and small symbiont genomes perform best on long timescales and mimic the outcome of eukaryogenesis. By designing and studying a constructive evolutionary model of obligate endosymbiosis, we uncovered some of the forces that may drive the patterns observed in nature. Our results provide a theoretical foundation for patterns related to mitochondrial endosymbiosis, such as genome size asymmetry, and reveal evolutionary outcomes that have not been considered so far, such as cell-cycle coordination without direct communication.}, } @article {pmid37493549, year = {2023}, author = {Jagielska, M and Hałakuc, P and Płecha, M and Milanowski, R}, title = {[Mitochondrial genomes – unity and diversity].}, journal = {Postepy biochemii}, volume = {69}, number = {2}, pages = {113-121}, doi = {10.18388/pb.2021_486}, pmid = {37493549}, issn = {0032-5422}, mesh = {*Genome, Mitochondrial ; Evolution, Molecular ; Mitochondria/genetics ; DNA, Mitochondrial/genetics ; Cell Nucleus ; Phylogeny ; }, abstract = {The emergence of mitochondria was one of the most important events in the history of life on Earth. The engulfed bacterial cell, transformed into a mitochondrion, retained its genome, which then underwent numerous modifications. Through massive loss and numerous gene transfers into the nuclear genome, the autonomous bacterium eventually evolved into the organelle we know today. As a result of changes taking place independently in different evolutionary lineages, we observe a great diversity of mitochondrial genomes with respect to structure and gene content. In most cases, mitochondrial DNA has a circular shape, but linear molecules of mitochondrial DNA are also observed in some eukaryotes. In extreme cases, such as in reduced mitochondrial-derived organelles, the genome has been completely lost. In this article, we discuss the diversity of mitochondrial genome structures within the largest groups of Eukarya.}, } @article {pmid37497665, year = {2023}, author = {Millet, AMC and Coustham, C and Champigny, C and Botella, M and Demeilliers, C and Devin, A and Galinier, A and Belenguer, P and Bordeneuve-Guibé, J and Davezac, N and Merabet, N}, title = {OPA1 deficiency impairs oxidative metabolism in cycling cells, underlining a translational approach for degenerative diseases.}, journal = {Disease models & mechanisms}, volume = {16}, number = {9}, pages = {}, pmid = {37497665}, issn = {1754-8411}, mesh = {Humans ; *Optic Atrophy, Autosomal Dominant/genetics/metabolism ; Reactive Oxygen Species/metabolism ; Mitochondria/metabolism ; Cell Respiration ; Oxidative Stress ; GTP Phosphohydrolases/genetics/metabolism ; }, abstract = {Dominant optic atrophy is an optic neuropathy with varying clinical symptoms and progression. A severe disorder is associated with certain OPA1 mutations and includes additional symptoms for >20% of patients. This underscores the consequences of OPA1 mutations in different cellular populations, not only retinal ganglionic cells. We assessed the effects of OPA1 loss of function on oxidative metabolism and antioxidant defences using an RNA-silencing strategy in a human epithelial cell line. We observed a decrease in the mitochondrial respiratory chain complexes, associated with a reduction in aconitase activity related to an increase in reactive oxygen species (ROS) production. In response, the NRF2 (also known as NFE2L2) transcription factor was translocated into the nucleus and upregulated SOD1 and GSTP1. This study highlights the effects of OPA1 deficiency on oxidative metabolism in replicative cells, as already shown in neurons. It underlines a translational process to use cycling cells to circumvent and describe oxidative metabolism. Moreover, it paves the way to predict the evolution of dominant optic atrophy using mathematical models that consider mitochondrial ROS production and their detoxifying pathways.}, } @article {pmid37498958, year = {2024}, author = {Schmid, LM and Manavski, N and Chi, W and Meurer, J}, title = {Chloroplast Ribosome Biogenesis Factors.}, journal = {Plant & cell physiology}, volume = {65}, number = {4}, pages = {516-536}, doi = {10.1093/pcp/pcad082}, pmid = {37498958}, issn = {1471-9053}, support = {ME 1794/10 TRR 175 A03//Deutsche Forschungsgemeinschaft/ ; 2022YFF1001700//National Key Research and Development Program of China/ ; }, mesh = {*Ribosomes/metabolism ; *Chloroplasts/metabolism ; RNA, Ribosomal/genetics/metabolism ; Plants/metabolism/genetics ; }, abstract = {The formation of chloroplasts can be traced back to an ancient event in which a eukaryotic host cell containing mitochondria ingested a cyanobacterium. Since then, chloroplasts have retained many characteristics of their bacterial ancestor, including their transcription and translation machinery. In this review, recent research on the maturation of rRNA and ribosome assembly in chloroplasts is explored, along with their crucial role in plant survival and their implications for plant acclimation to changing environments. A comparison is made between the ribosome composition and auxiliary factors of ancient and modern chloroplasts, providing insights into the evolution of ribosome assembly factors. Although the chloroplast contains ancient proteins with conserved functions in ribosome assembly, newly evolved factors have also emerged to help plants acclimate to changes in their environment and internal signals. Overall, this review offers a comprehensive analysis of the molecular mechanisms underlying chloroplast ribosome assembly and highlights the importance of this process in plant survival, acclimation and adaptation.}, } @article {pmid37502859, year = {2023}, author = {Cal, K and Leyva, A and Rodríguez-Duarte, J and Ruiz, S and Santos, L and Colella, L and Ingold, M and Vilaseca, C and Galliussi, G and Ziegler, L and Peclat, TR and Bresque, M and Handy, RM and King, R and Dos Reis, LM and Espasandin, C and Breining, P and Dapueto, R and Lopez, A and Thompson, KL and Agorrody, G and DeVallance, E and Meadows, E and Lewis, SE and Barbosa, GCS and de Souza, LOL and Chichierchio, MS and Valez, V and Aicardo, A and Contreras, P and Vendelbo, MH and Jakobsen, S and Kamaid, A and Porcal, W and Calliari, A and Verdes, JM and Du, J and Wang, Y and Hollander, JM and White, TA and Radi, R and Moyna, G and Quijano, C and O'Doherty, R and Moraes-Vieira, P and Holloway, GP and Leonardi, R and Mori, MA and Camacho-Pereira, J and Kelley, EE and Duran, R and Lopez, GV and Batthyány, C and Chini, EN and Escande, C}, title = {A nitroalkene derivative of salicylate alleviates diet-induced obesity by activating creatine metabolism and non-shivering thermogenesis.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37502859}, issn = {2693-5015}, support = {R01 HL128485/HL/NHLBI NIH HHS/United States ; R01 HL153532/HL/NHLBI NIH HHS/United States ; R35 GM119528/GM/NIGMS NIH HHS/United States ; R01 HL168290/HL/NHLBI NIH HHS/United States ; R01 DK124510/DK/NIDDK NIH HHS/United States ; }, abstract = {Obesity-related type II diabetes (diabesity) has increased global morbidity and mortality dramatically. Previously, the ancient drug salicylate demonstrated promise for the treatment of type II diabetes, but its clinical use was precluded due to high dose requirements. In this study, we present a nitroalkene derivative of salicylate, 5-(2-nitroethenyl)salicylic acid (SANA), a molecule with unprecedented beneficial effects in diet-induced obesity (DIO). SANA reduces DIO, liver steatosis and insulin resistance at doses up to 40 times lower than salicylate. Mechanistically, SANA stimulated mitochondrial respiration and increased creatine-dependent energy expenditure in adipose tissue. Indeed, depletion of creatine resulted in the loss of SANA action. Moreover, we found that SANA binds to creatine kinases CKMT1/2, and downregulation CKMT1 interferes with the effect of SANA in vivo. Together, these data demonstrate that SANA is a first-in-class activator of creatine-dependent energy expenditure and thermogenesis in adipose tissue and emerges as a candidate for the treatment of diabesity.}, } @article {pmid37503831, year = {2023}, author = {Sanchez-Puerta, MV and Ceriotti, LF and Gatica-Soria, LM and Roulet, ME and Garcia, LE and Sato, HA}, title = {Invited Review Beyond parasitic convergence: unravelling the evolution of the organellar genomes in holoparasites.}, journal = {Annals of botany}, volume = {132}, number = {5}, pages = {909-928}, pmid = {37503831}, issn = {1095-8290}, support = {PICT2020-01018//Fondo para la Investigación Científica y Tecnológica/ ; 06/A092-T1//Universidad Nacional de Cuyo/ ; }, mesh = {*Magnoliopsida/genetics ; Plants/genetics ; *Genome, Mitochondrial/genetics ; Evolution, Molecular ; Plastids ; Phylogeny ; }, abstract = {BACKGROUND: The molecular evolution of organellar genomes in angiosperms has been studied extensively, with some lineages, such as parasitic ones, displaying unique characteristics. Parasitism has emerged 12 times independently in angiosperm evolution. Holoparasitism is the most severe form of parasitism, and is found in ~10 % of parasitic angiosperms. Although a few holoparasitic species have been examined at the molecular level, most reports involve plastomes instead of mitogenomes. Parasitic plants establish vascular connections with their hosts through haustoria to obtain water and nutrients, which facilitates the exchange of genetic information, making them more susceptible to horizontal gene transfer (HGT). HGT is more prevalent in the mitochondria than in the chloroplast or nuclear compartments.

SCOPE: This review summarizes current knowledge on the plastid and mitochondrial genomes of holoparasitic angiosperms, compares the genomic features across the different lineages, and discusses their convergent evolutionary trajectories and distinctive features. We focused on Balanophoraceae (Santalales), which exhibits extraordinary traits in both their organelles.

CONCLUSIONS: Apart from morphological similarities, plastid genomes of holoparasitic plants also display other convergent features, such as rampant gene loss, biased nucleotide composition and accelerated evolutionary rates. In addition, the plastomes of Balanophoraceae have extremely low GC and gene content, and two unexpected changes in the genetic code. Limited data on the mitochondrial genomes of holoparasitic plants preclude thorough comparisons. Nonetheless, no obvious genomic features distinguish them from the mitochondria of free-living angiosperms, except for a higher incidence of HGT. HGT appears to be predominant in holoparasitic angiosperms with a long-lasting endophytic stage. Among the Balanophoraceae, mitochondrial genomes exhibit disparate evolutionary paths with notable levels of heteroplasmy in Rhopalocnemis and unprecedented levels of HGT in Lophophytum. Despite their differences, these Balanophoraceae share a multichromosomal mitogenome, a feature also found in a few free-living angiosperms.}, } @article {pmid37507225, year = {2023}, author = {Esposti, MD}, title = {Eukaryotes inherited inositol lipids from bacteria: implications for the models of eukaryogenesis.}, journal = {FEBS letters}, volume = {597}, number = {19}, pages = {2484-2496}, doi = {10.1002/1873-3468.14708}, pmid = {37507225}, issn = {1873-3468}, mesh = {*Bacteria/metabolism ; *Inositol/metabolism ; *Models, Biological ; Archaea/metabolism ; *Eukaryotic Cells/metabolism ; *Eukaryota/metabolism ; }, abstract = {The merger of two very different microbes, an anaerobic archaeon and an aerobic bacterium, led to the birth of eukaryotic cells. Current models hypothesize that an archaeon engulfed bacteria through external protrusions that then fused together forming the membrane organelles of eukaryotic cells, including mitochondria. Images of cultivated Lokiarchaea sustain this concept, first proposed in the inside-out model which assumes that the membrane traffic system of archaea drove the merging with bacterial cells through membrane expansions containing inositol lipids, considered to have evolved first in archaea. This assumption has been evaluated here in detail. The data indicate that inositol lipids first emerged in bacteria, not in archaea. The implications of this finding for the models of eukaryogenesis are discussed.}, } @article {pmid37508434, year = {2023}, author = {Preziuso, A and Piccirillo, S and Cerqueni, G and Serfilippi, T and Terenzi, V and Vinciguerra, A and Orciani, M and Amoroso, S and Magi, S and Lariccia, V}, title = {Exploring the Role of NCX1 and NCX3 in an In Vitro Model of Metabolism Impairment: Potential Neuroprotective Targets for Alzheimer's Disease.}, journal = {Biology}, volume = {12}, number = {7}, pages = {}, pmid = {37508434}, issn = {2079-7737}, support = {2017YH3SXK//Ministry of Education, Universities and Research/ ; }, abstract = {Alzheimer's disease (AD) is a widespread neurodegenerative disorder, affecting a large number of elderly individuals worldwide. Mitochondrial dysfunction, metabolic alterations, and oxidative stress are regarded as cooperating drivers of the progression of AD. In particular, metabolic impairment amplifies the production of reactive oxygen species (ROS), resulting in detrimental alterations to intracellular Ca[2+] regulatory processes. The Na[+]/Ca[2+] exchanger (NCX) proteins are key pathophysiological determinants of Ca[2+] and Na[+] homeostasis, operating at both the plasma membrane and mitochondria levels. Our study aimed to explore the role of NCX1 and NCX3 in retinoic acid (RA) differentiated SH-SY5Y cells treated with glyceraldehyde (GA), to induce impairment of the default glucose metabolism that typically precedes Aβ deposition or Tau protein phosphorylation in AD. By using an RNA interference-mediated approach to silence either NCX1 or NCX3 expression, we found that, in GA-treated cells, the knocking-down of NCX3 ameliorated cell viability, increased the intracellular ATP production, and reduced the oxidative damage. Remarkably, NCX3 silencing also prevented the enhancement of Aβ and pTau levels and normalized the GA-induced decrease in NCX reverse-mode activity. By contrast, the knocking-down of NCX1 was totally ineffective in preventing GA-induced cytotoxicity except for the increase in ATP synthesis. These findings indicate that NCX3 and NCX1 may differently influence the evolution of AD pathology fostered by glucose metabolic dysfunction, thus providing a potential target for preventing AD.}, } @article {pmid37511042, year = {2023}, author = {Luo, L and Xu, Y and Wang, S and Zhang, R and Guo, K and Xu, W and Zhao, Z}, title = {Complete Mitochondrial Genome Sequence and Phylogenetic Analysis of Procambarus clarkii and Cambaroides dauricus from China.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511042}, issn = {1422-0067}, support = {2020YFD0900402//the National Key Research and Development Project/ ; 2020TD56//the Central Public-interest Scientific Institution Basal Research Fund, Chinese Academy of Fishery Sciences/ ; }, mesh = {Animals ; *Genome, Mitochondrial/genetics ; Astacoidea/genetics ; Phylogeny ; NAD/genetics ; Sequence Analysis, DNA ; }, abstract = {To enhance the management and protection of crayfish genetic diversity and germplasm resources in Cambaroides dauricus (C. dauricus), a common species of Procambarus clarkii (P. clarkii) was used as a control group to compare the whole mitochondrial genome sequence using Illumina sequencing technology. This study found that the mitochondrial genome of C. dauricus is 15580 bp in length, with a base composition of A (31.84%), G (17.66%), C (9.42%), and T (41.08%) and a C + G content of 27.08%. The C + G in the D-loop is rich in 17.06%, indicating a significant preference. The mitochondrial genome of C. dauricus contains 13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes, with most of the genes labeled in the negative direction, except for a few genes that are labeled in the positive direction. The start codons of the ten coding sequences are ATG, and the quintessential TAA and TAG are the stop codons. This study also found that the Ka/Ks ratios of most protein-coding genes in the mitochondria of both shrimps are lower than 1, indicating weak natural selection, except for nad 2, nad 5, and cox 1. The Ka/Ks ratio of cox 3 is the lowest (less than 0.1), indicating that this protein-coding gene bears strong natural selection pressure and functional constraint in the process of mitochondrial genetic evolution of both shrimps. Furthermore, we constructed phylogenetic analyses based on the entire sequence, which effectively distinguishes the high body from other shrimp species of the genus based on the mitochondrial genome. This study provides molecular genetic data for the diversity investigation and protection of fishery resources with Chinese characteristics and a scientific reference for the evolutionary study of Procambarus.}, } @article {pmid37512520, year = {2023}, author = {Hu, M and Jiang, Y and Xu, JJ}, title = {Characterization of Arabidopsis thaliana Coq9 in the CoQ Biosynthetic Pathway.}, journal = {Metabolites}, volume = {13}, number = {7}, pages = {}, pmid = {37512520}, issn = {2218-1989}, support = {no//Yunnan Revitalization Talent Support Program "Top Team" Project/ ; PFGR202201//Open Fund of Shanghai Key Laboratory of Plant Functional Genomics and Resources under Grant/ ; 222414//Special Fund for Shanghai Landscaping Administration Bureau Program/ ; YDZX20223100001003//Ministry of Science and Technology of the People's Republic of China/ ; }, abstract = {Coenzyme Q, also known as ubiquinone, is a fat-soluble isoprene quinone that serves as a cofactor for numerous enzymes across all domains of life. However, the biosynthetic pathway for this important molecule in plants has been examined in only a limited number of studies. In yeast and mammals, Coq9, an isoprenoid-lipid-binding protein, is essential for CoQ biosynthesis. Previous studies showed that Arabidopsis thaliana Coq9 failed to complement the fission yeast Schizosaccharomyces pombe coq9 null mutant, and its function in plants remains unknown. In this study, we demonstrated that expression of Arabidopsis Coq9 rescued the growth of a yeast temperature-sensitive coq9 mutant and increased CoQ content. Phylogenetic analysis revealed that Coq9 is widely present in green plants. Green fluorescent protein (GFP) fusion experiments showed that Arabidopsis Coq9 is targeted to mitochondria. Disruption of the Coq9 gene in Arabidopsis results in lower amounts of CoQ. Our work suggests that plant Coq9 is required for efficient CoQ biosynthesis. These findings provide new insights into the evolution of CoQ biosynthesis in plants. The identification of Coq9 as a key player in CoQ biosynthesis in plants opens up new avenues for understanding the regulation of this important metabolic pathway.}, } @article {pmid37515372, year = {2024}, author = {Fernández-Moncada, I and Rodrigues, RS and Fundazuri, UB and Bellocchio, L and Marsicano, G}, title = {Type-1 cannabinoid receptors and their ever-expanding roles in brain energy processes.}, journal = {Journal of neurochemistry}, volume = {168}, number = {5}, pages = {693-703}, doi = {10.1111/jnc.15922}, pmid = {37515372}, issn = {1471-4159}, support = {//INSERM/ ; Micabra, ERC-2017-AdG-786467//the European Research Council/ ; DRM20101220445//Fondation pour la Recherche Medicale/ ; ALTF87-2018//EMBO/ ; //the Human Frontiers Science Program/ ; 17219710//Region Aquitaine/ ; CanBrain, AAP2022A-2021-16763610//Region Aquitaine/ ; ANR-19-CE14-0039//French State/Agence Nationale de la Recherche/ ; ERA-Net Neuron CanShank, ANR-21-NEU2-0001-04//French State/Agence Nationale de la Recherche/ ; MitObesity, ANR 18-CE14-0029-01//French State/Agence Nationale de la Recherche/ ; CaCoVi, ANR 18-CE16-0001-02//French State/Agence Nationale de la Recherche/ ; GPR BRAIN_2030//University of Bordeaux's IdEx "Investments for the Future" program/ ; }, mesh = {*Receptor, Cannabinoid, CB1/metabolism ; Humans ; Animals ; *Brain/metabolism ; *Energy Metabolism/physiology ; Mitochondria/metabolism ; Neurons/metabolism ; }, abstract = {The brain requires large quantities of energy to sustain its functions. At the same time, the brain is isolated from the rest of the body, forcing this organ to develop strategies to control and fulfill its own energy needs. Likely based on these constraints, several brain-specific mechanisms emerged during evolution. For example, metabolically specialized cells are present in the brain, where intercellular metabolic cycles are organized to separate workload and optimize the use of energy. To orchestrate these strategies across time and space, several signaling pathways control the metabolism of brain cells. One of such controlling systems is the endocannabinoid system, whose main signaling hub in the brain is the type-1 cannabinoid (CB1) receptor. CB1 receptors govern a plethora of different processes in the brain, including cognitive function, emotional responses, or feeding behaviors. Classically, the mechanisms of action of CB1 receptors on brain function had been explained by its direct targeting of neuronal synaptic function. However, new discoveries have challenged this view. In this review, we will present and discuss recent data about how a small fraction of CB1 receptors associated to mitochondrial membranes (mtCB1), are able to exert a powerful control on brain functions and behavior. mtCB1 receptors impair mitochondrial functions both in neurons and astrocytes. In the latter cells, this effect is linked to an impairment of astrocyte glycolytic function, resulting in specific behavioral outputs. Finally, we will discuss the potential implications of (mt)CB1 expression on oligodendrocytes and microglia metabolic functions, with the aim to encourage interdisciplinary approaches to better understand the role of (mt)CB1 receptors in brain function and behavior.}, } @article {pmid37518286, year = {2023}, author = {Zhang, G and Gao, JJ and Takano, KT and Yafuso, M and Suwito, A and Meleng, PA and Toda, MJ}, title = {Phylogenetic classification and palm-inflorescence anthophily of the Colocasiomyia zeylanica species group (Diptera: Drosophilidae), with descriptions of five new species.}, journal = {Zootaxa}, volume = {5278}, number = {2}, pages = {201-238}, doi = {10.11646/zootaxa.5278.2.1}, pmid = {37518286}, issn = {1175-5334}, mesh = {Animals ; *Diptera ; *Drosophilidae/genetics ; Phylogeny ; Inflorescence ; Mitochondria ; }, abstract = {The zeylanica group is one of the six species groups of the anthophilic genus Colocasiomyia de Meijere in the family Drosophilidae. In addition to two known species, five morphospecies have been recognized as members of this species group but left undescribed formally. In this study, species delimitation of these putatively new species was determined by barcoding of the mitochondrial COI (cytochrome c oxydase subunit I) gene and morphological comparison. Phylogenetic relationships within the genus Colocasiomyia were inferred by a cladistic analysis of 89 morphological characters. Based on the results of these analyses, we redefined the zeylanica species group and established two subgroups within it: the zeylanica subgroup comprised of C. zeylanica, C. nepalensis, C. pinangae sp. nov., C. besaris sp. nov. and C. luciphila sp. nov., and the oligochaeta subgroup of C. oligochaeta sp. nov. and C. grimaldii sp. nov. In addition, we briefly address the anthophilic habits of drosophilid flies using palm (Arecaceae) inflorescences, especially of the zeylanica group, compiling scattered collection records from the Oriental and Papuan regions.}, } @article {pmid37518493, year = {2023}, author = {Tomimori, Y and Matsui, M and Okawa, H and Nishikawa, K and Tanabe, S and Kamasaka, R}, title = {Reassessment of species delimitation using nuclear markers in three lentic-breeding salamanders from the Chugoku District of Japan (Amphibia: Caudata: Hynobiidae).}, journal = {Zootaxa}, volume = {5293}, number = {1}, pages = {145-160}, doi = {10.11646/zootaxa.5293.1.6}, pmid = {37518493}, issn = {1175-5334}, mesh = {Animals ; *Caudata/genetics ; Phylogeny ; Japan ; *DNA, Mitochondrial/genetics ; Mitochondria/genetics ; }, abstract = {Hynobius akiensis sensu lato has recently been split into three species based on short sequence analyses of cyt-b gene of mtDNA and without data of nuclear DNA, and strange sympatric distribution in some areas has been indicated in two species. We analyzed nuclear DNA marker (SNPs) and complete sequence of cyt-b in H. akiensis sensu lato to reassess species delimitation and genetic introgression among species. As a result, we found two lineages with discordant mitochondrial and nuclear DNA in some areas. Of H. akiensis sensu lato, each of the two contains the type locality of two species recently reported (H. sumidai and H. geiyoensis), and the use of these names has been previously advocated. However, their sympatric distribution was rejected based on nuclear DNA data, which we consider is more reliable than mtDNA. We thus clarify geographic boundary of these two species and revise the species delimitations.}, } @article {pmid37518527, year = {2023}, author = {Kuhara, N and Nozaki, T and Zhang, AO and Zhou, X}, title = {DNA barcoding facilitates discovery and description of two new species of the Mystacides azureus Species Group (Trichoptera: Leptoceridae) in Japan.}, journal = {Zootaxa}, volume = {5306}, number = {2}, pages = {215-231}, doi = {10.11646/zootaxa.5306.2.3}, pmid = {37518527}, issn = {1175-5334}, mesh = {Female ; Animals ; Male ; Japan ; *DNA Barcoding, Taxonomic ; Phylogeny ; *Holometabola ; Mitochondria ; }, abstract = {We examined adult specimens of the Mystacides azureus Species Group (Trichoptera: Leptoceridae) collected in Japan and confirm three species including M. azureus Linnaeus 1761 and two new species, M. rivularis and M. moritai. Males and females of the new species are described. Mystacides azureus in Japan is shown to have a considerable variation in morphology of the male tergum X. We analyzed mitochondrial COI barcodes of the genus Mystacides including these three species to confirm their species status. A maximum likelihood phylogeny based on COI barcodes shows monophyly of the new species. It also supports the hypothesis that morphological variation of the male tergum X in Japanese populations is intraspecific in only M. azureus.}, } @article {pmid37518710, year = {2023}, author = {Russell, PJC and Pateman, JE and Gagarina, AV and Lukhtanov, VA}, title = {Investigations into the Melitaea ornata species complex in the Levant: M. telona and the newly erected species Melitaea klili Benyamini, 2021 (Lepidoptera: Nymphalidae).}, journal = {Zootaxa}, volume = {5285}, number = {1}, pages = {187-195}, doi = {10.11646/zootaxa.5285.1.9}, pmid = {37518710}, issn = {1175-5334}, mesh = {Male ; Animals ; *Butterflies/genetics ; Phylogeny ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Genes, Mitochondrial ; DNA Barcoding, Taxonomic ; }, abstract = {Melitaea klili Benyamini, 2021 was recently described from Israel as a species closely related to M. telona Fruhstorfer, 1908, but different in phenology, ecological preferences and with an allopatric distribution. Here, based on comparative examinations of mitochondrial DNA-barcodes, male genitalia and larval behaviour under laboratory conditions, we synonymize M. klili with M. telona. The COI barcodes of M. klili were found to be identical to those of M. telona. Analysis of 658 bp fragment of the mitochondrial gene COI demonstrated that the minimum uncorrected p-distance between M. ornata and M. telona was 1.98%. This value is remarkably less than the 3% threshold traditionally accepted as a species boundary in DNA barcoding studies. The morphological differences between these taxa are minimal. In fact, M. ornata and M. telona represent two phylogenetic lineages, the taxonomic status of which (separate species or subspecies of the same species) is intermediate and debatable.}, } @article {pmid37522604, year = {2023}, author = {Chukaew, T and Isomura, N and Mezaki, T and Matsumoto, H and Kitano, YF and Nozawa, Y and Tachikawa, H and Fukami, H}, title = {Molecular Phylogeny and Taxonomy of the Coral Genus Cyphastrea (Cnidaria, Scleractinia, Merulinidae) in Japan, With the First Records of Two Species.}, journal = {Zoological science}, volume = {40}, number = {4}, pages = {326-340}, doi = {10.2108/zs230009}, pmid = {37522604}, issn = {0289-0003}, mesh = {Animals ; Phylogeny ; *Anthozoa/genetics ; Japan ; DNA, Ribosomal/genetics ; Mitochondria/genetics ; Sequence Analysis, DNA ; }, abstract = {The scleractinian coral genus Cyphastrea is widely distributed in the Indo-Pacific region and is common from the subtropical to the warm-temperate regions in Japan. Three new species in this genus have recently been reported from south-eastern Australia or the Red Sea. However, taxonomic and species diversity have been little studied so far in Japan. In this study, we analyzed 112 specimens of Cyphastrea collected from the subtropical to the warm-temperate regions in Japan to clarify the species diversity in the country. This analysis was based on skeletal morphological and molecular analyses using three genetic markers of the nuclear 28S rDNA, histone H3 gene, and the mitochondrial noncoding intergenic region between COI and tRNAmet. The molecular phylogenetic trees showed that our specimens are separated mainly into four clades. Considering the morphological data with the molecular phylogenetic relationships, we confirmed a total of nine species, including two species, C. magna and C. salae, recorded for the first time in Japan. Although eight out of nine species were genetically included within Cyphastrea, one species, C. agassizi, was genetically distant from all other species and was closely related to the genus Leptastrea, suggesting the return of this species to the genus to which it was originally ascribed. Two newly recorded species were reciprocally monophyletic, while the other six species (excluding C. agassizi) clustered in two clades without forming species-specific lineages, including three polyphyletic species. Thus, the species boundary between species in Cyphastrea remains unclear in most species using these three sequenced loci.}, } @article {pmid37538245, year = {2023}, author = {Zhang, H and Li, X and Fan, W and Pandovski, S and Tian, Y and Dillin, A}, title = {Inter-tissue communication of mitochondrial stress and metabolic health.}, journal = {Life metabolism}, volume = {2}, number = {1}, pages = {}, pmid = {37538245}, issn = {2755-0230}, support = {R01 AG059566/AG/NIA NIH HHS/United States ; R01 ES021667/ES/NIEHS NIH HHS/United States ; }, abstract = {Mitochondria function as a hub of the cellular metabolic network. Mitochondrial stress is closely associated with aging and a variety of diseases, including neurodegeneration and cancer. Cells autonomously elicit specific stress responses to cope with mitochondrial stress to maintain mitochondrial homeostasis. Interestingly, mitochondrial stress responses may also be induced in a non-autonomous manner in cells or tissues that are not directly experiencing such stress. Such non-autonomous mitochondrial stress responses are mediated by secreted molecules called mitokines. Due to their significant translational potential in improving human metabolic health, there has been a surge in mitokine-focused research. In this review, we summarize the findings regarding inter-tissue communication of mitochondrial stress in animal models. In addition, we discuss the possibility of mitokine-mediated intercellular mitochondrial communication originating from bacterial quorum sensing.}, } @article {pmid37548336, year = {2023}, author = {Ryan, K and Greenway, R and Landers, J and Arias-Rodriguez, L and Tobler, M and Kelley, JL}, title = {Selection on standing genetic variation mediates convergent evolution in extremophile fish.}, journal = {Molecular ecology}, volume = {32}, number = {18}, pages = {5042-5054}, doi = {10.1111/mec.17081}, pmid = {37548336}, issn = {1365-294X}, mesh = {Animals ; *Hydrogen Sulfide/toxicity ; *Extremophiles ; Ecosystem ; Sulfides ; *Poecilia/genetics ; Genetic Variation/genetics ; Selection, Genetic ; }, abstract = {Hydrogen sulfide is a toxic gas that disrupts numerous biological processes, including energy production in the mitochondria, yet fish in the Poecilia mexicana species complex have independently evolved sulfide tolerance several times. Despite clear evidence for convergence at the phenotypic level in these fishes, it is unclear if the repeated evolution of hydrogen sulfide tolerance is the result of similar genomic changes. To address this gap, we used a targeted capture approach to sequence genes associated with sulfide processes and toxicity from five sulfidic and five nonsulfidic populations in the species complex. By comparing sequence variation in candidate genes to a reference set, we identified similar population structure and differentiation, suggesting that patterns of variation in most genes associated with sulfide processes and toxicity are due to demographic history and not selection. But the presence of tree discordance for a subset of genes suggests that several loci are evolving divergently between ecotypes. We identified two differentiation outlier genes that are associated with sulfide detoxification in the mitochondria that have signatures of selection in all five sulfidic populations. Further investigation into these regions identified long, shared haplotypes among sulfidic populations. Together, these results reveal that selection on standing genetic variation in putatively adaptive genes may be driving phenotypic convergence in this species complex.}, } @article {pmid37551058, year = {2023}, author = {Huynh, SD and Melonek, J and Colas des Francs-Small, C and Bond, CS and Small, I}, title = {A unique C-terminal domain contributes to the molecular function of Restorer-of-fertility proteins in plant mitochondria.}, journal = {The New phytologist}, volume = {240}, number = {2}, pages = {830-845}, doi = {10.1111/nph.19166}, pmid = {37551058}, issn = {1469-8137}, mesh = {*Genes, Plant ; Mitochondria/metabolism ; Cytoplasm/metabolism ; Plant Proteins/metabolism ; *Arabidopsis/genetics/metabolism ; Fertility/genetics ; Plant Infertility/genetics ; }, abstract = {Restorer-of-fertility (Rf) genes encode pentatricopeptide repeat (PPR) proteins that are targeted to mitochondria where they specifically bind to transcripts that induce cytoplasmic male sterility and repress their expression. In searching for a molecular signature unique to this class of proteins, we found that a majority of known Rf proteins have a distinct domain, which we called RfCTD (Restorer-of-fertility C-terminal domain), and its presence correlates with the ability to induce cleavage of the mitochondrial RNA target. A screen of 219 angiosperm genomes from 123 genera using a sequence profile that can quickly and accurately identify RfCTD sequences revealed considerable variation in RFL/RfCTD gene numbers across flowering plants. We observed that plant genera with bisexual flowers have significantly higher numbers of RFL genes compared to those with unisexual flowers, consistent with a role of these proteins in restoration of male fertility. We show that removing the RfCTD from the RFL protein RNA PROCESSING FACTOR 2-nad6 prevented cleavage of its RNA target, the nad6 transcript, in Arabidopsis thaliana mitochondria. We provide a simple way of identifying putative Rf candidates in genome sequences, new insights into the molecular mode of action of Rf proteins and the evolution of fertility restoration in flowering plants.}, } @article {pmid37556561, year = {2023}, author = {Raval, PK and Martin, WF and Gould, SB}, title = {Mitochondrial evolution: Gene shuffling, endosymbiosis, and signaling.}, journal = {Science advances}, volume = {9}, number = {32}, pages = {eadj4493}, pmid = {37556561}, issn = {2375-2548}, mesh = {*Symbiosis/genetics ; *Mitochondria/genetics ; Eukaryotic Cells/metabolism ; Genes, Mitochondrial ; Phylogeny ; Biological Evolution ; Evolution, Molecular ; }, abstract = {Genes for cardiolipin and ceramide synthesis occur in some alphaproteobacterial genomes. They shed light on mitochondrial origin and signaling in the first eukaryotic cells.}, } @article {pmid37557975, year = {2023}, author = {Weaver, RJ and McDonald, AE}, title = {Mitochondrial alternative oxidase across the tree of life: Presence, absence, and putative cases of lateral gene transfer.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1864}, number = {4}, pages = {149003}, doi = {10.1016/j.bbabio.2023.149003}, pmid = {37557975}, issn = {1879-2650}, mesh = {Animals ; *Gene Transfer, Horizontal ; *Plant Proteins/genetics ; Oxidoreductases/genetics ; Mitochondria/genetics ; Plants ; Eukaryota/genetics ; Alternative Oxidase ; }, abstract = {The alternative oxidase (AOX) is a terminal oxidase in the electron transport system that plays a role in mitochondrial bioenergetics. The past 20 years of research shows AOX has a wide yet patchy distribution across the tree of life. AOX has been suggested to have a role in stress tolerance, growth, and development in plants, but less is known about its function in other groups, including animals. In this study, we analyzed the taxonomic distribution of AOX across >2800 species representatives from prokaryotes and eukaryotes and developed a standardized workflow for finding and verifying the authenticity of AOX sequences. We found that AOX is limited to proteobacteria among prokaryotes, but is widely distributed in eukaryotes, with the highest prevalence in plants, fungi, and protists. AOX is present in many invertebrates, but is absent in others including most arthropods, and is absent from vertebrates. We found aberrant AOX sequences associated with some animal groups. Some of these aberrant AOXs were contaminants, but we also found putative cases of lateral gene transfer of AOX from fungi and protists to nematodes, springtails, fungus gnats, and rotifers. Our findings provide a robust and detailed analysis of the distribution of AOX and a method for identifying and verifying putative AOX sequences, which will be useful as more sequence data becomes available on public repositories.}, } @article {pmid37558671, year = {2023}, author = {Kuhle, B and Hirschi, M and Doerfel, LK and Lander, GC and Schimmel, P}, title = {Structural basis for a degenerate tRNA identity code and the evolution of bimodal specificity in human mitochondrial tRNA recognition.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {4794}, pmid = {37558671}, issn = {2041-1723}, support = {R01 NS095892/NS/NINDS NIH HHS/United States ; R01 NS092829/NS/NINDS NIH HHS/United States ; S10 OD021634/OD/NIH HHS/United States ; R01 GM125908/GM/NIGMS NIH HHS/United States ; R21 GM142196/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; RNA, Mitochondrial ; *RNA, Transfer/genetics/metabolism ; *Amino Acyl-tRNA Synthetases/genetics/metabolism ; Mitochondria/genetics/metabolism ; }, abstract = {Animal mitochondrial gene expression relies on specific interactions between nuclear-encoded aminoacyl-tRNA synthetases and mitochondria-encoded tRNAs. Their evolution involves an antagonistic interplay between strong mutation pressure on mtRNAs and selection pressure to maintain their essential function. To understand the molecular consequences of this interplay, we analyze the human mitochondrial serylation system, in which one synthetase charges two highly divergent mtRNA[Ser] isoacceptors. We present the cryo-EM structure of human mSerRS in complex with mtRNA[Ser(UGA)], and perform a structural and functional comparison with the mSerRS-mtRNA[Ser(GCU)] complex. We find that despite their common function, mtRNA[Ser(UGA)] and mtRNA[Ser(GCU)] show no constrain to converge on shared structural or sequence identity motifs for recognition by mSerRS. Instead, mSerRS evolved a bimodal readout mechanism, whereby a single protein surface recognizes degenerate identity features specific to each mtRNA[Ser]. Our results show how the mutational erosion of mtRNAs drove a remarkable innovation of intermolecular specificity rules, with multiple evolutionary pathways leading to functionally equivalent outcomes.}, } @article {pmid37565789, year = {2023}, author = {Yang, Y and Oldenkott, B and Ramanathan, S and Lesch, E and Takenaka, M and Schallenberg-Rüdinger, M and Knoop, V}, title = {DYW cytidine deaminase domains have a long-range impact on RNA recognition by the PPR array of chimeric plant C-to-U RNA editing factors and strongly affect target selection.}, journal = {The Plant journal : for cell and molecular biology}, volume = {116}, number = {3}, pages = {840-854}, doi = {10.1111/tpj.16412}, pmid = {37565789}, issn = {1365-313X}, mesh = {RNA, Plant/metabolism ; *Plant Proteins/metabolism ; *RNA Editing/genetics ; Cytidine Deaminase/chemistry/genetics/metabolism ; Chloroplasts/metabolism ; }, abstract = {The protein factors for the specific C-to-U RNA editing events in plant mitochondria and chloroplasts possess unique arrays of RNA-binding pentatricopeptide repeats (PPRs) linked to carboxy-terminal cytidine deaminase DYW domains via the extension motifs E1 and E2. The E1 and E2 motifs have distant similarities to tetratricopeptide repeats known to mediate protein-protein interactions but their precise function is unclear. Here, we investigate the tolerance of PPR56 and PPR65, two functionally characterized RNA editing factors of the moss Physcomitrium patens, for the creation of chimeras by variably replacing their C-terminal protein regions. Making use of a heterologous RNA editing assay system in Escherichia coli we find that heterologous DYW domains can strongly restrict or widen the spectrum of off-targets in the bacterial transcriptome for PPR56. Surprisingly, our data suggest that these changes are not only caused by the preference of a given heterologous DYW domain for the immediate sequence environment of the cytidine to be edited but also by a long-range impact on the nucleotide selectivity of the upstream PPRs.}, } @article {pmid37569876, year = {2023}, author = {Antos-Krzeminska, N and Kicinska, A and Nowak, W and Jarmuszkiewicz, W}, title = {Acanthamoeba castellanii Uncoupling Protein: A Complete Sequence, Activity, and Role in Response to Oxidative Stress.}, journal = {International journal of molecular sciences}, volume = {24}, number = {15}, pages = {}, pmid = {37569876}, issn = {1422-0067}, support = {OPUS 2020/37/B/NZ1/01188//National Science Centre/ ; }, mesh = {*Oxidative Stress ; *Acanthamoeba castellanii/metabolism/genetics ; Phylogeny ; *Mitochondrial Uncoupling Proteins/genetics/metabolism/chemistry ; Saccharomyces cerevisiae/genetics/metabolism ; Reactive Oxygen Species/metabolism ; *Protozoan Proteins/genetics/metabolism/chemistry ; Mitochondria/metabolism ; Membrane Potential, Mitochondrial ; Amino Acid Sequence ; }, abstract = {Uncoupling proteins (UCPs) are mitochondrial inner membrane transporters that mediate free-fatty-acid-induced, purine-nucleotide-inhibited proton leak into the mitochondrial matrix, thereby uncoupling respiratory substrate oxidation from ATP synthesis. The aim of this study was to provide functional evidence that the putative Acucp gene of the free-living protozoan amoeba, A. castellanii, encodes the mitochondrial protein with uncoupling activity characteristic of UCPs and to investigate its role during oxidative stress. We report the sequencing and cloning of a complete Acucp coding sequence, its phylogenetic analysis, and the heterologous expression of AcUCP in the S. cerevisiae strain InvSc1. Measurements of mitochondrial respiratory activity and membrane potential indicate that the heterologous expression of AcUCP causes AcUCP-mediated uncoupling activity. In addition, in a model of oxidative stress with increased reactive oxygen species levels (superoxide dismutase 1 knockout yeasts), AcUCP expression strongly promotes cell survival and growth. The level of superoxide anion radicals is greatly reduced in the ΔSOD1 strain expressing AcUCP. These results suggest that AcUCP targeted to yeast mitochondria causes uncoupling and may act as an antioxidant system. Phylogenetic analysis shows that the A. castellanii UCP diverges very early from other UCPs, but clearly locates within the UCP subfamily rather than among other mitochondrial anion carrier proteins.}, } @article {pmid37577532, year = {2023}, author = {Wolters, JF and LaBella, AL and Opulente, DA and Rokas, A and Hittinger, CT}, title = {Mitochondrial Genome Diversity across the Subphylum Saccharomycotina.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37577532}, issn = {2692-8205}, support = {R01 AI153356/AI/NIAID NIH HHS/United States ; T32 HG002760/HG/NHGRI NIH HHS/United States ; }, abstract = {Eukaryotic life depends on the functional elements encoded by both the nuclear genome and organellar genomes, such as those contained within the mitochondria. The content, size, and structure of the mitochondrial genome varies across organisms with potentially large implications for phenotypic variance and resulting evolutionary trajectories. Among yeasts in the subphylum Saccharomycotina, extensive differences have been observed in various species relative to the model yeast Saccharomyces cerevisiae, but mitochondrial genome sampling across many groups has been scarce, even as hundreds of nuclear genomes have become available. By extracting mitochondrial assemblies from existing short-read genome sequence datasets, we have greatly expanded both the number of available genomes and the coverage across sparsely sampled clades. Comparison of 353 yeast mitochondrial genomes revealed that, while size and GC content were fairly consistent across species, those in the genera Metschnikowia and Saccharomyces trended larger, while several species in the order Saccharomycetales, which includes S. cerevisiae, exhibited lower GC content. Extreme examples for both size and GC content were scattered throughout the subphylum. All mitochondrial genomes shared a core set of protein-coding genes for Complexes III, IV, and V, but they varied in the presence or absence of mitochondrially-encoded canonical Complex I genes. We traced the loss of Complex I genes to a major event in the ancestor of the orders Saccharomycetales and Saccharomycodales, but we also observed several independent losses in the orders Phaffomycetales, Pichiales, and Dipodascales. In contrast to prior hypotheses based on smaller-scale datasets, comparison of evolutionary rates in protein-coding genes showed no bias towards elevated rates among aerobically fermenting (Crabtree/Warburg-positive) yeasts. Mitochondrial introns were widely distributed, but they were highly enriched in some groups. The majority of mitochondrial introns were poorly conserved within groups, but several were shared within groups, between groups, and even across taxonomic orders, which is consistent with horizontal gene transfer, likely involving homing endonucleases acting as selfish elements. As the number of available fungal nuclear genomes continues to expand, the methods described here to retrieve mitochondrial genome sequences from these datasets will prove invaluable to ensuring that studies of fungal mitochondrial genomes keep pace with their nuclear counterparts.}, } @article {pmid37582787, year = {2023}, author = {Meadows, JRS and Kidd, JM and Wang, GD and Parker, HG and Schall, PZ and Bianchi, M and Christmas, MJ and Bougiouri, K and Buckley, RM and Hitte, C and Nguyen, AK and Wang, C and Jagannathan, V and Niskanen, JE and Frantz, LAF and Arumilli, M and Hundi, S and Lindblad-Toh, K and Ginja, C and Agustina, KK and André, C and Boyko, AR and Davis, BW and Drögemüller, M and Feng, XY and Gkagkavouzis, K and Iliopoulos, G and Harris, AC and Hytönen, MK and Kalthoff, DC and Liu, YH and Lymberakis, P and Poulakakis, N and Pires, AE and Racimo, F and Ramos-Almodovar, F and Savolainen, P and Venetsani, S and Tammen, I and Triantafyllidis, A and vonHoldt, B and Wayne, RK and Larson, G and Nicholas, FW and Lohi, H and Leeb, T and Zhang, YP and Ostrander, EA}, title = {Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture.}, journal = {Genome biology}, volume = {24}, number = {1}, pages = {187}, pmid = {37582787}, issn = {1474-760X}, support = {R01 GM140135/GM/NIGMS NIH HHS/United States ; R24 GM082910/GM/NIGMS NIH HHS/United States ; R25 GM086262/GM/NIGMS NIH HHS/United States ; }, mesh = {Dogs ; Animals ; *Wolves/genetics ; Chromosome Mapping ; Alleles ; Polymorphism, Single Nucleotide ; Nucleotides ; Demography ; }, abstract = {BACKGROUND: The international Dog10K project aims to sequence and analyze several thousand canine genomes. Incorporating 20 × data from 1987 individuals, including 1611 dogs (321 breeds), 309 village dogs, 63 wolves, and four coyotes, we identify genomic variation across the canid family, setting the stage for detailed studies of domestication, behavior, morphology, disease susceptibility, and genome architecture and function.

RESULTS: We report the analysis of > 48 M single-nucleotide, indel, and structural variants spanning the autosomes, X chromosome, and mitochondria. We discover more than 75% of variation for 239 sampled breeds. Allele sharing analysis indicates that 94.9% of breeds form monophyletic clusters and 25 major clades. German Shepherd Dogs and related breeds show the highest allele sharing with independent breeds from multiple clades. On average, each breed dog differs from the UU_Cfam_GSD_1.0 reference at 26,960 deletions and 14,034 insertions greater than 50 bp, with wolves having 14% more variants. Discovered variants include retrogene insertions from 926 parent genes. To aid functional prioritization, single-nucleotide variants were annotated with SnpEff and Zoonomia phyloP constraint scores. Constrained positions were negatively correlated with allele frequency. Finally, the utility of the Dog10K data as an imputation reference panel is assessed, generating high-confidence calls across varied genotyping platform densities including for breeds not included in the Dog10K collection.

CONCLUSIONS: We have developed a dense dataset of 1987 sequenced canids that reveals patterns of allele sharing, identifies likely functional variants, informs breed structure, and enables accurate imputation. Dog10K data are publicly available.}, } @article {pmid37584544, year = {2023}, author = {Yang, C and Li, X and Zhou, J and Gao, C}, title = {Autophagy contributes to positive feedback regulation of SnRK1 signaling in plants.}, journal = {Autophagy}, volume = {19}, number = {12}, pages = {3248-3250}, pmid = {37584544}, issn = {1554-8635}, mesh = {*Arabidopsis Proteins/metabolism ; AMP-Activated Protein Kinases/metabolism ; Feedback ; Autophagy ; *Arabidopsis/metabolism ; Plants/metabolism ; Transcription Factors/metabolism ; Adenosine Monophosphate ; Gene Expression Regulation, Plant ; Protein Serine-Threonine Kinases/metabolism ; Vesicular Transport Proteins/metabolism ; }, abstract = {SnRK1 (SNF1-related protein kinase 1) is a plant ortholog of yeast Snf1 and mammalian adenosine monophosphate-activated protein kinase (AMPK) that acts as a positive regulator of macroautophagy/autophagy. However, whether and how the autophagy pathway modulates SnRK1 activity remains elusive. Recently, we identified a clade of plant-specific FLZ (FCS-like zinc finger) proteins as novel ATG8 (autophagy-related 8)-interacting partners in Arabidopsis thaliana. These AtFLZs, which mainly localize on the surface of mitochondria, can inhibit SnRK1 signaling by repressing the T-loop phosphorylation of its catalytic α subunits, thereby negatively regulating carbon starvation-induced autophagy and plant tolerance to energy deprivation. Upon energy starvation, autophagy is activated to mediate the degradation of these AtFLZs, thus relieving their repression of SnRK1. More importantly, the ATG8-FLZ-SnRK1 regulatory axis appears to be functionally conserved during seed plant evolution. These findings highlight the positive role of autophagy in SnRK1 signaling activation under energy-limiting conditions in plants.Abbreviations: ADS, AIMs docking site; AIM, ATG8-interacting motif; AMPK, adenosine monophosphate-activated protein kinase; ATG, autophagy-related; ESCRT, endosomal sorting complexes required for transport; FLZ, FCS-like zinc finger protein; FREE1, FYVE DOMAIN PROTEIN REQUIRED FOR ENDOSOMAL SORTING 1; RAPTOR, REGULATORY-ASSOCIATED PROTEIN OF TOR; Snf1, SUCROSE NON-FERMENTING 1; SnRK1, SNF1-related kinase 1; TOR, TARGET OF RAPAMYCIN.}, } @article {pmid37587350, year = {2023}, author = {Merchant, A and Ramirez, BI and Reyes, MN and Van, D and Martinez-Colin, M and Ojo, DO and Mazuca, EL and De La O, HJ and Glenn, AM and Lira, CG and Ehsan, H and Yu, E and Kaneko, G}, title = {Genomic loss of the HSP70cA gene in the vertebrate lineage.}, journal = {Cell stress & chaperones}, volume = {28}, number = {6}, pages = {1053-1067}, pmid = {37587350}, issn = {1466-1268}, mesh = {Animals ; Phylogeny ; *Evolution, Molecular ; *Vertebrates/genetics ; Genome/genetics ; Genomics ; }, abstract = {Metazoan 70 kDa heat shock protein (HSP70) genes have been classified into four lineages: cytosolic A (HSP70cA), cytosolic B (HSP70cB), endoplasmic reticulum (HSP70er), and mitochondria (HSP70m). Because previous studies have identified no HSP70cA genes in vertebrates, we hypothesized that this gene was lost on the evolutionary path to vertebrates. To test this hypothesis, the present study conducted a comprehensive database search followed by phylogenetic and synteny analyses. HSP70cA genes were found in invertebrates and in two of the three subphyla of Chordata, Cephalochordata (lancelets) and Tunicata (tunicates). However, no HSP70cA gene was found in the genomes of Craniata (another subphylum of Chordata; lamprey, hagfish, elephant shark, and coelacanth), suggesting the loss of the HSP70cA gene in the early period of vertebrate evolution. Synteny analysis using available genomic resources indicated that the synteny around the HSP70 genes was generally conserved between tunicates but was largely different between tunicates and lamprey. These results suggest the presence of dynamic chromosomal rearrangement in early vertebrates that possibly caused the loss of the HSP70cA gene in the vertebrate lineage.}, } @article {pmid37596708, year = {2024}, author = {Golik, P}, title = {RNA processing and degradation mechanisms shaping the mitochondrial transcriptome of budding yeasts.}, journal = {IUBMB life}, volume = {76}, number = {1}, pages = {38-52}, doi = {10.1002/iub.2779}, pmid = {37596708}, issn = {1521-6551}, mesh = {*Transcriptome ; Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomycetales/genetics/metabolism ; Transcription, Genetic ; RNA Processing, Post-Transcriptional ; RNA ; RNA, Transfer/genetics/metabolism ; }, abstract = {Yeast mitochondrial genes are expressed as polycistronic transcription units that contain RNAs from different classes and show great evolutionary variability. The promoters are simple, and transcriptional control is rudimentary. Posttranscriptional mechanisms involving RNA maturation, stability, and degradation are thus the main force shaping the transcriptome and determining the expression levels of individual genes. Primary transcripts are fragmented by tRNA excision by RNase P and tRNase Z, additional processing events occur at the dodecamer site at the 3' end of protein-coding sequences. groups I and II introns are excised in a self-splicing reaction that is supported by protein splicing factors encoded by the nuclear genes, or by the introns themselves. The 3'-to-5' exoribonucleolytic complex called mtEXO is the main RNA degradation activity involved in RNA turnover and processing, supported by an auxiliary 5'-to-3' exoribonuclease Pet127p. tRNAs and, to a lesser extent, rRNAs undergo several different base modifications. This complex gene expression system relies on the coordinated action of mitochondrial and nuclear genes and undergoes rapid evolution, contributing to speciation events. Moving beyond the classical model yeast Saccharomyces cerevisiae to other budding yeasts should provide important insights into the coevolution of both genomes that constitute the eukaryotic genetic system.}, } @article {pmid37599162, year = {2024}, author = {Braun, HP and Klusch, N}, title = {Promotion of oxidative phosphorylation by complex I-anchored carbonic anhydrases?.}, journal = {Trends in plant science}, volume = {29}, number = {1}, pages = {64-71}, doi = {10.1016/j.tplants.2023.07.007}, pmid = {37599162}, issn = {1878-4372}, mesh = {*Carbonic Anhydrases/chemistry/metabolism ; Oxidative Phosphorylation ; Mitochondria/metabolism ; Plants/metabolism ; Hydrogen-Ion Concentration ; }, abstract = {The mitochondrial NADH-dehydrogenase complex of the respiratory chain, known as complex I, includes a carbonic anhydrase (CA) module attached to its membrane arm on the matrix side in protozoans, algae, and plants. Its physiological role is so far unclear. Recent electron cryo-microscopy (cryo-EM) structures show that the CA module may directly provide protons for translocation across the inner mitochondrial membrane at complex I. CAs can have a central role in adjusting the proton concentration in the mitochondrial matrix. We suggest that CA anchoring in complex I represents the original configuration to secure oxidative phosphorylation (OXPHOS) in the context of early endosymbiosis. After development of 'modern mitochondria' with pronounced cristae structures, this anchoring became dispensable, but has been retained in protozoans, algae, and plants.}, } @article {pmid37602330, year = {2023}, author = {Das, P and Pal, S and Das, N and Chakraborty, K and Chatterjee, K and Mal, S and Choudhuri, T}, title = {Endogenous PTEN acts as the key determinant for mTOR inhibitor sensitivity by inducing the stress-sensitized PTEN-mediated death axis in KSHV-associated malignant cells.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1062462}, pmid = {37602330}, issn = {2296-889X}, abstract = {As a part of viral cancer evolution, KSHV-infected human endothelial cells exert a unique transcriptional program via upregulated mTORC1 signaling. This event makes them sensitive to mTOR inhibitors. Master transcriptional regulator PTEN acts as the prime regulator of mTOR and determining factor for mTOR inhibitory drug resistance and sensitivity. PTEN is post-translationally modified in KSHV-associated cell lines and infected tissues. Our current study is an attempt to understand the functional role of upstream modulator PTEN in determining the sensitivity of mTOR inhibitors against KSHV-infected cells in an in vitro stress-responsive model. Our analysis shows that, despite phosphorylation, endogenous levels of intact PTEN in different KSHV-infected cells compared to normal and non-infected cells are quite high. Genetic overexpression of intact PTEN showed functional integrity of this gene in the infected cells in terms of induction of a synchronized cell death process via cell cycle regulation and mitochondria-mediated apoptosis. PTEN overexpression enhanced the mTOR inhibitory drug activity, the silencing of which hampers the process against KSHV-infected cells. Additionally, we have shown that endogenous PTEN acts as a stress balancer molecule inside KSHV-infected cells and can induce stress-sensitized death program post mTOR inhibitor treatment, lined up in the ATM-chk2-p53 axis. Moreover, autophagic regulation was found as a major regulator in mTOR inhibitor-induced PTEN-mediated death axis from our study. The current work critically intersected the PTEN-mediated stress balancing mechanism where autophagy has been utilized as a part of the KSHV stress management system and is specifically fitted and switched toward autophagy-mediated apoptosis directing toward a therapeutic perspective.}, } @article {pmid37603398, year = {2023}, author = {Ratliffe, J and Kataura, T and Otten, EG and Korolchuk, VI}, title = {The evolution of selective autophagy as a mechanism of oxidative stress response: The evolutionarily acquired ability of selective autophagy receptors to respond to oxidative stress is beneficial for human longevity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {45}, number = {11}, pages = {e2300076}, pmid = {37603398}, issn = {1521-1878}, support = {EP/W524700/1//EPSRC PhD studentship/ ; BB/M023389/1//BBSRC/ ; BB/R008167/2//BBSRC/ ; //The International Medical Research Foundation/ ; //Uehara Memorial Foundation/ ; }, mesh = {Humans ; *Oxidative Stress ; *Autophagy ; *Longevity ; *Reactive Oxygen Species/metabolism ; Animals ; Aging/metabolism/genetics ; Mitochondria/metabolism ; Biological Evolution ; Oxidation-Reduction ; }, abstract = {Ageing is associated with a decline in autophagy and elevated reactive oxygen species (ROS), which can breach the capacity of antioxidant systems. Resulting oxidative stress can cause further cellular damage, including DNA breaks and protein misfolding. This poses a challenge for longevous organisms, including humans. In this review, we hypothesise that in the course of human evolution selective autophagy receptors (SARs) acquired the ability to sense and respond to localised oxidative stress. We posit that in the vicinity of protein aggregates and dysfunctional mitochondria oxidation of key cysteine residues in SARs induces their oligomerisation which initiates autophagy. The degradation of damaged cellular components thus could reduce ROS production and restore redox homeostasis. This evolutionarily acquired function of SARs may represent one of the biological adaptations that contributed to longer lifespan. Inversely, loss of this mechanism can lead to age-related diseases associated with impaired autophagy and oxidative stress.}, } @article {pmid37604791, year = {2023}, author = {Fernández-Álvarez, FÁ and Sanchez, G and Deville, D and Taite, M and Villanueva, R and Allcock, AL}, title = {Atlantic Oceanic Squids in the "Grey Speciation Zone".}, journal = {Integrative and comparative biology}, volume = {63}, number = {6}, pages = {1214-1225}, pmid = {37604791}, issn = {1557-7023}, support = {IJC2020-043170-I//Generalitat de Catalunya/ ; GOIPD/2019/460//Irish Research Council/ ; 22K15085//Grant-in-Aid for Early-Career Scientists/ ; //Ministerio de Ciencia e Innovación/ ; //European Union/ ; CEX2019-000928-S//Spanish Government/ ; CTM2016-78853-R//FEDER/ ; }, mesh = {Animals ; Phylogeny ; *Decapodiformes ; Oceans and Seas ; *Biodiversity ; Mitochondria ; }, abstract = {Cryptic species complexes represent an important challenge for the adequate characterization of Earth's biodiversity. Oceanic organisms tend to have greater unrecognized cryptic biodiversity since the marine realm was often considered to lack hard barriers to genetic exchange. Here, we tested the effect of several Atlantic and Mediterranean oceanic barriers on 16 morphospecies of oceanic squids of the orders Oegopsida and Bathyteuthida using three mitochondrial and one nuclear molecular marker and five species delimitation methods. Number of species recognized within each morphospecies differed among different markers and analyses, but we found strong evidence of cryptic biodiversity in at least four of the studied species (Chtenopteryx sicula, Chtenopteryx canariensis, Ancistrocheirus lesueurii, and Galiteuthis armata). There were highly geographically structured units within Helicocranchia navossae that could either represent recently diverged species or population structure. Although the species studied here can be considered relatively passive with respect to oceanic currents, cryptic speciation patterns showed few signs of being related to oceanic currents. We hypothesize that the bathymetry of the egg masses and duration of the paralarval stage might influence the geographic distribution of oceanic squids. Because the results of different markers and different species delimitation methods are inconsistent and because molecular data encompassing broad geographic sampling areas for oceanic squids are scarce and finding morphological diagnostic characters for early life stages is difficult, it is challenging to assess the species boundaries for many of these species. Thus, we consider many to be in the "grey speciation zone." As many oceanic squids have cosmopolitan distributions, new studies combining genomic and morphological information from specimens collected worldwide are needed to correctly assess the actual oceanic squid biodiversity.}, } @article {pmid37628587, year = {2023}, author = {Hernández, CL}, title = {Mitochondrial DNA in Human Diversity and Health: From the Golden Age to the Omics Era.}, journal = {Genes}, volume = {14}, number = {8}, pages = {}, pmid = {37628587}, issn = {2073-4425}, mesh = {Humans ; *DNA, Mitochondrial/genetics ; *Mitochondria/genetics ; Anthropology ; Biological Evolution ; Inheritance Patterns ; }, abstract = {Mitochondrial DNA (mtDNA) is a small fraction of our hereditary material. However, this molecule has had an overwhelming presence in scientific research for decades until the arrival of high-throughput studies. Several appealing properties justify the application of mtDNA to understand how human populations are-from a genetic perspective-and how individuals exhibit phenotypes of biomedical importance. Here, I review the basics of mitochondrial studies with a focus on the dawn of the field, analysis methods and the connection between two sides of mitochondrial genetics: anthropological and biomedical. The particularities of mtDNA, with respect to inheritance pattern, evolutionary rate and dependence on the nuclear genome, explain the challenges of associating mtDNA composition and diseases. Finally, I consider the relevance of this single locus in the context of omics research. The present work may serve as a tribute to a tool that has provided important insights into the past and present of humankind.}, } @article {pmid37628588, year = {2023}, author = {Baldo, MS and Nogueira, C and Pereira, C and Janeiro, P and Ferreira, S and Lourenço, CM and Bandeira, A and Martins, E and Magalhães, M and Rodrigues, E and Santos, H and Ferreira, AC and Vilarinho, L}, title = {Leigh Syndrome Spectrum: A Portuguese Population Cohort in an Evolutionary Genetic Era.}, journal = {Genes}, volume = {14}, number = {8}, pages = {}, pmid = {37628588}, issn = {2073-4425}, mesh = {Child ; Infant ; Humans ; *Leigh Disease/genetics ; Portugal ; DNA, Mitochondrial/genetics ; Mitochondria ; Biological Evolution ; }, abstract = {Mitochondrial diseases are the most common inherited inborn error of metabolism resulting in deficient ATP generation, due to failure in homeostasis and proper bioenergetics. The most frequent mitochondrial disease manifestation in children is Leigh syndrome (LS), encompassing clinical, neuroradiological, biochemical, and molecular features. It typically affects infants but occurs anytime in life. Considering recent updates, LS clinical presentation has been stretched, and is now named LS spectrum (LSS), including classical LS and Leigh-like presentations. Apart from clinical diagnosis challenges, the molecular characterization also progressed from Sanger techniques to NGS (next-generation sequencing), encompassing analysis of nuclear (nDNA) and mitochondrial DNA (mtDNA). This upgrade resumed steps and favored diagnosis. Hereby, our paper presents molecular and clinical data on a Portuguese cohort of 40 positive cases of LSS. A total of 28 patients presented mutation in mtDNA and 12 in nDNA, with novel mutations identified in a heterogeneous group of genes. The present results contribute to the better knowledge of the molecular basis of LS and expand the clinical spectrum associated with this syndrome.}, } @article {pmid37628665, year = {2023}, author = {Havaš Auguštin, D and Šarac, J and Reidla, M and Tamm, E and Grahovac, B and Kapović, M and Novokmet, N and Rudan, P and Missoni, S and Marjanović, D and Korolija, M}, title = {Refining the Global Phylogeny of Mitochondrial N1a, X, and HV2 Haplogroups Based on Rare Mitogenomes from Croatian Isolates.}, journal = {Genes}, volume = {14}, number = {8}, pages = {}, pmid = {37628665}, issn = {2073-4425}, mesh = {Humans ; Phylogeny ; Croatia ; *Genome, Mitochondrial/genetics ; Mitochondria/genetics ; DNA, Mitochondrial/genetics ; }, abstract = {Mitochondrial DNA (mtDNA) has been used for decades as a predominant tool in population genetics and as a valuable addition to forensic genetic research, owing to its unique maternal inheritance pattern that enables the tracing of individuals along the maternal lineage across numerous generations. The dynamic interplay between evolutionary forces, primarily genetic drift, bottlenecks, and the founder effect, can exert significant influence on genetic profiles. Consequently, the Adriatic islands have accumulated a subset of lineages that exhibits remarkable absence or rarity within other European populations. This distinctive genetic composition underscores the islands' potential as a significant resource in phylogenetic research, with implications reaching beyond regional boundaries to contribute to a global understanding. In the initial attempt to expand the mitochondrial forensic database of the Croatian population with haplotypes from small isolated communities, we sequenced mitogenomes of rare haplogroups from different Croatian island and mainland populations using next-generation sequencing (NGS). In the next step and based on the obtained results, we refined the global phylogeny of haplogroup N1a, HV2, and X by analyzing rare haplotypes, which are absent from the current phylogenetic tree. The trees were based on 16 novel and 52 previously published samples, revealing completely novel branches in the X and HV2 haplogroups and a new European cluster in the ancestral N1a variant, previously believed to be an exclusively African-Asian haplogroup. The research emphasizes the importance of investigating geographically isolated populations and their unique characteristics within a global context.}, } @article {pmid37629077, year = {2023}, author = {Zalewska, A and Antonowicz, B and Szulimowska, J and Zieniewska-Siemieńczuk, I and Leśniewska, B and Borys, J and Zięba, S and Kostecka-Sochoń, P and Żendzian-Piotrowska, M and Lo Giudice, R and Lo Giudice, G and Żukowski, P and Maciejczyk, M}, title = {Mitochondrial Redox Balance of Fibroblasts Exposed to Ti-6Al-4V Microplates Subjected to Different Types of Anodizing.}, journal = {International journal of molecular sciences}, volume = {24}, number = {16}, pages = {}, pmid = {37629077}, issn = {1422-0067}, support = {B.SUB.23.309//Medical University in Bialystok/ ; }, mesh = {Humans ; *Titanium/pharmacology ; *Mitochondria ; Fibroblasts ; Oxidation-Reduction ; Alloys ; }, abstract = {Despite the high biocompatibility of titanium and its alloys, the need to remove titanium implants is increasingly being debated due to the potential for adverse effects associated with long-term retention. Therefore, new solutions are being sought to enhance the biocompatibility of titanium implants. One of them is to increase the thickness of the passive layer of the implant made of titanium dioxide. We were the first to evaluate the effect of hard-anodized (type II) Ti-6Al-4V alloy discs on the cytotoxicity, mitochondrial function, and redox balance of fibroblasts mitochondria compared to standard-anodized (type III) and non-anodized discs. The study used fibroblasts obtained from human gingival tissue. The test discs were applied to the bottom of 12-well plates. Cells were cultured for 24 h and 7, 14, and 21 days and mitochondria were isolated. We demonstrated the occurrence of oxidative stress in the mitochondria of fibroblasts of all tested groups, regardless of the presence and type of anodization. Type II anodization prevented changes in complex II activity (vs. control). The lowest degree of citrate synthase inhibition occurred in mitochondria exposed to titanium discs with type II anodization. In the last phase of culture, the presence of type II anodization reduced the degree of cytochrome c oxidase inhibition compared to the other tests groups and the control group, and prevented apoptosis. Throughout the experiment, the release of titanium, aluminium, and vanadium ions from titanium discs with a hard-anodized passive layer was higher than from the other titanium discs, but decreased with time. The obtained results proved the existence of dysfunction and redox imbalance in the mitochondria of fibroblasts exposed to hard-anodized titanium discs, suggesting the need to search for new materials perhaps biodegradable in tissues of the human body.}, } @article {pmid37629135, year = {2023}, author = {Cai, H and Ren, Y and Du, J and Liu, L and Long, L and Yang, M}, title = {Analysis of the RNA Editing Sites and Orthologous Gene Function of Transcriptome and Chloroplast Genomes in the Evolution of Five Deutzia Species.}, journal = {International journal of molecular sciences}, volume = {24}, number = {16}, pages = {}, pmid = {37629135}, issn = {1422-0067}, support = {No.21326301D//Province Key Research and Development Program of Hebei/ ; }, mesh = {*Transcriptome/genetics ; *Genome, Chloroplast ; Phylogeny ; RNA Editing/genetics ; Gene Expression Profiling ; }, abstract = {In this study, the chloroplast genomes and transcriptomes of five Deutzia genus species were sequenced, characterized, combined, and analyzed. A phylogenetic tree was constructed, including 32 other chloroplast genome sequences of Hydrangeoideae species. The results showed that the five Deutzia chloroplast genomes were typical circular genomes 156,860-157,025 bp in length, with 37.58-37.6% GC content. Repeat analysis showed that the Deutzia species had 41-45 scattered repeats and 199-201 simple sequence repeats. Comparative genomic and pi analyses indicated that the genomes are conservative and that the gene structures are stable. According to the phylogenetic tree, Deutzia species appear to be closely related to Kirengeshoma palmata and Philadelphus. By combining chloroplast genomic and transcriptomic analyses, 29-31 RNA editing events and 163-194 orthologous genes were identified. The ndh, rpo, rps, and atp genes had the most editing sites, and all RNA editing events were of the C-to-U type. Most of the orthologous genes were annotated to the chloroplast, mitochondria, and nucleus, with functions including energy production and conversion, translation, and protein transport. Genes related to the biosynthesis of monoterpenoids and flavonoids were also identified from the transcriptome of Deutzia spp. Our results will contribute to further studies of the genomic information and potential uses of the Deutzia spp.}, } @article {pmid37634556, year = {2023}, author = {Theriault, JE and Shaffer, C and Dienel, GA and Sander, CY and Hooker, JM and Dickerson, BC and Barrett, LF and Quigley, KS}, title = {A functional account of stimulation-based aerobic glycolysis and its role in interpreting BOLD signal intensity increases in neuroimaging experiments.}, journal = {Neuroscience and biobehavioral reviews}, volume = {153}, number = {}, pages = {105373}, pmid = {37634556}, issn = {1873-7528}, support = {R01 AG071173/AG/NIA NIH HHS/United States ; R01 MH109464/MH/NIMH NIH HHS/United States ; R21 MH129902/MH/NIMH NIH HHS/United States ; R01 MH113234/MH/NIMH NIH HHS/United States ; U01 CA193632/CA/NCI NIH HHS/United States ; R01 CA258269/CA/NCI NIH HHS/United States ; R00 DA043629/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; *Glycolysis/physiology ; *Adenosine Triphosphate ; Brain/diagnostic imaging/metabolism ; Glucose/metabolism ; Neuroimaging ; }, abstract = {In aerobic glycolysis, oxygen is abundant, and yet cells metabolize glucose without using it, decreasing their ATP per glucose yield by 15-fold. During task-based stimulation, aerobic glycolysis occurs in localized brain regions, presenting a puzzle: why produce ATP inefficiently when, all else being equal, evolution should favor the efficient use of metabolic resources? The answer is that all else is not equal. We propose that a tradeoff exists between efficient ATP production and the efficiency with which ATP is spent to transmit information. Aerobic glycolysis, despite yielding little ATP per glucose, may support neuronal signaling in thin (< 0.5 µm), information-efficient axons. We call this the efficiency tradeoff hypothesis. This tradeoff has potential implications for interpretations of task-related BOLD "activation" observed in fMRI. We hypothesize that BOLD "activation" may index local increases in aerobic glycolysis, which support signaling in thin axons carrying "bottom-up" information, or "prediction error"-i.e., the BIAPEM (BOLD increases approximate prediction error metabolism) hypothesis. Finally, we explore implications of our hypotheses for human brain evolution, social behavior, and mental disorders.}, } @article {pmid37636259, year = {2023}, author = {Fiedler, L and Middendorf, M and Bernt, M}, title = {Fully automated annotation of mitochondrial genomes using a cluster-based approach with de Bruijn graphs.}, journal = {Frontiers in genetics}, volume = {14}, number = {}, pages = {1250907}, pmid = {37636259}, issn = {1664-8021}, abstract = {A wide range of scientific fields, such as forensics, anthropology, medicine, and molecular evolution, benefits from the analysis of mitogenomic data. With the development of new sequencing technologies, the amount of mitochondrial sequence data to be analyzed has increased exponentially over the last few years. The accurate annotation of mitochondrial DNA is a prerequisite for any mitogenomic comparative analysis. To sustain with the growth of the available mitochondrial sequence data, highly efficient automatic computational methods are, hence, needed. Automatic annotation methods are typically based on databases that contain information about already annotated (and often pre-curated) mitogenomes of different species. However, the existing approaches have several shortcomings: 1) they do not scale well with the size of the database; 2) they do not allow for a fast (and easy) update of the database; and 3) they can only be applied to a relatively small taxonomic subset of all species. Here, we present a novel approach that does not have any of these aforementioned shortcomings, (1), (2), and (3). The reference database of mitogenomes is represented as a richly annotated de Bruijn graph. To generate gene predictions for a new user-supplied mitogenome, the method utilizes a clustering routine that uses the mapping information of the provided sequence to this graph. The method is implemented in a software package called DeGeCI (De Bruijn graph Gene Cluster Identification). For a large set of mitogenomes, for which expert-curated annotations are available, DeGeCI generates gene predictions of high conformity. In a comparative evaluation with MITOS2, a state-of-the-art annotation tool for mitochondrial genomes, DeGeCI shows better database scalability while still matching MITOS2 in terms of result quality and providing a fully automated means to update the underlying database. Moreover, unlike MITOS2, DeGeCI can be run in parallel on several processors to make use of modern multi-processor systems.}, } @article {pmid37636868, year = {2023}, author = {Le Cam, S and Brémaud, J and Malkócs, T and Kreckelbergh, E and Becquet, V and Dubillot, E and Garcia, P and Breton, S and Pante, E}, title = {LAMP-based molecular sexing in a gonochoric marine bivalve (Macoma balthica rubra) with divergent sex-specific mitochondrial genomes.}, journal = {Ecology and evolution}, volume = {13}, number = {8}, pages = {e10320}, pmid = {37636868}, issn = {2045-7758}, abstract = {Taking advantage of the unique system of doubly uniparental inheritance (DUI) of mitochondria, we developed a reliable molecular method to sex individuals of the marine bivalve Macoma balthica rubra. In species with DUI (~100 known bivalves), both sexes transmit their mitochondria: males bear both a male- and female-type mitogenome, while females bear only the female type. Male and female mitotypes are sufficiently divergent to reliably PCR-amplify them specifically. Loop-mediated isothermal amplification (LAMP) is a precise, economical and portable alternative to PCR for molecular sexing and we demonstrate its application in this context. We used 154 individuals sampled along the Atlantic coast of France and sexed microscopically by gonad examination to test for the congruence among gamete type, PCR sexing and LAMP sexing. We show an exact match among the sexing results from these three methods using the male and female mt-cox1 genes. DUI can be disrupted in inter-specific hybrids, causing unexpected distribution of mitogenomes, such as homoplasmic males or heteroplasmic females. To our knowledge, DUI disruption at the intra-specific scale has never been tested. We applied our sexing protocol to control for unexpected heteroplasmy caused by hybridization between divergent genetic lineages and found no evidence of disruption in the mode of mitochondrial inheritance in M. balthica rubra. We propose LAMP as a useful tool to accelerate eco-evolutionary studies of DUI. It offers the opportunity to investigate the potential role of, previously unaccounted-for, sex-specific patterns such as sexual selection or sex-specific dispersal bias in the evolution of free-spawning benthic species.}, } @article {pmid37638880, year = {2023}, author = {Gupta, SV and Campos, L and Schmidt, KH}, title = {Mitochondrial superoxide dismutase Sod2 suppresses nuclear genome instability during oxidative stress.}, journal = {Genetics}, volume = {225}, number = {2}, pages = {}, pmid = {37638880}, issn = {1943-2631}, support = {R01 GM132821/GM/NIGMS NIH HHS/United States ; R01 GM139296/GM/NIGMS NIH HHS/United States ; R01GM018245/NH/NIH HHS/United States ; }, mesh = {Antioxidants ; DNA ; Genomic Instability ; Oxidative Stress ; Reactive Oxygen Species ; RecQ Helicases/metabolism ; *Saccharomyces cerevisiae/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; Superoxide Dismutase/genetics/metabolism ; Superoxide Dismutase 2 ; }, abstract = {Oxidative stress can damage DNA and thereby contribute to genome instability. To avoid an imbalance or overaccumulation of reactive oxygen species (ROS), cells are equipped with antioxidant enzymes that scavenge excess ROS. Cells lacking the RecQ-family DNA helicase Sgs1, which contributes to homology-dependent DNA break repair and chromosome stability, are known to accumulate ROS, but the origin and consequences of this oxidative stress phenotype are not fully understood. Here, we show that the sgs1 mutant exhibits elevated mitochondrial superoxide, increased mitochondrial mass, and accumulation of recombinogenic DNA lesions that can be suppressed by antioxidants. Increased mitochondrial mass in the sgs1Δ mutant is accompanied by increased mitochondrial branching, which was also inducible in wildtype cells by replication stress. Superoxide dismutase Sod2 genetically interacts with Sgs1 in the suppression of nuclear chromosomal rearrangements under paraquat (PQ)-induced oxidative stress. PQ-induced chromosome rearrangements in the absence of Sod2 are promoted by Rad51 recombinase and the polymerase subunit Pol32. Finally, the dependence of chromosomal rearrangements on the Rev1/Pol ζ mutasome suggests that under oxidative stress successful DNA synthesis during DNA break repair depends on translesion DNA synthesis.}, } @article {pmid37644003, year = {2023}, author = {French, CM and Bertola, LD and Carnaval, AC and Economo, EP and Kass, JM and Lohman, DJ and Marske, KA and Meier, R and Overcast, I and Rominger, AJ and Staniczenko, PPA and Hickerson, MJ}, title = {Global determinants of insect mitochondrial genetic diversity.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5276}, pmid = {37644003}, issn = {2041-1723}, mesh = {Animals ; *Insecta/genetics ; *Mitochondria ; DNA, Mitochondrial/genetics ; Biodiversity ; Genetic Variation ; }, abstract = {Understanding global patterns of genetic diversity is essential for describing, monitoring, and preserving life on Earth. To date, efforts to map macrogenetic patterns have been restricted to vertebrates, which comprise only a small fraction of Earth's biodiversity. Here, we construct a global map of predicted insect mitochondrial genetic diversity from cytochrome c oxidase subunit 1 sequences, derived from open data. We calculate the mitochondrial genetic diversity mean and genetic diversity evenness of insect assemblages across the globe, identify their environmental correlates, and make predictions of mitochondrial genetic diversity levels in unsampled areas based on environmental data. Using a large single-locus genetic dataset of over 2 million globally distributed and georeferenced mtDNA sequences, we find that mitochondrial genetic diversity evenness follows a quadratic latitudinal gradient peaking in the subtropics. Both mitochondrial genetic diversity mean and evenness positively correlate with seasonally hot temperatures, as well as climate stability since the last glacial maximum. Our models explain 27.9% and 24.0% of the observed variation in mitochondrial genetic diversity mean and evenness in insects, respectively, making an important step towards understanding global biodiversity patterns in the most diverse animal taxon.}, } @article {pmid37662149, year = {2023}, author = {Liu, H and Hou, Z and Xu, L and Ma, Q and Wei, M and Tembrock, LR and Zhang, S and Wu, Z}, title = {Comparative analysis of organellar genomes between diploid and tetraploid Chrysanthemum indicum with its relatives.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1228551}, pmid = {37662149}, issn = {1664-462X}, abstract = {Chrysanthemum indicum, a species native to Eastern Asia is well known as one of the progenitor species of the cultivated Chrysanthemum which is grown for its ornamental and medicinal value. Previous genomic studies on Chrysanthemum have largely ignored the dynamics of plastid genome (plastome) and mitochondria genome (mitogenome) evolution when analyzing this plant lineage. In this study, we sequenced and assembled the plastomes and mitogenomes of diploid and tetraploid C. indicum as well as the morphologically divergent variety C. indicum var. aromaticum. We used published data from 27 species with both plastome and mitogenome complete sequences to explore differences in sequence evolution between the organellar genomes. The size and structure of organellar genome between diploid and tetraploid C. indicum were generally similar but the tetraploid C. indicum and C. indicum var. aromaticum were found to contain unique sequences in the mitogenomes which also contained previously undescribed open reading frames (ORFs). Across Chrysanthemum mitogenome structure varied greatly but sequences transferred from plastomes in to the mitogenomes were conserved. Finally, differences observed between mitogenome and plastome gene trees may be the result of the difference in the rate of sequence evolution between genes in these two genomes. In total the findings presented here greatly expand the resources for studying Chrysanthemum organellar genome evolution with possible applications to conservation, breeding, and gene banking in the future.}, } @article {pmid37664184, year = {2023}, author = {Mendoza-Hoffmann, F and Yang, L and Buratto, D and Brito-Sánchez, J and Garduño-Javier, G and Salinas-López, E and Uribe-Álvarez, C and Ortega, R and Sotelo-Serrano, O and Cevallos, MÁ and Ramírez-Silva, L and Uribe-Carvajal, S and Pérez-Hernández, G and Celis-Sandoval, H and García-Trejo, JJ}, title = {Inhibitory to non-inhibitory evolution of the ζ subunit of the F1FO-ATPase of Paracoccus denitrificans and α-proteobacteria as related to mitochondrial endosymbiosis.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1184200}, pmid = {37664184}, issn = {2296-889X}, abstract = {Introduction: The ζ subunit is a potent inhibitor of the F1FO-ATPase of Paracoccus denitrificans (PdF1FO-ATPase) and related α-proteobacteria different from the other two canonical inhibitors of bacterial (ε) and mitochondrial (IF1) F1FO-ATPases. ζ mimics mitochondrial IF1 in its inhibitory N-terminus, blocking the PdF1FO-ATPase activity as a unidirectional pawl-ratchet and allowing the PdF1FO-ATP synthase turnover. ζ is essential for the respiratory growth of P. denitrificans, as we showed by a Δζ knockout. Given the vital role of ζ in the physiology of P. denitrificans, here, we assessed the evolution of ζ across the α-proteobacteria class. Methods: Through bioinformatic, biochemical, molecular biology, functional, and structural analyses of several ζ subunits, we confirmed the conservation of the inhibitory N-terminus of ζ and its divergence toward its C-terminus. We reconstituted homologously or heterologously the recombinant ζ subunits from several α-proteobacteria into the respective F-ATPases, including free-living photosynthetic, facultative symbiont, and intracellular facultative or obligate parasitic α-proteobacteria. Results and discussion: The results show that ζ evolved, preserving its inhibitory function in free-living α-proteobacteria exposed to broad environmental changes that could compromise the cellular ATP pools. However, the ζ inhibitory function was diminished or lost in some symbiotic α-proteobacteria where ζ is non-essential given the possible exchange of nutrients and ATP from hosts. Accordingly, the ζ gene is absent in some strictly parasitic pathogenic Rickettsiales, which may obtain ATP from the parasitized hosts. We also resolved the NMR structure of the ζ subunit of Sinorhizobium meliloti (Sm-ζ) and compared it with its structure modeled in AlphaFold. We found a transition from a compact ordered non-inhibitory conformation into an extended α-helical inhibitory N-terminus conformation, thus explaining why the Sm-ζ cannot exert homologous inhibition. However, it is still able to inhibit the PdF1FO-ATPase heterologously. Together with the loss of the inhibitory function of α-proteobacterial ε, the data confirm that the primary inhibitory function of the α-proteobacterial F1FO-ATPase was transferred from ε to ζ and that ζ, ε, and IF1 evolved by convergent evolution. Some key evolutionary implications on the endosymbiotic origin of mitochondria, as most likely derived from α-proteobacteria, are also discussed.}, } @article {pmid37667092, year = {2023}, author = {Kar, C and Mariyambi, PC and Raghavan, R and Sureshkumar, S}, title = {Mitochondrial phylogeny of fusilier fishes (family Caesionidae) from the Laccadive archipelago reveals a new species and two new records from the Central Indian Ocean.}, journal = {Journal of fish biology}, volume = {103}, number = {6}, pages = {1445-1451}, doi = {10.1111/jfb.15553}, pmid = {37667092}, issn = {1095-8649}, support = {CRG/2020/004498//Department of Science and Technology, Government of India/ ; 200510341520//University Grants Commission/ ; }, mesh = {Animals ; Phylogeny ; Indian Ocean ; *Fishes/genetics ; *Mitochondria/genetics ; Genes, Mitochondrial ; Pacific Ocean ; }, abstract = {Fusiliers of the family Caesionidae comprise a group of Indo-Pacific reef fishes important in the live bait and artisanal fisheries in many parts of its range, particularly in the Indian Ocean region. Using newly generated mitochondrial COI sequences of 10 species of caesionid fishes from the Laccadive archipelago, we carried out a molecular phylogenetic analysis, which has helped improve our understanding of the diversity, distribution, and systematics of this poorly known group of fishes. The two speciose genera within Caesionidae, Caesio and Pterocaesio, were revealed to be paraphyletic, and as a result, four names earlier considered as subgenera within Caesionidae (Flavicaesio, Odontonectes, Pisinnicaesio, and Squamosicaesio) were elevated to the status of distinct genera. We also discovered the presence of a new lineage in the Central Indian Ocean, sister to Caesio caerulaurea and Caesio xanthalytos, but distinct from both in several morphological characters and a genetic distance of between 2% and 3% in the mitochondrial COI gene. We describe this lineage as Caesio idreesi, a new species, with a distribution spanning the Laccadive Sea and the Bay of Bengal. Our genetic data also helped confirm the first confirmed records of two species, Pisinnicaesio digramma and Squamosicaesio randalli, from the Central Indian Ocean, and a new distribution record for C. xanthalytos in the Laccadive Sea. Combined, these results have helped bridge key biodiversity knowledge gaps of the family Caesionidae and form an excellent baseline for further investigations on their taxonomy, systematics, and life history.}, } @article {pmid37685874, year = {2023}, author = {Maffeo, B and Panuzzo, C and Moraca, A and Cilloni, D}, title = {A Leukemic Target with a Thousand Faces: The Mitochondria.}, journal = {International journal of molecular sciences}, volume = {24}, number = {17}, pages = {}, pmid = {37685874}, issn = {1422-0067}, mesh = {Humans ; *Mitochondria ; Cell Division ; Clonal Evolution ; Clone Cells ; *Leukemia ; }, abstract = {In the era of personalized medicine greatly improved by molecular diagnosis and tailor-made therapies, the survival rate of acute myeloid leukemia (AML) at 5 years remains unfortunately low. Indeed, the high heterogeneity of AML clones with distinct metabolic and molecular profiles allows them to survive the chemotherapy-induced changes, thus leading to resistance, clonal evolution, and relapse. Moreover, leukemic stem cells (LSCs), the quiescent reservoir of residual disease, can persist for a long time and activate the recurrence of disease, supported by significant metabolic differences compared to AML blasts. All these points highlight the relevance to develop combination therapies, including metabolism inhibitors to improve treatment efficacy. In this review, we summarized the metabolic differences in AML blasts and LSCs, the molecular pathways related to mitochondria and metabolism are druggable and targeted in leukemia therapies, with a distinct interest for Venetoclax, which has revolutionized the therapeutic paradigms of several leukemia subtype, unfit for intensive treatment regimens.}, } @article {pmid37708410, year = {2023}, author = {Khachaturyan, M and Reusch, TBH and Dagan, T}, title = {Worldwide Population Genomics Reveal Long-Term Stability of the Mitochondrial Genome Architecture in a Keystone Marine Plant.}, journal = {Genome biology and evolution}, volume = {15}, number = {9}, pages = {}, pmid = {37708410}, issn = {1759-6653}, mesh = {Humans ; Metagenomics ; *Genome, Mitochondrial ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; *Magnoliopsida/genetics ; }, abstract = {Mitochondrial genomes (mitogenomes) of flowering plants are composed of multiple chromosomes. Recombination within and between the mitochondrial chromosomes may generate diverse DNA molecules termed isoforms. The isoform copy number and composition can be dynamic within and among individual plants due to uneven replication and homologous recombination. Nonetheless, despite their functional importance, the level of mitogenome conservation within species remains understudied. Whether the ontogenetic variation translates to evolution of mitogenome composition over generations is currently unknown. Here we show that the mitogenome composition of the seagrass Zostera marina is conserved among worldwide populations that diverged ca. 350,000 years ago. Using long-read sequencing, we characterized the Z. marina mitochondrial genome and inferred the repertoire of recombination-induced configurations. To characterize the mitochondrial genome architecture worldwide and study its evolution, we examined the mitogenome in Z. marina meristematic region sampled in 16 populations from the Pacific and Atlantic oceans. Our results reveal a striking similarity in the isoform relative copy number, indicating a high conservation of the mitogenome composition among distantly related populations and within the plant germline, despite a notable variability during individual ontogenesis. Our study supplies a link between observations of dynamic mitogenomes at the level of plant individuals and long-term mitochondrial evolution.}, } @article {pmid37715276, year = {2023}, author = {Leal-Dutra, CA and Yuen, LM and Guedes, BAM and Contreras-Serrano, M and Marques, PE and Shik, JZ}, title = {Evidence that the domesticated fungus Leucoagaricus gongylophorus recycles its cytoplasmic contents as nutritional rewards to feed its leafcutter ant farmers.}, journal = {IMA fungus}, volume = {14}, number = {1}, pages = {19}, pmid = {37715276}, issn = {2210-6340}, support = {ERC-2017-STG-757810/ERC_/European Research Council/International ; }, abstract = {Leafcutter ants farm a fungal cultivar (Leucoagaricus gongylophorus) that converts inedible vegetation into food that sustains colonies with up to millions of workers. Analogous to edible fruits of crops domesticated by humans, L. gongylophorus has evolved specialized nutritional rewards-swollen hyphal cells called gongylidia that package metabolites and are consumed by ant farmers. Yet, little is known about how gongylidia form, and thus how fungal physiology and ant provisioning collectively govern farming performance. We explored the process of gongylidium formation using advanced microscopy to image the cultivar at scales of nanometers, and both in vitro experiments and in silico analyses to examine the mechanisms of gongylidia formation when isolated from ant farmers. We first used transmission electron, fluorescence, and confocal microscopy imaging to see inside hyphal cells. This imaging showed that the cultivar uses a process called autophagy to recycle its own cellular material (e.g. cytosol, mitochondria) and then shuttles the resulting metabolites into a vacuole whose continual expansion displaces other organelles and causes the gongylidium cell's bulging bulb-like appearance. We next used scanning electron microscopy and light microscopy to link this intracellular rearrangement to the external branching patterns of gongylidium cells as they clump together into edible bundles called staphyla. We next confirmed that autophagy plays a critical role in gongylidium formation both: (1) in vitro as gongylidium suppression occurred when isolated fungal cultures were grown on media with autophagy inhibitors, and (2) in silico as differential transcript expression (RNA-seq) analyses showed upregulation of multiple autophagy gene isoforms in gongylidia relative to undifferentiated hyphae. While autophagy is a ubiquitous and often highly derived process across the tree of life, our study reveals a new role for autophagy as a mechanism of functional integration between ant farmers and their fungal crop, and potentially as a signifier of higher-level homeostasis between uniquely life-time committed ectosymbionts.}, } @article {pmid37717227, year = {2024}, author = {Chen, S and Tran, TTT and Yeh, AY and Yang, H and Chen, J and Yang, Y and Wang, X}, title = {The Globodera rostochiensis Gr29D09 Effector with a Role in Defense Suppression Targets the Potato Hexokinase 1 Protein.}, journal = {Molecular plant-microbe interactions : MPMI}, volume = {37}, number = {1}, pages = {25-35}, doi = {10.1094/MPMI-07-23-0095-R}, pmid = {37717227}, issn = {0894-0282}, mesh = {Animals ; *Solanum tuberosum ; Hexokinase/genetics ; Reactive Oxygen Species ; Phylogeny ; Proteins/genetics ; *Nematoda ; *Tylenchoidea/physiology ; }, abstract = {The potato cyst nematode (Globodera rostochiensis) is an obligate root pathogen of potatoes. G. rostochiensis encodes several highly expanded effector gene families, including the Gr4D06 family; however, little is known about the function of this effector family. We cloned four 29D09 genes from G. rostochiensis (named Gr29D09v1/v2/v3/v4) that share high sequence similarity and are homologous to the Hg29D09 and Hg4D06 effector genes from the soybean cyst nematode (Heterodera glycines). Phylogenetic analysis revealed that Gr29D09 genes belong to a subgroup of the Gr4D06 family. We showed that Gr29D09 genes are expressed exclusively within the nematode's dorsal gland cell and are dramatically upregulated in parasitic stages, indicating involvement of Gr29D09 effectors in nematode parasitism. Transgenic potato lines overexpressing Gr29D09 variants showed increased susceptibility to G. rostochiensis. Transient expression assays in Nicotiana benthamiana demonstrated that Gr29D09v3 could suppress reactive oxygen species (ROS) production and defense gene expression induced by flg22 and cell death mediated by immune receptors. These results suggest a critical role of Gr29D09 effectors in defense suppression. The use of affinity purification coupled with nanoliquid chromatography-tandem mass spectrometry identified potato hexokinase 1 (StHXK1) as a candidate target of Gr29D09. The Gr29D09-StHXK1 interaction was further confirmed using in planta protein-protein interaction assays. Plant HXKs have been implicated in defense regulation against pathogen infection. Interestingly, we found that StHXK1 could enhance flg22-induced ROS production, consistent with a positive role of plant HXKs in defense. Altogether, our results suggest that targeting StHXK1 by Gr29D09 effectors may impair the positive function of StHXK1 in plant immunity, thereby aiding nematode parasitism. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.}, } @article {pmid37735485, year = {2023}, author = {Sidorczuk, K and Mackiewicz, P and Pietluch, F and Gagat, P}, title = {Characterization of signal and transit peptides based on motif composition and taxon-specific patterns.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {15751}, pmid = {37735485}, issn = {2045-2322}, mesh = {Amino Acid Sequence ; *Amino Acids ; *Antimicrobial Peptides ; Chloroplasts ; Computational Biology ; }, abstract = {Targeting peptides or presequences are N-terminal extensions of proteins that encode information about their cellular localization. They include signal peptides (SP), which target proteins to the endoplasmic reticulum, and transit peptides (TP) directing proteins to the organelles of endosymbiotic origin: chloroplasts and mitochondria. TPs were hypothesized to have evolved from antimicrobial peptides (AMPs), which are responsible for the host defence against microorganisms, including bacteria, fungi and viruses. In this study, we performed comprehensive bioinformatic analyses of amino acid motifs of targeting peptides and AMPs using a curated set of experimentally verified proteins. We identified motifs frequently occurring in each type of presequence showing specific patterns associated with their amino acid composition, and investigated their position within the presequence. We also compared motif patterns among different taxonomic groups and identified taxon-specific features, providing some evolutionary insights. Considering the functional relevance and many practical applications of targeting peptides and AMPs, we believe that our analyses will prove useful for their design, and better understanding of protein import mechanism and presequence evolution.}, } @article {pmid37742881, year = {2024}, author = {Zhang, T and Vďačný, P}, title = {Deciphering phylogenetic relationships of and delimiting species boundaries within the controversial ciliate genus Conchophthirus using an integrative morpho-evo approach.}, journal = {Molecular phylogenetics and evolution}, volume = {190}, number = {}, pages = {107931}, doi = {10.1016/j.ympev.2023.107931}, pmid = {37742881}, issn = {1095-9513}, mesh = {Phylogeny ; Sequence Analysis, DNA ; *Oligohymenophorea ; *Ciliophora/genetics ; Mitochondria ; }, abstract = {The phylum Ciliophora (ciliates) comprises about 2600 symbiotic and over 5500 free-living species. The inclusion of symbiotic ciliates in phylogenetic analyses often challenges traditional classification frameworks due to their morphological adaptions to the symbiotic lifestyle. Conchophthirus is such a controversial obligate endocommensal genus whose affinities to other symbiotic and free-living scuticociliates are still poorly understood. Using uni- and multivariate morphometrics as well as 2D-based molecular and phylogenetic analyses, we attempted to test for the monophyly of Conchophthirus, study the boundaries of Conchophthirus species isolated from various bivalves at mesoscale, and reveal the phylogenetic relationships of Conchophthirus to other scuticociliates. Multidimensional analyses of morphometric and cell geometric data generated the same homogenous clusters, as did phylogenetic analyses based on 144 new sequences of two mitochondrial and five nuclear molecular markers. Conchophthirus is not closely related to 'core' scuticociliates represented by the orders Pleuronematida and Philasterida, as assumed in the past using morphological data. Nuclear and mitochondrial markers consistently showed the free-living Dexiotricha and the mouthless endosymbiotic Haptophrya to be the nearest relatives of Conchophthirus. These three highly morphologically and ecologically dissimilar genera represent an orphan clade from the early radiation of scuticociliates in molecular phylogenies.}, } @article {pmid37744141, year = {2021}, author = {Clergeot, PH and Olson, Å}, title = {Mitonuclear Genetic Interactions in the Basidiomycete Heterobasidion parviporum Involve a Non-conserved Mitochondrial Open Reading Frame.}, journal = {Frontiers in fungal biology}, volume = {2}, number = {}, pages = {779337}, pmid = {37744141}, issn = {2673-6128}, abstract = {The mitochondrial and nuclear genomes of Eukaryotes are inherited separately and consequently follow distinct evolutionary paths. Nevertheless, the encoding of many mitochondrial proteins by the nuclear genome shows the high level of integration they have reached, which makes mitonuclear genetic interactions all the more conceivable. For each species, natural selection has fostered the evolution of coadapted alleles in both genomes, but a population-wise divergence of such alleles could lead to important phenotypic variation, and, ultimately, to speciation. In this study in the Basidiomycete Heterobasidion parviporum, we have investigated the genetic basis of phenotypic variation among laboratory-designed heterokaryons carrying the same pair of haploid nuclei, but a different mitochondrial genome. Radial growth rate data of thirteen unrelated homokaryotic parents and of their heterokaryotic offspring were combined with SNP data extracted from parental genome sequences to identify nuclear and mitochondrial loci involved in mitonuclear interactions. Two nuclear loci encoding mitochondrial proteins appeared as best candidates to engage in a genetic interaction affecting radial growth rate with a non-conserved mitochondrial open reading frame of unknown function and not reported apart from the Russulales order of Basidiomycete fungi. We believe our approach could be useful to investigate several important traits of fungal biology where mitonuclear interactions play a role, including virulence of fungal pathogens.}, } @article {pmid37744223, year = {2023}, author = {Suárez Menéndez, M and Rivera-León, VE and Robbins, J and Berube, M and Palsbøll, PJ}, title = {PHFinder: assisted detection of point heteroplasmy in Sanger sequencing chromatograms.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e16028}, pmid = {37744223}, issn = {2167-8359}, mesh = {Animals ; *Heteroplasmy ; Fluorescence ; *Humpback Whale ; Mitochondria ; Nucleotides ; }, abstract = {Heteroplasmy is the presence of two or more organellar genomes (mitochondrial or plastid DNA) in an organism, tissue, cell or organelle. Heteroplasmy can be detected by visual inspection of Sanger sequencing chromatograms, where it appears as multiple peaks of fluorescence at a single nucleotide position. Visual inspection of chromatograms is both consuming and highly subjective, as heteroplasmy is difficult to differentiate from background noise. Few software solutions are available to automate the detection of point heteroplasmies, and those that are available are typically proprietary, lack customization or are unsuitable for automated heteroplasmy assessment in large datasets. Here, we present PHFinder, a Python-based, open-source tool to assist in the detection of point heteroplasmies in large numbers of Sanger chromatograms. PHFinder automatically identifies point heteroplasmies directly from the chromatogram trace data. The program was tested with Sanger sequencing data from 100 humpback whales (Megaptera novaeangliae) tissue samples with known heteroplasmies. PHFinder detected most (90%) of the known heteroplasmies thereby greatly reducing the amount of visual inspection required. PHFinder is flexible and enables explicit specification of key parameters to infer double peaks (i.e., heteroplasmies).}, } @article {pmid37748065, year = {2023}, author = {Zhang, K and Zhao, X and Zhao, Y and Zhang, Z and Liu, Z and Liu, Z and Yu, Y and Li, J and Ma, Y and Dong, Y and Pang, X and Jin, X and Li, N and Liu, B and Wendel, JF and Zhai, J and Long, Y and Wang, T and Gong, L}, title = {Cell type-specific cytonuclear coevolution in three allopolyploid plant species.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {40}, pages = {e2310881120}, pmid = {37748065}, issn = {1091-6490}, mesh = {*Mitochondria/genetics ; *Plastids ; Cell Differentiation ; Solitary Nucleus ; }, abstract = {Cytonuclear disruption may accompany allopolyploid evolution as a consequence of the merger of different nuclear genomes in a cellular environment having only one set of progenitor organellar genomes. One path to reconcile potential cytonuclear mismatch is biased expression for maternal gene duplicates (homoeologs) encoding proteins that target to plastids and/or mitochondria. Assessment of this transcriptional form of cytonuclear coevolution at the level of individual cells or cell types remains unexplored. Using single-cell (sc-) and single-nucleus (sn-) RNAseq data from eight tissues in three allopolyploid species, we characterized cell type-specific variations of cytonuclear coevolutionary homoeologous expression and demonstrated the temporal dynamics of expression patterns across development stages during cotton fiber development. Our results provide unique insights into transcriptional cytonuclear coevolution in plant allopolyploids at the single-cell level.}, } @article {pmid37752851, year = {2023}, author = {Togashi, T and Parker, GA and Horinouchi, Y}, title = {Mitochondrial uniparental inheritance achieved after fertilization challenges the nuclear-cytoplasmic conflict hypothesis for anisogamy evolution.}, journal = {Biology letters}, volume = {19}, number = {9}, pages = {20230352}, pmid = {37752851}, issn = {1744-957X}, mesh = {Male ; Humans ; *Mitochondria ; *DNA, Mitochondrial/genetics ; Inheritance Patterns ; Polymerase Chain Reaction ; Fertilization ; }, abstract = {In eukaryotes, a fundamental phenomenon underlying sexual selection is the evolution of gamete size dimorphism between the sexes (anisogamy) from an ancestral gametic system with gametes of the same size in both mating types (isogamy). The nuclear-cytoplasmic conflict hypothesis has been one of the major theoretical hypotheses for the evolution of anisogamy. It proposes that anisogamy evolved as an adaptation for preventing nuclear-cytoplasmic conflict by minimizing male gamete size to inherit organelles uniparentally. In ulvophycean green algae, biparental inheritance of organelles is observed in isogamous species, as the hypothesis assumes. So we tested the hypothesis by examining whether cytoplasmic inheritance is biparental in Monostroma angicava, a slightly anisogamous ulvophycean that produces large male gametes. We tracked the fates of mitochondria in intraspecific crosses with PCR-RFLP markers. We confirmed that mitochondria are maternally inherited. However, paternal mitochondria enter the zygote, where their DNA can be detected for over 14 days. This indicates that uniparental inheritance is enforced by eliminating paternal mitochondrial DNA in the zygote, rather than by decreasing male gamete size to the minimum. Thus, uniparental cytoplasmic inheritance is achieved by an entirely different mechanism, and is unlikely to drive the evolution of anisogamy in ulvophyceans.}, } @article {pmid37758449, year = {2023}, author = {Claramunt, S and Haddrath, O}, title = {No Signs of Adaptations for High Flight Intensity in the Mitochondrial Genome of Birds.}, journal = {Genome biology and evolution}, volume = {15}, number = {10}, pages = {}, pmid = {37758449}, issn = {1759-6653}, mesh = {Animals ; *Genome, Mitochondrial ; *Flight, Animal ; *Birds/genetics/physiology ; *Adaptation, Physiological/genetics ; Phylogeny ; }, abstract = {Mitochondrial genomes are expected to show adaptations for optimizing aerobic respiration in birds that make intense use of flight. However, there is limited empirical evidence of such a relationship. We here examine correlates of several mitochondrial genome characteristics and flight use across a diverse sample of 597 bird species. We developed an index of flight use intensity that ranged from 0 in flightless species to 9 in migratory hummingbirds and examined its association with nucleobase composition, amino acid class composition, and amino acid site allelic variation using phylogenetic comparative methods. We found no evidence of mitochondrial genome adaptations to flight intensity. Neither nucleotide composition nor amino acid properties showed consistent patterns related to flight use. While specific sites in mitochondrial genes exhibited variation associated with flight intensity, there was limited association between specific amino acid residues and flight intensity levels. Our findings suggest a complex genetic architecture for aerobic performance traits, where multiple genes in both mitochondria and the nucleus may contribute to overall performance. Other factors, such as gene expression regulation and anatomical adaptations, may play a more significant role in influencing flight performance than changes in mitochondrial genes. These findings highlight the need for comprehensive genomic analyses to unravel the intricate relationship between genetic variants and aerobic performance in birds.}, } @article {pmid37759714, year = {2023}, author = {Byrne, KL and Szeligowski, RV and Shen, H}, title = {Phylogenetic Analysis Guides Transporter Protein Deorphanization: A Case Study of the SLC25 Family of Mitochondrial Metabolite Transporters.}, journal = {Biomolecules}, volume = {13}, number = {9}, pages = {}, pmid = {37759714}, issn = {2218-273X}, support = {R35 GM150619/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Caenorhabditis elegans/genetics/metabolism ; Drosophila melanogaster/metabolism/genetics ; Mitochondria/metabolism/genetics ; Mitochondrial Membrane Transport Proteins/genetics/metabolism ; *Mitochondrial Proteins/chemistry/genetics/metabolism ; *Organic Anion Transporters/chemistry/genetics/metabolism ; Phylogeny ; Saccharomyces cerevisiae/metabolism/genetics ; }, abstract = {Homology search and phylogenetic analysis have commonly been used to annotate gene function, although they are prone to error. We hypothesize that the power of homology search in functional annotation depends on the coupling of sequence variation to functional diversification, and we herein focus on the SoLute Carrier (SLC25) family of mitochondrial metabolite transporters to survey this coupling in a family-wide manner. The SLC25 family is the largest family of mitochondrial metabolite transporters in eukaryotes that translocate ligands of different chemical properties, ranging from nucleotides, amino acids, carboxylic acids and cofactors, presenting adequate experimentally validated functional diversification in ligand transport. Here, we combine phylogenetic analysis to profile SLC25 transporters across common eukaryotic model organisms, from Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, to Homo sapiens, and assess their sequence adaptations to the transported ligands within individual subfamilies. Using several recently studied and poorly characterized SLC25 transporters, we discuss the potentials and limitations of phylogenetic analysis in guiding functional characterization.}, } @article {pmid37760086, year = {2023}, author = {Subczynski, WK and Pasenkiewicz-Gierula, M and Widomska, J}, title = {Protecting the Eye Lens from Oxidative Stress through Oxygen Regulation.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {9}, pages = {}, pmid = {37760086}, issn = {2076-3921}, support = {R01 EY015526/EY/NEI NIH HHS/United States ; }, abstract = {Molecular oxygen is a primary oxidant that is involved in the formation of active oxygen species and in the oxidation of lipids and proteins. Thus, controlling oxygen partial pressure (concentration) in the human organism, tissues, and organs can be the first step in protecting them against oxidative stress. However, it is not an easy task because oxygen is necessary for ATP synthesis by mitochondria and in many biochemical reactions taking place in all cells in the human body. Moreover, the blood circulatory system delivers oxygen to all parts of the body. The eye lens seems to be the only organ that is protected from the oxidative stress through the regulation of oxygen partial pressure. The basic mechanism that developed during evolution to protect the eye lens against oxidative damage is based on the maintenance of a very low concentration of oxygen within the lens. This antioxidant mechanism is supported by the resistance of both the lipid components of the lens membrane and cytosolic proteins to oxidation. Any disturbance, continuous or acute, in the working of this mechanism increases the oxygen concentration, in effect causing cataract development. Here, we describe the biophysical basis of the mechanism and its correlation with lens transparency.}, } @article {pmid37761841, year = {2023}, author = {Koshkina, O and Deniskova, T and Dotsev, A and Kunz, E and Selionova, M and Medugorac, I and Zinovieva, N}, title = {Phylogenetic Analysis of Russian Native Sheep Breeds Based on mtDNA Sequences.}, journal = {Genes}, volume = {14}, number = {9}, pages = {}, pmid = {37761841}, issn = {2073-4425}, mesh = {Sheep/genetics ; Animals ; *DNA, Mitochondrial/genetics ; Phylogeny ; *Mitochondria/genetics ; Animals, Domestic/genetics ; Russia ; }, abstract = {Eurasia is represented by all climatic zones and various environments. A unique breed variety of farm animals has been developed in Russia, whose territory covers a large area of the continent. A total of 69 local breeds and types of dairy, wool, and meat sheep (Ovis aries) are maintained here. However, the genetic diversity and maternal origin of these local breeds have not been comprehensively investigated. In this study, we describe the diversity and phylogeny of Russian sheep breeds inhabiting different geographical regions based on the analysis of complete sequences of mitochondrial genomes (mtDNA). Complete mtDNA sequences of the studied sheep were obtained using next-generation sequencing technology (NGS). All investigated geographical groups of sheep were characterized by high haplotype (Hd = 0.9992) and nucleotide diversity (π = 0.00378). Analysis of the AMOVA results showed that genetic diversity was majorly determined by within-population differences (77.87%). We identified 128 haplotypes in all studied sheep. Haplotypes belonged to the following haplogroups: B (64.8%), A (28.9%), C (5.5%), and D (0.8%). Haplogroup B was predominant in the western part of Russia. A high level of mtDNA polymorphism in the studied groups of local sheep indicates the presence of a significant reserve of unique genotypes in Russia, which is to be explored.}, } @article {pmid37761909, year = {2023}, author = {Mendivil, A and Ramírez, R and Morin, J and Ramirez, JL and Siccha-Ramirez, R and Britzke, R and Rivera, F and Ampuero, A and Oliveros, N and Congrains, C}, title = {Comparative Mitogenome Analysis of Two Native Apple Snail Species (Ampullariidae, Pomacea) from Peruvian Amazon.}, journal = {Genes}, volume = {14}, number = {9}, pages = {}, pmid = {37761909}, issn = {2073-4425}, mesh = {Animals ; Peru ; Phylogeny ; *Genome, Mitochondrial/genetics ; Snails/genetics ; Mitochondria/genetics ; }, abstract = {Apple snails of the genus Pomacea Perry, 1810 (Mollusca: Caenogastropoda: Ampullariidae) are native to the Neotropics and exhibit high species diversity, holding cultural and ecological significance as an important protein source in Peru. However, most genetic studies in Pomacea have focused mostly on invasive species, especially in Southeast Asia, where they are considered important pests. In this study, we assembled and annotated the mitochondrial genomes of two Pomacea species native to the Peruvian Amazon: Pomacea reevei Ampuero & Ramírez, 2023 and Pomacea aulanieri (Deville & Hupé, 1850). The mitogenomes of P. reevei and P. aulanieri comprise 15,660 and 16,096 bp, respectively, and contain the typical 37 genes of the animal mitochondria with a large control region of 292 bp in P. reevei and 524 bp in P. aulanieri-which fall within the range of what is currently known in Pomacea. Comparisons with previously published mitogenomes in Pomacea revealed differences in the overlapping of adjacent genes, the size of certain protein-coding genes (PCGs) and the secondary structure of some tRNAs that are consistent with the phylogenetic relationships between these species. These findings provide valuable insights into the systematics and genomics of the genus Pomacea.}, } @article {pmid37766465, year = {2023}, author = {Dial, DT and Weglarz, KM and Brunet, BMT and Havill, NP and von Dohlen, CD and Burke, GR}, title = {Whole-genome sequence of the Cooley spruce gall adelgid, Adelges cooleyi (Hemiptera: Sternorrhyncha: Adelgidae).}, journal = {G3 (Bethesda, Md.)}, volume = {14}, number = {1}, pages = {}, pmid = {37766465}, issn = {2160-1836}, support = {DEB-1655182//National Science Foundation/ ; //Utah Agricultural Experiment Station/ ; }, mesh = {Animals ; *Hemiptera/genetics ; Ecosystem ; *Aphids/genetics ; Ecology ; North America ; }, abstract = {The adelgids (Adelgidae) are a small family of sap-feeding insects, which, together with true aphids (Aphididae) and phylloxerans (Phylloxeridae), make up the infraorder Aphidomorpha. Some adelgid species are highly destructive to forest ecosystems such as Adelges tsugae, Adelges piceae, Adelges laricis, Pineus pini, and Pineus boerneri. Despite this, there are no high-quality genomic resources for adelgids, hindering advanced genomic analyses within Adelgidae and among Aphidomorpha. Here, we used PacBio continuous long-read and Illumina RNA-sequencing to construct a high-quality draft genome assembly for the Cooley spruce gall adelgid, Adelges cooleyi (Gillette), a gall-forming species endemic to North America. The assembled genome is 270.2 Mb in total size and has scaffold and contig N50 statistics of 14.87 and 7.18 Mb, respectively. There are 24,967 predicted coding sequences, and the assembly completeness is estimated at 98.1 and 99.6% with core BUSCO gene sets of Arthropoda and Hemiptera, respectively. Phylogenomic analysis using the A. cooleyi genome, 3 publicly available adelgid transcriptomes, 4 phylloxera transcriptomes, the Daktulosphaira vitifoliae (grape phylloxera) genome, 4 aphid genomes, and 2 outgroup coccoid genomes fully resolves adelgids and phylloxerans as sister taxa. The mitochondrial genome is 24 kb, among the largest in insects sampled to date, with 39.4% composed of noncoding regions. This genome assembly is currently the only genome-scale, annotated assembly for adelgids and will be a valuable resource for understanding the ecology and evolution of Aphidomorpha.}, } @article {pmid37778286, year = {2023}, author = {Duarte Hospital, C and Tête, A and Debizet, K and Imler, J and Tomkiewicz-Raulet, C and Blanc, EB and Barouki, R and Coumoul, X and Bortoli, S}, title = {SDHi fungicides: An example of mitotoxic pesticides targeting the succinate dehydrogenase complex.}, journal = {Environment international}, volume = {180}, number = {}, pages = {108219}, doi = {10.1016/j.envint.2023.108219}, pmid = {37778286}, issn = {1873-6750}, mesh = {Animals ; Humans ; *Fungicides, Industrial/toxicity ; *Pesticides ; Succinate Dehydrogenase/genetics/metabolism ; Fungi/metabolism ; Succinic Acid ; Succinates ; }, abstract = {Succinate dehydrogenase inhibitors (SDHi) are fungicides used to control the proliferation of pathogenic fungi in crops. Their mode of action is based on blocking the activity of succinate dehydrogenase (SDH), a universal enzyme expressed by all species harboring mitochondria. The SDH is involved in two interconnected metabolic processes for energy production: the transfer of electrons in the mitochondrial respiratory chain and the oxidation of succinate to fumarate in the Krebs cycle. In humans, inherited SDH deficiencies may cause major pathologies including encephalopathies and cancers. The cellular and molecular mechanisms related to such genetic inactivation have been well described in neuroendocrine tumors, in which it induces an oxidative stress, a pseudohypoxic phenotype, a metabolic, epigenetic and transcriptomic remodeling, and alterations in the migration and invasion capacities of cancer cells, in connection with the accumulation of succinate, an oncometabolite, substrate of the SDH. We will discuss recent studies reporting toxic effects of SDHi in non-target organisms and their implications for risk assessment of pesticides. Recent data show that the SDH structure is highly conserved during evolution and that SDHi can inhibit SDH activity in mitochondria of non-target species, including humans. These observations suggest that SDHi are not specific inhibitors of fungal SDH. We hypothesize that SDHi could have toxic effects in other species, including humans. Moreover, the analysis of regulatory assessment reports shows that most SDHi induce tumors in animals without evidence of genotoxicity. Thus, these substances could have a non-genotoxic mechanism of carcinogenicity that still needs to be fully characterized and that could be related to SDH inhibition. The use of pesticides targeting mitochondrial enzymes encoded by tumor suppressor genes raises questions on the risk assessment framework of mitotoxic pesticides. The issue of SDHi fungicides is therefore a textbook case that highlights the urgent need for changes in regulatory assessment.}, } @article {pmid37783374, year = {2023}, author = {Igamberdiev, AU and Gordon, R}, title = {Macroevolution, differentiation trees, and the growth of coding systems.}, journal = {Bio Systems}, volume = {234}, number = {}, pages = {105044}, doi = {10.1016/j.biosystems.2023.105044}, pmid = {37783374}, issn = {1872-8324}, mesh = {*Cell Differentiation/genetics ; Morphogenesis/genetics ; Phylogeny ; }, abstract = {An open process of evolution of multicellular organisms is based on the rearrangement and growth of the program of differentiation that underlies biological morphogenesis. The maintenance of the final (adult) stable non-equilibrium state (stasis) of a developmental system determines the direction of the evolutionary process. This state is achieved via the sequence of differentiation events representable as differentiation trees. A special type of morphogenetic code, acting as a metacode governing gene expression, may include electromechanical signals appearing as differentiation waves. The excessive energy due to the incorporation of mitochondria in eukaryotic cells resulted not only in more active metabolism but also in establishing the differentiation code for interconnecting cells and forming tissues, which fueled the evolutionary process. The "invention" of "continuing differentiation" distinguishes multicellular eukaryotes from other organisms. The Janus-faced control, involving both top-down control by differentiation waves and bottom-up control via the mechanical consequences of cell differentiations, underlies the process of morphogenesis and results in the achievement of functional stable final states. Duplications of branches of the differentiation tree may be the basis for continuing differentiation and macroevolution, analogous to gene duplication permitting divergence of genes. Metamorphoses, if they are proven to be fusions of disparate species, may be classified according to the topology of fusions of two differentiation trees. In the process of unfolding of morphogenetic structures, microevolution can be defined as changes of the differentiation tree that preserve topology of the tree, while macroevolution represents any change that alters the topology of the differentiation tree.}, } @article {pmid37792908, year = {2023}, author = {Motyčková, A and Voleman, L and Najdrová, V and Arbonová, L and Benda, M and Dohnálek, V and Janowicz, N and Malych, R and Šuťák, R and Ettema, TJG and Svärd, S and Stairs, CW and Doležal, P}, title = {Adaptation of the late ISC pathway in the anaerobic mitochondrial organelles of Giardia intestinalis.}, journal = {PLoS pathogens}, volume = {19}, number = {10}, pages = {e1010773}, pmid = {37792908}, issn = {1553-7374}, mesh = {Humans ; *Giardia lamblia/genetics/metabolism ; Anaerobiosis ; *Iron-Sulfur Proteins/genetics/metabolism ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; }, abstract = {Mitochondrial metabolism is entirely dependent on the biosynthesis of the [4Fe-4S] clusters, which are part of the subunits of the respiratory chain. The mitochondrial late ISC pathway mediates the formation of these clusters from simpler [2Fe-2S] molecules and transfers them to client proteins. Here, we characterized the late ISC pathway in one of the simplest mitochondria, mitosomes, of the anaerobic protist Giardia intestinalis that lost the respiratory chain and other hallmarks of mitochondria. In addition to IscA2, Nfu1 and Grx5 we identified a novel BolA1 homologue in G. intestinalis mitosomes. It specifically interacts with Grx5 and according to the high-affinity pulldown also with other core mitosomal components. Using CRISPR/Cas9 we were able to establish full bolA1 knock out, the first cell line lacking a mitosomal protein. Despite the ISC pathway being the only metabolic role of the mitosome no significant changes in the mitosome biology could be observed as neither the number of the mitosomes or their capability to form [2Fe-2S] clusters in vitro was affected. We failed to identify natural client proteins that would require the [2Fe-2S] or [4Fe-4S] cluster within the mitosomes, with the exception of [2Fe-2S] ferredoxin, which is itself part of the ISC pathway. The overall uptake of iron into the cellular proteins remained unchanged as also observed for the grx5 knock out cell line. The pull-downs of all late ISC components were used to build the interactome of the pathway showing specific position of IscA2 due to its interaction with the outer mitosomal membrane proteins. Finally, the comparative analysis across Metamonada species suggested that the adaptation of the late ISC pathway identified in G. intestinalis occurred early in the evolution of this supergroup of eukaryotes.}, } @article {pmid37796022, year = {2023}, author = {Usey, MM and Huet, D}, title = {ATP synthase-associated coiled-coil-helix-coiled-coil-helix (CHCH) domain-containing proteins are critical for mitochondrial function in Toxoplasma gondii.}, journal = {mBio}, volume = {14}, number = {5}, pages = {e0176923}, pmid = {37796022}, issn = {2150-7511}, support = {R00 AI137218/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Toxoplasma/genetics/metabolism ; Mitochondria/metabolism ; Proteins/metabolism ; *Parasites/metabolism ; Nitric Oxide Synthase/metabolism ; Adenosine Triphosphate/metabolism ; Protozoan Proteins/genetics/metabolism ; Mitochondrial Proteins/metabolism ; }, abstract = {Members of the coiled-coil-helix-coiled-coil-helix (CHCH) domain protein family are transported into the mitochondrial intermembrane space, where they play important roles in the biogenesis and function of the organelle. Unexpectedly, the ATP synthase of the apicomplexan Toxoplasma gondii harbors CHCH domain-containing subunits of unknown function. As no other ATP synthase studied to date contains this class of proteins, characterizing their function will be of broad interest to the fields of molecular parasitology and mitochondrial evolution. Here, we demonstrate that that two T. gondii ATP synthase subunits containing CHCH domains are required for parasite survival and for stability and function of the ATP synthase. We also show that knockdown disrupts multiple aspects of the mitochondrial morphology of T. gondii and that mutation of key residues in the CHCH domains caused mis-localization of the proteins. This work provides insight into the unique features of the apicomplexan ATP synthase, which could help to develop therapeutic interventions against this parasite and other apicomplexans, such as the malaria-causing parasite Plasmodium falciparum.}, } @article {pmid37810794, year = {2023}, author = {Rodriguez, D and Harding, SF and Sirsi, S and McNichols-O'Rourke, K and Morris, T and Forstner, MRJ and Schwalb, AN}, title = {Mitochondrial sequence data reveal population structure within Pustulosa pustulosa.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e15974}, pmid = {37810794}, issn = {2167-8359}, mesh = {Humans ; Animals ; Phylogeny ; Mitochondria ; *Bivalvia ; *Unionidae/genetics ; Texas ; Ontario ; }, abstract = {Unionid mussels are among the most imperiled group of organisms in North America, and Pustulosa pustulosa is a freshwater species with a relatively wide latitudinal distribution that extends from southern Ontario, Canada, to Texas, USA. Considerable morphological and geographic variation in the genus Pustulosa (formerly Cyclonaias) has led to uncertainty over species boundaries, and recent studies have suggested revisions to species-level classifications by synonymizing C. aurea, C. houstonensis, C. mortoni, and C. refulgens with C. pustulosa (currently P. pustulosa). Owing to its wide range and shallow phylogenetic differentiation, we analyzed individuals of P. pustulosa using mitochondrial DNA sequence data under a population genetics framework. We included 496 individuals, which were comprised of 166 samples collected during this study and 330 additional sequences retrieved from GenBank. Pairwise ΦST measures based on ND1 data suggested there may be up to five major geographic groups present within P. pustulosa. Genetic differentiation between regions within Texas was higher compared to populations from the Mississippi and Great Lakes populations, which may reflect differences in historical connectivity. Mitochondrial sequence data also revealed varying demographic histories for each major group suggesting each geographic region has also experienced differential population dynamics in the past. Future surveys should consider exploring variation within species after phylogeographic delimitation has been performed. In this study, we begin to address this need for freshwater mussels via the P. pustulosa system.}, } @article {pmid37815994, year = {2023}, author = {Chen, YH and Miller, WB and Hay, A}, title = {Postharvest bacterial succession on cut flowers and vase water.}, journal = {PloS one}, volume = {18}, number = {10}, pages = {e0292537}, pmid = {37815994}, issn = {1932-6203}, mesh = {*Water ; RNA, Ribosomal, 16S/genetics ; Phylogeny ; Ecosystem ; *Asteraceae ; Flowers ; Bacteria/genetics ; }, abstract = {In cut flowers, xylem occlusion or blockage by bacteria negatively affects water balance and postharvest quality. Many studies have used culture-based methods to examine bacterial populations in vase water and their effects on flower longevity. It is still unclear if and how bacterial communities at the 16S rRNA gene (16S) level change during the vase period and how such change might correlate with postharvest longevity. This study compared the sequences of 16S amplicons from 4 different types of flowers and their vase water over the course of 7 days (Rosa spp., Gerbera jamesonii, and two Lilium varieties). The relative abundance of plant chloroplast and mitochondria 16S decreased significantly over the course 7 days in all 4 flowers as bacterial diversity increased. Richness and evenness of the bacterial communities increased over time, as did the number of rare taxa and phylogenetic diversity. Bacterial communities varied with time, as well as by flower source, types, and sample location (water, stem surface, whole stem). Some taxa, such as Enterobacteriacea and Bradyhizobiaceae decreased significantly over time while others such as Pseudomonas spp. increased. For example, Pseudomonas veronii, implicated in soft rot of calla lily, increased in both whole stem samples and water samples from Gerbera jamesonii. Erwinia spp., which includes plant pathogenic species, also increased in water samples. This work highlights the dynamic and complex nature of bacterial succession in the flower vase ecosystem. More work is needed to understand if and how bacterial community structure can be managed to improve cut flower vase life.}, } @article {pmid37818890, year = {2023}, author = {Chen, H and Shi, BY and Du, LN and Sun, HY}, title = {Description of a New Species of Hua (Gastropoda: Semisulcospiridae) from Guizhou, China, Based on Morphology and Molecular Evidence.}, journal = {Zoological science}, volume = {40}, number = {5}, pages = {414-421}, doi = {10.2108/zs230025}, pmid = {37818890}, issn = {0289-0003}, mesh = {Female ; Animals ; *Gastropoda/anatomy & histology ; Phylogeny ; China ; Mitochondria ; }, abstract = {A new species of Hua, Hua qiannanensis sp. nov., is described from Guizhou Province, China, based on morphological and molecular evidence. The new species can be distinguished from its congeners by the following combination of characters: the smooth shell, only three smaller cusps of lateral teeth on the inner side, outer marginal teeth with eight flattened and rounded denticles, an ovipositor pore in females, and BW/H ≥ 80%, B/H = 76.8-82.3%. Molecular analysis based on partial mitochondrial COI and 16S rDNA also supports the systematic position of the new taxon.}, } @article {pmid37843218, year = {2024}, author = {Zhang, J and Zhu, Q and Wang, J and Peng, Z and Zhuang, Z and Hang, C and Li, W}, title = {Mitochondrial dysfunction and quality control lie at the heart of subarachnoid hemorrhage.}, journal = {Neural regeneration research}, volume = {19}, number = {4}, pages = {825-832}, pmid = {37843218}, issn = {1673-5374}, abstract = {The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow. Mitochondria are directly affected by direct factors such as ischemia, hypoxia, excitotoxicity, and toxicity of free hemoglobin and its degradation products, which trigger mitochondrial dysfunction. Dysfunctional mitochondria release large amounts of reactive oxygen species, inflammatory mediators, and apoptotic proteins that activate apoptotic pathways, further damaging cells. In response to this array of damage, cells have adopted multiple mitochondrial quality control mechanisms through evolution, including mitochondrial protein quality control, mitochondrial dynamics, mitophagy, mitochondrial biogenesis, and intercellular mitochondrial transfer, to maintain mitochondrial homeostasis under pathological conditions. Specific interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid hemorrhage. This review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage, particularly mitochondrial quality control mechanisms. It also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.}, } @article {pmid37844192, year = {2023}, author = {Borghi, F and Saiardi, A}, title = {Evolutionary perspective on mammalian inorganic polyphosphate (polyP) biology.}, journal = {Biochemical Society transactions}, volume = {51}, number = {5}, pages = {1947-1956}, pmid = {37844192}, issn = {1470-8752}, support = {MR/T028904/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Polyphosphates ; *Mammals ; Eukaryotic Cells ; Mitochondria ; Biology ; }, abstract = {Inorganic polyphosphate (polyP), the polymeric form of phosphate, is attracting ever-growing attention due to the many functions it appears to perform within mammalian cells. This essay does not aim to systematically review the copious mammalian polyP literature. Instead, we examined polyP synthesis and functions in various microorganisms and used an evolutionary perspective to theorise key issues of this field and propose solutions. By highlighting the presence of VTC4 in distinct species of very divergent eucaryote clades (Opisthokonta, Viridiplantae, Discoba, and the SAR), we propose that whilst polyP synthesising machinery was present in the ancestral eukaryote, most lineages subsequently lost it during evolution. The analysis of the bacteria-acquired amoeba PPK1 and its unique polyP physiology suggests that eukaryote cells must have developed mechanisms to limit cytosolic polyP accumulation. We reviewed the literature on polyP in the mitochondria from the perspective of its endosymbiotic origin from bacteria, highlighting how mitochondria could possess a polyP physiology reminiscent of their 'bacterial' beginning that is not yet investigated. Finally, we emphasised the similarities that the anionic polyP shares with the better-understood negatively charged polymers DNA and RNA, postulating that the nucleus offers an ideal environment where polyP physiology might thrive.}, } @article {pmid37847106, year = {2023}, author = {Sharma, A and Ahlawat, S and Sharma, R and Arora, R and Singh, KV and Malik, D and Banik, S and Singh, TR and Tantia, MS}, title = {Tracing the genetic footprints: India's role as a gateway for pig migration and domestication across continents.}, journal = {Animal biotechnology}, volume = {34}, number = {9}, pages = {5173-5179}, doi = {10.1080/10495398.2023.2268683}, pmid = {37847106}, issn = {1532-2378}, mesh = {Swine/genetics ; Animals ; *Domestication ; *Sus scrofa/genetics ; India ; Mitochondria/genetics ; Haplotypes/genetics ; Phylogeny ; Genetic Variation/genetics ; DNA, Mitochondrial/genetics ; }, abstract = {This study explored the maternal genetic diversity in the pig genetic resources of India by analyzing a mitochondrial D-loop fragment and comparing it with the corresponding sequences of previously published studies involving domestic pigs and wild boars. Sequencing of 103 samples representing different domestic pig populations revealed existence of 32 maternal haplotypes. The indices of haplotype and nucleotide diversity in Indian domestic pigs were 0.9421 and 0.015, respectively. Median-Joining network revealed that Indian pigs belong to Clade A and show conformity to 6 haplogroups reported worldwide (D1a, D1a1, D1a2, D1e, D1h and D3a). Among these, D1e and D1a2 were shared with Asian wild boars too. Interestingly, haplotype sharing was evident between Indian pigs and samples from other countries representing Africa, Asia, Europe and Oceania. This study substantiates India's contribution as a possible pig domestication center and highlights the importance of the Indian subcontinent in dispersal of the species to other continents. Additionally, genetic evidence suggested the influence of trading routes and historical interactions in shaping pig genetic exchange. Overall, this investigation provides valuable insights into the genetic diversity, historical migration, and domestication of Indian domestic pigs, contributing to the broader understanding of global pig genetic resources and their evolutionary history.}, } @article {pmid37850870, year = {2023}, author = {Nicolini, F and Ghiselli, F and Luchetti, A and Milani, L}, title = {Bivalves as Emerging Model Systems to Study the Mechanisms and Evolution of Sex Determination: A Genomic Point of View.}, journal = {Genome biology and evolution}, volume = {15}, number = {10}, pages = {}, pmid = {37850870}, issn = {1759-6653}, mesh = {Humans ; Animals ; Phylogeny ; *Bivalvia/genetics ; Genome ; Genomics ; Mitochondria/genetics ; Sex Determination Processes/genetics ; Biological Evolution ; }, abstract = {Bivalves are a diverse group of molluscs that have recently attained a central role in plenty of biological research fields, thanks to their peculiar life history traits. Here, we propose that bivalves should be considered as emerging model systems also in sex-determination (SD) studies, since they would allow to investigate: 1) the transition between environmental and genetic SD, with respect to different reproductive backgrounds and sexual systems (from species with strict gonochorism to species with various forms of hermaphroditism); 2) the genomic evolution of sex chromosomes (SCs), considering that no heteromorphic SCs are currently known and that homomorphic SCs have been identified only in a few species of scallops; 3) the putative role of mitochondria at some level of the SD signaling pathway, in a mechanism that may resemble the cytoplasmatic male sterility of plants; 4) the evolutionary history of SD-related gene (SRG) families with respect to other animal groups. In particular, we think that this last topic may lay the foundations for expanding our understanding of bivalve SD, as our current knowledge is quite fragmented and limited to a few species. As a matter of fact, tracing the phylogenetic history and diversity of SRG families (such as the Dmrt, Sox, and Fox genes) would allow not only to perform more targeted functional experiments and genomic analyses, but also to foster the possibility of establishing a solid comparative framework.}, } @article {pmid37859594, year = {2024}, author = {Waters, ER and Bezanilla, M and Vierling, E}, title = {ATAD3 Proteins: Unique Mitochondrial Proteins Essential for Life in Diverse Eukaryotic Lineages.}, journal = {Plant & cell physiology}, volume = {65}, number = {4}, pages = {493-502}, doi = {10.1093/pcp/pcad122}, pmid = {37859594}, issn = {1471-9053}, support = {IOS 1354960 MCB 2215727//National Science Foundation/ ; }, mesh = {*Mitochondrial Proteins/metabolism/genetics ; *Arabidopsis Proteins/metabolism/genetics ; Arabidopsis/genetics/metabolism ; Mitochondria/metabolism ; ATPases Associated with Diverse Cellular Activities/metabolism/genetics ; Eukaryota/genetics/metabolism ; Adenosine Triphosphatases/metabolism/genetics ; Phylogeny ; Animals ; }, abstract = {ATPase family AAA domain-containing 3 (ATAD3) proteins are unique mitochondrial proteins that arose deep in the eukaryotic lineage but that are surprisingly absent in Fungi and Amoebozoa. These ∼600-amino acid proteins are anchored in the inner mitochondrial membrane and are essential in metazoans and Arabidopsis thaliana. ATAD3s comprise a C-terminal ATPases Associated with a variety of cellular Activities (AAA+) matrix domain and an ATAD3_N domain, which is located primarily in the inner membrane space but potentially extends to the cytosol to interact with the ER. Sequence and structural alignments indicate that ATAD3 proteins are most similar to classic chaperone unfoldases in the AAA+ family, suggesting that they operate in mitochondrial protein quality control. A. thaliana has four ATAD3 genes in two distinct clades that appear first in the seed plants, and both clades are essential for viability. The four genes are generally coordinately expressed, and transcripts are highest in growing apices and imbibed seeds. Plants with disrupted ATAD3 have reduced growth, aberrant mitochondrial morphology, diffuse nucleoids and reduced oxidative phosphorylation complex I. These and other pleiotropic phenotypes are also observed in ATAD3 mutants in metazoans. Here, we discuss the distribution of ATAD3 proteins as they have evolved in the plant kingdom, their unique structure, what we know about their function in plants and the challenges in determining their essential roles in mitochondria.}, } @article {pmid37871810, year = {2024}, author = {Coto, ALS and Pereira, AA and Oliveira, SD and Moritz, MNO and Franco da Rocha, AM and Dores-Silva, PR and da Silva, NSM and de Araújo Nogueira, AR and Gava, LM and Seraphim, TV and Borges, JC}, title = {Structural characterization of the human DjC20/HscB cochaperone in solution.}, journal = {Biochimica et biophysica acta. Proteins and proteomics}, volume = {1872}, number = {1}, pages = {140970}, doi = {10.1016/j.bbapap.2023.140970}, pmid = {37871810}, issn = {1878-1454}, mesh = {Humans ; Adenosine Triphosphatases/metabolism ; Edetic Acid ; *Heat-Shock Proteins/chemistry ; *HSP70 Heat-Shock Proteins/chemistry ; Molecular Chaperones/chemistry ; }, abstract = {J-domain proteins (JDPs) form a very large molecular chaperone family involved in proteostasis processes, such as protein folding, trafficking through membranes and degradation/disaggregation. JDPs are Hsp70 co-chaperones capable of stimulating ATPase activity as well as selecting and presenting client proteins to Hsp70. In mitochondria, human DjC20/HscB (a type III JDP that possesses only the conserved J-domain in some region of the protein) is involved in [FeS] protein biogenesis and assists human mitochondrial Hsp70 (HSPA9). Human DjC20 possesses a zinc-finger domain in its N-terminus, which closely contacts the J-domain and appears to be essential for its function. Here, we investigated the hDjC20 structure in solution as well as the importance of Zn[+2] for its stability. The recombinant hDjC20 was pure, folded and capable of stimulating HSPA9 ATPase activity. It behaved as a slightly elongated monomer, as attested by small-angle X-ray scattering and SEC-MALS. The presence of Zn[2+] in the hDjC20 samples was verified, a stoichiometry of 1:1 was observed, and its removal by high concentrations of EDTA and DTPA was unfeasible. However, thermal and chemical denaturation in the presence of EDTA led to a reduction in protein stability, suggesting a synergistic action between the chelating agent and denaturators that facilitate protein unfolding depending on metal removal. These data suggest that the affinity of Zn[+2] for the protein is very high, evidencing its importance for the hDjC20 structure.}, } @article {pmid37877347, year = {2024}, author = {Choi, SW and Yu, HJ and Kim, JK}, title = {Comparative ontogeny and phylogenetic relationships of eight lizardfish species (Synodontidae) from the Northwest Pacific, with a focus on Trachinocephalus monophyly.}, journal = {Journal of fish biology}, volume = {104}, number = {1}, pages = {284-303}, doi = {10.1111/jfb.15595}, pmid = {37877347}, issn = {1095-8649}, support = {R2023001//the National Institute of Fisheries Science/ ; 2023//the National Marine Biodiversity Institute of Korea/ ; }, mesh = {Animals ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Fishes/anatomy & histology ; *DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Larva ; }, abstract = {Lizardfish (Aulopiforms: Synodontidae), distributed broadly in temperate to tropical waters, are represented globally by 83 species across four genera, with 10 species in Korea. Despite these numbers, few studies have been conducted on the early life history of lizardfishes compared to their adult counterparts. Thus, we conducted molecular identification of 123 Synodontidae larvae collected from the Northwest Pacific (Korea Strait, Yellow Sea, East China Sea, and East Sea) between June 2017 and July 2021, using mitochondrial DNA COI and 16S rRNA sequences. Significant morphological differences were observed in the larvae and juvenile, including variation in melanophore, count, morphometric characteristics, and body shape. The morphological traits of eight species (Harpadon nehereus, Saurida macrolepis, Saurida wanieso, Saurida sp., Synodus hoshinonis, Synodus kaianus, Synodus macrops, and Trachinocephalus trachinus) served as vital data for interpreting the phylogenetic relationships within the Northwest Pacific Synodontidae. Ultimately, the identification key revealed by this study will enable accurate identification of Synodontid larvae and juveniles, and further facilitate our understanding of the phylogenetic relationships within this family.}, } @article {pmid37885664, year = {2023}, author = {Ni, Y and Zhang, X and Li, J and Lu, Q and Chen, H and Ma, B and Liu, C}, title = {Genetic diversity of Coffea arabica L. mitochondrial genomes caused by repeat- mediated recombination and RNA editing.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1261012}, pmid = {37885664}, issn = {1664-462X}, abstract = {BACKGROUND: Coffea arabica L. is one of the most important crops widely cultivated in 70 countries across Asia, Africa, and Latin America. Mitochondria are essential organelles that play critical roles in cellular respiration, metabolism, and differentiation. C. arabica's nuclear and chloroplast genomes have been reported. However, its mitochondrial genome remained unreported. Here, we intended to sequence and characterize its mitochondrial genome to maximize the potential of its genomes for evolutionary studies, molecular breeding, and molecular marker developments.

RESULTS: We sequenced the total DNA of C. arabica using Illumina and Nanopore platforms. We then assembled the mitochondrial genome with a hybrid strategy using Unicycler software. We found that the mitochondrial genome comprised two circular chromosomes with lengths of 867,678 bp and 153,529 bp, encoding 40 protein-coding genes, 26 tRNA genes, and three rRNA genes. We also detected 270 Simple Sequence Repeats and 34 tandem repeats in the mitochondrial genome. We found 515 high-scoring sequence pairs (HSPs) for a self-to-self similarity comparison using BLASTn. Three HSPs were found to mediate recombination by the mapping of long reads. Furthermore, we predicted 472 using deep-mt with the convolutional neural network model. Then we randomly validated 90 RNA editing events by PCR amplification and Sanger sequencing, with the majority being non-synonymous substitutions and only three being synonymous substitutions. These findings provide valuable insights into the genetic characteristics of the C. arabica mitochondrial genome, which can be helpful for future study on coffee breeding and mitochondrial genome evolution.

CONCLUSION: Our study sheds new light on the evolution of C. arabica organelle genomes and their potential use in genetic breeding, providing valuable data for developing molecular markers that can improve crop productivity and quality. Furthermore, the discovery of RNA editing events in the mitochondrial genome of C. arabica offers insights into the regulation of gene expression in this species, contributing to a better understanding of coffee genetics and evolution.}, } @article {pmid37895071, year = {2023}, author = {Olla, S and Siguri, C and Fais, A and Era, B and Fantini, MC and Di Petrillo, A}, title = {Inhibitory Effect of Quercetin on Oxidative Endogen Enzymes: A Focus on Putative Binding Modes.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37895071}, issn = {1422-0067}, mesh = {*Quercetin/pharmacology ; Reactive Oxygen Species/metabolism ; *Antioxidants/pharmacology/metabolism ; Molecular Docking Simulation ; Oxidative Stress ; Xanthine Oxidase/metabolism ; Monoamine Oxidase/metabolism ; }, abstract = {Oxidative stress is defined as an imbalance between the production of free radicals and reactive oxygen species (ROS) and the ability of the body to neutralize them by anti-oxidant defense systems. Cells can produce ROS during physiological processes, but excessive ROS can lead to non-specific and irreversible damage to biological molecules, such as DNA, lipids, and proteins. Mitochondria mainly produce endogenous ROS during both physiological and pathological conditions. Enzymes like nicotinamide adenine dinucleotide phosphate oxidase (NOX), xanthine oxidase (XO), lipoxygenase (LOX), myeloperoxidase (MPO), and monoamine oxidase (MAO) contribute to this process. The body has enzymatic and non-enzymatic defense systems to neutralize ROS. The intake of bioactive phenols, like quercetin (Que), can protect against pro-oxidative damage by quenching ROS through a non-enzymatic system. In this study, we evaluate the ability of Que to target endogenous oxidant enzymes involved in ROS production and explore the mechanisms of action underlying its anti-oxidant properties. Que can act as a free radical scavenger by donating electrons through the negative charges in its phenolic and ketone groups. Additionally, it can effectively inhibit the activity of several endogenous oxidative enzymes by binding them with high affinity and specificity. Que had the best molecular docking results with XO, followed by MAO-A, 5-LOX, NOX, and MPO. Que's binding to these enzymes was confirmed by subsequent molecular dynamics, revealing different stability phases depending on the enzyme bound. The 500 ns simulation showed a net evolution of binding for NOX and MPO. These findings suggest that Que has potential as a natural therapy for diseases related to oxidative stress.}, } @article {pmid37900311, year = {2023}, author = {Gonzalez-Jimenez, I and Perlin, DS and Shor, E}, title = {Reactive oxidant species induced by antifungal drugs: identity, origins, functions, and connection to stress-induced cell death.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1276406}, pmid = {37900311}, issn = {2235-2988}, support = {R01 AI109025/AI/NIAID NIH HHS/United States ; R21 AI168729/AI/NIAID NIH HHS/United States ; }, mesh = {*Antifungal Agents/pharmacology/therapeutic use ; Reactive Oxygen Species/metabolism ; *Oxidants ; Echinocandins/pharmacology ; Apoptosis ; }, abstract = {Reactive oxidant species (ROS) are unstable, highly reactive molecules that are produced by cells either as byproducts of metabolism or synthesized by specialized enzymes. ROS can be detrimental, e.g., by damaging cellular macromolecules, or beneficial, e.g., by participating in signaling. An increasing body of evidence shows that various fungal species, including both yeasts and molds, increase ROS production upon exposure to the antifungal drugs currently used in the clinic: azoles, polyenes, and echinocandins. However, the implications of these findings are still largely unclear due to gaps in knowledge regarding the chemical nature, molecular origins, and functional consequences of these ROS. Because the detection of ROS in fungal cells has largely relied on fluorescent probes that lack specificity, the chemical nature of the ROS is not known, and it may vary depending on the specific fungus-drug combination. In several instances, the origin of antifungal drug-induced ROS has been identified as the mitochondria, but further experiments are necessary to strengthen this conclusion and to investigate other potential cellular ROS sources, such as the ER, peroxisomes, and ROS-producing enzymes. With respect to the function of the ROS, several studies have shown that they contribute to the drugs' fungicidal activities and may be part of drug-induced programmed cell death (PCD). However, whether these "pro-death" ROS are a primary consequence of the antifungal mechanism of action or a secondary consequence of drug-induced PCD remains unclear. Finally, several recent studies have raised the possibility that ROS induction can serve an adaptive role, promoting antifungal drug tolerance and the evolution of drug resistance. Filling these gaps in knowledge will reveal a new aspect of fungal biology and may identify new ways to potentiate antifungal drug activity or prevent the evolution of antifungal drug resistance.}, } @article {pmid37901222, year = {2023}, author = {Brun, C and Chalet, L and Moulin, F and Bochaton, T and Ducreux, S and Paillard, M and Crola Da Silva, C}, title = {A bibliometric analysis: Ca[2+] fluxes and inflammatory phenotyping by flow cytometry in peripheral blood mononuclear cells.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1272809}, pmid = {37901222}, issn = {1664-3224}, mesh = {Humans ; *Leukocytes, Mononuclear/metabolism ; Flow Cytometry/methods ; Cell Line ; *Signal Transduction ; Inflammation/metabolism ; }, abstract = {BACKGROUND: The immune system, composed of organs, tissues, cells, and proteins, is the key to protecting the body from external biological attacks and inflammation. The latter occurs in several pathologies, such as cancers, type 1 diabetes, and human immunodeficiency virus infection. Immunophenotyping by flow cytometry is the method of choice for diagnosing these pathologies. Under inflammatory conditions, the peripheral blood mononuclear cells (PBMCs) are partially activated and generate intracellular pathways involving Ca[2+]-dependent signaling cascades leading to transcription factor expression. Ca[2+] signaling is typically studied by microscopy in cell lines but can present some limitations to explore human PBMCs, where flow cytometry can be a good alternative.

OBJECTIVE: In this review, we dived into the research field of inflammation and Ca[2+] signaling in PBMCs. We aimed to investigate the structure and evolution of this field in a physio-pathological context, and then we focused our review on flow cytometry analysis of Ca[2+] fluxes in PBMCs.

METHODS: From 1984 to 2022, 3865 articles on inflammation and Ca[2+] signaling in PBMCs were published, according to The Clarivate Web of Science (WOS) database used in this review. A bibliometric study was designed for this collection and consisted of a co-citation and bibliographic coupling analysis.

RESULTS: The co-citation analysis was performed on 133 articles: 4 clusters highlighted the global context of Ca[2+] homeostasis, including chemical probe development, identification of the leading players in Ca[2+] signaling, and the link with chemokine production in immune cell function. Next, the bibliographic coupling analysis combined 998 articles in 8 clusters. This analysis outlined the mechanisms of PBMC activation, from signal integration to cellular response. Further explorations of the bibliographic coupling network, focusing on flow cytometry, revealed 21 articles measuring cytosolic Ca[2+] in PBMCs, with only 5 since 2016. This final query showed that Ca[2+] signaling analysis in human PBMCs using flow cytometry is still underdeveloped and investigates mainly the cytosolic Ca[2+] compartment.

CONCLUSION: Our review uncovers remaining knowledge gaps of intracellular players involved in Ca[2+] signaling in PBMCs, such as reticulum and mitochondria, and presents flow cytometry as a solid option to supplement gold-standard microscopy studies.}, } @article {pmid37903625, year = {2024}, author = {Hacker, C and Sendra, K and Keisham, P and Filipescu, T and Lucocq, J and Salimi, F and Ferguson, S and Bhella, D and MacNeill, SA and Embley, M and Lucocq, J}, title = {Biogenesis, inheritance, and 3D ultrastructure of the microsporidian mitosome.}, journal = {Life science alliance}, volume = {7}, number = {1}, pages = {}, pmid = {37903625}, issn = {2575-1077}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Fungal Proteins/metabolism ; Mitochondria/metabolism ; *Microsporidia/genetics/metabolism ; Saccharomyces cerevisiae/metabolism ; Dynamins ; Mammals/metabolism ; Quinazolinones ; }, abstract = {During the reductive evolution of obligate intracellular parasites called microsporidia, a tiny remnant mitochondrion (mitosome) lost its typical cristae, organellar genome, and most canonical functions. Here, we combine electron tomography, stereology, immunofluorescence microscopy, and bioinformatics to characterise mechanisms of growth, division, and inheritance of this minimal mitochondrion in two microsporidia species (grown within a mammalian RK13 culture-cell host). Mitosomes of Encephalitozoon cuniculi (2-12/cell) and Trachipleistophora hominis (14-18/nucleus) displayed incremental/non-phasic growth and division and were closely associated with an organelle identified as equivalent to the fungal microtubule-organising centre (microsporidian spindle pole body; mSPB). The mitosome-mSPB association was resistant to treatment with microtubule-depolymerising drugs nocodazole and albendazole. Dynamin inhibitors (dynasore and Mdivi-1) arrested mitosome division but not growth, whereas bioinformatics revealed putative dynamins Drp-1 and Vps-1, of which, Vps-1 rescued mitochondrial constriction in dynamin-deficient yeast (Schizosaccharomyces pombe). Thus, microsporidian mitosomes undergo incremental growth and dynamin-mediated division and are maintained through ordered inheritance, likely mediated via binding to the microsporidian centrosome (mSPB).}, } @article {pmid37917792, year = {2023}, author = {Namasivayam, S and Sun, C and Bah, AB and Oberstaller, J and Pierre-Louis, E and Etheridge, RD and Feschotte, C and Pritham, EJ and Kissinger, JC}, title = {Massive invasion of organellar DNA drives nuclear genome evolution in Toxoplasma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {45}, pages = {e2308569120}, pmid = {37917792}, issn = {1091-6490}, support = {R01 AI068908/AI/NIAID NIH HHS/United States ; R35 GM122550/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Toxoplasma/genetics ; Genome ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Evolution, Molecular ; Cell Nucleus/genetics ; Sequence Analysis, DNA ; }, abstract = {Toxoplasma gondii is a zoonotic protist pathogen that infects up to one third of the human population. This apicomplexan parasite contains three genome sequences: nuclear (65 Mb); plastid organellar, ptDNA (35 kb); and mitochondrial organellar, mtDNA (5.9 kb of non-repetitive sequence). We find that the nuclear genome contains a significant amount of NUMTs (nuclear integrants of mitochondrial DNA) and NUPTs (nuclear integrants of plastid DNA) that are continuously acquired and represent a significant source of intraspecific genetic variation. NUOT (nuclear DNA of organellar origin) accretion has generated 1.6% of the extant T. gondii ME49 nuclear genome-the highest fraction ever reported in any organism. NUOTs are primarily found in organisms that retain the non-homologous end-joining repair pathway. Significant movement of organellar DNA was experimentally captured via amplicon sequencing of a CRISPR-induced double-strand break in non-homologous end-joining repair competent, but not ku80 mutant, Toxoplasma parasites. Comparisons with Neospora caninum, a species that diverged from Toxoplasma ~28 mya, revealed that the movement and fixation of five NUMTs predates the split of the two genera. This unexpected level of NUMT conservation suggests evolutionary constraint for cellular function. Most NUMT insertions reside within (60%) or nearby genes (23% within 1.5 kb), and reporter assays indicate that some NUMTs have the ability to function as cis-regulatory elements modulating gene expression. Together, these findings portray a role for organellar sequence insertion in dynamically shaping the genomic architecture and likely contributing to adaptation and phenotypic changes in this important human pathogen.}, } @article {pmid37919084, year = {2023}, author = {Zhang, X and Lu, YC and Wang, JL}, title = {Assembly and Characterization of the Mitochondrial Genome of Fallopia aubertii (L. Henry) Holub.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {28}, number = {10}, pages = {233}, doi = {10.31083/j.fbl2810233}, pmid = {37919084}, issn = {2768-6698}, mesh = {*Genome, Mitochondrial/genetics ; *Fallopia/genetics ; Phylogeny ; Genes, Mitochondrial ; }, abstract = {BACKGROUND: Fallopia aubertii (L. Henry) Holub is a perennial semi-shrub with both ornamental and medicinal value. The mitochondrial genomes of plants contain valuable genetic traits that can be utilized for the exploitation of genetic resources. The parsing of F. aubertii mitochondrial genome can provide insight into the role of mitochondria in plant growth and development, metabolism regulation, evolution, and response to environmental stress.

METHODS: In this study, we sequenced the mitochondrial genome of F. aubertii using the Illumina NovaSeq 6000 platform and Nanopore platform. We conducted a comprehensive analysis of the mitochondrial genome of F. aubertii, which involved examining various aspects such as gene composition, repetitive sequences, RNA editing sites, phylogeny, and organelle genome homology. To achieve this, we employed several bioinformatics methods including sequence alignment analysis, repetitive sequence analysis, phylogeny analysis, and more.

RESULTS: The mitochondrial genome of F. aubertii has 64 genes, including 34 protein-coding genes (PCGs), three rRNAs, and 27 tRNAs. There were 77 short tandem repeat sequences detected in the mitochondrial genome, five tandem repeat sequences identified by Tandem Repeats Finder (TRF), and 50 scattered repeat sequences observed, including 22 forward repeat sequences and 28 palindrome repeat sequences. A total of 367 RNA coding sites were predicted in PCGs, with the highest number (33) found within ccmB. Ka/Ks values estimated for mitochondrial genes of F. aubertii and three closely related species representing Caryophyllales were less than 1 for most of the genes. The maximum likelihood evolutionary tree showed that F. aubertii and Nepenthes ×ventrata are most closely related.

CONCLUSIONS: In this study, we obtained basic information on the mitochondrial genome of F. aubertii and this study investigated repeat sequences and homologous segments, predicted RNA editing sites, and utilized the Ka/Ks ratio to estimate the selection pressure on mitochondrial genes of F. aubertii. We also discussed the systematic evolutionary position of F. aubertii based on mitochondrial genome sequences. Our study revealed variations in the sequence and structure of mitochondrial genomes in Caryophyllales. These findings are of great significance for identifying and improving valuable plant traits and serve as a reference for future molecular studies of F. aubertii.}, } @article {pmid37924024, year = {2023}, author = {Lu, G and Wang, W and Mao, J and Li, Q and Que, Y}, title = {Complete mitogenome assembly of Selenicereus monacanthus revealed its molecular features, genome evolution, and phylogenetic implications.}, journal = {BMC plant biology}, volume = {23}, number = {1}, pages = {541}, pmid = {37924024}, issn = {1471-2229}, support = {XZ202301ZY0020N//the Science and Technology Program of Tibet Autonomous Region/ ; }, mesh = {Phylogeny ; *Genome, Mitochondrial ; Genomics ; Evolution, Molecular ; *Cactaceae/genetics ; }, abstract = {BACKGROUND: Mitochondria are the powerhouse of the cell and are critical for plant growth and development. Pitaya (Selenicereus or Hylocereus) is the most important economic crop in the family Cactaceae and is grown worldwide, however its mitogenome is unreported.

RESULTS: This study assembled the complete mitogenome of the red skin and flesh of pitaya (Selenicereus monacanthus). It is a full-length, 2,290,019 bp circular molecule encoding 59 unique genes that only occupy 2.17% of the entire length. In addition, 4,459 pairs of dispersed repeats (≥ 50 bp) were identified, accounting for 84.78% of the total length, and three repeats (394,588, 124,827, and 13,437 bp) mediating genomic recombination were identified by long read mapping and Sanger sequencing. RNA editing events were identified in all 32 protein-coding genes (PCGs), among which four sites (nad1-2, nad4L-2, atp9-copy3-223, and ccmFC-1309) were associated with the initiation or termination of PCGs. Seventy-eight homologous fragments of the chloroplast genome were identified in the mitogenome, the longest having 4,523 bp. In addition, evolutionary analyses suggest that S. monacanthus may have undergone multiple genomic reorganization events during evolution, with the loss of at least nine PCGs (rpl2, rpl10, rps2, rps3, rps10, rps11, rps14, rps19, and sdh3).

CONCLUSIONS: This study revealed the genetic basis of the S. monacanthus mitogenome, and provided a scientific basis for further research on phenotypic traits and germplasm resource development.}, } @article {pmid37929337, year = {2023}, author = {Ibrahim, MK and Haria, A and Mehta, NV and Degani, MS}, title = {Antimicrobial potential of quaternary phosphonium salt compounds: a review.}, journal = {Future medicinal chemistry}, volume = {15}, number = {22}, pages = {2113-2141}, doi = {10.4155/fmc-2023-0188}, pmid = {37929337}, issn = {1756-8927}, mesh = {Phylogeny ; Microbial Sensitivity Tests ; *Anti-Infective Agents/pharmacology/chemistry ; Anti-Bacterial Agents/pharmacology/chemistry ; Mitochondria ; Quaternary Ammonium Compounds/chemistry ; }, abstract = {Given that mitochondrial dysregulation is a biomarker of many cancers, cationic quaternary phosphonium salt (QPS) conjugation is a widely utilized strategy for anticancer drug design. QPS-conjugated compounds exhibit greater cell permeation and accumulation in negatively charged mitochondria, and thus, show enhanced activity. Phylogenetic similarities between mitochondria and bacteria have provided a rationale for exploring the antibacterial properties of mitochondria-targeted compounds. Additionally, due to the importance of mitochondria in the survival of pathogenic microbes, including fungi and parasites, this strategy can be extended to these organisms as well. This review examines recent literature on the antimicrobial activities of various QPS-conjugated compounds and provides future directions for exploring the medicinal chemistry of these compounds.}, } @article {pmid37930986, year = {2023}, author = {Diaz-Recio Lorenzo, C and Patel, T and Arsenault-Pernet, EJ and Poitrimol, C and Jollivet, D and Martinez Arbizu, P and Gollner, S}, title = {Highly structured populations of deep-sea copepods associated with hydrothermal vents across the Southwest Pacific, despite contrasting life history traits.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0292525}, pmid = {37930986}, issn = {1932-6203}, mesh = {Animals ; *Copepoda/genetics ; *Hydrothermal Vents ; *Life History Traits ; DNA, Mitochondrial ; Mitochondria/genetics ; Phylogeny ; Ecosystem ; }, abstract = {Hydrothermal vents are extreme environments, where abundant communities of copepods with contrasting life history traits co-exist along hydrothermal gradients. Here, we discuss how these traits may contribute to the observed differences in molecular diversity and population genetic structure. Samples were collected from vent locations across the globe including active ridges and back-arc basins and compared to existing deep-sea hydrothermal vent and shallow water data, covering a total of 22 vents and 3 non-vent sites. A total of 806 sequences of mtDNA from the Cox1 gene were used to reconstruct the phylogeny, haplotypic relationship and demography within vent endemic copepods (Dirivultidae, Stygiopontius spp.) and non-vent-endemic copepods (Ameiridae, Miraciidae and Laophontidae). A species complex within Stygiopontius lauensis was studied across five pacific back-arc basins at eight hydrothermal vent fields, with cryptic species being restricted to the basins they were sampled from. Copepod populations from the Lau, North Fiji and Woodlark basins are undergoing demographic expansion, possibly linked to an increase in hydrothermal activity in the last 10 kya. Highly structured populations of Amphiascus aff. varians 2 were also observed from the Lau to the Woodlark basins with populations also undergoing expansion. Less abundant harpacticoids exhibit little to no population structure and stable populations. This study suggests that similarities in genetic structure and demography may arise in vent-associated copepods despite having different life history traits. As structured meta-populations may be at risk of local extinction should major anthropogenic impacts, such as deep-sea mining, occur, we highlight the importance of incorporating a trait-based approach to investigate patterns of genetic connectivity and demography, particularly regarding area-based management tools and environmental management plans.}, } @article {pmid37931036, year = {2023}, author = {Gu, H and Wen, J and Zhao, X and Zhang, X and Ren, X and Cheng, H and Qu, L}, title = {Evolution, Inheritance, and Strata Formation of the W Chromosome in Duck (Anas platyrhynchos).}, journal = {Genome biology and evolution}, volume = {15}, number = {11}, pages = {}, pmid = {37931036}, issn = {1759-6653}, mesh = {Animals ; Female ; *Ducks/genetics ; *Evolution, Molecular ; Sex Chromosomes ; Birds/genetics ; Inheritance Patterns ; }, abstract = {The nonrecombining female-limited W chromosome is predicted to experience unique evolutionary processes. Difficulties in assembling W chromosome sequences have hindered the identification of duck W-linked sequences and their evolutionary footprint. To address this, we conducted three initial contig-level genome assemblies and developed a rigorous pipeline by which to successfully expand the W-linked data set, including 11 known genes and 24 newly identified genes. Our results indicate that the W chromosome expression may not be subject to female-specific selection; a significant convergent pattern of upregulation associated with increased female-specific selection was not detected. The genetic stability of the W chromosome is also reflected in the strong evolutionary correlation between it and the mitochondria; the complete consistency of the cladogram topology constructed from their gene sequences proves the shared maternal coevolution. By detecting the evolutionary trajectories of W-linked sequences, we have found that recombination suppression started in four distinct strata, of which three were conserved across Neognathae. Taken together, our results have revealed a unique evolutionary pattern and an independent stratum evolutionary pattern for sex chromosomes.}, } @article {pmid37933590, year = {2024}, author = {Khan, M and Joshi, M and Espeland, M and Huemer, P and Lopez-Vaamonde, C and Mutanen, M}, title = {Patterns of speciation in a parapatric pair of Saturnia moths as revealed by target capture.}, journal = {Molecular ecology}, volume = {33}, number = {1}, pages = {e17194}, doi = {10.1111/mec.17194}, pmid = {37933590}, issn = {1365-294X}, support = {314702//Academy of Finland/ ; 101081280//COFUND/ ; 00230503//Suomen Kulttuurirahasto/ ; projectInfoBioS//European Regional Development Fund (ERDF)/ ; EX011185//European Regional Development Fund (ERDF)/ ; }, mesh = {Animals ; Phylogeny ; *Moths/genetics ; Biological Evolution ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; }, abstract = {The focus of this study has been to understand the evolutionary relationships and taxonomy of a widely distributed parapatric species pair of wild silk moths in Europe: Saturnia pavonia and Saturnia pavoniella (Lepidoptera: Saturniidae). To address species delimitation in these parapatric taxa, target enrichment and mtDNA sequencing was employed alongside phylogenetic, admixture, introgression, and species delimitation analyses. The dataset included individuals from both species close to and farther away from the contact zone as well as two hybrids generated in the lab. Nuclear markers strongly supported both S. pavonia and S. pavoniella as two distinct species, with hybrids forming a sister group to S. pavoniella. However, the Maximum Likelihood (ML) tree generated from mtDNA sequencing data presented a different picture, showing both taxa to be phylogenetically intermixed. This inconsistency is likely attributable to mitonuclear discordance, which can arise from biological factors (e.g., introgressive hybridization and/or incomplete lineage sorting). Our analyses indicate that past introgressions have taken place, but that there is no evidence to suggest an ongoing admixture between the two species, demonstrating that the taxa have reached full postzygotic reproductive isolation and hence represent two distinct biological species. Finally, we discuss our results from an evolutionary point of view taking into consideration the past climatic oscillations that have likely shaped the present dynamics between the two species. Overall, our study demonstrates the effectiveness of the target enrichment approach in resolving shallow phylogenetic relationships under complex evolutionary circumstances and that this approach is useful in establishing robust and well-informed taxonomic delimitations involving parapatric taxa.}, } @article {pmid37935058, year = {2023}, author = {Smith, CH and Mejia-Trujillo, R and Breton, S and Pinto, BJ and Kirkpatrick, M and Havird, JC}, title = {Mitonuclear Sex Determination? Empirical Evidence from Bivalves.}, journal = {Molecular biology and evolution}, volume = {40}, number = {11}, pages = {}, pmid = {37935058}, issn = {1537-1719}, support = {R35 GM142836/GM/NIGMS NIH HHS/United States ; 1R35GM142836/NH/NIH HHS/United States ; }, mesh = {Female ; Animals ; *Bivalvia/genetics ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Genes, Mitochondrial ; *RNA, Small Untranslated ; }, abstract = {Genetic elements encoded in nuclear DNA determine the sex of an individual in many animals. In certain bivalve lineages that possess doubly uniparental inheritance (DUI), mitochondrial DNA (mtDNA) has been hypothesized to contribute to sex determination. In these cases, females transmit a female mtDNA to all offspring, while male mtDNA (M mtDNA) is transmitted only from fathers to sons. Because M mtDNA is inherited in the same way as Y chromosomes, it has been hypothesized that mtDNA may be responsible for sex determination. However, the role of mitochondrial and nuclear genes in sex determination has yet to be validated in DUI bivalves. In this study, we used DNA, RNA, and mitochondrial short noncoding RNA (sncRNA) sequencing to explore the role of mitochondrial and nuclear elements in the sexual development pathway of the freshwater mussel Potamilus streckersoni (Bivalvia: Unionida). We found that the M mtDNA sheds a sncRNA partially within a male-specific mitochondrial gene that targets a pathway hypothesized to be involved in female development and mitophagy. RNA-seq confirmed the gene target was significantly upregulated in females, supporting a direct role of mitochondrial sncRNAs in gene silencing. These findings support the hypothesis that M mtDNA inhibits female development. Genome-wide patterns of genetic differentiation and heterozygosity did not support a nuclear sex-determining region, although we cannot reject that nuclear factors are involved with sex determination. Our results provide further evidence that mitochondrial loci contribute to diverse, nonrespiratory functions and additional insights into an unorthodox sex-determining system.}, } @article {pmid37939146, year = {2023}, author = {Garcia, PS and Barras, F and Gribaldo, S}, title = {Components of iron-Sulfur cluster assembly machineries are robust phylogenetic markers to trace the origin of mitochondria and plastids.}, journal = {PLoS biology}, volume = {21}, number = {11}, pages = {e3002374}, pmid = {37939146}, issn = {1545-7885}, mesh = {Phylogeny ; *Iron-Sulfur Proteins/genetics/metabolism ; Plastids/genetics/metabolism ; Mitochondria/genetics/metabolism ; Iron/metabolism ; Sulfur/metabolism ; }, abstract = {Establishing the origin of mitochondria and plastids is key to understand 2 founding events in the origin and early evolution of eukaryotes. Recent advances in the exploration of microbial diversity and in phylogenomics approaches have indicated a deep origin of mitochondria and plastids during the diversification of Alphaproteobacteria and Cyanobacteria, respectively. Here, we strongly support these placements by analyzing the machineries for assembly of iron-sulfur ([Fe-S]) clusters, an essential function in eukaryotic cells that is carried out in mitochondria by the ISC machinery and in plastids by the SUF machinery. We assessed the taxonomic distribution of ISC and SUF in representatives of major eukaryotic supergroups and analyzed the phylogenetic relationships with their prokaryotic homologues. Concatenation datasets of core ISC proteins show an early branching of mitochondria within Alphaproteobacteria, right after the emergence of Magnetococcales. Similar analyses with the SUF machinery place primary plastids as sister to Gloeomargarita within Cyanobacteria. Our results add to the growing evidence of an early emergence of primary organelles and show that the analysis of essential machineries of endosymbiotic origin provide a robust signal to resolve ancient and fundamental steps in eukaryotic evolution.}, } @article {pmid37940011, year = {2023}, author = {Lopez-Jimenez, J and Herrera, J and Alzate, JF}, title = {Expanding the knowledge frontier of mitoviruses in Cannabis sativa.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {116}, number = {}, pages = {105523}, doi = {10.1016/j.meegid.2023.105523}, pmid = {37940011}, issn = {1567-7257}, mesh = {*Cannabis/genetics ; Phylogeny ; *RNA Viruses/genetics ; Mitochondria/genetics ; Fungi ; }, abstract = {Mitoviruses were initially known for their presence in the mitochondria of fungi and were considered exclusive to these organisms. However, recent studies have shown that they are also present in a large number of plant species. Despite the potential impact that mitoviruses might have on the mitochondria of plant cells, there is a lack of information about these ancient RNA viruses, especially within the Cannabaceae family. Cannabis sativa has been in the spotlight in recent years due to the growing industrial applications of plant derivatives, such as fiber and secondary metabolites. Given the importance of Cannabis in today's agriculture, our study aimed to expand the knowledge frontier of Mitoviruses in C. sativa by increasing the number of reference genomes of CasaMV1 available in public databases and representing a larger number of crops in countries where its industrial-scale growth is legalized. To achieve this goal, we used transcriptomics to sequence the first mitoviral genomes of Colombian crops and analyzed RNA-seq datasets available in the SRA databank. Additionally, the evolutionary analysis performed using the mitovirus genomes revealed two main lineages of CasaMV1, termed CasaMV1_L1 and CasaMV1_L2. These mitoviral lineages showed strong clustering based on the geographic location of the crops and differential expression intensities.}, } @article {pmid37944010, year = {2024}, author = {Pegan, TM and Berv, JS and Gulson-Castillo, ER and Kimmitt, AA and Winger, BM}, title = {The pace of mitochondrial molecular evolution varies with seasonal migration distance.}, journal = {Evolution; international journal of organic evolution}, volume = {78}, number = {1}, pages = {160-173}, doi = {10.1093/evolut/qpad200}, pmid = {37944010}, issn = {1558-5646}, support = {2146950//National Science Foundation/ ; //Jean Wright Cohn Endowment Fund/ ; //Robert W. Storer Endowment Fund/ ; //Mary Rhoda Swales Museum of Zoology Research Fund/ ; //William G. Fargo Fund/ ; //University of Michigan Museum of Zoology/ ; //William A and Nancy R Klamm Endowment/ ; //Cleveland Museum of Natural History/ ; DGE 1256260//NSF Graduate Research Fellowship/ ; //University of Michigan Rackham Graduate Student Research/ ; }, mesh = {Animals ; Seasons ; *Animal Migration ; Birds/genetics ; Evolution, Molecular ; *Life History Traits ; }, abstract = {Animals that engage in long-distance seasonal migration experience strong selective pressures on their metabolic performance and life history, with potential consequences for molecular evolution. Species with slow life histories typically show lower rates of synonymous substitution (dS) than "fast" species. Previous research suggests long-distance seasonal migrants have a slower life history strategy than short-distance migrants, raising the possibility that rates of molecular evolution may covary with migration distance. Additionally, long-distance migrants may face strong selection on metabolically-important mitochondrial genes due to their long-distance flights. Using over 1,000 mitochondrial genomes, we assessed the relationship between migration distance and mitochondrial molecular evolution in 39 boreal-breeding migratory bird species. We show that migration distance correlates negatively with dS, suggesting that the slow life history associated with long-distance migration is reflected in rates of molecular evolution. Mitochondrial genes in every study species exhibited evidence of purifying selection, but the strength of selection was greater in short-distance migrants, contrary to our predictions. This result may indicate effects of selection for cold tolerance on mitochondrial evolution among species overwintering at high latitudes. Our study demonstrates that the pervasive correlation between life history and molecular evolutionary rates exists in the context of differential adaptations to seasonality.}, } @article {pmid37954502, year = {2022}, author = {Politis-Barber, V and Petrick, HL and Raajendiran, A and DesOrmeaux, GJ and Brunetta, HS and Dos Reis, LM and Mori, MA and Wright, DC and Watt, MJ and Holloway, GP}, title = {Ckmt1 is Dispensable for Mitochondrial Bioenergetics Within White/Beige Adipose Tissue.}, journal = {Function (Oxford, England)}, volume = {3}, number = {5}, pages = {zqac037}, pmid = {37954502}, issn = {2633-8823}, mesh = {Animals ; Humans ; Mice ; *Adipose Tissue, Beige/metabolism ; Adipose Tissue, White ; *Creatine/metabolism ; Creatine Kinase/metabolism ; Energy Metabolism/genetics ; Mitochondria/metabolism ; }, abstract = {Within brown adipose tissue (BAT), the brain isoform of creatine kinase (CKB) has been proposed to regulate the regeneration of ADP and phosphocreatine in a futile creatine cycle (FCC) that stimulates energy expenditure. However, the presence of FCC, and the specific creatine kinase isoforms regulating this theoretical model within white adipose tissue (WAT), remains to be fully elucidated. In the present study, creatine did not stimulate respiration in cultured adipocytes, isolated mitochondria or mouse permeabilized WAT. Additionally, while creatine kinase ubiquitous-type, mitochondrial (CKMT1) mRNA and protein were detected in human WAT, shRNA-mediated reductions in Ckmt1 did not decrease submaximal respiration in cultured adipocytes, and ablation of CKMT1 in mice did not alter energy expenditure, mitochondrial responses to pharmacological β3-adrenergic activation (CL 316, 243) or exacerbate the detrimental metabolic effects of consuming a high-fat diet. Taken together, these findings solidify CKMT1 as dispensable in the regulation of energy expenditure, and unlike in BAT, they do not support the presence of FCC within WAT.}, } @article {pmid37955101, year = {2023}, author = {Da Costa, RT and Riggs, LM and Solesio, ME}, title = {Inorganic polyphosphate and the regulation of mitochondrial physiology.}, journal = {Biochemical Society transactions}, volume = {51}, number = {6}, pages = {2153-2161}, pmid = {37955101}, issn = {1470-8752}, support = {R00 AG055701/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Energy Metabolism ; Mammals/metabolism ; *Mitochondria/metabolism ; Mitochondrial Permeability Transition Pore/metabolism ; Polymers ; *Polyphosphates/metabolism ; }, abstract = {Inorganic polyphosphate (polyP) is an ancient polymer that is well-conserved throughout evolution. It is formed by multiple subunits of orthophosphates linked together by phosphoanhydride bonds. The presence of these bonds, which are structurally similar to those found in ATP, and the high abundance of polyP in mammalian mitochondria, suggest that polyP could be involved in the regulation of the physiology of the organelle, especially in the energy metabolism. In fact, the scientific literature shows an unequivocal role for polyP not only in directly regulating oxidative a phosphorylation; but also in the regulation of reactive oxygen species metabolism, mitochondrial free calcium homeostasis, and the formation and opening of mitochondrial permeability transitions pore. All these processes are closely interconnected with the status of mitochondrial bioenergetics and therefore play a crucial role in maintaining mitochondrial and cell physiology. In this invited review, we discuss the main scientific literature regarding the regulatory role of polyP in mammalian mitochondrial physiology, placing a particular emphasis on its impact on energy metabolism. Although the effects of polyP on the physiology of the organelle are evident; numerous aspects, particularly within mammalian cells, remain unclear and require further investigation. These aspects encompass, for example, advancing the development of more precise analytical methods, unraveling the mechanism responsible for sensing polyP levels, and understanding the exact molecular mechanism that underlies the effects of polyP on mitochondrial physiology. By increasing our understanding of the biology of this ancient and understudied polymer, we could unravel new pharmacological targets in diseases where mitochondrial dysfunction, including energy metabolism dysregulation, has been broadly described.}, } @article {pmid37956860, year = {2024}, author = {Zhang, L and Liu, K and Liu, Z and Tao, H and Fu, X and Hou, J and Jia, G and Hou, Y}, title = {In pre-clinical study fetal hypoxia caused autophagy and mitochondrial impairment in ovary granulosa cells mitigated by melatonin supplement.}, journal = {Journal of advanced research}, volume = {64}, number = {}, pages = {15-30}, pmid = {37956860}, issn = {2090-1224}, mesh = {Animals ; *Melatonin/pharmacology ; Female ; *Autophagy/drug effects ; Mice ; *Granulosa Cells/metabolism/drug effects ; *Mitochondria/metabolism/drug effects ; *Fetal Hypoxia/drug therapy/metabolism ; Pregnancy ; Animals, Newborn ; Ovary/metabolism/drug effects ; Disease Models, Animal ; Signal Transduction/drug effects ; }, abstract = {INTRODUCTION: Fetal hypoxia has long-term effects on postnatal reproductive functions and the mitochondrial impairments of ovarian granulosa cells may be one of the causes. Melatonin applied to mitigate mitochondrial dysfunction and autophagy in mammalian cells has been reported. However, the potential mechanisms by which fetal hypoxia damages reproductive function in neonatal female mice and the melatonin effects on this problem remain unclear.

OBJECTIVES: This research aimed to explore the mechanism that fetal hypoxia damages reproductive function in neonatal female mice and attempt to improve the reproductive function by treating with melatonin in vivo and in vitro.

METHODS: We established a fetal hypoxia model and confirmed that fetal hypoxia affects ovarian function by inducing GC excessive autophagy. Transcriptomic analysis, gene interference, cell immunofluorescence, immunohistochemistry and western blot were conducted to explore and verify the underlying mechanisms in mice GCs and KGN cells. Finally, melatonin treatment was executed on hypoxia-treated mice GCs and KGN cells and melatonin injection to fetal-hypoxia-treated mice to determine its effect.

RESULTS: The results of in vitro experiments found that fetal hypoxia led to mitochondrial dysfunction in ovarian GCs causing autophagic cell death. And the PI3K/Akt/FoxO pathway mediated the occurrence of this process by transcriptome analysis of ovarian GCs from normal and fetal hypoxia mice, which was further verified in mice GCs and KGN cells. Additionally, melatonin administration prevented autophagic injuries and mitochondrial impairments in hypoxia-treated mice GCs and KGN cells. Meanwhile, in vivo experiments by melatonin injection ameliorated oxidative stress of ovary in fetal-hypoxia-treated mice and improved their low fertility.

CONCLUSION: Our data found that fetal hypoxia causes ovarian GCs excessive autophagy leading to low fertility in neonatal female mice and mitigated by melatonin. These results provide a potential therapy for hypoxic stress-related reproductive disorders.}, } @article {pmid37958068, year = {2023}, author = {Hui, M and Zhang, Y and Wang, A and Sha, Z}, title = {The First Genome Survey of the Snail Provanna glabra Inhabiting Deep-Sea Hydrothermal Vents.}, journal = {Animals : an open access journal from MDPI}, volume = {13}, number = {21}, pages = {}, pmid = {37958068}, issn = {2076-2615}, support = {XDA22050302 and XDB42000000//the Strategic Priority Research Program of the Chinese Academy of Sciences/ ; 42025603//National Science Foundation for Distinguished Young Scholars/ ; LSKJ202203104//the Science and Technology Innovation Project of Laoshan Laboratory/ ; }, abstract = {The snail P. glabra is an endemic species in deep-sea chemosynthetic ecosystems of the Northwest Pacific Ocean. To obtain more genetic information on this species and provide the basis for subsequent whole-genome map construction, a genome survey was performed on this snail from the hydrothermal vent of Okinawa Trough. The genomic size of P. glabra was estimated to be 1.44 Gb, with a heterozygosity of 1.91% and a repeated sequence content of 69.80%. Based on the sequencing data, a draft genome of 1.32 Gb was assembled. Transposal elements (TEs) accounted for 40.17% of the entire genome, with DNA transposons taking the highest proportion. It was found that most TEs were inserted in the genome recently. In the simple sequence repeats, the dinucleotide motif was the most enriched microsatellite type, accounting for 53% of microsatellites. A complete mitochondrial genome of P. glabra with a total length of 16,268 bp was assembled from the sequencing data. After comparison with the published mitochondrial genome of Provanna sp. from a methane seep, 331 potential single nucleotide polymorphism (SNP) sites were identified in protein-coding genes (PCGs). Except for the cox1 gene, nad2, nad4, nad5, and cob genes are expected to be candidate markers for population genetic and phylogenetic studies of P. glabra and other deep-sea snails. Compared with shallow-water species, three mitochondrial genes of deep-sea gastropods exhibited a higher evolutionary rate, indicating strong selection operating on mitochondria of deep-sea species. This study provides insights into the genome characteristics of P. glabra and supplies genomic resources for further studies on the adaptive evolution of the snail in extreme deep-sea chemosynthetic environments.}, } @article {pmid37978174, year = {2023}, author = {Mahendrarajah, TA and Moody, ERR and Schrempf, D and Szánthó, LL and Dombrowski, N and Davín, AA and Pisani, D and Donoghue, PCJ and Szöllősi, GJ and Williams, TA and Spang, A}, title = {ATP synthase evolution on a cross-braced dated tree of life.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {7456}, pmid = {37978174}, issn = {2041-1723}, support = {BB/N000919/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Phylogeny ; *Bacteria/genetics ; *Archaea/genetics ; Mitochondria/genetics ; Adenosine Triphosphate ; Evolution, Molecular ; Eukaryota/genetics ; Biological Evolution ; }, abstract = {The timing of early cellular evolution, from the divergence of Archaea and Bacteria to the origin of eukaryotes, is poorly constrained. The ATP synthase complex is thought to have originated prior to the Last Universal Common Ancestor (LUCA) and analyses of ATP synthase genes, together with ribosomes, have played a key role in inferring and rooting the tree of life. We reconstruct the evolutionary history of ATP synthases using an expanded taxon sampling set and develop a phylogenetic cross-bracing approach, constraining equivalent speciation nodes to be contemporaneous, based on the phylogenetic imprint of endosymbioses and ancient gene duplications. This approach results in a highly resolved, dated species tree and establishes an absolute timeline for ATP synthase evolution. Our analyses show that the divergence of ATP synthase into F- and A/V-type lineages was a very early event in cellular evolution dating back to more than 4 Ga, potentially predating the diversification of Archaea and Bacteria. Our cross-braced, dated tree of life also provides insight into more recent evolutionary transitions including eukaryogenesis, showing that the eukaryotic nuclear and mitochondrial lineages diverged from their closest archaeal (2.67-2.19 Ga) and bacterial (2.58-2.12 Ga) relatives at approximately the same time, with a slightly longer nuclear stem-lineage.}, } @article {pmid37988339, year = {2023}, author = {Kang, N and Hu, H}, title = {Adaptive evidence of mitochondrial genes in Pteromalidae and Eulophidae (Hymenoptera: Chalcidoidea).}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0294687}, pmid = {37988339}, issn = {1932-6203}, mesh = {Animals ; *Hymenoptera/genetics ; Genes, Mitochondrial ; Phylogeny ; Bayes Theorem ; Ecosystem ; Ultraviolet Rays ; Mitochondrial Proteins/genetics ; *Genome, Mitochondrial ; }, abstract = {Pteromalidae and Eulophidae are predominant and abundant taxa within Chalcidoidea (Hymenoptera: Apocrita). These taxa are found in diverse ecosystems, ranging from basin deserts (200 m) to alpine grasslands (4500 m). Mitochondria, cellular powerhouses responsible for energy production via oxidative phosphorylation, are sensitive to various environmental factors such as extreme cold, hypoxia, and intense ultraviolet radiation characteristic of alpine regions. Whether the molecular evolution of mitochondrial genes in these parasitoids corresponds to changes in the energy requirements and alpine environmental adaptations remains unknown. In this study, we performed a comparative analysis of mitochondrial protein-coding genes from 11 alpine species of Pteromalidae and Eulophidae, along with 18 lowland relatives, including 16 newly sequenced species. We further examined the codon usage preferences (RSCU, ENC-GC3s, neutrality, and PR2 bias plot) in these mitochondrial protein-coding sequences and conducted positive selection analysis based on their Bayesian phylogenetic relationships, and identified positive selection sites in the ATP6, ATP8, COX1, COX3, and CYTB genes, emphasizing the crucial role of mitochondrial gene adaptive evolution in the adaptation of Pteromalidae and Eulophidae to alpine environments. The phylogenetically independent contrast (PIC) analysis results verified the ω ratio of 13 PCGs from Pteromalidae and Eulophidae increased with elevation, and results from generalized linear model confirm that ATP6, ATP8, COX3, and ND1 are closely correlated with temperature-related environmental factors. This research not only enriched the molecular data of endemic alpine species but also underscores the significance of mitochondrial genes in facilitating the adaptation of these minor parasitoids to plateau habitats.}, } @article {pmid37994879, year = {2023}, author = {Záhonová, K and Füssy, Z and Stairs, CW and Leger, MM and Tachezy, J and Čepička, I and Roger, AJ and Hampl, V}, title = {Comparative analysis of mitochondrion-related organelles in anaerobic amoebozoans.}, journal = {Microbial genomics}, volume = {9}, number = {11}, pages = {}, pmid = {37994879}, issn = {2057-5858}, support = {//CIHR/Canada ; /ERC_/European Research Council/International ; }, mesh = {Anaerobiosis ; *Mitochondria/genetics ; *Eukaryota ; Iron ; Sulfates ; }, abstract = {Archamoebae comprises free-living or endobiotic amoebiform protists that inhabit anaerobic or microaerophilic environments and possess mitochondrion-related organelles (MROs) adapted to function anaerobically. We compared in silico reconstructed MRO proteomes of eight species (six genera) and found that the common ancestor of Archamoebae possessed very few typical components of the protein translocation machinery, electron transport chain and tricarboxylic acid cycle. On the other hand, it contained a sulphate activation pathway and bacterial iron-sulphur (Fe-S) assembly system of MIS-type. The metabolic capacity of the MROs, however, varies markedly within this clade. The glycine cleavage system is widely conserved among Archamoebae, except in Entamoeba, probably owing to its role in catabolic function or one-carbon metabolism. MRO-based pyruvate metabolism was dispensed within subgroups Entamoebidae and Rhizomastixidae, whereas sulphate activation could have been lost in isolated cases of Rhizomastix libera, Mastigamoeba abducta and Endolimax sp. The MIS (Fe-S) assembly system was duplicated in the common ancestor of Mastigamoebidae and Pelomyxidae, and one of the copies took over Fe-S assembly in their MRO. In Entamoebidae and Rhizomastixidae, we hypothesize that Fe-S cluster assembly in both compartments may be facilitated by dual localization of the single system. We could not find evidence for changes in metabolic functions of the MRO in response to changes in habitat; it appears that such environmental drivers do not strongly affect MRO reduction in this group of eukaryotes.}, } @article {pmid37995039, year = {2024}, author = {Lee, YJ and Uh, YR and Kim, YM and Kim, CM and Jang, CS}, title = {Characterization and comparative analysis of the complete organelle genomes of three red macroalgae species (Neoporphyra dentata, Neoporphyra seriata, and Neopyropia yezoensis) and development of molecular makers for their identification.}, journal = {Genes & genomics}, volume = {46}, number = {3}, pages = {355-365}, pmid = {37995039}, issn = {2092-9293}, support = {20210656//Korea Institute of Marine Science and Technology promotion/ ; }, mesh = {Humans ; *Seaweed/genetics ; Phylogeny ; *Rhodophyta/genetics ; Chloroplasts/genetics ; *Edible Seaweeds ; *Porphyra ; }, abstract = {BACKGROUND: Many species of red algae belonging to the phylum Rhodophyta are consumed by humans as raw materials for nutrition and medicine. As the seaweed market grows, the importance of the laver species has increased. The classification of red algal species has changed significantly, and the accuracy of this classification has improved significantly in recent years. Here, we report the complete circular genomes of the chloroplasts (cp) and mitochondria (mt) of three laver species (Neoporphyra dentata, Neoporphyra seriata, and Neopyropia yezoensis).

OBJECTIVE: This study aims to assemble, annotate, and characterize the organization of the organelle genomes of three laver species, conduct comparative genomic studies, and develop molecular markers based on SNPs.

METHODS: We analyzed organelle genome structures, repeat sequences, sequence divergence, gene rearrangements, and phylogenetic relationships of three laver species.

RESULTS: The chloroplast genomes of the three species contained an average of 212 protein-coding genes (PCGs), while the mitochondrial genomes contained an average of 25 PCGs. We reconstructed the phylogenetic trees based on both chloroplast and mitochondrial genomes using 201 and 23 PCGs (in cp and mt genomes, respectively) shared in the class Bangiophyceae (and five species of Florideophyceae class used as an outgroup). In addition, 12 species-specific molecular markers were developed for qRT-PCR analysis.

CONCLUSIONS: This is the first report of Neoporphyra seriata complete organellar genomes. With the results, this study provides useful genetic information regarding taxonomic discrepancies, the reconstruction of phylogenetic trees, and the evolution of red algae. Moreover, the species-specific markers can be used as fast and easy methods to identify a target species.}, } @article {pmid37996801, year = {2023}, author = {Song, Y and Du, X and Li, A and Fan, A and He, L and Sun, Z and Niu, Y and Qiao, Y}, title = {Assembly and analysis of the complete mitochondrial genome of Forsythia suspensa (Thunb.) Vahl.}, journal = {BMC genomics}, volume = {24}, number = {1}, pages = {708}, pmid = {37996801}, issn = {1471-2164}, support = {20210302123390//the Basic Research Program of Shanxi Province/ ; 2023//Shanxi Province Modern Agricultural Chinese Herbal Medicine Industry Technology System Project/ ; CXGC2023041//Shanxi Agricultural University Science and Technology Innovation Promotion Project/ ; }, mesh = {*Forsythia/genetics/chemistry ; *Genome, Mitochondrial/genetics ; Phylogeny ; *Plants, Medicinal/chemistry/genetics ; *Nucleic Acids ; *Genome, Chloroplast ; }, abstract = {BACKGROUND: Forsythia suspensa (Thunb.) Vahl is a valuable ornamental and medicinal plant. Although the nuclear and chloroplast genomes of F. suspensa have been published, its complete mitochondrial genome sequence has yet to be reported. In this study, the genomic DNA of F. suspensa yellowish leaf material was extracted, sequenced by using a mixture of Illumina Novaseq6000 short reads and Oxford Nanopore PromethION long reads, and the sequencing data were assembled and annotated.

RESULT: The F. suspensa mitochondrial genome was obtained in the length of 535,692 bp with a circular structure, and the GC content was 44.90%. The genome contains 60 genes, including 36 protein-coding genes, 21 tRNA genes, and three rRNA genes. We further analyzed RNA editing of the protein-coding genes, relative synonymous codon usage, and sequence repeats based on the genomic data. There were 25 homologous sequences between F. suspensa mitochondria and chloroplast genome, which involved the transfer of 8 mitochondrial genes, and 9473 homologous sequences between mitochondrial and nuclear genomes. Analysis of the nucleic acid substitution rate, nucleic acid diversity, and collinearity of protein-coding genes of the F. suspensa mitochondrial genome revealed that the majority of genes may have undergone purifying selection, exhibiting a slower rate of evolution and a relatively conserved structure. Analysis of the phylogenetic relationships among different species revealed that F. suspensa was most closely related to Olea europaea subsp. Europaea.

CONCLUSION: In this study, we sequenced, assembled, and annotated a high-quality F. suspensa mitochondrial genome. The results of this study will enrich the mitochondrial genome data of Forsythia, lay a foundation for the phylogenetic development of Forsythia, and promote the evolutionary analysis of Oleaceae species.}, } @article {pmid37999092, year = {2023}, author = {Liu, SP and Yin, HD and Li, WJ and Qin, ZH and Yang, Y and Huang, ZZ and Zong, L and Liu, XK and Du, Z and Fan, WL and Zhang, YQ and Zhang, D and Zhang, YE and Liu, XY and Yang, D and Ge, SQ}, title = {The Morphological Transformation of the Thorax during the Eclosion of Drosophila melanogaster (Diptera: Drosophilidae).}, journal = {Insects}, volume = {14}, number = {11}, pages = {}, pmid = {37999092}, issn = {2075-4450}, support = {32270460//National Science Foundation of China/ ; 2021xjkk0605//Third Xinjiang Scientific Expedition Program/ ; }, abstract = {The model organism Drosophila melanogaster, as a species of Holometabola, undergoes a series of transformations during metamorphosis. To deeply understand its development, it is crucial to study its anatomy during the key developmental stages. We describe the anatomical systems of the thorax, including the endoskeleton, musculature, nervous ganglion, and digestive system, from the late pupal stage to the adult stage, based on micro-CT and 3D visualizations. The development of the endoskeleton causes original and insertional changes in muscles. Several muscles change their shape during development in a non-uniform manner with respect to both absolute and relative size; some become longer and broader, while others shorten and become narrower. Muscular shape may vary during development. The number of muscular bundles also increases or decreases. Growing muscles are probably anchored by the tissues in the stroma. Some muscles and tendons are absent in the adult stage, possibly due to the hardened sclerites. Nearly all flight muscles are present by the third day of the pupal stage, which may be due to the presence of more myofibers with enough mitochondria to support flight power. There are sexual differences in the same developmental period. In contrast to the endodermal digestive system, the functions of most thoracic muscles change in the development from the larva to the adult in order to support more complex locomotion under the control of a more structured ventral nerve cord based on the serial homology proposed herein.}, } @article {pmid38002320, year = {2023}, author = {Nusir, A and Sinclair, P and Kabbani, N}, title = {Mitochondrial Proteomes in Neural Cells: A Systematic Review.}, journal = {Biomolecules}, volume = {13}, number = {11}, pages = {}, pmid = {38002320}, issn = {2218-273X}, mesh = {Humans ; *Proteome/metabolism ; *Neurodegenerative Diseases/metabolism ; Proteomics ; Mitochondria/metabolism ; Neurons/metabolism ; Mitochondrial Proteins/metabolism ; }, abstract = {Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular control. There are over 1000 known proteins that either reside within the mitochondria or are transiently associated with it. These mitochondrial proteins represent a functional subcellular protein network (mtProteome) that is encoded by mitochondrial and nuclear genomes and significantly varies between cell types and conditions. In neurons, the high metabolic demand and differential energy requirements at the synapses are met by specific modifications to the mtProteome, resulting in alterations in the expression and functional properties of the proteins involved in energy production and quality control, including fission and fusion. The composition of mtProteomes also impacts the localization of mitochondria in axons and dendrites with a growing number of neurodegenerative diseases associated with changes in mitochondrial proteins. This review summarizes the findings on the composition and properties of mtProteomes important for mitochondrial energy production, calcium and lipid signaling, and quality control in neural cells. We highlight strategies in mass spectrometry (MS) proteomic analysis of mtProteomes from cultured cells and tissue. The research into mtProteome composition and function provides opportunities in biomarker discovery and drug development for the treatment of metabolic and neurodegenerative disease.}, } @article {pmid38006556, year = {2024}, author = {Duplouy, A}, title = {Validating a Mitochondrial Sweep Accompanying the Rapid Spread of a Maternally Inherited Symbiont.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2739}, number = {}, pages = {239-247}, pmid = {38006556}, issn = {1940-6029}, mesh = {*Maternal Inheritance ; *Mitochondria/genetics ; DNA, Mitochondrial/genetics ; Polymorphism, Genetic ; Biological Evolution ; Symbiosis/genetics ; Phylogeny ; }, abstract = {Maternally inherited symbiotic bacteria that interfere with the reproduction of their hosts can contribute to selective sweeps of mitochondrial haplotypes through hitch-hiking or coordinate inheritance of cytoplasmic bacteria and host mitochondria. The sweep will be manifested by genetic variations of mitochondrial genomic DNA of symbiont-infected hosts relative to their uninfected counterparts. In particular, at the population level, infected specimens will show a reduced mitochondrial DNA polymorphism compared to that in the nuclear DNA. This may challenge the use of mitochondrial DNA sequences as neutral genetic markers, as the mitochondrial patterns will reflect the evolutionary history of parasitism, rather than the sole evolutionary history of the host. Here, I describe a detailed step-by-step procedure to infer the occurrence and timing of symbiont-induced mitochondrial sweeps in host species.}, } @article {pmid38007160, year = {2024}, author = {Gao, X and Feng, B and Du, C and Hou, C and Jin, S and Tang, D and Zhu, J and Lv, Y}, title = {Expression dynamics indicate the involvement of SPG7 in the reproduction and spermiogenesis of Phascolosoma esculenta.}, journal = {Gene}, volume = {895}, number = {}, pages = {148028}, doi = {10.1016/j.gene.2023.148028}, pmid = {38007160}, issn = {1879-0038}, mesh = {Animals ; Male ; ATPases Associated with Diverse Cellular Activities/genetics/metabolism ; *Mitochondria/genetics/metabolism ; Spermatogenesis/genetics ; *Spastic Paraplegia, Hereditary/genetics ; Metalloendopeptidases/genetics ; }, abstract = {Spastic paraplegia 7 (SPG7) is an m-AAA protease subunit involved in mitochondrial morphology and physiology. However, its function in animal reproduction is yet to be evaluated. In this study, its molecular features, subcellular localization, and expression dynamics were investigated to analyze its potential function in the reproduction of male Phascolosoma esculenta, an economically important marine species in China. The full-length cDNA of P. esculenta spg7 (Pe-spg7) measures 3053 bp and encodes an 853-amino acid protein (Pe-SPG7). Pe-SPG7 includes two transmembrane domains, an AAA domain and a proteolytic domain. Amino acid sequence alignment revealed that SPG7 was conserved during evolution. The mRNA and protein expression of spg7 indicated its involvement in reproduction. Its expression was the highest in coelomic fluid, where spermatids develop, and it was significantly higher in the breeding stage than in the nonbreeding stage. SPG7 was mainly found in the mitochondria of spermatids in the coelomic fluid, indicating that it functions in this organelle in spermatids. Immunofluorescence experiments showed that SPG7 was expressed and colocalized in the mitochondria during spermiogenesis, suggesting its involvement in P. esculenta spermiogenesis. Therefore, SPG7 may participate in spermiogenesis by functioning in the mitochondria and regulate the reproduction of male P. esculenta. This study provided insights into the function of SPG7 in animal reproduction and P. esculenta gametogenesis.}, } @article {pmid38019044, year = {2024}, author = {Osiewacz, HD}, title = {Impact of Mitochondrial Architecture, Function, Redox Homeostasis, and Quality Control on Organismic Aging: Lessons from a Fungal Model System.}, journal = {Antioxidants & redox signaling}, volume = {40}, number = {16-18}, pages = {948-967}, doi = {10.1089/ars.2023.0487}, pmid = {38019044}, issn = {1557-7716}, mesh = {*Mitochondria/metabolism ; *Homeostasis ; *Oxidation-Reduction ; *Aging/metabolism ; *Podospora/metabolism/genetics ; Humans ; *Reactive Oxygen Species/metabolism ; Oxidative Stress ; Models, Biological ; }, abstract = {Significance: Mitochondria are eukaryotic organelles with various essential functions. They are both the source and the targets of reactive oxygen species (ROS). Different branches of a mitochondrial quality control system (mQCS), such as ROS balancing, degradation of damaged proteins, or whole mitochondria, can mitigate the adverse effects of ROS stress. However, the capacity of mQCS is limited. Overwhelming this capacity leads to dysfunctions and aging. Strategies to interfere into mitochondria-dependent human aging with the aim to increase the healthy period of life, the health span, rely on the precise knowledge of mitochondrial functions. Experimental models such as Podospora anserina, a filamentous fungus with a clear mitochondrial aging etiology, proved to be instrumental to reach this goal. Recent Advances: Investigations of the P. anserina mQCS revealed that it is constituted by a complex network of different branches. Moreover, mitochondrial architecture and lipid homeostasis emerged to affect aging. Critical Issues: The regulation of the mQCS is only incompletely understood. Details about the involved signaling molecules and interacting pathways remain to be elucidated. Moreover, most of the currently generated experimental data were generated in well-controlled experiments that do not reflect the constantly changing natural life conditions and bear the danger to miss relevant aspects leading to incorrect conclusions. Future Directions: In P. anserina, the precise impact of redox signaling as well as of molecular damaging for aging remains to be defined. Moreover, natural fluctuation of environmental conditions needs to be considered to generate a realistic picture of aging mechanisms as they developed during evolution.}, } @article {pmid38036853, year = {2024}, author = {Ando, R and Shimozono, S and Ago, H and Takagi, M and Sugiyama, M and Kurokawa, H and Hirano, M and Niino, Y and Ueno, G and Ishidate, F and Fujiwara, T and Okada, Y and Yamamoto, M and Miyawaki, A}, title = {StayGold variants for molecular fusion and membrane-targeting applications.}, journal = {Nature methods}, volume = {21}, number = {4}, pages = {648-656}, pmid = {38036853}, issn = {1548-7105}, support = {JP15dm0207001//Japan Agency for Medical Research and Development (AMED)/ ; JP21am0101070//Japan Agency for Medical Research and Development (AMED)/ ; 21H05041//Ministry of Education, Culture, Sports, Science and Technology (MEXT)/ ; 19H05794, 19H05795//Ministry of Education, Culture, Sports, Science and Technology (MEXT)/ ; JPM JCR20E2//MEXT | JST | Core Research for Evolutional Science and Technology (CREST)/ ; }, mesh = {*Mitochondria/chemistry ; *Golgi Apparatus/metabolism ; Microtubules/metabolism ; Microscopy, Confocal/methods ; }, abstract = {Although StayGold is a bright and highly photostable fluorescent protein, its propensity for obligate dimer formation may hinder applications in molecular fusion and membrane targeting. To attain monovalent as well as bright and photostable labeling, we engineered tandem dimers of StayGold to promote dispersibility. On the basis of the crystal structure of this fluorescent protein, we disrupted the dimerization to generate a monomeric variant that offers improved photostability and brightness compared to StayGold. We applied the new monovalent StayGold tools to live-cell imaging experiments using spinning-disk laser-scanning confocal microscopy or structured illumination microscopy. We achieved cell-wide, high-spatiotemporal resolution and sustained imaging of dynamic subcellular events, including the targeting of endogenous condensin I to mitotic chromosomes, the movement of the Golgi apparatus and its membranous derivatives along microtubule networks, the distribution of cortical filamentous actin and the remolding of cristae membranes within mobile mitochondria.}, } @article {pmid38042216, year = {2024}, author = {Kong, D and Gan, Z and Li, X}, title = {Phylogenetic relationships and adaptation in deep-sea carideans revealed by mitogenomes.}, journal = {Gene}, volume = {896}, number = {}, pages = {148054}, doi = {10.1016/j.gene.2023.148054}, pmid = {38042216}, issn = {1879-0038}, mesh = {Humans ; Phylogeny ; *Genome, Mitochondrial/genetics ; RNA, Transfer/genetics ; RNA, Ribosomal/genetics ; }, abstract = {The deep-sea environment is characterized by extreme and inhospitable conditions, including oxygen depletion, low temperatures, high pressure, absence of light, and limited food availability. Mitochondria and mitogenomes play a crudial role in aerobic respiration to generate energy for eukaryotes. Here, using the Illumina Hiseq 4000 platform, we performed mitogenome sequencing for five deep-sea caridean species: Lebbeus shinkaiae, Lebbeus Formosus, Glyphocrangon regalis, Heterocarpus dorsalis, and Heterocarpus laevigatus, and five deep-sea caridean mitogenomes were assembled and identified. Each of the five mitogenomes contained 13 protein-coding genes, 2 rRNAs and 22 tRNAs. Specific elements, such as tandem repeats and AT-rich sequences, were observed in the control regions of Lebbeus formosus and Lebbeus shinkaiae, potentially take a role in regulating mitochondrial genome replication and transcription. The gene order of all obtained mitogenomes follows caridean ancestral type organization. Phylogenetic analysis shows a robustly supported phylogenetic tree for the infraorder Caridea. The monophyly of the families included in this study was strongly supported. This study supports the monophyly of Oplophoroidea, but rejects the monophyletic status of Nematocarcinoidea, Crangonoidea, and Alpheoidea. At the genus level, Plesionika is polyphyletic and Rimicaris is paraphyletic in our analysis. Furthermore, Paralebbeus may be considered invalid and synonymous with Lebbeus. Positive selection analysis reveals evidence for adaptive changes in the mitogenome of different deep-sea caridean lineages. Nine residues located in cox1, cox3, atp6, nad1, nad2, nad4, nad5, nad6 and cytb were determined to have undergone positive selection. Mitogenome of different deep-sea lineages experienced different positive selection, and the lineage represented by Alvinocarididae living in deep-sea hydrothermal vents experienced the strongest positive selection. This study provides valuable insights into the adaptive evolution of deep-sea shrimps at the mitochondrial, highlighting the mitogenomic strategy that contribute to their unique adaptations in the deep-sea environment.}, } @article {pmid38047014, year = {2023}, author = {Kobayashi, G}, title = {Buried treasure in a public repository: Mining mitochondrial genes of 32 annelid species from sequence reads deposited in the Sequence Read Archive (SRA).}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e16446}, pmid = {38047014}, issn = {2167-8359}, mesh = {Humans ; Animals ; Genes, Mitochondrial ; Phylogeny ; *Annelida ; DNA, Mitochondrial/genetics ; *Polychaeta/genetics ; }, abstract = {BACKGROUND: The mitochondrial genomes (mitogenomes) of metazoans generally include the same set of protein-coding genes, which ensures the homology of mitochondrial genes between species. The mitochondrial genes are often used as reference data for species identification based on genetic data (DNA barcoding). The need for such reference data has been increasing due to the application of environmental DNA (eDNA) analysis for environmental assessments. Recently, the number of publicly available sequence reads obtained with next-generation sequencing (NGS) has been increasing in the public database (the NCBI Sequence Read Archive, SRA). Such freely available NGS reads would be promising sources for assembling mitochondrial protein-coding genes (mPCGs) of organisms whose mitochondrial genes are not available in GenBank. The present study aimed to assemble annelid mPCGs from raw data deposited in the SRA.

METHODS: The recent progress in the classification of Annelida was briefly introduced. In the present study, the mPCGs of 32 annelid species of 19 families in clitellates and allies in Sedentaria (echiurans and polychaetes) were newly assembled from the reads deposited in the SRA. Assembly was performed with a recently published pipeline mitoRNA, which includes cycles of Bowtie2 mapping and Trinity assembly. Assembled mPCGs were deposited in GenBank as Third Party Data (TPA) data. A phylogenetic tree was reconstructed with maximum likelihood (ML) analysis, together with other mPCGs deposited in GenBank.

RESULTS AND DISCUSSION: mPCG assembly was largely successful except for Travisia forbesii; only four genes were detected from the assembled contigs of the species probably due to the reads targeting its parasite. Most genes were largely successfully obtained, whereas atp8, nad2, and nad4l were only successful in 22-24 species. The high nucleotide substitution rates of these genes might be relevant to the failure in the assembly although nad6, which showed a similarly high substitution rate, was successfully assembled. Although the phylogenetic positions of several lineages were not resolved in the present study, the phylogenetic relationships of some polychaetes and leeches that were not inferred by transcriptomes were well resolved probably due to a more dense taxon sampling than previous phylogenetic analyses based on transcriptomes. Although NGS data are generally better sources for resolving phylogenetic relationships of both higher and lower classifications, there are ensuring needs for specific loci of the mitochondrial genes for analyses that do not require high resolutions, such as DNA barcoding, eDNA, and phylogenetic analysis among lower taxa. Assembly from publicly available NGS reads would help design specific primers for the mitochondrial gene sequences of species, whose mitochondrial genes are hard to amplify by Sanger sequencing using universal primers.}, } @article {pmid38047232, year = {2023}, author = {Charrasse, S and Poquillon, T and Saint-Omer, C and Pastore, M and Bordignon, B and Frye, RE and Reynes, C and Racine, V and Aouacheria, A}, title = {Quantitative assessment of mitochondrial morphology relevant for studies on cellular health and environmental toxicity.}, journal = {Computational and structural biotechnology journal}, volume = {21}, number = {}, pages = {5609-5619}, pmid = {38047232}, issn = {2001-0370}, abstract = {Mitochondria are essential organelles that play crucial roles in cellular energy metabolism, calcium signaling and apoptosis. Their importance in tissue homeostasis and stress responses, combined to their ability to transition between various structural and functional states, make them excellent organelles for monitoring cellular health. Quantitative assessment of mitochondrial morphology can therefore provide valuable insights into environmentally-induced cell damage. High-content screening (HCS) provides a powerful tool for analyzing organelles and cellular substructures. We developed a fully automated and miniaturized HCS wet-plus-dry pipeline (MITOMATICS) exploiting mitochondrial morphology as a marker for monitoring cellular health or damage. MITOMATICS uses an in-house, proprietary software (MitoRadar) to enable fast, exhaustive and cost-effective analysis of mitochondrial morphology and its inherent diversity in live cells. We applied our pipeline and big data analytics software to assess the mitotoxicity of selected chemicals, using the mitochondrial uncoupler CCCP as an internal control. Six different pesticides (inhibiting complexes I, II and III of the mitochondrial respiratory chain) were tested as individual compounds and five other pesticides present locally in Occitanie (Southern France) were assessed in combination to determine acute mitotoxicity. Our results show that the assayed pesticides exhibit specific signatures when used as single compounds or chemical mixtures and that they function synergistically to impact mitochondrial architecture. Study of environment-induced mitochondrial damage has the potential to open new fields in mechanistic toxicology, currently underexplored by regulatory toxicology and exposome research. Such exploration could inform health policy guidelines and foster pharmacological intervention, water, air and soil pollution control and food safety.}, } @article {pmid38052127, year = {2024}, author = {Fernández Miyakawa, ME and Casanova, NA and Kogut, MH}, title = {How did antibiotic growth promoters increase growth and feed efficiency in poultry?.}, journal = {Poultry science}, volume = {103}, number = {2}, pages = {103278}, pmid = {38052127}, issn = {1525-3171}, mesh = {Animals ; *Poultry ; Anti-Bacterial Agents/pharmacology/metabolism ; Chickens ; Mitochondria/metabolism ; *Gastrointestinal Microbiome ; }, abstract = {It has been hypothesized that reducing the bioenergetic costs of gut inflammation as an explanation for the effect of antibiotic growth promoters (AGPs) on animal efficiency, framing some observations but not explaining the increase in growth rate or the prevention of infectious diseases. The host's ability to adapt to alterations in environmental conditions and to maintain health involves managing all physiological interactions that regulate homeostasis. Thus, metabolic pathways are vital in regulating physiological health as the energetic demands of the host guides most biological functions. Mitochondria are not only the metabolic heart of the cell because of their role in energy metabolism and oxidative phosphorylation, but also a central hub of signal transduction pathways that receive messages about the health and nutritional states of cells and tissues. In response, mitochondria direct cellular and tissue physiological alterations throughout the host. The endosymbiotic theory suggests that mitochondria evolved from prokaryotes, emphasizing the idea that these organelles can be affected by some antibiotics. Indeed, therapeutic levels of several antibiotics can be toxic to mitochondria, but subtherapeutic levels may improve mitochondrial function and defense mechanisms by inducing an adaptive response of the cell, resulting in mitokine production which coordinates an array of adaptive responses of the host to the stressor(s). This adaptive stress response is also observed in several bacteria species, suggesting that this protective mechanism has been preserved during evolution. Concordantly, gut microbiome modulation by subinhibitory concentration of AGPs could be the result of direct stimulation rather than inhibition of determined microbial species. In eukaryotes, these adaptive responses of the mitochondria to internal and external environmental conditions, can promote growth rate of the organism as an evolutionary strategy to overcome potential negative conditions. We hypothesize that direct and indirect subtherapeutic AGP regulation of mitochondria functional output can regulate homeostatic control mechanisms in a manner similar to those involved with disease tolerance.}, } @article {pmid38053364, year = {2023}, author = {Camus, MF and Inwongwan, S}, title = {Mitonuclear interactions modulate nutritional preference.}, journal = {Biology letters}, volume = {19}, number = {12}, pages = {20230375}, pmid = {38053364}, issn = {1744-957X}, mesh = {Animals ; Genotype ; *Mitochondria/genetics ; Haplotypes ; Drosophila/genetics ; *Life History Traits ; DNA, Mitochondrial/genetics ; Cell Nucleus/genetics ; }, abstract = {In nature, organisms are faced with constant nutritional options which fuel key life-history traits. Studies have shown that species can actively make nutritional decisions based on internal and external cues. Metabolism itself is underpinned by complex genomic interactions involving components from both nuclear and mitochondrial genomes. Products from these two genomes must coordinate how nutrients are extracted, used and recycled. Given the complicated nature of metabolism, it is not well understood how nutritional choices are affected by mitonuclear interactions. This is under the rationale that changes in genomic interactions will affect metabolic flux and change physiological requirements. To this end we used a large Drosophila mitonuclear genetic panel, comprising nine isogenic nuclear genomes coupled to nine mitochondrial haplotypes, giving a total of 81 different mitonuclear genotypes. We use a capillary-based feeding assay to screen this panel for dietary preference between carbohydrate and protein. We find significant mitonuclear interactions modulating nutritional choices, with these epistatic interactions also being dependent on sex. Our findings support the notion that complex genomic interactions can place a constraint on metabolic flux. This work gives us deeper insights into how key metabolic interactions can have broad implications on behaviour.}, } @article {pmid38060519, year = {2023}, author = {Novák, LVF and Treitli, SC and Pyrih, J and Hałakuc, P and Pipaliya, SV and Vacek, V and Brzoň, O and Soukal, P and Eme, L and Dacks, JB and Karnkowska, A and Eliáš, M and Hampl, V}, title = {Genomics of Preaxostyla Flagellates Illuminates the Path Towards the Loss of Mitochondria.}, journal = {PLoS genetics}, volume = {19}, number = {12}, pages = {e1011050}, pmid = {38060519}, issn = {1553-7404}, support = {R21 ES021028/ES/NIEHS NIH HHS/United States ; /ERC_/European Research Council/International ; }, mesh = {Phylogeny ; *Eukaryota/genetics ; *Oxymonadida/genetics/metabolism ; Mitochondria/genetics ; Genomics ; }, abstract = {The notion that mitochondria cannot be lost was shattered with the report of an oxymonad Monocercomonoides exilis, the first eukaryote arguably without any mitochondrion. Yet, questions remain about whether this extends beyond the single species and how this transition took place. The Oxymonadida is a group of gut endobionts taxonomically housed in the Preaxostyla which also contains free-living flagellates of the genera Trimastix and Paratrimastix. The latter two taxa harbour conspicuous mitochondrion-related organelles (MROs). Here we report high-quality genome and transcriptome assemblies of two Preaxostyla representatives, the free-living Paratrimastix pyriformis and the oxymonad Blattamonas nauphoetae. We performed thorough comparisons among all available genomic and transcriptomic data of Preaxostyla to further decipher the evolutionary changes towards amitochondriality, endobiosis, and unstacked Golgi. Our results provide insights into the metabolic and endomembrane evolution, but most strikingly the data confirm the complete loss of mitochondria for all three oxymonad species investigated (M. exilis, B. nauphoetae, and Streblomastix strix), suggesting the amitochondriate status is common to a large part if not the whole group of Oxymonadida. This observation moves this unique loss to 100 MYA when oxymonad lineage diversified.}, } @article {pmid38062387, year = {2023}, author = {Ouyang, L and Liu, Y and Yao, R and He, D and Yan, L and Chen, Y and Huai, D and Wang, Z and Yu, B and Kang, Y and Jiang, H and Lei, Y and Liao, B and Wang, X}, title = {Genome-wide analysis of UDP-glycosyltransferase gene family and identification of a flavonoid 7-O-UGT (AhUGT75A) enhancing abiotic stress in peanut (Arachis hypogaea L.).}, journal = {BMC plant biology}, volume = {23}, number = {1}, pages = {626}, pmid = {38062387}, issn = {1471-2229}, support = {CARS-13//earmarked fund for China Agricultural Research System/ ; CARS-13//earmarked fund for China Agricultural Research System/ ; CARS-13//earmarked fund for China Agricultural Research System/ ; CAAS-ASTIP-2021-OCRI//Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences/ ; CAAS-ASTIP-2021-OCRI//Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences/ ; CAAS-ASTIP-2021-OCRI//Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences/ ; 32170278//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Arachis/genetics ; Glycosyltransferases/genetics ; Phylogeny ; Flavonoids ; Plant Breeding ; Stress, Physiological/genetics ; *Arabidopsis ; Uridine Diphosphate ; }, abstract = {BACKGROUND: Glycosylation, catalyzed by UDP-glycosyltransferase (UGT), was important for enhancing solubility, bioactivity, and diversity of flavonoids. Peanut (Arachis hypogaea L.) is an important oilseed and cash crop worldwide. In addition to provide high quality of edible oils and proteins, peanut seeds contain a rich source of flavonoid glycosides that benefit human health. However, information of UGT gene family was quite limited in peanut.

RESULTS: In present study, a total of 267 AhUGTs clustered into 15 phylogenetic groups were identified in peanut genome. Group I has greatly expanded to contain the largest number of AhUGT genes. Segmental duplication was the major driving force for AhUGT gene family expansion. Transcriptomic analysis of gene expression profiles in various tissues and under different abiotic stress treatments indicated AhUGTs were involved in peanut growth and abiotic stress response. AhUGT75A (UGT73CG33), located in mitochondria, was characterized as a flavonoid 7-O-UGT by in vitro enzyme assays. The transcript level of AhUGT75A was strongly induced by abiotic stress. Overexpression of AhUGT75A resulted in accumulating less amount of malondialdehyde (MDA) and superoxide, and enhancing tolerance against drought and/or salt stress in transgenic Arabidopsis. These results indicated AhUGT75A played important roles in conferring abiotic stress tolerance through reactive oxygen species scavenging.

CONCLUSIONS: Our research only not provides valuable information for functional characterization of UGTs in peanut, but also gives new insights into potential applications in breeding new cultivars with both desirable stress tolerance and health benefits.}, } @article {pmid38070787, year = {2024}, author = {Das, PJ and Kumar, S and Choudhury, M and Banik, S and Pegu, SR and Kumar, S and Deb, R and Gupta, VK}, title = {Characterization of the complete mitochondrial genome and identification of signature sequence of Indian wild pig.}, journal = {Gene}, volume = {897}, number = {}, pages = {148070}, doi = {10.1016/j.gene.2023.148070}, pmid = {38070787}, issn = {1879-0038}, mesh = {Animals ; *Genome, Mitochondrial/genetics ; Phylogeny ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Genomics ; Sequence Analysis, DNA ; }, abstract = {Mitochondrial DNA (mtDNA) serves as a valuable molecular marker for constructing matrilineal genealogies and tracing the evolutionary history of animals. This study aimed to characterize the complete mitochondrial genome of the Indian wild pig (IWB) (Sus scrofa cristatus) and identify IWB-specific DNA sequences that could be used as genomic signatures to differentiate IWB from domestic Indian pigs (IDP) in forensic cases. For the purpose, three wild IWB from a rescue centre were used for the characterization of the mitochondrial genome of the IWB. The mitochondrial genome was sequenced by the primer walking technique using 30 overlapping primers. The mitochondrial genome of the IWB was found to be 16,689 bp long containing 37 genes coding for 2 rRNAs, 22 tRNAs, 13 protein coding genes, and 1 D-loop region similar to the mitogenome of other pigs. Sequence analysis of the D-loop of IWB with other IDP indicated some signature sequence for IWB like duplication and transition event from 1090[th] to 1099[th] position, deletion of a 10 bp sequence at the 755[th] position, insertion of (CA) at the 137[th] position, and substitution of AT to GA at the 638[th] position. These variations specially the duplication along with transition event causes creation of unique signature sequence (-ACACAAACCT-) in the IWB that could serve as signature sequences for the IWB and be used as markers for differentiation of IWB from IDP breeds in academic as well as forensic or vetero-legal cases. Overall, a total of 36 polymorphic positions were identified in the IWB, with 29 sites being unique to the IWB only and seven being common to the Doom and HDK75 pig breeds. None of the common polymorphic sites were identified in prevailing domestic pig populations. Phylogenetic analysis of the mitochondrial genome revealed the distinct separation of the IWB from IDP. The results of genetic distance evaluation showed that the Doom pig breed was the closest to the IWB. This study provides valuable insights into the mitogenome characterisation, signature sequence and genetic distance analysis of the IWB and establishes a foundation for future studies on the conservation of this protected species.}, } @article {pmid38073308, year = {2024}, author = {Lin, Y and Yang, H and Liu, H and Lu, X and Cao, H and Li, B and Chang, Y and Guo, Z and Ding, D and Hu, Y and Xue, Y and Liu, Z and Tang, J}, title = {A P-type pentatricopeptide repeat protein ZmRF5 promotes 5' region partial cleavages of atp6c transcripts to restore the fertility of CMS-C maize by recruiting a splicing factor.}, journal = {Plant biotechnology journal}, volume = {22}, number = {5}, pages = {1269-1281}, pmid = {38073308}, issn = {1467-7652}, support = {32272165//National Natural Science Foundation of China/ ; 31571745//National Natural Science Foundation of China/ ; }, mesh = {*Zea mays/genetics ; RNA Splicing Factors ; Cytoplasm/genetics ; *Fertility/genetics ; Mitochondria/genetics ; Plant Infertility/genetics ; }, abstract = {A fast evolution within mitochondria genome(s) often generates discords between nuclear and mitochondria, which is manifested as cytoplasmic male sterility (CMS) and fertility restoration (Rf) system. The maize CMS-C trait is regulated by the chimeric mitochondrial gene, atp6c, and can be recovered by the restorer gene ZmRf5. Through positional cloning in this study, we identified the nuclear restorer gene, ZmRf5, which encodes a P-type pentatricopeptide repeat (PPR) family protein. The over-expression of ZmRf5 brought back the fertility to CMS-C plants, whereas its genomic editing by CRISPR/Cas9 induced abortive pollens in the restorer line. ZmRF5 is sorted to mitochondria, and recruited RS31A, a splicing factor, through MORF8 to form a cleaving/restoring complex, which promoted the cleaving of the CMS-associated transcripts atp6c by shifting the major cleavage site from 480th nt to 344 th nt for fast degradation, and preserved just right amount of atp6c RNA for protein translation, providing adequate ATP6C to assembly complex V, thus restoring male fertility. Interestingly, ATP6C in the sterile line CMo17A, with similar cytology and physiology changes to YU87-1A, was accumulated much less than it in NMo17B, exhibiting a contrary trend in the YU87-1 nuclear genome previously reported, and was restored to normal level in the presence of ZmRF5. Collectively these findings unveil a new molecular mechanism underlying fertility restoration by which ZmRF5 cooperates with MORF8 and RS31A to restore CMS-C fertility in maize, complemented and perfected the sterility mechanism, and enrich the perspectives on communications between nucleus and mitochondria.}, } @article {pmid38075892, year = {2023}, author = {Wolters, JF and LaBella, AL and Opulente, DA and Rokas, A and Hittinger, CT}, title = {Mitochondrial genome diversity across the subphylum Saccharomycotina.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1268944}, pmid = {38075892}, issn = {1664-302X}, support = {R01 AI153356/AI/NIAID NIH HHS/United States ; T32 HG002760/HG/NHGRI NIH HHS/United States ; }, abstract = {INTRODUCTION: Eukaryotic life depends on the functional elements encoded by both the nuclear genome and organellar genomes, such as those contained within the mitochondria. The content, size, and structure of the mitochondrial genome varies across organisms with potentially large implications for phenotypic variance and resulting evolutionary trajectories. Among yeasts in the subphylum Saccharomycotina, extensive differences have been observed in various species relative to the model yeast Saccharomyces cerevisiae, but mitochondrial genome sampling across many groups has been scarce, even as hundreds of nuclear genomes have become available.

METHODS: By extracting mitochondrial assemblies from existing short-read genome sequence datasets, we have greatly expanded both the number of available genomes and the coverage across sparsely sampled clades.

RESULTS: Comparison of 353 yeast mitochondrial genomes revealed that, while size and GC content were fairly consistent across species, those in the genera Metschnikowia and Saccharomyces trended larger, while several species in the order Saccharomycetales, which includes S. cerevisiae, exhibited lower GC content. Extreme examples for both size and GC content were scattered throughout the subphylum. All mitochondrial genomes shared a core set of protein-coding genes for Complexes III, IV, and V, but they varied in the presence or absence of mitochondrially-encoded canonical Complex I genes. We traced the loss of Complex I genes to a major event in the ancestor of the orders Saccharomycetales and Saccharomycodales, but we also observed several independent losses in the orders Phaffomycetales, Pichiales, and Dipodascales. In contrast to prior hypotheses based on smaller-scale datasets, comparison of evolutionary rates in protein-coding genes showed no bias towards elevated rates among aerobically fermenting (Crabtree/Warburg-positive) yeasts. Mitochondrial introns were widely distributed, but they were highly enriched in some groups. The majority of mitochondrial introns were poorly conserved within groups, but several were shared within groups, between groups, and even across taxonomic orders, which is consistent with horizontal gene transfer, likely involving homing endonucleases acting as selfish elements.

DISCUSSION: As the number of available fungal nuclear genomes continues to expand, the methods described here to retrieve mitochondrial genome sequences from these datasets will prove invaluable to ensuring that studies of fungal mitochondrial genomes keep pace with their nuclear counterparts.}, } @article {pmid38077409, year = {2023}, author = {Santamaria, CA and Griffiths, CL}, title = {Cryptic diversity and phylogeographic patterns of Deto echinata (Isopoda: Detonidae) in southern Africa.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e16529}, pmid = {38077409}, issn = {2167-8359}, mesh = {Humans ; Animals ; *Isopoda/genetics ; Phylogeny ; Phylogeography ; Africa, Southern ; Mitochondria ; }, abstract = {Recent phylogeographic studies of poorly-dispersing coastal invertebrates in highly biodiverse regions have led to the discovery of high levels of cryptic diversity and complex phylogeographic patterns that suggest isolation, geological, and ecological processes have shaped their biodiversity. Studies of southern African coastal invertebrates have uncovered cryptic diversity for various taxa and phylogeographic patterns that, although sharing some similarities across taxa, do differ. These findings underscore the need for additional studies to better understand the biodiversity levels, distributional patterns, and processes responsible for producing coastal biodiversity in that region. The coastal isopod Deto echinata is of particular interest, as its complex taxonomic history, poor dispersal capabilities, and broad geographic distribution suggest the potential for cryptic diversity. We use mitochondrial and nuclear sequences to characterize D. echinata individuals from localities ranging from northern Namibia to Glentana, about 2,500 km along the coastline on the south coast of South Africa. These are used to assess whether D. echinata harbors cryptic genetic diversity and whether phylogeographic distributional patterns correlate with those previously documented for other coastal isopods in the region. Analysis of mitochondrial and nuclear sequences revealed two deeply-divergent lineages that exhibit a distributional break in the Cape Peninsula region. These findings suggest D. echinata is a cryptic species complex in need of taxonomic revision and highlight the need for further taxonomic and phylogeographic studies of similarly poorly-dispersing coastal invertebrates in southern Africa.}, } @article {pmid38092275, year = {2024}, author = {Gaudó, P and de Tomás-Mateo, E and Garrido-Pérez, N and Santana, A and Ruiz-Pesini, E and Montoya, J and Bayona-Bafaluy, P}, title = {"ATAD3C regulates ATAD3A assembly and function in the mitochondrial membrane".}, journal = {Free radical biology & medicine}, volume = {211}, number = {}, pages = {114-126}, doi = {10.1016/j.freeradbiomed.2023.12.006}, pmid = {38092275}, issn = {1873-4596}, mesh = {Humans ; *Adenosine Triphosphatases/genetics/metabolism ; ATPases Associated with Diverse Cellular Activities/genetics/chemistry/metabolism ; Gene Duplication ; Membrane Proteins/genetics/metabolism ; Mitochondria/genetics/metabolism ; *Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/metabolism ; }, abstract = {Mitochondrial ATAD3A is an ATPase Associated with diverse cellular Activities (AAA) domain containing enzyme, involved in the structural organization of the inner mitochondrial membrane and of increasing importance in childhood disease. In humans, two ATAD3A paralogs arose by gene duplication during evolution: ATAD3B and ATAD3C. Here we investigate the cellular activities of the ATAD3C paralog that has been considered a pseudogene. We detected unique ATAD3C peptides in HEK 293T cells, with expression similar to that in human tissues, and showed that it is an integral membrane protein that exposes its carboxy-terminus to the intermembrane space. Overexpression of ATAD3C, but not of ATAD3A, in fibroblasts caused a decrease in cell proliferation and oxygen consumption rate, and an increase of cellular ROS. This was due to the incorporation of ATAD3C monomers in ATAD3A complex in the mitochondrial membrane reducing its size. Consistent with a negative regulation of ATAD3A function in mitochondrial membrane organization, ATAD3C expression led to increased accumulation of respiratory chain dimeric CIII in the inner membrane, to the detriment to that assembled in respiratory supercomplexes. Our results demonstrate a negative dominant role of the ATAD3C paralog with implications for mitochondrial OXPHOS function and suggest that its expression regulates ATAD3A in the cell.}, } @article {pmid38093186, year = {2023}, author = {Hamza, H and Villa, S and Torre, S and Marchesini, A and Benabderrahim, MA and Rejili, M and Sebastiani, F}, title = {Whole mitochondrial and chloroplast genome sequencing of Tunisian date palm cultivars: diversity and evolutionary relationships.}, journal = {BMC genomics}, volume = {24}, number = {1}, pages = {772}, pmid = {38093186}, issn = {1471-2164}, support = {GeenPalm//PRIMA/ ; GeenPalm//PRIMA/ ; GeenPalm//PRIMA/ ; GeenPalm//PRIMA/ ; GeenPalm//PRIMA/ ; GeenPalm//PRIMA/ ; GeenPalm//PRIMA/ ; }, mesh = {*Phoeniceae/genetics ; *Genome, Chloroplast ; Phylogeny ; Plant Breeding ; Chloroplasts/genetics ; Mitochondria/genetics ; }, abstract = {BACKGROUND: Date palm (Phoenix dactylifera L.) is the most widespread crop in arid and semi-arid regions and has great traditional and socioeconomic importance, with its fruit well-known for its high nutritional and health value. However, the genetic variation of date palm cultivars is often neglected. The advent of high-throughput sequencing has made possible the resequencing of whole organelle (mitochondria and chloroplast) genomes to explore the genetic diversity and phylogenetic relationships of cultivated plants with unprecedented detail.

RESULTS: Whole organelle genomes of 171 Tunisian accessions (135 females and 36 males) were sequenced. Targeted bioinformatics pipelines were used to identify date palm haplotypes and genome variants, aiming to provide variant annotation and investigate patterns of evolutionary relationship. Our results revealed the existence of unique haplotypes, identified by 45 chloroplastic and 156 mitochondrial SNPs. Estimation of the effect of these SNPs on genes functions was predicted in silico.

CONCLUSIONS: The results of this study have important implications, in the light of ongoing environmental changes, for the conservation and sustainable use of the genetic resources of date palm cultivars in Tunisia, where monoculture threatens biodiversity leading to genetic erosion. These data will be useful for breeding and genetic improvement programs of the date palm through selective cross-breeding.}, } @article {pmid38095728, year = {2023}, author = {Chen, W and Zhang, H and Meng, R and Zhang, X and Duo, H and Guo, Z and Shen, X and Chen, C and Li, Z and Fu, Y}, title = {Genome-wide phylogenetic and genetic evolutionary analyses of mitochondria in Hypoderma bovis and H. sinense on the Qinghai-Tibetan Plateau.}, journal = {Parasitology research}, volume = {123}, number = {1}, pages = {43}, pmid = {38095728}, issn = {1432-1955}, mesh = {Animals ; Cattle ; Humans ; Phylogeny ; RNA, Ribosomal, 16S ; Tibet ; *Diptera ; Mitochondria/genetics ; Mammals ; }, abstract = {Hypoderma bovis (H. bovis) and Hypoderma sinense (H. sinense) are insects that cause hypodermosis in yaks and Bos taurus. Hypodermosis is a severe skin condition that not only impairs the development of local animal husbandry but also poses threats to human health as a zoonosis. The Qinghai-Tibetan Plateau (QTP) is known as the "Roof of the World." Its unique geographical environment and climate conditions have supported the growth of a wide range of mammals, providing favorable conditions for Hypoderma spp. to complete their life cycles. In this study, the whole mitochondrial genomes of H. bovis and H. sinense collected from the QTP were sequenced and phylogenetically analyzed. We found that the whole genomes of H. bovis and H. sinense are 16,283 bp and 16,300 bp in length, respectively. Both the H. bovis and H. sinense genomes have 37 mitochondrial genes, which include two rRNA genes (16S rRNA and 12S rRNA), 22 tRNA genes, the control region (D-loop region), the light chain replication initiation region, and 13 protein-coding genes (PCGs). The phylogenetic tree generated based on the 13 PCGs revealed close phylogenetic relationships between H. sinense, H. bovis, and Hypoderma lineatum. A similar result was also found in our phylogenetic analysis based on 18S rRNA and 28S rRNA. However, analysis of cytochrome oxidase subunit I (COI) showed cluster of H. bovis, H. sinense, and Cuterebra spp. on the same branch, all belonging to Oestridae. The differentiation time generated based on 13 PCGs indicates that H. bovis and H. sinense differentiated and formed ~4.69 million years ago (Mya) and ~4.06 Mya, respectively. This timing coincides with the differentiation and appearance of yak and Bos taurus in the Pliocene (~4.7 Mya), indicating that the parasites and mammals diverged in close temporal proximity. Of note, this period also witnessed a rapid uplift of the QTP, causing significant climate and environmental changes. Thus, we conjecture that the differentiation of Hypoderma spp. is potentially related to the differentiation of their host species, as well as climate changes caused by the uplift of the QTP. Overall, our study can provide valuable data to support further studies on the phylogeny and differentiation of Hypoderma spp. on the QTP.}, } @article {pmid38097150, year = {2024}, author = {Hew, YX and Ya'cob, Z and Chen, CD and Lau, KW and Sofian-Azirun, M and Muhammad-Rasul, AH and Putt, QY and Tan, TK and Hadi, UK and Suana, IW and Takaoka, H and Low, VL}, title = {Co-occurrence of dual lineages within Simulium (Gomphostilbia) atratum De Meijere in the Indonesian Archipelago along Wallace's Line.}, journal = {Acta tropica}, volume = {250}, number = {}, pages = {107097}, doi = {10.1016/j.actatropica.2023.107097}, pmid = {38097150}, issn = {1873-6254}, mesh = {Animals ; Indonesia ; *Simuliidae/genetics ; Mitochondria ; Phylogeny ; Genetic Variation ; }, abstract = {Mitochondrial cytochrome c oxidase subunit I (COI) sequences were utilized to infer the population genetic structure of Simulium (Gomphostilbia) atratum De Meijere, an endemic simulid species to Indonesia. Both median-joining haplotype network and maximum-likelihood tree revealed two genetic lineages (A and B) within the species, with an overlap distribution in Lombok, which is situated along Wallace's line. Genetic differentiation and gene flow with varying frequencies (FST = 0.02-0.967; Nm = 0.01-10.58) were observed between populations of S. (G.) atratum, of which population pairs of different lineages showed high genetic differentiation. Notably, the high genetic distance of up to 5.92 % observed within S. (G.) atratum in Lombok was attributed to the existence of two genetically distinct lineages. The co-occurrence of distinct lineages in Lombok indicated that Wallace's line did not act as faunistic border for S. (G.) atratum in the present study. Moreover, both lineages also exhibited unimodal distributions and negative values of neutrality tests, suggesting a pattern of population expansion. The expansion and divergence time estimation suggested that the two lineages of S. (G.) atratum diverged and expanded during the Pleistocene era in Indonesia.}, } @article {pmid38100746, year = {2024}, author = {Araujo, TQ and King-Trudeau, S and VanDyke, J and Hochberg, R}, title = {First ultrastructural description of an apomictic opsiblastic egg in freshwater Gastrotricha.}, journal = {Journal of morphology}, volume = {285}, number = {1}, pages = {e21659}, doi = {10.1002/jmor.21659}, pmid = {38100746}, issn = {1097-4687}, support = {//National Science Foundation/ ; }, mesh = {Animals ; Phylogeny ; *Oocytes/ultrastructure ; *Oogenesis ; Endoplasmic Reticulum ; Fresh Water ; }, abstract = {Freshwater gastrotrichs have a biphasic lifecycle that reputedly involves the production of three types of eggs: apomictic and fast hatching (tachyblastic ova), apomictic and delayed hatching (opsiblastic ova), and plaque-bearing eggs (potentially derived from mixis). While some details of oogenesis and eggshell structure are known for tachyblastic ova, there are few details on other egg types. Here, we provide the first ultrastructural description of the oviposited opsiblastic eggs of the freshwater gastrotrich, Lepidodermella squamata. Scanning electron microscopy revealed the eggshell surface to be ornamented with long flattened pillar-like structures centered on polygonal plates that are pitted along their periphery. Transmission electron microscopy showed the pits to lead to a vast labyrinth of tubular spaces and larger cavities throughout the thick apical layer of the shell. The basal layer of the shell is amorphous and connected to a network of fine fibers that traverse an extra-oocyte space and forms a protective sheet around the uncleaved oocyte. The uncleaved oocyte has a dense layer of peripheral ooplasm surrounding a core of organelles including mitochondria, membrane-bound secretion granules, endoplasmic reticulum, and a single nucleus in a granular, ribosome-rich cytoplasm. Secretion granules are the most abundant organelles and presumably contain lipid-rich yolk that will be used as energy for delayed cleavage, thus functioning in temporal dispersal. These data are compared to the fine structure of invertebrate resting eggs across the phylogenetic spectrum to determine the novelty of opsiblastic egg structure in L. squamata.}, } @article {pmid38103543, year = {2024}, author = {Wang, S and He, B and Wu, H and Cai, Q and Ramírez-Sánchez, O and Abreu-Goodger, C and Birch, PRJ and Jin, H}, title = {Plant mRNAs move into a fungal pathogen via extracellular vesicles to reduce infection.}, journal = {Cell host & microbe}, volume = {32}, number = {1}, pages = {93-105.e6}, pmid = {38103543}, issn = {1934-6069}, support = {R35 GM136379/GM/NIGMS NIH HHS/United States ; }, mesh = {RNA, Messenger/genetics/metabolism ; RNA ; *Arabidopsis/genetics/microbiology ; Plants/genetics ; *Extracellular Vesicles ; Plant Diseases/microbiology ; }, abstract = {Cross-kingdom small RNA trafficking between hosts and microbes modulates gene expression in the interacting partners during infection. However, whether other RNAs are also transferred is unclear. Here, we discover that host plant Arabidopsis thaliana delivers mRNAs via extracellular vesicles (EVs) into the fungal pathogen Botrytis cinerea. A fluorescent RNA aptamer reporter Broccoli system reveals host mRNAs in EVs and recipient fungal cells. Using translating ribosome affinity purification profiling and polysome analysis, we observe that delivered host mRNAs are translated in fungal cells. Ectopic expression of two transferred host mRNAs in B. cinerea shows that their proteins are detrimental to infection. Arabidopsis knockout mutants of the genes corresponding to these transferred mRNAs are more susceptible. Thus, plants have a strategy to reduce infection by transporting mRNAs into fungal cells. mRNAs transferred from plants to pathogenic fungi are translated to compromise infection, providing knowledge that helps combat crop diseases.}, } @article {pmid38103995, year = {2024}, author = {Yu, Y and Li, YP and Ren, K and Hao, X and Fru, EC and Rønn, R and Rivera, WL and Becker, K and Feng, R and Yang, J and Rensing, C}, title = {A brief history of metal recruitment in protozoan predation.}, journal = {Trends in microbiology}, volume = {32}, number = {5}, pages = {465-476}, doi = {10.1016/j.tim.2023.11.008}, pmid = {38103995}, issn = {1878-4380}, mesh = {*Metals/metabolism ; *Phagocytosis ; *Dictyostelium/metabolism/physiology ; Biological Evolution ; Acanthamoeba ; Animals ; Phagosomes/metabolism ; Zinc/metabolism ; Metalloids/metabolism ; Copper/metabolism ; Biological Availability ; Mitochondria/metabolism ; }, abstract = {Metals and metalloids are used as weapons for predatory feeding by unicellular eukaryotes on prokaryotes. This review emphasizes the role of metal(loid) bioavailability over the course of Earth's history, coupled with eukaryogenesis and the evolution of the mitochondrion to trace the emergence and use of the metal(loid) prey-killing phagosome as a feeding strategy. Members of the genera Acanthamoeba and Dictyostelium use metals such as zinc (Zn) and copper (Cu), and possibly metalloids, to kill their bacterial prey after phagocytosis. We provide a potential timeline on when these capacities first evolved and how they correlate with perceived changes in metal(loid) bioavailability through Earth's history. The origin of phagotrophic eukaryotes must have postdated the Great Oxidation Event (GOE) in agreement with redox-dependent modification of metal(loid) bioavailability for phagotrophic poisoning. However, this predatory mechanism is predicted to have evolved much later - closer to the origin of the multicellular metazoans and the evolutionary development of the immune systems.}, } @article {pmid38105202, year = {2023}, author = {Baleva, MV and Piunova, UE and Chicherin, IV and Levitskii, SA and Kamenski, PA}, title = {Diversity and Evolution of Mitochondrial Translation Apparatus.}, journal = {Biochemistry. Biokhimiia}, volume = {88}, number = {11}, pages = {1832-1843}, doi = {10.1134/S0006297923110135}, pmid = {38105202}, issn = {1608-3040}, mesh = {*Mitochondria/genetics/metabolism ; Protein Biosynthesis ; *Genome, Mitochondrial ; Mitochondrial Proteins/genetics/metabolism ; }, abstract = {The evolution of mitochondria has proceeded independently in different eukaryotic lines, which is reflected in the diversity of mitochondrial genomes and mechanisms of their expression in eukaryotic species. Mitochondria have lost most of bacterial ancestor genes by transferring them to the nucleus or eliminating them. However, mitochondria of almost all eukaryotic cells still retain relatively small genomes, as well as their replication, transcription, and translation apparatuses. The dependence on the nuclear genome, specific features of mitochondrial transcripts, and synthesis of highly hydrophobic membrane proteins in the mitochondria have led to significant changes in the translation apparatus inherited from the bacterial ancestor, which retained the basic structure necessary for protein synthesis but became more specialized and labile. In this review, we discuss specific properties of translation initiation in the mitochondria and how the evolution of mitochondria affected the functions of main factors initiating protein biosynthesis in these organelles.}, } @article {pmid38112480, year = {2024}, author = {He, Z and Fang, Y and Zhang, F and Liu, Y and Cheng, X and Wang, J and Li, D and Chen, D and Wu, F}, title = {Adenine nucleotide translocase 2 (Ant2) is required for individualization of spermatogenesis of Drosophila melanogaster.}, journal = {Insect science}, volume = {31}, number = {4}, pages = {1055-1072}, doi = {10.1111/1744-7917.13309}, pmid = {38112480}, issn = {1744-7917}, support = {CARS-18-SYZ10//China Agricultural Research System of MOF and MARA/ ; 2021-620-000-001-009//Hubei Province Agricultural Science and Technology Innovation Center Project/ ; 2022BBA0079//Hubei Province key Research and Development Project/ ; }, mesh = {Animals ; Male ; *Drosophila melanogaster/genetics/metabolism/growth & development ; *Spermatogenesis ; *Drosophila Proteins/genetics/metabolism ; Testis/metabolism ; Adenine Nucleotide Translocator 2/metabolism/genetics ; Spermatids/metabolism ; }, abstract = {Successful completion of spermatogenesis is crucial for the perpetuation of the species. In Drosophila, spermatid individualization, a process involving changes in mitochondrial structure and function is critical to produce functional mature sperm. Ant2, encoding a mitochondrial adenine nucleotide translocase, is highly expressed in male testes and plays a role in energy metabolism in the mitochondria. However, its molecular function remains unclear. Here, we identified an important role of Ant2 in spermatid individualization. In Ant2 knockdown testes, spermatid individualization complexes composed of F-actin cones exhibited a diffuse distribution, and mature sperms were absent in the seminal vesicle, thus leading to male sterility. The most striking effects in Ant2-knockdown spermatids were decrease in tubulin polyglycylation and disruption of proper mitochondria derivatives function. Excessive apoptotic cells were also observed in Ant2-knockdown testes. To further investigate the phenotype of Ant2 knockdown in testes at the molecular level, complementary transcriptome and proteome analyses were performed. At the mRNA level, 868 differentially expressed genes were identified, of which 229 genes were upregulated and 639 were downregulated induced via Ant2 knockdown. iTRAQ-labeling proteome analysis revealed 350 differentially expressed proteins, of which 117 proteins were upregulated and 233 were downregulated. The expression of glutathione transferase (GstD5, GstE5, GstE8, and GstD3), proteins involved in reproduction were significantly regulated at both the mRNA and protein levels. These results indicate that Ant2 is crucial for spermatid maturation by affecting mitochondrial morphogenesis.}, } @article {pmid38123538, year = {2023}, author = {Cui, Z and Zhong, Y and Sun, Z and Jiang, Z and Deng, J and Wang, Q and Nielsen, J and Hou, J and Qi, Q}, title = {Reconfiguration of the reductive TCA cycle enables high-level succinic acid production by Yarrowia lipolytica.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {8480}, pmid = {38123538}, issn = {2041-1723}, support = {22208192//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {*Yarrowia/genetics/metabolism ; Succinic Acid/metabolism ; NAD/metabolism ; Citric Acid Cycle ; Fermentation ; Glucose/metabolism ; Metabolic Engineering ; }, abstract = {Succinic acid (SA) is an important C4-dicarboxylic acid. Microbial production of SA at low pH results in low purification costs and hence good overall process economics. However, redox imbalances limited SA biosynthesis from glucose via the reductive tricarboxylic acid (TCA) cycle in yeast. Here, we engineer the strictly aerobic yeast Yarrowia lipolytica for efficient SA production without pH control. Introduction of the reductive TCA cycle into the cytosol of a succinate dehydrogenase-disrupted yeast strain causes arrested cell growth. Although adaptive laboratory evolution restores cell growth, limited NADH supply restricts SA production. Reconfiguration of the reductive SA biosynthesis pathway in the mitochondria through coupling the oxidative and reductive TCA cycle for NADH regeneration results in improved SA production. In pilot-scale fermentation, the engineered strain produces 111.9 g/L SA with a yield of 0.79 g/g glucose within 62 h. This study paves the way for industrial production of biobased SA.}, } @article {pmid38124445, year = {2024}, author = {Uvizl, M and Puechmaille, SJ and Power, S and Pippel, M and Carthy, S and Haerty, W and Myers, EW and Teeling, EC and Huang, Z}, title = {Comparative Genome Microsynteny Illuminates the Fast Evolution of Nuclear Mitochondrial Segments (NUMTs) in Mammals.}, journal = {Molecular biology and evolution}, volume = {41}, number = {1}, pages = {}, pmid = {38124445}, issn = {1537-1719}, mesh = {Animals ; Phylogeny ; *Genomics ; Mitochondria/genetics ; DNA, Mitochondrial/genetics ; Mammals/genetics ; Sequence Analysis, DNA ; Cell Nucleus/genetics ; *Genome, Mitochondrial ; Evolution, Molecular ; }, abstract = {The escape of DNA from mitochondria into the nuclear genome (nuclear mitochondrial DNA, NUMT) is an ongoing process. Although pervasively observed in eukaryotic genomes, their evolutionary trajectories in a mammal-wide context are poorly understood. The main challenge lies in the orthology assignment of NUMTs across species due to their fast evolution and chromosomal rearrangements over the past 200 million years. To address this issue, we systematically investigated the characteristics of NUMT insertions in 45 mammalian genomes and established a novel, synteny-based method to accurately predict orthologous NUMTs and ascertain their evolution across mammals. With a series of comparative analyses across taxa, we revealed that NUMTs may originate from nonrandom regions in mtDNA, are likely found in transposon-rich and intergenic regions, and unlikely code for functional proteins. Using our synteny-based approach, we leveraged 630 pairwise comparisons of genome-wide microsynteny and predicted the NUMT orthology relationships across 36 mammals. With the phylogenetic patterns of NUMT presence-and-absence across taxa, we constructed the ancestral state of NUMTs given the mammal tree using a coalescent method. We found support on the ancestral node of Fereuungulata within Laurasiatheria, whose subordinal relationships are still controversial. This study broadens our knowledge on NUMT insertion and evolution in mammalian genomes and highlights the merit of NUMTs as alternative genetic markers in phylogenetic inference.}, } @article {pmid38135240, year = {2024}, author = {Bľandová, G and Janoštiaková, N and Kodada, D and Pastorek, M and Lipták, R and Hodosy, J and Šebeková, K and Celec, P and Krasňanská, G and Eliaš, V and Wachsmannová, L and Konečný, M and Repiská, V and Baldovič, M}, title = {Mitochondrial DNA variability and Covid-19 in the Slovak population.}, journal = {Mitochondrion}, volume = {75}, number = {}, pages = {101827}, doi = {10.1016/j.mito.2023.101827}, pmid = {38135240}, issn = {1872-8278}, mesh = {Humans ; *DNA, Mitochondrial/genetics ; Phylogeny ; Slovakia/epidemiology ; Haplotypes ; *COVID-19/genetics ; Mitochondria/genetics ; }, abstract = {Recent studies have shown that mitochondria are involved in the pathogenesis of Covid-19. Mitochondria play a role in production of reactive oxygen species and induction of an innate immune response, both important during infections. Common variability of mitochondrial DNA (mtDNA) can affect oxidative phosphorylation and the risk or lethality of cardiovascular, neurodegenerative diseases and sepsis. However, it is unclear whether susceptibility of severe Covid-19 might be affected by mtDNA variation. Thus, we have analyzed mtDNA in a sample of 446 Slovak patients hospitalized due to Covid-19 and a control population group consisting of 1874 individuals. MtDNA variants in the HVRI region have been analyzed and classified into haplogroups at various phylogenetic levels. Binary logistic regression was used to assess the risk of Covid-19. Haplogroups T1, H11, K and variants 16256C > T, 16265A > C, 16293A > G, 16311 T > C and 16399A > G were associated with an increased Covid-19 risk. On contrary, Haplogroup J1, haplogroup clusters H + U5b and T2b + U5b, and the mtDNA variant 16189 T > C were associated with decreased risk of Covid-19. Following the application of the Bonferroni correction, statistical significance was observed exclusively for the cluster of haplogroups H + U5b. Unsurprisingly, the most significant factor contributing to the mortality of patients with Covid-19 is the age of patients. Our findings suggest that mtDNA haplogroups can play a role in Covid-19 pathogenesis, thus potentially useful in identifying susceptibility to its severe form. To confirm these associations, further studies taking into account the nuclear genome or other non-biological influences are needed.}, } @article {pmid38139163, year = {2023}, author = {He, X and Zhang, X and Deng, Y and Yang, R and Yu, LX and Jia, S and Zhang, T}, title = {Structural Reorganization in Two Alfalfa Mitochondrial Genome Assemblies and Mitochondrial Evolution in Medicago Species.}, journal = {International journal of molecular sciences}, volume = {24}, number = {24}, pages = {}, pmid = {38139163}, issn = {1422-0067}, support = {SJCZFY2022-3//Breeding of New Alfalfa Varieties/ ; 2022JBGS0020//Breeding and Industrialization Demonstration of New High-quality Alfalfa Varieties/ ; }, mesh = {*Genome, Mitochondrial ; Medicago sativa/genetics ; DNA, Mitochondrial/genetics ; Medicago/genetics ; Mitochondria/genetics ; }, abstract = {Plant mitochondria are crucial for species evolution, phylogenetics, classification, and identification as maternal genetic material. However, the presence of numerous repetitive sequences, complex structures, and a low number of genes in the mitochondrial genome has hindered its complete assembly and related research endeavors. In this study, we assembled two mitochondrial genomes of alfalfa varieties of Zhongmu No.1 (299,123 bp) and Zhongmu No.4 (306,983 bp), based on a combination of PacBio, Illumina, and Hi-C sequences. The comparison of genome assemblies revealed that the same number of mitochondrial genes, including thirty-three protein-coding genes, sixteen tRNA genes, and three rRNA genes existed in the two varieties. Additionally, large fragments of repetitive sequences were found underlying frequent mitochondrial recombination events. We observed extensive transfer of mitochondrial fragments into the nuclear genome of Zhongmu No.4. Analysis of the cox1 and rrn18s genes in 35 Medicago accessions revealed the presence of population-level deletions and substitutions in the rrn18s gene. We propose that mitochondrial structural reorganizations may contribute to alfalfa evolution.}, } @article {pmid38140813, year = {2024}, author = {Griseti, E and Bello, AA and Bieth, E and Sabbagh, B and Iacovoni, JS and Bigay, J and Laurell, H and Čopič, A}, title = {Molecular mechanisms of perilipin protein function in lipid droplet metabolism.}, journal = {FEBS letters}, volume = {598}, number = {10}, pages = {1170-1198}, doi = {10.1002/1873-3468.14792}, pmid = {38140813}, issn = {1873-3468}, support = {856404/ERC_/European Research Council/International ; }, mesh = {Humans ; *Lipid Droplets/metabolism ; Animals ; *Perilipins/metabolism/genetics ; Lipid Metabolism ; Lipolysis ; Perilipin-1/metabolism/genetics ; }, abstract = {Perilipins are abundant lipid droplet (LD) proteins present in all metazoans and also in Amoebozoa and fungi. Humans express five perilipins, which share a similar domain organization: an amino-terminal PAT domain and an 11-mer repeat region, which can fold into amphipathic helices that interact with LDs, followed by a structured carboxy-terminal domain. Variations of this organization that arose during vertebrate evolution allow for functional specialization between perilipins in relation to the metabolic needs of different tissues. We discuss how different features of perilipins influence their interaction with LDs and their cellular targeting. PLIN1 and PLIN5 play a direct role in lipolysis by regulating the recruitment of lipases to LDs and LD interaction with mitochondria. Other perilipins, particularly PLIN2, appear to protect LDs from lipolysis, but the molecular mechanism is not clear. PLIN4 stands out with its long repetitive region, whereas PLIN3 is most widely expressed and is used as a nascent LD marker. Finally, we discuss the genetic variability in perilipins in connection with metabolic disease, prominent for PLIN1 and PLIN4, underlying the importance of understanding the molecular function of perilipins.}, } @article {pmid38142270, year = {2024}, author = {Khan, MM and Suhail, SM and Majid, HA and Ahmad, I and Sadique, U and Khan, R and Ahmad, I and Ijaz, A and Khan, K and Ali, F and Khan, MS and El-Mansi, AA}, title = {Morpometric and molecular characterization of Surguli goat through CO1 gene in district Kohat.}, journal = {Animal biotechnology}, volume = {35}, number = {1}, pages = {2290528}, pmid = {38142270}, issn = {1532-2378}, mesh = {Animals ; *Goats/genetics ; Phylogeny ; Base Sequence ; *DNA, Mitochondrial/genetics ; Mitochondria/genetics ; }, abstract = {The present study was designed with the aim to study morphometric characterization as well as phylogeny and diversity of the local Surguli goat at their breeding tract district Kohat through mitochondrial DNA region, i.e., Cytochrome C Oxidase Subunit One (CO1) gene. Morphometric data and blood samples were collected from thirty (30) pure goats. Morphometric analysis showed that sex had significant effect (p < 0.05) on body weight, body length, hearth girth and horn length while no significant effect (p > 0.05) was observed for other characteristics. The results also indicated that age had significant effect (p < 0.05) on height at rump, ear length, horn length and tail length while no significant effect (p > 0.05) was observed for other characteristics. The phylogenetic analysis through CO1 nucleotide sequences within nucleotide range 1-767 showed nine polymorphic sites segregating into eight haplotypes. The mean intraspecific diversity and mean interspecific diversity were calculated as 0.23 and 2.36%, respectively. Phylogenetic tree revealed that Capra Ibex and native Surguli goat have common ancestors. The morphometric and molecular results obtained from the present study can be exploited as a selection tool for breeding and overall improvement.}, } @article {pmid38142841, year = {2024}, author = {Buonvicino, D and Pratesi, S and Ranieri, G and Pistolesi, A and Guasti, D and Chiarugi, A}, title = {The mitochondriogenic but not the immunosuppressant effects of mTOR inhibitors prompt neuroprotection and delay disease evolution in a mouse model of progressive multiple sclerosis.}, journal = {Neurobiology of disease}, volume = {191}, number = {}, pages = {106387}, doi = {10.1016/j.nbd.2023.106387}, pmid = {38142841}, issn = {1095-953X}, mesh = {Female ; Animals ; Mice ; *Multiple Sclerosis/pathology ; MTOR Inhibitors ; Fingolimod Hydrochloride/pharmacology/therapeutic use ; Neuroprotection ; Everolimus/pharmacology/therapeutic use ; Mice, Inbred NOD ; Immunosuppressive Agents/pharmacology/therapeutic use ; Sirolimus/pharmacology/therapeutic use ; Dexamethasone/pharmacology ; *Encephalomyelitis, Autoimmune, Experimental/pathology ; Mice, Inbred C57BL ; }, abstract = {INTRODUCTION: Purportedly, the progression of multiple sclerosis (MS) occurs when neurodegenerative processes due to derangement of axonal bioenergetics take over the autoimmune response. However, a clear picture of the causative interrelationship between autoimmunity and axonal mitochondrial dysfunction in progressive MS (PMS) pathogenesis waits to be provided.

METHODS: In the present study, by adopting the NOD mouse model of PMS, we compared the pharmacological effects of the immunosuppressants dexamethasone and fingolimod with those of mTOR inhibitors rapamycin and everolimus that, in addition to immunosuppression, also regulate mitochondrial functioning. Female Non-Obese Diabetic (NOD) mice were immunized with MOG35-55 and treated with drugs to evaluate functional, immune and mitochondrial parameters during disease evolution.

RESULTS: We found that dexamethasone and fingolimod did not affect the pattern of progression as well as survival. Conversely, mTOR inhibitors rapamycin and everolimus delayed disease progression and robustly extended survival of immunized mice. The same effects were obtained when treatment was delayed by 30 days after immunization. Remarkably, dexamethasone and fingolimod prompted the same degree of immunosuppression of rapamycin within both spleen and spinal cord of mice. However, only rapamycin prompted mitochondriogenesis by increasing mitochondrial content, and expression of several mitochondrial respiratory complex subunits, thereby preventing mtDNA reduction in the spinal cords of immunized mice. These pharmacodynamic effects were not reproduced in healthy NOD mice, suggesting a disease context-dependent pharmacodynamic effect.

DISCUSSION: Data corroborate the key role of mitochondriogenesis to treatment of MS progression, and for the first time disclose the translational potential of mTOR inhibitors in PMS therapy.}, } @article {pmid38147995, year = {2023}, author = {Yang, J and Gao, J and Li, W and Liu, J and Huo, J and Ren, Z and Li, L and Chen, B and Mao, J and Ma, Z}, title = {[Identification and expression analysis of apple PDHB-1 gene family].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {39}, number = {12}, pages = {4965-4981}, doi = {10.13345/j.cjb.230011}, pmid = {38147995}, issn = {1872-2075}, mesh = {*Malus/genetics/chemistry/metabolism ; Fruit/genetics ; Protein Structure, Secondary ; }, abstract = {Pyruvate dehydrogenase E1 component subunit beta-1 (PDHB-1) is a gene encoding the β-subunit of pyruvate dehydrogenase complex, which plays an important role in fruit acid accumulation. The aim of this study was to investigate the evolution characteristics of apple PDHB-1 family and its expression in apples with different acid contents. Bioinformatics analysis was performed using databases including NCBI, Pfam and software including ClustalX, MEGA, and TBtools. By combining titratable acid content determination and quantitative real-time PCR (qRT-PCR), the expression of this family genes in the peel and pulp of apple 'Asda' and 'Chengji No.1' with different acid content were obtained, respectively. The family members were mainly located in chloroplast, cytoplasm and mitochondria. α-helix and random coil were the main factors for the formation of secondary structure in this family. Tissue-specific expression profiles showed that the expression of most members were higher in fruit than in other tissues. qRT-PCR results showed that the expression profile of most members was consistent with the profile of titratable acid contents. In the peel, the expression levels of 14 members in 'Asda' apples with high acid content were significantly higher than that in 'Chengji No.1' apples with low acid content, where the expression difference of MdPDHB1-15 was the most significant. In the pulp, the expression levels of 17 members in 'Asda' apples were significantly higher than that in 'Chengji No.1' apples, where MdPDHB1-01 was the most highly expressed. It was predicted that PDHB-1 gene family in apple plays an important role in the regulation of fruit acidity.}, } @article {pmid38149397, year = {2023}, author = {Shen, Q and Yuan, Y and Jin, J}, title = {[Relationship between Notch signaling pathway and mitochondrial energy metabolism].}, journal = {Zhonghua wei zhong bing ji jiu yi xue}, volume = {35}, number = {12}, pages = {1321-1326}, doi = {10.3760/cma.j.cn121430-20230719-00532}, pmid = {38149397}, issn = {2095-4352}, mesh = {*Signal Transduction/physiology ; *Mitochondria ; Receptors, Notch/metabolism ; Cell Differentiation/physiology ; Energy Metabolism ; }, abstract = {Notch signaling pathway is a highly conserved signaling pathway in the process of evolution. It is composed of three parts: Notch receptor, ligand and effector molecules responsible for intracellular signal transduction. It plays an important role in cell proliferation, differentiation, development, migration, apoptosis and other processes, and has a regulatory effect on tissue homeostasis and homeostasis. Mitochondria are the sites of oxidative metabolism in eukaryotes, where sugars, fats and proteins are finally oxidized to release energy. In recent years, the regulation of Notch signaling pathway on mitochondrial energy metabolism has attracted more and more attention. A large number of data have shown that Notch signaling pathway has a significant effect on mitochondrial energy metabolism, but the relationship between Notch signaling pathway and mitochondrial energy metabolism needs to be specifically and systematically discussed. In this paper, the relationship between Notch signaling pathway and mitochondrial energy metabolism is reviewed, in order to improve the understanding of them and provide new ideas for the treatment of related diseases.}, } @article {pmid38157080, year = {2023}, author = {Kuprina, K and Smorkatcheva, A and Rudyk, A and Galkina, S}, title = {Numerous insertions of mitochondrial DNA in the genome of the northern mole vole, Ellobius talpinus.}, journal = {Molecular biology reports}, volume = {51}, number = {1}, pages = {36}, pmid = {38157080}, issn = {1573-4978}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; Phylogeny ; Genome ; Mitochondria/genetics ; Arvicolinae/genetics ; Sequence Analysis, DNA ; *Genome, Mitochondrial/genetics ; }, abstract = {BACKGROUND: Ellobius talpinus is a subterranean rodent representing an attractive model in population ecology studies due to its highly special lifestyle and sociality. In such studies, mitochondrial DNA (mtDNA) is widely used. However, if nuclear copies of mtDNA, aka NUMTs, are present, they may co-amplify with the target mtDNA fragment, generating misleading results. The aim of this study was to determine whether NUMTs are present in E. talpinus.

METHODS AND RESULTS: PCR amplification of the putative mtDNA CytB-D-loop fragment using 'universal' primers from 56 E. talpinus samples produced multiple double peaks in 90% of the sequencing chromatograms. To reveal NUMTs, molecular cloning and sequencing of PCR products of three specimens was conducted, followed by phylogenetic analysis. The pseudogene nature of three out of the seven detected haplotypes was confirmed by their basal positions in relation to other Ellobius haplotypes in the phylogenetic tree. Additionally, 'haplotype B' was basal in relation to other E. talpinus haplotypes and found present in very distant sampling sites. BLASTN search revealed 195 NUMTs in the E. talpinus nuclear genome, including fragments of all four PCR amplified pseudogenes. Although the majority of the NUMTs studied were short, the entire mtDNA had copies in the nuclear genome. The most numerous NUMTs were found for rrnL, COXI, and D-loop.

CONCLUSIONS: Numerous NUMTs are present in E. talpinus and can be difficult to discriminate against mtDNA sequences. Thus, in future population or phylogenetic studies in E. talpinus, the possibility of cryptic NUMTs amplification should always be taken into account.}, } @article {pmid38157451, year = {2024}, author = {Yang, X and Li, G and Lou, P and Zhang, M and Yao, K and Xiao, J and Chen, Y and Xu, J and Tian, S and Deng, M and Pan, Y and Li, M and Wu, X and Liu, R and Shi, X and Tian, Y and Yu, L and Ke, H and Jiao, B and Cong, Y and Plikus, MV and Liu, X and Yu, Z and Lv, C}, title = {Excessive nucleic acid R-loops induce mitochondria-dependent epithelial cell necroptosis and drive spontaneous intestinal inflammation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {1}, pages = {e2307395120}, pmid = {38157451}, issn = {1091-6490}, support = {82025006//MOST | National Natural Science Foundation of China (NSFC)/ ; 82230017//MOST | National Natural Science Foundation of China (NSFC)/ ; 82000498//MOST | National Natural Science Foundation of China (NSFC)/ ; 82270588//MOST | National Natural Science Foundation of China (NSFC)/ ; 2022YFA1104001//National Basic Research Program of China/ ; 2022YFC3602102//National Basic Research Program of China/ ; 2022YFD1300403//National Basic Research Program of China/ ; 2021YFF1000603//National Basic Research Program of China/ ; 82300635//MOST | National Natural Science Foundation of China (NSFC)/ ; 2022M723412//Postdoctoral Science Foundation of China/ ; 88220019//MOST | National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Humans ; Animals ; Mice ; *Necroptosis ; NAD/metabolism ; R-Loop Structures ; *Inflammatory Bowel Diseases/metabolism ; Epithelial Cells/metabolism ; Intestinal Mucosa/metabolism ; Inflammation/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Mitochondria/metabolism ; }, abstract = {Oxidative stress, which can be activated by a variety of environmental risk factors, has been implicated as an important pathogenic factor for inflammatory bowel disease (IBD). However, how oxidative stress drives IBD onset remains elusive. Here, we found that oxidative stress was strongly activated in inflamed tissues from both ulcerative colitis patients and Crohn's disease patients, and it caused nuclear-to-cytosolic TDP-43 transport and a reduction in the TDP-43 protein level. To investigate the function of TDP-43 in IBD, we inducibly deleted exons 2 to 3 of Tardbp (encoding Tdp-43) in mouse intestinal epithelium, which disrupted its nuclear localization and RNA-processing function. The deletion gave rise to spontaneous intestinal inflammation by inducing epithelial cell necroptosis. Suppression of the necroptotic pathway with deletion of Mlkl or the RIP1 inhibitor Nec-1 rescued colitis phenotypes. Mechanistically, disruption of nuclear TDP-43 caused excessive R-loop accumulation, which triggered DNA damage and genome instability and thereby induced PARP1 hyperactivation, leading to subsequent NAD[+] depletion and ATP loss, consequently activating mitochondrion-dependent necroptosis in intestinal epithelial cells. Importantly, restoration of cellular NAD[+] levels with NAD[+] or NMN supplementation, as well as suppression of ALKBH7, an α-ketoglutarate dioxygenase in mitochondria, rescued TDP-43 deficiency-induced cell death and intestinal inflammation. Furthermore, TDP-43 protein levels were significantly inversely correlated with γ-H2A.X and p-MLKL levels in clinical IBD samples, suggesting the clinical relevance of TDP-43 deficiency-induced mitochondrion-dependent necroptosis. Taken together, these findings identify a unique pathogenic mechanism that links oxidative stress to intestinal inflammation and provide a potent and valid strategy for IBD intervention.}, } @article {pmid38161329, year = {2023}, author = {Hambardikar, V and Akosah, YA and Scoma, ER and Guitart-Mampel, M and Urquiza, P and Da Costa, RT and Perez, MM and Riggs, LM and Patel, R and Solesio, ME}, title = {Toolkit for cellular studies of mammalian mitochondrial inorganic polyphosphate.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1302585}, pmid = {38161329}, issn = {2296-634X}, support = {R00 AG055701/AG/NIA NIH HHS/United States ; S10 OD026699/OD/NIH HHS/United States ; }, abstract = {Introduction: Inorganic polyphosphate (polyP) is an ancient polymer which is extremely well-conserved throughout evolution, and found in every studied organism. PolyP is composed of orthophosphates linked together by high-energy bonds, similar to those found in ATP. The metabolism and the functions of polyP in prokaryotes and simple eukaryotes are well understood. However, little is known about its physiological roles in mammalian cells, mostly due to its unknown metabolism and lack of systematic methods and effective models for the study of polyP in these organisms. Methods: Here, we present a comprehensive set of genetically modified cellular models to study mammalian polyP. Specifically, we focus our studies on mitochondrial polyP, as previous studies have shown the potent regulatory role of mammalian polyP in the organelle, including bioenergetics, via mechanisms that are not yet fully understood. Results: Using SH-SY5Y cells, our results show that the enzymatic depletion of mitochondrial polyP affects the expression of genes involved in the maintenance of mitochondrial physiology, as well as the structure of the organelle. Furthermore, this depletion has deleterious effects on mitochondrial respiration, an effect that is dependent on the length of polyP. Our results also show that the depletion of mammalian polyP in other subcellular locations induces significant changes in gene expression and bioenergetics; as well as that SH-SY5Y cells are not viable when the amount and/or the length of polyP are increased in mitochondria. Discussion: Our findings expand on the crucial role of polyP in mammalian mitochondrial physiology and place our cell lines as a valid model to increase our knowledge of both mammalian polyP and mitochondrial physiology.}, } @article {pmid38164224, year = {2023}, author = {Labbadia, J}, title = {Potential roles for mitochondria-to-HSF1 signaling in health and disease.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1332658}, pmid = {38164224}, issn = {2296-889X}, abstract = {The ability to respond rapidly and efficiently to protein misfolding is crucial for development, reproduction and long-term health. Cells respond to imbalances in cytosolic/nuclear protein homeostasis through the Heat Shock Response, a tightly regulated transcriptional program that enhances protein homeostasis capacity by increasing levels of protein quality control factors. The Heat Shock Response is driven by Heat Shock Factor 1, which is rapidly activated by the appearance of misfolded proteins and drives the expression of genes encoding molecular chaperones and protein degradation factors, thereby restoring proteome integrity. HSF1 is critical for organismal health, and this has largely been attributed to the preservation of cytosolic and nuclear protein homeostasis. However, evidence is now emerging that HSF1 is also a key mediator of mitochondrial function, raising the possibility that many of the health benefits conferred by HSF1 may be due to the maintenance of mitochondrial homeostasis. In this review, I will discuss our current understanding of the interplay between HSF1 and mitochondria and consider how mitochondria-to-HSF1 signaling may influence health and disease susceptibility.}, } @article {pmid38170710, year = {2024}, author = {Graham, AM and Lavretsky, P and Wilson, RE and McCracken, KG}, title = {High-altitude adaptation is accompanied by strong signatures of purifying selection in the mitochondrial genomes of three Andean waterfowl.}, journal = {PloS one}, volume = {19}, number = {1}, pages = {e0294842}, pmid = {38170710}, issn = {1932-6203}, mesh = {*Genome, Mitochondrial/genetics ; Altitude ; Genetic Drift ; Mitochondria/genetics ; Environment ; Adaptation, Physiological/genetics ; Selection, Genetic ; }, abstract = {Evidence from a variety of organisms points to convergent evolution on the mitochondria associated with a physiological response to oxygen deprivation or temperature stress, including mechanisms for high-altitude adaptation. Here, we examine whether demography and/or selection explains standing mitogenome nucleotide diversity in high-altitude adapted populations of three Andean waterfowl species: yellow-billed pintail (Anas georgica), speckled teal (Anas flavirostris), and cinnamon teal (Spatula cyanoptera). We compared a total of 60 mitogenomes from each of these three duck species (n = 20 per species) across low and high altitudes and tested whether part(s) or all of the mitogenome exhibited expected signatures of purifying selection within the high-altitude populations of these species. Historical effective population sizes (Ne) were inferred to be similar between high- and low-altitude populations of each species, suggesting that selection rather than genetic drift best explains the reduced genetic variation found in mitochondrial genes of high-altitude populations compared to low-altitude populations of the same species. Specifically, we provide evidence that establishment of these three Andean waterfowl species in the high-altitude environment, coincided at least in part with a persistent pattern of negative purifying selection acting on oxidative phosphorylation (OXPHOS) function of the mitochondria. Our results further reveal that the extent of gene-specific purifying selection has been greatest in the speckled teal, the species with the longest history of high-altitude occupancy.}, } @article {pmid38170752, year = {2024}, author = {Cui, M and Yamano, K and Yamamoto, K and Yamamoto-Imoto, H and Minami, S and Yamamoto, T and Matsui, S and Kaminishi, T and Shima, T and Ogura, M and Tsuchiya, M and Nishino, K and Layden, BT and Kato, H and Ogawa, H and Oki, S and Okada, Y and Isaka, Y and Kosako, H and Matsuda, N and Yoshimori, T and Nakamura, S}, title = {HKDC1, a target of TFEB, is essential to maintain both mitochondrial and lysosomal homeostasis, preventing cellular senescence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {2}, pages = {e2306454120}, pmid = {38170752}, issn = {1091-6490}, support = {23K18140//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22H04982//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; N/A//Astellas Foundation for Research on Metabolic Disorders/ ; N/A//Takeda Science Foundation (TSF)/ ; N/A//Mitsubishi Foundation (The Mitsubishi Foundation)/ ; 21H02428//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; S10 OD027016/OD/NIH HHS/United States ; N/A//Mochida Memorial Foundation for Medical and Pharmaceutical Research ()/ ; T32 AG057468/AG/NIA NIH HHS/United States ; JPMJCR17H6//MEXT | JST | Core Research for Evolutional Science and Technology (CREST)/ ; JP22gm1410014//Japan Agency for Medical Research and Development (AMED)/ ; 21H05145//Ministry of Education, Culture, Sports, Science and Technology (MEXT)/ ; N/A//NOVARTIS Foundation (Japan) for the Promotion of Science (NOVARTIS Foundation (Japan))/ ; N/A//China Scholarship Council (CSC)/ ; 23jm0610091h0001//Japan Agency for Medical Research and Development (AMED)/ ; }, mesh = {*Hexokinase/genetics/metabolism ; Prospective Studies ; *Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics/metabolism ; Mitochondria/metabolism ; Lysosomes/metabolism ; Protein Kinases/metabolism ; Cellular Senescence/genetics ; Homeostasis ; Autophagy/genetics ; }, abstract = {Mitochondrial and lysosomal functions are intimately linked and are critical for cellular homeostasis, as evidenced by the fact that cellular senescence, aging, and multiple prominent diseases are associated with concomitant dysfunction of both organelles. However, it is not well understood how the two important organelles are regulated. Transcription factor EB (TFEB) is the master regulator of lysosomal function and is also implicated in regulating mitochondrial function; however, the mechanism underlying the maintenance of both organelles remains to be fully elucidated. Here, by comprehensive transcriptome analysis and subsequent chromatin immunoprecipitation-qPCR, we identified hexokinase domain containing 1 (HKDC1), which is known to function in the glycolysis pathway as a direct TFEB target. Moreover, HKDC1 was upregulated in both mitochondrial and lysosomal stress in a TFEB-dependent manner, and its function was critical for the maintenance of both organelles under stress conditions. Mechanistically, the TFEB-HKDC1 axis was essential for PINK1 (PTEN-induced kinase 1)/Parkin-dependent mitophagy via its initial step, PINK1 stabilization. In addition, the functions of HKDC1 and voltage-dependent anion channels, with which HKDC1 interacts, were essential for the clearance of damaged lysosomes and maintaining mitochondria-lysosome contact. Interestingly, HKDC1 regulated mitophagy and lysosomal repair independently of its prospective function in glycolysis. Furthermore, loss function of HKDC1 accelerated DNA damage-induced cellular senescence with the accumulation of hyperfused mitochondria and damaged lysosomes. Our results show that HKDC1, a factor downstream of TFEB, maintains both mitochondrial and lysosomal homeostasis, which is critical to prevent cellular senescence.}, } @article {pmid38174367, year = {2024}, author = {Chi, HM and Davies, MR and Garcia, SM and Montenegro, C and Sharma, S and Lizarraga, M and Wang, Z and Nuthalapati, P and Kim, HT and Liu, X and Feeley, BT}, title = {Defining Endogenous Mitochondrial Transfer in Muscle After Rotator Cuff Injury.}, journal = {The American journal of sports medicine}, volume = {52}, number = {2}, pages = {451-460}, doi = {10.1177/03635465231214225}, pmid = {38174367}, issn = {1552-3365}, mesh = {Humans ; Mice ; Animals ; *Rotator Cuff Injuries/surgery ; Rotator Cuff/surgery ; Mice, Transgenic ; Muscular Atrophy/pathology ; Mitochondria ; *Red Fluorescent Protein ; }, abstract = {BACKGROUND: Rotator cuff muscle degeneration leads to poor clinical outcomes for patients with rotator cuff tears. Fibroadipogenic progenitors (FAPs) are resident muscle stem cells with the ability to differentiate into fibroblasts as well as white and beige adipose tissue. Induction of the beige adipose phenotype in FAPs has been shown to improve muscle quality after rotator cuff tears, but the mechanisms of how FAPs exert their beneficial effects have not been fully elucidated.

PURPOSE: To study the horizontal transfer of mitochondria from FAPs to myogenic cells and examine the effects of β-agonism on this novel process.

STUDY DESIGN: Controlled laboratory study.

METHODS: In mice that had undergone a massive rotator cuff tear, single-cell RNA sequencing was performed on isolated FAPs for genes associated with mitochondrial biogenesis and transfer. Murine FAPs were isolated by fluorescence-activated cell sorting and treated with a β-agonist versus control. FAPs were stained with mitochondrial dyes and cocultured with recipient C2C12 myoblasts, and the rate of transfer was measured after 24 hours by flow cytometry. PdgfraCre[ERT]/MitoTag mice were generated to study the effects of a rotator cuff injury on mitochondrial transfer. PdgfraCre[ERT]/tdTomato mice were likewise generated to perform lineage tracing of PDGFRA[+] cells in this injury model. Both populations of transgenic mice underwent tendon transection and denervation surgery, and MitoTag-labeled mitochondria from Pdgfra[+] FAPs were visualized by fluorescent microscopy, spinning disk confocal microscopy, and 2-photon microscopy; overall mitochondrial quantity was compared between mice treated with β-agonists and dimethyl sulfoxide.

RESULTS: Single-cell RNA sequencing in mice that underwent rotator cuff tear demonstrated an association between transcriptional markers of adipogenic differentiation and genes associated with mitochondrial biogenesis. In vitro cocultures of murine FAPs with C2C12 cells revealed that treatment of cells with a β-agonist increased mitochondrial transfer compared to control conditions (17.8% ± 9.9% to 99.6% ± 0.13% P < .0001). Rotator cuff injury in PdgfraCre[ERT]/MitoTag mice resulted in a robust increase in MitoTag signal in adjacent myofibers compared with uninjured mice. No accumulation of tdTomato signal from PDGFRA[+] cells was seen in injured fibers at 6 weeks after injury, suggesting that FAPs do not fuse with injured muscle fibers but rather contribute their mitochondria.

CONCLUSION: The authors have described a novel process of endogenous mitochondrial transfer that can occur within the injured rotator cuff between FAPs and myogenic cells. This process may be leveraged therapeutically with β-agonist treatment and represents an exciting target for improving translational therapies available for rotator cuff muscle degeneration.

CLINICAL RELEVANCE: Promoting endogenous mitochondrial transfer may represent a novel translational strategy to address muscle degeneration after rotator cuff tears.}, } @article {pmid38177203, year = {2024}, author = {Yonezawa, T and Mannen, H and Honma, K and Matsunaga, M and Rakotondraparany, F and Ratsoavina, FM and Wu, J and Nishibori, M and Yamamoto, Y}, title = {Origin and spatial population structure of Malagasy native chickens based on mitochondrial DNA.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {569}, pmid = {38177203}, issn = {2045-2322}, support = {21KK0122//JSPS KAKENHI/ ; 21KK0122//JSPS KAKENHI/ ; 21KK0122//JSPS KAKENHI/ ; 21KK0122//JSPS KAKENHI/ ; }, mesh = {Animals ; Africa ; *Chickens/genetics ; *DNA, Mitochondrial/genetics ; Genetic Variation ; Genetics, Population ; Haplotypes/genetics ; Madagascar ; Mitochondria/genetics ; Phylogeny ; }, abstract = {Since Malagasy human culture became established in a multi-layered way by genetic admixture of Austronesian (Indonesia), Bantu (East Africa) and West Asian populations, the Malagasy native livestock should also have originated from these regions. While recent genetic studies revealed that Malagasy native dogs and goats were propagated from Africa, the origin of Malagasy native chickens is still controversial. Here, we conducted a phylogeographic analysis of the native chickens, focusing on the historical relationships among the Indian Ocean rim countries and based on mitochondrial D-loop sequences. Although previous work suggested that the rare Haplogroup D occurs with high frequencies in Island Southeast Asia-Pacific, East Africa and Madagascar, the major mitochondrial lineage in Malagasy populations is actually not Haplogroup D but the Sub-haplogroup C2, which is also observed in East Africa, North Africa, India and West Asia. We demonstrate that the Malagasy native chickens were propagated directly from West Asia (including India and North Africa), and not via East Africa. Furthermore, they display clear genetic differentiation within Madagascar, separated into the Highland and Lowland regions as seen in the human genomic landscape on this island. Our findings provide new insights for better understanding the intercommunion of material/non-material cultures within and around Madagascar.}, } @article {pmid38185291, year = {2024}, author = {Bian, C and Ji, S and Xue, R and Zhou, L and Sun, J and Ji, H}, title = {Molecular cloning and characterization of BNIP3 and NIX1/2 and their role in DHA-induced mitophagy and apoptosis in grass carp (Ctenopharyngodon idellus) adipocytes.}, journal = {Gene}, volume = {899}, number = {}, pages = {148140}, doi = {10.1016/j.gene.2024.148140}, pmid = {38185291}, issn = {1879-0038}, mesh = {Animals ; *Mitophagy/genetics ; *Carps/genetics ; Phylogeny ; Apoptosis/genetics ; Adipocytes/metabolism ; Cloning, Molecular ; Mammals/genetics ; }, abstract = {B-cell lymphoma-2 and adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) and BNIP3 like (BNIP3L or NIX) play a vital role in regulating mitophagy and the intrinsic apoptosis in mammals, but their gene characterizations remain unclear in fish. Herein, bnip3, nix1 and nix2 were isolated and characterized from grass carp (Ctenopharyngodon idellus), which encode peptides of 194, 233 and 222 amino acids, respectively. As typical BH3-only proteins, grass carp BNIP3, NIX1 and NIX2 proteins contain BH3 and C-terminal transmembrane domains for inducing apoptosis. Moreover, the LC3-interacting region motif of BNIP3, NIX1 and NIX2 is also conserved in grass carp. Phylogenetic analyses also demonstrated that nix1 and nix2 may have originated from the genome duplication event. Expression pattern analysis indicated that bnip3, nix1 and nix2 were highest expressed in brain, followed by eye (bnip3) and liver (nix1 and nix2). BNIP3, NIX1 and NIX2 localized to the nucleus and the cytoplasm, with a predominant localization to mitochondria within the cytoplasm. In the present study, we found that 200 μM DHA impaired the mitochondrial function, manifested as the decreased antioxidant ability, cellular ATP content and mitochondrial membrane potential in grass carp adipocytes. In addition, the gene expression and enzyme activities of caspase family were significantly increased in 200 μM DHA group, indicating that adipocyte apoptosis was induced. Meanwhile, DHA increased the gene expression of bnip3, nix1 and nix2 in a dose-dependent manner in grass carp adipocytes. The colocalization of mitochondria and lysosomes was promoted by 200 μM DHA treatment, implying that BNIP3/NIX-related mitophagy was activated in adipocytes. Based on these findings, it can be inferred that BNIP3/NIX-related mitophagy may be involved in the adipocyte apoptosis induced by DHA in grass carp.}, } @article {pmid38185351, year = {2024}, author = {Zhang, D and Jakovlić, I and Zou, H and Liu, F and Xiang, CY and Gusang, Q and Tso, S and Xue, S and Zhu, WJ and Li, Z and Wu, J and Wang, GT}, title = {Strong mitonuclear discordance in the phylogeny of Neodermata and evolutionary rates of Polyopisthocotylea.}, journal = {International journal for parasitology}, volume = {54}, number = {5}, pages = {213-223}, doi = {10.1016/j.ijpara.2024.01.001}, pmid = {38185351}, issn = {1879-0135}, mesh = {Animals ; Phylogeny ; RNA, Ribosomal, 16S ; *Trematoda/genetics ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; *Genome, Mitochondrial ; }, abstract = {The genomic evolution of Polyopisthocotylea remains poorly understood in comparison to the remaining three classes of Neodermata: Monopisthocotylea, Cestoda, and Trematoda. Moreover, the evolutionary sequence of major events in the phylogeny of Neodermata remains unresolved. Herein we sequenced the mitogenome and transcriptome of the polyopisthocotylean Diplorchis sp., and conducted comparative evolutionary analyses using nuclear (nDNA) and mitochondrial (mtDNA) genomic datasets of Neodermata. We found strong mitonuclear discordance in the phylogeny of Neodermata. Polyopisthocotylea exhibited striking mitonuclear discordance in relative evolutionary rates: the fastest-evolving mtDNA in Neodermata and a comparatively slowly-evolving nDNA genome. This was largely attributable to its very long stem branch in mtDNA topologies, not exhibited by the nDNA data. We found indications that the fast evolution of mitochondrial genomes of Polyopisthocotylea may be driven both by relaxed purifying selection pressures and elevated levels of directional selection. We identified mitochondria-associated genes encoded in the nuclear genome: they exhibited unique evolutionary rates, but not correlated with the evolutionary rate of mtDNA, and there is no evidence for compensatory evolution (they evolved slower than the rest of the genome). Finally, there appears to exist an exceptionally large (≈6.3 kb) nuclear mitochondrial DNA segment (numt) in the nuclear genome of newly sequenced Diplorchis sp. A 3'-end segment of the 16S rRNA gene encoded by the numt was expressed, suggesting that this gene acquired novel, regulatory functions after the transposition to the nuclear genome. In conclusion, Polyopisthocotylea appears to be the lineage with the fastest-evolving mtDNA sequences among all of Bilateria, but most of the substitutions were accumulated deep in the evolutionary history of this lineage. As the nuclear genome does not exhibit a similar pattern, the circumstances underpinning this evolutionary phenomenon remain a mystery.}, } @article {pmid38186271, year = {2024}, author = {Thoral, E and Dargère, L and Medina-Suárez, I and Clair, A and Averty, L and Sigaud, J and Morales, A and Salin, K and Teulier, L}, title = {Non-lethal sampling for assessment of mitochondrial function does not affect metabolic rate and swimming performance.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {379}, number = {1896}, pages = {20220483}, pmid = {38186271}, issn = {1471-2970}, mesh = {Animals ; *Swimming ; *Biological Evolution ; Mitochondria ; Muscles ; Oxygen Consumption ; }, abstract = {A fundamental issue in the metabolic field is whether it is possible to understand underlying mechanisms that characterize individual variation. Whole-animal performance relies on mitochondrial function as it produces energy for cellular processes. However, our lack of longitudinal measures to evaluate how mitochondrial function can change within and among individuals and with environmental context makes it difficult to assess individual variation in mitochondrial traits. The aims of this study were to test the repeatability of muscle mitochondrial metabolism by performing two biopsies of red muscle, and to evaluate the effects of biopsies on whole-animal performance in goldfish Carassius auratus. Our results show that basal mitochondrial respiration and net phosphorylation efficiency are repeatable at 14-day intervals. We also show that swimming performance (optimal cost of transport and critical swimming speed) was repeatable in biopsied fish, whereas the repeatability of individual oxygen consumption (standard and maximal metabolic rates) seemed unstable over time. However, we noted that the means of individual and mitochondrial traits did not change over time in biopsied fish. This study shows that muscle biopsies allow the measurement of mitochondrial metabolism without sacrificing animals and that two muscle biopsies 14 days apart affect the intraspecific variation in fish performance without affecting average performance of individuals. This article is part of the theme issue 'The evolutionary significance of variation in metabolic rates'.}, } @article {pmid38186275, year = {2024}, author = {Prokkola, JM and Chew, KK and Anttila, K and Maamela, KS and Yildiz, A and Åsheim, ER and Primmer, CR and Aykanat, T}, title = {Tissue-specific metabolic enzyme levels covary with whole-animal metabolic rates and life-history loci via epistatic effects.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {379}, number = {1896}, pages = {20220482}, pmid = {38186275}, issn = {1471-2970}, mesh = {Animals ; Humans ; Anaerobiosis ; Biological Evolution ; Genotype ; Heart ; *Muscles ; *Salmo salar ; Transcription Factors ; Energy Metabolism/physiology ; }, abstract = {Metabolic rates, including standard (SMR) and maximum (MMR) metabolic rate have often been linked with life-history strategies. Variation in context- and tissue-level metabolism underlying SMR and MMR may thus provide a physiological basis for life-history variation. This raises a hypothesis that tissue-specific metabolism covaries with whole-animal metabolic rates and is genetically linked to life history. In Atlantic salmon (Salmo salar), variation in two loci, vgll3 and six6, affects life history via age-at-maturity as well as MMR. Here, using individuals with known SMR and MMR with different vgll3 and six6 genotype combinations, we measured proxies of mitochondrial density and anaerobic metabolism, i.e. maximal activities of the mitochondrial citrate synthase (CS) and lactate dehydrogenase (LDH) enzymes, in four tissues (heart, intestine, liver, white muscle) across low- and high-food regimes. We found enzymatic activities were related to metabolic rates, mainly SMR, in the intestine and heart. Individual loci were not associated with the enzymatic activities, but we found epistatic effects and genotype-by-environment interactions in CS activity in the heart and epistasis in LDH activity in the intestine. These effects suggest that mitochondrial density and anaerobic capacity in the heart and intestine may partly mediate variation in metabolic rates and life history via age-at-maturity. This article is part of the theme issue 'The evolutionary significance of variation in metabolic rates'.}, } @article {pmid38187609, year = {2024}, author = {Sizek, H and Deritei, D and Fleig, K and Harris, M and Regan, PL and Glass, K and Regan, ER}, title = {Unlocking Mitochondrial Dysfunction-Associated Senescence (MiDAS) with NAD [+] - a Boolean Model of Mitochondrial Dynamics and Cell Cycle Control.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.12.18.572194}, pmid = {38187609}, issn = {2692-8205}, abstract = {UNLABELLED: The steady accumulation of senescent cells with aging creates tissue environments that aid cancer evolution. Aging cell states are highly heterogeneous. 'Deep senescent' cells rely on healthy mitochondria to fuel a strong proinflammatory secretome, including cytokines, growth and transforming signals. Yet, the physiological triggers of senescence such as the reactive oxygen species (ROS) can also trigger mitochondrial dysfunction, and sufficient energy deficit to alter their secretome and cause chronic oxidative stress - a state termed Mitochondrial Dysfunction-Associated Senescence (MiDAS). Here, we offer a mechanistic hypothesis for the molecular processes leading to MiDAS, along with testable predictions. To do this we have built a Boolean regulatory network model that qualitatively captures key aspects of mitochondrial dynamics during cell cycle progression (hyper-fusion at the G1/S boundary, fission in mitosis), apoptosis (fission and dysfunction) and glucose starvation (reversible hyper-fusion), as well as MiDAS in response to SIRT3 knockdown or oxidative stress. Our model reaffirms the protective role of NAD [+] and external pyruvate. We offer testable predictions about the growth factor- and glucose-dependence of MiDAS and its reversibility at different stages of reactive oxygen species (ROS)-induced senescence. Our model provides mechanistic insights into the distinct stages of DNA-damage induced senescence, the relationship between senescence and epithelial-to-mesenchymal transition in cancer and offers a foundation for building multiscale models of tissue aging.

HIGHLIGHTS: Boolean regulatory network model reproduces mitochondrial dynamics during cell cycle progression, apoptosis, and glucose starvation. Model offers a mechanistic explanation for the positive feedback loop that locks in Mitochondrial Dysfunction-Associated Senescence (MiDAS), involving autophagy-resistant, hyperfused, dysfunctional mitochondria. Model reproduces ROS-mediated mitochondrial dysfunction and suggests that MiDAS is part of the early phase of damage-induced senescence. Model predicts that cancer-driving mutations that bypass the G1/S checkpoint generally increase the incidence of MiDAS, except for p53 loss.}, } @article {pmid38188667, year = {2023}, author = {Riew, TR and Hwang, JW and Jin, X and Kim, HL and Jung, SJ and Lee, MY}, title = {Astrocytes are involved in the formation of corpora amylacea-like structures from neuronal debris in the CA1 region of the rat hippocampus after ischemia.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1308247}, pmid = {38188667}, issn = {1662-5102}, abstract = {Recently, we demonstrated that the corpora amylacea (CA), a glycoprotein-rich aggregate frequently found in aged brains, accumulates in the ischemic hippocampus and that osteopontin (OPN) mediates the entire process of CA formation. Therefore, this study aimed to elucidate the mechanisms by which astrocytes and microglia participate in CA formation during the late phase (4-12 weeks) of brain ischemia. Based on various morphological analyses, including immunohistochemistry, in situ hybridization, immunoelectron microscopy, and correlative light and electron microscopy, we propose that astrocytes are the primary cells responsible for CA formation after ischemia. During the subacute phase after ischemia, astrocytes, rather than microglia, express Opn messenger ribonucleic acid and OPN protein, a surrogate marker and key component of CA. Furthermore, the specific localization of OPN in the Golgi complex suggests that it is synthesized and secreted by astrocytes. Astrocytes were in close proximity to type I OPN deposits, which accumulated in the mitochondria of degenerating neurons before fully forming the CA (type III OPN deposits). Throughout CA formation, astrocytes remained closely attached to OPN deposits, with their processes exhibiting well-developed gap junctions. Astrocytic cytoplasmic protein S100β, a calcium-binding protein, was detected within the fully formed CA. Additionally, ultrastructural analysis revealed direct contact between astroglial fibrils and the forming facets of the CA. Overall, we demonstrated that astrocytes play a central role in mediating CA formation from the initial stages of OPN deposit accumulation to the evolution of fully formed CA following transient ischemia in the hippocampus.}, } @article {pmid38189676, year = {2024}, author = {Huttner, WB and Heide, M and Mora-Bermúdez, F and Namba, T}, title = {Neocortical neurogenesis in development and evolution-Human-specific features.}, journal = {The Journal of comparative neurology}, volume = {532}, number = {2}, pages = {e25576}, doi = {10.1002/cne.25576}, pmid = {38189676}, issn = {1096-9861}, support = {//Max Planck Society/ ; }, mesh = {Animals ; Humans ; *Neural Stem Cells/metabolism ; *Neanderthals/metabolism ; Ependymoglial Cells/metabolism ; *Neocortex/metabolism ; Neurogenesis/physiology ; Transketolase/metabolism ; GTPase-Activating Proteins/metabolism ; }, abstract = {In this review, we focus on human-specific features of neocortical neurogenesis in development and evolution. Two distinct topics will be addressed. In the first section, we discuss the expansion of the neocortex during human evolution and concentrate on the human-specific gene ARHGAP11B. We review the ability of ARHGAP11B to amplify basal progenitors and to expand a primate neocortex. We discuss the contribution of ARHGAP11B to neocortex expansion during human evolution and its potential implications for neurodevelopmental disorders and brain tumors. We then review the action of ARHGAP11B in mitochondria as a regulator of basal progenitor metabolism, and how it promotes glutaminolysis and basal progenitor proliferation. Finally, we discuss the increase in cognitive performance due to the ARHGAP11B-induced neocortical expansion. In the second section, we focus on neocortical development in modern humans versus Neanderthals. Specifically, we discuss two recent findings pointing to differences in neocortical neurogenesis between these two hominins that are due to a small number of amino acid substitutions in certain key proteins. One set of such proteins are the kinetochore-associated proteins KIF18a and KNL1, where three modern human-specific amino acid substitutions underlie the prolongation of metaphase during apical progenitor mitosis. This prolongation in turn is associated with an increased fidelity of chromosome segregation to the apical progenitor progeny during modern human neocortical development, with implications for the proper formation of radial units. Another such key protein is transketolase-like 1 (TKTL1), where a single modern human-specific amino acid substitution endows TKTL1 with the ability to amplify basal radial glia, resulting in an increase in upper-layer neuron generation. TKTL1's ability is based on its action in the pentose phosphate pathway, resulting in increased fatty acid synthesis. The data imply greater neurogenesis during neocortical development in modern humans than Neanderthals due to TKTL1, in particular in the developing frontal lobe.}, } @article {pmid38200362, year = {2024}, author = {Liu, J and Hu, JY and Li, DZ}, title = {Remarkable mitochondrial genome heterogeneity in Meniocus linifolius (Brassicaceae).}, journal = {Plant cell reports}, volume = {43}, number = {2}, pages = {36}, pmid = {38200362}, issn = {1432-203X}, support = {XDB31000000//Strategic Priority Research Program (Type-B), Chinese Academy of Science/ ; }, mesh = {*Genome, Mitochondrial/genetics ; *Brassicaceae/genetics ; Phylogeny ; Biological Evolution ; DNA, Mitochondrial/genetics ; }, abstract = {Detailed analyses of 16 genomes identified a remarkable acceleration of mutation rate, hence mitochondrial sequence and structural heterogeneity, in Meniocus linifolius (Brassicaceae). The powerhouse, mitochondria, in plants feature high levels of structural variation, while the encoded genes are normally conserved. However, the substitution rates and spectra of mitochondria DNA within the Brassicaceae, a family with substantial scientific and economic importance, have not been adequately deciphered. Here, by analyzing three newly assembled and 13 known mitochondrial genomes (mitogenomes), we report the highly variable genome structure and mutation rates in Brassicaceae. The genome sizes and GC contents are 196,604 bp and 46.83%, 288,122 bp and 44.79%, and 287,054 bp and 44.93%, for Meniocus linifolius (Mli), Crucihimalaya lasiocarpa (Cla), and Lepidium sativum (Lsa), respectively. In total, 29, 33, and 34 protein-coding genes (PCGs) and 14, 18, and 18 tRNAs are annotated for Mli, Cla, and Lsa, respectively, while all mitogenomes contain one complete circular molecule with three rRNAs and abundant RNA editing sites. The Mli mitogenome features four conformations likely mediated by the two pairs of long repeats, while at the same time seems to have an unusual evolutionary history due to higher GC content, loss of more genes and sequences, but having more repeats and plastid DNA insertions. Corroborating with these, an ambiguous phylogenetic position with long branch length and elevated synonymous substitution rate in nearly all PCGs are observed for Mli. Taken together, our results reveal a high level of mitogenome heterogeneity at the family level and provide valuable resources for further understanding the evolutionary pattern of organelle genomes in Brassicaceae.}, } @article {pmid38200446, year = {2024}, author = {Korolija, M and Sukser, V and Vlahoviček, K}, title = {Mitochondrial point heteroplasmy: insights from deep-sequencing of human replicate samples.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {48}, pmid = {38200446}, issn = {1471-2164}, mesh = {Humans ; *Heteroplasmy ; Phylogeny ; *Mitochondria/genetics ; High-Throughput Nucleotide Sequencing ; DNA, Mitochondrial/genetics ; }, abstract = {BACKGROUND: Human mitochondrial heteroplasmy is an extensively investigated phenomenon in the context of medical diagnostics, forensic identification and molecular evolution. However, technical limitations of high-throughput sequencing hinder reliable determination of point heteroplasmies (PHPs) with minor allele frequencies (MAFs) within the noise threshold.

RESULTS: To investigate the PHP landscape at an MAF threshold down to 0.1%, we sequenced whole mitochondrial genomes at approximately 7.700x coverage, in multiple technical and biological replicates of longitudinal blood and buccal swab samples from 11 human donors (159 libraries in total). The results obtained by two independent sequencing platforms and bioinformatics pipelines indicate distinctive PHP patterns below and above the 1% MAF cut-off. We found a high inter-individual prevalence of low-level PHPs (MAF < 1%) at polymorphic positions of the mitochondrial DNA control region (CR), their tissue preference, and a tissue-specific minor allele linkage. We also established the position-dependent potential of minor allele expansion in PHPs, and short-term PHP instability in a mitotically active tissue. We demonstrate that the increase in sensitivity of PHP detection to minor allele frequencies below 1% within a robust experimental and analytical pipeline, provides new information with potential applicative value.

CONCLUSIONS: Our findings reliably show different mutational loads between tissues at sub-1% allele frequencies, which may serve as an informative medical biomarker of time-dependent, tissue-specific mutational burden, or help discriminate forensically relevant tissues in a single person, close maternal relatives or unrelated individuals of similar phylogenetic background.}, } @article {pmid38203264, year = {2023}, author = {Baleva, MV and Piunova, U and Chicherin, I and Vasilev, R and Levitskii, S and Kamenski, P}, title = {Mitochondrial Protein SLIRP Affects Biosynthesis of Cytochrome c Oxidase Subunits in HEK293T Cells.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203264}, issn = {1422-0067}, support = {21-14-00008//Russian Science Foundation/ ; 24-2-21//Moscow University State Assignment/ ; }, mesh = {Humans ; *Electron Transport Complex IV/genetics ; *Mitochondrial Proteins/genetics ; HEK293 Cells ; Mitochondria/genetics ; Eukaryotic Cells ; RNA-Binding Proteins ; }, abstract = {Mitochondria carry out various vital roles in eukaryotic cells, including ATP energy synthesis, the regulation of apoptosis, Fe-S cluster formation, and the metabolism of fatty acids, amino acids, and nucleotides. Throughout evolution, mitochondria lost most of their ancestor's genome but kept the replication, transcription, and translation machinery. Protein biosynthesis in mitochondria is specialized in the production of highly hydrophobic proteins encoded by mitochondria. These proteins are components of oxidative phosphorylation chain complexes. The coordination of protein synthesis must be precise to ensure the correct assembly of nuclear-encoded subunits for these complexes. However, the regulatory mechanisms of mitochondrial translation in human cells are not yet fully understood. In this study, we examined the contribution of the SLIRP protein in regulating protein biosynthesis in mitochondria. Using a click-chemistry approach, we discovered that deletion of the SLIRP gene disturbs mitochondrial translation, leading to the dysfunction of complexes I and IV, but it has no significant effect on complexes III and V. We have shown that this protein interacts only with the small subunit of the mitochondrial ribosome, which may indicate its involvement in the regulation of the mitochondrial translation initiation stage.}, } @article {pmid38206324, year = {2024}, author = {Crino, OL and Head, ML and Jennions, MD and Noble, DWA}, title = {Mitochondrial function and sexual selection: can physiology resolve the 'lek paradox'?.}, journal = {The Journal of experimental biology}, volume = {227}, number = {2}, pages = {}, doi = {10.1242/jeb.245569}, pmid = {38206324}, issn = {1477-9145}, support = {DP210101152//Australian Research Council/ ; }, mesh = {Female ; Male ; Humans ; *Reproduction ; *Biological Evolution ; Exercise ; Food ; Mitochondria/genetics ; }, abstract = {Across many taxa, males use elaborate ornaments or complex displays to attract potential mates. Such sexually selected traits are thought to signal important aspects of male 'quality'. Female mating preferences based on sexual traits are thought to have evolved because choosy females gain direct benefits that enhance their lifetime reproductive success (e.g. greater access to food) and/or indirect benefits because high-quality males contribute genes that increase offspring fitness. However, it is difficult to explain the persistence of female preferences when males only provide genetic benefits, because female preferences should erode the heritable genetic variation in fitness that sexually selected traits signal. This 'paradox of the lek' has puzzled evolutionary biologists for decades, and inspired many hypotheses to explain how heritable variation in sexually selected traits is maintained. Here, we discuss how factors that affect mitochondrial function can maintain variation in sexually selected traits despite strong female preferences. We discuss how mitochondrial function can influence the expression of sexually selected traits, and we describe empirical studies that link the expression of sexually selected traits to mitochondrial function. We explain how mothers can affect mitochondrial function in their offspring by (a) influencing their developmental environment through maternal effects and (b) choosing a mate to increase the compatibility of mitochondrial and nuclear genes (i.e. the 'mitonuclear compatibility model of sexual selection'). Finally, we discuss how incorporating mitochondrial function into models of sexual selection might help to resolve the paradox of the lek, and we suggest avenues for future research.}, } @article {pmid38216865, year = {2024}, author = {Cao, L and Chen, P and Hou, X and Ma, J and Yang, N and Lu, Y and Huang, H}, title = {rDNA and mtDNA analysis for the identification of genetic characters in the hybrid grouper derived from hybridization of Cromileptes altivelis (female) × Epinephelus lanceolatus (male).}, journal = {BMC genomic data}, volume = {25}, number = {1}, pages = {5}, pmid = {38216865}, issn = {2730-6844}, support = {YSPTZX202103//The Innovation Platform for Academicians of Hainan Province/ ; RHDRC202010//Scientific Research Foundation of Hainan Tropical Ocean University/ ; 321QN263//Hainan Provincial Natural Science Foundation of China/ ; 32160861//National Natural Science Foundation of China/ ; ZDKJ2021017//The Major Science and Technology plan of Hainan Province/ ; 2020KF001//State Key Laboratory of Developmental Biology of Freshwater Fish/ ; }, mesh = {Animals ; *Bass/genetics/anatomy & histology ; DNA, Mitochondrial/genetics ; DNA, Ribosomal/genetics ; Phylogeny ; Mitochondria/genetics ; }, abstract = {BACKGROUND: Hybridization is a useful strategy to produce offspring with more desirable phenotypic characteristics than those of parents. The hybrid grouper derived from the cross of Cromileptes altivelis (♀, 2n = 48) with Epinephelus lanceolatus (♂, 2n = 48) exhibits improved growth compared with its female parent, which makes it valuable to aquaculture. However, the genetic traits of the hybrid grouper are poorly understood.

RESULTS: The observations showed that the hybrid grouper was diploid (2n = 48) and displayed intermediate morphology with the parent's measurable characteristics. The ribosomal DNA (rDNA) and mitochondria DNA (mtDNA) were characterized at molecular and phylogenetic level. High similarity and low genetic distance of 5S rDNA and mtDNA sequences between the hybrid grouper and C. altivelis showed that the hybrid grouper had a closer genetic relationship with female parents. The reconstructed phylogenetic tree based on COI gene and D-loop region of mtDNA recovered that mtDNA was maternally inherited in the hybrid grouper. Additionally, the DNA methylation level of 5S rDNA intergenic spacers (IGS) sequence was tested in here. The results showed that the DNA methylation status of the hybrid grouper was significantly lower than that of C. altivelis.

CONCLUSION: Results of this study provide important data on the genetic characteristics of the hybrid derived from the cross of C. altivelis and E. lanceolatus, and contribute the knowledge of both evolution and marine fish breeding.}, } @article {pmid38220520, year = {2024}, author = {Wang, J and Kan, S and Liao, X and Zhou, J and Tembrock, LR and Daniell, H and Jin, S and Wu, Z}, title = {Plant organellar genomes: much done, much more to do.}, journal = {Trends in plant science}, volume = {29}, number = {7}, pages = {754-769}, doi = {10.1016/j.tplants.2023.12.014}, pmid = {38220520}, issn = {1878-4372}, mesh = {*Genome, Plant/genetics ; Gene Editing/methods ; Plants/genetics ; Organelles/genetics ; Plastids/genetics ; Mitochondria/genetics ; Evolution, Molecular ; CRISPR-Cas Systems ; }, abstract = {Plastids and mitochondria are the only organelles that possess genomes of endosymbiotic origin. In recent decades, advances in sequencing technologies have contributed to a meteoric rise in the number of published organellar genomes, and have revealed greatly divergent evolutionary trajectories. In this review, we quantify the abundance and distribution of sequenced plant organellar genomes across the plant tree of life. We compare numerous genomic features between the two organellar genomes, with an emphasis on evolutionary trajectories, transfers, the current state of organellar genome editing by transcriptional activator-like effector nucleases (TALENs), transcription activator-like effector (TALE)-mediated deaminase, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas), as well as genetic transformation. Finally, we propose future research to understand these different evolutionary trajectories, and genome-editing strategies to promote functional studies and eventually improve organellar genomes.}, } @article {pmid38221179, year = {2024}, author = {Antoniolli, HRM and Carvalho, TL and Gottschalk, MS and Loreto, ELS and Robe, LJ and Depr, M}, title = {Systematics and spatio-temporal evolutionary patterns of the flavopilosa group of Drosophila (Diptera, Drosophilidae).}, journal = {Zootaxa}, volume = {5399}, number = {1}, pages = {1-18}, doi = {10.11646/zootaxa.5399.1.1}, pmid = {38221179}, issn = {1175-5334}, mesh = {Animals ; *Drosophila/genetics ; Phylogeny ; *Plant Breeding ; Biological Evolution ; Mitochondria/genetics ; }, abstract = {The Drosophila flavopilosa group comprises morphologically cryptic species that are ecologically restricted to feeding, breeding and ovipositing on flowers of Cestrum and Sessea (Solanaceae). Previous studies confirmed the monophyly of the group and the success of DNA barcoding in identifying a subset of its species, but several others remain yet to be evaluated. Furthemore, the taxonomy of the group remains incomplete, with only nine of the 17 species assigned to subgroups. Here, we accessed the phylogenetic relationships and spatio-temporal evolutionary patterns of the flavopilosa group based on a mitochondrial and two nuclear genes, providing the first molecular support to the subdivision of the group and suggesting a new taxonomic scheme for its species. Barcoding proved to be an effective tool, as all species were reciprocally monophyletic and different analyses of species delimitation yielded congruent results. The close relationship of D. flavopilosa with D. cestri and D. cordeiroi was strongly supported, suggesting that the latter should be placed in the flavopilosa subgroup together with the first. Furthermore, D. mariaehelenae was positioned as sister to D. incompta, supporting its inclusion in the nesiota subgroup. Despite new taxonomic assignments, the synapomorphic status of the diagnostic characters proposed for both subgroups was supported. Based on them, each of the remaining species were placed into one of both subgroups. Divergence time estimates suggest that their diversification coincided with the divergence of Sessea and Cestrum, providing an interesting case of coevolution.}, } @article {pmid38221354, year = {2023}, author = {Hoare, RJB and Patrick, BH and Buckley, TR and Brav-Cubitt, T}, title = {Wing pattern variation and DNA barcodes defy taxonomic splitting in the New Zealand Pimelea Looper Notoreas perornata (Walker) (Lepidoptera: Geometridae: Larentiinae): the importance of populations as conservation units.}, journal = {Zootaxa}, volume = {5346}, number = {1}, pages = {1-27}, doi = {10.11646/zootaxa.5346.1.1}, pmid = {38221354}, issn = {1175-5334}, mesh = {Animals ; *Lepidoptera/genetics ; DNA Barcoding, Taxonomic ; New Zealand ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; *Moths/genetics/anatomy & histology ; Phylogeny ; }, abstract = {The endemic Notoreas perornata (Walker, 1863) complex (Lepidoptera: Geometridae: Larentiinae) from the North Island and northern South Island of New Zealand is reviewed. Larvae feed on Pimelea spp. (Thymelaeaceae), frequently in highly fragmented and threatened shrubland habitats. Allopatric populations tend to differ in size and wing pattern characteristics, but not in genitalia; moreover extensive variation renders recognition of subspecies / allopatric species based on any species concept problematic. A mitochondrial DNA gene tree is not congruent with morphology and indicates rapid recent divergence that has not settled into diagnosable lineages. Based on our results, we synonymise Notoreas simplex Hudson, 1898 with N. perornata (Walker, 1863), and retain N. perornata as a single, highly diverse but monotypic species. All known populations are illustrated to display variation. For conservation purposes, we recommend the continued recognition within the species of 10 populations or groups of populations that appear to be on the way to diverging at subspecific level based on morphological and/or DNA data. The conservation status of all these populations is reviewed. One conservation unit, comprising the populations from Westland, has not been seen since 1998 and is feared possibly extinct.}, } @article {pmid38221380, year = {2023}, author = {Doniol-Valcroze, P and Coiffard, P and Alstrm, P and Robb, M and Dufour, P and Crochet, PA}, title = {Molecular and acoustic evidence support the species status of Anthus rubescens rubescens and Anthus [rubescens] japonicus (Passeriformes: Motacillidae).}, journal = {Zootaxa}, volume = {5343}, number = {2}, pages = {173-192}, doi = {10.11646/zootaxa.5343.2.4}, pmid = {38221380}, issn = {1175-5334}, mesh = {Animals ; *Passeriformes/genetics ; Plant Breeding ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Phylogeny ; }, abstract = {The Buff-bellied Pipit Anthus rubescens comprises two allopatric subspecies groups: A. r. rubescens and A. r. alticola in North America and A. [r.] japonicus in north-east Asia. Despite their great morphological resemblance in breeding plumage, most individuals can be assigned to one or the other subspecies group in non-breeding plumage. Allopatric distributions, morphological differentiation and previously reported molecular divergence suggested the need for additional taxonomic study to assess the rank of these two populations. To resolve the taxonomy of the Buff-bellied Pipit species complex we analysed i) two mitochondrial DNA (mtDNA) loci and ii) nine bioacoustic parameters across 69 sound recordings (338 flight calls) recovered from public databases using principal component analysis and Euclidean distance measures. By comparing our mtDNA and call divergence measures with similar values measured between long-recognised species pairs of the genus, we show that the level of mitochondrial and acoustic divergence between the two Buff-bellied Pipit subspecies groups is typical of species-level divergence in the genus Anthus. Therefore, we recommend splitting the Buff-bellied Pipit species complex into two species: Anthus rubescens (American Pipit) and Anthus japonicus (Siberian Pipit). Our results also suggest that the Water Pipit A. spinoletta deserves taxonomic reassessment as its lineages are highly divergent in acoustics and mtDNA, while mtDNA relationships suggest paraphyly relative to the Rock Pipit A. petrosus. Our work highlights the crucial importance of integrative approaches in taxonomy and the usefulness of bioacoustics in studying cryptic diversity.}, } @article {pmid38228651, year = {2024}, author = {Krishnan, N and Csiszár, V and Móri, TF and Garay, J}, title = {Genesis of ectosymbiotic features based on commensalistic syntrophy.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {1366}, pmid = {38228651}, issn = {2045-2322}, support = {955708//Horizon 2020/ ; 125569//NKFIH/ ; }, mesh = {Humans ; Phylogeny ; *Symbiosis ; *Eukaryota ; Mitochondria ; Biological Evolution ; }, abstract = {The symbiogenetic origin of eukaryotes with mitochondria is considered a major evolutionary transition. The initial interactions and conditions of symbiosis, along with the phylogenetic affinity of the host, are widely debated. Here, we focus on a possible evolutionary path toward an association of individuals of two species based on unidirectional syntrophy. With the backing of a theoretical model, we hypothesize that the first step in the evolution of such symbiosis could be the appearance of a linking structure on the symbiont's membrane, using which it forms an ectocommensalism with its host. We consider a commensalistic model based on the syntrophy hypothesis in the framework of coevolutionary dynamics and mutant invasion into a monomorphic resident system (evolutionary substitution). We investigate the ecological and evolutionary stability of the consortium (or symbiotic merger), with vertical transmissions playing a crucial role. The impact of the 'effectiveness of vertical transmission' on the dynamics is also analyzed. We find that the transmission of symbionts and the additional costs incurred by the mutant determine the conditions of fixation of the consortia. Additionally, we observe that small and highly metabolically active symbionts are likely to form the consortia.}, } @article {pmid38231368, year = {2024}, author = {Nevarez-Lopez, CA and Muhlia-Almazan, A and Gamero-Mora, E and Sanchez-Paz, A and Sastre-Velasquez, CD and Lopez-Martinez, J}, title = {The branched mitochondrial respiratory chain from the jellyfish Stomolophus sp2 as a probable adaptive response to environmental changes.}, journal = {Journal of bioenergetics and biomembranes}, volume = {56}, number = {2}, pages = {101-115}, pmid = {38231368}, issn = {1573-6881}, support = {171862//Consejo Nacional de Ciencia y Tecnología/ ; }, mesh = {Animals ; Electron Transport ; Phylogeny ; *Mitochondrial Membranes/metabolism ; *Scyphozoa/chemistry/metabolism ; Mitochondria/metabolism ; Electron Transport Complex IV ; }, abstract = {During their long evolutionary history, jellyfish have faced changes in multiple environmental factors, to which they may selectively fix adaptations, allowing some species to survive and inhabit diverse environments. Previous findings have confirmed the jellyfish's ability to synthesize large ATP amounts, mainly produced by mitochondria, in response to environmental challenges. This study characterized the respiratory chain from the mitochondria of the jellyfish Stomolophus sp2 (previously misidentified as Stomolophus meleagris). The in-gel activity from isolated jellyfish mitochondria confirmed that the mitochondrial respiratory chain contains the four canonical complexes I to IV and F0F1-ATP synthase. Specific additional activity bands, immunodetection, and mass spectrometry identification confirmed the occurrence of four alternative enzymes integrated into a branched mitochondrial respiratory chain of Stomolophus sp2: an alternative oxidase and three dehydrogenases (two NADH type II enzymes and a mitochondrial glycerol-3-phosphate dehydrogenase). The analysis of each transcript sequence, their phylogenetic relationships, and each protein's predicted models confirmed the mitochondrial alternative enzymes' identity and specific characteristics. Although no statistical differences were found among the mean values of transcript abundance of each enzyme in the transcriptomes of jellyfish exposed to three different temperatures, it was confirmed that each gene was expressed at all tested conditions. These first-time reported enzymes in cnidarians suggest the adaptative ability of jellyfish's mitochondria to display rapid metabolic responses, as previously described, to maintain energetic homeostasis and face temperature variations due to climate change.}, } @article {pmid38235059, year = {2023}, author = {Bayazit, MB and Francois, A and McGrail, E and Accornero, F and Stratton, MS}, title = {mt-tRNAs in the polymerase gamma mutant heart.}, journal = {The journal of cardiovascular aging}, volume = {3}, number = {4}, pages = {}, pmid = {38235059}, issn = {2768-5993}, support = {K01 AG056848/AG/NIA NIH HHS/United States ; R01 HL154001/HL/NHLBI NIH HHS/United States ; T32 GM141955/GM/NIGMS NIH HHS/United States ; R01 HL136951/HL/NHLBI NIH HHS/United States ; R01 HL158971/HL/NHLBI NIH HHS/United States ; F31 HL162513/HL/NHLBI NIH HHS/United States ; }, abstract = {INTRODUCTION: Mice harboring a D257A mutation in the proofreading domain of the mitochondrial DNA polymerase, Polymerase Gamma (POLG), experience severe metabolic dysfunction and display hallmarks of accelerated aging. We previously reported a mitochondrial unfolded protein response (UPT[mt]) - like (UPR[mt]-like) gene and protein expression pattern in the right ventricular tissue of POLG mutant mice.

AIM: We sought to determine if POLG mutation altered the expression of genes encoded by the mitochondria in a way that might also reduce proteotoxic stress.

METHODS AND RESULTS: The expression of genes encoded by the mitochondrial DNA was interrogated via RNA-seq and northern blot analysis. A striking, location-dependent effect was seen in the expression of mitochondrial-encoded tRNAs in the POLG mutant as assayed by RNA-seq. These expression changes were negatively correlated with the tRNA partner amino acid's amyloidogenic potential. Direct measurement by northern blot was conducted on candidate mt-tRNAs identified from the RNA-seq. This analysis confirmed reduced expression of MT-TY in the POLG mutant but failed to show increased expression of MT-TP, which was dramatically increased in the RNA-seq data.

CONCLUSION: We conclude that reduced expression of amyloid-associated mt-tRNAs is another indication of adaptive response to severe mitochondrial dysfunction in the POLG mutant. Incongruence between RNA-seq and northern blot measurement of MT-TP expression points towards the existence of mt-tRNA post-transcriptional modification regulation in the POLG mutant that alters either polyA capture or cDNA synthesis in RNA-seq library generation. Together, these data suggest that 1) evolution has distributed mt-tRNAs across the circular mitochondrial genome to allow chromosomal location-dependent mt-tRNA regulation (either by expression or PTM) and 2) this regulation is cognizant of the tRNA partner amino acid's amyloidogenic properties.}, } @article {pmid38238104, year = {2024}, author = {Ali, NA and Song, W and Huang, J and Wu, D and Zhao, X}, title = {Recent advances and biotechnological applications of RNA metabolism in plant chloroplasts and mitochondria.}, journal = {Critical reviews in biotechnology}, volume = {44}, number = {8}, pages = {1552-1573}, doi = {10.1080/07388551.2023.2299789}, pmid = {38238104}, issn = {1549-7801}, mesh = {*Chloroplasts/metabolism ; *Mitochondria/metabolism ; *Biotechnology ; Plants/metabolism ; RNA, Plant/metabolism/genetics ; }, abstract = {The chloroplast and mitochondrion are semi-autonomous organelles that play essential roles in cell function. These two organelles are embellished with prokaryotic remnants and contain many new features emerging from the co-evolution of organelles and the nucleus. A typical plant chloroplast or mitochondrion genome encodes less than 100 genes, and the regulation of these genes' expression is remarkably complex. The regulation of chloroplast and mitochondrion gene expression can be achieved at multiple levels during development and in response to environmental cues, in which, RNA metabolism, including: RNA transcription, processing, translation, and degradation, plays an important role. RNA metabolism in plant chloroplasts and mitochondria combines bacterial-like traits with novel features evolved in the host cell and is regulated by a large number of nucleus-encoded proteins. Among these, pentatricopeptide repeat (PPR) proteins are deeply involved in multiple aspects of the RNA metabolism of organellar genes. Research over the past decades has revealed new insights into different RNA metabolic events in plant organelles, such as the composition of chloroplast and mitochondrion RNA editosomes. We summarize and discuss the most recent knowledge and biotechnological implications of various RNA metabolism processes in plant chloroplasts and mitochondria, with a focus on the nucleus-encoded factors supporting them, to gain a deeper understanding of the function and evolution of these two organelles in plant cells. Furthermore, a better understanding of the role of nucleus-encoded factors in chloroplast and mitochondrion RNA metabolism will motivate future studies on manipulating the plant gene expression machinery with engineered nucleus-encoded factors.}, } @article {pmid38241813, year = {2024}, author = {Satoh, S and Miyake, K and Adachi, Y and Masuhiro, K and Futami, S and Naito, Y and Shiroyama, T and Koyama, S and Yamaguchi, Y and Konaka, H and Takamatsu, H and Okuzaki, D and Nagatomo, I and Takeda, Y and Kumanogoh, A}, title = {Cancer-associated SNRPD3 mutation confers resistance to hypoxia, which is attenuated by DRP1 inhibition.}, journal = {Biochemical and biophysical research communications}, volume = {696}, number = {}, pages = {149511}, doi = {10.1016/j.bbrc.2024.149511}, pmid = {38241813}, issn = {1090-2104}, mesh = {Humans ; Dynamins/genetics/metabolism ; *GTP Phosphohydrolases/metabolism ; Hypoxia/metabolism ; Mitochondria/metabolism ; Mitochondrial Dynamics/genetics ; Mutation ; *Neoplasms/genetics/metabolism ; snRNP Core Proteins ; }, abstract = {RNA splicing is a fundamental cellular mechanism performed by spliceosomes that synthesise multiple mature RNA isoforms from a single gene. The association between spliceosome abnormality and solid cancers remains largely unknown. Here, we demonstrated that Sm proteins, which are common components of the spliceosomes and constitute the Sm ring, were overexpressed in multiple cancers and their expression levels were correlated with clinical prognosis. In a pan-cancer mutational hotspot in the Sm ring at SNRPD3 G96V, we found that the G96V substitution confers resistance to hypoxia. RNA-seq detected numerous differentially spliced events between the wild-type and mutation-carrying cells cultured under hypoxia, wherein skipping exons and mutually exclusive exons were frequently observed. This was observed in DNM1L mRNA, which encodes the DRP1 protein that regulates mitochondrial fission. The mitochondria of cells carrying this mutation were excessively fragmented compared with those of wild-type cells. Furthermore, treatment with a DRP1 inhibitor (Mdivi-1) recovered the over-fragmented mitochondria, leading to the attenuation of hypoxia resistance in the mutant cells. These results propose a novel correlation between the cancer-related spliceosome abnormality and mitochondrial fission. Thus, targeting SNRPD3 G96V with a DRP1 inhibitor is a potential treatment strategy for cancers with spliceosome abnormalities.}, } @article {pmid38243053, year = {2024}, author = {Seesamut, T and Oba, Y and Jirapatrasilp, P and Martinsson, S and Lindström, M and Erséus, C and Panha, S}, title = {Global species delimitation of the cosmopolitan marine littoral earthworm Pontodrilus litoralis (Grube, 1855).}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {1753}, pmid = {38243053}, issn = {2045-2322}, support = {TRF-DPG628001//Thailand Research Fund/ ; BDC-PG2-161002//Center of Excellence on Biodiversity/ ; N35E660138//National Research Council of Thailand/ ; }, mesh = {Animals ; Phylogeny ; *Oligochaeta/genetics ; Mitochondria ; Asia ; Australia ; }, abstract = {The marine littoral earthworm Pontodrilus litoralis (Grube, 1855) is widely distributed and is reported as a single species. This study utilized an integrative taxonomic approach based upon morphological examination, phylogenetic reconstruction, and molecular species delimitation, to test whether the taxon is a single species or a species complex. For this, a total of 114 P. litoralis specimens collected from North America, Africa, Australia and Oceania, Europe and Asia were used. The phylogenetic analyses revealed deeply divergent mitochondrial lineages and a high level of genetic diversity among P. litoralis populations. Both single and multi-locus species delimitation analyses yielded several molecular operational taxonomic units. Therefore, due to the homogeneity of morphological characteristics, it is likely that the morphospecies P. litoralis is a complex of four or more cryptic species, suggesting that more sampling is required and that the population structure genetic data and gene flow need to be investigated.}, } @article {pmid38243701, year = {2024}, author = {Gangavarapu, K and Ji, X and Baele, G and Fourment, M and Lemey, P and Matsen, FA and Suchard, MA}, title = {Many-core algorithms for high-dimensional gradients on phylogenetic trees.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {2}, pages = {}, pmid = {38243701}, issn = {1367-4811}, support = {R01 AI153044/AI/NIAID NIH HHS/United States ; R01 AI162611/AI/NIAID NIH HHS/United States ; U19 AI135995/AI/NIAID NIH HHS/United States ; R01 AI153044/NH/NIH HHS/United States ; }, mesh = {Phylogeny ; *Software ; Bayes Theorem ; *Algorithms ; Codon ; Nucleotides ; }, abstract = {MOTIVATION: Advancements in high-throughput genomic sequencing are delivering genomic pathogen data at an unprecedented rate, positioning statistical phylogenetics as a critical tool to monitor infectious diseases globally. This rapid growth spurs the need for efficient inference techniques, such as Hamiltonian Monte Carlo (HMC) in a Bayesian framework, to estimate parameters of these phylogenetic models where the dimensions of the parameters increase with the number of sequences N. HMC requires repeated calculation of the gradient of the data log-likelihood with respect to (wrt) all branch-length-specific (BLS) parameters that traditionally takes O(N2) operations using the standard pruning algorithm. A recent study proposes an approach to calculate this gradient in O(N), enabling researchers to take advantage of gradient-based samplers such as HMC. The CPU implementation of this approach makes the calculation of the gradient computationally tractable for nucleotide-based models but falls short in performance for larger state-space size models, such as Markov-modulated and codon models. Here, we describe novel massively parallel algorithms to calculate the gradient of the log-likelihood wrt all BLS parameters that take advantage of graphics processing units (GPUs) and result in many fold higher speedups over previous CPU implementations.

RESULTS: We benchmark these GPU algorithms on three computing systems using three evolutionary inference examples exploring complete genomes from 997 dengue viruses, 62 carnivore mitochondria and 49 yeasts, and observe a >128-fold speedup over the CPU implementation for codon-based models and >8-fold speedup for nucleotide-based models. As a practical demonstration, we also estimate the timing of the first introduction of West Nile virus into the continental Unites States under a codon model with a relaxed molecular clock from 104 full viral genomes, an inference task previously intractable.

We provide an implementation of our GPU algorithms in BEAGLE v4.0.0 (https://github.com/beagle-dev/beagle-lib), an open-source library for statistical phylogenetics that enables parallel calculations on multi-core CPUs and GPUs. We employ a BEAGLE-implementation using the Bayesian phylogenetics framework BEAST (https://github.com/beast-dev/beast-mcmc).}, } @article {pmid38255908, year = {2024}, author = {Mirra, S and Marfany, G}, title = {From Beach to the Bedside: Harnessing Mitochondrial Function in Human Diseases Using New Marine-Derived Strategies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {2}, pages = {}, pmid = {38255908}, issn = {1422-0067}, support = {PID2022-140957OB-I00//Ministerio de Ciencia e Innovación/ ; 2021SGR-01093//Government of Catalonia/ ; }, mesh = {Humans ; *Ecosystem ; *Mitochondria ; Cell Death ; Eukaryotic Cells ; Oxidative Stress ; }, abstract = {Mitochondria are double-membrane organelles within eukaryotic cells that act as cellular power houses owing to their ability to efficiently generate the ATP required to sustain normal cell function. Also, they represent a "hub" for the regulation of a plethora of processes, including cellular homeostasis, metabolism, the defense against oxidative stress, and cell death. Mitochondrial dysfunctions are associated with a wide range of human diseases with complex pathologies, including metabolic diseases, neurodegenerative disorders, and cancer. Therefore, regulating dysfunctional mitochondria represents a pivotal therapeutic opportunity in biomedicine. Marine ecosystems are biologically very diversified and harbor a broad range of organisms, providing both novel bioactive substances and molecules with meaningful biomedical and pharmacological applications. Recently, many mitochondria-targeting marine-derived molecules have been described to regulate mitochondrial biology, thus exerting therapeutic effects by inhibiting mitochondrial abnormalities, both in vitro and in vivo, through different mechanisms of action. Here, we review different strategies that are derived from marine organisms which modulate specific mitochondrial processes or mitochondrial molecular pathways and ultimately aim to find key molecules to treat a wide range of human diseases characterized by impaired mitochondrial function.}, } @article {pmid38258637, year = {2024}, author = {Li, X and Li, W and Huo, J and Li, L and Chen, B and Guo, Z and Ma, Z}, title = {[Identification and expression analysis of citrate synthase 3 gene family members in apple].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {40}, number = {1}, pages = {137-149}, doi = {10.13345/j.cjb.230166}, pmid = {38258637}, issn = {1872-2075}, mesh = {*Citric Acid ; *Malus/genetics ; Citrate (si)-Synthase ; Phylogeny ; Citrates ; }, abstract = {As one of the key enzymes in cell metabolism, the activity of citrate synthase 3 (CS3) regulates the substance and energy metabolism of organisms. The protein members of CS3 family were identified from the whole genome of apple, and bioinformatics analysis was performed and expression patterns were analyzed to provide a theoretical basis for studying the potential function of CS3 gene in apple. BLASTp was used to identify members of the apple CS3 family based on the GDR database, and the basic information of CS3 protein sequence, subcellular localization, domain composition, phylogenetic relationship and chromosome localization were analyzed by Pfam, SMART, MEGA5.0, clustalx.exe, ExPASy Proteomics Server, MEGAX, SOPMA, MEME, WoLF PSORT and other software. The tissue expression and inducible expression characteristics of 6 CS3 genes in apple were determined by acid content and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Apple CS3 gene family contains 6 members, and these CS3 proteins contain 473-608 amino acid residues, with isoelectric point distribution between 7.21 and 8.82. Subcellular localization results showed that CS3 protein was located in mitochondria and chloroplasts, respectively. Phylogenetic analysis divided them into 3 categories, and the number of genes in each subfamily was 2. Chromosome localization analysis showed that CS3 gene was distributed on different chromosomes of apple. The secondary structure of protein is mainly α-helix, followed by random curling, and the proportion of β-angle is the smallest. The 6 members were all expressed in different apple tissues. The overall expression trend from high to low was the highest relative expression content of MdCS3.4, followed by MdCS3.6, and the relative expression level of other members was in the order of MdCS3.3 > MdCS3.2 > MdCS3.1 > MdCS3.5. qRT-PCR results showed that MdCS3.1 and MdCS3.3 genes had the highest relative expression in the pulp of 'Chengji No. 1' with low acid content, and MdCS3.2 and MdCS3.3 genes in the pulp of 'Asda' with higher acid content had the highest relative expression. Therefore, in this study, the relative expression of CS3 gene in apple cultivars with different acid content in different apple varieties was detected, and its role in apple fruit acid synthesis was analyzed. The experimental results showed that the relative expression of CS3 gene in different apple varieties was different, which provided a reference for the subsequent study of the quality formation mechanism of apple.}, } @article {pmid38259100, year = {2024}, author = {Zhang, Y and Li, H and Wang, Y and Nie, M and Zhang, K and Pan, J and Zhang, Y and Ye, Z and Zufall, RA and Lynch, M and Long, H}, title = {Mitogenomic architecture and evolution of the soil ciliates Colpoda.}, journal = {mSystems}, volume = {9}, number = {2}, pages = {e0116123}, pmid = {38259100}, issn = {2379-5077}, support = {R35 GM122566/GM/NIGMS NIH HHS/United States ; }, mesh = {Evolution, Molecular ; Soil ; Phylogeny ; Genomics ; *Genome, Mitochondrial/genetics ; *Ciliophora/genetics ; }, abstract = {Colpoda are cosmopolitan unicellular eukaryotes primarily inhabiting soil and benefiting plant growth, but they remain one of the least understood taxa in genetics and genomics within the realm of ciliated protozoa. Here, we investigate the architecture of de novo assembled mitogenomes of six Colpoda species, using long-read sequencing and involving 36 newly isolated natural strains in total. The mitogenome sizes span from 43 to 63 kbp and typically contain 28-33 protein-coding genes. They possess a linear structure with variable telomeres and central repeats, with one Colpoda elliotti strain isolated from Tibet harboring the longest telomeres among all studied ciliates. Phylogenomic analyses reveal that Colpoda species started to diverge more than 326 million years ago, eventually evolving into two distinct groups. Collinearity analyses also reveal significant genomic divergences and a lack of long collinear blocks. One of the most notable features is the exceptionally high level of gene rearrangements between mitochondrial genomes of different Colpoda species, dominated by gene loss events. Population-level mitogenomic analysis on natural strains also demonstrates high sequence divergence, regardless of geographic distance, but the gene order remains highly conserved within species, offering a new species identification criterion for Colpoda species. Furthermore, we identified underlying heteroplasmic sites in the majority of strains of three Colpoda species, albeit without a discernible recombination signal to account for this heteroplasmy. This comprehensive study systematically unveils the mitogenomic structure and evolution of these ancient and ecologically significant Colpoda ciliates, thus laying the groundwork for a deeper understanding of the evolution of unicellular eukaryotes.IMPORTANCEColpoda, one of the most widespread ciliated protozoa in soil, are poorly understood in regard to their genetics and evolution. Our research revealed extreme mitochondrial gene rearrangements dominated by gene loss events, potentially leading to the streamlining of Colpoda mitogenomes. Surprisingly, while interspecific rearrangements abound, our population-level mitogenomic study revealed a conserved gene order within species, offering a potential new identification criterion. Phylogenomic analysis traced their lineage over 326 million years, revealing two distinct groups. Substantial genomic divergence might be associated with the lack of extended collinear blocks and relaxed purifying selection. This study systematically reveals Colpoda ciliate mitogenome structures and evolution, providing insights into the survival and evolution of these vital soil microorganisms.}, } @article {pmid38261394, year = {2024}, author = {Sequeira, AN and O'Keefe, IP and Katju, V and Bergthorsson, U}, title = {Friend turned foe: selfish behavior of a spontaneously arising mitochondrial deletion in an experimentally evolved Caenorhabditis elegans population.}, journal = {G3 (Bethesda, Md.)}, volume = {14}, number = {4}, pages = {}, pmid = {38261394}, issn = {2160-1836}, support = {MCB-1817762//National Science Foundation/ ; //Department of Veterinary Integrative Biosciences/ ; //College of Veterinary Medicine and Biomedical Sciences, Texas A and M University/ ; }, mesh = {Animals ; Humans ; *Caenorhabditis elegans/genetics ; Friends ; Mitochondria/genetics ; DNA, Mitochondrial/genetics ; Mutation ; *Genome, Mitochondrial ; }, abstract = {Selfish mitochondrial DNA (mtDNA) mutations are variants that can proliferate within cells and enjoy a replication or transmission bias without fitness benefits for the host. mtDNA deletions in Caenorhabditis elegans can reach high heteroplasmic frequencies despite significantly reducing fitness, illustrating how new mtDNA variants can give rise to genetic conflict between different levels of selection and between the nuclear and mitochondrial genomes. During a mutation accumulation experiment in C. elegans, a 1,034-bp deletion originated spontaneously and reached an 81.7% frequency within an experimental evolution line. This heteroplasmic mtDNA deletion, designated as meuDf1, eliminated portions of 2 protein-coding genes (coxIII and nd4) and tRNA-thr in entirety. mtDNA copy number in meuDf1 heteroplasmic individuals was 35% higher than in individuals with wild-type mitochondria. After backcrossing into a common genetic background, the meuDf1 mitotype was associated with reduction in several fitness traits and independent competition experiments found a 40% reduction in composite fitness. Experiments that relaxed individual selection by single individual bottlenecks demonstrated that the deletion-bearing mtDNA possessed a strong transmission bias, thereby qualifying it as a novel selfish mitotype.}, } @article {pmid38262211, year = {2024}, author = {Tang, W and Li, X and Ye, B and Shi, B and Zhang, H and Dang, Z and Sun, Y and Danqu, L and Xia, C and Quzhen, D and Zhao, X and Chui, W and Huang, F}, title = {Characterization of the complete mitochondrial genome and phylogenetic analyses of Haemaphysalis tibetensis Hoogstraal, 1965 (Acari: Ixodidae).}, journal = {Ticks and tick-borne diseases}, volume = {15}, number = {2}, pages = {102311}, doi = {10.1016/j.ttbdis.2024.102311}, pmid = {38262211}, issn = {1877-9603}, mesh = {Animals ; Humans ; Phylogeny ; *Ixodidae ; *Genome, Mitochondrial ; RNA, Ribosomal/genetics ; Tibet ; }, abstract = {Ticks are specialized ectoparasites that feed on blood, causing physical harm to the host and facilitating pathogen transmission. The genus Haemaphysalis contains vectors for numerous infectious agents. These agents cause various diseases in humans and animals. Mitochondrial genome sequences serve as reliable molecular markers, forming a crucial basis for evolutionary analyses, studying species origins, and exploring molecular phylogeny. We extracted mitochondrial genome from the enriched mitochondria of Haemaphysalis tibetensis and obtained a 14,714-bp sequence. The mitochondrial genome consists of 13 protein-coding genes (PCGs), two ribosomal RNA, 22 transfer RNAs (tRNAs), and two control regions. The nucleotide composition of H. tibetensis mitochondrial genome was 38.38 % for A, 9.61 % for G, 39.32 % for T, and 12.69 % for C. The A + T content of H. tibetensis mitochondrial genome was 77.7 %, significantly higher than the G + C content. The repeat units of H. tibetensis exhibited two identical repeat units of 33 bp in length, positioned downstream of nad1 and rrnL genes. Furthermore, phylogenetic analyses based on the 13 PCGs indicated that Haemaphysalis tibetensis (subgenus Allophysalis) formed a monophyletic clade with Haemaphysalis nepalensis (subgenus Herpetobia) and Haemaphysalis danieli (subgenus Allophysalis). Although the species Haemaphysalis inermis, Haemaphysalis kitaokai, Haemaphysalis kolonini, and Haemaphysalis colasbelcouri belong to the subgenus Alloceraea, which were morphologically primitive hemaphysalines just like H. tibetensis, these four tick species cannot form a single clade with H. tibetensis. In this study, the whole mitochondrial genome sequence of H. tibetensis from Tibet was obtained, which enriched the mitochondrial genome data of ticks and provided genetic markers to study the population heredity and molecular evolution of the genus Haemaphysalis.}, } @article {pmid38262350, year = {2024}, author = {Eglit, Y and Shiratori, T and Jerlström-Hultqvist, J and Williamson, K and Roger, AJ and Ishida, KI and Simpson, AGB}, title = {Meteora sporadica, a protist with incredible cell architecture, is related to Hemimastigophora.}, journal = {Current biology : CB}, volume = {34}, number = {2}, pages = {451-459.e6}, doi = {10.1016/j.cub.2023.12.032}, pmid = {38262350}, issn = {1879-0445}, mesh = {Phylogeny ; *Eukaryota ; *Eukaryotic Cells ; Flagella ; Microscopy, Electron, Transmission ; }, abstract = {"Kingdom-level" branches are being added to the tree of eukaryotes at a rate approaching one per year, with no signs of slowing down.[1][,][2][,][3][,][4] Some are completely new discoveries, whereas others are morphologically unusual protists that were previously described but lacked molecular data. For example, Hemimastigophora are predatory protists with two rows of flagella that were known since the 19[th] century but proved to represent a new deep-branching eukaryote lineage when phylogenomic analyses were conducted.[2]Meteora sporadica[5] is a protist with a unique morphology; cells glide over substrates along a long axis of anterior and posterior projections while a pair of lateral "arms" swing back and forth, a motility system without any obvious parallels. Originally, Meteora was described by light microscopy only, from a short-term enrichment of deep-sea sediment. A small subunit ribosomal RNA (SSU rRNA) sequence was reported recently, but the phylogenetic placement of Meteora remained unresolved.[6] Here, we investigated two cultivated Meteora sporadica isolates in detail. Transmission electron microscopy showed that both the anterior-posterior projections and the arms are supported by microtubules originating from a cluster of subnuclear microtubule organizing centers (MTOCs). Neither have a flagellar axoneme-like structure. Sequencing the mitochondrial genome showed this to be among the most gene-rich known, outside jakobids. Remarkably, phylogenomic analyses of 254 nuclear protein-coding genes robustly support a close relationship with Hemimastigophora. Our study suggests that Meteora and Hemimastigophora together represent a morphologically diverse "supergroup" and thus are important for resolving the tree of eukaryote life and early eukaryote evolution.}, } @article {pmid38267054, year = {2024}, author = {Takusagawa, M and Misumi, O and Nozaki, H and Kato, S and Maruyama, S and Tsujimoto-Inui, Y and Yagisawa, F and Ohnuma, M and Kuroiwa, H and Kuroiwa, T and Matsunaga, S}, title = {Complete mitochondrial and chloroplast DNA sequences of the freshwater green microalga Medakamo hakoo.}, journal = {Genes & genetic systems}, volume = {98}, number = {6}, pages = {353-360}, doi = {10.1266/ggs.23-00275}, pmid = {38267054}, issn = {1880-5779}, mesh = {DNA, Chloroplast/genetics ; *Microalgae ; Mitochondria/genetics ; *Genome, Mitochondrial ; Chloroplasts/genetics ; *Chlorophyta/genetics ; Fresh Water ; Phylogeny ; DNA, Mitochondrial/genetics ; }, abstract = {We report the complete organellar genome sequences of an ultrasmall green alga, Medakamo hakoo strain M-hakoo 311, which has the smallest known nuclear genome in freshwater green algae. Medakamo hakoo has 90.8-kb chloroplast and 36.5-kb mitochondrial genomes containing 80 and 33 putative protein-coding genes, respectively. The mitochondrial genome is the smallest in the Trebouxiophyceae algae studied so far. The GC content of the nuclear genome is 73%, but those of chloroplast and mitochondrial genomes are 41% and 35%, respectively. Codon usages in the organellar genomes have a different tendency from that in the nuclear genome. The organellar genomes have unique characteristics, such as the biased encoding of mitochondrial genes on a single strand and the absence of operon structures in chloroplast ribosomal genes. Medakamo hakoo will be helpful for understanding the evolution of the organellar genome and the regulation of gene expression in chloroplasts and mitochondria.}, } @article {pmid38267606, year = {2024}, author = {Sloan, DB and Conover, JL and Grover, CE and Wendel, JF and Sharbrough, J}, title = {Polyploid plants take cytonuclear perturbations in stride.}, journal = {The Plant cell}, volume = {36}, number = {4}, pages = {829-839}, pmid = {38267606}, issn = {1532-298X}, support = {IOS-1829176//National Science Foundation/ ; IOS-2209085//Postdoctoral Research Fellowship in Biology/ ; }, mesh = {*Cell Nucleus/genetics/metabolism ; *Polyploidy ; Plastids/genetics/metabolism ; Mitochondria/genetics ; Hybridization, Genetic ; Genome, Plant/genetics ; Evolution, Molecular ; }, abstract = {Hybridization in plants is often accompanied by nuclear genome doubling (allopolyploidy), which has been hypothesized to perturb interactions between nuclear and organellar (mitochondrial and plastid) genomes by creating imbalances in the relative copy number of these genomes and producing genetic incompatibilities between maternally derived organellar genomes and the half of the allopolyploid nuclear genome from the paternal progenitor. Several evolutionary responses have been predicted to ameliorate these effects, including selection for changes in protein sequences that restore cytonuclear interactions; biased gene retention/expression/conversion favoring maternal nuclear gene copies; and fine-tuning of relative cytonuclear genome copy numbers and expression levels. Numerous recent studies, however, have found that evolutionary responses are inconsistent and rarely scale to genome-wide generalities. The apparent robustness of plant cytonuclear interactions to allopolyploidy may reflect features that are general to allopolyploids such as the lack of F2 hybrid breakdown under disomic inheritance, and others that are more plant-specific, including slow sequence divergence in organellar genomes and preexisting regulatory responses to changes in cell size and endopolyploidy during development. Thus, cytonuclear interactions may only rarely act as the main barrier to establishment of allopolyploid lineages, perhaps helping to explain why allopolyploidy is so pervasive in plant evolution.}, } @article {pmid38271287, year = {2024}, author = {Harada, R and Hirakawa, Y and Yabuki, A and Kim, E and Yazaki, E and Kamikawa, R and Nakano, K and Eliáš, M and Inagaki, Y}, title = {Encyclopedia of Family A DNA Polymerases Localized in Organelles: Evolutionary Contribution of Bacteria Including the Proto-Mitochondrion.}, journal = {Molecular biology and evolution}, volume = {41}, number = {2}, pages = {}, pmid = {38271287}, issn = {1537-1719}, support = {18KK0203//Japan Society for Promotion of Sciences projects/ ; 21-19664S//Czech Science Foundation/ ; //National Institute for Environmental Studies/ ; //Ministry of Education, Culture, Sports, Science and Technology/ ; //National Institute of Genetics/ ; //University of Tsukuba/ ; }, mesh = {*Organelles/genetics ; Phylogeny ; DNA-Directed DNA Polymerase/genetics ; Plastids/genetics ; Mitochondria ; *Cyanobacteria/genetics ; Symbiosis ; }, abstract = {DNA polymerases synthesize DNA from deoxyribonucleotides in a semiconservative manner and serve as the core of DNA replication and repair machinery. In eukaryotic cells, there are 2 genome-containing organelles, mitochondria, and plastids, which were derived from an alphaproteobacterium and a cyanobacterium, respectively. Except for rare cases of genome-lacking mitochondria and plastids, both organelles must be served by nucleus-encoded DNA polymerases that localize and work in them to maintain their genomes. The evolution of organellar DNA polymerases has yet to be fully understood because of 2 unsettled issues. First, the diversity of organellar DNA polymerases has not been elucidated in the full spectrum of eukaryotes. Second, it is unclear when the DNA polymerases that were used originally in the endosymbiotic bacteria giving rise to mitochondria and plastids were discarded, as the organellar DNA polymerases known to date show no phylogenetic affinity to those of the extant alphaproteobacteria or cyanobacteria. In this study, we identified from diverse eukaryotes 134 family A DNA polymerase sequences, which were classified into 10 novel types, and explored their evolutionary origins. The subcellular localizations of selected DNA polymerases were further examined experimentally. The results presented here suggest that the diversity of organellar DNA polymerases has been shaped by multiple transfers of the PolI gene from phylogenetically broad bacteria, and their occurrence in eukaryotes was additionally impacted by secondary plastid endosymbioses. Finally, we propose that the last eukaryotic common ancestor may have possessed 2 mitochondrial DNA polymerases, POP, and a candidate of the direct descendant of the proto-mitochondrial DNA polymerase I, rdxPolA, identified in this study.}, } @article {pmid38271341, year = {2024}, author = {Serrano, MJ and Goudet, J and Cumer, T}, title = {Characterization of the diversity of barn owl's mitochondrial genome reveals high copy number variations in the control region.}, journal = {PloS one}, volume = {19}, number = {1}, pages = {e0295595}, pmid = {38271341}, issn = {1932-6203}, support = {31003A_179358/SNSF_/Swiss National Science Foundation/Switzerland ; 310030_215709/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {Animals ; Humans ; DNA Copy Number Variations ; *Strigiformes/genetics ; *Genome, Mitochondrial ; Base Sequence ; Tandem Repeat Sequences/genetics ; }, abstract = {Mitochondria are known to play an essential role in the cell. These organelles contain their own DNA, which is divided in a coding and non-coding region (NCR). While much of the NCR's function is unknown, tandem repeats have been observed in several vertebrates, with extreme intra-individual, intraspecific and interspecific variation. Taking advantage of a new complete reference for the mitochondrial genome of the Afro-European Barn Owl (Tyto alba), as well as 172 whole genome-resequencing; we (i) describe the reference mitochondrial genome with a special focus on the repeats in the NCR, (ii) quantify the variation in number of copies between individuals, and (iii) explore the possible factors associated with the variation in the number of repetitions. The reference mitochondrial genome revealed a long (256bp) and a short (80bp) tandem repeat in the NCR region. The re-sequenced genomes showed a great variation in number of copies between individuals, with 4 to 38 copies of the Long and 6 to 135 copies of the short repeat. Among the factors associated with this variation between individuals, the tissue used for extraction was the most significant. The exact mechanisms of the formations of these repeats are still to be discovered and understanding them will help explain the maintenance of the polymorphism in the number of copies, as well as their interactions with the metabolism, the aging and health of the individuals.}, } @article {pmid38271822, year = {2024}, author = {Alcantara da Silva, JV and Ispada, J and Nociti, RP and da Fonseca Junior, AM and de Lima, CB and Dos Santos, EC and Chiaratti, MR and Milazzotto, MP}, title = {The central role of pyruvate metabolism on the epigenetic maturation and transcriptional profile of bovine oocytes.}, journal = {Reproduction (Cambridge, England)}, volume = {167}, number = {4}, pages = {}, doi = {10.1530/REP-23-0181}, pmid = {38271822}, issn = {1741-7899}, mesh = {Animals ; Cattle ; Female ; *In Vitro Oocyte Maturation Techniques/veterinary/methods ; Acetyl Coenzyme A/metabolism ; *Histones/metabolism ; Oocytes/metabolism ; Pyruvic Acid/pharmacology/metabolism ; Epigenesis, Genetic ; Cumulus Cells ; }, abstract = {IN BRIEF: Pyruvate metabolism is one of the main metabolic pathways during oocyte maturation. This study demonstrates that pyruvate metabolism also regulates the epigenetic and molecular maturation in bovine oocytes.

ABSTRACT: Pyruvate, the final product of glycolysis, undergoes conversion into acetyl-CoA within the mitochondria of oocytes, serving as a primary fuel source for the tricarboxylic acid (TCA) cycle. The citrate generated in the TCA cycle can be transported to the cytoplasm and converted back into acetyl-CoA. This acetyl-CoA can either fuel lipid synthesis or act as a substrate for histone acetylation. This study aimed to investigate how pyruvate metabolism influences lysine 9 histone 3 acetylation (H3K9ac) dynamics and RNA transcription in bovine oocytes during in vitro maturation (IVM). Bovine cumulus-oocyte complexes were cultured in vitro for 24 h, considering three experimental groups: Control (IVM medium only), DCA (IVM supplemented with sodium dichloroacetate, a stimulant of pyruvate oxidation into acetyl-CoA), or IA (IVM supplemented with sodium iodoacetate, a glycolysis inhibitor). The results revealed significant alterations in oocyte metabolism in both treatments, promoting the utilization of lipids as an energy source. These changes during IVM affected the dynamics of H3K9ac, subsequently influencing the oocyte's transcriptional activity. In the DCA and IA groups, a total of 148 and 356 differentially expressed genes were identified, respectively, compared to the control group. These findings suggest that modifications in pyruvate metabolism trigger the activation of metabolic pathways, particularly lipid metabolism, changing acetyl-CoA availability and H3K9ac levels, ultimately impacting the mRNA content of in vitro matured bovine oocytes.}, } @article {pmid38273274, year = {2024}, author = {Butenko, A and Lukeš, J and Speijer, D and Wideman, JG}, title = {Mitochondrial genomes revisited: why do different lineages retain different genes?.}, journal = {BMC biology}, volume = {22}, number = {1}, pages = {15}, pmid = {38273274}, issn = {1741-7007}, support = {DBI-2119963//Division of Biological Infrastructure/ ; 23-07695S//Grantová Agentura České Republiky/ ; 23-06479X//Grantová Agentura České Republiky/ ; }, mesh = {*Genome, Mitochondrial ; Evolution, Molecular ; Eukaryota/genetics ; Mitochondria/genetics ; Base Sequence ; Phylogeny ; }, abstract = {The mitochondria contain their own genome derived from an alphaproteobacterial endosymbiont. From thousands of protein-coding genes originally encoded by their ancestor, only between 1 and about 70 are encoded on extant mitochondrial genomes (mitogenomes). Thanks to a dramatically increasing number of sequenced and annotated mitogenomes a coherent picture of why some genes were lost, or relocated to the nucleus, is emerging. In this review, we describe the characteristics of mitochondria-to-nucleus gene transfer and the resulting varied content of mitogenomes across eukaryotes. We introduce a 'burst-upon-drift' model to best explain nuclear-mitochondrial population genetics with flares of transfer due to genetic drift.}, } @article {pmid38275595, year = {2023}, author = {Li, K and Yu, SW and Hu, H and Feng, YF and Storey, KB and Ma, Y and Zhang, JY and Yu, DN}, title = {The Phylogenetic Relationship of Lamiinae (Coleoptera: Cerambycidae) Using Mitochondrial Genomes.}, journal = {Genes}, volume = {15}, number = {1}, pages = {}, pmid = {38275595}, issn = {2073-4425}, support = {LY23C040002//the Natural Science Foundation of Zhejiang Province/ ; }, mesh = {Animals ; Phylogeny ; *Genome, Mitochondrial ; *Coleoptera/genetics ; Bayes Theorem ; Mitochondria/genetics ; }, abstract = {Lamiinae is the largest subfamily of the Cerambycidae (longhorn beetles), with approximately 21,863 described species. Previous phylogenetic studies of Lamiinae showed that this subfamily was monophyletic, but the relationship between the tribes of Lamiinae is still controversial. Partial molecular data and species morphological characteristics are not sufficient to resolve species phylogenetic studies perfectly. At the same time, the full mitochondrial genome contains more comprehensive genetic data. Benefiting from the development of next-generation sequencing (NGS), mitochondrial genomes can be easily acquired and used as reliable molecular markers to investigate phylogenetic relationships within Cerambycidae. Using NGS technology, we obtained 11 mitochondrial genome sequences of Lamiinae species. Based on this newly generated mitochondrial genome dataset matrix, we reconstructed the phylogeny of Lamiinae. The Bayesian Inference and Maximum Likelihood analyses strongly support the monophyly of four tribes (Lamiini, Batocerini, Mesosini, and Saperdini), whereas the tribe Acanthocinini was identified as paraphyletic. Other mitochondrial structural features were also observed: the start codon in the nad1 gene of all 11 mitochondrial genomes is TTG; 17-22 bp intergenic spacers (IGS) with a 'TACTA' motif were found between trnS2 and nad1. Moreover, two long IGS were found in Mesosa myops and Batocera sp. Tandem repeats were found in the IGS of Batocera sp.}, } @article {pmid38288498, year = {2024}, author = {Meng, X and Wang, D and Pang, Q and Wang, H and Zhou, H}, title = {Multiple independent origins of duplicated mitochondrial control regions indicate an apomorphy in the Thysanoptera (Insecta).}, journal = {Archives of insect biochemistry and physiology}, volume = {115}, number = {1}, pages = {e22087}, doi = {10.1002/arch.22087}, pmid = {38288498}, issn = {1520-6327}, support = {2021YFD1400200//National Key R&D program of China/ ; }, mesh = {Animals ; *Thysanoptera/genetics ; Evolution, Molecular ; Phylogeny ; Mitochondria/genetics ; Gene Rearrangement ; DNA, Mitochondrial/genetics ; }, abstract = {The mitochondrial genome (mitogenome) of thrips is characterized by the presence of control region (CR) duplication. However, the evolution pattern of duplicated CRs in thrips is still unclear. In this study, the multiple independent origins of duplicated CR indicated that the CR duplication was not an ancestral state for Thysanoptera. The macroevolutionary pattern suggested that the earliest CR duplication event occurred in the middle Cretaceous (94.85 Ma) coincided with rearrangement events forming the ancestors of Aeolothripidae, but much later than that forming the ancestors of the suborder Terebrantia. The mitogenome with duplicated CRs showed a higher rate of gene rearrangement. The sequence similarity of the CR copies and divergence time were negatively correlated, indicating age-related deterioration of mitochondrial function. No significant differences were found in the mitochondrial DNA, the P123 and P4FD between the single and multiple-CR charactered mitogenomes, which suggested that the duplicated CRs may not affect the replication process in thrip mitogenome. The mitogenomes with duplicated CRs (mean: 0.0088 subs/s/my) show a significantly increased evolutionary rate than that with a single one (mean: 0.0058 subs/s/my). However, it seems that this higher evolutionary rate did not have adaptive mechanisms in Terebrantia. We speculated that the duplicated CRs may cause a more intense production of energy by mitochondria, and an accelerated mutation and substitution rate is expected in such mitogenomes. Our study provided new insights into the presence of CR duplications and their evolution in the mitogenomes of thrips.}, } @article {pmid38290047, year = {2024}, author = {Cao, J and Luo, Y and Chen, Y and Wu, Z and Zhang, J and Wu, Y and Hu, W}, title = {Maternal mitochondrial function affects paternal mitochondrial inheritance in Drosophila.}, journal = {Genetics}, volume = {226}, number = {4}, pages = {}, pmid = {38290047}, issn = {1943-2631}, support = {32160177//National Natural Science Foundation of China/ ; }, mesh = {Male ; Animals ; *DNA, Mitochondrial/genetics ; *Drosophila/genetics ; Genes, Mitochondrial ; Drosophila melanogaster/genetics ; Mitochondria/genetics ; }, abstract = {The maternal inheritance of mitochondria is a widely accepted paradigm, and mechanisms that prevent paternal mitochondria transmission to offspring during spermatogenesis and postfertilization have been described. Although certain species do retain paternal mitochondria, the factors affecting paternal mitochondria inheritance in these cases are unclear. More importantly, the evolutionary benefit of retaining paternal mitochondria and their ultimate fate are unknown. Here we show that transplanted exogenous paternal D. yakuba mitochondria can be transmitted to offspring when maternal mitochondria are dysfunctional in D. melanogaster. Furthermore, we show that the preserved paternal mitochondria are functional, and can be stably inherited, such that the proportion of paternal mitochondria increases gradually in subsequent generations. Our work has important implications that paternal mitochondria inheritance should not be overlooked as a genetic phenomenon in evolution, especially when paternal mitochondria are of significant differences from the maternal mitochondria or the maternal mitochondria are functionally abnormal. Our results improve the understanding of mitochondrial inheritance and provide a new model system for its study.}, } @article {pmid38291287, year = {2024}, author = {Li, X and Zhu, Y and Ruiz-Lozano, P and Wei, K}, title = {Mitochondrial-to-nuclear communications through multiple routes regulate cardiomyocyte proliferation.}, journal = {Cell regeneration (London, England)}, volume = {13}, number = {1}, pages = {2}, pmid = {38291287}, issn = {2045-9769}, support = {2018YFA0800104//Ministry of Science and Technology of the People's Republic of China/ ; 92168205//National Natural Science Foundation of China/ ; 32070823//National Natural Science Foundation of China/ ; 22120230471//Fundamental Research Funds for the Central Universities/ ; }, abstract = {The regenerative capacity of the adult mammalian heart remains a formidable challenge in biological research. Despite extensive investigations into the loss of regenerative potential during evolution and development, unlocking the mechanisms governing cardiomyocyte proliferation remains elusive. Two recent groundbreaking studies have provided fresh perspectives on mitochondrial-to-nuclear communication, shedding light on novel factors that regulate cardiomyocyte proliferation. The studies identified two mitochondrial processes, fatty acid oxidation and protein translation, as key players in restricting cardiomyocyte proliferation. Inhibition of these processes led to increased cell cycle activity in cardiomyocytes, mediated by reduction in H3k4me3 levels through accumulated α-ketoglutarate (αKG), and activation of the mitochondrial unfolded protein response (UPR[mt]), respectively. In this research highlight, we discuss the novel insights into mitochondrial-to-nuclear communication presented in these studies, the broad implications in cardiomyocyte biology and cardiovascular diseases, as well as the intriguing scientific questions inspired by the studies that may facilitate future investigations into the detailed molecular mechanisms of cardiomyocyte metabolism, proliferation, and mitochondrial-to-nuclear communications.}, } @article {pmid38305563, year = {2024}, author = {McCallum, Q and Askelson, K and Fogarty, FF and Natola, L and Nikelski, E and Huang, A and Irwin, D}, title = {Pronounced differentiation on the Z chromosome and parts of the autosomes in crowned sparrows contrasts with mitochondrial paraphyly: implications for speciation.}, journal = {Journal of evolutionary biology}, volume = {37}, number = {2}, pages = {171-188}, doi = {10.1093/jeb/voae004}, pmid = {38305563}, issn = {1420-9101}, support = {RGPIN-2017-03919//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Animals ; *Sparrows/genetics ; Genetics, Population ; Genetic Speciation ; Sex Chromosomes/genetics ; Gene Flow ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; }, abstract = {When a single species evolves into multiple descendent species, some parts of the genome can play a key role in the evolution of reproductive isolation while other parts flow between the evolving species via interbreeding. Genomic evolution during the speciation process is particularly interesting when major components of the genome-for instance, sex chromosomes vs. autosomes vs. mitochondrial DNA-show widely differing patterns of relationships between three diverging populations. The golden-crowned sparrow (Zonotrichia atricapilla) and the white-crowned sparrow (Zonotrichia leucophrys) are phenotypically differentiated sister species that are largely reproductively isolated despite possessing similar mitochondrial genomes, likely due to recent introgression. We assessed variation in more than 45,000 single nucleotide polymorphisms to determine the structure of nuclear genomic differentiation between these species and between two hybridizing subspecies of Z. leucophrys. The two Z. leucophrys subspecies show moderate levels of relative differentiation and patterns consistent with a history of recurrent selection in both ancestral and daughter populations, with much of the sex chromosome Z and a large region on the autosome 1A showing increased differentiation compared to the rest of the genome. The two species Z. leucophrys and Z. atricapilla show high relative differentiation and strong heterogeneity in the level of differentiation among various chromosomal regions, with a large portion of the sex chromosome (Z) showing highly divergent haplotypes between these species. Studies of speciation often emphasize mitochondrial DNA differentiation, but speciation between Z. atricapilla and Z. leucophrys appears primarily associated with Z chromosome divergence and more moderately associated with autosomal differentiation, whereas mitochondria are highly similar due apparently to recent introgression. These results add to the growing body of evidence for highly heterogeneous patterns of genomic differentiation during speciation, with some genomic regions showing a lack of gene flow between populations many hundreds of thousands of years before other genomic regions.}, } @article {pmid38307786, year = {2024}, author = {Muñoz-Gómez, SA}, title = {The energetic costs of cellular complexity in evolution.}, journal = {Trends in microbiology}, volume = {32}, number = {8}, pages = {746-755}, doi = {10.1016/j.tim.2024.01.003}, pmid = {38307786}, issn = {1878-4380}, mesh = {*Energy Metabolism ; *Biological Evolution ; Evolution, Molecular ; }, abstract = {The evolutionary history of cells has been marked by drastic increases in complexity. Some hypothesize that such cellular complexification requires a massive energy flux as the origin of new features is hypothetically more energetically costly than their evolutionary maintenance. However, it remains unclear how increases in cellular complexity demand more energy. I propose that the early evolution of new genes with weak functions imposes higher energetic costs by overexpression before their functions are evolutionarily refined. In the long term, the accumulation of new genes deviates resources away from growth and reproduction. Accrued cellular complexity further requires additional infrastructure for its maintenance. Altogether, this suggests that larger and more complex cells are defined by increased survival but lower reproductive capacity.}, } @article {pmid38309455, year = {2024}, author = {Miyakawa, Y and Otsuka, M and Shibata, C and Seimiya, T and Yamamoto, K and Ishibashi, R and Kishikawa, T and Tanaka, E and Isagawa, T and Takeda, N and Kamio, N and Imai, K and Fujishiro, M}, title = {Gut Bacteria-derived Membrane Vesicles Induce Colonic Dysplasia by Inducing DNA Damage in Colon Epithelial Cells.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {17}, number = {5}, pages = {745-767}, pmid = {38309455}, issn = {2352-345X}, mesh = {Mice ; Animals ; Humans ; *Colon/microbiology ; Reactive Oxygen Species ; Base Composition ; Phylogeny ; RNA, Ribosomal, 16S ; Sequence Analysis, DNA ; *Induced Pluripotent Stem Cells ; Epithelial Cells ; Bacteria/genetics ; }, abstract = {BACKGROUND & AIMS: Colorectal cancer (CRC) is the third most common cancer in the world. Gut microbiota has recently been implicated in the development of CRC. Actinomyces odontolyticus is one of the most abundant bacteria in the gut of patients with very early stages of CRC. A odontolyticus is an anaerobic bacterium existing principally in the oral cavity, similar to Fusobacterium nucleatum, which is known as a colon carcinogenic bacterium. Here we newly determined the biological functions of A odontolyticus on colonic oncogenesis.

METHODS: We examined the induction of intracellular signaling by A odontolyticus in human colonic epithelial cells (CECs). DNA damage levels in CECs were confirmed using the human induced pluripotent stem cell-derived gut organoid model and mouse colon tissues in vivo.

RESULTS: A odontolyticus secretes membrane vesicles (MVs), which induce nuclear factor kappa B signaling and also produce excessive reactive oxygen species (ROS) in colon epithelial cells. We found that A odontolyticus secretes lipoteichoic acid-rich MVs, promoting inflammatory signaling via TLR2. Simultaneously, those MVs are internalized into the colon epithelial cells, co-localize with the mitochondria, and cause mitochondrial dysfunction, resulting in excessive ROS production and DNA damage. Induction of excessive DNA damage in colonic cells by A odontolyticus-derived MVs was confirmed in the gut organoid model and also in mouse colon tissues.

CONCLUSIONS: A odontolyticus secretes MVs, which cause chronic inflammation and ROS production in colonic epithelial cells, leading to the initiation of CRC.}, } @article {pmid38316513, year = {2024}, author = {Liu, X and You, Q and Liu, M and Bo, C and Zhu, Y and Duan, Y and Xue, J and Wang, D and Xue, T}, title = {Assembly and comparative analysis of the complete mitochondrial genome of Pinellia ternata.}, journal = {Functional plant biology : FPB}, volume = {51}, number = {}, pages = {}, doi = {10.1071/FP23256}, pmid = {38316513}, issn = {1445-4416}, mesh = {*Pinellia/genetics ; *Genome, Mitochondrial/genetics ; Phylogeny ; *Plants, Medicinal/genetics ; Plant Tubers ; }, abstract = {Pinellia ternata is an important natural medicinal herb in China. However, it is susceptible to withering when exposed to high temperatures during growth, which limits its tuber production. Mitochondria usually function in stress response. The P . ternata mitochondrial (mt) genome has yet to be explored. Therefore, we integrated PacBio and Illumina sequencing reads to assemble and annotate the mt genome of P . ternata . The circular mt genome of P . ternata is 876 608bp in length and contains 38 protein-coding genes (PCGs), 20 tRNA genes and three rRNA genes. Codon usage, sequence repeats, RNA editing and gene migration from chloroplast (cp) to mt were also examined. Phylogenetic analysis based on the mt genomes of P . ternata and 36 other taxa revealed the taxonomic and evolutionary status of P . ternata . Furthermore, we investigated the mt genome size and GC content by comparing P . ternata with the other 35 species. An evaluation of non-synonymous substitutions and synonymous substitutions indicated that most PCGs in the mt genome underwent negative selection. Our results provide comprehensive information on the P . ternata mt genome, which may facilitate future research on the high-temperature response of P . ternata and provide new molecular insights on the Araceae family.}, } @article {pmid38325701, year = {2024}, author = {Wang, C and Yu, X and Wang, J and Zhao, Z and Wan, J}, title = {Genetic and molecular mechanisms of reproductive isolation in the utilization of heterosis for breeding hybrid rice.}, journal = {Journal of genetics and genomics = Yi chuan xue bao}, volume = {51}, number = {6}, pages = {583-593}, doi = {10.1016/j.jgg.2024.01.007}, pmid = {38325701}, issn = {1673-8527}, mesh = {*Oryza/genetics ; *Hybrid Vigor/genetics ; *Reproductive Isolation ; *Plant Breeding/methods ; *Hybridization, Genetic ; Mitochondria/genetics ; }, abstract = {Heterosis, also known as hybrid vigor, is commonly observed in rice crosses. The hybridization of rice species or subspecies exhibits robust hybrid vigor, however, the direct harnessing of this vigor is hindered by reproductive isolation. Here, we review recent advances in the understanding of the molecular mechanisms governing reproductive isolation in inter-subspecific and inter-specific hybrids. This review encompasses the genetic model of reproductive isolation within and among Oryza sativa species, emphasizing the essential role of mitochondria in this process. Additionally, we delve into the molecular intricacies governing the interaction between mitochondria and autophagosomes, elucidating their significant contribution to reproductive isolation. Furthermore, our exploration extends to comprehending the evolutionary dynamics of reproductive isolation and speciation in rice. Building on these advances, we offer a forward-looking perspective on how to overcome the challenges of reproductive isolation and facilitate the utilization of heterosis in future hybrid rice breeding endeavors.}, } @article {pmid38326590, year = {2024}, author = {Murphy, MP and O'Neill, LAJ}, title = {A break in mitochondrial endosymbiosis as a basis for inflammatory diseases.}, journal = {Nature}, volume = {626}, number = {7998}, pages = {271-279}, pmid = {38326590}, issn = {1476-4687}, mesh = {Humans ; Autoimmune Diseases/etiology/metabolism/pathology ; Diet/adverse effects ; Homeostasis ; *Inflammation/etiology/metabolism/pathology ; *Mitochondria/metabolism/pathology/physiology ; Mitochondrial Proteins/metabolism ; *Models, Biological ; Nucleic Acids/metabolism ; Obesity/complications/metabolism/pathology ; Phospholipids/metabolism ; Reactive Oxygen Species/metabolism ; *Symbiosis/physiology ; Animals ; }, abstract = {Mitochondria retain bacterial traits due to their endosymbiotic origin, but host cells do not recognize them as foreign because the organelles are sequestered. However, the regulated release of mitochondrial factors into the cytosol can trigger cell death, innate immunity and inflammation. This selective breakdown in the 2-billion-year-old endosymbiotic relationship enables mitochondria to act as intracellular signalling hubs. Mitochondrial signals include proteins, nucleic acids, phospholipids, metabolites and reactive oxygen species, which have many modes of release from mitochondria, and of decoding in the cytosol and nucleus. Because these mitochondrial signals probably contribute to the homeostatic role of inflammation, dysregulation of these processes may lead to autoimmune and inflammatory diseases. A potential reason for the increased incidence of these diseases may be changes in mitochondrial function and signalling in response to such recent phenomena as obesity, dietary changes and other environmental factors. Focusing on the mixed heritage of mitochondria therefore leads to predictions for future insights, research paths and therapeutic opportunities. Thus, whereas mitochondria can be considered 'the enemy within' the cell, evolution has used this strained relationship in intriguing ways, with increasing evidence pointing to the recent failure of endosymbiosis being critical for the pathogenesis of inflammatory diseases.}, } @article {pmid38328137, year = {2024}, author = {Iverson, ENK and Criswell, A and Havird, JC}, title = {Stronger evidence for relaxed selection than adaptive evolution in high-elevation animal mtDNA.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38328137}, issn = {2692-8205}, support = {R35 GM142836/GM/NIGMS NIH HHS/United States ; }, abstract = {Mitochondrial (mt) genes are the subject of many adaptive hypotheses due to the key role of mitochondria in energy production and metabolism. One widespread adaptive hypothesis is that selection imposed by life at high elevation leads to the rapid fixation of beneficial alleles in mtDNA, reflected in the increased rates of mtDNA evolution documented in many high-elevation species. However, the assumption that fast mtDNA evolution is caused by positive, rather than relaxed purifying selection has rarely been tested. Here, we calculated the dN/dS ratio, a metric of nonsynonymous substitution bias, and explicitly tested for relaxed selection in the mtDNA of over 700 species of terrestrial vertebrates, freshwater fishes, and arthropods, with information on elevation and latitudinal range limits, range sizes, and body sizes. We confirmed that mitochondrial genomes of high-elevation taxa have slightly higher dN/dS ratios compared to low-elevation relatives. High-elevation species tend to have smaller ranges, which predict higher dN/dS ratios and more relaxed selection across species and clades, while absolute elevation and latitude do not predict higher dN/dS. We also find a positive relationship between body mass and dN/dS, supporting a role for small effective population size leading to relaxed selection. We conclude that higher mt dN/dS among high-elevation species is more likely to reflect relaxed selection due to smaller ranges and reduced effective population size than adaptation to the environment. Our results highlight the importance of rigorously testing adaptive stories against non-adaptive alternative hypotheses, especially in mt genomes.}, } @article {pmid38332473, year = {2024}, author = {Wang, Y and Li, H and Niu, G and Li, Y and Huang, Z and Cheng, S and Zhang, K and Li, H and Fu, Q and Jiang, Y}, title = {Boosting Sono-immunotherapy of Prostate Carcinoma through Amplifying Domino-Effect of Mitochondrial Oxidative Stress Using Biodegradable Cascade-Targeting Nanocomposites.}, journal = {ACS nano}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsnano.3c12511}, pmid = {38332473}, issn = {1936-086X}, abstract = {Sono-immunotherapy faces challenges from poor immunogenicity and low response rate due to complex biological barriers. Herein, we prepared MCTH nanocomposites (NCs) consisting of disulfide bonds (S-S) doped mesoporous organosilica (MONs), Cu-modified protoporphyrin (CuPpIX), mitochondria-targeting triphenylphosphine (TPP), and CD44-targeting hyaluronic acid (HA). MCTH NCs efficiently accumulate at the tumor site due to the overexpressed CD44 receptors on the membrane of the cancer cells. Under the function of HAase and glutathione (GSH), MCTH degrades and exposes TPP to deliver CuPpIX to the mitochondrial site and induce a reactive oxygen species (ROS) burst in situ under ultrasound irradiations, thereby causing severe mitochondria dysfunction. This cascade-targeting ability of MCTH NCs not only reinforces oxidative stress in cancer cells but also amplifies immunogenic cell death (ICD) to stimulate the body's immune response and alleviate the tumor immunosuppressive microenvironment. These NCs significantly enhance the infiltration of immune cells into the tumor, particularly CD8[+] T cells, for a powerful antitumor sono-immunotherapy. The proposed cascade-targeting strategy holds promise for strengthening sono-immunotherapy for prostate cancer treatment and overcoming the limitations of traditional immunotherapy.}, } @article {pmid38337951, year = {2024}, author = {Guan, J and Zhang, Z and Shi, G}, title = {Genome-Wide Identification of the Ferric Chelate Reductase (FRO) Gene Family in Peanut and Its Diploid Progenitors: Structure, Evolution, and Expression Profiles.}, journal = {Plants (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {38337951}, issn = {2223-7747}, abstract = {The ferric chelate reductase (FRO) family plays a vital role in metal ion homeostasis in a variety of locations in the plants. However, little is known about this family in peanut (Arachis hypogaea). This study aimed to identify FRO genes from the genomes of peanut and the two diploid progenitors (A. duranensis and A. ipaensis) and to analyze their gene/protein structures and evolution. In addition, transcriptional responses of AhFRO genes to Fe deficiency and/or Cu exposure were investigated in two peanut cultivars with different Fe deficiency tolerance (Silihong and Fenghua 1). A total of nine, four, and three FRO genes were identified in peanut, A. duranensis, and A. ipaensis, respectively, which were divided into three groups. Most AhFRO genes underwent WGD/segmental duplication, leading to the expansion of the AhFRO gene family. In general, clustered members share similar gene/protein structures. However, significant divergences occurred in AhFRO2 genes. Three out of five AhFRO2 genes were lowly expressed in all tissues under normal conditions, which may be beneficial for avoiding gene loss. Transcription analysis revealed that AhFRO2 and AhFRO7 genes might be involved in the reduction of Fe/Cu in plasma membranes and plastids, respectively. AhFRO8 genes appear to confer Fe reduction in the mitochondria. Moreover, Fe deficiency induced an increase of Cu accumulation in peanut plants in which AhFRO2.2/2.4/2.5 and FRO7.1/7.2 might be involved. Our findings provided new clues for further understanding the roles of AhFRO genes in the Fe/Cu interaction in peanut.}, } @article {pmid38346534, year = {2024}, author = {Fehsenfeld, S and Yoon, GR and Quijada-Rodriguez, AR and Kandachi-Toujas, H and Calosi, P and Breton, S and Weihrauch, D}, title = {Short-term exposure to high pCO2 leads to decreased branchial cytochrome C oxidase activity in the presence of octopamine in a decapod.}, journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology}, volume = {291}, number = {}, pages = {111603}, doi = {10.1016/j.cbpa.2024.111603}, pmid = {38346534}, issn = {1531-4332}, mesh = {Animals ; Hypercapnia/metabolism ; Electron Transport Complex IV/metabolism ; Octopamine/metabolism ; *Acidosis, Respiratory/metabolism ; *Decapoda ; *Brachyura/physiology ; Gills/metabolism ; }, abstract = {In a recent mechanistic study, octopamine was shown to promote proton transport over the branchial epithelium in green crabs, Carcinus maenas. Here, we follow up on this finding by investigating the involvement of octopamine in an environmental and physiological context that challenges acid-base homeostasis, the response to short-term high pCO2 exposure (400 Pa) in a brackish water environment. We show that hyperregulating green crabs experienced a respiratory acidosis as early as 6 h of exposure to hypercapnia, with a rise in hemolymph pCO2 accompanied by a simultaneous drop of hemolymph pH. The slightly delayed increase in hemolymph HCO3[-] observed after 24 h helped to restore hemolymph pH to initial values by 48 h. Circulating levels of the biogenic amine octopamine were significantly higher in short-term high pCO2 exposed crabs compared to control crabs after 48 h. Whole animal metabolic rates, intracellular levels of octopamine and cAMP, as well as branchial mitochondrial enzyme activities for complex I + III and citrate synthase were unchanged in posterior gill #7 after 48 h of hypercapnia. However, application of octopamine in gill respirometry experiments suppressed branchial metabolic rate in posterior gills of short-term high pCO2 exposed animals. Furthermore, branchial enzyme activity of cytochrome C oxidase decreased in high pCO2 exposed crabs after 48 h. Our results indicate that hyperregulating green crabs are capable of quickly counteracting a hypercapnia-induced respiratory acidosis. The role of octopamine in the acclimation of green crabs to short-term hypercapnia seems to entail the alteration of branchial metabolic pathways, possibly targeting mitochondrial cytochrome C in the gill. Our findings help advancing our current limited understanding of endocrine components in hypercapnia acclimation. SUMMARY STATEMENT: Acid-base compensation upon short-term high pCO2 exposure in hyperregulating green crabs started after 6 h and was accomplished by 48 h with the involvement of the biogenic amine octopamine, accumulation of hemolymph HCO3[-], and regulation of mitochondrial complex IV (cytochrome C oxidase).}, } @article {pmid38349189, year = {2024}, author = {Lanza, A and Kimura, S and Hirono, I and Yoshitake, K and Kinoshita, S and Asakawa, S}, title = {Transcriptome analysis of Edwardsiella piscicida during intracellular infection reveals excludons are involved with the activation of a mitochondrion-like energy generation program.}, journal = {mBio}, volume = {15}, number = {3}, pages = {e0352623}, pmid = {38349189}, issn = {2150-7511}, support = {20H00429//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; //Toagosei (Toagosei Co., Ltd.)/ ; }, mesh = {Animals ; Zebrafish ; Phylogeny ; *Edwardsiella/genetics ; Gene Expression Profiling ; *Enterobacteriaceae Infections/microbiology ; *Fish Diseases/microbiology ; }, abstract = {Phylogenetic evidence suggests a shared ancestry between mitochondria and modern Proteobacteria, a phylum including several genera of intracellular pathogens. Studying these diverse pathogens, particularly during intracellular infection of their hosts, can reveal characteristics potentially representative of the mitochondrial-Proteobacterial ancestor by identifying traits shared with mitochondria. While transcriptomic approaches can provide global insights into intracellular acclimatization by pathogens, they are often limited by excess host RNAs in extracts. Here, we developed a method employing magnetic nanoparticles to enrich RNA from an intracellular Gammaproteobacterium, Edwardsiella piscicida, within zebrafish, Danio rerio, fin fibroblasts, enabling comprehensive exploration of the bacterial transcriptome. Our findings revealed that the intracellular E. piscicida transcriptome reflects a mitochondrion-like energy generation program characterized by the suppression of glycolysis and sugar transport, coupled with upregulation of the tricarboxylic acid (TCA) cycle and alternative import of simple organic acids that directly flux into TCA cycle intermediates or electron transport chain donors. Additionally, genes predicted to be members of excludons, loci of gene pairs antagonistically co-regulated by overlapping antisense transcription, are significantly enriched in the set of all genes with perturbed sense and antisense transcription, suggesting a general but important involvement of excludons with intracellular acclimatization. Notably, genes involved with the activation of the mitochondrion-like energy generation program, specifically with metabolite import and glycolysis, are also members of predicted excludons. Other intracellular Proteobacterial pathogens appear to employ a similar mitochondrion-like energy generation program, suggesting a potentially conserved mechanism for optimized energy acquisition from hosts centered around the TCA cycle.IMPORTANCEPhylogenetic evidence suggests that mitochondria and Proteobacteria, a phylum encompassing various intracellular pathogens, share a common ancestral lineage. In this study, we developed a novel method employing magnetic nanoparticles to explore the transcriptome of an aquatic Gammaproteobacterium, Edwardsiella piscicida, during intracellular infection of host cells. We show that the strategy E. piscicida uses to generate energy strikingly mirrors the function of mitochondria-energy generators devoid of glycolytic processes. Notably, several implicated genes are members of excludons-gene pairs antagonistically co-regulated by overlapping antisense transcription. Other intracellular Proteobacterial pathogens appear to adopt a similar mitochondrion-like energy generation program, indicating a possibly conserved strategy for optimized energy acquisition from hosts centered around the tricarboxylic acid cycle.}, } @article {pmid38351074, year = {2024}, author = {Choudhury, C and Gill, MK and McAleese, CE and Butcher, NJ and Ngo, ST and Steyn, FJ and Minchin, RF}, title = {The Arylamine N-Acetyltransferases as Therapeutic Targets in Metabolic Diseases Associated with Mitochondrial Dysfunction.}, journal = {Pharmacological reviews}, volume = {76}, number = {2}, pages = {300-320}, doi = {10.1124/pharmrev.123.000835}, pmid = {38351074}, issn = {1521-0081}, mesh = {Humans ; *Arylamine N-Acetyltransferase/genetics/metabolism ; Acetyltransferases/genetics/metabolism ; Substrate Specificity ; *Metabolic Diseases/drug therapy ; *Mitochondrial Diseases/drug therapy ; }, abstract = {In humans, there are two arylamine N-acetyltransferase genes that encode functional enzymes (NAT1 and NAT2) as well as one pseudogene, all of which are located together on chromosome 8. Although they were first identified by their role in the acetylation of drugs and other xenobiotics, recent studies have shown strong associations for both enzymes in a variety of diseases, including cancer, cardiovascular disease, and diabetes. There is growing evidence that this association may be causal. Consistently, NAT1 and NAT2 are shown to be required for healthy mitochondria. This review discusses the current literature on the role of both NAT1 and NAT2 in mitochondrial bioenergetics. It will attempt to relate our understanding of the evolution of the two genes with biologic function and then present evidence that several major metabolic diseases are influenced by NAT1 and NAT2. Finally, it will discuss current and future approaches to inhibit or enhance NAT1 and NAT2 activity/expression using small-molecule drugs. SIGNIFICANCE STATEMENT: The arylamine N-acetyltransferases (NATs) NAT1 and NAT2 share common features in their associations with mitochondrial bioenergetics. This review discusses mitochondrial function as it relates to health and disease, and the importance of NAT in mitochondrial function and dysfunction. It also compares NAT1 and NAT2 to highlight their functional similarities and differences. Both NAT1 and NAT2 are potential drug targets for diseases where mitochondrial dysfunction is a hallmark of onset and progression.}, } @article {pmid38361161, year = {2024}, author = {Serrano, IM and Hirose, M and Valentine, CC and Roesner, S and Schmidt, E and Pratt, G and Williams, L and Salk, J and Ibrahim, S and Sudmant, PH}, title = {Mitochondrial haplotype and mito-nuclear matching drive somatic mutation and selection throughout ageing.}, journal = {Nature ecology & evolution}, volume = {8}, number = {5}, pages = {1021-1034}, pmid = {38361161}, issn = {2397-334X}, support = {R35GM142916//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; N/A//Vallee Foundation (Bert L. & N. Kuggie Vallee Foundation)/ ; R35 GM142916/GM/NIGMS NIH HHS/United States ; 2146752//NSF | Directorate for Education & Human Resources | Division of Graduate Education (DGE)/ ; N/A//Ford Foundation/ ; 1752814//NSF | Directorate for Education & Human Resources | Division of Graduate Education (DGE)/ ; }, mesh = {Animals ; *Haplotypes ; *Aging/genetics ; *Mutation ; *Selection, Genetic ; Mice ; *Genome, Mitochondrial ; DNA, Mitochondrial/genetics ; Cell Nucleus/genetics ; Female ; Mitochondria/genetics ; Mice, Inbred C57BL ; Male ; }, abstract = {Mitochondrial genomes co-evolve with the nuclear genome over evolutionary timescales and are shaped by selection in the female germline. Here we investigate how mismatching between nuclear and mitochondrial ancestry impacts the somatic evolution of the mitochondrial genome in different tissues throughout ageing. We used ultrasensitive duplex sequencing to profile ~2.5 million mitochondrial genomes across five mitochondrial haplotypes and three tissues in young and aged mice, cataloguing ~1.2 million mitochondrial somatic and ultralow-frequency inherited mutations, of which 81,097 are unique. We identify haplotype-specific mutational patterns and several mutational hotspots, including at the light strand origin of replication, which consistently exhibits the highest mutation frequency. We show that rodents exhibit a distinct mitochondrial somatic mutational spectrum compared with primates with a surfeit of reactive oxygen species-associated G > T/C > A mutations, and that somatic mutations in protein-coding genes exhibit signatures of negative selection. Lastly, we identify an extensive enrichment in somatic reversion mutations that 're-align' mito-nuclear ancestry within an organism's lifespan. Together, our findings demonstrate that mitochondrial genomes are a dynamically evolving subcellular population shaped by somatic mutation and selection throughout organismal lifetimes.}, } @article {pmid38361280, year = {2024}, author = {Degli Esposti, M}, title = {Did mitophagy follow the origin of mitochondria?.}, journal = {Autophagy}, volume = {20}, number = {5}, pages = {985-993}, pmid = {38361280}, issn = {1554-8635}, mesh = {*Mitophagy/physiology ; *Mitochondria/metabolism ; Humans ; Animals ; Prohibitins ; Mitochondrial Membranes/metabolism ; Signal Transduction ; }, abstract = {Mitophagy is the process of selective autophagy that removes superfluous and dysfunctional mitochondria. Mitophagy was first characterized in mammalian cells and is now recognized to follow several pathways including basal forms in specific organs. Mitophagy pathways are regulated by multiple, often interconnected factors. The present review aims to streamline this complexity and evaluate common elements that may define the evolutionary origin of mitophagy. Key issues surrounding mitophagy signaling at the mitochondrial surface may fundamentally derive from mitochondrial membrane dynamics. Elements of such membrane dynamics likely originated during the endosymbiosis of the alphaproteobacterial ancestor of our mitochondria but underwent an evolutionary leap forward in basal metazoa that determined the currently known variations in mitophagy signaling.Abbreviations: AGPAT, 1-acylglycerol-3-phosphate O-acyltransferase; ATG, autophagy related; BCL2L13, BCL2 like 13; BNIP3, BCL2 interacting protein 3; BNIP3L, BCL2 interacting protein 3 like; CALCOCO, calcium binding and coiled-coil domain; CL, cardiolipin; ER, endoplasmic reticulum; ERMES, ER-mitochondria encounter structure; FBXL4, F-box and leucine rich repeat protein 4; FUNDC1, FUN14 domain containing 1; GABARAPL1, GABA type A receptor associated protein like 1; HIF, hypoxia inducible factor; IMM, inner mitochondrial membrane; LBPA/BMP, lysobisphosphatidic acid; LIR, LC3-interacting region; LPA, lysophosphatidic acid; MAM, mitochondria-associated membranes; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MCL, monolysocardiolipin; ML, maximum likelihood; NBR1, NBR1 autophagy cargo receptor; OMM, outer mitochondrial membrane; PA, phosphatidic acid; PACS2, phosphofurin acidic cluster sorting protein 2; PC/PLC, phosphatidylcholine; PE, phosphatidylethanolamine; PHB2, prohibitin 2; PINK1, PTEN induced kinase 1; PtdIns, phosphatidylinositol; SAR, Stramenopiles, Apicomplexa and Rhizaria; TAX1BP1, Tax1 binding protein 1; ULK1, unc-51 like autophagy activating kinase 1; VDAC/porin, voltage dependent anion channel.}, } @article {pmid38363119, year = {2024}, author = {Tetzlaff, S and Hillebrand, A and Drakoulis, N and Gluhic, Z and Maschmann, S and Lyko, P and Wicke, S and Schmitz-Linneweber, C}, title = {Small RNAs from mitochondrial genome recombination sites are incorporated into T. gondii mitoribosomes.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {38363119}, issn = {2050-084X}, support = {IRTG2290-B01//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Genome, Mitochondrial ; Mitochondrial Ribosomes/metabolism ; Escherichia coli/genetics ; RNA, Ribosomal/metabolism ; RNA, Messenger/genetics ; *RNA, Small Untranslated/genetics/metabolism ; Recombination, Genetic ; }, abstract = {The mitochondrial genomes of apicomplexans comprise merely three protein-coding genes, alongside a set of thirty to forty genes encoding small RNAs (sRNAs), many of which exhibit homologies to rRNA from E. coli. The expression status and integration of these short RNAs into ribosomes remains unclear and direct evidence for active ribosomes within apicomplexan mitochondria is still lacking. In this study, we conducted small RNA sequencing on the apicomplexan Toxoplasma gondii to investigate the occurrence and function of mitochondrial sRNAs. To enhance the analysis of sRNA sequencing outcomes, we also re-sequenced the T. gondii mitochondrial genome using an improved organelle enrichment protocol and Nanopore sequencing. It has been established previously that the T. gondii genome comprises 21 sequence blocks that undergo recombination among themselves but that their order is not entirely random. The enhanced coverage of the mitochondrial genome allowed us to characterize block combinations at increased resolution. Employing this refined genome for sRNA mapping, we find that many small RNAs originated from the junction sites between protein-coding blocks and rRNA sequence blocks. Surprisingly, such block border sRNAs were incorporated into polysomes together with canonical rRNA fragments and mRNAs. In conclusion, apicomplexan ribosomes are active within polysomes and are indeed assembled through the integration of sRNAs, including previously undetected sRNAs with merged mRNA-rRNA sequences. Our findings lead to the hypothesis that T. gondii's block-based genome organization enables the dual utilization of mitochondrial sequences as both messenger RNAs and ribosomal RNAs, potentially establishing a link between the regulation of rRNA and mRNA expression.}, } @article {pmid38368456, year = {2024}, author = {Széliová, D and Müller, S and Zanghellini, J}, title = {Costs of ribosomal RNA stabilization affect ribosome composition at maximum growth rate.}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {196}, pmid = {38368456}, issn = {2399-3642}, mesh = {*Escherichia coli/metabolism ; *Ribosomes/genetics/metabolism ; RNA, Ribosomal/genetics/metabolism ; Ribosomal Proteins/genetics/metabolism ; RNA/metabolism ; }, abstract = {Ribosomes are key to cellular self-fabrication and limit growth rate. While most enzymes are proteins, ribosomes consist of 1/3 protein and 2/3 ribonucleic acid (RNA) (in E. coli).Here, we develop a mechanistic model of a self-fabricating cell, validated across diverse growth conditions. Through resource balance analysis (RBA), we explore the variation in maximum growth rate with ribosome composition, assuming constant kinetic parameters.Our model highlights the importance of RNA instability. If we neglect it, RNA synthesis is always cheaper than protein synthesis, leading to an RNA-only ribosome at maximum growth rate. Upon accounting for RNA turnover, we find that a mixed ribosome composed of RNA and proteins maximizes growth rate. To account for RNA turnover, we explore two scenarios regarding the activity of RNases. In (a) degradation is proportional to RNA content. In (b) ribosomal proteins cooperatively mitigate RNA instability by protecting it from misfolding and subsequent degradation. In both cases, higher protein content elevates protein synthesis costs and simultaneously lowers RNA turnover expenses, resulting in mixed RNA-protein ribosomes. Only scenario (b) aligns qualitatively with experimental data across varied growth conditions.Our research provides fresh insights into ribosome biogenesis and evolution, paving the way for understanding protein-rich ribosomes in archaea and mitochondria.}, } @article {pmid38378784, year = {2024}, author = {Li, H and Akella, S and Engstler, C and Omini, JJ and Rodriguez, M and Obata, T and Carrie, C and Cerutti, H and Mower, JP}, title = {Recurrent evolutionary switches of mitochondrial cytochrome c maturation systems in Archaeplastida.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {1548}, pmid = {38378784}, issn = {2041-1723}, support = {MCB 2212075//National Science Foundation (NSF)/ ; }, mesh = {Amino Acid Sequence ; *Cytochromes c/genetics/metabolism ; *Mitochondria/genetics/metabolism ; }, abstract = {Mitochondrial cytochrome c maturation (CCM) requires heme attachment via distinct pathways termed systems I and III. The mosaic distribution of these systems in Archaeplastida raises questions about the genetic mechanisms and evolutionary forces promoting repeated evolution. Here, we show a recurrent shift from ancestral system I to the eukaryotic-specific holocytochrome c synthase (HCCS) of system III in 11 archaeplastid lineages. Archaeplastid HCCS is sufficient to rescue mutants of yeast system III and Arabidopsis system I. Algal HCCS mutants exhibit impaired growth and respiration, and altered biochemical and metabolic profiles, likely resulting from deficient CCM and reduced cytochrome c-dependent respiratory activity. Our findings demonstrate that archaeplastid HCCS homologs function as system III components in the absence of system I. These results elucidate the evolutionary trajectory and functional divergence of CCM pathways in Archaeplastida, providing insight into the causes, mechanisms, and consequences of repeated cooption of an entire biological pathway.}, } @article {pmid38381321, year = {2024}, author = {Liu, T and Ji, D and Li, X and Liu, J and Xu, F and Miao, Z and Chang, Y and Tian, M and Xu, C}, title = {Population genetics reveals new introgression in the nucleus herd of min pigs.}, journal = {Genes & genomics}, volume = {46}, number = {4}, pages = {389-398}, pmid = {38381321}, issn = {2092-9293}, support = {LH2019C017//Natural Science Foundation of Heilongjiang Province/ ; 2022ZX02B10-2//Heilongjiang Provincial Key R&D Program/ ; }, mesh = {Swine/genetics ; Animals ; *Genetic Variation ; *Genetics, Population ; Polymorphism, Genetic ; Mitochondria/genetics ; Heterozygote ; }, abstract = {OBJECTIVE: Min pigs are a unique genetic resource among local pig breeds in China. They have more excellent characteristics in cold and stress resistance, good meat quality, and a high reproductive rate. However, the genetic structure and driving factors remain unclear in the nucleus herd. In this study, the genetic diversity of Min pigs was studied to reveal the formation mechanism of its unique genetic structure. We hope to protect and develop the genetic resources of Min pigs.

METHODS: We analyzed different types of genes to identify the genetic structure and gene introgression pattern of Min pigs. The nuclear DNA dataset includes information on 21 microsatellite loci and 6 Y-chromosome genes, and the mitochondrial D-loop gene is selected to represent maternal lineages. The above genes are all from the nucleus herd of Min pigs.

RESULTS: The results of genetic structure identification and analysis of potential exogenous gene introgression patterns indicate that the nucleus herd of Min pigs maintains a high level of genetic diversity (polymorphism information content = 0.713, expected heterozygosity = 0.662, observed heterozygosity = 0.612). Compared with other Asian pig breeds, the formation of Min pig breeds is more special. Gene introgression from European pig breeds to Min pigs has occurred, which is characterized by complete introgression of paternal genes and incomplete introgression of maternal genes.

CONCLUSION: Gene introgression caused by cross-breeding is not the main factor leading to the formation of the current genetic structure of Min pigs, but this process has increased the level of genetic diversity in the nucleus herd. Compared with the influence of gene introgression, our research suggest that artificial selection and environmental adaptive evolution make Min pigs form unique genetic characteristics.}, } @article {pmid38391484, year = {2024}, author = {Kan, S and Liao, X and Lan, L and Kong, J and Wang, J and Nie, L and Zou, J and An, H and Wu, Z}, title = {Cytonuclear Interactions and Subgenome Dominance Shape the Evolution of Organelle-Targeted Genes in the Brassica Triangle of U.}, journal = {Molecular biology and evolution}, volume = {41}, number = {3}, pages = {}, pmid = {38391484}, issn = {1537-1719}, mesh = {*Genome, Plant ; *Evolution, Molecular ; Mustard Plant/genetics ; Plastids/genetics ; Polyploidy ; }, abstract = {The interaction and coevolution between nuclear and cytoplasmic genomes are one of the fundamental hallmarks of eukaryotic genome evolution and, 2 billion yr later, are still major contributors to the formation of new species. Although many studies have investigated the role of cytonuclear interactions following allopolyploidization, the relative magnitude of the effect of subgenome dominance versus cytonuclear interaction on genome evolution remains unclear. The Brassica triangle of U features 3 diploid species that together have formed 3 separate allotetraploid species on similar evolutionary timescales, providing an ideal system for understanding the contribution of the cytoplasmic donor to hybrid polyploid. Here, we investigated the evolutionary pattern of organelle-targeted genes in Brassica carinata (BBCC) and 2 varieties of Brassica juncea (AABB) at the whole-genome level, with particular focus on cytonuclear enzyme complexes. We found partial evidence that plastid-targeted genes experience selection to match plastid genomes, but no obvious corresponding signal in mitochondria-targeted genes from these 2 separately formed allopolyploids. Interestingly, selection acting on plastid genomes always reduced the retention rate of plastid-targeted genes encoded by the B subgenome, regardless of whether the Brassica nigra (BB) subgenome was contributed by the paternal or maternal progenitor. More broadly, this study illustrates the distinct selective pressures experienced by plastid- and mitochondria-targeted genes, despite a shared pattern of inheritance and natural history. Our study also highlights an important role for subgenome dominance in allopolyploid genome evolution, even in genes whose function depends on separately inherited molecules.}, } @article {pmid38402284, year = {2024}, author = {Li, G and Zhang, H and Lin, Z and Li, H and Xu, G and Xu, Y and Ji, R and Luo, W and Qiu, Y and Qiu, S and Tang, H}, title = {Comparative analysis of chloroplast and mitochondrial genomes of sweet potato provides evidence of gene transfer.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4547}, pmid = {38402284}, issn = {2045-2322}, mesh = {*Ipomoea batatas/genetics ; Phylogeny ; *Genome, Mitochondrial/genetics ; *Ipomoea/genetics ; *Genome, Chloroplast/genetics ; Chloroplasts/genetics ; Amino Acids/genetics ; RNA, Transfer/genetics ; }, abstract = {The increasing number of plant mitochondrial DNA genomes (mtDNA) sequenced reveals the extent of transfer from both chloroplast DNA genomes (cpDNA) and nuclear DNA genomes (nDNA). This study created a library and assembled the chloroplast and mitochondrial genomes of the leafy sweet potato better to understand the extent of mitochondrial and chloroplast gene transfer. The full-length chloroplast genome of the leafy sweet potato (OM808940) is 161,387 bp, with 132 genes annotated, including 87 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. The mitochondrial genome (OM808941) was 269,578 bp in length and contained 69 functional genes, including 39 protein-coding genes, 6 rRNA genes, and 24 tRNA genes. 68 SSR loci were found in the leafy sweet potato organelle genome, including 54 in the chloroplast genome and 14 in the mitochondria genome. In the sweet potato mitochondrial genome, most genes have RNA editing sites, and the conversion ratio from hydrophilic amino acids to hydrophobic amino acids is the highest, reaching 47.12%. Horizontal transfer occurs in the sweet potato organelle genome and nuclear genome. 40 mitochondrial genome segments share high homology with 14 chloroplast genome segments, 33 of which may be derived from chloroplast genome horizontal transfer. 171 mitochondrial genome sequences come from the horizontal transfer of nuclear genome. The phylogenetic analysis of organelle genes revealed that the leafy sweet potato was closely related to the tetraploid wild species Ipomoea tabascana and the wild diploid species Ipomoea trifida.}, } @article {pmid38402551, year = {2024}, author = {Xu, R and Li, T and Luo, J and Zhang, X and Wang, T and Wang, Y and Ma, Y and Yang, B and Jia, J and Dmytriw, AA and Li, W and Jiao, L}, title = {PCSK9 increases vulnerability of carotid plaque by promoting mitochondrial dysfunction and apoptosis of vascular smooth muscle cells.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {2}, pages = {e14640}, pmid = {38402551}, issn = {1755-5949}, support = {DFL20220702//Beijing Hospitals Authority's Ascent Plan/ ; 82171303//National Natural Science Foundation of China/ ; Z201100005520019//Beijing Scientific and Technologic Project/ ; Z201100005520020//Beijing Scientific and Technologic Project/ ; 7244353//Beijing Municipal Natural Science Foundation/ ; }, mesh = {Humans ; *Muscle, Smooth, Vascular ; Proprotein Convertase 9/genetics ; Apoptosis ; *Mitochondrial Diseases ; }, abstract = {BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recognized as a novel lipid-lowing target. Recent clinical studies suggested the value of inhibiting PCSK9 in decreasing the vulnerability of coronary plaques. However, the evidence of PCSK9-regulated evolution of unstable carotid plaques is unclear, which has limited the use of PCSK9 inhibitor in carotid plaques. This study aimed to determine the effect and molecular mechanisms of PCSK9 on vulnerability of carotid plaques, to provide potential therapeutic targets for stabilizing carotid plaques.

METHODS: The expression of PCSK9 in stable and unstable carotid plaques were examined in tissue and plasma. Human aortic vascular smooth muscle cells (VSMCs) and carotid VSMCs were employed to transfect lentivirus for overexpression and knockdown of PCSK9, respectively. Morphological and functional changes of mitochondria were observed by live-cell imaging. Cell apoptosis was evaluated by propidium iodide staining. RNA-sequencing and biological examinations were performed to explore and validate the underlying mechanisms. Truncated plasmids were employed to identify the functional domain of PCSK9 in regulation of VSMCs' mitochondrial morphology, function and apoptosis.

RESULTS: Clinically, PCSK9 was closely related with vulnerability of human carotid plaques. Increased expression of PCSK9 in human VSMCs was accompanied by higher level of apoptosis. At subcellular level of VSMCs, the morphology of mitochondria was shifted toward the fission state, followed by mitochondrial dysfunction. Inhibition of p38 MAPK activation partially rescued the above morphological and behavioral changes caused by PCSK9. Furthermore, inhibiting of dynamin-related protein 1 (DRP1) attenuated PCSK9-related mitochondrial dysfunction and cell apoptosis. The 1-149aa domain of PCSK9 protein was essential to achieve functional regulation to VSMCs.

CONCLUSION: Our findings demonstrated that PCSK9 induced morphology-related mitochondrial dysfunction and apoptosis of VSMCs, which may be related to increased vulnerability of carotid plaque.}, } @article {pmid38411429, year = {2024}, author = {Selosse, MA}, title = {[Mitochondria, organelles or bacteria?].}, journal = {Medecine sciences : M/S}, volume = {40}, number = {2}, pages = {197-198}, doi = {10.1051/medsci/2024001}, pmid = {38411429}, issn = {1958-5381}, mesh = {Humans ; *Mitochondria ; *Bacteria ; }, } @article {pmid38411741, year = {2024}, author = {Cardoso, DC and Baldez, BCL and Pereira, AH and Kalapothakis, E and Rosse, IC and Cristiano, MP}, title = {De novo assembly of the complete mitochondrial genome of Mycetophylax simplex Emery, 1888 through organelle targeting revels no substantial expansion of gene spacers, but rather some slightly shorter genes.}, journal = {Molecular genetics and genomics : MGG}, volume = {299}, number = {1}, pages = {16}, pmid = {38411741}, issn = {1617-4623}, support = {PPM199-18//Fundação de Amparo à Pesquisa do Estado de Minas Gerais/ ; 001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, mesh = {Animals ; *Genome, Mitochondrial/genetics ; Ecosystem ; Bayes Theorem ; Phylogeny ; Mitochondria/genetics ; *Ants/genetics ; }, abstract = {Mitochondria play a key role in cell biology and have their own genome, residing in a highly oxidative environment that induces faster changes than the nuclear genome. Because of this, mitochondrial markers have been exploited to reconstruct phylogenetic and phylogeographic relationships in studies of adaptation and molecular evolution. In this study, we determined the complete mitogenome of the fungus-farming ant Mycetophylax simplex (Hymenoptera, Formicidae) and conducted a comparative analysis among 29 myrmicine ant mitogenomes. Mycetophylax simplex is an endemic ant that inhabits sand dunes along the southern Atlantic coast. Specifically, the species occur in the ecosystem known as "restinga", within the Atlantic Forest biome. Due to habitat degradation, land use and decline of restinga habitats, the species is considered locally extinct in extremely urban beaches and is listed as vulnerable on the Brazilian Red List (ICMBio). We employed a mitochondrion-targeting approach to obtain the complete mitogenome through high-throughput DNA sequencing technology. This method allowed us to determine the mitogenome with high performance, coverage and low cost. The circular mitogenome has a length of 16,367 base pairs enclosing 37 genes (13 protein-coding genes, 22 tRNAs and 2 rRNAs) along with one control region (CR). All the protein-coding genes begin with a typical ATN codon and end with the canonical stop codons. All tRNAs formed the fully paired acceptor stems and fold into the typical cloverleaf-shaped secondary structures. The gene order is consistent with the shared Myrmicinae structure, and the A + T content of the majority strand is 81.51%. Long intergenic spacers were not found but some gene are slightly shorter. The phylogenetic relationships based on concatenated nucleotide and amino acid sequences of the 13 protein-coding genes, using Maximum Likelihood and Bayesian Inference methods, indicated that mitogenome sequences were useful in resolving higher-level relationship within Formicidae.}, } @article {pmid38413922, year = {2024}, author = {Xu, L and Wang, J and Zhang, T and Xiao, H and Wang, H}, title = {Characterizing complete mitochondrial genome of Aquilegia amurensis and its evolutionary implications.}, journal = {BMC plant biology}, volume = {24}, number = {1}, pages = {142}, pmid = {38413922}, issn = {1471-2229}, support = {nos. 32070244//National Natural Science Foundation of China/ ; nos.32300187//National Natural Science Foundation of China/ ; }, mesh = {Phylogeny ; *Aquilegia/genetics ; *Genome, Mitochondrial/genetics ; Mitochondria/genetics ; RNA, Transfer/genetics ; }, abstract = {BACKGROUND: Aquilegia is a model system for studying the evolution of adaptive radiation. However, very few studies have been conducted on the Aquilegia mitochondrial genome. Since mitochondria play a key role in plant adaptation to abiotic stress, analyzing the mitochondrial genome may provide a new perspective for understanding adaptive evolution.

RESULTS: The Aquilegia amurensis mitochondrial genome was characterized by a circular chromosome and two linear chromosomes, with a total length of 538,736 bp; the genes included 33 protein-coding genes, 24 transfer RNA (tRNA) genes and 3 ribosomal RNA (rRNA) genes. We subsequently conducted a phylogenetic analysis based on single nucleotide polymorphisms (SNPs) in the mitochondrial genomes of 18 Aquilegia species, which were roughly divided into two clades: the European-Asian clade and the North American clade. Moreover, the genes mttB and rpl5 were shown to be positively selected in European-Asian species, and they may help European and Asian species adapt to environmental changes.

CONCLUSIONS: In this study, we assembled and annotated the first mitochondrial genome of the adaptive evolution model plant Aquilegia. The subsequent analysis provided us with a basis for further molecular studies on Aquilegia mitochondrial genomes and valuable information on adaptive evolution in Aquilegia.}, } @article {pmid38419371, year = {2024}, author = {Chen, Z and Xie, X and Jia, C and Zhong, Q and Zhang, Q and Luo, D and Cao, Y and Mu, Y and Ren, C}, title = {Concentration-Driven Evolution of Adaptive Artificial Ion Channels or Nanopores with Specific Anticancer Activities.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {63}, number = {17}, pages = {e202318811}, doi = {10.1002/anie.202318811}, pmid = {38419371}, issn = {1521-3773}, support = {22271240//National Natural Science Foundation of China/ ; JCYJ20210324123411030//Science, Technology and Innovation Commission of Shenzhen Municipality/ ; JCYJ20220530143206013//Science, Technology and Innovation Commission of Shenzhen Municipality/ ; }, mesh = {Humans ; *Nanopores ; Ion Channels ; Organophosphorus Compounds/chemistry ; Doxorubicin/chemistry ; }, abstract = {In nature, ceramides are a class of sphingolipids possessing a unique ability to self-assemble into protein-permeable channels with intriguing concentration-dependent adaptive channel cavities. However, within the realm of artificial ion channels, this interesting phenomenon is scarcely represented. Herein, we report on a novel class of adaptive artificial channels, Pn-TPPs, based on PEGylated cholic acids bearing triphenylphosphonium (TPP) groups as anion binding motifs. Interestingly, the molecules self-assemble into chloride ion channels at low concentrations while transforming into small molecule-permeable nanopores at high concentrations. Moreover, the TPP groups endow the molecules with mitochondria-targeting properties, enabling them to selectively drill holes on the mitochondrial membrane of cancer cells and subsequently trigger the caspase 9 apoptotic pathway. The anticancer efficacies of Pn-TPPs correlate with their abilities to form nanopores. Significantly, the most active ensembles formed by P5-TPP exhibits impressive anticancer activity against human liver cancer cells, with an IC50 value of 3.8 μM. While demonstrating similar anticancer performance to doxorubicin, P5-TPP exhibits a selectivity index surpassing that of doxorubicin by a factor of 16.8.}, } @article {pmid38422090, year = {2024}, author = {Yu, TS and Park, K and Han, KH and Kwak, IS}, title = {Morphological and genetic analysis for the diversity conservation of rare species, Thamnaconus multilineatus (Tetraodontiformes: Monacanthidae).}, journal = {PloS one}, volume = {19}, number = {2}, pages = {e0292916}, pmid = {38422090}, issn = {1932-6203}, mesh = {Animals ; *Tetraodontiformes ; Phylogeny ; DNA, Mitochondrial/genetics ; Mitochondria ; Biodiversity ; Endangered Species ; }, abstract = {Climate changes have altered biodiversity and ultimately induced community changes that have threatened the survival of certain aquatic organisms such as fish species. Obtaining biological and genetic information on endangered fish species is critical for ecological population management. Thamnaconus multilineatus, registered as an endangered species by the IUCN in 2019, is a Data Deficient (DD) species with a remarkably small number of habitats worldwide and no known information other than its habitat and external form. In this study, we characterized the external and osteological morphology of a T. multilineatus specimen collected from eastern Jeju Island, South Korea, in 2020. We also investigated the phylogenetic relationships among related fish species through complete mitochondrial DNA (mtDNA) analysis of the T. multilineatus specimen. The external and skeletal characteristics of T. multilineatus were similar to those of previous reports describing other fish of the genus Thamnaconus, making it difficult to classify T. multilineatus as a similar species based only on morphological characteristics. As a result of analyzing the complete mtDNA of T. multilineatus, the length of the mtDNA was determined to be 16,435 bp, and the mitochondrial genome was found to have 37 CDCs, including 13 PCGs, 22 tRNAs, and 2 rRNAs. In the phylogenetic analysis within the suborder Balistoidei, T. multilineatus mtDNA formed a cluster with fish of the genus Thamnaconus. This study is the first to report on the skeletal structure and complete mtDNA of T. multilineatus. Since the current research on T. multilineatus has only been reported on morphology, the results of this study will be utilized as important information for the management and restoration of T. multilineatus as an endangered species and significant fishery resource.}, } @article {pmid38429489, year = {2024}, author = {Wang, J and Lin, Y and Xu, Z and Yan, C and Zhao, Y and Ji, K}, title = {Mitochondrial Dysfunction due to Novel COQ8A Variation with Poor Response to CoQ10 Treatment: A Comprehensive Study and Review of Literatures.}, journal = {Cerebellum (London, England)}, volume = {23}, number = {5}, pages = {1824-1838}, pmid = {38429489}, issn = {1473-4230}, support = {No.82301590//the National Natural Science Foundation of China/ ; No.82071412//the National Natural Science Foundation of China/ ; No.82171394//the National Natural Science Foundation of China/ ; 2023M742116//China Postdoctoral Science Foundation/ ; ZR2023QH106//Natural Science Foundation of Shandong Province/ ; SDBX2022061//Shandong Provincial Postdoctoral Innovation Talent Support Program/ ; No.2021YFC2700904//Grants from the National Key R&D Program of China/ ; 20-3-4-42-nsh//People's Benefit Project of Science and Technology in Qingdao/ ; }, mesh = {Humans ; *Ubiquinone/analogs & derivatives/therapeutic use/deficiency/genetics ; Adolescent ; *Mitochondrial Diseases/drug therapy/genetics ; Mitochondrial Proteins/genetics ; Male ; Ataxia/drug therapy/genetics ; Mitochondria/drug effects/metabolism ; Muscle Weakness/genetics/drug therapy ; }, abstract = {COQ8A plays an important role in the biosynthesis of coenzyme Q10 (CoQ10), and variations in COQ8A gene are associated with primary CoQ10 deficiency-4 (COQ10D4), also known as COQ8A-ataxia. The current understanding of the association between the specific variant type, the severity of CoQ10 deficiency, and the degree of oxidative stress in individuals with primary CoQ10 deficiencies remains uncertain. Here we provide a comprehensive analysis of the clinical and genetic characteristics of an 18-year-old patient with COQ8A-ataxia, who exhibited novel compound heterozygous variants (c.1904_1906del and c.637C > T) in the COQ8A gene. These variants reduced the expression levels of COQ8A and mitochondrial proteins in the patient's muscle and skin fibroblast samples, contributed to mitochondrial respiration deficiency, increased ROS production and altered mitochondrial membrane potential. It is worth noting that the optimal treatment for COQ8A-ataxia remains uncertain. Presently, therapy consists of CoQ10 supplementation, however, it did not yield significant improvement in our patient's symptoms. Additionally, we reviewed the response of CoQ10 supplementation and evolution of patients in previous literatures in detail. We found that only half of patients could got notable improvement in ataxia. This research aims to expand the genotype-phenotype spectrum of COQ10D4, address discrepancies in previous reviews regarding the effectiveness of CoQ10 in these disorders, and help to establish a standardized treatment protocol for COQ8A-ataxia.}, } @article {pmid38449346, year = {2024}, author = {Speijer, D}, title = {How mitochondrial cristae illuminate the important role of oxygen during eukaryogenesis.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {46}, number = {5}, pages = {e2300193}, doi = {10.1002/bies.202300193}, pmid = {38449346}, issn = {1521-1878}, mesh = {Animals ; Adenosine Triphosphate/metabolism ; Biological Evolution ; Eukaryota/metabolism/genetics ; Eukaryotic Cells/metabolism ; *Mitochondria/metabolism/genetics ; *Mitochondrial Membranes/metabolism ; *Oxygen/metabolism ; }, abstract = {Inner membranes of mitochondria are extensively folded, forming cristae. The observed overall correlation between efficient eukaryotic ATP generation and the area of internal mitochondrial inner membranes both in unicellular organisms and metazoan tissues seems to explain why they evolved. However, the crucial use of molecular oxygen (O2) as final acceptor of the electron transport chain is still not sufficiently appreciated. O2 was an essential prerequisite for cristae development during early eukaryogenesis and could be the factor allowing cristae retention upon loss of mitochondrial ATP generation. Here I analyze illuminating bacterial and unicellular eukaryotic examples. I also discuss formative influences of intracellular O2 consumption on the evolution of the last eukaryotic common ancestor (LECA). These considerations bring about an explanation for the many genes coming from other organisms than the archaeon and bacterium merging at the start of eukaryogenesis.}, } @article {pmid38456649, year = {2024}, author = {Kutzer, MAM and Cornish, B and Jamieson, M and Zawistowska, O and Monteith, KM and Vale, PF}, title = {Mitochondrial background can explain variable costs of immune deployment.}, journal = {Journal of evolutionary biology}, volume = {37}, number = {4}, pages = {442-450}, doi = {10.1093/jeb/voae027}, pmid = {38456649}, issn = {1420-9101}, support = {RPG-2018-369//Leverhulme Trust Research Project/ ; }, mesh = {Animals ; Female ; *Drosophila melanogaster/physiology ; *Mitochondria/genetics ; Longevity/genetics ; Genotype ; Fertility/genetics ; }, abstract = {Organismal health and survival depend on the ability to mount an effective immune response against infection. Yet immune defence may be energy-demanding, resulting in fitness costs if investment in immune function deprives other physiological processes of resources. While evidence of costly immunity resulting in reduced longevity and reproduction is common, the role of energy-producing mitochondria on the magnitude of these costs is unknown. Here we employed Drosophila melanogaster cybrid lines, where several mitochondrial genotypes (mitotypes) were introgressed onto a single nuclear genetic background, to explicitly test the role of mitochondrial variation on the costs of immune stimulation. We exposed female flies carrying one of nine distinct mitotypes to either a benign, heat-killed bacterial pathogen (stimulating immune deployment while avoiding pathology) or a sterile control and measured lifespan, fecundity, and locomotor activity. We observed mitotype-specific costs of immune stimulation and identified a positive genetic correlation between life span and the proportion of time cybrids spent moving while alive. Our results suggest that costs of immunity are highly variable depending on the mitochondrial genome, adding to a growing body of work highlighting the important role of mitochondrial variation in host-pathogen interactions.}, } @article {pmid38456969, year = {2024}, author = {Ovciarikova, J and Shikha, S and Lacombe, A and Courjol, F and McCrone, R and Hussain, W and Maclean, A and Lemgruber, L and Martins-Duarte, ES and Gissot, M and Sheiner, L}, title = {Two ancient membrane pores mediate mitochondrial-nucleus membrane contact sites.}, journal = {The Journal of cell biology}, volume = {223}, number = {4}, pages = {}, pmid = {38456969}, issn = {1540-8140}, support = {/WT_/Wellcome Trust/United Kingdom ; 217173/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; BB/N003675/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Eukaryotic Cells ; *Mitochondria/genetics/metabolism ; Mitochondria Associated Membranes ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/genetics/metabolism ; *Toxoplasma/cytology ; *Cell Nucleus/metabolism ; Nuclear Envelope/metabolism ; Nuclear Pore/metabolism ; Protozoan Proteins/metabolism ; }, abstract = {Coordination between nucleus and mitochondria is essential for cell survival, and thus numerous communication routes have been established between these two organelles over eukaryotic cell evolution. One route for organelle communication is via membrane contact sites, functional appositions formed by molecular tethers. We describe a novel nuclear-mitochondrial membrane contact site in the protozoan Toxoplasma gondii. We have identified specific contacts occurring at the nuclear pore and demonstrated an interaction between components of the nuclear pore and the mitochondrial protein translocon, highlighting them as molecular tethers. Genetic disruption of the nuclear pore or the TOM translocon components, TgNup503 or TgTom40, respectively, result in contact site reduction, supporting their potential involvement in this tether. TgNup503 depletion further leads to specific mitochondrial morphology and functional defects, supporting a role for nuclear-mitochondrial contacts in mediating their communication. The discovery of a contact formed through interaction between two ancient mitochondrial and nuclear complexes sets the ground for better understanding of mitochondrial-nuclear crosstalk in eukaryotes.}, } @article {pmid38461774, year = {2024}, author = {Diaz-Cuadros, M}, title = {Mitochondrial metabolism and the continuing search for ultimate regulators of developmental rate.}, journal = {Current opinion in genetics & development}, volume = {86}, number = {}, pages = {102178}, doi = {10.1016/j.gde.2024.102178}, pmid = {38461774}, issn = {1879-0380}, mesh = {*Mitochondria/metabolism/genetics ; Animals ; *Embryonic Development/genetics ; *Gene Expression Regulation, Developmental/genetics ; Species Specificity ; Humans ; Protein Biosynthesis ; }, abstract = {The rate of embryonic development is a species-specific trait that depends on the properties of the intracellular environment, namely, the rate at which gene products flow through the central dogma of molecular biology. Although any given step in the production and degradation of gene products could theoretically be co-opted by evolution to modulate developmental speed, species are observed to accelerate or slow down all steps simultaneously. This suggests the rate of these molecular processes is jointly regulated by an upstream, ultimate factor. Mitochondrial metabolism was recently proposed to act as an ultimate regulator by controlling the pace of protein synthesis upstream of developmental tempo. Alternative candidates for ultimate regulators include species-specific gene expression levels of factors involved in the central dogma, as well as species-specific cell size. Overall, much work remains to be done before we can confidently identify the ultimate causes of species-specific developmental rates.}, } @article {pmid38468713, year = {2024}, author = {Iverson, ENK}, title = {Conservation Mitonuclear Replacement: Facilitated mitochondrial adaptation for a changing world.}, journal = {Evolutionary applications}, volume = {17}, number = {3}, pages = {e13642}, pmid = {38468713}, issn = {1752-4571}, abstract = {Most species will not be able to migrate fast enough to cope with climate change, nor evolve quickly enough with current levels of genetic variation. Exacerbating the problem are anthropogenic influences on adaptive potential, including the prevention of gene flow through habitat fragmentation and the erosion of genetic diversity in small, bottlenecked populations. Facilitated adaptation, or assisted evolution, offers a way to augment adaptive genetic variation via artificial selection, induced hybridization, or genetic engineering. One key source of genetic variation, particularly for climatic adaptation, are the core metabolic genes encoded by the mitochondrial genome. These genes influence environmental tolerance to heat, drought, and hypoxia, but must interact intimately and co-evolve with a suite of important nuclear genes. These coadapted mitonuclear genes form some of the important reproductive barriers between species. Mitochondrial genomes can and do introgress between species in an adaptive manner, and they may co-introgress with nuclear genes important for maintaining mitonuclear compatibility. Managers should consider the relevance of mitonuclear genetic variability in conservation decision-making, including as a tool for facilitating adaptation. I propose a novel technique dubbed Conservation Mitonuclear Replacement (CmNR), which entails replacing the core metabolic machinery of a threatened species-the mitochondrial genome and key nuclear loci-with those from a closely related species or a divergent population, which may be better-adapted to climatic changes or carry a lower genetic load. The most feasible route to CmNR is to combine CRISPR-based nuclear genetic editing with mitochondrial replacement and assisted reproductive technologies. This method preserves much of an organism's phenotype and could allow populations to persist in the wild when no other suitable conservation options exist. The technique could be particularly important on mountaintops, where rising temperatures threaten an alarming number of species with almost certain extinction in the next century.}, } @article {pmid38468766, year = {2022}, author = {Fernández, MB and Bleidorn, C and Calcaterra, LA}, title = {Wolbachia Infection in Native Populations of the Invasive Tawny Crazy Ant Nylanderia fulva.}, journal = {Frontiers in insect science}, volume = {2}, number = {}, pages = {905803}, pmid = {38468766}, issn = {2673-8600}, abstract = {Antagonistic interactions can affect population growth and dispersal of an invasive species. Wolbachia are intracellular endosymbiont bacteria that infect arthropod and nematode hosts and are able to manipulate reproduction, which in some cases leads to cocladogenesis. Moreover, the presence of the strictly maternally transferred Wolbachia in a population can indirectly induce selective sweeps on the hosts' mitochondria. Ants have a Wolbachia infection rate of about 34%, which makes phylogenetic studies using mitochondrial markers vulnerable of being confounded by the effect of the endosymbiont. Nylanderia fulva is an invasive ant native to South America, considered a pest in the United States. Its distribution and biology are poorly known in its native range, and the taxonomic identity of this and its closely related species, Nylanderia pubens, has only recently been understood with the aid of molecular phylogenies. Aiming at estimating robust phylogenetic relationships of N. fulva in its native range, we investigated the presence and pattern of Wolbachia infection in populations of N. fulva from Argentina, part of its native range, to account for its possible effect on the host population structure. Using the ftsZ gene, 30 nests of N. fulva and four from sympatric Nylanderia species were screened for the presence of Wolbachia. We sequenced the MLST genes, the highly variable gene wsp, as well as glyQ, a novel target gene for which new primers were designed. Phylogeny of the ants was estimated using mtDNA (COI). We found supergroup A Wolbachia strains infecting 73% of N. fulva nests and two nests of Nylanderia sp. 1. Wolbachia phylogenetic tree inferred with MLST genes is partially congruent with the host phylogeny topology, with the exception of a lineage of strains shared by ants from different N. fulva clades. Furthermore, by comparing with Wolbachia sequences infecting other ants, we found that the strains infecting different N. fulva clades are not monophyletic. Our findings suggest there are three recent independent horizontally transmitted Wolbachia infections in N. fulva, and we found no evidence of influence of Wolbachia in the host mtDNA based phylogeny.}, } @article {pmid38474079, year = {2024}, author = {Mourokh, L and Friedman, J}, title = {Mitochondria at the Nanoscale: Physics Meets Biology-What Does It Mean for Medicine?.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38474079}, issn = {1422-0067}, support = {Award # 66061-00 54//PSC-CUNY/ ; }, mesh = {Humans ; *Mitochondria/physiology ; *Mitochondrial Membranes/metabolism ; Proton Pumps/metabolism ; Physics ; Biology ; }, abstract = {Mitochondria are commonly perceived as "cellular power plants". Intriguingly, power conversion is not their only function. In the first part of this paper, we review the role of mitochondria in the evolution of eukaryotic organisms and in the regulation of the human body, specifically focusing on cancer and autism in relation to mitochondrial dysfunction. In the second part, we overview our previous works, revealing the physical principles of operation for proton-pumping complexes in the inner mitochondrial membrane. Our proposed simple models reveal the physical mechanisms of energy exchange. They can be further expanded to answer open questions about mitochondrial functions and the medical treatment of diseases associated with mitochondrial disorders.}, } @article {pmid38475850, year = {2024}, author = {Vesala, L and Basikhina, Y and Tuomela, T and Nurminen, A and Siukola, E and Vale, PF and Salminen, TS}, title = {Mitochondrial perturbation in immune cells enhances cell-mediated innate immunity in Drosophila.}, journal = {BMC biology}, volume = {22}, number = {1}, pages = {60}, pmid = {38475850}, issn = {1741-7007}, support = {RPG-2018-369//Leverhulme Trust/ ; 322732//Academy of Finland/ ; 328979//Academy of Finland/ ; 353367//Academy of Finland/ ; 3122800849//Sigrid Juséliuksen Säätiö/ ; }, mesh = {Animals ; Humans ; *Drosophila ; Drosophila melanogaster/metabolism ; *Wasps/genetics ; Mitochondria ; Immunity, Innate ; Hemocytes/metabolism ; }, abstract = {BACKGROUND: Mitochondria participate in various cellular processes including energy metabolism, apoptosis, autophagy, production of reactive oxygen species, stress responses, inflammation and immunity. However, the role of mitochondrial metabolism in immune cells and tissues shaping the innate immune responses are not yet fully understood. We investigated the effects of tissue-specific mitochondrial perturbation on the immune responses at the organismal level. Genes for oxidative phosphorylation (OXPHOS) complexes cI-cV were knocked down in the fruit fly Drosophila melanogaster, targeting the two main immune tissues, the fat body and the immune cells (hemocytes).

RESULTS: While OXPHOS perturbation in the fat body was detrimental, hemocyte-specific perturbation led to an enhanced immunocompetence. This was accompanied by the formation of melanized hemocyte aggregates (melanotic nodules), a sign of activation of cell-mediated innate immunity. Furthermore, the hemocyte-specific OXPHOS perturbation induced immune activation of hemocytes, resulting in an infection-like hemocyte profile and an enhanced immune response against parasitoid wasp infection. In addition, OXPHOS perturbation in hemocytes resulted in mitochondrial membrane depolarization and upregulation of genes associated with the mitochondrial unfolded protein response.

CONCLUSIONS: Overall, we show that while the effects of mitochondrial perturbation on immune responses are highly tissue-specific, mild mitochondrial dysfunction can be beneficial in immune-challenged individuals and contributes to variation in infection outcomes among individuals.}, } @article {pmid38480132, year = {2024}, author = {Methou, P and Chen, C and Komai, T}, title = {Revision of the alvinocaridid shrimp genus Rimicaris Williams & Rona, 1986 (Decapoda: Caridea) with description of a new species from the Mariana Arc hydrothermal vents.}, journal = {Zootaxa}, volume = {5406}, number = {4}, pages = {501-518}, doi = {10.11646/zootaxa.5406.4.1}, pmid = {38480132}, issn = {1175-5334}, mesh = {Animals ; Phylogeny ; *Hydrothermal Vents ; *Decapoda ; Mitochondria ; }, abstract = {A new species of alvinocaridid shrimp is reported, from the Northwest Eifuku hydrothermal vent field at 16191667 m depth on the Mariana Arc. A comprehensive phylogenetic reconstruction of Alvinocarididae based on the mitochondrial cytochrome c oxidase subunit I (COI) gene including this new species reveals the paraphyly of the genus Rimicaris Williams & Rona, 1986 with four other generaAlvinocaridinides, Manuscaris, Opaepele, and Shinkaicarisnested within it. We re-examine material of these four problematic genera, and synonymise them under Rimicaris whose diagnosis has been amended, in order to maintain a monophyletic Rimicaris. Our new species, Rimicaris cambonae sp. nov. is genetically close to Rimicaris loihi (Williams & Dobbs, 1995) comb. nov. (previously Opaepele loihi) with which it co-occurs, but can be morphologically distinguished by the less elevated dorsal surface of the rostrum, this being devoid of a median carina, a stronger pterygostomial tooth on the carapace, and a blunt rather than acuminate proximolateral process on the antennular stylocerite. Species previously assigned to the above listed, synonymized genera are also discussed, with new material examined for three key species: R. loihi, R. acuminata, and R. leurokolos. Further, Alvinocaridinides formosa Komai & Chan, 2010 and Manuscaris liui Wang & Sha, 2016 are synonymized under Rimicaris leurokolos (Kikuchi & Hashimoto, 2000) comb. nov. and R. acuminata (Komai & Tsuchida, 2015) comb. nov., respectively. Revised diagnoses are presented for R. loihi, R. acuminata, and R. leurokolos. After the present revision revision, Rimicaris now consists of 15 species.}, } @article {pmid38480282, year = {2024}, author = {Gordon, DP and Quek, ZBR and Huang, D}, title = {Four new species and a ribosomal phylogeny of Rhabdopleura (Hemichordata: Graptolithina) from New Zealand, with a review and key to all described extant taxa.}, journal = {Zootaxa}, volume = {5424}, number = {3}, pages = {323-357}, doi = {10.11646/zootaxa.5424.3.3}, pmid = {38480282}, issn = {1175-5334}, mesh = {Animals ; Phylogeny ; New Zealand ; RNA, Ribosomal, 18S/genetics ; Base Sequence ; *Mitochondria/genetics ; }, abstract = {All eight extant species ofRhabdopleuradescribed between 1869 and 2018 are provisionally accepted as valid based on a review of the literature and new data on two little-known species from the Azores. Additionally, four new species are described from the New Zealand region, increasing global diversity by 50%, and a dichotomous key to all 12 described species is provided based on morphological criteria. The distinction between colony morphologies based on erect-tube inception is regarded as particularly helpful in initial characterization of species. Erect ringed tubes are either produced directly from the surface of creeping-tubes or indirectly, i.e. a short adherent side branch from a creeping tube is interpolated between the creeping tube and an erect tube; such side branches are blind-ending. These two modes of erect-tube origination are here respectively termeddirectandindirect. Species with indirect erect-tube budding are predominant in the North Atlantic whereas species with direct erect-tube budding dominate in New Zealand waters. The only indirect-erect species from New Zealand, Rhabdopleura chathamica n. sp., was discovered on deepwater coral from 10081075 m, constituting the deepest record of the genus to date. Rhabdopleura emancipata n. sp., collected only in a detached state, constitutes a three-dimensional tangled growth that grew freely into the water columna unique morphology hitherto unknown among extant species. Owing to this growth mode, it provided a substratum for epibionts from several phyla. Rhabdopleura francesca n. sp. and Rhabdopleura decipula n. sp. are morphologically very similar but are distinguishable by their distinct placements in a phylogeny based on 16S mitochondrial and 18S nuclear rRNA genes. Phylogenetic reconstructions based on rRNA and mitochondrial genome data contribute to an updated phylogeny of all Rhabdopleura species sequenced thus far, some of which require more molecular sequences and morphological analyses for taxonomic determination.}, } @article {pmid38480360, year = {2024}, author = {Ghamizi, M and Falniowski, A and Boudellah, A and Hofman, S and Rharras, AE and Assad, N and Moutaouakil, S and Jaszczyska, A}, title = {Two new genera and species of the valvatiform hydrobiid snails (Caenogastropoda: Truncatelloidea: Hydrobiidae) from Morocco.}, journal = {Zootaxa}, volume = {5418}, number = {3}, pages = {223-239}, doi = {10.11646/zootaxa.5418.3.2}, pmid = {38480360}, issn = {1175-5334}, mesh = {Animals ; RNA, Ribosomal, 16S/genetics ; Morocco ; *Snails/genetics ; Phylogeny ; *Mitochondria/genetics ; }, abstract = {Stygobiont and crenobiont minute gastropods representing the family Hydrobiidae (Caenogastropoda: Truncatelloidea), characterized by the valvatoid low-spired shell, were collected from one spring and four wells in Bouregreg region, NW Morocco. The shells were photographed and measured; shell biometry is illustrated with principal component analysis. Penes were illustrated and described. Mitochondrial cytochrome oxidase subunit 1 (COI) and 16S rRNA, as well as nuclear 18S rRNA sequences were used to infer the phylogeny. The snails represented two genera, both new to science. Their closest relatives were taxa from the Iberian Peninsula, the rough molecular estimate of the time of divergence between these Moroccan and Iberian genera coincided with the Pliocene Flooding, which restored the Strait of Gibraltar to connect the Mediterranean Basin with Atlantic Ocean.}, } @article {pmid38485105, year = {2024}, author = {Na, I and Campos, C and Lax, G and Kwong, WK and Keeling, PJ}, title = {Phylogenomics reveals Adeleorina are an ancient and distinct subgroup of Apicomplexa.}, journal = {Molecular phylogenetics and evolution}, volume = {195}, number = {}, pages = {108060}, doi = {10.1016/j.ympev.2024.108060}, pmid = {38485105}, issn = {1095-9513}, mesh = {Animals ; Humans ; Phylogeny ; Plastids/genetics ; Genome ; *Apicomplexa/genetics ; *Genome, Plastid ; }, abstract = {Apicomplexans are a diverse phylum of unicellular eukaryotes that share obligate relationships with terrestrial and aquatic animal hosts. Many well-studied apicomplexans are responsible for several deadly zoonotic and human diseases, most notably malaria caused by Plasmodium. Interest in the evolutionary origin of apicomplexans has also spurred recent work on other more deeply-branching lineages, especially gregarines and sister groups like squirmids and chrompodellids. But a full picture of apicomplexan evolution is still lacking several lineages, and one major, diverse lineage that is notably absent is the adeleorinids. Adeleorina apicomplexans comprises hundreds of described species that infect invertebrate and vertebrate hosts across the globe. Although historically considered coccidians, phylogenetic trees based on limited data have shown conflicting branch positions for this subgroup, leaving this question unresolved. Phylogenomic trees and large-scale analyses comparing cellular functions and metabolism between major subgroups of apicomplexans have not incorporated Adeleorina because only a handful of molecular markers and a couple organellar genomes are available, ultimately excluding this group from contributing to our understanding of apicomplexan evolution and biology. To address this gap, we have generated complete genomes from mitochondria and plastids, as well as multiple deep-coverage single-cell transcriptomes of nuclear genes from two Adeleorina species, Klossia helicina and Legerella nova, and inferred a 206-protein phylogenomic tree of Apicomplexa. We observed distinct structures reported in species descriptions as remnant host structures surrounding adeleorinid oocysts. Klossia helicina and L. nova branched, as expected, with monoxenous adeleorinids within the Adeleorina and their mitochondrial and plastid genomes exhibited similarity to published organellar adeleorinid genomes. We show with a phylogeneomic tree and subsequent phylogenomic analyses that Adeleorina are not closely related to any of the currently sampled apicomplexan subgroups, and instead fall as a sister to a large clade encompassing Coccidia, Protococcidia, Hematozoa, and Nephromycida, collectively. This resolves Adeleorina as a key independently-branching group, separate from coccidians, on the tree of Apicomplexa, which now has all known major lineages sampled.}, } @article {pmid38485499, year = {2024}, author = {Li, CY and Liu, XC and Li, YZ and Wang, Y and Nie, YH and Xu, YT and Zhang, XT and Lu, Y and Sun, Q}, title = {Generation of mitochondrial replacement monkeys by female pronucleus transfer.}, journal = {Zoological research}, volume = {45}, number = {2}, pages = {292-298}, pmid = {38485499}, issn = {2095-8137}, mesh = {Mice ; Humans ; Female ; Animals ; *Mitochondrial Diseases/genetics/prevention & control/veterinary ; Haplorhini/genetics ; Mitochondria/genetics ; DNA, Mitochondrial/genetics ; Primates/genetics ; *Rodent Diseases ; }, abstract = {Mutations in mitochondrial DNA (mtDNA) are maternally inherited and have the potential to cause severe disorders. Mitochondrial replacement therapies, including spindle, polar body, and pronuclear transfers, are promising strategies for preventing the hereditary transmission of mtDNA diseases. While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos, its application in non-human primates has not been previously reported. In this study, we successfully generated four healthy cynomolgus monkeys (Macaca fascicularis) via female pronuclear transfer. These individuals all survived for more than two years and exhibited minimal mtDNA carryover (3.8%-6.7%), as well as relatively stable mtDNA heteroplasmy dynamics during development. The successful establishment of this non-human primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.}, } @article {pmid38488948, year = {2024}, author = {Ren, P and Zhang, J and Vijg, J}, title = {Somatic mutations in aging and disease.}, journal = {GeroScience}, volume = {46}, number = {5}, pages = {5171-5189}, pmid = {38488948}, issn = {2509-2723}, support = {AG038072/GF/NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; AG047200/GF/NIH HHS/United States ; 82172461//National Natural Science Foundation of China/ ; U19 AG056278/AG/NIA NIH HHS/United States ; P01 AG017242/AG/NIA NIH HHS/United States ; ES029519/GF/NIH HHS/United States ; AG056278/GF/NIH HHS/United States ; BC180689P1//DOD grant/ ; AG017242/GF/NIH HHS/United States ; HL145560/GF/NIH HHS/United States ; }, mesh = {*Aging/genetics ; Humans ; Animals ; *Mutation ; Mice ; Mutation Rate ; DNA Repair/genetics ; High-Throughput Nucleotide Sequencing ; }, abstract = {Time always leaves its mark, and our genome is no exception. Mutations in the genome of somatic cells were first hypothesized to be the cause of aging in the 1950s, shortly after the molecular structure of DNA had been described. Somatic mutation theories of aging are based on the fact that mutations in DNA as the ultimate template for all cellular functions are irreversible. However, it took until the 1990s to develop the methods to test if DNA mutations accumulate with age in different organs and tissues and estimate the severity of the problem. By now, numerous studies have documented the accumulation of somatic mutations with age in normal cells and tissues of mice, humans, and other animals, showing clock-like mutational signatures that provide information on the underlying causes of the mutations. In this review, we will first briefly discuss the recent advances in next-generation sequencing that now allow quantitative analysis of somatic mutations. Second, we will provide evidence that the mutation rate differs between cell types, with a focus on differences between germline and somatic mutation rate. Third, we will discuss somatic mutational signatures as measures of aging, environmental exposure, and activities of DNA repair processes. Fourth, we will explain the concept of clonally amplified somatic mutations, with a focus on clonal hematopoiesis. Fifth, we will briefly discuss somatic mutations in the transcriptome and in our other genome, i.e., the genome of mitochondria. We will end with a brief discussion of a possible causal contribution of somatic mutations to the aging process.}, } @article {pmid38492251, year = {2024}, author = {Keeling, PJ and Mtawali, M and Trznadel, M and Livingston, SJ and Wakeman, KC}, title = {Parallel functional reduction in the mitochondria of apicomplexan parasites.}, journal = {European journal of protistology}, volume = {94}, number = {}, pages = {126065}, doi = {10.1016/j.ejop.2024.126065}, pmid = {38492251}, issn = {1618-0429}, mesh = {*Apicomplexa/genetics/physiology/classification ; *Mitochondria/genetics ; Biological Evolution ; }, abstract = {Extreme functional reduction of mitochondria has taken place in parallel in many distantly related lineages of eukaryotes, leading to a number of recurring metabolic states with variously lost electron transport chain (ETC) complexes, loss of the tricarboxylic acid (TCA) cycle, and/or loss of the mitochondrial genome. The resulting mitochondria-related organelles (MROs) are generally structurally reduced and in the most extreme cases barely recognizable features of the cell with no role in energy metabolism whatsoever (e.g., mitosomes, which generally only make iron-sulfur clusters). Recently, a wide diversity of MROs were discovered to be hiding in plain sight: in gregarine apicomplexans. This diverse group of invertebrate parasites has been known and observed for centuries, but until recent applications of culture-free genomics, their mitochondria were unremarkable. The genomics, however, showed that mitochondrial function has reduced in parallel in multiple gregarine lineages to several different endpoints, including the most reduced mitosomes. Here we review this remarkable case of parallel evolution of MROs, and some of the interesting questions this work raises.}, } @article {pmid38493987, year = {2024}, author = {Wang, S and Li, Y and Jiang, K and Zhou, J and Chen, J and Liang, J and Ndoni, A and Xue, H and Ye, Z and Bu, W}, title = {Identifying a potentially invasive population in the native range of a species: The enlightenment from the phylogeography of the yellow spotted stink bug, Erthesina fullo (Hemiptera: Pentatomidae).}, journal = {Molecular phylogenetics and evolution}, volume = {195}, number = {}, pages = {108056}, doi = {10.1016/j.ympev.2024.108056}, pmid = {38493987}, issn = {1095-9513}, mesh = {Animals ; Phylogeography ; Phylogeny ; *Heteroptera/genetics ; Biological Evolution ; Mitochondria/genetics ; DNA, Mitochondrial/genetics ; Genetic Variation ; }, abstract = {The yellow spotted stink bug (YSSB), Erthesina fullo (Thunberg, 1783) is an important Asian pest that has recently successfully invaded Europe and an excellent material for research on the initial stage of biological invasion. Here, we reported the native evolutionary history, recent invasion history, and potential invasion threats of YSSB for the first time based on population genetic methods [using double digest restriction-site associated DNA (ddRAD) data and mitochondrial COI and CYTB] and ecological niche modelling. The results showed that four lineages (east, west, southwest, and Hainan Island) were established in the native range with a strong east-west differentiation phylogeographical structure, and the violent climate fluctuation might cause population divergence during the Middle and Upper Pleistocene. In addition, land bridges and monsoon promote dispersal and directional genetic exchanging between island populations and neighboring continental populations. The east lineage (EA) was identified as the source of invasion in Albania. EA had the widest geographical distribution among all other lineages, with a star-like haplotype network with the main haplotype as the core. It also had a rapid population expansion history, indicating that the source lineage might have stronger diffusion ability and adaptability. Our findings provided a significant biological basis for fine tracking of invasive source at the lineage or population level and promote early invasion warning of potential invasive species on a much subtler lineage level.}, } @article {pmid38496441, year = {2024}, author = {Dondi, A and Borgsmüller, N and Ferreira, PF and Haas, BJ and Jacob, F and Heinzelmann-Schwarz, V and , and Beerenwinkel, N}, title = {De novo detection of somatic variants in high-quality long-read single-cell RNA sequencing data.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38496441}, issn = {2692-8205}, support = {U24 CA180922/CA/NCI NIH HHS/United States ; }, abstract = {In cancer, genetic and transcriptomic variations generate clonal heterogeneity, leading to treatment resistance. Long-read single-cell RNA sequencing (LR scRNA-seq) has the potential to detect genetic and transcriptomic variations simultaneously. Here, we present LongSom, a computational workflow leveraging high-quality LR scRNA-seq data to call de novo somatic single-nucleotide variants (SNVs), including in mitochondria (mtSNVs), copy-number alterations (CNAs), and gene fusions, to reconstruct the tumor clonal heterogeneity. Before somatic variants calling, LongSom re-annotates marker gene based cell types using cell mutational profiles. LongSom distinguishes somatic SNVs from noise and germline polymorphisms by applying an extensive set of hard filters and statistical tests. Applying LongSom to human ovarian cancer samples, we detected clinically relevant somatic SNVs that were validated against matched DNA samples. Leveraging somatic SNVs and fusions, LongSom found subclones with different predicted treatment outcomes. In summary, LongSom enables de novo variants detection without the need for normal samples, facilitating the study of cancer evolution, clonal heterogeneity, and treatment resistance.}, } @article {pmid38500026, year = {2024}, author = {Yang, Y and Duan, C}, title = {Mitochondrial genome features and systematic evolution of diospyros kaki thunb 'Taishuu'.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {285}, pmid = {38500026}, issn = {1471-2164}, support = {YCKJ-2021021//Modern Agriculture Project of Yuncheng/ ; YCKJ-2021021//Modern Agriculture Project of Yuncheng/ ; }, mesh = {*Diospyros/genetics ; *Genome, Mitochondrial ; Repetitive Sequences, Nucleic Acid ; Codon, Terminator ; RNA, Transfer/genetics ; Phylogeny ; }, abstract = {BACKGROUND: 'Taishuu' has a crisp texture, abundant juice, and sweet flavor with hints of cantaloupe. The availability of mitochondrial genome data of Diospyros species is far from the known number of species.

RESULTS: The sequencing data were assembled into a closed circular mitochondrial chromosome with a 421,308 bp length and a 45.79% GC content. The mitochondrial genome comprised 40 protein-coding, 24 tRNA, and three rRNA genes. The most common codons for arginine (Arg), proline (Pro), glycine (Gly), tryptophan (Trp), valine (Val), alanine (Ala), and leucine (Leu) were AGA, CCA, GGA, UGG, GUA, GCA, and CUA, respectively. The start codon for cox1 and nad4L protein-coding genes was ACG (ATG), whereas the remaining protein-coding genes started with ATG. There are four types of stop codons: CGA, TAA, TAG, and TGA, with TAA being the most frequently used stop codon (45.24%). In the D. kaki Thunb. 'Taishuu' mitochondrial genome, a total of 645 repeat sequences were identified, including 125 SSRs, 7 tandem repeats, and 513 dispersed repeats. Collinearity analysis revealed a close relationship between D. kaki Thunb. 'Taishuu' and Diospyros oleifera, with conserved homologous gene fragments shared among these species in large regions of the mitochondrial genome. The protein-coding genes ccmB and nad4L were observed to undergo positive selection. Analysis of homologous sequences between chloroplasts and mitochondria identified 28 homologous segments, with a total length of 24,075 bp, accounting for 5.71% of the mitochondrial genome. These homologous segments contain 8 annotated genes, including 6 tRNA genes and 2 protein-coding genes (rrn18 and ccmC). There are 23 homologous genes between chloroplasts and nuclei. Mitochondria, chloroplasts, and nuclei share two homologous genes, which are trnV-GAC and trnW-CCA.

CONCLUSION: In conclusion, a high-quality chromosome-level draft genome for D. kaki was generated in this study, which will contribute to further studies of major economic traits in the genus Diospyros.}, } @article {pmid38502495, year = {2024}, author = {Maréchal, E}, title = {How Did Thylakoids Emerge in Cyanobacteria, and How Were the Primary Chloroplast and Chromatophore Acquired?.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2776}, number = {}, pages = {3-20}, pmid = {38502495}, issn = {1940-6029}, mesh = {Thylakoids/metabolism ; Chloroplasts/genetics/metabolism ; Photosynthesis/genetics ; *Cyanobacteria/genetics/metabolism ; Eukaryota ; *Chromatophores ; Symbiosis/genetics ; }, abstract = {The emergence of thylakoid membranes in cyanobacteria is a key event in the evolution of all oxygenic photosynthetic cells, from prokaryotes to eukaryotes. Recent analyses show that they could originate from a unique lipid phase transition rather than from a supposed vesicular budding mechanism. Emergence of thylakoids coincided with the great oxygenation event, more than two billion years ago. The acquisition of semi-autonomous organelles, such as the mitochondrion, the chloroplast, and, more recently, the chromatophore, is a critical step in the evolution of eukaryotes. They resulted from primary endosymbiotic events that seem to share general features, i.e., an acquisition of a bacterium/cyanobacteria likely via a phagocytic membrane, a genome reduction coinciding with an escape of genes from the organelle to the nucleus, and, finally, the appearance of an active system translocating nuclear-encoded proteins back to the organelles. An intense mobilization of foreign genes of bacterial origin, via horizontal gene transfers, plays a critical role. Some third partners, like Chlamydia, might have facilitated the transition from cyanobacteria to the early chloroplast. This chapter further details our current understanding of primary endosymbiosis, focusing on primary chloroplasts, thought to have appeared over a billion years ago, and the chromatophore, which appeared around a hundred years ago.}, } @article {pmid38502499, year = {2024}, author = {Kuntz, M and Dimnet, L and Pullara, S and Moyet, L and Rolland, N}, title = {The Main Functions of Plastids.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2776}, number = {}, pages = {89-106}, pmid = {38502499}, issn = {1940-6029}, mesh = {*Plastids/metabolism ; *Mitochondria/genetics ; }, abstract = {Plastids are semi-autonomous organelles like mitochondria and derive from a cyanobacterial ancestor that was engulfed by a host cell. During evolution, they have recruited proteins originating from the nuclear genome, and only parts of their ancestral metabolic properties were conserved and optimized to limit functional redundancy with other cell compartments. Furthermore, large disparities in metabolic functions exist among various types of plastids, and the characterization of their various metabolic properties is far from being accomplished. In this review, we provide an overview of the main functions, known to be achieved by plastids or shared by plastids and other compartments of the cell. In short, plastids appear at the heart of all main plant functions.}, } @article {pmid38503345, year = {2024}, author = {Nuryadi, H and Mandagi, IF and Masengi, KWA and Kusumi, J and Inomata, N and Yamahira, K}, title = {Evidence for hybridization-driven heteroplasmy maintained across generations in a ricefish endemic to a Wallacean ancient lake.}, journal = {Biology letters}, volume = {20}, number = {3}, pages = {20230385}, pmid = {38503345}, issn = {1744-957X}, mesh = {Humans ; Animals ; *Heteroplasmy ; Lakes ; Phylogeny ; *Oryzias/genetics ; DNA, Mitochondrial/genetics ; }, abstract = {Heteroplasmy, the presence of multiple mitochondrial DNA (mtDNA) haplotypes within cells of an individual, is caused by mutation or paternal leakage. However, heteroplasmy is usually resolved to homoplasmy within a few generations because of germ-line bottlenecks; therefore, instances of heteroplasmy are limited in nature. Here, we report heteroplasmy in the ricefish species Oryzias matanensis, endemic to Lake Matano, an ancient lake in Sulawesi Island, in which one individual was known to have many heterozygous sites in the mitochondrial NADH dehydrogenase subunit 2 (ND2) gene. In this study, we cloned the ND2 gene for some additional individuals with heterozygous sites and demonstrated that they are truly heteroplasmic. Phylogenetic analysis revealed that the extra haplotype within the heteroplasmic O. matanensis individuals clustered with haplotypes of O. marmoratus, a congeneric species inhabiting adjacent lakes. This indicated that the heteroplasmy originated from paternal leakage due to interspecific hybridization. The extra haplotype was unique and contained two non-synonymous substitutions. These findings demonstrate that this hybridization-driven heteroplasmy was maintained across generations for a long time to the extent that the extra mitochondria evolved within the new host.}, } @article {pmid38503840, year = {2024}, author = {Duran, DP and Laroche, RA and Roman, SJ and Godwin, W and Herrmann, DP and Bull, E and Egan, SP}, title = {Species delimitation, discovery and conservation in a tiger beetle species complex despite discordant genetic data.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {6617}, pmid = {38503840}, issn = {2045-2322}, mesh = {Animals ; Phylogeny ; *DNA, Mitochondrial/genetics ; Mitochondria ; Biodiversity ; *Coleoptera/genetics ; Species Specificity ; }, abstract = {In an age of species declines, delineating and discovering biodiversity is critical for both taxonomic accuracy and conservation. In recent years, there has been a movement away from using exclusively morphological characters to delineate and describe taxa and an increase in the use of molecular markers to describe diversity or through integrative taxonomy, which employs traditional morphological characters, as well as genetic or other data. Tiger beetles are charismatic, of conservation concern, and much work has been done on the morphological delineation of species and subspecies, but few of these taxa have been tested with genetic analyses. In this study, we tested morphologically based taxonomic hypotheses of polymorphic tiger beetles in the Eunota circumpicta (LaFerté-Sénectère, 1841) species complex using multilocus genomic and mtDNA analyses. We find multiple cryptic species within the previous taxonomic concept of Eunota circumpicta, some of which were historically recognized as subspecies. We found that the mtDNA and genomic datasets did not identify the same taxonomic units and that the mtDNA was most at odds with all other genetic and morphological patterns. Overall, we describe new cryptic diversity, which raises important conservation concerns, and provide a working example for testing species and subspecies validity despite discordant data.}, } @article {pmid38525035, year = {2024}, author = {Krasovec, G and Horkan, HR and Quéinnec, É and Chambon, JP}, title = {Intrinsic apoptosis is evolutionarily divergent among metazoans.}, journal = {Evolution letters}, volume = {8}, number = {2}, pages = {267-282}, pmid = {38525035}, issn = {2056-3744}, abstract = {Apoptosis is regulated cell death that depends on caspases. A specific initiator caspase is involved upstream of each apoptotic signaling pathway. Characterized in nematode, fly, and mammals, intrinsic apoptosis is considered to be ancestral, conserved among animals, and depends on shared initiators: caspase-9, Apaf-1 and Bcl-2. However, the biochemical role of mitochondria, the pivotal function of cytochrome c and the modality of caspase activation remain highly heterogeneous and hide profound molecular divergence among apoptotic pathways in animals. Uncovering the phylogenetic history of apoptotic actors, especially caspases, is crucial to shed light on the evolutionary history of intrinsic apoptosis. Here, we demonstrate with phylogenetic analyses that caspase-9, the fundamental key of intrinsic apoptosis, is deuterostome-specific, while caspase-2 is ancestral to bilaterians. Our analysis of Bcl-2 and Apaf-1 confirms heterogeneity in functional organization of apoptotic pathways in animals. Our results support emergence of distinct intrinsic apoptotic pathways during metazoan evolution.}, } @article {pmid38531492, year = {2024}, author = {López-Hervas, K and Santos, JC and Ron, SR and Betancourth-Cundar, M and Cannatella, DC and Tarvin, RD}, title = {Deep divergences among inconspicuously colored clades of Epipedobates poison frogs.}, journal = {Molecular phylogenetics and evolution}, volume = {195}, number = {}, pages = {108065}, doi = {10.1016/j.ympev.2024.108065}, pmid = {38531492}, issn = {1095-9513}, mesh = {Animals ; Phylogeny ; *Poison Frogs ; *Anura/genetics ; Mitochondria ; Ecuador ; }, abstract = {Poison frogs (Dendrobatidae) are famous for their aposematic species, having a combination of diverse color patterns and defensive skin toxins, yet most species in this family are inconspicuously colored and considered non-aposematic. Epipedobates is among the youngest genus-level clades of Dendrobatidae that includes both aposematic and inconspicuous species. Using Sanger-sequenced mitochondrial and nuclear markers, we demonstrate deep genetic divergences among inconspicuous species of Epipedobates but relatively shallow genetic divergences among conspicuous species. Our phylogenetic analysis includes broad geographic sampling of the inconspicuous lineages typically identified as E. boulengeri and E. espinosai, which reveals two putative new species, one in west-central Colombia (E. sp. 1) and the other in north-central Ecuador (E. aff. espinosai). We conclude that E. darwinwallacei is a junior subjective synonym of E. espinosai. We also clarify the geographic distributions of inconspicuous Epipedobates species including the widespread E. boulengeri. We provide a qualitative assessment of the phenotypic diversity in each nominal species, with a focus on the color and pattern of inconspicuous species. We conclude that Epipedobates contains eight known valid species, six of which are inconspicuous. A relaxed molecular clock analysis suggests that the most recent common ancestor of Epipedobates is ∼11.1 million years old, which nearly doubles previous estimates. Last, genetic information points to a center of species diversity in the Chocó at the southwestern border of Colombia with Ecuador. A Spanish translation of this text is available in the supplementary materials.}, } @article {pmid38534456, year = {2024}, author = {Casey, W and Kumaran, T and Massey, SE and Mishra, B}, title = {How Mitochondrial Signaling Games May Shape and Stabilize the Nuclear-Mitochondrial Symbiosis.}, journal = {Biology}, volume = {13}, number = {3}, pages = {}, pmid = {38534456}, issn = {2079-7737}, abstract = {The eukaryotic lineage has enjoyed a long-term "stable" mutualism between nucleus and mitochondrion, since mitochondrial endosymbiosis began about 2 billion years ago. This mostly cooperative interaction has provided the basis for eukaryotic expansion and diversification, which has profoundly altered the forms of life on Earth. While we ignore the exact biochemical details of how the alpha-proteobacterial ancestor of mitochondria entered into endosymbiosis with a proto-eukaryote, in more general terms, we present a signaling games perspective of how the cooperative relationship became established, and has been maintained. While games are used to understand organismal evolution, information-asymmetric games at the molecular level promise novel insights into endosymbiosis. Using a previously devised biomolecular signaling games approach, we model a sender-receiver information asymmetric game, in which the informed mitochondrial sender signals and the uninformed nuclear receiver may take actions (involving for example apoptosis, senescence, regeneration and autophagy/mitophagy). The simulation shows that cellularization is a stabilizing mechanism for Pareto efficient sender/receiver strategic interaction. In stark contrast, the extracellular environment struggles to maintain efficient outcomes, as senders are indifferent to the effects of their signals upon the receiver. Our hypothesis has translational implications, such as in cellular therapy, as mitochondrial medicine matures. It also inspires speculative conjectures about how an analogous human-AI endosymbiosis may be engineered.}, } @article {pmid38540407, year = {2024}, author = {Zhang, G and Jiao, Y and Zhao, Z and Chen, Q and Wang, Z and Zhu, J and Lv, N and Sun, G}, title = {Genome-Wide and Expression Pattern Analysis of the HIT4 Gene Family Uncovers the Involvement of GHHIT4_4 in Response to Verticillium Wilt in Gossypium hirsutum.}, journal = {Genes}, volume = {15}, number = {3}, pages = {}, pmid = {38540407}, issn = {2073-4425}, mesh = {*Gossypium/metabolism ; *Verticillium/genetics ; Phylogeny ; Disease Resistance/genetics ; Chromosome Mapping ; }, abstract = {Chromatin remodelers are essential for regulating plant growth, development, and responses to environmental stresses. HIT4 (HEAT-INTOLERANT 4) is a novel stress-induced chromatin remodeling factor that has been less studied in abiotic stress and stress resistance, particularly in cotton. In this study, we conducted a comprehensive analysis of the members of the HIT4 gene family in Gossypium hirsutum using bioinformatics methods, including phylogenetic relationships, gene organization, transcription profiles, phylogenetic connections, selection pressure, and stress response. A total of 18 HIT4 genes were identified in four cotton species, with six HIT4 gene members in upland cotton. Based on the evolutionary relationships shown in the phylogenetic tree, the 18 HIT4 protein sequences were classified into four distinct subgroups. Furthermore, we conducted chromosome mapping to determine the genomic locations of these genes and visually represented the structural characteristics of HIT4 in G. hirsutum. In addition, we predicted the regulatory elements in HIT4 in G. hirsutum and conducted an analysis of repetitive sequences and gene collinearity among HIT4 in four cotton species. Moreover, we calculated the Ka/Ks ratio for homologous genes to assess the selection pressure acting on HIT4. Using RNA-seq, we explored the expression patterns of HIT4 genes in G. hirsutum and Gossypium barbadense. Through weighted gene co-expression network analysis (WGCNA), we found that GHHIT4_4 belonged to the MEblue module, which was mainly enriched in pathways such as DNA replication, phagosome, pentose and glucuronate interconversions, steroid biosynthesis, and starch and sucrose metabolism. This module may regulate the mechanism of upland cotton resistance to Verticillium wilt through DNA replication, phagosome, and various metabolic pathways. In addition, we performed heterologous overexpression of GH_D11G0591 (GHHIT4_4) in tobacco, and the results showed a significant reduction in disease index compared to the wild type, with higher expression levels of disease resistance genes in the transgenic tobacco. After conducting a VIGS (virus-induced gene silencing) experiment in cotton, the results indicated that silencing GHHIT4_4 had a significant impact, the resistance to Verticillium wilt weakened, and the internode length of the plants significantly decreased by 30.7% while the number of true leaves increased by 41.5%. qRT-PCR analysis indicated that GHHIT4_4 mainly enhanced cotton resistance to Verticillium wilt by indirectly regulating the PAL, 4CL, and CHI genes. The subcellular localization results revealed that GHHIT4_4 was predominantly distributed in the mitochondria and nucleus. This study offers preliminary evidence for the involvement of the GHHIT4_4 in cotton resistance to Verticillium wilt and lays the foundation for further research on the disease resistance mechanism of this gene in cotton.}, } @article {pmid38543688, year = {2024}, author = {Ramos-González, PL and Alexandre, MAV and Potsclam-Barro, M and Duarte, LML and Michea Gonzalez, GL and Chabi-Jesus, C and Ramos, AF and Harakava, R and Lorenzi, H and Freitas-Astúa, J and Kitajima, EW}, title = {Two Novel Betarhabdovirins Infecting Ornamental Plants and the Peculiar Intracellular Behavior of the Cytorhabdovirus in the Liana Aristolochia gibertii.}, journal = {Viruses}, volume = {16}, number = {3}, pages = {}, pmid = {38543688}, issn = {1999-4915}, support = {PNPD20132154 - 33141010001P4 - PNPD - IBSP, 88882.157041/2017-01//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 17/50334-3//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2019/25078-9//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2021/02179-4//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {*Aristolochia/genetics ; *Mirabilis/genetics ; Genome, Viral ; *Rhabdoviridae ; Plants/genetics ; Phylogeny ; Plant Diseases ; }, abstract = {Two novel members of the subfamily Betarhabdovirinae, family Rhabdoviridae, were identified in Brazil. Overall, their genomes have the typical organization 3'-N-P-P3-M-G-L-5' observed in mono-segmented plant-infecting rhabdoviruses. In aristolochia-associated cytorhabdovirus (AaCV), found in the liana aristolochia (Aristolochia gibertii Hook), an additional short orphan ORF encoding a transmembrane helix was detected between P3 and M. The AaCV genome and inferred encoded proteins share the highest identity values, consistently < 60%, with their counterparts of the yerba mate chlorosis-associated virus (Cytorhabdovirus flaviyerbamate). The second virus, false jalap virus (FaJV), was detected in the herbaceous plant false jalap (Mirabilis jalapa L.) and represents together with tomato betanucleorhabdovirus 2, originally found in tomato plants in Slovenia, a tentative new species of the genus Betanucleorhabdovirus. FaJV particles accumulate in the perinuclear space, and electron-lucent viroplasms were observed in the nuclei of the infected cells. Notably, distinct from typical rhabdoviruses, most virions of AaCV were observed to be non-enclosed within membrane-bounded cavities. Instead, they were frequently seen in close association with surfaces of mitochondria or peroxisomes. Unlike FaJV, AaCV was successfully graft-transmitted to healthy plants of three species of the genus Aristolochia, while mechanical and seed transmission proved unsuccessful for both viruses. Data suggest that these viruses belong to two new tentative species within the subfamily Betarhabdovirinae.}, } @article {pmid38547143, year = {2024}, author = {Charrasse, S and Racine, V and Saint-Omer, C and Poquillon, T and Lionnard, L and Ledru, M and Gonindard, C and Delaunois, S and Kissa, K and Frye, RE and Pastore, M and Reynes, C and Frechet, M and Chajra, H and Aouacheria, A}, title = {Quantitative imaging and semiotic phenotyping of mitochondrial network morphology in live human cells.}, journal = {PloS one}, volume = {19}, number = {3}, pages = {e0301372}, pmid = {38547143}, issn = {1932-6203}, mesh = {Humans ; *Hydrogen Peroxide/pharmacology/metabolism ; *Mitochondria/metabolism ; Software ; Image Processing, Computer-Assisted/methods ; Algorithms ; }, abstract = {The importance of mitochondria in tissue homeostasis, stress responses and human diseases, combined to their ability to transition between various structural and functional states, makes them excellent organelles for monitoring cell health. There is therefore a need for technologies to accurately analyze and quantify changes in mitochondrial organization in a variety of cells and cellular contexts. Here we present an innovative computerized method that enables accurate, multiscale, fast and cost-effective analysis of mitochondrial shape and network architecture from confocal fluorescence images by providing more than thirty features. In order to facilitate interpretation of the quantitative results, we introduced two innovations: the use of Kiviat-graphs (herein named MitoSpider plots) to present highly multidimensional data and visualization of the various mito-cellular configurations in the form of morphospace diagrams (called MitoSigils). We tested our fully automated image analysis tool on rich datasets gathered from live normal human skin cells cultured under basal conditions or exposed to specific stress including UVB irradiation and pesticide exposure. We demonstrated the ability of our proprietary software (named MitoTouch) to sensitively discriminate between control and stressed dermal fibroblasts, and between normal fibroblasts and other cell types (including cancer tissue-derived fibroblasts and primary keratinocytes), showing that our automated analysis captures subtle differences in morphology. Based on this novel algorithm, we report the identification of a protective natural ingredient that mitigates the deleterious impact of hydrogen peroxide (H2O2) on mitochondrial organization. Hence we conceived a novel wet-plus-dry pipeline combining cell cultures, quantitative imaging and semiotic analysis for exhaustive analysis of mitochondrial morphology in living adherent cells. Our tool has potential for broader applications in other research areas such as cell biology and medicine, high-throughput drug screening as well as predictive and environmental toxicology.}, } @article {pmid38547729, year = {2024}, author = {Queiroz, MIC and Lazaro, CM and Dos Santos, LMB and Rentz, T and Virgilio-da-Silva, JV and Moraes-Vieira, PMM and Cunha, FAS and Santos, JCC and Vercesi, AE and Leite, ACR and Oliveira, HCF}, title = {In vivo chronic exposure to inorganic mercury worsens hypercholesterolemia, oxidative stress and atherosclerosis in the LDL receptor knockout mice.}, journal = {Ecotoxicology and environmental safety}, volume = {275}, number = {}, pages = {116254}, doi = {10.1016/j.ecoenv.2024.116254}, pmid = {38547729}, issn = {1090-2414}, mesh = {Animals ; Mice ; *Atherosclerosis/chemically induced ; Hydrogen Peroxide ; *Hypercholesterolemia ; Kidney Diseases ; *Mercury/toxicity ; Mice, Knockout ; Oxidative Stress/physiology ; Receptors, LDL/genetics ; }, abstract = {Heavy metal exposure leads to multiple system dysfunctions. The mechanisms are likely multifactorial and involve inflammation and oxidative stress. The aim of this study was to evaluate markers and risk factors for atherosclerosis in the LDL receptor knockout mouse model chronically exposed to inorganic mercury (Hg) in the drinking water. Results revealed that Hg exposed mice present increased plasma levels of cholesterol, without alterations in glucose. As a major source and target of oxidants, we evaluated mitochondrial function. We found that liver mitochondria from Hg treated mice show worse respiratory control, lower oxidative phosphorylation efficiency and increased H2O2 release. In addition, Hg induced mitochondrial membrane permeability transition. Erythrocytes from Hg treated mice showed a 50% reduction in their ability to take up oxygen, lower levels of reduced glutathione (GSH) and of antioxidant enzymes (SOD, catalase and GPx). The Hg treatment disturbed immune system cells counting and function. While lymphocytes were reduced, monocytes, eosinophils and neutrophils were increased. Peritoneal macrophages from Hg treated mice showed increased phagocytic activity. Hg exposed mice tissues present metal impregnation and parenchymal architecture alterations. In agreement, increased systemic markers of liver and kidney dysfunction were observed. Plasma, liver and kidney oxidative damage indicators (MDA and carbonyl) were increased while GSH and thiol groups were diminished by Hg exposure. Importantly, atherosclerotic lesion size in the aorta root of Hg exposed mice were larger than in controls. In conclusion, in vivo chronic exposure to Hg worsens the hypercholesterolemia, impairs mitochondrial bioenergetics and redox function, alters immune cells profile and function, causes several tissues oxidative damage and accelerates atherosclerosis development.}, } @article {pmid38548188, year = {2024}, author = {He, X and Qian, Z and Gichira, AW and Chen, J and Li, Z}, title = {Assembly and comparative analysis of the first complete mitochondrial genome of the invasive water hyacinth, Eichhornia crassipes.}, journal = {Gene}, volume = {914}, number = {}, pages = {148416}, doi = {10.1016/j.gene.2024.148416}, pmid = {38548188}, issn = {1879-0038}, mesh = {*Genome, Mitochondrial ; *Eichhornia/genetics ; *Phylogeny ; Introduced Species ; RNA, Transfer/genetics ; Base Composition ; RNA Editing ; Genome, Plant ; }, abstract = {Eichhornia crassipes is an aquatic plant in tropical and subtropical regions, renowned for its notorious invasive tendencies. In this study, we assembled the complete mitogenome of E. crassipes into a single circle molecule of 397,361 bp. The mitogenome has 58 unique genes, including 37 protein-coding genes (PCGs), 18 tRNA genes, three rRNA genes, and 47 % GC content. Sixteen (6.93 %) homologous fragments, ranging from 31 bp to 8548 bp, were identified, indicating the transfer of genetic material from chloroplasts to mitochondria. In addition, we detected positive selection in six PCGs (ccmB, ccmC, ccmFC, nad3, nad4 and sdh4), along with the identification of 782 RNA editing sites across 37 mt-PCGs. These findings suggest a potential contribution to the robust adaptation of this invasive plant to the stressful environment. Lastly, we inferred that phylogenetic conflicts of E. crassipes between the plastome and mitogenome may be attributed to the difference in nucleotide substitution rates between the two organelle genomes. In conclusion, our study provided vital genomic resources for further understanding the invasive mechanism of this species and exploring the dynamic evolution of mitogenomes within the monocot clade.}, } @article {pmid38554118, year = {2024}, author = {Laugier, F and Saclier, N and Béthune, K and Braun, A and Konecny, L and Lefébure, T and Luquet, E and Plénet, S and Romiguier, J and David, P}, title = {Both nuclear and cytoplasmic polymorphisms are involved in genetic conflicts over male fertility in the gynodioecious snail, Physa acuta.}, journal = {Evolution; international journal of organic evolution}, volume = {78}, number = {7}, pages = {1227-1236}, doi = {10.1093/evolut/qpae053}, pmid = {38554118}, issn = {1558-5646}, support = {ANR-19-CE02-0017//MINIGAN/ ; //French National Research Agency/ ; }, mesh = {Animals ; *Polymorphism, Genetic ; Male ; *Snails/genetics/physiology ; *Genome, Mitochondrial ; Cell Nucleus/genetics ; Fertility/genetics ; Hermaphroditic Organisms/genetics ; Evolution, Molecular ; Female ; Cytoplasm/genetics ; Infertility, Male/genetics ; }, abstract = {Gynodioecy, the coexistence of hermaphrodites with females, often reflects conflicts between cytoplasmic male sterility (CMS) genes and nuclear genes restoring male fertility. CMS is frequent in plants and has been recently discovered in one animal: the freshwater snail, Physa acuta. In this system, CMS was linked to a single divergent mitochondrial genome (D), devoid of apparent nuclear restoration. Our study uncovers a second, novel CMS-associated mitogenome (K) in Physa acuta, demonstrating an extraordinary acceleration of molecular evolution throughout the entire K mitochondrial genome, akin to the previously observed pattern in D. This suggests a pervasive occurrence of accelerated evolution in both CMS-associated lineages. Through a 17-generation introgression experiment, we further show that nuclear polymorphisms in K-mitogenome individuals contribute to the restoration of male function in natural populations. Our results underscore shared characteristics in gynodioecy between plants and animals, emphasizing the presence of multiple CMS mitotypes and cytonuclear conflicts. This reaffirms the pivotal role of mitochondria in influencing male function and in generating genomic conflicts that impact reproductive processes in animals.}, } @article {pmid38555796, year = {2024}, author = {Casimir, P and Iwata, R and Vanderhaeghen, P}, title = {Linking mitochondria metabolism, developmental timing, and human brain evolution.}, journal = {Current opinion in genetics & development}, volume = {86}, number = {}, pages = {102182}, pmid = {38555796}, issn = {1879-0380}, mesh = {Humans ; *Mitochondria/metabolism/genetics ; *Brain/growth & development/metabolism ; Animals ; *Biological Evolution ; *Neurons/metabolism/cytology ; Species Specificity ; Neurogenesis/genetics ; Mice ; }, abstract = {Changes in developmental timing are an important factor of evolution in organ shape and function. This is particularly striking for human brain development, which, compared with other mammals, is considerably prolonged at the level of the cerebral cortex, resulting in brain neoteny. Here, we review recent findings that indicate that mitochondria and metabolism contribute to species differences in the tempo of cortical neuron development. Mitochondria display species-specific developmental timeline and metabolic activity patterns that are highly correlated with the speed of neuron maturation. Enhancing mitochondrial activity in human cortical neurons results in their accelerated maturation, while its reduction leads to decreased maturation rates in mouse neurons. Together with other global and gene-specific mechanisms, mitochondria thus act as a cellular hourglass of neuronal developmental tempo and may thereby contribute to species-specific features of human brain ontogeny.}, } @article {pmid38561677, year = {2024}, author = {Chen, L and Dong, X and Huang, H and Xu, H and Rono, PC and Cai, X and Hu, G}, title = {Assembly and comparative analysis of the initial complete mitochondrial genome of Primulina hunanensis (Gesneriaceae): a cave-dwelling endangered plant.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {322}, pmid = {38561677}, issn = {1471-2164}, mesh = {*Genome, Mitochondrial ; Phylogeny ; DNA, Mitochondrial/genetics ; *Lamiales/genetics ; Mitochondria/genetics ; *Genome, Chloroplast ; }, abstract = {BACKGROUND: Primulina hunanensis, a troglobitic plant within the Primulina genus of Gesneriaceae family, exhibits robust resilience to arid conditions and holds great horticultural potential as an ornamental plant. The work of chloroplast genome (cpDNA) has been recently accomplished, however, the mitochondrial genome (mtDNA) that is crucial for plant evolution has not been reported.

RESULTS: In this study, we sequenced and assembled the P. hunanensis complete mtDNA, and elucidated its evolutionary and phylogenetic relationships. The assembled mtDNA spans 575,242 bp with 43.54% GC content, encompassing 60 genes, including 37 protein-coding genes (PCGs), 20 tRNA genes, and 3 rRNA genes. Notably, high number of repetitive sequences in the mtDNA and substantial sequence translocation from chloroplasts to mitochondria were observed. To determine the evolutionary and taxonomic positioning of P. hunanensis, a phylogenetic tree was constructed using mitochondrial PCGs from P. hunanensis and 32 other taxa. Furthermore, an exploration of PCGs relative synonymous codon usage, identification of RNA editing events, and an investigation of collinearity with closely related species were conducted.

CONCLUSIONS: This study reports the initial assembly and annotation of P. hunanensis mtDNA, contributing to the limited mtDNA repository for Gesneriaceae plants and advancing our understanding of their evolution for improved utilization and conservation.}, } @article {pmid38568891, year = {2024}, author = {D'Ercole, J and Dapporto, L and Opler, P and Schmidt, CB and Ho, C and Menchetti, M and Zakharov, EV and Burns, JM and Hebert, PDN}, title = {A genetic atlas for the butterflies of continental Canada and United States.}, journal = {PloS one}, volume = {19}, number = {4}, pages = {e0300811}, pmid = {38568891}, issn = {1932-6203}, mesh = {Animals ; United States ; *Butterflies/genetics ; Phylogeography ; DNA, Mitochondrial/genetics/chemistry ; Mitochondria/genetics ; Haplotypes ; Genetic Variation ; DNA Barcoding, Taxonomic ; Phylogeny ; }, abstract = {Multi-locus genetic data for phylogeographic studies is generally limited in geographic and taxonomic scope as most studies only examine a few related species. The strong adoption of DNA barcoding has generated large datasets of mtDNA COI sequences. This work examines the butterfly fauna of Canada and United States based on 13,236 COI barcode records derived from 619 species. It compiles i) geographic maps depicting the spatial distribution of haplotypes, ii) haplotype networks (minimum spanning trees), and iii) standard indices of genetic diversity such as nucleotide diversity (π), haplotype richness (H), and a measure of spatial genetic structure (GST). High intraspecific genetic diversity and marked spatial structure were observed in the northwestern and southern North America, as well as in proximity to mountain chains. While species generally displayed concordance between genetic diversity and spatial structure, some revealed incongruence between these two metrics. Interestingly, most species falling in this category shared their barcode sequences with one at least other species. Aside from revealing large-scale phylogeographic patterns and shedding light on the processes underlying these patterns, this work also exposed cases of potential synonymy and hybridization.}, } @article {pmid38587065, year = {2024}, author = {Shen, C and Xu, H and Huang, WZ and Zhao, Q and Zhu, RL}, title = {Is RNA editing truly absent in the complex thalloid liverworts (Marchantiopsida)? Evidence of extensive RNA editing from Cyathodium cavernarum.}, journal = {The New phytologist}, volume = {242}, number = {6}, pages = {2817-2831}, doi = {10.1111/nph.19750}, pmid = {38587065}, issn = {1469-8137}, support = {//East China Normal University/ ; 31970215//National Natural Science Foundation of China/ ; 32370218//National Natural Science Foundation of China/ ; }, mesh = {*RNA Editing/genetics ; *Hepatophyta/genetics ; *Phylogeny ; Plant Proteins/genetics/metabolism ; Chloroplasts/genetics/metabolism ; Mitochondria/genetics/metabolism ; Genes, Plant ; Amino Acid Sequence ; }, abstract = {RNA editing is a crucial modification in plants' organellar transcripts that converts cytidine to uridine (C-to-U; and sometimes uridine to cytidine) in RNA molecules. This post-transcriptional process is controlled by the PLS-class protein with a DYW domain, which belongs to the pentatricopeptide repeat (PPR) protein family. RNA editing is widespread in land plants; however, complex thalloid liverworts (Marchantiopsida) are the only group reported to lack both RNA editing and DYW-PPR protein. The liverwort Cyathodium cavernarum (Marchantiopsida, Cyathodiaceae), typically found in cave habitats, was newly found to have 129 C-to-U RNA editing sites in its chloroplast and 172 sites in its mitochondria. The Cyathodium genus, specifically C. cavernarum, has a large number of PPR editing factor genes, including 251 DYW-type PPR proteins. These DYW-type PPR proteins may be responsible for C-to-U RNA editing in C. cavernarum. Cyathodium cavernarum possesses both PPR DYW proteins and RNA editing. Our analysis suggests that the remarkable RNA editing capability of C. cavernarum may have been acquired alongside the emergence of DYW-type PPR editing factors. These findings provide insight into the evolutionary pattern of RNA editing in land plants.}, } @article {pmid38592734, year = {2024}, author = {Kwasniak-Owczarek, M and Janska, H}, title = {Experimental approaches to studying translation in plant semi-autonomous organelles.}, journal = {Journal of experimental botany}, volume = {75}, number = {17}, pages = {5175-5187}, pmid = {38592734}, issn = {1460-2431}, mesh = {*Chloroplasts/metabolism ; *Protein Biosynthesis ; *Mitochondria/metabolism ; Plants/metabolism/genetics ; Organelles/metabolism ; Plant Proteins/metabolism/genetics ; }, abstract = {Plant mitochondria and chloroplasts are semi-autonomous organelles originated from free-living bacteria that have retained reduced genomes during evolution. As a consequence, relatively few of the mitochondrial and chloroplast proteins are encoded in the organellar genomes and synthesized by the organellar ribosomes. Since both organellar genomes encode mainly components of the energy transduction systems, oxidative phosphorylation in mitochondria and photosynthetic apparatus in chloroplasts, understanding organellar translation is critical for a thorough comprehension of key aspects of mitochondrial and chloroplast activity affecting plant growth and development. Recent studies have clearly shown that translation is a key regulatory node in the expression of plant organellar genes, underscoring the need for an adequate methodology to study this unique stage of gene expression. The organellar translatome can be analysed by studying newly synthesized proteins or the mRNA pool recruited to the organellar ribosomes. In this review, we present experimental approaches used for studying translation in plant bioenergetic organelles. Their benefits and limitations, as well as the critical steps, are discussed. Additionally, we briefly mention several recently developed strategies to study organellar translation that have not yet been applied to plants.}, } @article {pmid38594641, year = {2024}, author = {Shen, B and Shen, A and Liu, L and Tan, Y and Li, S and Tan, Z}, title = {Assembly and comparative analysis of the complete multichromosomal mitochondrial genome of Cymbidium ensifolium, an orchid of high economic and ornamental value.}, journal = {BMC plant biology}, volume = {24}, number = {1}, pages = {255}, pmid = {38594641}, issn = {1471-2229}, support = {Xiangzi Caihuan Zhi (2022) No. 64; Xiangzi Caihuan Zhi (2022) No. 67; Xiangzi Caihuan Zhi (2023) No. 26; Xiangzi Caihuan Zhi (2023) No. 72//the Hunan Provincial Forestry Ecological Protection, Restoration and Development Special Fund Project/ ; 2023JJ50073//the Hunan Provincial Natural Science Foundation/ ; }, mesh = {*Genome, Mitochondrial/genetics ; Phylogeny ; Mitochondria/genetics ; DNA ; *Orchidaceae/genetics ; }, abstract = {BACKGROUND: Orchidaceae is one of the largest groups of angiosperms, and most species have high economic value and scientific research value due to their ornamental and medicinal properties. In China, Chinese Cymbidium is a popular ornamental orchid with high economic value and a long history. However, to date, no detailed information on the mitochondrial genome of any species of Chinese Cymbidium has been published.

RESULTS: Here, we present the complete assembly and annotation of the mitochondrial genome of Cymbidium ensifolium (L.) Sw. The mitogenome of C. ensifolium was 560,647 bp in length and consisted of 19 circular subgenomes ranging in size from 21,995 bp to 48,212 bp. The genome encoded 35 protein-coding genes, 36 tRNAs, 3 rRNAs, and 3405 ORFs. Repeat sequence analysis and prediction of RNA editing sites revealed a total of 915 dispersed repeats, 162 simple repeats, 45 tandem repeats, and 530 RNA editing sites. Analysis of codon usage showed a preference for codons ending in A/T. Interorganellar DNA transfer was identified in 13 of the 19 chromosomes, with plastid-derived DNA fragments representing 6.81% of the C. ensifolium mitochondrial genome. The homologous fragments of the mitochondrial genome and nuclear genome were also analysed. Comparative analysis showed that the GC content was conserved, but the size, structure, and gene content of the mitogenomes varied greatly among plants with multichromosomal mitogenome structure. Phylogenetic analysis based on the mitogenomes reflected the evolutionary and taxonomic statuses of C. ensifolium. Interestingly, compared with the mitogenomes of Cymbidium lancifolium Hook. and Cymbidium macrorhizon Lindl., the mitogenome of C. ensifolium lost 8 ribosomal protein-coding genes.

CONCLUSION: In this study, we assembled and annotated the mitogenome of C. ensifolium and compared it with the mitogenomes of other Liliidae and plants with multichromosomal mitogenome structures. Our findings enrich the mitochondrial genome database of orchid plants and reveal the rapid structural evolution of Cymbidium mitochondrial genomes, highlighting the potential for mitochondrial genes to help decipher plant evolutionary history.}, } @article {pmid38597829, year = {2024}, author = {Regina-Ferreira, L and Valdivieso-Rivera, F and Angelim, MKSC and Menezes Dos Reis, L and Furino, VO and Morari, J and Maia de Sousa, L and Consonni, SR and Sponton, CH and Moraes-Vieira, PM and Velloso, LA}, title = {Inhibition of Crif1 protects fatty acid-induced POMC neuron-like cell-line damage by increasing CPT-1 function.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {326}, number = {5}, pages = {E681-E695}, doi = {10.1152/ajpendo.00420.2023}, pmid = {38597829}, issn = {1522-1555}, support = {2013/07607-8//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; }, mesh = {Animals ; Mice ; *Carnitine O-Palmitoyltransferase/metabolism/genetics ; Cell Line ; *Fatty Acids/metabolism ; Hypothalamus/metabolism/drug effects ; *Mitochondria/metabolism/drug effects ; Neurons/drug effects/metabolism ; Pro-Opiomelanocortin/metabolism/genetics ; Reactive Oxygen Species/metabolism ; *Cell Cycle Proteins/antagonists & inhibitors/metabolism ; }, abstract = {Hypothalamic proopiomelanocortin (POMC) neurons are sensors of signals that reflect the energy stored in the body. Inducing mild stress in proopiomelanocortin neurons protects them from the damage promoted by the consumption of a high-fat diet, mitigating the development of obesity; however, the cellular mechanisms behind these effects are unknown. Here, we induced mild stress in a proopiomelanocortin neuron cell line by inhibiting Crif1. In proopiomelanocortin neurons exposed to high levels of palmitate, the partial inhibition of Crif1 reverted the defects in mitochondrial respiration and ATP production; this was accompanied by improved mitochondrial fusion/fission cycling. Furthermore, the partial inhibition of Crif1 resulted in increased reactive oxygen species production, increased fatty acid oxidation, and reduced dependency on glucose for mitochondrial respiration. These changes were dependent on the activity of CPT-1. Thus, we identified a CPT-1-dependent metabolic shift toward greater utilization of fatty acids as substrates for respiration as the mechanism behind the protective effect of mild stress against palmitate-induced damage of proopiomelanocortin neurons.NEW & NOTEWORTHY Saturated fats can damage hypothalamic neurons resulting in positive energy balance, and this is mitigated by mild cellular stress; however, the mechanisms behind this protective effect are unknown. Using a proopiomelanocortin cell line, we show that under exposure to a high concentration of palmitate, the partial inhibition of the mitochondrial protein Crif1 results in protection due to a metabolic shift warranted by the increased expression and activity of the mitochondrial fatty acid transporter CPT-1.}, } @article {pmid38601302, year = {2024}, author = {Fukasawa, Y and Driguez, P and Bougouffa, S and Carty, K and Putra, A and Cheung, MS and Ermini, L}, title = {Plasticity of repetitive sequences demonstrated by the complete mitochondrial genome of Eucalyptus camaldulensis.}, journal = {Frontiers in plant science}, volume = {15}, number = {}, pages = {1339594}, pmid = {38601302}, issn = {1664-462X}, abstract = {The tree Eucalyptus camaldulensis is a ubiquitous member of the Eucalyptus genus, which includes several hundred species. Despite the extensive sequencing and assembly of nuclear genomes from various eucalypts, the genus has only one fully annotated and complete mitochondrial genome (mitogenome). Plant mitochondria are characterized by dynamic genomic rearrangements, facilitated by repeat content, a feature that has hindered the assembly of plant mitogenomes. This complexity is evident in the paucity of available mitogenomes. This study, to the best of our knowledge, presents the first E. camaldulensis mitogenome. Our findings suggest the presence of multiple isomeric forms of the E. camaldulensis mitogenome and provide novel insights into minor rearrangements triggered by nested repeat sequences. A comparative sequence analysis of the E. camaldulensis and E. grandis mitogenomes unveils evolutionary changes between the two genomes. A significant divergence is the evolution of a large repeat sequence, which may have contributed to the differences observed between the two genomes. The largest repeat sequences in the E. camaldulensis mitogenome align well with significant yet unexplained structural variations in the E. grandis mitogenome, highlighting the adaptability of repeat sequences in plant mitogenomes.}, } @article {pmid38603509, year = {2024}, author = {Coale, TH and Loconte, V and Turk-Kubo, KA and Vanslembrouck, B and Mak, WKE and Cheung, S and Ekman, A and Chen, JH and Hagino, K and Takano, Y and Nishimura, T and Adachi, M and Le Gros, M and Larabell, C and Zehr, JP}, title = {Nitrogen-fixing organelle in a marine alga.}, journal = {Science (New York, N.Y.)}, volume = {384}, number = {6692}, pages = {217-222}, doi = {10.1126/science.adk1075}, pmid = {38603509}, issn = {1095-9203}, mesh = {*Cyanobacteria/genetics/metabolism ; *Haptophyta/microbiology ; *Nitrogen/metabolism ; *Nitrogen Fixation/genetics ; Seawater/microbiology ; Symbiosis ; *Mitochondria/metabolism ; Chloroplasts/metabolism ; }, abstract = {Symbiotic interactions were key to the evolution of chloroplast and mitochondria organelles, which mediate carbon and energy metabolism in eukaryotes. Biological nitrogen fixation, the reduction of abundant atmospheric nitrogen gas (N2) to biologically available ammonia, is a key metabolic process performed exclusively by prokaryotes. Candidatus Atelocyanobacterium thalassa, or UCYN-A, is a metabolically streamlined N2-fixing cyanobacterium previously reported to be an endosymbiont of a marine unicellular alga. Here we show that UCYN-A has been tightly integrated into algal cell architecture and organellar division and that it imports proteins encoded by the algal genome. These are characteristics of organelles and show that UCYN-A has evolved beyond endosymbiosis and functions as an early evolutionary stage N2-fixing organelle, or "nitroplast."}, } @article {pmid38611479, year = {2024}, author = {Qian, F and Zuo, D and Zeng, T and Gu, L and Wang, H and Du, X and Zhu, B and Ou, J}, title = {Identification, Evolutionary Dynamics, and Gene Expression Patterns of the ACP Gene Family in Responding to Salt Stress in Brassica Genus.}, journal = {Plants (Basel, Switzerland)}, volume = {13}, number = {7}, pages = {}, pmid = {38611479}, issn = {2223-7747}, support = {32060463//National Natural Science Foundation of China/ ; 32260460//National Natural Science Foundation of China/ ; Qian Kehe Support [2022] key 026//Guizhou Provincial Science and Technology Plan Project/ ; Qiankehezhicheng【2022】Key 031//The Scientific and Technological Key Program of Guizhou province/ ; }, abstract = {Acyl carrier proteins (ACPs) have been reported to play a crucial role in responding to biotic and abiotic stresses, regulating growth and development. However, the biological function of the ACP gene family in the Brassica genus has been limited until now. In this study, we conducted a comprehensive analysis and identified a total of 120 ACP genes across six species in the Brassica genus. Among these, there were 27, 26, and 30 ACP genes in the allotetraploid B. napus, B. juncea, and B. carinata, respectively, and 14, 13, and 10 ACP genes in the diploid B. rapa, B. oleracea, and B. nigra, respectively. These ACP genes were further classified into six subclades, each containing conserved motifs and domains. Interestingly, the majority of ACP genes exhibited high conservation among the six species, suggesting that the genome evolution and polyploidization processes had relatively minor effects on the ACP gene family. The duplication modes of the six Brassica species were diverse, and the expansion of most ACPs in Brassica occurred primarily through dispersed duplication (DSD) events. Furthermore, most of the ACP genes were under purifying selection during the process of evolution. Subcellular localization experiments demonstrated that ACP genes in Brassica species are localized in chloroplasts and mitochondria. Cis-acting element analysis revealed that most of the ACP genes were associated with various abiotic stresses. Additionally, RNA-seq data revealed differential expression levels of BnaACP genes across various tissues in B. napus, with particularly high expression in seeds and buds. qRT-PCR analysis further indicated that BnaACP genes play a significant role in salt stress tolerance. These findings provide a comprehensive understanding of ACP genes in Brassica plants and will facilitate further functional analysis of these genes.}, } @article {pmid38630841, year = {2024}, author = {Gonzalez, RC and Bezerra de Lima, LC and Passos, P and Silva, MJJ}, title = {The good, the bad and the boa: An unexpected new species of a true boa revealed by morphological and molecular evidence.}, journal = {PloS one}, volume = {19}, number = {4}, pages = {e0298159}, pmid = {38630841}, issn = {1932-6203}, mesh = {Animals ; Male ; Phylogeny ; *Boidae/genetics ; Mitochondria/genetics ; Brazil ; *Lepidoptera ; }, abstract = {Snakes of the genus Boa are outstanding elements of the New World biota with a broad sociological influence on pop culture. Historically, several taxa have been recognized in the past 300 years, being mostly described in the early days of binomial nomenclature. As a rule, these taxa were recognized based on a suite of phenotypic characters mainly those from the external morphology. However, there is a huge disagreement with respect to the current taxonomy and available molecular phylogenies. In order to reconcile both lines of evidence, we investigate the phylogenetic reconstruction (using mitochondrial and nuclear genes) of the genus in parallel to the detailed study of some phenotypic systems from a geographically representative sample of the cis-Andean mainland Boa constrictor. We used cyt-b only (744bp) from 73 samples, and cyt-b, ND4, NTF3, and ODC partial sequences (in a total of 2305 bp) from 35 samples, comprising nine currently recognized taxa (species or subspecies), to infer phylogenetic relationships of boas. Topologies recovered along all the analyses and genetic distances obtained allied to a unique combination of morphological traits (colouration, pholidosis, meristic, morphometric, and male genitalia features) allowed us to recognize B. constrictor lato sensu, B. nebulosa, B. occidentalis, B. orophias and a distinct lineage from the eastern coast of Brazil, which we describe here as a new species, diagnosing it from the previously recognized taxa. Finally, we discuss the minimally necessary changes in the taxonomy of Boa constrictor complex; the value of some usually disregarded phenotypic character system; and we highlight the urgency of continuing environmental policy to preserve one of the most impacted Brazilian hotspots, the Atlantic Forest, which represents an ecoregion full of endemism.}, } @article {pmid38646826, year = {2024}, author = {Aronowitz, DI and Geoffrion, TR and Piel, S and Benson, EJ and Morton, SR and Starr, J and Melchior, RW and Gaudio, HA and Degani, RE and Widmann, NJ and Weeks, MK and Ko, TS and Licht, DJ and Hefti, M and Gaynor, JW and Kilbaugh, TJ and Mavroudis, CD}, title = {Early Impairment of Cerebral Bioenergetics After Cardiopulmonary Bypass in Neonatal Swine.}, journal = {World journal for pediatric & congenital heart surgery}, volume = {15}, number = {4}, pages = {459-466}, doi = {10.1177/21501351241232077}, pmid = {38646826}, issn = {2150-136X}, mesh = {Animals ; *Cardiopulmonary Bypass/adverse effects ; Swine ; *Energy Metabolism/physiology ; *Animals, Newborn ; *Mitochondria/metabolism ; Disease Models, Animal ; Brain/metabolism ; Lactic Acid/metabolism/blood/analysis ; Pyruvic Acid/metabolism ; Glycerol/metabolism ; }, abstract = {Objectives: We previously demonstrated cerebral mitochondrial dysfunction in neonatal swine immediately following a period of full-flow cardiopulmonary bypass (CPB). The extent to which this dysfunction persists in the postoperative period and its correlation with other markers of cerebral bioenergetic failure and injury is unknown. We utilized a neonatal swine model to investigate the early evolution of mitochondrial function and cerebral bioenergetic failure after CPB. Methods: Twenty piglets (mean weight 4.4 ± 0.5 kg) underwent 3 h of CPB at 34 °C via cervical cannulation and were followed for 8, 12, 18, or 24 h (n = 5 per group). Markers of brain tissue damage (glycerol) and bioenergetic dysfunction (lactate to pyruvate ratio) were continuously measured in cerebral microdialysate samples. Control animals (n = 3, mean weight 4.1 ± 1.2 kg) did not undergo cannulation or CPB. Brain tissue was extracted immediately after euthanasia to obtain ex-vivo cortical mitochondrial respiration and frequency of cortical microglial nodules (indicative of cerebral microinfarctions) via neuropathology. Results: Both the lactate to pyruvate ratio (P < .0001) and glycerol levels (P = .01) increased in cerebral microdialysate within 8 h after CPB. At 24 h post-CPB, cortical mitochondrial respiration was significantly decreased compared with controls (P = .046). The presence of microglial nodules increased throughout the study period (24 h) (P = .01, R[2 ]= 0.9). Conclusion: CPB results in impaired cerebral bioenergetics that persist for at least 24 h. During this period of bioenergetic impairment, there may be increased susceptibility to secondary injury related to alterations in metabolic delivery or demand, such as hypoglycemia, seizures, and decreased cerebral blood flow.}, } @article {pmid38652016, year = {2024}, author = {Kwok van der Giezen, FM and Viljoen, A and Campbell-Clause, L and Dao, NT and Colas des Francs-Small, C and Small, I}, title = {Insights into U-to-C RNA editing from the lycophyte Phylloglossum drummondii.}, journal = {The Plant journal : for cell and molecular biology}, volume = {119}, number = {1}, pages = {445-459}, doi = {10.1111/tpj.16775}, pmid = {38652016}, issn = {1365-313X}, support = {DP200102981//Australian Research Council/ ; }, mesh = {*RNA Editing/genetics ; *RNA, Plant/genetics ; Genome, Mitochondrial/genetics ; Transcriptome ; Uridine/metabolism/genetics ; Genome, Chloroplast ; Phylogeny ; Mitochondria/genetics/metabolism ; }, abstract = {The lycophyte Phylloglossum drummondii is the sole inhabitant of its genus in the Huperzioideae group and one of a small minority of plants which perform uridine to cytidine RNA editing. We assembled the P. drummondii chloroplast and mitochondrial genomes and used RNA sequence data to build a comprehensive profile of organellar RNA editing events. In addition to many C-to-U editing events in both organelles, we found just four U-to-C editing events in the mitochondrial transcripts cob, nad1, nad5 and rpl2. These events are conserved in related lycophytes in the genera Huperzia and Phlegmariurus. De novo transcriptomes for three of these lycophytes were assembled to search for putative U-to-C RNA editing enzymes. Four putative U-to-C editing factors could be matched to the four mitochondrial U-to-C editing sites. Due to the unusually few numbers of U-to-C RNA editing sites, P. drummondii and related lycophytes are useful models for studying this poorly understood mechanism.}, } @article {pmid38658152, year = {2024}, author = {Fan, C and Yang, J and Chen, R and Liu, W and Xiang, X}, title = {[Identification and expression analysis of the HSP70 gene family under abiotic stresses in Litchi chinensis].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {40}, number = {4}, pages = {1102-1119}, doi = {10.13345/j.cjb.230450}, pmid = {38658152}, issn = {1872-2075}, mesh = {*Litchi/genetics/metabolism ; *HSP70 Heat-Shock Proteins/genetics/metabolism ; *Stress, Physiological/genetics ; *Gene Expression Regulation, Plant ; *Plant Proteins/genetics/metabolism/biosynthesis ; *Phylogeny ; *Droughts ; Multigene Family ; Salt Stress/genetics ; }, abstract = {HSP70 protein, as an important member of the heat shock protein (HSP) family, plays an important role in plant growth, development, and response to biotic and abiotic stresses. In order to explore the role of HSP70 gene family members in Litchi chinensis under low temperature, high temperature, drought, and salt stress, bioinformatics methods were used to identify the HSP70 gene family members within the entire L. chinensis genome. The expression of these genes under various abiotic stresses was then detected using quantitative real-time PCR (qRT-PCR). The results showed that the LcHSP70 gene family consisted of 18 members, which were unevenly distributed across ten L. chinensis chromosomes. The LcHSP70 protein contained 479-851 amino acids, with isoelectric points ranging from 5.07 to 6.95, and molecular weights from 52.44 kDa to 94.07 kDa. The predicted subcellular localization showed that LcHSP70 protein was present in the nucleus, cytoplasm, endoplasmic reticulum, mitochondria, and chloroplast. Phylogenetic analysis divided the LcHSP70 proteins into five subgroups, namely Ⅰ, Ⅱ, Ⅲ, Ⅳ, and Ⅵ. The promoter regions of the LcHSP70 genes contained various cis-acting elements related to plant growth, development, hormone response, and stress response. Moreover, the expression of LcHSP70 genes displayed distint tissue-specific expression level, categorized into universal expression and specific expression. From the selected 6 LcHSP70 genes (i.e., LcHSP70-1, LcHSP70-5, LcHSP70-10, LcHSP70-14, LcHSP70-16, and LcHSP70-18), their relative expression levels were assessed under different abiotic stresses using qRT-PCR. The results indicated that the gene family members exhibited diverse responses to low temperature, high temperature, drought, and salt stress, with significant variations in their expression levels across different time periods. These results provide a foundation for further exploration of the function of the LcHSP70 gene family.}, } @article {pmid38658571, year = {2024}, author = {Xing, L and Gkini, V and Nieminen, AI and Zhou, HC and Aquilino, M and Naumann, R and Reppe, K and Tanaka, K and Carmeliet, P and Heikinheimo, O and Pääbo, S and Huttner, WB and Namba, T}, title = {Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3468}, pmid = {38658571}, issn = {2041-1723}, support = {340179, 351966, 336234//Academy of Finland (Suomen Akatemia)/ ; }, mesh = {*Neocortex/metabolism/embryology/growth & development/cytology ; Humans ; Animals ; *Glutamate Dehydrogenase/metabolism/genetics ; *GTPase-Activating Proteins/metabolism/genetics ; Ketoglutaric Acids/metabolism ; Neuroglia/metabolism ; Glutamic Acid/metabolism ; Mitochondria/metabolism/genetics ; Mice ; Citric Acid Cycle/genetics ; Female ; }, abstract = {Metabolism has recently emerged as a major target of genes implicated in the evolutionary expansion of human neocortex. One such gene is the human-specific gene ARHGAP11B. During human neocortex development, ARHGAP11B increases the abundance of basal radial glia, key progenitors for neocortex expansion, by stimulating glutaminolysis (glutamine-to-glutamate-to-alpha-ketoglutarate) in mitochondria. Here we show that the ape-specific protein GLUD2 (glutamate dehydrogenase 2), which also operates in mitochondria and converts glutamate-to-αKG, enhances ARHGAP11B's ability to increase basal radial glia abundance. ARHGAP11B + GLUD2 double-transgenic bRG show increased production of aspartate, a metabolite essential for cell proliferation, from glutamate via alpha-ketoglutarate and the TCA cycle. Hence, during human evolution, a human-specific gene exploited the existence of another gene that emerged during ape evolution, to increase, via concerted changes in metabolism, progenitor abundance and neocortex size.}, } @article {pmid38668357, year = {2024}, author = {Martinez, P and Baghli, I and Gourjon, G and Seyfried, TN}, title = {Mitochondrial-Stem Cell Connection: Providing Additional Explanations for Understanding Cancer.}, journal = {Metabolites}, volume = {14}, number = {4}, pages = {}, pmid = {38668357}, issn = {2218-1989}, abstract = {The cancer paradigm is generally based on the somatic mutation model, asserting that cancer is a disease of genetic origin. The mitochondrial-stem cell connection (MSCC) proposes that tumorigenesis may result from an alteration of the mitochondria, specifically a chronic oxidative phosphorylation (OxPhos) insufficiency in stem cells, which forms cancer stem cells (CSCs) and leads to malignancy. Reviewed evidence suggests that the MSCC could provide a comprehensive understanding of all the different stages of cancer. The metabolism of cancer cells is altered (OxPhos insufficiency) and must be compensated by using the glycolysis and the glutaminolysis pathways, which are essential to their growth. The altered mitochondria regulate the tumor microenvironment, which is also necessary for cancer evolution. Therefore, the MSCC could help improve our understanding of tumorigenesis, metastases, the efficiency of standard treatments, and relapses.}, } @article {pmid38668970, year = {2024}, author = {Muthye, V and Lavrov, DV}, title = {Characterization of the Mitochondrial Proteome in the Ctenophore Mnemiopsis leidyi Using MitoPredictor.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2757}, number = {}, pages = {239-257}, pmid = {38668970}, issn = {1940-6029}, support = {R01 NS114491/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Ctenophora/metabolism/genetics ; *Proteome ; *Mitochondrial Proteins/metabolism/genetics ; Computational Biology/methods ; Mitochondria/metabolism ; Proteomics/methods ; Software ; }, abstract = {Mitochondrial proteomes have been experimentally characterized for only a handful of animal species. However, the increasing availability of genomic and transcriptomic data allows one to infer mitochondrial proteins using computational tools. MitoPredictor is a novel random forest classifier, which utilizes orthology search, mitochondrial targeting signal (MTS) identification, and protein domain content to infer mitochondrial proteins in animals. MitoPredictor's output also includes an easy-to-use R Shiny applet for the visualization and analysis of the results. In this article, we provide a guide for predicting and analyzing the mitochondrial proteome of the ctenophore Mnemiopsis leidyi using MitoPredictor.}, } @article {pmid38673928, year = {2024}, author = {Aleshina, YA and Aleshin, VA}, title = {Evolutionary Changes in Primate Glutamate Dehydrogenases 1 and 2 Influence the Protein Regulation by Ligands, Targeting and Posttranslational Modifications.}, journal = {International journal of molecular sciences}, volume = {25}, number = {8}, pages = {}, pmid = {38673928}, issn = {1422-0067}, support = {23-74-10036//Russian Science Foundation/ ; }, mesh = {Animals ; Humans ; *Evolution, Molecular ; *Glutamate Dehydrogenase/metabolism/genetics/chemistry ; Ligands ; Mutation ; Primates/genetics ; *Protein Processing, Post-Translational ; }, abstract = {There are two paralogs of glutamate dehydrogenase (GDH) in humans encoded by the GLUD1 and GLUD2 genes as a result of a recent retroposition during the evolution of primates. The two human GDHs possess significantly different regulation by allosteric ligands, which is not fully characterized at the structural level. Recent advances in identification of the GDH ligand binding sites provide a deeper perspective on the significance of the accumulated substitutions within the two GDH paralogs. In this review, we describe the evolution of GLUD1 and GLUD2 after the duplication event in primates using the accumulated sequencing and structural data. A new gibbon GLUD2 sequence questions the indispensability of ancestral R496S and G509A mutations for GLUD2 irresponsiveness to GTP, providing an alternative with potentially similar regulatory features. The data of both GLUD1 and GLUD2 evolution not only confirm substitutions enhancing GLUD2 mitochondrial targeting, but also reveal a conserved mutation in ape GLUD1 mitochondrial targeting sequence that likely reduces its transport to mitochondria. Moreover, the information of GDH interactors, posttranslational modification and subcellular localization are provided for better understanding of the GDH mutations. Medically significant point mutations causing deregulation of GDH are considered from the structural and regulatory point of view.}, } @article {pmid38692277, year = {2024}, author = {Kumar, A and Gok, MO and Nguyen, KN and Connor, OM and Reese, ML and Wideman, JG and Muñoz-Gómez, SA and Friedman, JR}, title = {A dynamin superfamily-like pseudoenzyme coordinates with MICOS to promote cristae architecture.}, journal = {Current biology : CB}, volume = {34}, number = {12}, pages = {2606-2622.e9}, pmid = {38692277}, issn = {1879-0445}, support = {S10 OD021685/OD/NIH HHS/United States ; S10 OD028630/OD/NIH HHS/United States ; P30 CA142543/CA/NCI NIH HHS/United States ; R01 AI150715/AI/NIAID NIH HHS/United States ; R21 AI171227/AI/NIAID NIH HHS/United States ; R35 GM137894/GM/NIGMS NIH HHS/United States ; }, mesh = {*Schizosaccharomyces/metabolism/genetics ; *Schizosaccharomyces pombe Proteins/metabolism/genetics ; *Mitochondrial Membranes/metabolism ; *Mitochondrial Proteins/metabolism/genetics ; Dynamins/metabolism/genetics ; Mitochondria/metabolism ; Mitochondria Associated Membranes ; }, abstract = {Mitochondrial cristae architecture is crucial for optimal respiratory function of the organelle. Cristae shape is maintained in part by the mitochondrial contact site and cristae organizing system (MICOS) complex. While MICOS is required for normal cristae morphology, the precise mechanistic role of each of the seven human MICOS subunits, and how the complex coordinates with other cristae-shaping factors, has not been fully determined. Here, we examine the MICOS complex in Schizosaccharomyces pombe, a minimal model whose genome only encodes for four core subunits. Using an unbiased proteomics approach, we identify a poorly characterized inner mitochondrial membrane protein that interacts with MICOS and is required to maintain cristae morphology, which we name Mmc1. We demonstrate that Mmc1 works in concert with MICOS to promote normal mitochondrial morphology and respiratory function. Mmc1 is a distant relative of the dynamin superfamily of proteins (DSPs), GTPases, which are well established to shape and remodel membranes. Similar to DSPs, Mmc1 self-associates and forms high-molecular-weight assemblies. Interestingly, however, Mmc1 is a pseudoenzyme that lacks key residues required for GTP binding and hydrolysis, suggesting that it does not dynamically remodel membranes. These data are consistent with the model that Mmc1 stabilizes cristae architecture by acting as a scaffold to support cristae ultrastructure on the matrix side of the inner membrane. Our study reveals a new class of proteins that evolved early in fungal phylogeny and is required for the maintenance of cristae architecture. This highlights the possibility that functionally analogous proteins work with MICOS to establish cristae morphology in metazoans.}, } @article {pmid38713727, year = {2024}, author = {K Raval, P and MacLeod, AI and Gould, SB}, title = {A molecular atlas of plastid and mitochondrial proteins reveals organellar remodeling during plant evolutionary transitions from algae to angiosperms.}, journal = {PLoS biology}, volume = {22}, number = {5}, pages = {e3002608}, pmid = {38713727}, issn = {1545-7885}, mesh = {*Plastids/metabolism/genetics ; *Magnoliopsida/genetics/metabolism ; *Mitochondrial Proteins/metabolism/genetics ; *Phylogeny ; Evolution, Molecular ; Biological Evolution ; Mitochondria/metabolism/genetics ; Plant Proteins/metabolism/genetics ; Proteome/metabolism ; Symbiosis/genetics ; Organelles/metabolism/genetics ; }, abstract = {Algae and plants carry 2 organelles of endosymbiotic origin that have been co-evolving in their host cells for more than a billion years. The biology of plastids and mitochondria can differ significantly across major lineages and organelle changes likely accompanied the adaptation to new ecological niches such as the terrestrial habitat. Based on organelle proteome data and the genomes of 168 phototrophic (Archaeplastida) versus a broad range of 518 non-phototrophic eukaryotes, we screened for changes in plastid and mitochondrial biology across 1 billion years of evolution. Taking into account 331,571 protein families (or orthogroups), we identify 31,625 protein families that are unique to primary plastid-bearing eukaryotes. The 1,906 and 825 protein families are predicted to operate in plastids and mitochondria, respectively. Tracing the evolutionary history of these protein families through evolutionary time uncovers the significant remodeling the organelles experienced from algae to land plants. The analyses of gained orthogroups identifies molecular changes of organelle biology that connect to the diversification of major lineages and facilitated major transitions from chlorophytes en route to the global greening and origin of angiosperms.}, } @article {pmid38731291, year = {2024}, author = {Zhang, J and Xu, C and Wang, S and Wang, S and Li, Y}, title = {Variations in Genetic Diversity of Invasive Species Lithobates catesbeianus in China.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {9}, pages = {}, pmid = {38731291}, issn = {2076-2615}, support = {32030070//National Science Foundation of China/ ; 2019QZKK0501//Second Tibetan Plateau Scientific Expedition and Research (STEP) Program/ ; 050001-521100222045//the High-Level Talents Research Start-Up Project of Hebei University/ ; C2022201042//Hebei Natural Science Foundation/ ; Sino-BON//China's Biodiversity Observation Network/ ; }, abstract = {The introduction and subsequent range expansion of the American bullfrog (Lithobates catesbeianus) is part of a rising trend of troublesome biological invasions happening in China. This detrimental amphibious invasive species has strong adaptability. After its introduction and spread, it established its own ecological niche in many provinces of China, and its range has continued to expand to more areas. Previous studies recorded the introduction time of bullfrogs and calculated the changes in their genetic diversity in China using mitochondria, but the specific introduction route in China is still unknown. Expanding upon previous research, we employed whole-genome scans (utilizing 2b-RAD genomic sequencing) to examine single nucleotide polymorphisms (SNPs) and microsatellites within Lithobates catesbeianus to screen the genomes of these invasive amphibian species from eight Chinese provinces and two U.S. states, including Kansas, where bullfrogs originate. A total of 1,336,475 single nucleotide polymorphic loci and 17 microsatellite loci were used to calculate the genetic diversity of bullfrogs and their migration pathways. Our results suggest that the population in Hunan was the first to be introduced and to spread, and there may have been multiple introductions of subpopulations. Additionally, the genetic diversity of both the SNP and microsatellite loci in the Chinese bullfrog population was lower than that of the US population due to bottleneck effects, but the bullfrogs can adapt and spread rapidly. This study will offer crucial insights for preventing and controlling future introductions into the natural habitats in China. Additionally, it will assist in devising more precise strategies to manage the existing populations and curtail their continued expansion, as well as aim to improve clarity and originality while mitigating plagiarism risk.}, } @article {pmid38733988, year = {2024}, author = {Sangineto, M and Ciarnelli, M and Colangelo, T and Moola, A and Bukke, VN and Duda, L and Villani, R and Romano, A and Giandomenico, S and Kanwal, H and Serviddio, G}, title = {Monocyte bioenergetics: An immunometabolic perspective in metabolic dysfunction-associated steatohepatitis.}, journal = {Cell reports. Medicine}, volume = {5}, number = {5}, pages = {101564}, pmid = {38733988}, issn = {2666-3791}, mesh = {Humans ; *Energy Metabolism ; Animals ; *Monocytes/metabolism/immunology ; Mice ; *Mitochondria/metabolism ; Fatty Liver/metabolism/pathology/immunology ; Male ; Glycolysis ; Reactive Oxygen Species/metabolism ; Mice, Inbred C57BL ; Macrophages/metabolism/immunology ; Female ; Liver/metabolism/pathology ; }, abstract = {Monocytes (Mos) are crucial in the evolution of metabolic dysfunction-associated steatotic liver disease (MASLD) to metabolic dysfunction-associated steatohepatitis (MASH), and immunometabolism studies have recently suggested targeting leukocyte bioenergetics in inflammatory diseases. Here, we reveal a peculiar bioenergetic phenotype in circulating Mos of patients with MASH, characterized by high levels of glycolysis and mitochondrial (mt) respiration. The enhancement of mt respiratory chain activity, especially complex II (succinate dehydrogenase [SDH]), is unbalanced toward the production of reactive oxygen species (ROS) and is sustained at the transcriptional level with the involvement of the AMPK-mTOR-PGC-1α axis. The modulation of mt activity with dimethyl malonate (DMM), an SDH inhibitor, restores the metabolic profile and almost abrogates cytokine production. Analysis of a public single-cell RNA sequencing (scRNA-seq) dataset confirms that in murine models of MASH, liver Mo-derived macrophages exhibit an upregulation of mt and glycolytic energy pathways. Accordingly, the DMM injection in MASH mice contrasts Mo infiltration and macrophagic enrichment, suggesting immunometabolism as a potential target in MASH.}, } @article {pmid38735623, year = {2024}, author = {Strücker, GK and Jaramillo, ML and de Quadros, T and Nazari, EM}, title = {UVB radiation exposure modulates mitophagy in embryonic cells of freshwater prawn Macrobrachium olfersii: Exploring a protective organelle quality control mechanism.}, journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology}, volume = {295}, number = {}, pages = {111664}, doi = {10.1016/j.cbpa.2024.111664}, pmid = {38735623}, issn = {1531-4332}, mesh = {Animals ; *Ultraviolet Rays/adverse effects ; *Mitophagy/radiation effects ; *Palaemonidae/radiation effects/embryology/genetics ; Mitochondria/metabolism/radiation effects ; Embryo, Nonmammalian/radiation effects/metabolism ; Arthropod Proteins/metabolism/genetics ; Phylogeny ; Organelles/metabolism/radiation effects ; }, abstract = {Aquatic environments are subject to ultraviolet B (UVB) radiation incidence, and its effects on organisms are dose-dependent. Besides DNA, mitochondria are an important target of this radiation that causes structural damage and impairs its functional dynamics. Here, we hypothesize that mitophagy acts as an organelle quality control mechanism to mitigate UVB impacts in embryonic cells. Then, freshwater prawn Macrobrachium olfersii embryos was used as a model to investigate the effects of UVB on genes (Tomm20, Opa1, Pink, Prkn, Sqstm1, and Map1lc3) and proteins (TOM20, PINK1, p62 and LC3B) involved in mitophagy modulation. The choice of genes and proteins was based on the identification of mitochondrial membrane (Tomm20, Opa1 and TOM20), mediation of mitophagy (Pink1, Prkn and PINK1), and recognition of mitochondria by the autophagosome membrane (Sqstm1, Map1lc3, p62 and LC3B). First, the phylogeny of all genes presented bootstrap values >80 and conserved domains among crustacean species. Gene expression was inherently modulated during development, with transcripts (Tomm20, Opa1, Pink, Prkn, Sqstm1, and Map1lc3) overexpressed in the initial and final stages of development. Moreover, UVB radiation induced upregulation of Tomm20, Opa1, Pink, Prkn, Sqstm1, and Map1lc3 genes at 6 h after exposure. Interestingly, after 12 h, the protein content of PINK1, p62, and LC3B increased, while TOM20 was not responsive. Despite UVB radiation's harmful effects on embryonic cells, the chronology of gene expression and protein content indicates rapid activation of mitophagy, serving as an organelle quality control mechanism, given the analyzed cells' integrity.}, } @article {pmid38740227, year = {2024}, author = {Zhang, M and Li, W and Zhang, X and Bi, M and Wang, X and Sun, F and Lu, J and Chi, Y and Han, Y and Li, Q and Li, T}, title = {Lamprey VDAC2: Suppressing hydrogen peroxide-induced 293T cell apoptosis by downregulating BAK expression.}, journal = {Fish & shellfish immunology}, volume = {150}, number = {}, pages = {109622}, doi = {10.1016/j.fsi.2024.109622}, pmid = {38740227}, issn = {1095-9947}, mesh = {Animals ; Humans ; Amino Acid Sequence ; *Apoptosis ; bcl-2 Homologous Antagonist-Killer Protein/metabolism ; Down-Regulation/drug effects ; *Fish Proteins/genetics/immunology ; Gene Expression Profiling/veterinary ; Gene Expression Regulation ; HEK293 Cells ; Hydrogen Peroxide ; *Lampreys/genetics/immunology ; Phylogeny ; Sequence Alignment/veterinary ; *Voltage-Dependent Anion Channel 2/metabolism ; }, abstract = {The voltage-dependent anion channel 2 (VDAC2) is the abundant protein in the outer mitochondrial membrane. Opening VDAC2 pores leads to the induction of mitochondrial energy and material transport, facilitating interaction with various mitochondrial proteins implicated in essential processes such as cell apoptosis and proliferation. To investigate the VDAC2 in lower vertebrates, we identified Lr-VDAC2, a homologue of VDAC2 found in lamprey (Lethenteron reissneri), sharing a sequence identity of greater than 50 % with its counterparts. Phylogenetic analysis revealed that the position of Lr-VDAC2 aligns with the lamprey phylogeny, indicating its evolutionary relationship within the species. The Lr-VDAC2 protein was primarily located in the mitochondria of lamprey cells. The expression of the Lr-VDAC2 protein was elevated in high energy-demanding tissues, such as the gills, muscles, and myocardial tissue in normal lampreys. Lr-VDAC2 suppressed H2O2 (hydrogen peroxide)-induced 293 T cell apoptosis by reducing the expression levels of Caspase 3, Caspase 9, and Cyt C (cytochrome c). Further research into the mechanism indicated that the Lr-VDAC2 protein inhibited the pro-apoptotic activity of BAK (Bcl-2 antagonist/killer) protein by downregulating its expression at the protein translational level, thus exerting an anti-apoptotic function similar to the role of VDAC2 in humans.}, } @article {pmid38740928, year = {2024}, author = {Rakotonirina, A and Dauga, C and Pol, M and Hide, M and Vuth, L and Ballan, V and Kilama, S and Russet, S and Marcombe, S and Boyer, S and Pocquet, N}, title = {Speciation patterns of Aedes mosquitoes in the Scutellaris Group: a mitochondrial perspective.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {10930}, pmid = {38740928}, issn = {2045-2322}, mesh = {Animals ; *Aedes/genetics/classification ; *Genetic Speciation ; *Phylogeny ; *Electron Transport Complex IV/genetics ; *Mitochondria/genetics ; Genetic Variation ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Asia ; }, abstract = {The Scutellaris Group of Aedes comprises 47 mosquito species, including Aedes albopictus. While Ae. albopictus is widely distributed, the other species are mostly found in the Asia-Pacific region. Evolutionary history researches of Aedes species within the Scutellaris Group have mainly focused on Ae. albopictus, a species that raises significant public health concerns, neglecting the other species. In this study, we aimed to assess genetic diversity and estimate speciation times of several species within the Scutellaris Group. Mosquitoes were therefore collected from various Asia-Pacific countries. Their mitochondrial cytochrome c oxidase subunit 1 (cox1) and subunit 3 (cox3) sequences were analyzed alongside those of other Scutellaris Group species available in the GenBank database. To estimate the divergence time, we analyzed 1849 cox1 gene sequences from 21 species, using three species (Aedes aegypti, Aedes notoscriptus and Aedes vigilax) as outgroups. We found that most of the speciation dates occurred during the Paleogene and the Neogene periods. A separation between the Scutellaris Subgroup and the Albopictus Subgroup occurred approximately 64-61 million years ago (MYA). We also identified a split between species found in Asia/Micronesia and those collected in Melanesia/Polynesia approximately 36-35 MYA. Our findings suggest that the speciation of Aedes species within the Scutellaris Group may be driven by diversity in mammalian hosts, climate and environmental changes, and geological dynamics rather than human migration.}, } @article {pmid38741523, year = {2024}, author = {Hervas, LS and do Amaral-Silva, L and Sartori, MR and Guadalupe-Silva, A and Gargaglioni, LH and Lerchner, J and Oliveira, MT and Bícego, KC}, title = {Mitochondrial function in skeletal muscle contributes to reproductive endothermy in tegu lizards (Salvator merianae).}, journal = {Acta physiologica (Oxford, England)}, volume = {240}, number = {7}, pages = {e14162}, doi = {10.1111/apha.14162}, pmid = {38741523}, issn = {1748-1716}, support = {2021/10910-0//São Paulo State Research Foundation-FAPESP/ ; 2021/06711-2//São Paulo State Research Foundation-FAPESP/ ; 2020/10961-1//São Paulo State Research Foundation-FAPESP/ ; 2020/07520-3//São Paulo State Research Foundation-FAPESP/ ; 309899/2022-2//CNPq/ ; 148915/2019-1//CNPq/ ; 147536/2018-9//CNPq/ ; 88887.194785/2018-00//CAPES PrInt/ ; }, mesh = {Animals ; *Lizards/physiology/metabolism ; *Muscle, Skeletal/metabolism/physiology ; *Reproduction/physiology ; Thermogenesis/physiology ; Female ; Male ; Seasons ; Mitochondria, Muscle/metabolism ; Energy Metabolism/physiology ; }, abstract = {AIM: In cyclic climate variations, including seasonal changes, many animals regulate their energy demands to overcome critical transitory moments, restricting their high-demand activities to phases of resource abundance, enabling rapid growth and reproduction. Tegu lizards (Salvator merianae) are ectotherms with a robust annual cycle, being active during summer, hibernating during winter, and presenting a remarkable endothermy during reproduction in spring. Here, we evaluated whether changes in mitochondrial respiratory physiology in skeletal muscle could serve as a mechanism for the increased thermogenesis observed during the tegu's reproductive endothermy.

METHODS: We performed high-resolution respirometry and calorimetry in permeabilized red and white muscle fibers, sampled during summer (activity) and spring (high activity and reproduction), in association with citrate synthase measurements.

RESULTS: During spring, the muscle fibers exhibited increased oxidative phosphorylation. They also enhanced uncoupled respiration and heat production via adenine nucleotide translocase (ANT), but not via uncoupling proteins (UCP). Citrate synthase activity was higher during the spring, suggesting greater mitochondrial density compared to the summer. These findings were consistent across both sexes and muscle types (red and white).

CONCLUSION: The current results highlight potential cellular thermogenic mechanisms in an ectothermic reptile that contribute to transient endothermy. Our study indicates that the unique feature of transitioning to endothermy through nonshivering thermogenesis during the reproductive phase may be facilitated by higher mitochondrial density, function, and uncoupling within the skeletal muscle. This knowledge contributes significant elements to the broader picture of models for the evolution of endothermy, particularly in relation to the enhancement of aerobic capacity.}, } @article {pmid38750421, year = {2024}, author = {Wang, X and Pei, J and Xiong, L and Bao, P and Chu, M and Ma, X and La, Y and Liang, C and Yan, P and Guo, X}, title = {Genetic diversity, phylogeography, and maternal origin of yak (Bos grunniens).}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {481}, pmid = {38750421}, issn = {1471-2164}, support = {CARS-37//the China Agriculture Research System of MOF and MARA/ ; 25-LZIHPS-01//the Innovation Project of Chinese Academy of Agricultural Sciences/ ; }, mesh = {Animals ; Cattle/genetics ; *Phylogeography ; *Genetic Variation ; *Haplotypes ; *Phylogeny ; *Genome, Mitochondrial ; Maternal Inheritance ; Female ; DNA, Mitochondrial/genetics ; }, abstract = {BACKGROUND: There is no consensus as to the origin of the domestic yak (Bos grunniens). Previous studies on yak mitochondria mainly focused on mitochondrial displacement loop (D-loop), a region with low phylogenetic resolution. Here, we analyzed the entire mitochondrial genomes of 509 yaks to obtain greater phylogenetic resolution and a comprehensive picture of geographical diversity.

RESULTS: A total of 278 haplotypes were defined in 509 yaks from 21 yak breeds. Among them, 28 haplotypes were shared by different varieties, and 250 haplotypes were unique to specific varieties. The overall haplotype diversity and nucleotide diversity of yak were 0.979 ± 0.0039 and 0.00237 ± 0.00076, respectively. Phylogenetic tree and network analysis showed that yak had three highly differentiated genetic branches with high support rate. The differentiation time of clades I and II were about 0.4328 Ma, and the differentiation time of clades (I and II) and III were 0.5654 Ma. Yushu yak is shared by all haplogroups. Most (94.70%) of the genetic variation occurred within populations, and only 5.30% of the genetic variation occurred between populations. The classification showed that yaks and wild yaks were first clustered together, and yaks were clustered with American bison as a whole. Altitude had the highest impact on the distribution of yaks.

CONCLUSIONS: Yaks have high genetic diversity and yak populations have experienced population expansion and lack obvious phylogeographic structure. During the glacial period, yaks had at least three or more glacial refugia.}, } @article {pmid38750703, year = {2024}, author = {Gong, Y and Luo, X and Zhang, T and Zhou, G and Li, J and Zhang, B and Li, P and Huang, H}, title = {Assembly and comparative analysis of the complete mitochondrial genome of white towel gourd (Luffa cylindrica).}, journal = {Genomics}, volume = {116}, number = {3}, pages = {110859}, doi = {10.1016/j.ygeno.2024.110859}, pmid = {38750703}, issn = {1089-8646}, mesh = {*Genome, Mitochondrial ; *Phylogeny ; *Luffa/genetics ; RNA, Transfer/genetics ; Genome, Plant ; Plant Proteins/genetics/metabolism ; }, abstract = {Mitochondria play an important role in the energy production of plant cells through independent genetic systems. This study has aimed to assemble and annotate the functions of the mitochondrial (mt) genome of Luffa cylindrica. The mt genome of L. cylindrica contained two chromosomes with lengths of 380,879 bp and 67,982 bp, respectively. Seventy-seven genes including 39 protein-coding genes, 34 tRNA genes, 3 rRNA genes, and 1 pseudogene, were identified. About 90.63% of the codons ended with A or U bases, and 98.63% of monomers contained A/T, which contributed to the high A/T content (55.91%) of the complete mt genome. Six genes (ATP8, CCMFC, NAD4, RPL10, RPL5 and RPS4) showed positive selection. Phylogenetic analysis indicates that L. cylindrica is closely related to L. acutangula. The present results provide the mt genome of L. cylindrica, which may facilitate possible genetic variation, evolutionary, and molecular breeding studies of L. cylindrica.}, } @article {pmid38753873, year = {2024}, author = {Thielen, M and Gärtner, B and Knoop, V and Schallenberg-Rüdinger, M and Lesch, E}, title = {Conquering new grounds: plant organellar C-to-U RNA editing factors can be functional in the plant cytosol.}, journal = {The Plant journal : for cell and molecular biology}, volume = {119}, number = {2}, pages = {895-915}, doi = {10.1111/tpj.16804}, pmid = {38753873}, issn = {1365-313X}, support = {SCHA 1952 2-2//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*RNA Editing ; *Chloroplasts/metabolism/genetics ; *Cytosol/metabolism ; *Bryopsida/genetics/metabolism ; *Mitochondria/metabolism/genetics ; *RNA, Plant/genetics/metabolism ; Plant Proteins/genetics/metabolism ; Cytidine/metabolism/genetics ; RNA-Binding Proteins/metabolism/genetics ; Gene Expression Regulation, Plant ; Uridine/metabolism/genetics ; }, abstract = {Plant mitochondrial and chloroplast transcripts are subject to numerous events of specific cytidine-to-uridine (C-to-U) RNA editing to correct genetic information. Key protein factors for this process are specific RNA-binding pentatricopeptide repeat (PPR) proteins, which are encoded in the nucleus and post-translationally imported into the two endosymbiotic organelles. Despite hundreds of C-to-U editing sites in the plant organelles, no comparable editing has been found for nucleo-cytosolic mRNAs raising the question why plant RNA editing is restricted to chloroplasts and mitochondria. Here, we addressed this issue in the model moss Physcomitrium patens, where all PPR-type RNA editing factors comprise specific RNA-binding and cytidine deamination functionalities in single proteins. To explore whether organelle-type RNA editing can principally also take place in the plant cytosol, we expressed PPR56, PPR65 and PPR78, three editing factors recently shown to also function in a bacterial setup, together with cytosolic co-transcribed native targets in Physcomitrium. While we obtained unsatisfying results upon their constitutive expression, we found strong cytosolic RNA editing under hormone-inducible expression. Moreover, RNA-Seq analyses revealed varying numbers of up to more than 900 off-targets in other cytosolic transcripts. We conclude that PPR-mediated C-to-U RNA editing is not per se incompatible with the plant cytosol but that its limited target specificity has restricted its occurrence to the much less complex transcriptomes of mitochondria and chloroplast in the course of evolution.}, } @article {pmid38758976, year = {2024}, author = {Giannakis, K and Richards, L and Dauda, KA and Johnston, IG}, title = {Connecting Species-Specific Extents of Genome Reduction in Mitochondria and Plastids.}, journal = {Molecular biology and evolution}, volume = {41}, number = {6}, pages = {}, pmid = {38758976}, issn = {1537-1719}, support = {//BBSRC/ ; //MIBTP Doctoral Training Scheme/ ; /ERC_/European Research Council/International ; 805046//European Union's Horizon 2020/ ; //EvoConBiO/ ; TMS2021TMT09//Trond Mohn Foundation/ ; //Centre for Antimicrobial Resistance in Western Norway/ ; TMS2020TMT11//CAMRIA/ ; }, mesh = {*Genome, Mitochondrial ; *Genome, Plastid ; *Plastids/genetics ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Mitochondria/genetics ; Species Specificity ; Biological Evolution ; Eukaryota/genetics ; }, abstract = {Mitochondria and plastids have both dramatically reduced their genomes since the endosymbiotic events that created them. The similarities and differences in the evolution of the two organelle genome types have been the target of discussion and investigation for decades. Ongoing work has suggested that similar mechanisms may modulate the reductive evolution of the two organelles in a given species, but quantitative data and statistical analyses exploring this picture remain limited outside of some specific cases like parasitism. Here, we use cross-eukaryote organelle genome data to explore evidence for coevolution of mitochondrial and plastid genome reduction. Controlling for differences between clades and pseudoreplication due to relatedness, we find that extents of mtDNA and ptDNA gene retention are related to each other across taxa, in a generally positive correlation that appears to differ quantitatively across eukaryotes, for example, between algal and nonalgal species. We find limited evidence for coevolution of specific mtDNA and ptDNA gene pairs, suggesting that the similarities between the two organelle types may be due mainly to independent responses to consistent evolutionary drivers.}, } @article {pmid38772414, year = {2024}, author = {Dohnálek, V and Doležal, P}, title = {Installation of LYRM proteins in early eukaryotes to regulate the metabolic capacity of the emerging mitochondrion.}, journal = {Open biology}, volume = {14}, number = {5}, pages = {240021}, pmid = {38772414}, issn = {2046-2441}, support = {//Gordon and Betty Moore Foundation and Simons Foundation/ ; //Czech Science Foundation/ ; }, mesh = {*Mitochondria/metabolism ; *Mitochondrial Proteins/metabolism/genetics ; Animals ; Evolution, Molecular ; Eukaryota/metabolism ; Acyl Carrier Protein/metabolism/genetics ; Phylogeny ; Models, Molecular ; Humans ; Amino Acid Sequence ; }, abstract = {Core mitochondrial processes such as the electron transport chain, protein translation and the formation of Fe-S clusters (ISC) are of prokaryotic origin and were present in the bacterial ancestor of mitochondria. In animal and fungal models, a family of small Leu-Tyr-Arg motif-containing proteins (LYRMs) uniformly regulates the function of mitochondrial complexes involved in these processes. The action of LYRMs is contingent upon their binding to the acylated form of acyl carrier protein (ACP). This study demonstrates that LYRMs are structurally and evolutionarily related proteins characterized by a core triplet of α-helices. Their widespread distribution across eukaryotes suggests that 12 specialized LYRMs were likely present in the last eukaryotic common ancestor to regulate the assembly and folding of the subunits that are conserved in bacteria but that lack LYRM homologues. The secondary reduction of mitochondria to anoxic environments has rendered the function of LYRMs and their interaction with acylated ACP dispensable. Consequently, these findings strongly suggest that early eukaryotes installed LYRMs in aerobic mitochondria as orchestrated switches, essential for regulating core metabolism and ATP production.}, } @article {pmid38773202, year = {2024}, author = {Pfingstl, T and Hiruta, SF and Shimano, S}, title = {Mitochondrial metagenomics reveal the independent colonization of the world's coasts by intertidal oribatid mites (Acari, Oribatida, Ameronothroidea).}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {11634}, pmid = {38773202}, issn = {2045-2322}, support = {I 3815//Austrian Science Fund/ ; }, mesh = {Animals ; *Mites/genetics/classification ; *Phylogeny ; *Metagenomics/methods ; Genome, Mitochondrial ; Mitochondria/genetics ; Metagenome ; Evolution, Molecular ; Ecosystem ; }, abstract = {Oribatid mites are an ancient group that already roamed terrestrial ecosystems in the early and middle Devonian. The superfamily of Ameronothroidea, a supposedly monophyletic lineage, represents the only group of oribatid mites that has successfully invaded the marine coastal environment. By using mitogenome data and nucleic ribosomal RNA genes (18S, 5.8S, 28S), we show that Ameronothroidea are a paraphyletic assemblage and that the land-to-sea transition happened three times independently. Common ancestors of the tropical Fortuyniidae and Selenoribatidae were the first to colonize the coasts and molecular calibration of our phylogeny dates this event to a period in the Triassic and Jurassic era (225-146 mya), whereas present-day distribution indicates that this event might have happened early in this period during the Triassic, when the supercontinent Pangaea still existed. The cold temperate northern hemispheric Ameronothridae colonized the marine littoral later in the late Jurassic-Early Cretaceous and had an ancient distribution on Laurasian coasts. The third and final land-to-sea transition happened in the same geological period, but approx. 30 my later when ancestors of Podacaridae invaded coastal marine environments of the Gondwanan landmasses.}, } @article {pmid38776415, year = {2024}, author = {Liao, T and Wang, S and Zhang, H and Stüeken, EE and Luo, H}, title = {Dating Ammonia-Oxidizing Bacteria with Abundant Eukaryotic Fossils.}, journal = {Molecular biology and evolution}, volume = {41}, number = {5}, pages = {}, pmid = {38776415}, issn = {1537-1719}, support = {14107823//Hong Kong Research Grants Council (RGC) General Research Fund/ ; 42293294//Natural Science Foundation of China/ ; AoE/M-403/16//Hong Kong Research Grants Council Area of Excellence Scheme/ ; 2022A1515010844//Guangdong Basic and Applied Basic Research Foundation/ ; 2021M702296//China Postdoctoral Science Foundation/ ; }, mesh = {*Ammonia/metabolism ; *Oxidation-Reduction ; *Fossils ; Gammaproteobacteria/metabolism/genetics ; Bacteria/metabolism/genetics ; Biological Evolution ; Phylogeny ; Symbiosis ; Eukaryota/metabolism/genetics ; Nitrogen Cycle ; }, abstract = {Evolution of a complete nitrogen (N) cycle relies on the onset of ammonia oxidation, which aerobically converts ammonia to nitrogen oxides. However, accurate estimation of the antiquity of ammonia-oxidizing bacteria (AOB) remains challenging because AOB-specific fossils are absent and bacterial fossils amenable to calibrate molecular clocks are rare. Leveraging the ancient endosymbiosis of mitochondria and plastid, as well as using state-of-the-art Bayesian sequential dating approach, we obtained a timeline of AOB evolution calibrated largely by eukaryotic fossils. We show that the first AOB evolved in marine Gammaproteobacteria (Gamma-AOB) and emerged between 2.1 and 1.9 billion years ago (Ga), thus postdating the Great Oxidation Event (GOE; 2.4 to 2.32 Ga). To reconcile the sedimentary N isotopic signatures of ammonia oxidation occurring near the GOE, we propose that ammonia oxidation likely occurred at the common ancestor of Gamma-AOB and Gammaproteobacterial methanotrophs, or the actinobacterial/verrucomicrobial methanotrophs which are known to have ammonia oxidation activities. It is also likely that nitrite was transported from the terrestrial habitats where ammonia oxidation by archaea took place. Further, we show that the Gamma-AOB predated the anaerobic ammonia-oxidizing (anammox) bacteria, implying that the emergence of anammox was constrained by the availability of dedicated ammonia oxidizers which produce nitrite to fuel anammox. Our work supports a new hypothesis that N redox cycle involving nitrogen oxides evolved rather late in the ocean.}, } @article {pmid38782915, year = {2024}, author = {Hanson, SE and Dowdy, T and Larion, M and Doyle, MT and Bernstein, HD}, title = {The patatin-like protein PlpD forms structurally dynamic homodimers in the Pseudomonas aeruginosa outer membrane.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4389}, pmid = {38782915}, issn = {2041-1723}, support = {Intramural Program//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; Intramural Program//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; Intramural Program//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; }, mesh = {*Pseudomonas aeruginosa/metabolism/genetics ; *Bacterial Outer Membrane Proteins/metabolism/chemistry/genetics ; *Protein Multimerization ; Periplasm/metabolism ; Protein Domains ; Bacterial Outer Membrane/metabolism ; Models, Molecular ; Bacterial Proteins/metabolism/chemistry/genetics ; }, abstract = {Members of the Omp85 superfamily of outer membrane proteins (OMPs) found in Gram-negative bacteria, mitochondria and chloroplasts are characterized by a distinctive 16-stranded β-barrel transmembrane domain and at least one periplasmic POTRA domain. All previously studied Omp85 proteins promote critical OMP assembly and/or protein translocation reactions. Pseudomonas aeruginosa PlpD is the prototype of an Omp85 protein family that contains an N-terminal patatin-like (PL) domain that is thought to be translocated across the OM by a C-terminal β-barrel domain. Challenging the current dogma, we find that the PlpD PL-domain resides exclusively in the periplasm and, unlike previously studied Omp85 proteins, PlpD forms a homodimer. Remarkably, the PL-domain contains a segment that exhibits unprecedented dynamicity by undergoing transient strand-swapping with the neighboring β-barrel domain. Our results show that the Omp85 superfamily is more structurally diverse than currently believed and suggest that the Omp85 scaffold was utilized during evolution to generate novel functions.}, } @article {pmid38789593, year = {2024}, author = {Qu, K and Chen, Y and Liu, D and Guo, H and Xu, T and Jing, Q and Ge, L and Shu, X and Xin, X and Xie, X and Tong, B}, title = {Comprehensive analysis of the complete mitochondrial genome of Lilium tsingtauense reveals a novel multichromosome structure.}, journal = {Plant cell reports}, volume = {43}, number = {6}, pages = {150}, pmid = {38789593}, issn = {1432-203X}, support = {2020070316//National Forestry and Grassland Administration/ ; 2021070307//National Forestry and Grassland Administration/ ; Lu Financial Preliminary Guide [2021] No. 1//Shandong provincial department of finance/ ; 2021LZGC023//Department of Science and Technology of Shandong Province/ ; 2005-DKA21003//Chinese Academy of Forestry/ ; }, mesh = {*Genome, Mitochondrial/genetics ; *Lilium/genetics ; *Chromosomes, Plant/genetics ; *Phylogeny ; RNA, Transfer/genetics ; Genome, Plant/genetics ; Base Composition/genetics ; }, abstract = {Lilium tsingtauense mitogenome comprises 27 independent chromosome molecules, it undergoes frequent genomic recombination, and the rate of recombination and mutation between different repetitive sequences affects the formation of multichromosomal structures. Given the extremely large genome of Lily, which likely harbors additional genetic resources, it serves as an ideal material for studying the phylogenetic evolution of organisms. Although the Lilium chloroplast genome has been documented, the sequence of its mitochondrial genome (mitogenome) remains uncharted. Using BGI short reads and Nanopore long reads, we sequenced, assembled, and annotated the mitogenome of Lilium tsingtauense. This effort culminated in the characterization of Lilium's first complete mitogenome. Comparative analysis with other angiosperms revealed the unique multichromosomal structure of the L. tsingtauense mitogenome, spanning 1,125,108 bp and comprising 27 independent circular chromosomes. It contains 36 protein-coding genes, 12 tRNA genes, and 3 rRNA genes, with a GC content of 44.90%. Notably, three chromosomes in the L. tsingtauense mitogenome lack identifiable genes, hinting at the potential existence of novel genes and noncoding elements. The high degree of observed genome fragmentation implies frequent reorganization, with recombination and mutation rates among diverse repetitive sequences likely driving the formation of multichromosomal structures. Our comprehensive analysis, covering genome size, coding genes, structure, RNA editing, repetitive sequences, and sequence migration, sheds light on the evolutionary and molecular biology of multichromosomal mitochondria in Lilium. This high-quality mitogenome of L. tsingtauense not only enriches our understanding of multichromosomal mitogenomes but also establishes a solid foundation for future genome breeding and germplasm innovation in Lilium.}, } @article {pmid38791521, year = {2024}, author = {Singh, MK and Shin, Y and Han, S and Ha, J and Tiwari, PK and Kim, SS and Kang, I}, title = {Molecular Chaperonin HSP60: Current Understanding and Future Prospects.}, journal = {International journal of molecular sciences}, volume = {25}, number = {10}, pages = {}, pmid = {38791521}, issn = {1422-0067}, support = {NRF-2018R1A6A1A03025124//National Research Foundation/ ; }, mesh = {*Chaperonin 60/metabolism/genetics ; Humans ; Animals ; *Oxidative Stress ; *Mitochondria/metabolism ; Neoplasms/metabolism/genetics/pathology ; Apoptosis ; Neurodegenerative Diseases/metabolism ; Protein Folding ; Reactive Oxygen Species/metabolism ; }, abstract = {Molecular chaperones are highly conserved across evolution and play a crucial role in preserving protein homeostasis. The 60 kDa heat shock protein (HSP60), also referred to as chaperonin 60 (Cpn60), resides within mitochondria and is involved in maintaining the organelle's proteome integrity and homeostasis. The HSP60 family, encompassing Cpn60, plays diverse roles in cellular processes, including protein folding, cell signaling, and managing high-temperature stress. In prokaryotes, HSP60 is well understood as a GroEL/GroES complex, which forms a double-ring cavity and aids in protein folding. In eukaryotes, HSP60 is implicated in numerous biological functions, like facilitating the folding of native proteins and influencing disease and development processes. Notably, research highlights its critical involvement in sustaining oxidative stress and preserving mitochondrial integrity. HSP60 perturbation results in the loss of the mitochondria integrity and activates apoptosis. Currently, numerous clinical investigations are in progress to explore targeting HSP60 both in vivo and in vitro across various disease models. These studies aim to enhance our comprehension of disease mechanisms and potentially harness HSP60 as a therapeutic target for various conditions, including cancer, inflammatory disorders, and neurodegenerative diseases. This review delves into the diverse functions of HSP60 in regulating proteo-homeostasis, oxidative stress, ROS, apoptosis, and its implications in diseases like cancer and neurodegeneration.}, } @article {pmid38791655, year = {2024}, author = {Zhou, S and Wang, X and Wang, L and Gao, X and Lyu, T and Xia, T and Shi, L and Dong, Y and Mei, X and Zhang, Z and Zhang, H}, title = {Different Evolutionary Trends of Galloanseres: Mitogenomics Analysis.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {10}, pages = {}, pmid = {38791655}, issn = {2076-2615}, support = {32200407//National Natural Science Foundation of China/ ; 32270444//National Natural Science Foundation of China/ ; ZR2023ZD47//Natural Science Foundation of Shandong Province/ ; GZC20231394//Postdoctoral Fellowship Program of CPSF/ ; GZC20231395//Postdoctoral Fellowship Program of CPSF/ ; GZC20231396//Postdoctoral Fellowship Program of CPSF/ ; }, abstract = {The two existing clades of Galloanseres, orders Galliformes (landfowl) and Anseriformes (waterfowl), exhibit dramatically different evolutionary trends. Mitochondria serve as primary sites for energy production in organisms, and numerous studies have revealed their role in biological evolution and ecological adaptation. We assembled the complete mitogenome sequences of two species of the genus Aythya within Anseriformes: Aythya baeri and Aythya marila. A phylogenetic tree was constructed for 142 species within Galloanseres, and their divergence times were inferred. The divergence between Galliformes and Anseriformes occurred ~79.62 million years ago (Mya), followed by rapid evolution and diversification after the Middle Miocene (~13.82 Mya). The analysis of selective pressure indicated that the mitochondrial protein-coding genes (PCGs) of Galloanseres species have predominantly undergone purifying selection. The free-ratio model revealed that the evolutionary rates of COX1 and COX3 were lower than those of the other PCGs, whereas ND2 and ND6 had faster evolutionary rates. The CmC model also indicated that most PCGs in Anseriformes exhibited stronger selective constraints. Our study suggests that the distinct evolutionary trends and energy requirements of Galliformes and Anseriformes drive different evolutionary patterns in the mitogenome.}, } @article {pmid38804831, year = {2024}, author = {Wang, J and Taki, M and Ohba, Y and Arita, M and Yamaguchi, S}, title = {Fluorescence Lifetime Imaging of Lipid Heterogeneity in the Inner Mitochondrial Membrane with a Super-photostable Environment-Sensitive Probe.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {63}, number = {28}, pages = {e202404328}, doi = {10.1002/anie.202404328}, pmid = {38804831}, issn = {1521-3773}, support = {19H02849//Japan Society for the Promotion of Science/ ; 23K06101//Japan Society for the Promotion of Science/ ; JP22H04926//Japan Society for the Promotion of Science/ ; JPMJCR21O5//Core Research for Evolutional Science and Technology/ ; JPMJER2101//Exploratory Research for Advanced Technology/ ; }, mesh = {*Fluorescent Dyes/chemistry ; *Mitochondrial Membranes/metabolism/chemistry ; *Optical Imaging ; Humans ; Lipids/chemistry ; Microscopy, Fluorescence ; Reactive Oxygen Species/metabolism/analysis ; HeLa Cells ; Mitochondria/metabolism/chemistry ; }, abstract = {The inner mitochondrial membrane (IMM) undergoes dynamic morphological changes, which are crucial for the maintenance of mitochondrial functions as well as cell survival. As the dynamics of the membrane are governed by its lipid components, a fluorescent probe that can sense spatiotemporal alterations in the lipid properties of the IMM over long periods of time is required to understand mitochondrial physiological functions in detail. Herein, we report a red-emissive IMM-labeling reagent with excellent photostability and sensitivity to its environment, which enables the visualization of the IMM ultrastructure using super-resolution microscopy as well as of the lipid heterogeneity based on the fluorescence lifetime at the single mitochondrion level. Combining the probe and fluorescence lifetime imaging microscopy (FLIM) showed that peroxidation of unsaturated lipids in the IMM by reactive oxygen species caused an increase in the membrane order, which took place prior to mitochondrial swelling.}, } @article {pmid38805695, year = {2024}, author = {McElroy, KE and Masonbrink, R and Chudalayandi, S and Severin, AJ and Serb, JM}, title = {A chromosome-level genome assembly of the disco clam, Ctenoides ales.}, journal = {G3 (Bethesda, Md.)}, volume = {14}, number = {9}, pages = {}, pmid = {38805695}, issn = {2160-1836}, support = {DEB 1754331//National Science Foundation/ ; 1726447//NSF/ ; }, mesh = {Animals ; *Bivalvia/genetics ; *Genome ; *Molecular Sequence Annotation ; Chromosomes/genetics ; Genomics/methods ; Phylogeny ; }, abstract = {The bivalve subclass Pteriomorphia, which includes the economically important scallops, oysters, mussels, and ark clams, exhibits extreme ecological, morphological, and behavioral diversity. Among this diversity are five morphologically distinct eye types, making Pteriomorphia an excellent setting to explore the molecular basis for the evolution of novel traits. Of pteriomorphian bivalves, Limida is the only order lacking genomic resources, greatly limiting the potential phylogenomic analyses related to eyes and phototransduction. Here, we present a limid genome assembly, the disco clam, Ctenoides ales (C. ales), which is characterized by invaginated eyes, exceptionally long tentacles, and a flashing light display. This genome assembly was constructed with PacBio long reads and Dovetail Omni-CTM proximity-ligation sequencing. The final assembly is ∼2.3Gb and over 99% of the total length is contained in 18 pseudomolecule scaffolds. We annotated 41,064 protein coding genes and reported a BUSCO completeness of 91.9% for metazoa_obd10. Additionally, we report a complete and annotated mitochondrial genome, which also had been lacking from Limida. The ∼20Kb mitogenome has 12 protein coding genes, 22 tRNAs, 2 rRNA genes, and a 1,589 bp duplicated sequence containing the origin of replication. The C. ales nuclear genome size is substantially larger than other pteriomorphian genomes, mainly accounted for by transposable element sequences. We inventoried the genome for opsins, the signaling proteins that initiate phototransduction, and found that, unlike its closest eyed-relatives, the scallops, C. ales lacks duplication of the rhabdomeric Gq-protein-coupled opsin that is typically used for invertebrate vision. In fact, C. ales has uncharacteristically few opsins relative to the other pteriomorphian families, all of which have unique expansions of xenopsins, a recently discovered opsin subfamily. This chromosome-level assembly, along with the mitogenome, is a valuable resource for comparative genomics and phylogenetics in bivalves and particularly for the understudied but charismatic limids.}, } @article {pmid38809522, year = {2024}, author = {Li, W and Cai, Z and Schindler, F and Afjehi-Sadat, L and Montsch, B and Heffeter, P and Heiss, EH and Weckwerth, W}, title = {Elevated PINK1/Parkin-Dependent Mitophagy and Boosted Mitochondrial Function Mediate Protection of HepG2 Cells from Excess Palmitic Acid by Hesperetin.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {23}, pages = {13039-13053}, pmid = {38809522}, issn = {1520-5118}, support = {P 32600/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Humans ; Hep G2 Cells ; *Palmitic Acid/pharmacology ; *Hesperidin/pharmacology ; *Mitophagy/drug effects ; *Ubiquitin-Protein Ligases/metabolism/genetics ; *Mitochondria/drug effects/metabolism ; *Protein Kinases/metabolism/genetics ; Reactive Oxygen Species/metabolism ; Hepatocytes/drug effects/metabolism ; Membrane Potential, Mitochondrial/drug effects ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; Non-alcoholic Fatty Liver Disease/metabolism/drug therapy ; Protective Agents/pharmacology ; PTEN-Induced Putative Kinase ; }, abstract = {Deregulation of mitochondrial functions in hepatocytes contributes to many liver diseases, such as nonalcoholic fatty liver disease (NAFLD). Lately, it was referred to as MAFLD (metabolism-associated fatty liver disease). Hesperetin (Hst), a bioactive flavonoid constituent of citrus fruit, has been proven to attenuate NAFLD. However, a potential connection between its preventive activities and the modulation of mitochondrial functions remains unclear. Here, our results showed that Hst alleviates palmitic acid (PA)-triggered NLRP3 inflammasome activation and cell death by inhibition of mitochondrial impairment in HepG2 cells. Hst reinstates fatty acid oxidation (FAO) rates measured by seahorse extracellular flux analyzer and intracellular acetyl-CoA levels as well as intracellular tricarboxylic acid cycle metabolites levels including NADH and FADH2 reduced by PA exposure. In addition, Hst protects HepG2 cells against PA-induced abnormal energetic profile, ATP generation reduction, overproduction of mitochondrial reactive oxygen species, and collapsed mitochondrial membrane potential. Furthermore, Hst improves the protein expression involved in PINK1/Parkin-mediated mitophagy. Our results demonstrate that it restores PA-impaired mitochondrial function and sustains cellular homeostasis due to the elevation of PINK1/Parkin-mediated mitophagy and the subsequent disposal of dysfunctional mitochondria. These results provide therapeutic potential for Hst utilization as an effective intervention against fatty liver disease.}, } @article {pmid38812151, year = {2024}, author = {Zhang, XY and Yu, JC and Chen, WT and Zhou, DY and Yuan, Y and Liu, HG and Liang, YL}, title = {[Identification of HSP70 gene family members in Fritillaria cirrhosa and expression analysis in different tissues under high temperature stress].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {49}, number = {9}, pages = {2422-2433}, doi = {10.19540/j.cnki.cjcmm.20240214.101}, pmid = {38812151}, issn = {1001-5302}, mesh = {*HSP70 Heat-Shock Proteins/genetics/metabolism/chemistry ; *Plant Proteins/genetics/metabolism/chemistry ; *Fritillaria/genetics/chemistry ; *Phylogeny ; *Gene Expression Regulation, Plant ; Hot Temperature ; Stress, Physiological/genetics ; Gene Expression Profiling ; Multigene Family ; }, abstract = {The heat shock protein 70 family contains the stress proteins ubiquitous in plants. These proteins are involved in the responses to different abiotic stress conditions and have highly conserved gene sequences. However, little is known about the molecular mechanisms of Fritillaria cirrhosa in response to high-temperature stress. Here, 26 HSP70s, FcHSP70-1 to FcHSP70-26, were identified from the transcriptome data of root, bulb, stem, leaf, and fruit samples of F. cirrhosa. The proteins encoded by FcHSP70s had the lengths ranging from 560 aa to 944 aa, with the molecular weight of 61.64-100.01 kDa and the theoretical isoelectric point between 5.00 and 6.59. The secondary structural elements of HSP70s were mainly random coils and α-helixes. Subcellular localization prediction revealed that FcHSP70s were distributed in mitochondria, chloroplasts, nuclei, endoplasmic reticulum, and cytoplasm. The phylogenetic tree showed that 7 members of the HSP70 family belonged to the Dnak subfamily and 19 members belonged to the HSP110/SSE subfamily. In addition, the qRT-PCR results showed that the expression of FcHSP70-5, FcHSP70-8, FcHSP70-17, FcHSP70-18, and FcHSP70-23 in F. cirrhosa was significantly up-regulated at 35 ℃, which indicated that these genes might play a role in the response to high temperature stress. In addition, compared with other tissues, stems and leaves were sensitive to high temperature stress, with the expression of 18 genes up-regulated by 18.18 and 8.03 folds on average, respectively. These findings provide valuable information about the molecular mechanism of HSP70s of F. cirrhosa in response to high temperature stress.}, } @article {pmid38812744, year = {2024}, author = {Marques, E and Kramer, R and Ryan, DG}, title = {Multifaceted mitochondria in innate immunity.}, journal = {npj metabolic health and disease}, volume = {2}, number = {1}, pages = {6}, pmid = {38812744}, issn = {2948-2828}, abstract = {The ability of mitochondria to transform the energy we obtain from food into cell phosphorylation potential has long been appreciated. However, recent decades have seen an evolution in our understanding of mitochondria, highlighting their significance as key signal-transducing organelles with essential roles in immunity that extend beyond their bioenergetic function. Importantly, mitochondria retain bacterial motifs as a remnant of their endosymbiotic origin that are recognised by innate immune cells to trigger inflammation and participate in anti-microbial defence. This review aims to explore how mitochondrial physiology, spanning from oxidative phosphorylation (OxPhos) to signalling of mitochondrial nucleic acids, metabolites, and lipids, influences the effector functions of phagocytes. These myriad effector functions include macrophage polarisation, efferocytosis, anti-bactericidal activity, antigen presentation, immune signalling, and cytokine regulation. Strict regulation of these processes is critical for organismal homeostasis that when disrupted may cause injury or contribute to disease. Thus, the expanding body of literature, which continues to highlight the central role of mitochondria in the innate immune system, may provide insights for the development of the next generation of therapies for inflammatory diseases.}, } @article {pmid38813783, year = {2024}, author = {Wolyniak, MJ and Frazier, RH and Gemborys, PK and Loehr, HE}, title = {Malate dehydrogenase: a story of diverse evolutionary radiation.}, journal = {Essays in biochemistry}, volume = {68}, number = {2}, pages = {213-220}, pmid = {38813783}, issn = {1744-1358}, support = {//Hampden-Sydney College Office of Undergraduate Research/ ; }, mesh = {*Malate Dehydrogenase/metabolism/genetics ; *Evolution, Molecular ; Bacteria/enzymology/genetics ; Phylogeny ; Archaea/genetics/enzymology ; Symbiosis ; Humans ; Eukaryota/enzymology/genetics ; Gene Transfer, Horizontal ; }, abstract = {Malate dehydrogenase (MDH) is a ubiquitous enzyme involved in cellular respiration across all domains of life. MDH's ubiquity allows it to act as an excellent model for considering the history of life and how the rise of aerobic respiration and eukaryogenesis influenced this evolutionary process. Here, we present the diversity of the MDH family of enzymes across bacteria, archaea, and eukarya, the relationship between MDH and lactate dehydrogenase (LDH) in the formation of a protein superfamily, and the connections between MDH and endosymbiosis in the formation of mitochondria and chloroplasts. The development of novel and powerful DNA sequencing techniques has challenged some of the conventional wisdom underlying MDH evolution and suggests a history dominated by gene duplication, horizontal gene transfer, and cryptic endosymbiosis events and adaptation to a diverse range of environments across all domains of life over evolutionary time. The data also suggest a superfamily of proteins that do not share high levels of sequential similarity but yet retain strong conservation of core function via key amino acid residues and secondary structural components. As DNA sequencing and 'big data' analysis techniques continue to improve in the life sciences, it is likely that the story of MDH will continue to refine as more examples of superfamily diversity are recovered from nature and analyzed.}, } @article {pmid38813885, year = {2024}, author = {Bennett, GM and Kwak, Y and Maynard, R}, title = {Endosymbioses Have Shaped the Evolution of Biological Diversity and Complexity Time and Time Again.}, journal = {Genome biology and evolution}, volume = {16}, number = {6}, pages = {}, pmid = {38813885}, issn = {1759-6653}, support = {NSF-1347116//National Science Foundation/ ; GT15982/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Symbiosis ; *Biological Evolution ; Animals ; Bacteria/genetics ; Biodiversity ; Evolution, Molecular ; }, abstract = {Life on Earth comprises prokaryotes and a broad assemblage of endosymbioses. The pages of Molecular Biology and Evolution and Genome Biology and Evolution have provided an essential window into how these endosymbiotic interactions have evolved and shaped biological diversity. Here, we provide a current perspective on this knowledge by drawing on decades of revelatory research published in Molecular Biology and Evolution and Genome Biology and Evolution, and insights from the field at large. The accumulated work illustrates how endosymbioses provide hosts with novel phenotypes that allow them to transition between adaptive landscapes to access environmental resources. Such endosymbiotic relationships have shaped and reshaped life on Earth. The early serial establishment of mitochondria and chloroplasts through endosymbioses permitted massive upscaling of cellular energetics, multicellularity, and terrestrial planetary greening. These endosymbioses are also the foundation upon which all later ones are built, including everything from land-plant endosymbioses with fungi and bacteria to nutritional endosymbioses found in invertebrate animals. Common evolutionary mechanisms have shaped this broad range of interactions. Endosymbionts generally experience adaptive and stochastic genome streamlining, the extent of which depends on several key factors (e.g. mode of transmission). Hosts, in contrast, adapt complex mechanisms of resource exchange, cellular integration and regulation, and genetic support mechanisms to prop up degraded symbionts. However, there are significant differences between endosymbiotic interactions not only in how partners have evolved with each other but also in the scope of their influence on biological diversity. These differences are important considerations for predicting how endosymbioses will persist and adapt to a changing planet.}, } @article {pmid38816808, year = {2024}, author = {Xing, J and Zhang, Y and Song, W and Ali, NA and Su, K and Sun, X and Sun, Y and Jiang, Y and Zhao, X}, title = {Comprehensive identification, characterization, and expression analysis of the MORF gene family in Brassica napus.}, journal = {BMC plant biology}, volume = {24}, number = {1}, pages = {475}, pmid = {38816808}, issn = {1471-2229}, support = {32170556//National Natural Science Foundation of China/ ; the Hundred-Talent Program//Zhejiang University/ ; }, mesh = {*Brassica napus/genetics/metabolism ; *Multigene Family ; *Phylogeny ; *Plant Proteins/genetics/metabolism ; Gene Expression Regulation, Plant ; Genes, Plant ; RNA Editing ; Gene Expression Profiling ; Chloroplasts/genetics/metabolism ; }, abstract = {BACKGROUND: RNA editing in chloroplast and mitochondrion transcripts of plants is an important type of post-transcriptional RNA modification in which members of the multiple organellar RNA editing factor gene family (MORF) play a crucial role. However, a systematic identification and characterization of MORF members in Brassica napus is still lacking.

RESULTS: In this study, a total of 43 MORF genes were identified from the genome of the Brassica napus cultivar "Zhongshuang 11". The Brassica napus MORF (BnMORF) family members were divided into three groups through phylogenetic analysis. BnMORF genes distributed on 14 chromosomes and expanded due to segmental duplication and whole genome duplication repetitions. The majority of BnMORF proteins were predicted to be localized to mitochondria and chloroplasts. The promoter cis-regulatory element analysis, spatial-temporal expression profiling, and co-expression network of BnMORF genes indicated the involvement of BnMORF genes in stress and phytohormone responses, as well as growth and development.

CONCLUSION: This study provides a comprehensive analysis of BnMORF genes and lays a foundation for further exploring their physiological functions in Brassica napus.}, } @article {pmid38818026, year = {2024}, author = {Tower, J}, title = {Selectively advantageous instability in biotic and pre-biotic systems and implications for evolution and aging.}, journal = {Frontiers in aging}, volume = {5}, number = {}, pages = {1376060}, pmid = {38818026}, issn = {2673-6217}, abstract = {Rules of biology typically involve conservation of resources. For example, common patterns such as hexagons and logarithmic spirals require minimal materials, and scaling laws involve conservation of energy. Here a relationship with the opposite theme is discussed, which is the selectively advantageous instability (SAI) of one or more components of a replicating system, such as the cell. By increasing the complexity of the system, SAI can have benefits in addition to the generation of energy or the mobilization of building blocks. SAI involves a potential cost to the replicating system for the materials and/or energy required to create the unstable component, and in some cases, the energy required for its active degradation. SAI is well-studied in cells. Short-lived transcription and signaling factors enable a rapid response to a changing environment, and turnover is critical for replacement of damaged macromolecules. The minimal gene set for a viable cell includes proteases and a nuclease, suggesting SAI is essential for life. SAI promotes genetic diversity in several ways. Toxin/antitoxin systems promote maintenance of genes, and SAI of mitochondria facilitates uniparental transmission. By creating two distinct states, subject to different selective pressures, SAI can maintain genetic diversity. SAI of components of synthetic replicators favors replicator cycling, promoting emergence of replicators with increased complexity. Both classical and recent computer modeling of replicators reveals SAI. SAI may be involved at additional levels of biological organization. In summary, SAI promotes replicator genetic diversity and reproductive fitness, and may promote aging through loss of resources and maintenance of deleterious alleles.}, } @article {pmid38825738, year = {2024}, author = {Boscaro, V and James, ER and Fiorito, R and Del Campo, J and Scheffrahn, RH and Keeling, PJ}, title = {Updated classification of the phylum Parabasalia.}, journal = {The Journal of eukaryotic microbiology}, volume = {71}, number = {4}, pages = {e13035}, doi = {10.1111/jeu.13035}, pmid = {38825738}, issn = {1550-7408}, support = {RGPIN-2014-03994//Natural Sciences and Engineering Research Council of Canada/ ; //Gordon and Betty Moore Foundation/ ; }, mesh = {*Phylogeny ; Animals ; Parabasalidea/classification/genetics ; Symbiosis ; }, abstract = {The phylum Parabasalia includes very diverse single-cell organisms that nevertheless share a distinctive set of morphological traits. Most are harmless or beneficial gut symbionts of animals, but some have turned into parasites in other body compartments, the most notorious example being Trichomonas vaginalis in humans. Parabasalians have garnered attention for their nutritional symbioses with termites, their modified anaerobic mitochondria (hydrogenosomes), their character evolution, and the wholly unique features of some species. The molecular revolution confirmed the monophyly of Parabasalia, but considerably changed our view of their internal relationships, prompting a comprehensive reclassification 14 years ago. This classification has remained authoritative for many subgroups despite a greatly expanded pool of available data, but the large number of species and sequences that have since come out allow for taxonomic refinements in certain lineages, which we undertake here. We aimed to introduce as little disruption as possible but at the same time ensure that most taxa are truly monophyletic, and that the larger clades are subdivided into meaningful units. In doing so, we also highlighted correlations between the phylogeny of parabasalians and that of their hosts.}, } @article {pmid38827288, year = {2024}, author = {Liu, Y and Fu, X and Wang, Y and Liu, J and Liu, Y and Li, C and Dong, J}, title = {Exploring Barbronia species diversity and phylogenetic relationship within Suborder Erpobdelliformes (Clitellata: Annelida).}, journal = {PeerJ}, volume = {12}, number = {}, pages = {e17480}, pmid = {38827288}, issn = {2167-8359}, mesh = {Animals ; *Phylogeny ; Genome, Mitochondrial/genetics ; Leeches/genetics/classification ; High-Throughput Nucleotide Sequencing ; RNA, Ribosomal, 28S/genetics ; }, abstract = {BACKGROUND: Barbronia, a genus of freshwater macrophagous leeches, belongs to Erpobdelliformes (Salifidae: Clitellata: Annelida), and B. weberi, a well-known leech within this genus, has a worldwide distribution. However, the systematics of Barbronia have not yet been adequately investigated, primarily due to a few molecular markers, and only 20 Barbronia sequences available in the GenBank database. This gap significantly limits our understanding of the Barbronia species identification, as well as the phylogenetic placement of the genus Barbronia within Salifidae.

METHODS: Next-generation sequencing (NGS) was used to simultaneously capture the entire mitochondrial genome and the full-length 18S/28S rDNA sequences. The species boundary of Barbronia species was estimated using bGMYC and bPTP methods, based on all available Barbronia COI sequences. Uncorrected COI p-distance was calculated in MEGA. A molecular data matrix consisting of four loci (COI, 12S, 18S, and 28S rDNA) for outgroups (three Haemopis leeches) and 49 erpobdellid leeches, representing eight genera within the Suborder Erpobdelliformes was aligned using MAFFT and LocARNA. This matrix was used to reconstruct the phylogenetic relationship of Barbronia via Bayesian inference (BI) and the maximum likelihood (ML) method.

RESULTS: The full lengths of the mitochondrial genome, 18S and 28S rDNAs of B. cf. gwalagwalensis, are 14847 bp, 1876 bp 1876 bp, and 2863 bp, respectively. Both bGMYC and bPTP results based on COI data are generally congruent, suggesting that the previously proposed taxa (B. arcana, B. weberi formosana, and B. wuttkei or Erpobdella wuttkei) are synonyms of B. weberi. The specimens listed in the B. gwalagwalensis group, however, are split into at least two Primary Species Hypotheses (PSHs). The p-distance of the first PSH is less than 1.3% but increased to 4.5% when including the secondary PSH (i.e., B. cf. gwalagwalensis). In comparison, the interspecific p-distance between the B. weberi group and the B. gwalagwalensis group ranged from 6.4% to 8.7%, and the intraspecific p-distance within the B. weberi group is less than 0.8%. Considering the species delimitation results and the sufficient large p-distance, the specimen sampled in China is treated as B. cf. gwalagwalensis. The monophyly of the four Erpobdelliformes families Salifidae, Orobdellidae, Gastrostomobdellidae sensu stricto and Erpobdellidae is well supported in ML and BI analysis based on a data of four markers. Within the Salifidae, a well-supported Barbronia is closely related to a clade containing Odontobdella and Mimobdella, and these three genera are sister to a clade consisted of Salifa and Linta. According to the results of this study, the strategy of simultaneous obtaining both whole mitochondria and nuclear markers from extensively sampled Salifids species using NGS is expected to fathom both the species diversity of B. gwalagwalensis and the evolutionary relationship of Salifidae.}, } @article {pmid38833723, year = {2024}, author = {Mukhopadhyay, J and Hausner, G}, title = {Interconnected roles of fungal nuclear- and intron-encoded maturases: at the crossroads of mitochondrial intron splicing.}, journal = {Biochemistry and cell biology = Biochimie et biologie cellulaire}, volume = {102}, number = {5}, pages = {351-372}, doi = {10.1139/bcb-2024-0046}, pmid = {38833723}, issn = {1208-6002}, mesh = {*Introns ; *RNA Splicing ; *Mitochondria/metabolism/genetics ; *Cell Nucleus/metabolism ; Fungi/genetics/enzymology ; Fungal Proteins/metabolism/genetics ; Endoribonucleases ; Nucleotidyltransferases ; }, abstract = {Group I and II introns are large catalytic RNAs (ribozymes) that are frequently encountered in fungal mitochondrial genomes. The discovery of respiratory mutants linked to intron splicing defects demonstrated that for the efficient removal of organellar introns there appears to be a requirement of protein splicing factors. These splicing factors can be intron-encoded proteins with maturase activities that usually promote the splicing of the introns that encode them (cis-acting) and/or nuclear-encoded factors that can promote the splicing of a range of different introns (trans-acting). Compared to plants organellar introns, fungal mitochondrial intron splicing is still poorly explored, especially in terms of the synergy of nuclear factors with intron-encoded maturases that has direct impact on splicing through their association with intron RNA. In addition, nuclear-encoded accessory factors might drive the splicing impetus through translational activation, mitoribosome assembly, and phosphorylation-mediated RNA turnover. This review explores protein-assisted splicing of introns by nuclear and mitochondrial-encoded maturases as a means of mitonuclear interplay that could respond to environmental and developmental factors promoting phenotypic adaptation and potentially speciation. It also highlights key evolutionary events that have led to changes in structure and ATP-dependence to accommodate the dual functionality of nuclear and organellar splicing factors.}, } @article {pmid38834883, year = {2024}, author = {Tao, M and Chen, J and Cui, C and Xu, Y and Xu, J and Shi, Z and Yun, J and Zhang, J and Ou, GZ and Liu, C and Chen, Y and Zhu, ZR and Pan, R and Xu, S and Chen, XX and Rokas, A and Zhao, Y and Wang, S and Huang, J and Shen, XX}, title = {Identification of a longevity gene through evolutionary rate covariation of insect mito-nuclear genomes.}, journal = {Nature aging}, volume = {4}, number = {8}, pages = {1076-1088}, pmid = {38834883}, issn = {2662-8465}, support = {32071665//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32230015//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32325044//National Natural Science Foundation of China (National Science Foundation of China)/ ; DEB-2110404//National Science Foundation (NSF)/ ; }, mesh = {Animals ; *Longevity/genetics ; Humans ; *Caenorhabditis elegans/genetics ; *Evolution, Molecular ; Cell Nucleus/genetics/metabolism ; Oxidative Phosphorylation ; Insecta/genetics ; Genome, Insect/genetics ; Mitochondria/genetics/metabolism ; Cellular Senescence/genetics ; }, abstract = {Oxidative phosphorylation, essential for energy metabolism and linked to the regulation of longevity, involves mitochondrial and nuclear genes. The functions of these genes and their evolutionary rate covariation (ERC) have been extensively studied, but little is known about whether other nuclear genes not targeted to mitochondria evolutionarily and functionally interact with mitochondrial genes. Here we systematically examined the ERC of mitochondrial and nuclear benchmarking universal single-copy ortholog (BUSCO) genes from 472 insects, identifying 75 non-mitochondria-targeted nuclear genes. We found that the uncharacterized gene CG11837-a putative ortholog of human DIMT1-regulates insect lifespan, as its knockdown reduces median lifespan in five diverse insect species and Caenorhabditis elegans, whereas its overexpression extends median lifespans in fruit flies and C. elegans and enhances oxidative phosphorylation gene activity. Additionally, DIMT1 overexpression protects human cells from cellular senescence. Together, these data provide insights into the ERC of mito-nuclear genes and suggest that CG11837 may regulate longevity across animals.}, } @article {pmid38835243, year = {2024}, author = {Zwahlen, SM and Hayward, JA and Maguire, CS and Qin, AR and van Dooren, GG}, title = {A myzozoan-specific protein is an essential membrane-anchoring component of the succinate dehydrogenase complex in Toxoplasma parasites.}, journal = {Open biology}, volume = {14}, number = {6}, pages = {230463}, pmid = {38835243}, issn = {2046-2441}, support = {//National Health and Medical Research Council/ ; }, mesh = {*Toxoplasma/metabolism/genetics/enzymology ; *Succinate Dehydrogenase/metabolism/genetics ; *Protozoan Proteins/metabolism/genetics/chemistry ; Humans ; Mitochondrial Proteins/metabolism/genetics ; Mitochondria/metabolism ; Phylogeny ; Animals ; }, abstract = {Succinate dehydrogenase (SDH) is a protein complex that functions in the tricarboxylic acid cycle and the electron transport chain of mitochondria. In most eukaryotes, SDH is highly conserved and comprises the following four subunits: SdhA and SdhB form the catalytic core of the complex, while SdhC and SdhD anchor the complex in the membrane. Toxoplasma gondii is an apicomplexan parasite that infects one-third of humans worldwide. The genome of T. gondii encodes homologues of the catalytic subunits SdhA and SdhB, although the physiological role of the SDH complex in the parasite and the identity of the membrane-anchoring subunits are poorly understood. Here, we show that the SDH complex contributes to optimal proliferation and O2 consumption in the disease-causing tachyzoite stage of the T. gondii life cycle. We characterize a small membrane-bound subunit of the SDH complex called mitochondrial protein ookinete developmental defect (MPODD), which is conserved among myzozoans, a phylogenetic grouping that incorporates apicomplexan parasites and their closest free-living relatives. We demonstrate that TgMPODD is essential for SDH activity and plays a key role in attaching the TgSdhA and TgSdhB proteins to the membrane anchor of the complex. Our findings highlight a unique and important feature of mitochondrial energy metabolism in apicomplexan parasites and their relatives.}, } @article {pmid38842420, year = {2024}, author = {Dorrell, RG and Zhang, Y and Liang, Y and Gueguen, N and Nonoyama, T and Croteau, D and Penot-Raquin, M and Adiba, S and Bailleul, B and Gros, V and Pierella Karlusich, JJ and Zweig, N and Fernie, AR and Jouhet, J and Maréchal, E and Bowler, C}, title = {Complementary environmental analysis and functional characterization of lower glycolysis-gluconeogenesis in the diatom plastid.}, journal = {The Plant cell}, volume = {36}, number = {9}, pages = {3584-3610}, pmid = {38842420}, issn = {1532-298X}, support = {ANR-21-CE02-0014-01//ANR/ ; ANR-11-BTBR-0008//French Facility for Global Environment/ ; ANR-10-INBS-09-08//FRANCE GENOMIQUE/ ; ANR-10-LABX-54//MEMO LIFE/ ; ANR-11-IDEX-0001-02//PSL Research University/ ; /ERC_/European Research Council/International ; 835067//European Union's Horizon 2020/ ; ANR-19-CE20-0020//ANR/ ; 22-PEBB-0002//PEPR AlgAdvance/ ; 10-LABX-0049//European Regional Development Fund/ ; //University Grenoble Alpes/ ; ANR-17-EURE-0003//Ecoles Universitaires de Recherche/ ; 739582//European Union's Horizon 2020/ ; 715579//European Union's Horizon 2020/ ; }, mesh = {*Diatoms/metabolism/genetics ; *Plastids/metabolism/genetics ; *Glycolysis/genetics ; *Gluconeogenesis/genetics ; Phylogeny ; }, abstract = {Organic carbon fixed in chloroplasts through the Calvin-Benson-Bassham Cycle can be diverted toward different metabolic fates, including cytoplasmic and mitochondrial respiration, gluconeogenesis, and synthesis of diverse plastid metabolites via the pyruvate hub. In plants, pyruvate is principally produced via cytoplasmic glycolysis, although a plastid-targeted lower glycolytic pathway is known to exist in non-photosynthetic tissue. Here, we characterized a lower plastid glycolysis-gluconeogenesis pathway enabling the direct interconversion of glyceraldehyde-3-phosphate and phospho-enol-pyruvate in diatoms, ecologically important marine algae distantly related to plants. We show that two reversible enzymes required to complete diatom plastid glycolysis-gluconeogenesis, Enolase and bis-phosphoglycerate mutase (PGAM), originated through duplications of mitochondria-targeted respiratory isoforms. Through CRISPR-Cas9 mutagenesis, integrative 'omic analyses, and measured kinetics of expressed enzymes in the diatom Phaeodactylum tricornutum, we present evidence that this pathway diverts plastid glyceraldehyde-3-phosphate into the pyruvate hub, and may also function in the gluconeogenic direction. Considering experimental data, we show that this pathway has different roles dependent in particular on day length and environmental temperature, and show that the cpEnolase and cpPGAM genes are expressed at elevated levels in high-latitude oceans where diatoms are abundant. Our data provide evolutionary, meta-genomic, and functional insights into a poorly understood yet evolutionarily recurrent plastid metabolic pathway.}, } @article {pmid38851187, year = {2024}, author = {Árnadóttir, ER and Moore, KHS and Guðmundsdóttir, VB and Ebenesersdóttir, SS and Guity, K and Jónsson, H and Stefánsson, K and Helgason, A}, title = {The rate and nature of mitochondrial DNA mutations in human pedigrees.}, journal = {Cell}, volume = {187}, number = {15}, pages = {3904-3918.e8}, doi = {10.1016/j.cell.2024.05.022}, pmid = {38851187}, issn = {1097-4172}, mesh = {Humans ; *DNA, Mitochondrial/genetics ; *Pedigree ; Female ; Iceland ; Male ; Mutation ; Mutation Rate ; }, abstract = {We examined the rate and nature of mitochondrial DNA (mtDNA) mutations in humans using sequence data from 64,806 contemporary Icelanders from 2,548 matrilines. Based on 116,663 mother-child transmissions, 8,199 mutations were detected, providing robust rate estimates by nucleotide type, functional impact, position, and different alleles at the same position. We thoroughly document the true extent of hypermutability in mtDNA, mainly affecting the control region but also some coding-region variants. The results reveal the impact of negative selection on viable deleterious mutations, including rapidly mutating disease-associated 3243A>G and 1555A>G and pre-natal selection that most likely occurs during the development of oocytes. Finally, we show that the fate of new mutations is determined by a drastic germline bottleneck, amounting to an average of 3 mtDNA units effectively transmitted from mother to child.}, } @article {pmid38851366, year = {2024}, author = {Tapanainen, R and Aasumets, K and Fekete, Z and Goffart, S and Dufour, E and L O Pohjoismäki, J}, title = {Species-specific variation in mitochondrial genome tandem repeat polymorphisms in hares (Lepus spp., Lagomorpha, Leporidae) provides insight into their evolution.}, journal = {Gene}, volume = {926}, number = {}, pages = {148644}, doi = {10.1016/j.gene.2024.148644}, pmid = {38851366}, issn = {1879-0038}, mesh = {Animals ; *Hares/genetics ; *Genome, Mitochondrial ; *Tandem Repeat Sequences/genetics ; *DNA, Mitochondrial/genetics ; *Polymorphism, Genetic ; *Evolution, Molecular ; *Species Specificity ; Phylogeny ; }, abstract = {The non-coding regions of the mitochondrial DNAs (mtDNAs) of hares, rabbits, and pikas (Lagomorpha) contain short (∼20 bp) and long (130-160 bp) tandem repeats, absent in related mammalian orders. In the presented study, we provide in-depth analysis for mountain hare (Lepus timidus) and brown hare (L. europaeus) mtDNA non-coding regions, together with a species- and population-level analysis of tandem repeat variation. Mountain hare short tandem repeats (SRs) as well as other analyzed hare species consist of two conserved 10 bp motifs, with only brown hares exhibiting a single, more variable motif. Long tandem repeats (LRs) also differ in sequence and copy number between species. Mountain hares have four to seven LRs, median value five, while brown hares exhibit five to nine LRs, median value six. Interestingly, introgressed mountain hare mtDNA in brown hares obtained an intermediate LR length distribution, with median copy number being the same as with conspecific brown hare mtDNA. In contrast, transfer of brown hare mtDNA into cultured mtDNA-less mountain hare cells maintained the original LR number, whereas the reciprocal transfer caused copy number instability, suggesting that cellular environment rather than the nuclear genomic background plays a role in the LR maintenance. Due to their dynamic nature and separation from other known conserved sequence elements on the non-coding region of hare mitochondrial genomes, the tandem repeat elements likely to represent signatures of ancient genetic rearrangements. clarifying the nature and dynamics of these rearrangements may shed light on the possible role of NCR repeated elements in mitochondria and in species evolution.}, } @article {pmid38853081, year = {2025}, author = {Rackham, O and Saurer, M and Ban, N and Filipovska, A}, title = {Unique architectural features of mammalian mitochondrial protein synthesis.}, journal = {Trends in cell biology}, volume = {35}, number = {1}, pages = {11-23}, doi = {10.1016/j.tcb.2024.05.001}, pmid = {38853081}, issn = {1879-3088}, mesh = {Animals ; *Mitochondrial Proteins/metabolism ; *Protein Biosynthesis ; Humans ; *Mitochondria/metabolism ; Mammals/metabolism ; DNA, Mitochondrial/metabolism/genetics ; Ribosomal Proteins/metabolism ; }, abstract = {Mitochondria rely on coordinated expression of their own mitochondrial DNA (mtDNA) with that of the nuclear genome for their biogenesis. The bacterial ancestry of mitochondria has given rise to unique and idiosyncratic features of the mtDNA and its expression machinery that can be specific to different organisms. In animals, the mitochondrial protein synthesis machinery has acquired many new components and mechanisms over evolution. These include several new ribosomal proteins, new stop codons and ways to recognise them, and new mechanisms to deliver nascent proteins into the mitochondrial inner membrane. Here we describe the mitochondrial protein synthesis machinery in mammals and its unique mechanisms of action elucidated to date and highlight the technologies poised to reveal the next generation of discoveries in mitochondrial translation.}, } @article {pmid38864935, year = {2024}, author = {Mochizuki, H}, title = {Pathological mechanisms and treatment of sporadic Parkinson's disease: past, present, and future.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {131}, number = {6}, pages = {597-607}, pmid = {38864935}, issn = {1435-1463}, support = {JPMJCR18H4//Core Research for Evolutional Science and Technology/ ; JP18dm0207020//Japan Agency for Medical Research and Development/ ; JP22dm0207070//Japan Agency for Medical Research and Development/ ; 22H02951//Japan Society for the Promotion of Science London/ ; 23K18255//Japan Society for the Promotion of Science London/ ; }, mesh = {Humans ; *Parkinson Disease/therapy/pathology/metabolism ; Animals ; Substantia Nigra/pathology/metabolism ; alpha-Synuclein/metabolism ; }, abstract = {For a special issue, we review studies on the pathogenesis of nigral cell death and the treatment of sporadic Parkinson's disease (sPD) over the past few decades, with a focus on the studies performed by Prof. Mizuno and our group. Prof. Mizuno proposed the initial concept that mitochondrial function may be impaired in sPD. When working at Jichi Medical School, he found a decrease in complex I of the mitochondrial electron transfer complex in the substantia nigra of patients with Parkinson's disease (PD) and MPTP models. After moving to Juntendo University as a professor and chairman, he continued to study the mechanisms of cell death in the substantia nigra of patients with sPD. Under his supervision, I studied the relationships between PD and apoptosis, PD and iron involvement, mitochondrial dysfunction and apoptosis, and PD and neuroinflammation. Moving to Kitasato University, we focused on PD and the cytotoxicity of alpha synuclein (αSyn) as well as brain neuropathology. Eventually, I moved to Osaka University, where I continued working on PD and αSyn projects to promote therapeutic research. In this paper, we present the details of these studies in the following order: past, present, and future.}, } @article {pmid38866808, year = {2024}, author = {Faustino, M and Lourenço, T and Strobbe, S and Cao, D and Fonseca, A and Rocha, I and Van Der Straeten, D and Oliveira, MM}, title = {OsTH1 is a key player in thiamin biosynthesis in rice.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {13591}, pmid = {38866808}, issn = {2045-2322}, mesh = {*Oryza/genetics/metabolism ; *Thiamine/biosynthesis/metabolism ; *Plant Proteins/metabolism/genetics ; Phylogeny ; Gene Expression Regulation, Plant ; }, abstract = {Thiamin is a vital nutrient that acts as a cofactor for several enzymes primarily localized in the mitochondria. These thiamin-dependent enzymes are involved in energy metabolism, nucleic acid biosynthesis, and antioxidant machinery. The enzyme HMP-P kinase/thiamin monophosphate synthase (TH1) holds a key position in thiamin biosynthesis, being responsible for the phosphorylation of HMP-P into HMP-PP and for the condensation of HMP-PP and HET-P to form TMP. Through mathematical kinetic model, we have identified TH1 as a critical player for thiamin biofortification in rice. We further focused on the functional characterization of OsTH1. Sequence and gene expression analysis, along with phylogenetic studies, provided insights into OsTH1 bifunctional features and evolution. The indispensable role of OsTH1 in thiamin biosynthesis was validated by heterologous expression of OsTH1 and successful complementation of yeast knock-out mutants impaired in thiamin production. We also proved that the sole OsTH1 overexpression in rice callus significantly improves B1 concentration, resulting in 50% increase in thiamin accumulation. Our study underscores the critical role of OsTH1 in thiamin biosynthesis, shedding light on its bifunctional nature and evolutionary significance. The significant enhancement of thiamin accumulation in rice callus upon OsTH1 overexpression constitutes evidence of its potential application in biofortification strategies.}, } @article {pmid38868915, year = {2024}, author = {Baird, LM and Berndsen, CE and Monroe, JD}, title = {Malate dehydrogenase in plants: evolution, structure, and a myriad of functions.}, journal = {Essays in biochemistry}, volume = {68}, number = {2}, pages = {221-233}, doi = {10.1042/EBC20230089}, pmid = {38868915}, issn = {1744-1358}, support = {MCB-2322867//National Science Foundation (NSF)/ ; }, mesh = {*Malate Dehydrogenase/metabolism ; *Evolution, Molecular ; Plants/enzymology/metabolism ; Arabidopsis/enzymology ; }, abstract = {Malate dehydrogenase (MDH) catalyzes the interconversion of oxaloacetate and malate coupled to the oxidation/reduction of coenzymes NAD(P)H/NAD(P)+. While most animals have two isoforms of MDH located in the cytosol and mitochondria, all major groups of land plants have at least six MDHs localized to the cytosol, mitochondria, plastids, and peroxisomes. This family of enzymes participates in important reactions in plant cells including photosynthesis, photorespiration, lipid metabolism, and NH4+ metabolism. MDH also helps to regulate the energy balance in the cell and may help the plant cope with various environmental stresses. Despite their functional diversity, all of the plant MDH enzymes share a similar structural fold and act as dimers. In this review, we will introduce readers to our current understanding of the plant MDHs, including their evolution, structure, and function. The focus will be on the MDH enzymes of the model plant Arabidopsis thaliana.}, } @article {pmid38869631, year = {2024}, author = {de Jong, TJ and Shmida, A}, title = {Paternal Inheritance of Mitochondrial DNA May Lead to Dioecy in Conifers.}, journal = {Acta biotheoretica}, volume = {72}, number = {2}, pages = {7}, pmid = {38869631}, issn = {1572-8358}, mesh = {*DNA, Mitochondrial/genetics ; *Tracheophyta/genetics ; *Paternal Inheritance ; Reproduction/genetics ; Pollen/genetics ; DNA, Plant/genetics ; }, abstract = {In angiosperms cytoplasmic DNA is typically passed on maternally through ovules. Genes in the mtDNA may cause male sterility. When male-sterile (female) cytotypes produce more seeds than cosexuals, they pass on more copies of their mtDNA and will co-occur with cosexuals with a neutral cytotype. Cytoplasmic gynodioecy is a well-known phenomenon in angiosperms, both in wild and crop plants. In some conifer families (e.g. Pinaceae) mitochondria are also maternally inherited. However in some other families (e.g. Taxaceae and Cupressaceae) mtDNA is paternally inherited through the pollen. With paternal mtDNA inheritance, male cytotypes that produce more pollen than cosexuals are expected to co-occur with cosexuals. This is uncharted territory. An ESS model shows that the presence of male cytotypes selects for more female allocation in the cosexual, i.e. for sexual specialisation. An allele that switches sex from male to female can then invade. This leads to rapid loss of the neutral cytotype of the cosexual, fixation of the male cytotype and dioecy with 50% males and 50% females. The models suggest that paternal inheritance of mtDNA facilitates the evolution dioecy. Consistent with this hypothesis the Pinaceae are 100% monoecious, while dioecy is common in the Taxaceae family and in the genus Juniperus (Cupressaceae). However, no reliable data are yet available on both mode of inheritance of mtDNA and gender variation of the same species. When cosexuals benefit from reproductive assurance (high selfing rate, low inbreeding depression, low fertilisation) they maintain themselves next to males and females. This predicted pattern with three sex types present in the same population is observed in conifers in nature.}, } @article {pmid38877225, year = {2024}, author = {Hu, X and Hoffmann, DS and Wang, M and Schuhmacher, L and Stroe, MC and Schreckenberger, B and Elstner, M and Fischer, R}, title = {GprC of the nematode-trapping fungus Arthrobotrys flagrans activates mitochondria and reprograms fungal cells for nematode hunting.}, journal = {Nature microbiology}, volume = {9}, number = {7}, pages = {1752-1763}, pmid = {38877225}, issn = {2058-5276}, support = {FI 459/26-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; STR1784/1-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {Animals ; *Caenorhabditis elegans/microbiology/metabolism ; *Receptors, G-Protein-Coupled/metabolism/genetics ; *Mitochondria/metabolism ; *Ascomycota/metabolism/genetics ; *Fungal Proteins/metabolism/genetics ; Pheromones/metabolism ; Humans ; Gene Expression Regulation, Fungal ; }, abstract = {Initiation of development requires differential gene expression and metabolic adaptations. Here we show in the nematode-trapping fungus, Arthrobotrys flagrans, that both are achieved through a dual-function G-protein-coupled receptor (GPCR). A. flagrans develops adhesive traps and recognizes its prey, Caenorhabditis elegans, through nematode-specific pheromones (ascarosides). Gene-expression analyses revealed that ascarosides activate the fungal GPCR, GprC, at the plasma membrane and together with the G-protein alpha subunit GasA, reprograms the cell. However, GprC and GasA also reside in mitochondria and boost respiration. This dual localization of GprC in A. flagrans resembles the localization of the cannabinoid receptor CB1 in humans. The C. elegans ascaroside-sensing GPCR, SRBC66 and GPCRs of many fungi are also predicted for dual localization, suggesting broad evolutionary conservation. An SRBC64/66-GprC chimaeric protein was functional in A. flagrans, and C. elegans SRBC64/66 and DAF38 share ascaroside-binding sites with the fungal GprC receptor, suggesting 400-million-year convergent evolution.}, } @article {pmid38882704, year = {2024}, author = {Tomizawa, Y and Aizawa, M and Jouraku, A and Sonoda, S}, title = {Field survey of reproductive modes and sodium channel mutations associated with pyrethroid resistance in Thrips tabaci.}, journal = {Journal of pesticide science}, volume = {49}, number = {2}, pages = {122-129}, pmid = {38882704}, issn = {1348-589X}, abstract = {Using PCR-Restriction Fragment Length Polymorphism (RFLP) with mitochondrial cytochrome c oxidase subunit I sequences, we examined the reproductive modes of female adults of Thrips tabaci collected at 54 sites across Japan. Results showed the presence of heteroplasmic insects harboring mitochondria associated with arrhenotoky and thelytoky. Using the insects, we also applied PCR-RFLP to examine the genotypes for the amino acid mutation (T929I) site involved in pyrethroid resistance. Findings showed the presence of thelytokous heterozygotes under the circumstance that most arrhenotokous insects are resistant homozygotes, and many thelytokous insects are susceptible homozygotes. These results suggest that, in the field, genetic exchange occurs between insects through of both reproductive modes. A survey of the genotypes for the other amino acid mutations using nucleotide sequencing showed a decline of insects with an M918T and L1014F pair and an increase of insects with M918L. These results suggest the evolutional progression of amino acid mutations associated with pyrethroid resistance in T. tabaci.}, } @article {pmid38890582, year = {2024}, author = {Gendron, EMS and Qing, X and Sevigny, JL and Li, H and Liu, Z and Blaxter, M and Powers, TO and Thomas, WK and Porazinska, DL}, title = {Comparative mitochondrial genomics in Nematoda reveal astonishing variation in compositional biases and substitution rates indicative of multi-level selection.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {615}, pmid = {38890582}, issn = {1471-2164}, mesh = {Animals ; *Genome, Mitochondrial ; *Nematoda/genetics ; *Selection, Genetic ; *Genomics/methods ; *Phylogeny ; Base Composition ; Evolution, Molecular ; Codon/genetics ; }, abstract = {BACKGROUND: Nematodes are the most abundant and diverse metazoans on Earth, and are known to significantly affect ecosystem functioning. A better understanding of their biology and ecology, including potential adaptations to diverse habitats and lifestyles, is key to understanding their response to global change scenarios. Mitochondrial genomes offer high species level characterization, low cost of sequencing, and an ease of data handling that can provide insights into nematode evolutionary pressures.

RESULTS: Generally, nematode mitochondrial genomes exhibited similar structural characteristics (e.g., gene size and GC content), but displayed remarkable variability around these general patterns. Compositional strand biases showed strong codon position specific G skews and relationships with nematode life traits (especially parasitic feeding habits) equal to or greater than with predicted phylogeny. On average, nematode mitochondrial genomes showed low non-synonymous substitution rates, but also high clade specific deviations from these means. Despite the presence of significant mutational saturation, non-synonymous (dN) and synonymous (dS) substitution rates could still be significantly explained by feeding habit and/or habitat. Low ratios of dN:dS rates, particularly associated with the parasitic lifestyles, suggested the presence of strong purifying selection.

CONCLUSIONS: Nematode mitochondrial genomes demonstrated a capacity to accumulate diversity in composition, structure, and content while still maintaining functional genes. Moreover, they demonstrated a capacity for rapid evolutionary change pointing to a potential interaction between multi-level selection pressures and rapid evolution. In conclusion, this study helps establish a background for our understanding of the potential evolutionary pressures shaping nematode mitochondrial genomes, while outlining likely routes of future inquiry.}, } @article {pmid38892163, year = {2024}, author = {Hong, YH and Yuan, YN and Li, K and Storey, KB and Zhang, JY and Zhang, SS and Yu, DN}, title = {Differential Mitochondrial Genome Expression of Four Hylid Frog Species under Low-Temperature Stress and Its Relationship with Amphibian Temperature Adaptation.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38892163}, issn = {1422-0067}, support = {31801963//the National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Genome, Mitochondrial ; *Anura/genetics/physiology ; *Phylogeny ; Cold-Shock Response/genetics ; Cold Temperature ; Adaptation, Physiological/genetics ; Gene Expression Regulation ; }, abstract = {Extreme weather poses huge challenges for animals that must adapt to wide variations in environmental temperature and, in many cases, it can lead to the local extirpation of populations or even the extinction of an entire species. Previous studies have found that one element of amphibian adaptation to environmental stress involves changes in mitochondrial gene expression at low temperatures. However, to date, comparative studies of gene expression in organisms living at extreme temperatures have focused mainly on nuclear genes. This study sequenced the complete mitochondrial genomes of five Asian hylid frog species: Dryophytes japonicus, D. immaculata, Hyla annectans, H. chinensis and H. zhaopingensis. It compared the phylogenetic relationships within the Hylidae family and explored the association between mitochondrial gene expression and evolutionary adaptations to cold stress. The present results showed that in D. immaculata, transcript levels of 12 out of 13 mitochondria genes were significantly reduced under cold exposure (p < 0.05); hence, we put forward the conjecture that D. immaculata adapts by entering a hibernation state at low temperature. In H. annectans, the transcripts of 10 genes (ND1, ND2, ND3, ND4, ND4L, ND5, ND6, COX1, COX2 and ATP8) were significantly reduced in response to cold exposure, and five mitochondrial genes in H. chinensis (ND1, ND2, ND3, ND4L and ATP6) also showed significantly reduced expression and transcript levels under cold conditions. By contrast, transcript levels of ND2 and ATP6 in H. zhaopingensis were significantly increased at low temperatures, possibly related to the narrow distribution of this species primarily at low latitudes. Indeed, H. zhaopingensis has little ability to adapt to low temperature (4 °C), or maybe to enter into hibernation, and it shows metabolic disorder in the cold. The present study demonstrates that the regulatory trend of mitochondrial gene expression in amphibians is correlated with their ability to adapt to variable climates in extreme environments. These results can predict which species are more likely to undergo extirpation or extinction with climate change and, thereby, provide new ideas for the study of species extinction in highly variable winter climates.}, } @article {pmid38900713, year = {2024}, author = {Molinet, J and Navarrete, JP and Villarroel, CA and Villarreal, P and Sandoval, FI and Nespolo, RF and Stelkens, R and Cubillos, FA}, title = {Wild Patagonian yeast improve the evolutionary potential of novel interspecific hybrid strains for lager brewing.}, journal = {PLoS genetics}, volume = {20}, number = {6}, pages = {e1011154}, pmid = {38900713}, issn = {1553-7404}, mesh = {*Beer/microbiology ; *Fermentation/genetics ; *Saccharomyces cerevisiae/genetics/metabolism ; *Hybridization, Genetic ; Saccharomyces/genetics/metabolism ; Ethanol/metabolism ; Mitochondria/genetics/metabolism ; Genome, Fungal ; Evolution, Molecular ; Genetic Variation ; Maltose/metabolism ; Mutation ; }, abstract = {Lager yeasts are limited to a few strains worldwide, imposing restrictions on flavour and aroma diversity and hindering our understanding of the complex evolutionary mechanisms during yeast domestication. The recent finding of diverse S. eubayanus lineages from Patagonia offers potential for generating new lager yeasts with different flavour profiles. Here, we leverage the natural genetic diversity of S. eubayanus and expand the lager yeast repertoire by including three distinct Patagonian S. eubayanus lineages. We used experimental evolution and selection on desirable traits to enhance the fermentation profiles of novel S. cerevisiae x S. eubayanus hybrids. Our analyses reveal an intricate interplay of pre-existing diversity, selection on species-specific mitochondria, de-novo mutations, and gene copy variations in sugar metabolism genes, resulting in high ethanol production and unique aroma profiles. Hybrids with S. eubayanus mitochondria exhibited greater evolutionary potential and superior fitness post-evolution, analogous to commercial lager hybrids. Using genome-wide screens of the parental subgenomes, we identified genetic changes in IRA2, IMA1, and MALX genes that influence maltose metabolism, and increase glycolytic flux and sugar consumption in the evolved hybrids. Functional validation and transcriptome analyses confirmed increased maltose-related gene expression, influencing greater maltotriose consumption in evolved hybrids. This study demonstrates the potential for generating industrially viable lager yeast hybrids from wild Patagonian strains. Our hybridization, evolution, and mitochondrial selection approach produced hybrids with high fermentation capacity and expands lager beer brewing options.}, } @article {pmid38906137, year = {2024}, author = {Iwata, R and Vanderhaeghen, P}, title = {Metabolic mechanisms of species-specific developmental tempo.}, journal = {Developmental cell}, volume = {59}, number = {13}, pages = {1628-1639}, pmid = {38906137}, issn = {1878-1551}, mesh = {Animals ; *Species Specificity ; Humans ; Mitochondria/metabolism ; Biological Evolution ; Metabolic Networks and Pathways ; Gene Expression Regulation, Developmental ; }, abstract = {Development consists of a highly ordered suite of steps and transitions, like choreography. Although these sequences are often evolutionarily conserved, they can display species variations in duration and speed, thereby modifying final organ size or function. Despite their evolutionary significance, the mechanisms underlying species-specific scaling of developmental tempo have remained unclear. Here, we will review recent findings that implicate global cellular mechanisms, particularly intermediary and protein metabolism, as species-specific modifiers of developmental tempo. In various systems, from somitic cell oscillations to neuronal development, metabolic pathways display species differences. These have been linked to mitochondrial metabolism, which can influence the species-specific speed of developmental transitions. Thus, intermediary metabolic pathways regulate developmental tempo together with other global processes, including proteostasis and chromatin remodeling. By linking metabolism and the evolution of developmental trajectories, these findings provide opportunities to decipher how species-specific cellular timing can influence organism fitness.}, } @article {pmid38908469, year = {2024}, author = {Lu, H and Liu, C and Yang, C and He, Z and Wang, L and Song, L}, title = {Genome-wide identification of the HSP70 genes in Pacific oyster Magallana gigas and their response to heat stress.}, journal = {Cell stress & chaperones}, volume = {29}, number = {4}, pages = {589-602}, pmid = {38908469}, issn = {1466-1268}, mesh = {Animals ; *HSP70 Heat-Shock Proteins/genetics/metabolism ; *Heat-Shock Response/genetics ; Phylogeny ; Ostreidae/genetics/metabolism ; Crassostrea/genetics/metabolism ; Multigene Family ; Genome ; }, abstract = {Heat shock protein 70 (HSP70), the most prominent and well-characterized stress protein in animals, plays an important role in assisting animals in responding to various adverse conditions. In the present study, a total of 113 HSP70 gene family members were identified in the updated genome of Magallana gigas (designated MgHSP70) (previously known as Crassostrea gigas). There were 75, 12, 11, and 8 HSP70s located in the cytoplasm, nucleus, mitochondria, and endoplasmic reticulum, respectively, and 7 HSP70s were located in both the nucleus and cytoplasm. Among 113 MgHSP70 genes, 107 were unevenly distributed in 8 chromosomes of M. gigas with the greatest number in chromosome 07 (61 genes, 57.01%). The MgHSP70 gene family members were mainly assigned into five clusters, among which the HSPa12 subfamily underwent lineage-specific expansion, consisting of 89 members. A total of 68 MgHSP70 genes (60.18%) were tandemly duplicated and formed 30 gene pairs, among which 14 gene pairs were under strong positive selection. In general, the expression of MgHSP70s was tissue-specific, with the highest expression in labial palp and gill and the lowest expression in adductor muscle and hemocytes. There were 35, 31, and 47 significantly upregulated genes at 6, 12, and 24 h after heat shock treatment (28 °C), respectively. The expression patterns of different tandemly duplicated genes exhibited distinct characteristics after shock treatment, indicating that these genes may have different functions. Nevertheless, genes within the same tandemly duplicated group exhibit similar expression patterns. Most of the tandemly duplicated HSP70 gene pairs showed the highest expression levels at 24 h. This study provides a comprehensive description of the MgHSP70 gene family in M. gigas and offers valuable insights into the functions of HSP70 in the mollusc adaptation of oysters to environmental stress.}, } @article {pmid38915079, year = {2024}, author = {Wu, CS and Wang, RJ and Chaw, SM}, title = {Integration of large and diverse angiosperm DNA fragments into Asian Gnetum mitogenomes.}, journal = {BMC biology}, volume = {22}, number = {1}, pages = {140}, pmid = {38915079}, issn = {1741-7007}, support = {No. 2022B1111040003//Guangdong Provincial Key R&D Programme/ ; }, mesh = {*Phylogeny ; *Gene Transfer, Horizontal ; *Genome, Mitochondrial ; *Gnetum/genetics ; DNA, Plant/genetics ; Evolution, Molecular ; Magnoliopsida/genetics ; }, abstract = {BACKGROUND: Horizontal gene transfer (HGT) events have rarely been reported in gymnosperms. Gnetum is a gymnosperm genus comprising 25‒35 species sympatric with angiosperms in West African, South American, and Southeast Asian rainforests. Only a single acquisition of an angiosperm mitochondrial intron has been documented to date in Asian Gnetum mitogenomes. We wanted to develop a more comprehensive understanding of frequency and fragment length distribution of such events as well as their evolutionary history in this genus.

RESULTS: We sequenced and assembled mitogenomes from five Asian Gnetum species. These genomes vary remarkably in size and foreign DNA content. We identified 15 mitochondrion-derived and five plastid-derived (MTPT) foreign genes. Our phylogenetic analyses strongly indicate that these foreign genes were transferred from diverse eudicots-mostly from the Rubiaceae genus Coptosapelta and ten genera of Malpighiales. This indicates that Asian Gnetum has experienced multiple independent HGT events. Patterns of sequence evolution strongly suggest DNA-mediated transfer between mitochondria as the primary mechanism giving rise to these HGT events. Most Asian Gnetum species are lianas and often entwined with sympatric angiosperms. We therefore propose that close apposition of Gnetum and angiosperm stems presents opportunities for interspecific cell-to-cell contact through friction and wounding, leading to HGT.

CONCLUSIONS: Our study reveals that multiple HGT events have resulted in massive amounts of angiosperm mitochondrial DNA integrated into Asian Gnetum mitogenomes. Gnetum and its neighboring angiosperms are often entwined with each other, possibly accounting for frequent HGT between these two phylogenetically remote lineages.}, } @article {pmid38924467, year = {2024}, author = {Menegollo, M and Bentham, RB and Henriques, T and Ng, SQ and Ren, Z and Esculier, C and Agarwal, S and Tong, ETY and Lo, C and Ilangovan, S and Szabadkai, Z and Suman, M and Patani, N and Ghanate, A and Bryson, K and Stein, RC and Yuneva, M and Szabadkai, G}, title = {Multistate Gene Cluster Switches Determine the Adaptive Mitochondrial and Metabolic Landscape of Breast Cancer.}, journal = {Cancer research}, volume = {84}, number = {17}, pages = {2911-2925}, pmid = {38924467}, issn = {1538-7445}, support = {FC0010060//Francis Crick Institute (FCI)/ ; FS/20/4/34958//British Heart Foundation (BHF)/ ; //UCLH Biomedical Research Centre (UCL)/ ; C57633/A25043//Cancer Research UK (CRUK)/ ; 29264//Cancer Research UK (CRUK)/ ; IG13447//Fondazione AIRC per la Ricerca sul Cancro ETS (AIRC)/ ; 204458/Z/16/Z//Wellcome Trust (WT)/ ; BB/L020874/1//Biotechnology and Biological Sciences Research Council (BBSRC)/ ; FC001223/WT_/Wellcome Trust/United Kingdom ; IG22221//Fondazione AIRC per la ricerca sul cancro ETS (AIRC)/ ; BB/P018726/1//Biotechnology and Biological Sciences Research Council (BBSRC)/ ; }, mesh = {Humans ; *Breast Neoplasms/genetics/metabolism/pathology ; Female ; *Mitochondria/metabolism/genetics ; *Multigene Family ; Transcriptome ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Prognosis ; Energy Metabolism/genetics ; }, abstract = {Adaptive metabolic switches are proposed to underlie conversions between cellular states during normal development as well as in cancer evolution. Metabolic adaptations represent important therapeutic targets in tumors, highlighting the need to characterize the full spectrum, characteristics, and regulation of the metabolic switches. To investigate the hypothesis that metabolic switches associated with specific metabolic states can be recognized by locating large alternating gene expression patterns, we developed a method to identify interspersed gene sets by massive correlated biclustering and to predict their metabolic wiring. Testing the method on breast cancer transcriptome datasets revealed a series of gene sets with switch-like behavior that could be used to predict mitochondrial content, metabolic activity, and central carbon flux in tumors. The predictions were experimentally validated by bioenergetic profiling and metabolic flux analysis of 13C-labeled substrates. The metabolic switch positions also distinguished between cellular states, correlating with tumor pathology, prognosis, and chemosensitivity. The method is applicable to any large and heterogeneous transcriptome dataset to discover metabolic and associated pathophysiological states. Significance: A method for identifying the transcriptomic signatures of metabolic switches underlying divergent routes of cellular transformation stratifies breast cancer into metabolic subtypes, predicting their biology, architecture, and clinical outcome.}, } @article {pmid38934796, year = {2024}, author = {Khachaturyan, M and Santer, M and Reusch, TBH and Dagan, T}, title = {Heteroplasmy Is Rare in Plant Mitochondria Compared with Plastids despite Similar Mutation Rates.}, journal = {Molecular biology and evolution}, volume = {41}, number = {7}, pages = {}, pmid = {38934796}, issn = {1537-1719}, support = {HIDSS-0005)//Helmholtz School for Marine Data Science/ ; RGP0011/2022//HFSP/ ; 101043835//ERC/ ; }, mesh = {*Plastids/genetics ; *Mitochondria/genetics/metabolism ; *Mutation Rate ; *Heteroplasmy ; Alleles ; }, abstract = {Plant cells harbor two membrane-bound organelles containing their own genetic material-plastids and mitochondria. Although the two organelles coexist and coevolve within the same plant cells, they differ in genome copy number, intracellular organization, and mode of segregation. How these attributes affect the time to fixation or, conversely, loss of neutral alleles is currently unresolved. Here, we show that mitochondria and plastids share the same mutation rate, yet plastid alleles remain in a heteroplasmic state significantly longer compared with mitochondrial alleles. By analyzing genetic variants across populations of the marine flowering plant Zostera marina and simulating organelle allele dynamics, we examine the determinants of allele segregation and allele fixation. Our results suggest that the bottlenecks on the cell population, e.g. during branching or seeding, and stratification of the meristematic tissue are important determinants of mitochondrial allele dynamics. Furthermore, we suggest that the prolonged plastid allele dynamics are due to a yet unknown active plastid partition mechanism. The dissimilarity between plastid and mitochondrial novel allele fixation at different levels of organization may manifest in differences in adaptation processes. Our study uncovers fundamental principles of organelle population genetics that are essential for further investigations of long-term evolution and molecular dating of divergence events.}, } @article {pmid38936100, year = {2024}, author = {Montoliu Nebot, J and Iradi Casal, A and Cepeda Madrigal, S and Rissi, G and Sanz Saz, S and Molés Gimeno, JD and Miravet Sorribes, LM}, title = {[Physiological assessment and management of post-COVID patients with normal cardiopulmonary imaging and functional tests].}, journal = {Semergen}, volume = {50}, number = {8}, pages = {102282}, doi = {10.1016/j.semerg.2024.102282}, pmid = {38936100}, issn = {1578-8865}, mesh = {Humans ; Female ; Male ; Middle Aged ; *Exercise Test/methods ; *COVID-19/complications/physiopathology ; *Dyspnea/etiology/physiopathology/diagnosis ; Adult ; Exercise Tolerance/physiology ; Post-Acute COVID-19 Syndrome ; Oxygen Consumption/physiology ; Electrocardiography ; }, abstract = {OBJECTIVE: Contributing to elucidate the pathophysiology of dyspnoea and exertion intolerance in post-COVID syndrome patients with normal cardiopulmonary imaging and functional tests at rest, while determining their fitness and level of endurance in order to individualize working parameters for physical rehabilitation.

MATERIAL AND METHODS: After an anamnesis and clinical examination at rest, 27 subjects (50±11.9 years) (14 women) with post-COVID syndrome of more than 6 months of evolution performed a continuous maximal-incremental graded cardiopulmonary exercise test (CPET) with breath-by-breath gas-exchange monitoring and continuous ECG registration, on an electromagnetically braked cycle ergometer. The values obtained were compared with those of reference, gender or controls, using the Chi-square, t-Student or ANOVA test.

RESULTS: The clinical examination at rest and the CPET were clinically normal and without adverse events. Reasons for stopping exercise were leg discomfort. It is only worth noting a BMI=29.9±5.8kg/m[2] and a basal lactate concentration of 2.1±0.7mmol/L. The physiological assessment of endurance showed the following results relative to predicted VO2máx: 1)peakVO2=80.5±18.6%; 2)VO2 at ventilatory threshold1 (VO2VT1): 46.0±12.9%; 3)VO2VT2: 57.2±16.4%; 4)working time in acidosis: 5.6±3,0minutes; and 5)maximum lactate concentration: 5.1±2.2mmol/L.

CONCLUSIONS: The CPET identified limited aerobic metabolism and early increase in glycolytic metabolism as causes of dyspnoea and exercise intolerance, determined fitness for physical rehabilitation, and individualized it based on the level of endurance.}, } @article {pmid38940122, year = {2024}, author = {Sashittal, P and Chen, V and Pasarkar, A and Raphael, BJ}, title = {Joint inference of cell lineage and mitochondrial evolution from single-cell sequencing data.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {Suppl 1}, pages = {i218-i227}, pmid = {38940122}, issn = {1367-4811}, support = {U24 CA248453/CA/NCI NIH HHS/United States ; U24 CA264027/CA/NCI NIH HHS/United States ; //NIH/ ; U24CA248453/BC/NCI NIH HHS/United States ; }, mesh = {*Single-Cell Analysis/methods ; Humans ; *Cell Lineage/genetics ; *Mitochondria/genetics ; Mutation ; Genome, Mitochondrial ; Algorithms ; Evolution, Molecular ; }, abstract = {MOTIVATION: Eukaryotic cells contain organelles called mitochondria that have their own genome. Most cells contain thousands of mitochondria which replicate, even in nondividing cells, by means of a relatively error-prone process resulting in somatic mutations in their genome. Because of the higher mutation rate compared to the nuclear genome, mitochondrial mutations have been used to track cellular lineage, particularly using single-cell sequencing that measures mitochondrial mutations in individual cells. However, existing methods to infer the cell lineage tree from mitochondrial mutations do not model "heteroplasmy," which is the presence of multiple mitochondrial clones with distinct sets of mutations in an individual cell. Single-cell sequencing data thus provide a mixture of the mitochondrial clones in individual cells, with the ancestral relationships between these clones described by a mitochondrial clone tree. While deconvolution of somatic mutations from a mixture of evolutionarily related genomes has been extensively studied in the context of bulk sequencing of cancer tumor samples, the problem of mitochondrial deconvolution has the additional constraint that the mitochondrial clone tree must be concordant with the cell lineage tree.

RESULTS: We formalize the problem of inferring a concordant pair of a mitochondrial clone tree and a cell lineage tree from single-cell sequencing data as the Nested Perfect Phylogeny Mixture (NPPM) problem. We derive a combinatorial characterization of the solutions to the NPPM problem, and formulate an algorithm, MERLIN, to solve this problem exactly using a mixed integer linear program. We show on simulated data that MERLIN outperforms existing methods that do not model mitochondrial heteroplasmy nor the concordance between the mitochondrial clone tree and the cell lineage tree. We use MERLIN to analyze single-cell whole-genome sequencing data of 5220 cells of a gastric cancer cell line and show that MERLIN infers a more biologically plausible cell lineage tree and mitochondrial clone tree compared to existing methods.

https://github.com/raphael-group/MERLIN.}, } @article {pmid38944824, year = {2024}, author = {Sepúlveda-Espinoza, F and Cofré-Serrano, A and Veloso-Valeria, T and Quesada-Calderon, S and Guillemin, ML}, title = {Characterization of the organellar genomes of Mazzaella laminarioides and Mazzaella membranacea (Gigartinaceae, Rhodophyta).}, journal = {Journal of phycology}, volume = {60}, number = {4}, pages = {797-805}, doi = {10.1111/jpy.13478}, pmid = {38944824}, issn = {1529-8817}, support = {15150003//Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias/ ; NCN2021-033//Agencia Nacional de Investigación y Desarrollo/ ; 1221477//Fondo Nacional de Desarrollo Científico y Tecnológico/ ; 3210788//Fondo Nacional de Desarrollo Científico y Tecnológico/ ; }, mesh = {*Rhodophyta/genetics/classification ; *Genome, Mitochondrial ; *Genome, Chloroplast ; Phylogeny ; Chile ; }, abstract = {Mazzaella, a genus with no genomic resources available, has extensive distribution in the cold waters of the Pacific, where they represent ecologically and economically important species. In this study, we aimed to sequence, assemble, and annotate the complete mitochondrial and chloroplast genomes from two Mazzaella spp. and characterize the intraspecific variation among them. We report for the first time seven whole organellar genomes (mitochondria: OR915856, OR947465, OR947466, OR947467, OR947468, OR947469, OR947470; chloroplast: OR881974, OR909680, OR909681, OR909682, OR909683, OR909684, OR909685) obtained through high-throughput sequencing for six M. laminarioides sampled from three Chilean regions and one M. membranacea. Sequenced Mazzaella mitogenomes have identical gene number, gene order, and genome structure. The same results were observed for assembled plastomes. A total of 52 genes were identified in mitogenomes, and a total of 235 genes were identified in plastomes. Although the M. membranacea plastome included a full-length pbsA gene, in all M. laminarioides samples, the pbsA gene was split in three open reading frames (ORFs). Within M. laminarioides, we observed important plastome lineage-specific variations, such as the pseudogenization of the two hypothetical protein-coding genes, ycf23 and ycf45. Nonsense mutations in the ycf23 and ycf45 genes were only detected in the northern lineage. These results are consistent with phylogenetic reconstructions and divergence time estimation using concatenated coding sequences that not only support the monophyly of M. laminarioides but also underscore that the three M. laminarioides lineages are in an advanced stage of divergence. These new results open the question of the existence of still undisclosed species in M. laminarioides.}, } @article {pmid38946300, year = {2024}, author = {Elnegris, HM and Abdelrahman, AA and El-Roghy, ES}, title = {The potential therapeutic effects of exosomes derived from bone marrow mesenchymal stem cells on ileum injury of a rat sepsis model (histological and immunohistochemical study).}, journal = {Ultrastructural pathology}, volume = {48}, number = {4}, pages = {274-296}, doi = {10.1080/01913123.2024.2368011}, pmid = {38946300}, issn = {1521-0758}, mesh = {Animals ; *Sepsis/complications ; Rats ; *Ileum/pathology ; *Mesenchymal Stem Cells ; *Disease Models, Animal ; *Exosomes/metabolism ; Male ; Immunohistochemistry ; Rats, Wistar ; Nitric Oxide Synthase Type II/metabolism ; }, abstract = {Sepsis denotes a serious high mortality concern. The study was designed to evaluate the effect of mesenchymal stem cell exosomes (MSC-exosomes) on the evolution of the animal model of sepsis. In this study, 36 rats were distributed into three groups, (I) controls, (II) LPS-treated, and (III) LPS+MSC-EVs. Sepsis was simulated by administering E. coli-LPS to the laboratory animals. Group III was given MSC-exosomes four hours after the LPS injection. Forty-eight hours later rats were sacrificed. Ileum samples were excised, and processed for the histological assessment, immunohistochemical identification of CD44, and inducible nitric oxide synthase (iNOS). Ileum homogenate was used to estimate tumor necrosis factor α (TNF α) besides Cyclooxygenase-2 (COX 2). PCR was used for the detection of interleukin 1α (IL‑1α), and interleukin 17 (IL‑17). Statistical and morphometrical analysis was done. The LPS-treated group showed increased TNF-α, IL‑1α, IL‑17, and decreased COX 2. LPS administration led to cytoplasmic vacuolization of enterocytes, an increase in the vasculature, and cellular infiltrations invaded the lamina propria. There was a significant rise in goblet cells and the proportion of collagen fibers. Ultrastructurally, the enterocytes displayed nuclear irregularity, rough endoplasmic reticulum (rER) dilatation, and increased mitochondria number. Sepsis induces a significant increase in iNOS and a decrease in CD44 immune expressions. LPS+MSC-EVs group restored normal ileum structure and revealed a significant elevation in CD44 and a reduction in iNOS immunoreactions. LPS-sepsis induced an obvious ileum inflammatory deterioration ameliorated by MSC-exosomes, mostly through their antioxidant, anti-inflammatory, and anti-apoptotic properties.}, } @article {pmid38950860, year = {2024}, author = {Box, JM and Higgins, ME and Stuart, RA}, title = {Importance of conserved hydrophobic pocket region in yeast mitoribosomal mL44 protein for mitotranslation and transcript preference.}, journal = {The Journal of biological chemistry}, volume = {300}, number = {8}, pages = {107519}, pmid = {38950860}, issn = {1083-351X}, support = {R15 GM131237/GM/NIGMS NIH HHS/United States ; }, mesh = {*Saccharomyces cerevisiae Proteins/metabolism/genetics/chemistry ; *Saccharomyces cerevisiae/metabolism/genetics ; *Mitochondrial Proteins/genetics/metabolism/chemistry ; Humans ; *Protein Biosynthesis ; *Mitochondrial Ribosomes/metabolism/chemistry ; Hydrophobic and Hydrophilic Interactions ; Ribosomal Proteins/metabolism/genetics/chemistry ; Mitochondria/metabolism/genetics ; }, abstract = {The mitochondrial ribosome (mitoribosome) is responsible for the synthesis of key oxidative phosphorylation subunits encoded by the mitochondrial genome. Defects in mitoribosomal function therefore can have serious consequences for the bioenergetic capacity of the cell. Mutation of the conserved mitoribosomal mL44 protein has been directly linked to childhood cardiomyopathy and progressive neurophysiology issues. To further explore the functional significance of the mL44 protein in supporting mitochondrial protein synthesis, we have performed a mutagenesis study of the yeast mL44 homolog, the MrpL3/mL44 protein. We specifically investigated the conserved hydrophobic pocket region of the MrpL3/mL44 protein, where the known disease-related residue in the human mL44 protein (L156R) is located. While our findings identify a number of residues in this region critical for MrpL3/mL44's ability to support the assembly of translationally active mitoribosomes, the introduction of the disease-related mutation into the equivalent position in the yeast protein (residue A186) was found to not have a major impact on function. The human and yeast mL44 proteins share many similarities in sequence and structure; however results presented here indicate that these two proteins have diverged somewhat in evolution. Finally, we observed that mutation of the MrpL3/mL44 does not impact the translation of all mitochondrial encoded proteins equally, suggesting the mitochondrial translation system may exhibit a transcript hierarchy and prioritization.}, } @article {pmid38970720, year = {2024}, author = {Shannan, PZT and Suganya, SG and Ramesh, M and Jemima, EA}, title = {Molecular based identification and phylogenetic relationship of the leech Hirudinaria manillensis from India by using mitochondrial cytochrome c oxidase subunit I gene.}, journal = {Molecular biology reports}, volume = {51}, number = {1}, pages = {787}, pmid = {38970720}, issn = {1573-4978}, mesh = {Animals ; Base Sequence ; DNA, Mitochondrial/genetics ; *Electron Transport Complex IV/genetics ; India ; *Leeches/genetics/enzymology/classification ; Mitochondria/genetics/enzymology ; *Phylogeny ; Sequence Analysis, DNA/methods ; Cyclooxygenase 1 ; }, abstract = {BACKGROUND: A molecular approach for the identification of unknown species by the using mitochondrial cox1 gene is an effective and reliable as compared with morphological-based identification. Hirudinaria manillensis referred to as Asian Buffalo Leech, is found in South Asia and traditionally used as medicine owing to its medicinal properties.

METHODS AND RESULTS: The study aimed to isolate and identify the leech species using cox1 gene sequencing and their phylogenetic relationships. The nucleotide sequences of cytochrome c oxidase subunit I (cox1) mitochondrial genes were analyzed for species identification and the phylogenetic relationship of crucial therapeutic leech Hirudinaria manillensis. The isolated DNA from the leech sample was amplified with cox1 gene-specific primers. BLAST results with the H. manillensis sequence showed 89.24% homology with H. manillensis and phylogenetic tree analysis revealed the genetic relationship with other GenBank submitted sequences.

CONCLUSION: The present study concluded that the cox1 gene could be an effective way to identify the leech H. manillensis and provided sufficient phylogenetic information to distinguish H. manillensis indicating a significant mtDNA-based approach to species identification.}, } @article {pmid38980999, year = {2024}, author = {Gammuto, L and Serra, V and Petroni, G and Todaro, MA}, title = {Molecular phylogenetic position and description of a new genus and species of freshwater Chaetonotidae (Gastrotricha: Chaetonotida: Paucitubulatina), and the annotation of its mitochondrial genome.}, journal = {Invertebrate systematics}, volume = {38}, number = {}, pages = {}, doi = {10.1071/IS23059}, pmid = {38980999}, issn = {1447-2600}, mesh = {*Phylogeny ; *Genome, Mitochondrial/genetics ; Animals ; Species Specificity ; Fresh Water ; }, abstract = {Chaetonotidae is the most diversified family of the entire phylum Gastrotricha; it comprises ~430 species distributed across 16 genera. The current classification, established mainly on morphological traits, has been challenged in recent years by phylogenetic studies, indicating that the cuticular ornamentations used to discriminate among species may be misleading when used to identify groupings, which has been the practice until now. Therefore, a consensus is developing toward implementing novel approaches to better define species identity and affiliation at a higher taxonomic ranking. Using an integrative morphological and molecular approach, including annotation of the mitogenome, we report on some freshwater gastrotrichs characterised by a mixture of two types of cuticular scales diagnostic of the genera Aspidiophorus and Heterolepidoderma . Our specimens' overall anatomical characteristics find no correspondence in the taxa of these two genera, calling for their affiliation to a new species. Phylogenetic analyses based on the sequence of the ribosomal RNA genes of 96 taxa consistently found the new species unrelated to Aspidiophorus or Heterolepidoderma but allied with Chaetonotus aff. subtilis, as a subset of a larger clade, including mostly planktonic species. Morphological uniqueness and position along the non-monophyletic Chaetonotidae branch advocate erecting a new genus to accommodate the current specimens; consequently, the name Litigonotus ghinii gen. nov., sp. nov. is proposed. The complete mitochondrial genome of the new taxon resulted in a single circular molecule 14,384 bp long, including 13 protein-coding genes, 17 tRNA genes and 2 rRNAs genes, showing a perfect synteny and collinearity with the only other gastrotrich mitogenome available, a possible hint of a high level of conservation in the mitochondria of Chaetonotidae. ZooBank: urn:lsid:zoobank.org:pub:9803F659-306F-4EC3-A73B-8C704069F24A.}, } @article {pmid38995057, year = {2024}, author = {Smith, CH and Mejia-Trujillo, R and Havird, JC}, title = {Mitonuclear compatibility is maintained despite relaxed selection on male mitochondrial DNA in bivalves with doubly uniparental inheritance.}, journal = {Evolution; international journal of organic evolution}, volume = {78}, number = {11}, pages = {1790-1803}, pmid = {38995057}, issn = {1558-5646}, support = {R35 GM142836/GM/NIGMS NIH HHS/United States ; R35-GM142836/GF/NIH HHS/United States ; }, mesh = {Animals ; Male ; *DNA, Mitochondrial/genetics ; *Selection, Genetic ; Oxidative Phosphorylation ; Cell Nucleus/genetics ; Female ; Evolution, Molecular ; Bivalvia/genetics ; Phylogeny ; }, abstract = {Mitonuclear coevolution is common in eukaryotes, but bivalve lineages that have doubly uniparental inheritance (DUI) of mitochondria may be an interesting example. In this system, females transmit mtDNA (F mtDNA) to all offspring, while males transmit a different mtDNA (M mtDNA) solely to their sons. Molecular evolution and functional data suggest oxidative phosphorylation (OXPHOS) genes encoded in M mtDNA evolve under relaxed selection due to their function being limited to sperm only (vs. all other tissues for F mtDNA). This has led to the hypothesis that mitonuclear coevolution is less important for M mtDNA. Here, we use comparative phylogenetics, transcriptomics, and proteomics to understand mitonuclear interactions in DUI bivalves. We found nuclear OXPHOS proteins coevolve and maintain compatibility similarly with both F and M mtDNA OXPHOS proteins. Mitochondrial recombination did not influence mitonuclear compatibility and nuclear-encoded OXPHOS genes were not upregulated in tissues with M mtDNA to offset dysfunction. Our results support that selection maintains mitonuclear compatibility with F and M mtDNA despite relaxed selection on M mtDNA. Strict sperm transmission, lower effective population size, and higher mutation rates may explain the evolution of M mtDNA. Our study highlights that mitonuclear coevolution and compatibility may be broad features of eukaryotes.}, } @article {pmid38995516, year = {2024}, author = {Lin, YE and Chiu, HL and Wu, CS and Chaw, SM}, title = {Phylogenomics identifies parents of naturally occurring tetraploid bananas.}, journal = {Botanical studies}, volume = {65}, number = {1}, pages = {19}, pmid = {38995516}, issn = {1817-406X}, support = {23-23//Academia Sinica/ ; }, abstract = {BACKGROUND: Triploid bananas are almost sterile. However, we succeeded in harvesting seeds from two edible triploid banana individuals (Genotype: ABB) in our conservation repository where various wild diploid bananas were also grown. The resulting rare offspring survived to seedling stages. DNA content analyses reveal that they are tetraploid. Since bananas contain maternally inherited plastids and paternally inherited mitochondria, we sequenced and assembled plastomes and mitogenomes of these seedlings to trace their hybridization history.

RESULTS: The coding sequences of both organellar genomic scaffolds were extracted, aligned, and concatenated for constructing phylogenetic trees. Our results suggest that these tetraploid seedlings be derived from hybridization between edible triploid bananas and wild diploid Musa balbisiana (BB) individuals. We propose that generating female triploid gametes via apomeiosis may allow the triploid maternal bananas to produce viable seeds.

CONCLUSIONS: Our study suggests a practical avenue towards expanding genetic recombination and increasing genetic diversity of banana breeding programs. Further cellular studies are needed to understand the fusion and developmental processes that lead to formation of hybrid embryos in banana reproduction, polyploidization, and evolution.}, } @article {pmid39009246, year = {2024}, author = {Guttipatti, P and Saadallah, N and Ji, R and Avula, UMR and Goulbourne, CN and Wan, EY}, title = {Quantitative 3D electron microscopy characterization of mitochondrial structure, mitophagy, and organelle interactions in murine atrial fibrillation.}, journal = {Journal of structural biology}, volume = {216}, number = {3}, pages = {108110}, pmid = {39009246}, issn = {1095-8657}, support = {R01 HL152236/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Mitophagy ; Mice ; *Atrial Fibrillation/metabolism/pathology ; *Myocytes, Cardiac/ultrastructure/metabolism/pathology ; *Mitochondria/ultrastructure/metabolism/pathology ; Sarcoplasmic Reticulum/metabolism/ultrastructure/pathology ; Mitochondria, Heart/ultrastructure/metabolism/pathology ; Imaging, Three-Dimensional/methods ; Male ; Disease Models, Animal ; Microscopy, Electron, Scanning/methods ; }, abstract = {Atrial fibrillation (AF) is the most common clinical arrhythmia, however there is limited understanding of its pathophysiology including the cellular and ultrastructural changes rendered by the irregular rhythm, which limits pharmacological therapy development. Prior work has demonstrated the importance of reactive oxygen species (ROS) and mitochondrial dysfunction in the development of AF. Mitochondrial structure, interactions with other organelles such as sarcoplasmic reticulum (SR) and T-tubules (TT), and degradation of dysfunctional mitochondria via mitophagy are important processes to understand ultrastructural changes due to AF. However, most analysis of mitochondrial structure and interactome in AF has been limited to two-dimensional (2D) modalities such as transmission electron microscopy (EM), which does not fully visualize the morphological evolution of the mitochondria during mitophagy. Herein, we utilize focused ion beam-scanning electron microscopy (FIB-SEM) and perform reconstruction of three-dimensional (3D) EM from murine left atrial samples and measure the interactions of mitochondria with SR and TT. We developed a novel 3D quantitative analysis of FIB-SEM in a murine model of AF to quantify mitophagy stage, mitophagosome size in cardiomyocytes, and mitochondrial structural remodeling when compared with control mice. We show that in our murine model of spontaneous and continuous AF due to persistent late sodium current, left atrial cardiomyocytes have heterogenous mitochondria, with a significant number which are enlarged with increased elongation and structural complexity. Mitophagosomes in AF cardiomyocytes are located at Z-lines where they neighbor large, elongated mitochondria. Mitochondria in AF cardiomyocytes show increased organelle interaction, with 5X greater contact area with SR and are 4X as likely to interact with TT when compared to control. We show that mitophagy in AF cardiomyocytes involves 2.5X larger mitophagosomes that carry increased organelle contents. In conclusion, when oxidative stress overcomes compensatory mechanisms, mitophagy in AF faces a challenge of degrading bulky complex mitochondria, which may result in increased SR and TT contacts, perhaps allowing for mitochondrial Ca[2+] maintenance and antioxidant production.}, } @article {pmid39016375, year = {2024}, author = {Martini, D and De Cesari, C and Digregorio, M and Muscò, A and Giudetti, G and Giannaccini, M and Andreazzoli, M}, title = {Expression analysis of thg1l during Xenopus laevis development.}, journal = {The International journal of developmental biology}, volume = {68}, number = {2}, pages = {85-91}, doi = {10.1387/ijdb.240033ma}, pmid = {39016375}, issn = {1696-3547}, mesh = {Animals ; Embryo, Nonmammalian/metabolism/embryology ; Embryonic Development/genetics ; *Gene Expression Regulation, Developmental ; *Nucleotidyltransferases/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; *Xenopus laevis/metabolism/embryology/genetics ; *Xenopus Proteins/genetics/metabolism ; }, abstract = {The tRNA-histidine guanylyltransferase 1-like (THG1L), also known as induced in high glucose-1 (IHG-1), encodes for an essential mitochondria-associated protein highly conserved throughout evolution, that catalyses the 3'-5' addition of a guanine to the 5'-end of tRNA-histidine (tRNA[His]). Previous data indicated that THG1L plays a crucial role in the regulation of mitochondrial biogenesis and dynamics, in ATP production, and is critically involved in the modulation of apoptosis, cell-cycle progression and survival, as well as in cellular stress responses and redox homeostasis. Dysregulations of THG1L expression play a central role in various pathologies, including nephropathies, and neurodevelopmental disorders often characterized by developmental delay and cerebellar ataxia. Despite the essential role of THG1L, little is known about its expression during vertebrate development. Herein, we examined the detailed spatio-temporal expression of this gene in the developing Xenopus laevis. Our results show that thg1l is maternally inherited and its temporal expression suggests a role during the earliest stages of embryogenesis. Spatially, thg1l mRNA localizes in the ectoderm and marginal zone mesoderm during early stages of development. Then, at tadpole stages, thg1l transcripts mostly localise in neural crests and their derivatives, somites, developing kidney and central nervous system, therefore largely coinciding with territories displaying intense energy metabolism during organogenesis in Xenopus.}, } @article {pmid39031116, year = {2024}, author = {Korábek, O and Hausdorf, B}, title = {Accelerated mitochondrial evolution and asymmetric fitness of hybrids contribute to the persistence of Helix thessalica in the Helix pomatia range.}, journal = {Molecular ecology}, volume = {33}, number = {16}, pages = {e17474}, doi = {10.1111/mec.17474}, pmid = {39031116}, issn = {1365-294X}, support = {UNCE/24/SCI/006//Univerzita Karlova v Praze/ ; }, mesh = {Animals ; *DNA, Mitochondrial/genetics ; *Hybridization, Genetic ; *Gene Flow ; *Helix, Snails/genetics ; Genome, Mitochondrial ; Genetic Fitness ; Evolution, Molecular ; Genetics, Population ; Mitochondria/genetics ; Selection, Genetic ; }, abstract = {Interbreeding and introgression between recently diverged species is common. However, the processes that prevent these species from merging where they co-occur are not well understood. We studied the mechanisms that allowed an isolated group of populations of the snail Helix thessalica to persist within the range of the related Helix pomatia despite high gene flow. Using genomic cline analysis, we found that the nuclear gene flow between the two taxa across the mosaic hybrid zone was not different from that expected under neutral admixture, but that the exchange of mtDNA was asymmetric. Tests showed that there is relaxed selection in the mitochondrial genome of H. thessalica and that the substitution rate is elevated compared to that of H. pomatia. A lack of hybrids that combine the mtDNA of H. thessalica with a mainly (>46%) H. pomatia genomic background indicates that the nuclear-encoded mitochondrial proteins of H. pomatia are not well adapted to the more rapidly evolving proteins and RNAs encoded by the mitochondrion of H. thessalica. The presumed reduction of fitness of hybrids with the fast-evolving mtDNA of H. thessalica and a high H. pomatia ancestry, similar to 'Darwin's Corollary to Haldane's rule', resulted in a relative loss of H. pomatia nuclear ancestry compared to H. thessalica ancestry in the hybrid zone. This probably prevents the H. thessalica populations from merging quickly with the surrounding H. pomatia populations and supports the hypothesis that incompatibilities between rapidly evolving mitochondrial genes and nuclear genes contribute to speciation.}, } @article {pmid39039280, year = {2024}, author = {An, J and Nam, CH and Kim, R and Lee, Y and Won, H and Park, S and Lee, WH and Park, H and Yoon, CJ and An, Y and Kim, JH and Jun, JK and Bae, JM and Shin, EC and Kim, B and Cha, YJ and Kwon, HW and Oh, JW and Park, JY and Kim, MJ and Ju, YS}, title = {Mitochondrial DNA mosaicism in normal human somatic cells.}, journal = {Nature genetics}, volume = {56}, number = {8}, pages = {1665-1677}, pmid = {39039280}, issn = {1546-1718}, mesh = {Humans ; *DNA, Mitochondrial/genetics ; *Mosaicism ; *Mutation ; Heteroplasmy/genetics ; Mutation Rate ; Mitochondria/genetics ; Genome, Mitochondrial ; DNA Replication/genetics ; Female ; Male ; }, abstract = {Somatic cells accumulate genomic alterations with age; however, our understanding of mitochondrial DNA (mtDNA) mosaicism remains limited. Here we investigated the genomes of 2,096 clones derived from three cell types across 31 donors, identifying 6,451 mtDNA variants with heteroplasmy levels of ≳0.3%. While the majority of these variants were unique to individual clones, suggesting stochastic acquisition with age, 409 variants (6%) were shared across multiple embryonic lineages, indicating their origin from heteroplasmy in fertilized eggs. The mutational spectrum exhibited replication-strand bias, implicating mtDNA replication as a major mutational process. We evaluated the mtDNA mutation rate (5.0 × 10[-8] per base pair) and a turnover frequency of 10-20 per year, which are fundamental components shaping the landscape of mtDNA mosaicism over a lifetime. The expansion of mtDNA-truncating mutations toward homoplasmy was substantially suppressed. Our findings provide comprehensive insights into the origins, dynamics and functional consequences of mtDNA mosaicism in human somatic cells.}, } @article {pmid39048023, year = {2024}, author = {Makiuchi, T and Saito-Nakano, Y and Nozaki, T}, title = {Evidence of γ-secretase complex involved in the regulation of intramembrane proteolysis in Entamoeba histolytica.}, journal = {Parasitology international}, volume = {103}, number = {}, pages = {102925}, doi = {10.1016/j.parint.2024.102925}, pmid = {39048023}, issn = {1873-0329}, mesh = {*Entamoeba histolytica/genetics/enzymology/metabolism ; *Amyloid Precursor Protein Secretases/metabolism/genetics ; *Proteolysis ; *Protozoan Proteins/metabolism/genetics ; Cell Membrane/metabolism ; Phylogeny ; Humans ; }, abstract = {Presenilins (PSNs) are multifunctional membrane proteins involved in signal transduction, lysosomal acidification, and certain physiological processes related to mitochondria. The aspartic protease activity of PSN and the formation of a γ-secretase complex with other subunits such as nicastrin (NCT) are required for the biological functions. Although PSN is widely conserved in eukaryotes, most studies on PSN were conducted in metazoans. Homologous genes for PSN and NCT (EhPSN and EhNCT, respectively) are encoded in the genome of Entamoeba histolytica, however, their functions remain unknown. In this study, we showed that EhPSN and EhNCT form a complex on the cell membrane, demonstrating that the parasite possesses γ-secretase. The predicted structure of EhPSN was similar to the human homolog, demonstrated by the crystal structure, and phylogenetic analysis indicated good conservation between EhPSN and human PSN, supporting the premise that EhPSN functions as a subunit of γ-secretase. By contrast, EhNCT appears to have undergone remarkable structural changes during its evolution. Blue native-polyacrylamide gel electrophoresis combined with western blotting indicated that a 150-kDa single band contains both EhPSN (estimated molecular size: 47-kDa) and EhNCT (64-kDa), suggesting that the complex also contains other unknown components or post-translational modifications. Coimmunoprecipitation from amebic lysates also confirmed that EhPSN and EhNCT formed a complex. Indirect immunofluorescence analysis revealed that the complex localized to the plasma membrane. Moreover, EhPSN exhibited protease activity, which was suppressed by a γ-secretase inhibitor. This is the first report of a γ-secretase complex in protozoan parasites.}, } @article {pmid39050895, year = {2024}, author = {Da Costa, RT and Urquiza, P and Perez, MM and Du, Y and Khong, ML and Zheng, H and Guitart-Mampel, M and Elustondo, PA and Scoma, ER and Hambardikar, V and Ueberheide, B and Tanner, JA and Cohen, A and Pavlov, EV and Haynes, CM and Solesio, ME}, title = {Mitochondrial inorganic polyphosphate is required to maintain proteostasis within the organelle.}, journal = {Frontiers in cell and developmental biology}, volume = {12}, number = {}, pages = {1423208}, pmid = {39050895}, issn = {2296-634X}, support = {K99 AG055701/AG/NIA NIH HHS/United States ; R00 AG055701/AG/NIA NIH HHS/United States ; R35 GM139615/GM/NIGMS NIH HHS/United States ; }, abstract = {The existing literature points towards the presence of robust mitochondrial mechanisms aimed at mitigating protein dyshomeostasis within the organelle. However, the precise molecular composition of these mechanisms remains unclear. Our data show that inorganic polyphosphate (polyP), a polymer well-conserved throughout evolution, is a component of these mechanisms. In mammals, mitochondria exhibit a significant abundance of polyP, and both our research and that of others have already highlighted its potent regulatory effect on bioenergetics. Given the intimate connection between energy metabolism and protein homeostasis, the involvement of polyP in proteostasis has also been demonstrated in several organisms. For example, polyP is a bacterial primordial chaperone, and its role in amyloidogenesis has already been established. Here, using mammalian models, our study reveals that the depletion of mitochondrial polyP leads to increased protein aggregation within the organelle, following stress exposure. Furthermore, mitochondrial polyP is able to bind to proteins, and these proteins differ under control and stress conditions. The depletion of mitochondrial polyP significantly affects the proteome under both control and stress conditions, while also exerting regulatory control over gene expression. Our findings suggest that mitochondrial polyP is a previously unrecognized, and potent component of mitochondrial proteostasis.}, } @article {pmid39060773, year = {2024}, author = {Pang, B and Dong, G and Pang, T and Sun, X and Liu, X and Nie, Y and Chang, X}, title = {Emerging insights into the pathogenesis and therapeutic strategies for vascular endothelial injury-associated diseases: focus on mitochondrial dysfunction.}, journal = {Angiogenesis}, volume = {27}, number = {4}, pages = {623-639}, pmid = {39060773}, issn = {1573-7209}, mesh = {Humans ; *Mitochondria/metabolism/pathology ; Animals ; Endothelium, Vascular/pathology/metabolism/physiopathology ; Endothelial Cells/metabolism/pathology ; Reactive Oxygen Species/metabolism ; Vascular Diseases/metabolism/pathology/therapy/etiology ; }, abstract = {As a vital component of blood vessels, endothelial cells play a key role in maintaining overall physiological function by residing between circulating blood and semi-solid tissue. Various stress stimuli can induce endothelial injury, leading to the onset of corresponding diseases in the body. In recent years, the importance of mitochondria in vascular endothelial injury has become increasingly apparent. Mitochondria, as the primary site of cellular aerobic respiration and the organelle for "energy information transfer," can detect endothelial cell damage by integrating and receiving various external stress signals. The generation of reactive oxygen species (ROS) and mitochondrial dysfunction often determine the evolution of endothelial cell injury towards necrosis or apoptosis. Therefore, mitochondria are closely associated with endothelial cell function, helping to determine the progression of clinical diseases. This article comprehensively reviews the interconnection and pathogenesis of mitochondrial-induced vascular endothelial cell injury in cardiovascular diseases, renal diseases, pulmonary-related diseases, cerebrovascular diseases, and microvascular diseases associated with diabetes. Corresponding therapeutic approaches are also provided. Additionally, strategies for using clinical drugs to treat vascular endothelial injury-based diseases are discussed, aiming to offer new insights and treatment options for the clinical diagnosis of related vascular injuries.}, } @article {pmid39062606, year = {2024}, author = {Li, S and Jiao, B and Wang, J and Zhao, P and Dong, F and Yang, F and Ma, C and Guo, P and Zhou, S}, title = {Identification of Wheat Glutamate Synthetase Gene Family and Expression Analysis under Nitrogen Stress.}, journal = {Genes}, volume = {15}, number = {7}, pages = {}, pmid = {39062606}, issn = {2073-4425}, support = {2022KJCXZX-SSS-4//HAAFS Agriculture Science and Technology Innovation Project/ ; }, mesh = {*Triticum/genetics/metabolism ; *Nitrogen/metabolism ; *Gene Expression Regulation, Plant ; *Stress, Physiological/genetics ; *Plant Proteins/genetics/metabolism ; Glutamate Synthase/genetics/metabolism ; Multigene Family ; Promoter Regions, Genetic ; Plant Roots/genetics/metabolism/growth & development ; Seedlings/genetics/growth & development/metabolism ; Plant Leaves/genetics/metabolism ; Phylogeny ; }, abstract = {Nitrogen (N), as the main component of biological macromolecules, maintains the basic process of plant growth and development. GOGAT, as a key enzyme in the N assimilation process, catalyzes α-ketoglutaric acid and glutamine to form glutamate. In this study, six GOGAT genes in wheat (Triticum aestivum L.) were identified and classified into two subfamilies, Fd-GOGAT (TaGOGAT2s) and NADH-GOGAT (TaGOGAT3s), according to the type of electron donor. Subcellular localization prediction showed that TaGOGAT3-D was localized in mitochondria and that the other five TaGOGATs were localized in chloroplasts. Via the analysis of promoter elements, many binding sites related to growth and development, hormone regulation and plant stress resistance regulations were found on the TaGOGAT promoters. The tissue-specificity expression analysis showed that TaGOGAT2s were mainly expressed in wheat leaves and flag leaves, while TaGOGAT3s were highly expressed in roots and leaves. The expression level of TaGOGATs and the enzyme activity of TaGOGAT3s in the leaves and roots of wheat seedlings were influenced by the treatment of N deficiency. This study conducted a systematic analysis of wheat GOGAT genes, providing a theoretical basis not only for the functional analysis of TaGOGATs, but also for the study of wheat nitrogen use efficiency (NUE).}, } @article {pmid39062621, year = {2024}, author = {Aishan, Z and Mu, ZL and Li, ZC and Luo, XY and Huangfu, N}, title = {The First Three Mitochondrial Genomes for the Characterization of the Genus Egeirotrioza (Hemiptera: Triozidae) and Phylogenetic Implications.}, journal = {Genes}, volume = {15}, number = {7}, pages = {}, pmid = {39062621}, issn = {2073-4425}, support = {2022D01C403//Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; 5244031//Beijing Natural Science Foundation/ ; }, mesh = {Animals ; *Genome, Mitochondrial ; *Phylogeny ; *Hemiptera/genetics/classification ; Evolution, Molecular ; RNA, Transfer/genetics ; }, abstract = {(1) Background: Mitochondrial genomes are important markers for the study of phylogenetics and systematics. Triozidae includes some primary pests of Populus euphratica. The phylogenetic relationships of this group remain controversial due to the lack of molecular data. (2) Methods: Mitochondria of Egeirotrioza Boselli were sequenced and assembled. We analyzed the sequence length, nucleotide composition, and evolutionary rate of Triozidae, combined with the 13 published mitochondrial genomes. (3) Results: The evolutionary rate of protein-coding genes was as follows: ATP8 > ND6 > ND5 > ND2 > ND4 > ND4L > ND1 > ND3 > APT6 > CYTB > COX3 > COX2 > COX1. We reconstructed the phylogenetic relationships of Triozidae based on 16 triozid mitochondrial genomes (thirteen ingroups and three outgroups) using the maximum likelihood (ML) and Bayesian inference (BI) approaches. The phylogenetic analysis of the 16 Triozidae mitochondrial genomes showed that Egeirotrioza was closely related to Leptynoptera. (4) Conclusions: We have identified 13 PCGs, 22 tRNAs, 2 rRNAs, and 1 control region (CR) of all newly sequenced mitochondrial genomes, which were the mitochondrial gene type in animals. The results of this study provide valuable genomic information for the study of psyllid species.}, } @article {pmid39062690, year = {2024}, author = {Zhang, Y and Peng, Y and Zhang, H and Gao, Q and Song, F and Cui, X and Mo, F}, title = {Genome-Wide Identification of APX Gene Family in Citrus maxima and Expression Analysis at Different Postharvest Preservation Times.}, journal = {Genes}, volume = {15}, number = {7}, pages = {}, pmid = {39062690}, issn = {2073-4425}, support = {202427060300564//Innovation and Entrepreneurship Training Program for College Students/ ; }, mesh = {*Citrus/genetics ; *Gene Expression Regulation, Plant ; *Ascorbate Peroxidases/genetics/metabolism ; *Plant Proteins/genetics/metabolism ; *Multigene Family ; *Phylogeny ; Genome, Plant ; Fruit/genetics/metabolism ; Gene Expression Profiling/methods ; }, abstract = {Ascorbate peroxidase (APX) is a crucial enzyme involved in cellular antioxidant defense and plays a pivotal role in modulating reactive oxygen species (ROS) levels under various environmental stresses in plants. This study utilized bioinformatics methods to identify and analyze the APX gene family of pomelo, while quantitative real-time PCR (qRT-PCR) was employed to validate and analyze the expression of CmAPXs at different stages of fruit postharvest. This study identified 96 members of the CmAPX family in the entire pomelo genome, with uneven distribution across nine chromosomes and occurrences of gene fragment replication. The subcellular localization includes peroxisome, cytoplasm, chloroplasts, and mitochondria. The CmAPX family exhibits a similar gene structure, predominantly consisting of two exons. An analysis of the upstream promoter regions revealed a significant presence of cis-acting elements associated with light (Box 4, G-Box), hormones (ABRE, TCA-element), and stress-related (MBS, LTR, ARE) responses. Phylogenetic and collinearity analyses revealed that the CmAPX gene family can be classified into three subclasses, with seven collinear gene pairs. Furthermore, CmAPXs are closely related to citrus, pomelo, and lemon, followed by Arabidopsis, and exhibit low homology with rice. Additionally, the transcriptomic heat map and qPCR results revealed that the expression levels of CmAPX57, CmAPX34, CmAPX50, CmAPX4, CmAPX5, and CmAPX81 were positively correlated with granulation degree, indicating the activation of the endogenous stress resistance system in pomelo cells by these genes, thereby conferring resistance to ROS. This finding is consistent with the results of GO enrichment analysis. Furthermore, 38 miRNAs were identified as potential regulators targeting the CmAPX family for post-transcriptional regulation. Thus, this study has preliminarily characterized members of the APX gene family in pomelo and provided valuable insights for further research on their antioxidant function and molecular mechanism.}, } @article {pmid39062730, year = {2024}, author = {Domínguez-Ruiz, M and Olarte, M and Onecha, E and García-Vaquero, I and Gelvez, N and López, G and Villamar, M and Morín, M and Moreno-Pelayo, MA and Morales-Angulo, C and Polo, R and Tamayo, ML and Del Castillo, I}, title = {Novel Cases of Non-Syndromic Hearing Impairment Caused by Pathogenic Variants in Genes Encoding Mitochondrial Aminoacyl-tRNA Synthetases.}, journal = {Genes}, volume = {15}, number = {7}, pages = {}, pmid = {39062730}, issn = {2073-4425}, support = {PI20/00619//Instituto de Salud Carlos III/ ; S2017/ BMD3721//Regional Government of Madrid/ ; 00008286//Pontificia Universidad Javeriana/ ; }, mesh = {Humans ; *Amino Acyl-tRNA Synthetases/genetics ; Male ; Female ; Child ; Child, Preschool ; Adolescent ; Hearing Loss/genetics ; Mitochondrial Proteins/genetics ; Adult ; Pedigree ; Mitochondria/genetics ; Mutation ; Infant ; Deafness/genetics ; Phenotype ; Genetic Association Studies ; Lysine-tRNA Ligase/genetics ; }, abstract = {Dysfunction of some mitochondrial aminoacyl-tRNA synthetases (encoded by the KARS1, HARS2, LARS2 and NARS2 genes) results in a great variety of phenotypes ranging from non-syndromic hearing impairment (NSHI) to very complex syndromes, with a predominance of neurological signs. The diversity of roles that are played by these moonlighting enzymes and the fact that most pathogenic variants are missense and affect different domains of these proteins in diverse compound heterozygous combinations make it difficult to establish genotype-phenotype correlations. We used a targeted gene-sequencing panel to investigate the presence of pathogenic variants in those four genes in cohorts of 175 Spanish and 18 Colombian familial cases with non-DFNB1 autosomal recessive NSHI. Disease-associated variants were found in five cases. Five mutations were novel as follows: c.766C>T in KARS1, c.475C>T, c.728A>C and c.1012G>A in HARS2, and c.795A>G in LARS2. We provide audiograms from patients at different ages to document the evolution of the hearing loss, which is mostly prelingual and progresses from moderate/severe to profound, the middle frequencies being more severely affected. No additional clinical sign was observed in any affected subject. Our results confirm the involvement of KARS1 in DFNB89 NSHI, for which until now there was limited evidence.}, } @article {pmid39067796, year = {2024}, author = {Qu, K and Liu, D and Sun, L and Li, M and Xia, T and Sun, W and Xia, Y}, title = {De novo assembly and comprehensive analysis of the mitochondrial genome of Taxus wallichiana reveals different repeats mediate recombination to generate multiple conformations.}, journal = {Genomics}, volume = {116}, number = {5}, pages = {110900}, doi = {10.1016/j.ygeno.2024.110900}, pmid = {39067796}, issn = {1089-8646}, mesh = {*Taxus/genetics/classification ; *Genome, Mitochondrial ; *Phylogeny ; Recombination, Genetic ; RNA, Transfer/genetics ; RNA Editing ; Repetitive Sequences, Nucleic Acid ; }, abstract = {Taxus plants are the exclusive source of paclitaxel, an anticancer drug with significant medicinal and economic value. Interspecies hybridization and gene introgression during evolution have obscured distinctions among Taxus species, complicating their phylogenetic classification. While the chloroplast genome of Taxus wallichiana, a widely distributed species in China, has been sequenced, its mitochondrial genome (mitogenome) remains uncharacterized.We sequenced and assembled the T. wallichiana mitogenome using BGI short reads and Nanopore long reads, facilitating comparisons with other gymnosperm mitogenomes. The T. wallichiana mitogenome spanning 469,949 bp, predominantly forms a circular configuration with a GC content of 50.51%, supplemented by 3 minor configurations mediated by one pair of LRs and two pairs of IntRs. It includes 32 protein-coding genes, 7 tRNA genes, and 3 rRNA genes, several of which exist in multiple copies.We detailed the mitogenome's structure, codon usage, RNA editing, and sequence migration between organelles, constructing a phylogenetic tree to elucidate evolutionary relationships. Unlike typical gymnosperm mitochondria, T. wallichiana shows no evidence of mitochondrial-plastid DNA transfer (MTPT), highlighting its unique genomic architecture. Synteny analysis indicated extensive genomic rearrangements in T. wallichiana, likely driven by recombination among abundant repetitive sequences. This study offers a high-quality T. wallichiana mitogenome, enhancing our understanding of gymnosperm mitochondrial evolution and supporting further cultivation and utilization of Taxus species.}, } @article {pmid39071318, year = {2024}, author = {Sloan, DB and Broz, AK and Kuster, SA and Muthye, V and Peñafiel-Ayala, A and Marron, JR and Lavrov, DV and Brieba, LG}, title = {Expansion of the MutS Gene Family in Plants.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39071318}, issn = {2692-8205}, support = {R35 GM148134/GM/NIGMS NIH HHS/United States ; T32 GM132057/GM/NIGMS NIH HHS/United States ; }, abstract = {The MutS gene family is distributed across the tree of life and is involved in recombination, DNA repair, and protein translation. Multiple evolutionary processes have expanded the set of MutS genes in plants relative to other eukaryotes. Here, we investigate the origins and functions of these plant-specific genes. Land plants, green algae, red algae, and glaucophytes share cyanobacterial-like MutS1 and MutS2 genes that presumably were gained via plastid endosymbiotic gene transfer. MutS1 was subsequently lost in some taxa, including seed plants, whereas MutS2 was duplicated in Viridiplantae (i.e., land plants and green algae) with widespread retention of both resulting paralogs. Viridiplantae also have two anciently duplicated copies of the eukaryotic MSH6 gene (i.e., MSH6 and MSH7) and acquired MSH1 via horizontal gene transfer - potentially from a nucleocytovirus. Despite sharing the same name, "plant MSH1" is not directly related to the gene known as MSH1 in some fungi and animals, which may be an ancestral eukaryotic gene acquired via mitochondrial endosymbiosis and subsequently lost in most eukaryotic lineages. There has been substantial progress in understanding the functions of MSH1 and MSH6/MSH7 in plants, but the roles of the cyanobacterial-like MutS1 and MutS2 genes remain uncharacterized. Known functions of bacterial homologs and predicted protein structures, including fusions to diverse nuclease domains, provide hypotheses about potential molecular mechanisms. Because most plant-specific MutS proteins are targeted to the mitochondria and/or plastids, the expansion of this family appears to have played a large role in shaping plant organelle genetics.}, } @article {pmid39080514, year = {2024}, author = {Lu, G and Wang, W and Zhang, S and Yang, G and Zhang, K and Que, Y and Deng, L}, title = {The first complete mitochondrial genome of Grossulariaceae: Molecular features, structure recombination, and genetic evolution.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {744}, pmid = {39080514}, issn = {1471-2164}, mesh = {*Genome, Mitochondrial ; *Evolution, Molecular ; *Phylogeny ; Recombination, Genetic ; Ribes/genetics ; RNA Editing ; RNA, Transfer/genetics ; RNA, Ribosomal/genetics ; }, abstract = {BACKGROUND: Mitochondria play crucial roles in the growth, development, and adaptation of plants. Blackcurrant (Ribes nigrum L.) stands out as a significant berry species due to its rich nutritional profile, medicinal properties, and health benefits. Despite its importance, the mitochondrial genome of blackcurrant remains unassembled.

RESULTS: This study presents the first assembly of the mitochondrial genome of R. nigrum in the Grossulariaceae family. The genome spans 450,227 base pairs (bp) and encompasses 39 protein-coding genes (PCGs), 19 transfer RNAs (tRNAs), and three ribosomal RNAs (rRNAs). Protein-coding regions constitute 8.88% of the entire genome. Additionally, we identified 180 simple sequence repeats, 12 tandem repeats, and 432 pairs of dispersed repeats. Notably, the dispersed sequence R1 (cotig3, 1,129 bp) mediated genome recombination, resulting in the formation of two major conformations, namely master and double circles. Furthermore, we identified 731 C-to-U RNA editing sites within the PCGs. Among these, cox1-2, nad1-2, and nad4L-2 were associated with the creation of start codons, whereas atp6-718 and rps10-391 were linked to termination codons. We also detected fourteen plastome fragments within the mitogenome, constituting 1.11% of the total length. Phylogenetic analysis suggests that R. nigrum might have undergone multiple genomic reorganization and/or gene transfer events, resulting in the loss of two PCGs (rps2 and rps11) during its evolutionary history.

CONCLUSIONS: This investigation unveils the molecular characteristics of the R. nigrum mitogenome, shedding light on its evolutionary trajectory and phylogenetic implications. Furthermore, it serves as a valuable reference for evolutionary research and germplasm identification within the genus.}, } @article {pmid39080531, year = {2024}, author = {Liu, YJ and Zhang, TY and Wang, QQ and Draisma, SGA and Hu, ZM}, title = {Comparative structure and evolution of the organellar genomes of Padina usoehtunii (Dictyotales) with the brown algal crown radiation clade.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {747}, pmid = {39080531}, issn = {1471-2164}, mesh = {*Phaeophyceae/genetics ; *Phylogeny ; *Evolution, Molecular ; *Genome, Chloroplast ; Genome, Mitochondrial ; Inverted Repeat Sequences/genetics ; Chloroplasts/genetics ; }, abstract = {BACKGROUND: Organellar genomes have become increasingly essential for studying genetic diversity, phylogenetics, and evolutionary histories of seaweeds. The order Dictyotales (Dictyotophycidae), a highly diverse lineage within the Phaeophyceae, is long-term characterized by a scarcity of organellar genome datasets compared to orders of the brown algal crown radiation (Fucophycidae).

RESULTS: We sequenced the organellar genomes of Padina usoehtunii, a representative of the order Dictyotales, to investigate the structural and evolutionary differences by comparing to five other major brown algal orders. Our results confirmed previously reported findings that the rate of structural rearrangements in chloroplast genomes is higher than that in mitochondria, whereas mitochondrial sequences exhibited a higher substitution rate compared to chloroplasts. Such evolutionary patterns contrast with land plants and green algae. The expansion and contraction of the inverted repeat (IR) region in the chloroplast correlated with the changes in the number of boundary genes. Specifically, the size of the IR region influenced the position of the boundary gene rpl21, with complete rpl21 genes found within the IR region in Dictyotales, Sphacelariales and Ectocarpales, while the rpl21 genes in Desmarestiales, Fucales, and Laminariales span both the IR and short single copy (SSC) regions. The absence of the rbcR gene in the Dictyotales may indicate an endosymbiotic transfer from the chloroplast to the nuclear genome. Inversion of the SSC region occurred at least twice in brown algae. Once in a lineage only represented by the Ectocarpales in the present study and once in a lineage only represented by the Fucales. Photosystem genes in the chloroplasts experienced the strongest signature of purifying selection, while ribosomal protein genes in both chloroplasts and mitochondria underwent a potential weak purifying selection.

CONCLUSIONS: Variations in chloroplast genome structure among different brown algal orders are evolutionarily linked to their phylogenetic positions in the Phaeophyceae tree. Chloroplast genomes harbor more structural rearrangements than the mitochondria, despite mitochondrial genes exhibiting faster mutation rates. The position and the change in the number of boundary genes likely shaped the IR regions in the chloroplast, and the produced structural variability is important mechanistically to create gene diversity in brown algal chloroplast.}, } @article {pmid39084221, year = {2024}, author = {Moreira, D and Blaz, J and Kim, E and Eme, L}, title = {A gene-rich mitochondrion with a unique ancestral protein transport system.}, journal = {Current biology : CB}, volume = {34}, number = {16}, pages = {3812-3819.e3}, doi = {10.1016/j.cub.2024.07.017}, pmid = {39084221}, issn = {1879-0445}, mesh = {*Mitochondria/metabolism/genetics ; *Genome, Mitochondrial ; *Protein Transport ; Evolution, Molecular ; Phylogeny ; Symbiosis/genetics ; }, abstract = {Mitochondria originated from an ancient endosymbiosis involving an alphaproteobacterium.[1][,][2][,][3] Over time, these organelles reduced their gene content massively, with most genes being transferred to the host nucleus before the last eukaryotic common ancestor (LECA).[4] This process has yielded varying gene compositions in modern mitogenomes, including the complete loss of this organellar genome in some extreme cases.[5][,][6][,][7][,][8][,][9][,][10][,][11][,][12][,][13][,][14] At the other end of the spectrum, jakobids harbor the most gene-rich mitogenomes, encoding 60-66 proteins.[8] Here, we introduce the mitogenome of Mantamonas sphyraenae, a protist from the deep-branching CRuMs supergroup.[15][,][16] Remarkably, it boasts the most gene-rich mitogenome outside of jakobids, by housing 91 genes, including 62 protein-coding ones. These include rare homologs of the four subunits of the bacterial-type cytochrome c maturation system I (CcmA, CcmB, CcmC, and CcmF) alongside a unique ribosomal protein S6. During the early evolution of mitochondria, gene transfer from the proto-mitochondrial endosymbiont to the nucleus became possible thanks to systems facilitating the transport of proteins synthesized in the host cytoplasm back to the mitochondrion. In addition to the universally found eukaryotic protein import systems, jakobid mitogenomes were reported to uniquely encode the SecY transmembrane protein of the Sec general secretory pathway, whose evolutionary origin was however unclear. The Mantamonas mitogenome not only encodes SecY but also SecA, SecE, and SecG, making it the sole eukaryote known to house a complete mitochondrial Sec translocation system. Furthermore, our phylogenetic and comparative genomic analyses provide compelling evidence for the alphaproteobacterial origin of this system, establishing its presence in LECA.}, } @article {pmid39092472, year = {2024}, author = {Özdemir, M and Dennerlein, S}, title = {The TOM complex from an evolutionary perspective and the functions of TOMM70.}, journal = {Biological chemistry}, volume = {}, number = {}, pages = {}, pmid = {39092472}, issn = {1437-4315}, abstract = {In humans, up to 1,500 mitochondrial precursor proteins are synthesized at cytosolic ribosomes and must be imported into the organelle. This is not only essential for mitochondrial but also for many cytosolic functions. The majority of mitochondrial precursor proteins are imported over the translocase of the outer membrane (TOM). In recent years, high-resolution structure analyses from different organisms shed light on the composition and arrangement of the TOM complex. Although significant similarities have been found, differences were also observed, which have been favored during evolution and could reflect the manifold functions of TOM with cellular signaling and its response to altered metabolic situations. A key component within these regulatory mechanisms is TOMM70, which is involved in protein import, forms contacts to the ER and the nucleus, but is also involved in cellular defense mechanisms during infections.}, } @article {pmid39096545, year = {2024}, author = {Zhang, Y and Liu, J and Zheng, R and Hou, K and Zhang, Y and Jia, T and Lu, X and Samarawickrama, PN and Jia, S and He, Y and Liu, J}, title = {Curcumin analogue EF24 prevents alveolar epithelial cell senescence to ameliorate idiopathic pulmonary fibrosis via activation of PTEN.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {133}, number = {}, pages = {155882}, doi = {10.1016/j.phymed.2024.155882}, pmid = {39096545}, issn = {1618-095X}, mesh = {*Idiopathic Pulmonary Fibrosis/drug therapy ; Animals ; *Cellular Senescence/drug effects ; Humans ; *PTEN Phosphohydrolase/metabolism ; *Bleomycin ; Mice ; *Mice, Inbred C57BL ; *Alveolar Epithelial Cells/drug effects/metabolism ; Curcumin/pharmacology/analogs & derivatives ; A549 Cells ; Male ; Benzylidene Compounds/pharmacology ; Signal Transduction/drug effects ; Piperidones/pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; }, abstract = {BACKGROUND: Treating Idiopathic pulmonary fibrosis (IPF) remains challenging owing to its relentless progression, grim prognosis, and the scarcity of effective treatment options. Emerging evidence strongly supports the critical role of accelerated senescence in alveolar epithelial cells (AECs) in driving the progression of IPF. Consequently, targeting senescent AECs emerges as a promising therapeutic strategy for IPF.

PURPOSE: Curcumin analogue EF24 is a derivative of curcumin and shows heightened bioactivity encompassing anti-inflammatory, anti-tumor and anti-aging properties. The objective of this study was to elucidate the therapeutic potential and underlying molecular mechanisms of EF24 in the treatment of IPF.

METHODS: A549 and ATII cells were induced to become senescent using bleomycin. Senescence markers were examined using different methods including senescence-associated β-galactosidase (SA-β-gal) staining, western blotting, and q-PCR. Mice were intratracheally administrated with bleomycin to induce pulmonary fibrosis. This was validated by micro-computed tomography (CT), masson trichrome staining, and transmission electron microscope (TEM). The role and underlying mechanisms of EF24 in IPF were determined in vitro and in vivo by evaluating the expressions of PTEN, AKT/mTOR/NF-κB signaling pathway, and mitophagy using western blotting or flow cytometry.

RESULTS: We identified that the curcumin analogue EF24 was the most promising candidate among 12 compounds against IPF. EF24 treatment significantly reduced senescence biomarkers in bleomycin-induced senescent AECs, including SA-β-Gal, PAI-1, P21, and the senescence-associated secretory phenotype (SASP). EF24 also effectively inhibited fibroblast activation which was induced by senescent AECs or TGF-β. We revealed that PTEN activation was integral for EF24 to inhibit AECs senescence by suppressing the AKT/mTOR/NF-κB signaling pathway. Additionally, EF24 improved mitochondrial dysfunction through induction of mitophagy. Furthermore, EF24 administration significantly reduced the senescent phenotype induced by bleomycin in the lung tissues of mice. Notably, EF24 mitigates fibrosis and promotes overall health benefits in both the acute and chronic phases of IPF, suggesting its therapeutic potential in IPF treatment.

CONCLUSION: These findings collectively highlight EF24 as a new and effective therapeutic agent against IPF by inhibiting senescence in AECs.}, } @article {pmid39101615, year = {2024}, author = {Veeraragavan, S and Johansen, M and Johnston, IG}, title = {Evolution and maintenance of mtDNA gene content across eukaryotes.}, journal = {The Biochemical journal}, volume = {481}, number = {15}, pages = {1015-1042}, pmid = {39101615}, issn = {1470-8728}, mesh = {Animals ; *DNA, Mitochondrial/genetics/metabolism ; *Evolution, Molecular ; Eukaryota/genetics ; Humans ; Recombination, Genetic ; Mitochondria/genetics/metabolism ; Genes, Mitochondrial ; }, abstract = {Across eukaryotes, most genes required for mitochondrial function have been transferred to, or otherwise acquired by, the nucleus. Encoding genes in the nucleus has many advantages. So why do mitochondria retain any genes at all? Why does the set of mtDNA genes vary so much across different species? And how do species maintain functionality in the mtDNA genes they do retain? In this review, we will discuss some possible answers to these questions, attempting a broad perspective across eukaryotes. We hope to cover some interesting features which may be less familiar from the perspective of particular species, including the ubiquity of recombination outside bilaterian animals, encrypted chainmail-like mtDNA, single genes split over multiple mtDNA chromosomes, triparental inheritance, gene transfer by grafting, gain of mtDNA recombination factors, social networks of mitochondria, and the role of mtDNA dysfunction in feeding the world. We will discuss a unifying picture where organismal ecology and gene-specific features together influence whether organism X retains mtDNA gene Y, and where ecology and development together determine which strategies, importantly including recombination, are used to maintain the mtDNA genes that are retained.}, } @article {pmid39107687, year = {2024}, author = {Raynes, Y and Santiago, JC and Lemieux, FA and Darwin, L and Rand, DM}, title = {Sex, tissue, and mitochondrial interactions modify the transcriptional response to rapamycin in Drosophila.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {766}, pmid = {39107687}, issn = {1471-2164}, support = {F31 GM117851/GM/NIGMS NIH HHS/United States ; P20 GM109035/GM/NIGMS NIH HHS/United States ; R01 GM067862/GM/NIGMS NIH HHS/United States ; R35 GM139607/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Sirolimus/pharmacology ; Female ; Male ; *Mitochondria/metabolism/drug effects/genetics ; Drosophila melanogaster/genetics/drug effects ; Sex Factors ; TOR Serine-Threonine Kinases/metabolism ; Organ Specificity/genetics ; Drosophila/genetics/drug effects ; Transcription, Genetic/drug effects ; Gene Expression Profiling ; }, abstract = {BACKGROUND: Many common diseases exhibit uncontrolled mTOR signaling, prompting considerable interest in the therapeutic potential of mTOR inhibitors, such as rapamycin, to treat a range of conditions, including cancer, aging-related pathologies, and neurological disorders. Despite encouraging preclinical results, the success of mTOR interventions in the clinic has been limited by off-target side effects and dose-limiting toxicities. Improving clinical efficacy and mitigating side effects require a better understanding of the influence of key clinical factors, such as sex, tissue, and genomic background, on the outcomes of mTOR-targeting therapies.

RESULTS: We assayed gene expression with and without rapamycin exposure across three distinct body parts (head, thorax, abdomen) of D. melanogaster flies, bearing either their native melanogaster mitochondrial genome or the mitochondrial genome from a related species, D. simulans. The fully factorial RNA-seq study design revealed a large number of genes that responded to the rapamycin treatment in a sex-dependent and tissue-dependent manner, and relatively few genes with the transcriptional response to rapamycin affected by the mitochondrial background. Reanalysis of an earlier study confirmed that mitochondria can have a temporal influence on rapamycin response.

CONCLUSIONS: We found significant and wide-ranging effects of sex and body part, alongside a subtle, potentially time-dependent, influence of mitochondria on the transcriptional response to rapamycin. Our findings suggest a number of pathways that could be crucial for predicting potential side effects of mTOR inhibition in a particular sex or tissue. Further studies of the temporal response to rapamycin are necessary to elucidate the effects of the mitochondrial background on mTOR and its inhibition.}, } @article {pmid39111696, year = {2024}, author = {Wu, Y and Liu, Y and Feng, Y and Li, X and Lu, Z and Gu, H and Li, W and Hill, LJ and Ou, S}, title = {Evolution of therapeutic strategy based on oxidant-antioxidant balance for fuchs endothelial corneal dystrophy.}, journal = {The ocular surface}, volume = {34}, number = {}, pages = {247-261}, doi = {10.1016/j.jtos.2024.08.003}, pmid = {39111696}, issn = {1937-5913}, mesh = {Humans ; *Antioxidants/therapeutic use/metabolism ; Endothelium, Corneal/metabolism/pathology ; *Fuchs' Endothelial Dystrophy/genetics/metabolism/pathology/therapy ; Genetic Therapy/methods ; Oxidants/metabolism ; *Oxidative Stress ; }, abstract = {Fuchs endothelial corneal dystrophy (FECD) stands as the most prevalent primary corneal endothelial dystrophy worldwide, posing a significant risk to corneal homeostasis and clarity. Corneal endothelial cells exhibit susceptibility to oxidative stress, suggesting a nuanced relationship between oxidant-antioxidant imbalance and FECD pathogenesis, irrespective of FECD genotype. Given the constrained availability of corneal transplants, exploration into non-surgical interventions becomes crucial. This encompasses traditional antioxidants, small molecule compounds, biologics, and diverse non-drug therapies, such as gene-related therapy, hydrogen therapy and near infrared light therapy. This review concentrates on elucidating the mechanisms behind oxidant-antioxidant imbalance and the evolution of strategies to restore oxidant-antioxidant balance in FECD. It provides a comprehensive overview of both conventional and emerging therapeutic approaches, offering valuable insights for the advancement of non-surgical treatment modalities. The findings herein might establish a robust foundation for future research and the therapeutic strategy of FECD.}, } @article {pmid39119601, year = {2024}, author = {Zachos, KA and Gamboa, JA and Dewji, AS and Lee, J and Brijbassi, S and Andreazza, AC}, title = {The interplay between mitochondria, the gut microbiome and metabolites and their therapeutic potential in primary mitochondrial disease.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1428242}, pmid = {39119601}, issn = {1663-9812}, abstract = {The various roles of the mitochondria and the microbiome in health and disease have been thoroughly investigated, though they are often examined independently and in the context of chronic disease. However, the mitochondria and microbiome are closely connected, namely, through their evolution, maternal inheritance patterns, overlapping role in many diseases and their importance in the maintenance of human health. The concept known as the "mitochondria-microbiome crosstalk" is the ongoing bidirectional crosstalk between these two entities and warrants further exploration and consideration, especially in the context of primary mitochondrial disease, where mitochondrial dysfunction can be detrimental for clinical manifestation of disease, and the role and composition of the microbiome is rarely investigated. A potential mechanism underlying this crosstalk is the role of metabolites from both the mitochondria and the microbiome. During digestion, gut microbes modulate compounds found in food, which can produce metabolites with various bioactive effects. Similarly, mitochondrial metabolites are produced from substrates that undergo biochemical processes during cellular respiration. This review aims to provide an overview of current literature examining the mitochondria-microbiome crosstalk, the role of commonly studied metabolites serve in signaling and mediating these biochemical pathways, and the impact diet has on both the mitochondria and the microbiome. As a final point, this review highlights the up-to-date implications of the mitochondria-microbiome crosstalk in mitochondrial disease and its potential as a therapeutic tool or target.}, } @article {pmid39120309, year = {2024}, author = {Proust, B and Herak Bosnar, M and Ćetković, H and Tokarska-Schlattner, M and Schlattner, U}, title = {Mitochondrial NME6: A Paradigm Change within the NME/NDP Kinase Protein Family?.}, journal = {Cells}, volume = {13}, number = {15}, pages = {}, pmid = {39120309}, issn = {2073-4409}, support = {ANR-15-IDEX-02 SYMER//Agence Nationale de la Recherche/ ; IP-2022-10-7420//Croatian Science Foundation/ ; }, mesh = {Humans ; Animals ; *Mitochondria/metabolism ; Mitochondrial Proteins/metabolism/genetics ; NM23 Nucleoside Diphosphate Kinases/metabolism/genetics ; Nucleoside Diphosphate Kinase D/metabolism/genetics ; }, abstract = {Eukaryotic NMEs/NDP kinases are a family of 10 multifunctional proteins that occur in different cellular compartments and interact with various cellular components (proteins, membranes, and DNA). In contrast to the well-studied Group I NMEs (NME1-4), little is known about the more divergent Group II NMEs (NME5-9). Three recent publications now shed new light on NME6. First, NME6 is a third mitochondrial NME, largely localized in the matrix space, associated with the mitochondrial inner membrane. Second, while its monomeric form is inactive, NME6 gains NDP kinase activity through interaction with mitochondrial RCC1L. This challenges the current notion that mammalian NMEs require the formation of hexamers to become active. The formation of complexes between NME6 and RCC1L, likely heterodimers, seemingly obviates the necessity for hexamer formation, stabilizing a NDP kinase-competent conformation. Third, NME6 is involved in mitochondrial gene maintenance and expression by providing (d)NTPs for replication and transcription (in particular the pyrimidine nucleotides) and by a less characterized mechanism that supports mitoribosome function. This review offers an overview of NME evolution and structure and highlights the new insight into NME6. The new findings position NME6 as the most comprehensively studied protein in NME Group II and may even suggest it as a new paradigm for related family members.}, } @article {pmid39122659, year = {2024}, author = {Rhodes, EM and Yap, KN and Hill, GE and Hood, WR}, title = {A Comparison of the Mitochondrial Performance between Migratory and Sedentary Mimid Thrushes.}, journal = {Integrative and comparative biology}, volume = {64}, number = {6}, pages = {1859-1870}, doi = {10.1093/icb/icae137}, pmid = {39122659}, issn = {1557-7023}, support = {//Auburn University/ ; OIA1736150//National Science Foundation/ ; //Society for the Study of Evolution/ ; }, mesh = {Animals ; *Animal Migration/physiology ; Songbirds/physiology ; Flight, Animal/physiology ; Mitochondria/physiology ; Citrate (si)-Synthase/metabolism ; Species Specificity ; Pectoralis Muscles/physiology ; }, abstract = {Birds exhibit a variety of migration strategies. Because sustained flapping flight requires the production of elevated levels of energy compared to typical daily activities, migratory birds are well-documented to have several physiological adaptations to support the energy demands of migration. However, even though mitochondria are the source of ATP that powers flight, the respiratory performance of the mitochondria is almost unstudied in the context of migration. We hypothesized that migratory species would have higher mitochondrial respiratory performance during migration compared to species that do not migrate. To test this hypothesis, we compared variables related to mitochondrial respiratory function between two confamilial bird species-the migratory Gray Catbird (Dumetella carolinensis) and the non-migratory Northern Mockingbird (Mimus polyglottos). Birds were captured at the same location along the Alabama Gulf Coast, where we assumed that Gray Catbirds were migrants and where resident Northern Mockingbirds live year-round. We found a trend in citrate synthase activity, which suggests that Gray Catbirds have a greater mitochondrial volume in their pectoralis muscle, but we observed no other differences in mitochondrial respiration or complex enzymatic activities between individuals from the migrant vs. the non-migrant species. However, when we assessed the catbirds included in our study using well-established indicators of migratory physiology, birds fell into two groups: a group with physiological parameters indicating a physiology of birds engaged in migration and a group with the physiology of birds not migrating. Thus, our comparison included catbirds that appeared to be outside of migratory condition. When we compared the mitochondrial performance of these three groups, we found that the mitochondrial respiratory capacity of migrating catbirds was very similar to that of Northern Mockingbirds, while the catbirds judged to be not migrating were lowest. One explanation for these observations is these species display very different daily flight behaviors. While the mockingbirds we sampled were not breeding nor migrating, they are highly active birds, living in the open and engaging in flapping flights throughout each day. In contrast, Gray Catbirds live in shrubs and fly infrequently when not migrating. Such differences in baseline energy needs likely confounded our attempt to study adaptations to migration.}, } @article {pmid39122691, year = {2024}, author = {Williams, SK and Jerlström Hultqvist, J and Eglit, Y and Salas-Leiva, DE and Curtis, B and Orr, RJS and Stairs, CW and Atalay, TN and MacMillan, N and Simpson, AGB and Roger, AJ}, title = {Extreme mitochondrial reduction in a novel group of free-living metamonads.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {6805}, pmid = {39122691}, issn = {2041-1723}, support = {FRN-142349//Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)/ ; }, mesh = {*Mitochondria/metabolism/genetics ; *Phylogeny ; *Proteome/metabolism/genetics ; Transcriptome ; Eukaryota/genetics/metabolism/classification ; Gene Transfer, Horizontal ; Iron-Sulfur Proteins/metabolism/genetics ; }, abstract = {Metamonads are a diverse group of heterotrophic microbial eukaryotes adapted to living in hypoxic environments. All metamonads but one harbour metabolically altered 'mitochondrion-related organelles' (MROs) with reduced functions, however the degree of reduction varies. Here, we generate high-quality draft genomes, transcriptomes, and predicted proteomes for five recently discovered free-living metamonads. Phylogenomic analyses placed these organisms in a group we name the 'BaSk' (Barthelonids+Skoliomonads) clade, a deeply branching sister group to the Fornicata, a phylum that includes parasitic and free-living flagellates. Bioinformatic analyses of gene models shows that these organisms are predicted to have extremely reduced MRO proteomes in comparison to other free-living metamonads. Loss of the mitochondrial iron-sulfur cluster assembly system in some organisms in this group appears to be linked to the acquisition in their common ancestral lineage of a SUF-like minimal system Fe/S cluster pathway by lateral gene transfer. One of the isolates, Skoliomonas litria, appears to have lost all other known MRO pathways. No proteins were confidently assigned to the predicted MRO proteome of this organism suggesting that the organelle has been lost. The extreme mitochondrial reduction observed within this free-living anaerobic protistan clade demonstrates that mitochondrial functions may be completely lost even in free-living organisms.}, } @article {pmid39125940, year = {2024}, author = {Zhang, X and Ding, Z and Lou, H and Han, R and Ma, C and Yang, S}, title = {A Systematic Review and Developmental Perspective on Origin of CMS Genes in Crops.}, journal = {International journal of molecular sciences}, volume = {25}, number = {15}, pages = {}, pmid = {39125940}, issn = {1422-0067}, support = {No. 31200908 and No. 8176140709//the National Natural Science Foundation of China/ ; }, mesh = {*Crops, Agricultural/genetics/growth & development ; *Genome, Mitochondrial ; *DNA, Mitochondrial/genetics ; Plant Infertility/genetics ; Cytoplasm/genetics/metabolism ; Plant Breeding/methods ; Mitochondria/genetics/metabolism ; Genes, Mitochondrial ; }, abstract = {Cytoplasmic male sterility (CMS) arises from the incompatibility between the nucleus and cytoplasm as typical representatives of the chimeric structures in the mitochondrial genome (mitogenome), which has been extensively applied for hybrid seed production in various crops. The frequent occurrence of chimeric mitochondrial genes leading to CMS is consistent with the mitochondrial DNA (mtDNA) evolution. The sequence conservation resulting from faithfully maternal inheritance and the chimeric structure caused by frequent sequence recombination have been defined as two major features of the mitogenome. However, when and how these chimeric mitochondrial genes appear in the context of the highly conserved reproduction of mitochondria is an enigma. This review, therefore, presents the critical view of the research on CMS in plants to elucidate the mechanisms of this phenomenon. Generally, distant hybridization is the main mechanism to generate an original CMS source in natural populations and in breeding. Mitochondria and mitogenomes show pleomorphic and dynamic changes at key stages of the life cycle. The promitochondria in dry seeds develop into fully functioning mitochondria during seed imbibition, followed by massive mitochondria or mitogenome fusion and fission in the germination stage along with changes in the mtDNA structure and quantity. The mitogenome stability is controlled by nuclear loci, such as the nuclear gene Msh1. Its suppression leads to the rearrangement of mtDNA and the production of heritable CMS genes. An abundant recombination of mtDNA is also often found in distant hybrids and somatic/cybrid hybrids. Since mtDNA recombination is ubiquitous in distant hybridization, we put forward a hypothesis that the original CMS genes originated from mtDNA recombination during the germination of the hybrid seeds produced from distant hybridizations to solve the nucleo-cytoplasmic incompatibility resulting from the allogenic nuclear genome during seed germination.}, } @article {pmid39126033, year = {2024}, author = {Zhan, L and Chen, Y and He, J and Guo, Z and Wu, L and Storey, KB and Zhang, J and Yu, D}, title = {The Phylogenetic Relationships of Major Lizard Families Using Mitochondrial Genomes and Selection Pressure Analyses in Anguimorpha.}, journal = {International journal of molecular sciences}, volume = {25}, number = {15}, pages = {}, pmid = {39126033}, issn = {1422-0067}, support = {31801963//the National Natural Science Foundation of Chin/ ; LQ16C030001//the Zhejiang Province Natural Science Foundation/ ; }, mesh = {Animals ; *Lizards/genetics/classification ; *Phylogeny ; *Genome, Mitochondrial/genetics ; *Selection, Genetic ; Evolution, Molecular ; }, abstract = {Anguimorpha, within the order Squamata, represents a group with distinct morphological and behavioral characteristics in different ecological niches among lizards. Within Anguimorpha, there is a group characterized by limb loss, occupying lower ecological niches, concentrated within the subfamily Anguinae. Lizards with limbs and those without exhibit distinct locomotor abilities when adapting to their habitats, which in turn necessitate varying degrees of energy expenditure. Mitochondria, known as the metabolic powerhouses of cells, play a crucial role in providing approximately 95% of an organism's energy. Functionally, mitogenomes (mitochondrial genomes) can serve as a valuable tool for investigating potential adaptive evolutionary selection behind limb loss in reptiles. Due to the variation of mitogenome structures among each species, as well as its simple genetic structure, maternal inheritance, and high evolutionary rate, the mitogenome is increasingly utilized to reconstruct phylogenetic relationships of squamate animals. In this study, we sequenced the mitogenomes of two species within Anguimorpha as well as the mitogenomes of two species in Gekkota and four species in Scincoidea. We compared these data with the mitogenome content and evolutionary history of related species. Within Anguimorpha, between the mitogenomes of limbless and limbed lizards, a branch-site model analysis supported the presence of 10 positively selected sites: Cytb protein (at sites 183 and 187), ND2 protein (at sites 90, 155, and 198), ND3 protein (at site 21), ND5 protein (at sites 12 and 267), and ND6 protein (at sites 72 and 119). These findings suggested that positive selection of mitogenome in limbless lizards may be associated with the energy requirements for their locomotion. Additionally, we acquired data from 205 mitogenomes from the NCBI database. Bayesian inference (BI) and Maximum Likelihood (ML) trees were constructed using the 13 mitochondrial protein-coding genes (PCGs) and two rRNAs (12S rRNA and 16S rRNA) from 213 mitogenomes. Our phylogenetic tree and the divergence time estimates for Squamata based on mitogenome data are consistent with results from previous studies. Gekkota was placed at the root of Squamata in both BI and ML trees. However, within the Toxicofera clade, due to long-branch attraction, Anguimorpha and (Pleurodonta + (Serpentes + Acrodonta)) were closely related groupings, which might indicate errors and also demonstrate that mitogenome-based phylogenetic trees may not effectively resolve long-branch attraction issues. Additionally, we reviewed the origin and diversification of Squamata throughout the Mesozoic era, suggesting that Squamata originated in the Late Triassic (206.05 Mya), with the diversification of various superfamilies occurring during the Cretaceous period. Future improvements in constructing squamate phylogenetic relationships using mitogenomes will rely on identifying snake and acrodont species with slower evolutionary rates, ensuring comprehensive taxonomic coverage of squamate diversity, and increasing the number of genes analyzed.}, } @article {pmid39127314, year = {2024}, author = {Zhang, L and Liu, ZS and Dong, YZ and He, CF and Zhang, DD and Jiang, GZ and Liu, WB and Li, XF}, title = {Molecular cloning and functional characterization of mitochondrial RNA splicing 2 in fish Megalobrama amblycephala, and its potential roles in magnesium homeostasis and mitochondrial function.}, journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology}, volume = {297}, number = {}, pages = {111727}, doi = {10.1016/j.cbpa.2024.111727}, pmid = {39127314}, issn = {1531-4332}, mesh = {Animals ; *Magnesium/metabolism ; *Homeostasis ; *Cloning, Molecular ; *Mitochondria/metabolism/genetics ; *Amino Acid Sequence ; Fish Proteins/genetics/metabolism ; Cyprinidae/genetics/metabolism ; Phylogeny ; Base Sequence ; RNA Splicing ; }, abstract = {Mitochondrial function can be regulated by ion channels. Mitochondrial RNA splicing 2 (Mrs2) is a magnesium ion (Mg[2+]) channel located in the inner mitochondrial membrane, thereby mediating the Mg[2+] influx into the mitochondrial matrix. However, its potential role in regulating the Mg homeostasis and mitochondrial function in aquatic species is still unclear. This study molecularly characterizes the gene encoding Mrs2 in fish M. amblycephala with its functions in maintaining the Mg homeostasis and mitochondrial function verified. The mrs2 gene is 2133 bp long incorporating a 1269 bp open reading frame, which encodes 422 amino acids. The Mrs2 protein includes two transmembrane domains and a conserved tripeptide Gly-Met-Asn, and has a high homology (65.92-97.64%) with those of most vertebrates. The transcript of mrs2 was relatively high in the white muscle, liver and kidney. The inhibition of mrs2 reduces the expressions of Mg[2+] influx/efflux-related proteins, mitochondrial Mg content, and the activities of mitochondrial complex I and V in hepatocytes. However, the over-expression of mrs2 increases the expressions of Mg[2+] influx/efflux-related proteins, mitochondrial Mg content, and the complex V activity, but decreases the activities of mitochondrial complex III and IV and citrate synthase in hepatocytes. Collectively, Mrs2 is highly conserved among different species, and is prerequisite for maintaining Mg homeostasis and mitochondrial function in fish.}, } @article {pmid39128009, year = {2024}, author = {Harry, CJ and Hibshman, JD and Damatac, A and Davidson, PL and Estermann, MA and Flores-Flores, M and Holmes, CM and Lázaro, J and Legere, EA and Leyhr, J and Thendral, SB and Vincent, BA and Goldstein, B}, title = {Protocol for fluorescent live-cell staining of tardigrades.}, journal = {STAR protocols}, volume = {5}, number = {3}, pages = {103232}, pmid = {39128009}, issn = {2666-1667}, support = {R25 HD094666/HD/NICHD NIH HHS/United States ; }, mesh = {*Tardigrada/cytology ; Animals ; *Staining and Labeling/methods ; Lysosomes/metabolism ; Mitochondria/metabolism ; Microscopy, Fluorescence/methods ; Lipid Droplets/metabolism ; }, abstract = {Tardigrades are microscopic organisms with exceptional resilience to environmental extremes. Most protocols to visualize the internal anatomy of tardigrades rely on fixation, hampering our understanding of dynamic changes to organelles and other subcellular components. Here, we provide protocols for staining live tardigrade adults and other postembryonic stages, facilitating real-time visualization of structures including lipid droplets, mitochondria, lysosomes, and DNA.}, } @article {pmid39132738, year = {2024}, author = {Leung, A and Patel, R and Chirachon, V and Stata, M and Macfarlane, TD and Ludwig, M and Busch, FA and Sage, TL and Sage, RF}, title = {Tribulus (Zygophyllaceae) as a case study for the evolution of C2 and C4 photosynthesis.}, journal = {Plant, cell & environment}, volume = {47}, number = {9}, pages = {3541-3560}, doi = {10.1111/pce.15069}, pmid = {39132738}, issn = {1365-3040}, support = {//Queen Elizabeth II/Charles E. Eckenwalder Graduate Scholarship/ ; NE/W00674X/1//Natural Environment Research Council/ ; DP130102243//Australian Research Council/ ; RGPIN-2020-05925//Natural Sciences and Engineering Research Council/ ; RGPIN-2017-06476//Natural Sciences and Engineering Research Council/ ; }, mesh = {*Photosynthesis/physiology ; *Biological Evolution ; *Plant Leaves/physiology/metabolism ; Carbon Dioxide/metabolism ; Glycine Dehydrogenase (Decarboxylating)/metabolism ; }, abstract = {C2 photosynthesis is a photosynthetic pathway in which photorespiratory CO2 release and refixation are enhanced in leaf bundle sheath (BS) tissues. The evolution of C2 photosynthesis has been hypothesized to be a major step in the origin of C4 photosynthesis, highlighting the importance of studying C2 evolution. In this study, physiological, anatomical, ultrastructural, and immunohistochemical properties of leaf photosynthetic tissues were investigated in six non-C4 Tribulus species and four C4 Tribulus species. At 42°C, T. cristatus exhibited a photosynthetic CO2 compensation point in the absence of respiration (C*) of 21 µmol mol[-1], below the C3 mean C* of 73 µmol mol[-1]. Tribulus astrocarpus had a C* value at 42°C of 55 µmol mol[-1], intermediate between the C3 species and the C2 T. cristatus. Glycine decarboxylase (GDC) allocation to BS tissues was associated with lower C*. Tribulus cristatus and T. astrocarpus allocated 86% and 30% of their GDC to the BS tissues, respectively, well above the C3 mean of 11%. Tribulus astrocarpus thus exhibits a weaker C2 (termed sub-C2) phenotype. Increased allocation of mitochondria to the BS and decreased length-to-width ratios of BS cells, were present in non-C4 species, indicating a potential role in C2 and C4 evolution.}, } @article {pmid39145390, year = {2024}, author = {Kutzer, MAM and Cornish, B and Jamieson, M and Zawistowska, O and Monteith, KM and Vale, PF}, title = {Mitochondrial background can explain variable costs of immune deployment.}, journal = {Journal of evolutionary biology}, volume = {37}, number = {9}, pages = {1125-1133}, doi = {10.1093/jeb/voae082}, pmid = {39145390}, issn = {1420-9101}, support = {RPG-2018-369//Leverhulme Trust Research Project/ ; }, mesh = {Animals ; *Drosophila melanogaster/immunology/genetics/microbiology ; Female ; *Mitochondria/genetics ; *Longevity ; Fertility ; }, abstract = {Organismal health and survival depend on the ability to mount an effective immune response against infection. Yet immune defence may be energy-demanding, resulting in fitness costs if investment in immune function deprives other physiological processes of resources. While evidence of costly immunity resulting in reduced longevity and reproduction is common, the role of energy-producing mitochondria on the magnitude of these costs is unknown. Here, we employed Drosophila melanogaster cybrid lines, where several mitochondrial genotypes (mitotypes) were introgressed onto a single nuclear genetic background, to explicitly test the role of mitochondrial variation on the costs of immune stimulation. We exposed female flies carrying one of nine distinct mitotypes to either a benign, heat-killed bacterial pathogen (stimulating immune deployment while avoiding pathology) or to a sterile control and measured lifespan, fecundity, and locomotor activity. We observed mitotype-specific costs of immune stimulation and identified a positive genetic correlation in immune-stimulated flies between lifespan and the proportion of time cybrids spent moving while alive. Our results suggests that costs of immunity are highly variable depending on the mitochondrial genome, adding to a growing body of work highlighting the important role of mitochondrial variation in host-pathogen interactions.}, } @article {pmid39146359, year = {2024}, author = {von Känel, C and Stettler, P and Esposito, C and Berger, S and Amodeo, S and Oeljeklaus, S and Calderaro, S and Durante, IM and Rašková, V and Warscheid, B and Schneider, A}, title = {Pam16 and Pam18 were repurposed during Trypanosoma brucei evolution to regulate the replication of mitochondrial DNA.}, journal = {PLoS biology}, volume = {22}, number = {8}, pages = {e3002449}, pmid = {39146359}, issn = {1545-7885}, mesh = {*Trypanosoma brucei brucei/metabolism/genetics ; *Protozoan Proteins/metabolism/genetics ; *DNA Replication ; *DNA, Mitochondrial/genetics/metabolism ; Mitochondrial Proteins/metabolism/genetics ; Mitochondria/metabolism/genetics ; Evolution, Molecular ; }, abstract = {Protein import and genome replication are essential processes for mitochondrial biogenesis and propagation. The J-domain proteins Pam16 and Pam18 regulate the presequence translocase of the mitochondrial inner membrane. In the protozoan Trypanosoma brucei, their counterparts are TbPam16 and TbPam18, which are essential for the procyclic form (PCF) of the parasite, though not involved in mitochondrial protein import. Here, we show that during evolution, the 2 proteins have been repurposed to regulate the replication of maxicircles within the intricate kDNA network, the most complex mitochondrial genome known. TbPam18 and TbPam16 have inactive J-domains suggesting a function independent of heat shock proteins. However, their single transmembrane domain is essential for function. Pulldown of TbPam16 identifies a putative client protein, termed MaRF11, the depletion of which causes the selective loss of maxicircles, akin to the effects observed for TbPam18 and TbPam16. Moreover, depletion of the mitochondrial proteasome results in increased levels of MaRF11. Thus, we have discovered a protein complex comprising TbPam18, TbPam16, and MaRF11, that controls maxicircle replication. We propose a working model in which the matrix protein MaRF11 functions downstream of the 2 integral inner membrane proteins TbPam18 and TbPam16. Moreover, we suggest that the levels of MaRF11 are controlled by the mitochondrial proteasome.}, } @article {pmid39152292, year = {2024}, author = {Zhang, Y and Liu, S and Mostert, D and Yu, H and Zhuo, M and Li, G and Zuo, C and Haridas, S and Webster, K and Li, M and Grigoriev, IV and Yi, G and Viljoen, A and Li, C and Ma, LJ}, title = {Virulence of banana wilt-causing fungal pathogen Fusarium oxysporum tropical race 4 is mediated by nitric oxide biosynthesis and accessory genes.}, journal = {Nature microbiology}, volume = {9}, number = {9}, pages = {2232-2243}, pmid = {39152292}, issn = {2058-5276}, support = {IOS-165241//National Science Foundation (NSF)/ ; MASR-2009-04374//United States Department of Agriculture | National Institute of Food and Agriculture (NIFA)/ ; MAS00532//United States Department of Agriculture | National Institute of Food and Agriculture (NIFA)/ ; MAS00496//United States Department of Agriculture | National Institute of Food and Agriculture (NIFA)/ ; R01EY030150//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; }, mesh = {*Fusarium/genetics/pathogenicity/metabolism ; *Musa/microbiology ; *Plant Diseases/microbiology ; *Nitric Oxide/metabolism ; Virulence/genetics ; Virulence Factors/genetics/metabolism ; Fungal Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal ; Genes, Fungal ; Phylogeny ; }, abstract = {Fusarium wilt of banana, caused by Fusarium oxysporum f. sp. cubense (Foc), is one of the most damaging plant diseases known. Foc race 1 (R1) decimated the Gros Michel-based banana (Musa acuminata) trade, and now Foc tropical race 4 (TR4) threatens global production of its replacement, the Cavendish banana. Here population genomics revealed that all Cavendish banana-infecting Foc race 4 strains share an evolutionary origin distinct from that of R1 strains. Although TR4 lacks accessory chromosomes, it contains accessory genes at the ends of some core chromosomes that are enriched for virulence and mitochondria-related functions. Meta-transcriptomics revealed the unique induction of the entire mitochondrion-localized nitric oxide (NO) biosynthesis pathway upon TR4 infection. Empirically, we confirmed the unique induction of a NO burst in TR4, suggesting that nitrosative pressure may contribute to virulence. Targeted mutagenesis demonstrated the functional importance of fungal NO production and the accessory gene SIX4 as virulence factors.}, } @article {pmid39155336, year = {2025}, author = {Prajapati, MR and Diksha, D and Thapa, P and Sharma, SK and Gupta, N and Baranwal, VK}, title = {Identification of a novel mitovirus in grapevine through high-throughput sequencing.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {28}, number = {5}, pages = {909-916}, pmid = {39155336}, issn = {1618-1905}, support = {Ag.Edn.F.No./27/01/NP/2022-HRD//Indian Council of Agricultural Research/ ; }, mesh = {*Vitis/virology ; High-Throughput Nucleotide Sequencing ; Genome, Viral ; Phylogeny ; Open Reading Frames ; *RNA Viruses/genetics/classification/isolation & purification ; RNA, Viral/genetics ; Plant Diseases/virology ; RNA-Dependent RNA Polymerase/genetics ; *Plant Viruses/genetics/classification/isolation & purification ; Viral Proteins/genetics ; }, abstract = {BACKGROUND: Transcriptome data from a plant sample frequently include numerous reads originating from RNA virus genomes that were concurrently isolated during RNA preparation. These high-throughput sequencing reads from the virus can be assembled to form a new sequence for the plant RNA genome.

METHODS AND RESULTS: Here, we identify putative novel mitovirus, grapevine mitovirus 1 (GMV1) through high-throughput sequencing (HTS) of grapevine rootstocks (Vitis spp.), and the identified virus was confirmed using virus-specific primers in RT-PCR assay. The genomic RNA of GMV1 encodes complete open reading frame (ORF) of 2,496 nucleotides (nts) in length. RNA-dependent RNA polymerase (RdRp) encoded by the viral genome contained one RdRp conserved domain. BLASTx analysis of GMV1 genome showed sequence identity of 33.18-56.75% with the existing mitovirus sequences. Phylogenetic analysis based on genome sequences showed that GMV1 clustered in a distinct clade to other mitoviruses.

CONCLUSION: Grapevine mitovirus 1 represents a newly discovered species within the Unuamitovirus genus of the Mitoviridae family, targeting fungal mitochondria. While the majority of recognized mitoviruses typically lack a functional RdRp as per the plant mitochondrial genetic code, GMV1 encodes a complete RdRp in accordance with both fungal and plant mitochondrial genetic codes.}, } @article {pmid39158587, year = {2024}, author = {Ge, J and Li, H and Liang, X and Zhou, B}, title = {SLC30A9: an evolutionarily conserved mitochondrial zinc transporter essential for mammalian early embryonic development.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {357}, pmid = {39158587}, issn = {1420-9071}, support = {2018YFA0900100//National Key Research and Development Program of China/ ; 31971087//Nationa Natural Science Foundation of China/ ; KQTD20180413181837372//Shenzhen Science and Technology Innovation Program/ ; }, mesh = {Animals ; *Cation Transport Proteins/metabolism/genetics ; Humans ; *Zinc/metabolism ; Mice ; *Mitochondria/metabolism ; *Embryonic Development/genetics ; Drosophila melanogaster/metabolism/genetics/embryology ; Evolution, Molecular ; Mice, Knockout ; Amino Acid Sequence ; Mitochondrial Proteins/metabolism/genetics ; Transcription Factors ; Cell Cycle Proteins ; }, abstract = {SLC30A9 (ZnT9) is a mitochondria-resident zinc transporter. Mutations in SLC30A9 have been reported in human patients with a novel cerebro-renal syndrome. Here, we show that ZnT9 is an evolutionarily highly conserved protein, with many regions extremely preserved among evolutionarily distant organisms. In Drosophila melanogaster (the fly), ZnT9 (ZnT49B) knockdown results in acutely impaired movement and drastic mitochondrial deformation. Severe Drosophila ZnT9 (dZnT9) reduction and ZnT9-null mutant flies are pupal lethal. The phenotype of dZnT9 knockdown can be partially rescued by mouse ZnT9 expression or zinc chelator TPEN, indicating the defect of dZnT9 loss is indeed a result of zinc dyshomeostasis. Interestingly, in the mouse, germline loss of Znt9 produces even more extreme phenotypes: the mutant embryos exhibit midgestational lethality with severe development abnormalities. Targeted mutagenesis of Znt9 in the mouse brain leads to serious dwarfism and physical incapacitation, followed by death shortly. Strikingly, the GH/IGF-1 signals are almost non-existent in these tissue-specific knockout mice, consistent with the medical finding in some human patients with severe mitochondrial deficiecny. ZnT9 mutations cause mitochondrial zinc dyshomeostasis, and we demonstrate mechanistically that mitochondrial zinc elevation quickly and potently inhibits the activities of respiration complexes. These results reveal the critical role of ZnT9 and mitochondrial zinc homeostasis in mammalian development. Based on our functional analyses, we finally discussed the possible nature of the so far identified human SLC30A9 mutations.}, } @article {pmid39160470, year = {2024}, author = {Bajić, V and Schulmann, VH and Nowick, K}, title = {mtDNA "nomenclutter" and its consequences on the interpretation of genetic data.}, journal = {BMC ecology and evolution}, volume = {24}, number = {1}, pages = {110}, pmid = {39160470}, issn = {2730-7182}, mesh = {*DNA, Mitochondrial/genetics ; Humans ; *Haplotypes/genetics ; *Phylogeny ; Genetic Variation/genetics ; Terminology as Topic ; }, abstract = {Population-based studies of human mitochondrial genetic diversity often require the classification of mitochondrial DNA (mtDNA) haplotypes into more than 5400 described haplogroups, and further grouping those into hierarchically higher haplogroups. Such secondary haplogroup groupings (e.g., "macro-haplogroups") vary across studies, as they depend on the sample quality, technical factors of haplogroup calling, the aims of the study, and the researchers' understanding of the mtDNA haplogroup nomenclature. Retention of historical nomenclature coupled with a growing number of newly described mtDNA lineages results in increasingly complex and inconsistent nomenclature that does not reflect phylogeny well. This "clutter" leaves room for grouping errors and inconsistencies across scientific publications, especially when the haplogroup names are used as a proxy for secondary groupings, and represents a source for scientific misinterpretation. Here we explore the effects of phylogenetically insensitive secondary mtDNA haplogroup groupings, and the lack of standardized secondary haplogroup groupings on downstream analyses and interpretation of genetic data. We demonstrate that frequency-based analyses produce inconsistent results when different secondary mtDNA groupings are applied, and thus allow for vastly different interpretations of the same genetic data. The lack of guidelines and recommendations on how to choose appropriate secondary haplogroup groupings presents an issue for the interpretation of results, as well as their comparison and reproducibility across studies. To reduce biases originating from arbitrarily defined secondary nomenclature-based groupings, we suggest that future updates of mtDNA phylogenies aimed for the use in mtDNA haplogroup nomenclature should also provide well-defined and standardized sets of phylogenetically meaningful algorithm-based secondary haplogroup groupings such as "macro-haplogroups", "meso-haplogroups", and "micro-haplogroups". Ideally, each of the secondary haplogroup grouping levels should be informative about different human population history events. Those phylogenetically informative levels of haplogroup groupings can be easily defined using TreeCluster, and then implemented into haplogroup callers such as HaploGrep3. This would foster reproducibility across studies, provide a grouping standard for population-based studies, and reduce errors associated with haplogroup nomenclatures in future studies.}, } @article {pmid39162337, year = {2024}, author = {Klirs, Y and Novosolov, M and Gissi, C and Garić, R and Pupko, T and Stach, T and Huchon, D}, title = {Evolutionary Insights from the Mitochondrial Genome of Oikopleura dioica: Sequencing Challenges, RNA Editing, Gene Transfers to the Nucleus, and tRNA Loss.}, journal = {Genome biology and evolution}, volume = {16}, number = {9}, pages = {}, pmid = {39162337}, issn = {1759-6653}, support = {I-1454-203.13/2018//German-Israeli Foundation for Scientific Research and Development/ ; }, mesh = {Animals ; *Genome, Mitochondrial ; *RNA Editing ; *RNA, Transfer/genetics ; *Urochordata/genetics ; *Evolution, Molecular ; *Phylogeny ; Cell Nucleus/genetics ; }, abstract = {Sequencing the mitochondrial genome of the tunicate Oikopleura dioica is a challenging task due to the presence of long poly-A/T homopolymer stretches, which impair sequencing and assembly. Here, we report on the sequencing and annotation of the majority of the mitochondrial genome of O. dioica by means of combining several DNA and amplicon reads obtained by Illumina and MinIon Oxford Nanopore Technologies with public RNA sequences. We document extensive RNA editing, since all homopolymer stretches present in the mitochondrial DNA correspond to 6U-regions in the mitochondrial RNA. Out of the 13 canonical protein-coding genes, we were able to detect eight, plus an unassigned open reading frame that lacked sequence similarity to canonical mitochondrial protein-coding genes. We show that the nad3 gene has been transferred to the nucleus and acquired a mitochondria-targeting signal. In addition to two very short rRNAs, we could only identify a single tRNA (tRNA-Met), suggesting multiple losses of tRNA genes, supported by a corresponding loss of mitochondrial aminoacyl-tRNA synthetases in the nuclear genome. Based on the eight canonical protein-coding genes identified, we reconstructed maximum likelihood and Bayesian phylogenetic trees and inferred an extreme evolutionary rate of this mitochondrial genome. The phylogenetic position of appendicularians among tunicates, however, could not be accurately determined.}, } @article {pmid39163758, year = {2024}, author = {Sizek, H and Deritei, D and Fleig, K and Harris, M and Regan, PL and Glass, K and Regan, ER}, title = {Unlocking mitochondrial dysfunction-associated senescence (MiDAS) with NAD[+] - A Boolean model of mitochondrial dynamics and cell cycle control.}, journal = {Translational oncology}, volume = {49}, number = {}, pages = {102084}, pmid = {39163758}, issn = {1936-5233}, support = {R01 HL155749/HL/NHLBI NIH HHS/United States ; }, abstract = {The steady accumulation of senescent cells with aging creates tissue environments that aid cancer evolution. Aging cell states are highly heterogeneous. 'Deep senescent' cells rely on healthy mitochondria to fuel a strong proinflammatory secretome, including cytokines, growth and transforming signals. Yet, the physiological triggers of senescence such as reactive oxygen species (ROS) can also trigger mitochondrial dysfunction, and sufficient energy deficit to alter their secretome and cause chronic oxidative stress - a state termed Mitochondrial Dysfunction-Associated Senescence (MiDAS). Here, we offer a mechanistic hypothesis for the molecular processes leading to MiDAS, along with testable predictions. To do this we have built a Boolean regulatory network model that qualitatively captures key aspects of mitochondrial dynamics during cell cycle progression (hyper-fusion at the G1/S boundary, fission in mitosis), apoptosis (fission and dysfunction) and glucose starvation (reversible hyper-fusion), as well as MiDAS in response to SIRT3 knockdown or oxidative stress. Our model reaffirms the protective role of NAD[+] and external pyruvate. We offer testable predictions about the growth factor- and glucose-dependence of MiDAS and its reversibility at different stages of reactive oxygen species (ROS)-induced senescence. Our model provides mechanistic insights into the distinct stages of DNA-damage induced senescence, the relationship between senescence and epithelial-to-mesenchymal transition in cancer and offers a foundation for building multiscale models of tissue aging.}, } @article {pmid39164316, year = {2024}, author = {García-Merchán, VH and Palero, F and Rufino, M and Macpherson, E and Abelló, P and Pascual, M}, title = {Mitochondrial, nuclear and morphological differentiation in the swimming crab Liocarcinus depurator along the Atlantic-Mediterranean transition.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {19342}, pmid = {39164316}, issn = {2045-2322}, support = {PID2020-118550RB//Ministerio de Ciencia, Innovación y Universidades/ ; }, mesh = {Animals ; *Brachyura/genetics ; Mediterranean Sea ; *Microsatellite Repeats/genetics ; *DNA, Mitochondrial/genetics ; Atlantic Ocean ; Mitochondria/genetics ; Genetic Variation ; Genetics, Population ; Cell Nucleus/genetics ; Selection, Genetic ; }, abstract = {Environmental gradients in the sea may coincide with phenotypic or genetic gradients resulting from an evolutionary balance between selection and dispersal. The population differentiation of the swimming crab, Liocarcinus depurator, an important by-catch species in the Mediterranean Sea and North-East Atlantic, was assessed using both genetic and morphometric approaches. A total of 472 specimens were collected along its distribution area, and 17 morphometric landmarks, one mitochondrial gene (COI) and 11 polymorphic microsatellite markers were scored in 350, 287 and 280 individuals, respectively. Morphometric data lacked significant differences, but genetic analyses showed significant genetic differentiation between Atlantic and Mediterranean populations, with a steeper gradient in COI compared to microsatellite markers. Interestingly, nuclear differentiation was due to an outlier locus with a gradient in the Atlantic-Mediterranean transition area overlapping with the mtDNA gradient. Such overlapping clines are likely to be maintained by natural selection. Our results suggest a scenario of past isolation with local adaptation and secondary contact between the two basins. Local adaptation during the process of vicariance may reinforce genetic differentiation at loci maintained by environmental selection even after secondary contact.}, } @article {pmid39179249, year = {2024}, author = {Guo, Y and Wen, H and Chen, Z and Jiao, M and Zhang, Y and Ge, D and Liu, R and Gu, J}, title = {Conjoint analysis of succinylome and phosphorylome reveals imbalanced HDAC phosphorylation-driven succinylayion dynamic contibutes to lung cancer.}, journal = {Briefings in bioinformatics}, volume = {25}, number = {5}, pages = {}, pmid = {39179249}, issn = {1477-4054}, support = {20ZR1410800//Science and Technology Commission of Shanghai Municipality/ ; 82373371//National Science Foundation of China/ ; 2020YFC2008402//National Science and Technology Major Project of China/ ; //Program for Professor of Special Appointment/ ; //Shanghai Institutions of Higher Learning/ ; }, mesh = {Humans ; *Lung Neoplasms/metabolism/genetics/pathology ; Phosphorylation ; *Protein Processing, Post-Translational ; *Histone Deacetylases/metabolism ; Succinic Acid/metabolism ; Mitochondria/metabolism ; }, abstract = {Cancerous genetic mutations result in a complex and comprehensive post-translational modification (PTM) dynamics, in which protein succinylation is well known for its ability to reprogram cell metabolism and is involved in the malignant evolution. Little is known about the regulatory interactions between succinylation and other PTMs in the PTM network. Here, we developed a conjoint analysis and systematic clustering method to explore the intermodification communications between succinylome and phosphorylome from eight lung cancer patients. We found that the intermodification coorperation in both parallel and series. Besides directly participating in metabolism pathways, some phosphosites out of mitochondria were identified as an upstream regulatory modification directing succinylome dynamics in cancer metabolism reprogramming. Phosphorylated activation of histone deacetylase (HDAC) in lung cancer resulted in the removal of acetylation and favored the occurrence of succinylation modification of mitochondrial proteins. These results suggest a tandem regulation between succinylation and phosphorylation in the PTM network and provide HDAC-related targets for intervening mitochondrial succinylation and cancer metabolism reprogramming.}, } @article {pmid39192127, year = {2025}, author = {Bhattacharya, M and Bhowmik, D and Yin, Q}, title = {In Vitro Cleavage Assay to Characterize DENV NS2B3 Antagonism of cGAS.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2854}, number = {}, pages = {153-170}, pmid = {39192127}, issn = {1940-6029}, support = {R01 AI146330/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Viral Nonstructural Proteins/metabolism ; *Nucleotidyltransferases/metabolism/antagonists & inhibitors ; *Dengue Virus ; Proteolysis ; Recombinant Proteins/metabolism/genetics/isolation & purification ; Nucleotides, Cyclic/metabolism ; Dengue/virology/metabolism ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; }, abstract = {cGAS is a key cytosolic dsDNA receptor that senses viral infection and elicits interferon production through the cGAS-cGAMP-STING axis. cGAS is activated by dsDNA from viral and bacterial origins as well as dsDNA leaked from damaged mitochondria and nucleus. Eventually, cGAS activation launches the cell into an antiviral state to restrict the replication of both DNA and RNA viruses. Throughout the long co-evolution, viruses devise many strategies to evade cGAS detection or suppress cGAS activation. We recently reported that the Dengue virus protease NS2B3 proteolytically cleaves human cGAS in its N-terminal region, effectively reducing cGAS binding to DNA and consequent production of the second messenger cGAMP. Several other RNA viruses likely adopt the cleavage strategy. Here, we describe a protocol for the purification of recombinant human cGAS and Dengue NS2B3 protease, as well as the in vitro cleavage assay.}, } @article {pmid39199261, year = {2024}, author = {Tian, L and Luo, Y and Ren, J and Zhao, C}, title = {The Role of Oxidative Stress in Hypomagnetic Field Effects.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {}, pmid = {39199261}, issn = {2076-3921}, support = {YSBR-097//CAS Project for Young Scientists in Basic Research/ ; 42388101 and 42274099//National Natural Science Foundation of China/ ; }, abstract = {The geomagnetic field (GMF) is crucial for the survival and evolution of life on Earth. The weakening of the GMF, known as the hypomagnetic field (HMF), significantly affects various aspects of life on Earth. HMF has become a potential health risk for future deep space exploration. Oxidative stress is directly involved in the biological effects of HMF on animals or cells. Oxidative stress occurs when there is an imbalance favoring oxidants over antioxidants, resulting in cellular damage. Oxidative stress is a double-edged sword, depending on the degree of deviation from homeostasis. In this review, we summarize the important experimental findings from animal and cell studies on HMF exposure affecting intracellular reactive oxygen species (ROS), as well as the accompanying many physiological abnormalities, such as cognitive dysfunction, the imbalance of gut microbiota homeostasis, mood disorders, and osteoporosis. We discuss new insights into the molecular mechanisms underlying these HMF effects in the context of the signaling pathways related to ROS. Among them, mitochondria are considered to be the main organelles that respond to HMF-induced stress by regulating metabolism and ROS production in cells. In order to unravel the molecular mechanisms of HMF action, future studies need to consider the upstream and downstream pathways associated with ROS.}, } @article {pmid39199300, year = {2024}, author = {Wang, X and Wang, D and Zhang, R and Qin, X and Shen, X and You, C}, title = {Morphological Structure Identification, Comparative Mitochondrial Genomics and Population Genetic Analysis toward Exploring Interspecific Variations and Phylogenetic Implications of Malus baccata 'ZA' and Other Species.}, journal = {Biomolecules}, volume = {14}, number = {8}, pages = {}, pmid = {39199300}, issn = {2218-273X}, support = {32072520, 32172538//National Natural Science Foundation of China/ ; ZR2020MC132//Shandong Provincial Natural Science Foundation/ ; 2022YFD1201700//National Key Research and Development Program of China/ ; SDAIT-06-07//Fruit Industry System of Shandong Province/ ; }, mesh = {*Phylogeny ; *Genome, Mitochondrial/genetics ; *Malus/genetics/classification ; Genetics, Population ; Genomics ; Mitochondria/genetics ; }, abstract = {Malus baccata, a valuable germplasm resource in the genus Malus, is indigenous to China and widely distributed. However, little is known about the lineage composition and genetic basis of 'ZA', a mutant type of M. baccata. In this study, we compared the differences between 'ZA' and wild type from the perspective of morphology and ultrastructure and analyzed their chloroplast pigment content based on biochemical methods. Further, the complete mitogenome of M. baccata 'ZA' was assembled and obtained by next-generation sequencing. Subsequently, its molecular characteristics were analyzed using Geneious, MISA-web, and CodonW toolkits. Furthermore, by examining 106 Malus germplasms and 42 Rosaceae species, we deduced and elucidated the evolutionary position of M. baccata 'ZA', as well as interspecific variations among different individuals. In comparison, the total length of the 'ZA' mitogenome (GC content: 45.4%) is 374,023 bp, which is approximately 2.33 times larger than the size (160,202 bp) of the plastome (GC: 36.5%). The collinear analysis results revealed abundant repeats and genome rearrangements occurring between different Malus species. Additionally, we identified 14 plastid-driven fragment transfer events. A total of 54 genes have been annotated in the 'ZA' mitogenome, including 35 protein-coding genes, 16 tRNAs, and three rRNAs. By calculating nucleotide polymorphisms and selection pressure for 24 shared core mitochondrial CDSs from 42 Rosaceae species (including 'ZA'), we observed that the nad3 gene exhibited minimal variation, while nad4L appeared to be evolving rapidly. Population genetics analysis detected a total of 1578 high-quality variants (1424 SNPs, 60 insertions, and 94 deletions; variation rate: 1/237) among samples from 106 Malus individuals. Furthermore, by constructing phylogenetic trees based on both Malus and Rosaceae taxa datasets, it was preliminarily demonstrated that 'ZA' is closely related to M. baccata, M. sieversii, and other proximate species in terms of evolution. The sequencing data obtained in this study, along with our findings, contribute to expanding the mitogenomic resources available for Rosaceae research. They also hold reference significance for molecular identification studies as well as conservation and breeding efforts focused on excellent germplasms.}, } @article {pmid39201699, year = {2024}, author = {Li, H and Liang, T and Liu, Y and Wang, P and Wang, S and Zhao, M and Zhang, Y}, title = {Exploring Mitochondrial Heterogeneity and Evolutionary Dynamics in Thelephora ganbajun through Population Genomics.}, journal = {International journal of molecular sciences}, volume = {25}, number = {16}, pages = {}, pmid = {39201699}, issn = {1422-0067}, support = {31870009//National Natural Science Foundation of China/ ; YNWR-QNBJ-2018-355//Top Young Talents Program of the Ten Thousand Talents Plan in Yunnan Province/ ; 2021KF009//YNCUB/ ; }, mesh = {*Genome, Mitochondrial ; *Evolution, Molecular ; Phylogeny ; Introns/genetics ; Mitochondria/genetics ; Basidiomycota/genetics ; DNA, Mitochondrial/genetics ; Genomics/methods ; Gene Transfer, Horizontal ; }, abstract = {Limited exploration in fungal mitochondrial genetics has uncovered diverse inheritance modes. The mitochondrial genomes are inherited uniparentally in the majority of sexual eukaryotes, our discovery of persistent mitochondrial heterogeneity within the natural population of the basidiomycete fungus Thelephora ganbajun represents a significant advance in understanding mitochondrial inheritance and evolution in eukaryotes. Here, we present a comprehensive analysis by sequencing and assembling the complete mitogenomes of 40 samples exhibiting diverse cox1 heterogeneity patterns from various geographical origins. Additionally, we identified heterogeneous variants in the nad5 gene, which, similar to cox1, displayed variability across multiple copies. Notably, our study reveals a distinct prevalence of introns and homing endonucleases in these heterogeneous genes. Furthermore, we detected potential instances of horizontal gene transfer involving homing endonucleases. Population genomic analyses underscore regional variations in mitochondrial genome composition among natural samples exhibiting heterogeneity. Thus, polymorphisms in heterogeneous genes, introns, and homing endonucleases significantly influence mitochondrial structure, structural variation, and evolutionary dynamics in this species. This study contributes valuable insights into mitochondrial genome architecture, population dynamics, and the evolutionary implications of mitochondrial heterogeneity in sexual eukaryotes.}, } @article {pmid39202396, year = {2024}, author = {Wu, H and Qi, S and Fan, S and Li, H and Zhang, Y and Zhang, Y and Xu, Q and Chen, G}, title = {Analysis of the Mitochondrial COI Gene and Genetic Diversity of Endangered Goose Breeds.}, journal = {Genes}, volume = {15}, number = {8}, pages = {}, pmid = {39202396}, issn = {2073-4425}, support = {[2021YFD1200302]//the National Key Research and Development Program of China/ ; [JBGS [2021]023]//the Jiangsu Provincial Seed Industry Revitalization Announcement Leading Project/ ; }, mesh = {Animals ; *Geese/genetics ; *Endangered Species ; *Phylogeny ; *Haplotypes ; *Electron Transport Complex IV/genetics ; Genetic Variation ; DNA, Mitochondrial/genetics ; Breeding ; China ; Mitochondria/genetics ; }, abstract = {The mitochondrial cytochrome c oxidase subunit I (COI) genes of six endangered goose breeds (Xupu, Yangjiang, Yan, Wuzong, Baizi, and Lingxian) were sequenced and compared to assess the genetic diversity of endangered goose breeds. By constructing phylogenetic trees and evolutionary maps of genetic relationships, the affinities and degrees of genetic variations among the six different breeds were revealed. A total of 92 polymorphic sites were detected in the 741 bp sequence of the mtDNA COI gene after shear correction, and the GC content of the processed sequence (51.11%) was higher than that of the AT content (48.89%). The polymorphic loci within the populations of five of the six breeds (Xupu, Yangjiang, Yan, Baizi, and Lingxian) were more than 10, the haplotype diversity > 0.5, and the nucleotide diversity (Pi) > 0.005, with the Baizi geese being the exception. A total of 35 haplotypes were detected based on nucleotide variation among sequences, and the goose breed haplotypes showed a central star-shaped dispersion; the FST values were -0.03781 to 0.02645, The greatest genetic differentiation (FST = 0.02645) was observed in Yan and Wuzong breeds. The most frequent genetic exchange (Nm > 15.00) was between the Wuzong and Yangjiang geese. An analysis of molecular variance showed that the population genetic variation mainly came from within the population; the base mismatch differential distribution analysis of the goose breeds and the Tajima's D and Fu's Fs neutral detection of the historical occurrence dynamics of their populations were negative (p > 0.10). The distribution curve of the base mismatches showed a multimodal peak, which indicated that the population tended to be stabilised. These results provide important genetic information for the conservation and management of endangered goose breeds and a scientific basis for the development of effective conservation strategies.}, } @article {pmid39213749, year = {2024}, author = {Chen, X and Sun, W and Song, Y and Wu, S and Xie, S and Xiong, W and Peng, C and Peng, Y and Wang, Z and Lek, S and Hogstrand, C and Sørensen, M and Pan, L and Liu, D}, title = {Acute waterborne cadmium exposure induces liver ferroptosis in Channa argus.}, journal = {Ecotoxicology and environmental safety}, volume = {283}, number = {}, pages = {116947}, doi = {10.1016/j.ecoenv.2024.116947}, pmid = {39213749}, issn = {1090-2414}, mesh = {Animals ; *Ferroptosis/drug effects ; *Cadmium/toxicity ; *Water Pollutants, Chemical/toxicity ; *Liver/drug effects/pathology/metabolism ; *Fishes ; Signal Transduction/drug effects ; NF-E2-Related Factor 2/metabolism/genetics ; }, abstract = {The impact of cadmium (Cd) toxicity on fish liver injury has received much attention in recent years. Currently, autophagy, apoptosis and endoplasmic reticulum stress were reported in Cd exposed fish liver, and if there are other mechanisms (such as ferroptosis) and relevant signaling pathways involved in fish remains unknown. An experiment was conducted to investigate Cd toxicity in Channa argus (Cantor, 1842) exposed to 0, 1.0, and 2.0 mg Cd/L of water for 96 h. Cd disrupted the structure of mitochondria in the liver. Besides, Cd induced ferroptosis by significantly increasing the level of Fe[2+], ROS, MDA and significantly decreasing the level of Ferritin, GSH, GSH-Px, GPX4, GST and SOD (p < 0.05 in all cases). In addition, the mRNA expression of ferroptosis related genes, gpx4 and slc7a11, were significantly downregulated by Cd. Moreover, Cd exposure significantly inhibited the Nrf2/Keap1 signaling pathway, one of the pathways involved in ferroptosis, by upregulating the mRNA levels of keap1a and keap1b, and downregulating the mRNA levels of nrf2 and its target genes (ho-1, nqo1 and cat). Cd exposure also caused extensive accumulation of vacuoles and lipid droplets in liver, as well as an increase in triglyceride content. Cd significantly affected lipid metabolism related enzyme activity and gene expression, which were also regulated by Nrf2/Keap1 signaling pathway. In summary, these results indicate that ferroptosis is a mechanism in waterborne Cd exposed fish liver injury via the Nrf2/Keap1 signaling pathway and the Cd induced hepatic steatosis is also modulated by Nrf2/Keap1 pathway at the whole-body level in fish. These findings provide new insights into the fish liver injury and molecular basis of Cd toxicity.}, } @article {pmid39222118, year = {2024}, author = {Santos, YS and Vidal, AH and Abreu, EFM and Nogueira, I and Faleiro, FG and Lacorte, CC and Melo, FL and de Araújo Campos, M and de Rezende, RR and Morgan, T and Varsani, A and Alfenas-Zerbini, P and Ribeiro, SG}, title = {Detection and molecular characterization of a novel mitovirus associated with Passiflora edulis Sims.}, journal = {Archives of virology}, volume = {169}, number = {9}, pages = {190}, pmid = {39222118}, issn = {1432-8798}, support = {APQ-00661-18//Fundação de Amparo à Pesquisa do Estado de Minas Gerais/ ; }, mesh = {*Passiflora/virology ; *Phylogeny ; *Open Reading Frames ; *Genome, Viral/genetics ; *Plant Diseases/virology ; Brazil ; *RNA-Dependent RNA Polymerase/genetics ; RNA Viruses/genetics/isolation & purification/classification ; Viral Proteins/genetics ; RNA, Viral/genetics ; Amino Acid Sequence ; }, abstract = {Mitoviruses are cryptic capsidless viruses belonging to the family Mitoviridae that replicate and are maintained in the mitochondria of fungi. Complete mitovirus-like sequences were recently assembled from plant transcriptome data and plant leaf tissue samples. Passion fruit (Passiflora spp.) is an economically important crop for numerous tropical and subtropical countries worldwide, and many virus-induced diseases impact its production. From a large-scale genomic study targeting viruses infecting Passiflora spp. in Brazil, we detected a de novo-assembled contig with similarity to other plant-associated mitoviruses. The contig is ∼2.6 kb long, with a single open reading frame (ORF) encoding an RNA-dependent RNA polymerase (RdRP). This contig has been named "passion fruit mitovirus-like 1" (PfMv1). An alignment of the predicted amino acid sequence of the RdRP of PfMv1 and those of other plant-associated mitoviruses revealed the presence of the six conserved motifs of mitovirus RdRPs. PfMv1 has 79% coverage and 50.14% identity to Humulus lupulus mitovirus 1. Phylogenetic analysis showed that PfMV1 clustered with other plant-associated mitoviruses in the genus Duamitovirus. Using RT-PCR, we detected a PfMv1-derived fragment, but no corresponding DNA was identified, thus excluding the possibility that this is an endogenized viral-like sequence. This is the first evidence of a replicating mitovirus associated with Passiflora edulis, and it should be classified as a member of a new species, for which we propose the name "Duamitovirus passiflorae".}, } @article {pmid39226300, year = {2024}, author = {de Ree, V and Nath, TC and Barua, P and Harbecke, D and Lee, D and Rödelsperger, C and Streit, A}, title = {Genomic analysis of Strongyloides stercoralis and Strongyloides fuelleborni in Bangladesh.}, journal = {PLoS neglected tropical diseases}, volume = {18}, number = {9}, pages = {e0012440}, pmid = {39226300}, issn = {1935-2735}, mesh = {Animals ; Bangladesh/epidemiology ; *Strongyloidiasis/epidemiology/veterinary/parasitology ; Humans ; Dogs ; *Strongyloides stercoralis/genetics/isolation & purification/classification ; *Phylogeny ; *Strongyloides/genetics/isolation & purification/classification ; Dog Diseases/parasitology/epidemiology ; Genomics ; }, abstract = {BACKGROUND: About 600 million people are estimated to be infected with Strongyloides stercoralis, the species that causes most of the human strongyloidiasis cases. S. stercoralis can also infect non-human primates (NHPs), dogs and cats, rendering these animals putative sources for zoonotic human S. stercoralis infection. S. fuelleborni is normally found in old world NHPs but occasionally also infects humans, mainly in Africa. Dogs in southeast Asia carry at least two types of Strongyloides, only one of which appears to be shared with humans ("dog only" and "human and dog" types). For S. stercoralis with molecular taxonomic information, there is a strong sampling bias towards southeast and east Asia and Australia.

In order to extend the geographic range of sampling, we collected human and dog derived Strongyloides spp. and hookworms from two locations in Bangladesh and subjected them to molecular taxonomic and genomic analysis based on nuclear and mitochondrial sequences. All hookworms found were Necator americanus. Contrary to earlier studies in Asia, we noticed a rather high incidence of S. fuelleborni in humans. Also in this study, we found the two types of S. stercoralis and no indication for genetic isolation from the southeast Asian populations. However, we found one genomically "dog only" type S. stercoralis in a human sample and we found two worms in a dog sample that had a nuclear genome of the "dog only" but a mitochondrial genome of the "human and dog" type.

CONCLUSIONS/SIGNIFICANCE: S. fuelleborni may play a more prominent role as a human parasite in certain places in Asia than previously thought. The introgression of a mitochondria haplotype into the "dog only" population suggests that rare interbreeding between the two S. stercoralis types does occur and that exchange of genetic properties, for example a drug resistance, between the two types is conceivable.}, } @article {pmid39226386, year = {2024}, author = {Amaya Romero, JE and Chenal, C and Ben Chehida, Y and Miles, A and Clarkson, CS and Pedergnana, V and Wertheim, B and Fontaine, MC}, title = {Mitochondrial Variation in Anopheles gambiae and Anopheles coluzzii: Phylogeographic Legacy and Mitonuclear Associations With Metabolic Resistance to Pathogens and Insecticides.}, journal = {Genome biology and evolution}, volume = {16}, number = {9}, pages = {}, pmid = {39226386}, issn = {1759-6653}, mesh = {Animals ; *Anopheles/genetics ; *Phylogeography ; *Phylogeny ; *DNA, Mitochondrial/genetics ; *Insecticide Resistance/genetics ; Genome, Mitochondrial ; Evolution, Molecular ; Genetic Variation ; Insecticides/pharmacology ; Mitochondria/genetics ; Africa ; }, abstract = {Mitochondrial DNA has been a popular marker in phylogeography, phylogeny, and molecular ecology, but its complex evolution is increasingly recognized. Here, we investigated mitochondrial DNA variation in Anopheles gambiae and Anopheles coluzzii, in relation to other species in the Anopheles gambiae complex, by assembling the mitogenomes of 1,219 mosquitoes across Africa. The mitochondrial DNA phylogeny of the Anopheles gambiae complex was consistent with previously reported highly reticulated evolutionary history, revealing important discordances with the species tree. The three most widespread species (An. gambiae, An. coluzzii, and Anopheles arabiensis), known for extensive historical introgression, could not be discriminated based on mitogenomes. Furthermore, a monophyletic clustering of the three saltwater-tolerant species (Anopheles merus, Anopheles melas, and Anopheles bwambae) in the Anopheles gambiae complex also suggested that introgression and possibly selection shaped mitochondrial DNA evolution. Mitochondrial DNA variation in An. gambiae and An. coluzzii across Africa revealed significant partitioning among populations and species. A peculiar mitochondrial DNA lineage found predominantly in An. coluzzii and in the hybrid taxon of the African "far-west" exhibited divergence comparable to the interspecies divergence in the Anopheles gambiae complex, with a geographic distribution matching closely An. coluzzii's geographic range. This phylogeographic relict of the An. coluzzii and An. gambiae split was associated with population and species structure, but not with the rare Wolbachia occurrence. The lineage was significantly associated with single nucleotide polymorphisms in the nuclear genome, particularly in genes associated with pathogen and insecticide resistance. These findings underline potential mitonuclear coevolution history and the role played by mitochondria in shaping metabolic responses to pathogens and insecticides in Anopheles.}, } @article {pmid39226612, year = {2024}, author = {Forbes, K and Barrera, M and Nielsen-Roine, K and Hersh, E and Janes, J and Harrower, W and Gorrell, J}, title = {Stabilizing selection and mitochondrial heteroplasmy in the Canada lynx (Lynx canadensis).}, journal = {Genome}, volume = {67}, number = {12}, pages = {493-502}, doi = {10.1139/gen-2023-0094}, pmid = {39226612}, issn = {1480-3321}, mesh = {*Lynx/genetics ; Animals ; *Haplotypes ; *DNA, Mitochondrial/genetics ; Heteroplasmy/genetics ; Selection, Genetic ; Polymorphism, Single Nucleotide ; Mitochondria/genetics ; Genome, Mitochondrial ; Phylogeny ; Canada ; }, abstract = {Mitochondrial DNA is commonly used in population genetic studies to investigate spatial structure, intraspecific variation, and phylogenetic relationships. The control region is the most rapidly evolving and largest non-coding region, but its analysis can be complicated by heteroplasmic signals of genome duplication in many mammals, including felids. Here, we describe the presence of heteroplasmy in the control region of Canada lynx (Lynx canadensis) through intra-individual sequence variation. Our results demonstrate multiple haplotypes of varying length in each lynx, resulting from different copy numbers of the repetitive sequence RS-2 and suggest possible heteroplasmic single nucleotide polymorphisms in both repetitive sequences RS-2 and RS-3. Intra-individual variation was only observed in the repetitive sequences while inter-individual variation was detected in the flanking regions outside of the repetitive sequences, indicating that heteroplasmic mutations are restricted to these repeat regions. Although each lynx displayed multiple haplotypes of varying length, we found the most common variant contained three complete copies of the RS-2 repeat unit, suggesting copy number is regulated by stabilizing selection. While genome duplication offers potential for increased diversity, heteroplasmy may lead to a selective advantage or detriment in the face of mitochondrial function and disease, which could have significant implications for wildlife populations experiencing decline (e.g., bottlenecks) as a result of habitat modification or climate change.}, } @article {pmid39231786, year = {2024}, author = {Duan, X and Shi, X and Zhang, P and Du, X and Chen, S and Zhang, L and Li, H and Zhang, Y and Wang, J and Ding, Y and Liu, S}, title = {Identification of concurrent infection with Jaagsiekte sheep retrovirus and maedi-visna virus in China.}, journal = {Journal of veterinary science}, volume = {25}, number = {5}, pages = {e61}, pmid = {39231786}, issn = {1976-555X}, support = {2021ZD0010//Science and Technology Major Project of Inner Mongolia/China ; 20151031//Grassland Talents Innovative Team Project of Inner Mongolia/China ; BR22-13-08//Innovation Team Project of Cattle and Sheep Disease Prevention and Development Engineering of Inner Mongolia/China ; NMGIRT2412//Veterinary Basic and Cattle and Sheep Disease Prevention and Control Technology Research and Innovation Team Project/China ; B20231072Z//Postgraduate Research Innovation Funding Program/China ; 32072819/NNSFC/National Natural Science Foundation of China/China ; 32360863/NNSFC/National Natural Science Foundation of China/China ; }, mesh = {Animals ; *Jaagsiekte sheep retrovirus ; Sheep ; China ; *Pulmonary Adenomatosis, Ovine/virology/pathology ; *Visna-maedi virus ; Male ; Coinfection/veterinary/virology ; Phylogeny ; Lung/virology/pathology ; Sheep Diseases/virology/pathology ; Visna/virology/pathology ; }, abstract = {IMPORTANCE: Ovine pulmonary adenomatosis (OPA) and maedi-visna disease (MVD) are chronic and progressive infectious diseases in sheep caused by Jaagsiekte sheep retrovirus (JSRV) and maedi-visna virus (MVV), respectively.

OBJECTIVE: To investigate the pathological changes and conduct viral gene analysis of OPA and MVD co-occurrence in Inner Mongolia, China.

METHODS: Using gross pathology, histopathology, immunohistochemistry, ultrastructural pathology, PCR, and sequence analysis, we investigated the concurrent infection of JSRV and MVV in 319 Dorper rams slaughtered in a private slaughterhouse in Inner Mongolia, in 2022.

RESULTS: Of the 319 rams included, 3 showed concurrent JSRV and MVV infection. Gross lung pathology showed diffuse enlargement, consolidation, and greyish-white miliary nodules on the lung surface; the trachea was filled with a white foamy fluid; hilar and mediastinal lymph nodes were significantly enlarged. Histopathology results revealed typical OPA and MVD lesions in the lung tissue. Immunohistochemical results were positive for JSRV envelope protein (Env) in the tumor cells and MVV CA in alveolar macrophages. Transmission electron microscopy showed several virions and autophagosomes in the lung tissue, severely damaged mitochondria, and the induced mitophagy. Nucleotide sequences obtained for JSRV env and MVV gag showed the highest homology with the Inner Mongolian strains of JSRV env (JQ837489) and MVV gag (MW248464).

CONCLUSIONS AND RELEVANCE: Our study confirmed that OPA and MVD co-occurrence and identified the pathological changes in Inner Mongolia, China, thereby providing references for the identification of concurrent JSRV and MVV infections.}, } @article {pmid39232676, year = {2024}, author = {Ou, T and Wu, Z and Tian, C and Yang, Y and Li, Z}, title = {Complete mitochondrial genome of Agropyron cristatum reveals gene transfer and RNA editing events.}, journal = {BMC plant biology}, volume = {24}, number = {1}, pages = {830}, pmid = {39232676}, issn = {1471-2229}, mesh = {*Genome, Mitochondrial ; *RNA Editing ; *Agropyron/genetics ; RNA, Transfer/genetics ; Phylogeny ; Genome, Plant ; }, abstract = {BACKGROUND: As an important forage in arid and semi-arid regions, Agropyron cristatum provides livestock with exceptionally high nutritional value. Additionally, A. cristatum exhibits outstanding genetic characteristics to endure drought and disease. Therefore, rich genetic diversity serves as a cornerstone for the improvement of major food crops. The purposes of this study were to systematically describe mitogenome of A.cristatum and preliminarily analyze its internal variations.

RESULT: The A. cristatum mitogenome was a single-ring molecular structure of 381,065 bp that comprised 52 genes, including 35 protein-coding, 3 rRNA and 14 tRNA genes. Among these, two pseudoprotein-coding genes and multiple copies of tRNA genes were observed. A total of 320 repetitive sequences was found to cover more than 10% of the mitogenome (105 simple sequences, 185 dispersed and 30 tandem repeats), which led to a large number of fragment rearrangements in the mitogenome of A. cristatum. Leucine was the most frequent amino acid (n = 1087,10.8%) in the protein-coding genes of A. cristatum mitogenome, and the highest usage codon was ATG (initiation codon). The number of A/T changes at the third base of the codon was much higher than that of G/C. Among 23 PCGs, the range of Pi values is from 0.0021 to 0.0539, with an average of 0.013. Additionally, 81 RNA editing sites were predicted, which were considerably fewer than those reported in other plant mitogenomes. Most of the RNA editing site base positions were concentrated at the first and second codon bases, which were C to T transitions. Moreover, we identified 95 sequence fragments (total length of 34, 343 bp) that were transferred from the chloroplast to mitochondria genes, introns, and intergenic regions. The stability of the tRNA genes was maintained during this process. Selection pressure analysis of 23 protein-coding genes shared by 15 Poaceae plants, showed that most genes were subjected to purifying selection during evolution, whereas rps4, cob, mttB, and ccmB underwent positive selection in different plants. Finally, a phylogenetic tree was constructed based on 22 plant mitogenomes, which showed that Agropyron plants have a high degree of independent heritability in Triticeae.

CONCLUSION: The findings of this study provide new data for a better understanding of A. cristatum genes, and demonstrate that mitogenomes are suitable for the study of plant classifications, such as those of Agropyron. Moreover, it provides a reference for further exploration of the phylogenetic relationships within Agropyron species, and establishes a theoretical basis for the subsequent development and utilization of A. cristatum plant germplasm resources.}, } @article {pmid39243912, year = {2024}, author = {Liu, GH and Zuo, YW and Shan, Y and Yu, J and Li, JX and Chen, Y and Gong, XY and Liao, XM}, title = {Structural analysis of the mitochondrial genome of Santalum album reveals a complex branched configuration.}, journal = {Genomics}, volume = {116}, number = {5}, pages = {110935}, doi = {10.1016/j.ygeno.2024.110935}, pmid = {39243912}, issn = {1089-8646}, mesh = {*Genome, Mitochondrial ; *Santalum/genetics ; *Phylogeny ; RNA Editing ; RNA, Transfer/genetics/chemistry ; Plant Proteins/genetics/metabolism/chemistry ; }, abstract = {BACKGROUND: Santalum album L. is an evergreen tree which is mainly distributes throughout tropical and temperate regions. And it has a great medicinal and economic value.

RESULTS: In this study, the complete mitochondrial genome of S. album were assembled and annotated, which could be descried by a complex branched structure consisting of three contigs. The lengths of these three contigs are 165,122 bp, 93,430 bp and 92,491 bp. We annotated 34 genes coding for proteins (PCGs), 26 tRNA genes, and 4 rRNA genes. The analysis of repeated elements shows that there are 89 SSRs and 242 pairs of dispersed repeats in S. album mitochondrial genome. Also we found 20 MTPTs among the chloroplast and mitochondria. The 20 MTPTs sequences span a combined length of 22,353 bp, making up 15.52 % of the plastome, 6.37 % of the mitochondrial genome. Additionally, by using the Deepred-mt tool, we found 628 RNA editing sites in 34 PCGs. Moreover, significant genomic rearrangement is observed between S. album and its associated mitochondrial genomes. Finally, based on mitochondrial genome PCGs, we deduced the phylogenetic ties between S. album and other angiosperms.

CONCLUSIONS: We reported the mitochondrial genome from Santalales for the first time, which provides a crucial genetic resource for our study of the evolution of mitochondrial genome.}, } @article {pmid39252884, year = {2024}, author = {Thoral, E and Dawson, NJ and Bettinazzi, S and Rodríguez, E}, title = {An evolving roadmap: using mitochondrial physiology to help guide conservation efforts.}, journal = {Conservation physiology}, volume = {12}, number = {1}, pages = {coae063}, pmid = {39252884}, issn = {2051-1434}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {The crucial role of aerobic energy production in sustaining eukaryotic life positions mitochondrial processes as key determinants of an animal's ability to withstand unpredictable environments. The advent of new techniques facilitating the measurement of mitochondrial function offers an increasingly promising tool for conservation approaches. Herein, we synthesize the current knowledge on the links between mitochondrial bioenergetics, ecophysiology and local adaptation, expanding them to the wider conservation physiology field. We discuss recent findings linking cellular bioenergetics to whole-animal fitness, in the current context of climate change. We summarize topics, questions, methods, pitfalls and caveats to help provide a comprehensive roadmap for studying mitochondria from a conservation perspective. Our overall aim is to help guide conservation in natural populations, outlining the methods and techniques that could be most useful to assess mitochondrial function in the field.}, } @article {pmid39261613, year = {2024}, author = {Vosseberg, J and van Hooff, JJE and Köstlbacher, S and Panagiotou, K and Tamarit, D and Ettema, TJG}, title = {The emerging view on the origin and early evolution of eukaryotic cells.}, journal = {Nature}, volume = {633}, number = {8029}, pages = {295-305}, pmid = {39261613}, issn = {1476-4687}, support = {/NWO_/Dutch Research Council/Netherlands ; /ERC_/European Research Council/International ; //Volkswagen Foundation/ ; }, mesh = {Animals ; Archaea/classification/cytology ; Bacteria/classification/cytology/metabolism ; *Biological Evolution ; *Eukaryota/classification/cytology/metabolism ; *Eukaryotic Cells/cytology/metabolism ; Mitochondria/metabolism ; Phylogeny ; Prokaryotic Cells/cytology/metabolism/classification ; *Symbiosis ; *Models, Biological ; }, abstract = {The origin of the eukaryotic cell, with its compartmentalized nature and generally large size compared with bacterial and archaeal cells, represents a cornerstone event in the evolution of complex life on Earth. In a process referred to as eukaryogenesis, the eukaryotic cell is believed to have evolved between approximately 1.8 and 2.7 billion years ago from its archaeal ancestors, with a symbiosis with a bacterial (proto-mitochondrial) partner being a key event. In the tree of life, the branch separating the first from the last common ancestor of all eukaryotes is long and lacks evolutionary intermediates. As a result, the timing and driving forces of the emergence of complex eukaryotic features remain poorly understood. During the past decade, environmental and comparative genomic studies have revealed vital details about the identity and nature of the host cell and the proto-mitochondrial endosymbiont, enabling a critical reappraisal of hypotheses underlying the symbiotic origin of the eukaryotic cell. Here we outline our current understanding of the key players and events underlying the emergence of cellular complexity during the prokaryote-to-eukaryote transition and discuss potential avenues of future research that might provide new insights into the enigmatic origin of the eukaryotic cell.}, } @article {pmid39264945, year = {2024}, author = {Zang, C and Wang, X and Liu, Y and Wang, H and Sun, Q and Cheng, P and Zhang, Y and Gong, M and Liu, H}, title = {Wolbachia and mosquitoes: Exploring transmission modes and coevolutionary dynamics in Shandong Province, China.}, journal = {PLoS neglected tropical diseases}, volume = {18}, number = {9}, pages = {e0011944}, pmid = {39264945}, issn = {1935-2735}, mesh = {*Wolbachia/physiology/genetics ; Animals ; *Culex/microbiology/virology/physiology ; China ; *Mosquito Vectors/microbiology/physiology ; Symbiosis ; Female ; Vector Borne Diseases/transmission ; Biological Coevolution ; Male ; }, abstract = {Vector-borne diseases leave a large footprint on global health. Notable culprits include West Nile virus (WNV), St. Louis encephalitis virus (SLEV), and Japanese encephalitis virus (JEV), all transmitted by Culex mosquitoes. Chemical insecticides have been widely used to reduce the spread of mosquito-borne diseases. Still, mosquitoes are becoming more and more resistant to most chemical insecticides which cause particular harm to the ecology. Wolbachia belongs to the family Ehrlichiaceae in the order Rickettsiales and is a matrilineally inherited endosymbiont present in 60% of insects in nature. Wolbachia is capable of inducing a wide range of reproductive abnormalities in its hosts, such as cytoplasmic incompatibility, and can alter mosquito resistance to pathogen infection. Wolbachia has been proposed as a biological alternative to chemical vector control, and specific research progress and effectiveness have been achieved. Despite the importance of Wolbachia, this strategy has not been tested in Culex pipiens pallens, the most prevalent mosquito species in Shandong Province, China. Little is known about how the mass release of Wolbachia-infected mosquitoes may impact the genetic structure of Culex pipiens pallens, and how the symbiotic bacterium Wolbachia interacts with mitochondria during host mosquito transmission. Based on the population genetic structure of Culex pipiens pallens in Shandong Province, this study investigated the infection rate and infection type of Wolbachia in Shandong Province and jointly analysed the evolutionary relationship between the host mosquito and the symbiotic bacterium Wolbachia. Our study showed that Wolbachia naturally infected by Culex pipiens pallens in Shandong Province was less homologous to Wolbachia infected by Aedes albopictus released from mosquito factory in Guangzhou. Our results also show that Culex pipiens pallens is undergoing demographic expansion in Shandong Province. The overall Wolbachia infection rate of Culex pipiens pallens was 92.8%, and a total of 15 WSP haplotypes were detected. We found that the genetic diversity of Wolbachia was low in Culex pipiens pallens from Shandong Province, and the mosquitoes were infected only with type B Wolbachia. Visualizing the relationship between Culex pipiens pallens and Wolbachia using a tanglegram revealed patterns of widespread associations. A specific coevolutionary relationship exists between the host mosquito and Wolbachia. Knowledge of this mosquito-Wolbachia relationship will provide essential scientific information required for Wolbachia-based vector control approaches in Shandong Province and will lead to a better understanding of the diversity and evolution of Wolbachia for its utility as a biocontrol agent.}, } @article {pmid39280847, year = {2024}, author = {Golubenko, MV and Puzyrev, VP}, title = {Liberties of the genome: insertions of mitochondrial DNA fragments into nuclear genome.}, journal = {Vavilovskii zhurnal genetiki i selektsii}, volume = {28}, number = {5}, pages = {467-475}, doi = {10.18699/vjgb-24-53}, pmid = {39280847}, issn = {2500-0462}, abstract = {The transition of detached fragments of mitochondrial DNA into the nucleus and their integration into chromosomal DNA is a special kind of genetic variability that highlights the relation between the two genomes and their interaction in a eukaryotic cell. The human genome contains several hundreds of insertions of mtDNA fragments (NUMTS). This paper presents an overview of the current state of research in this area. To date, evidence has been obtained that the occurrence of new mtDNA insertions in the nuclear genome is a seldom but not exceptionally rare event. The integration of new mtDNA fragments into the nuclear genome occurs during double-strand DNA break repair through the non-homologous end joining mechanism. Along with evolutionarily stable "genetic fossils" that were integrated into the nuclear genome millions of years ago and are shared by many species, there are NUMTS that could be species-specific, polymorphic in a species, or "private". Partial copies of mitochondrial DNA in the human nuclear genome can interfere with mtDNA during experimental studies of the mitochondrial genome, such as genotyping, heteroplasmy assessment, mtDNA methylation analysis, and mtDNA copy number estimation. In some cases, the insertion of multiple copies of the complete mitochondrial genome sequence may mimic paternal inheritance of mtDNA. The functional significance of NUMTS is poorly understood. For instance, they may be a source of variability for expression and splicing modulation. The role of NUMTS as a cause of hereditary diseases is negligible, since only a few cases of diseases caused by NUMTS have been described so far. In addition, NUMTS can serve as markers for evolutionary genetic studies. Of particular interest is the meaning of NUMTS in eukaryotic genome evolution. The constant flow of functionally inactive DNA sequences from mitochondria into the nucleus and its significance could be studied in view of the modern concepts of evolutionary theory suggesting non-adaptive complexity and the key role of stochastic processes in the formation of genomic structure.}, } @article {pmid39284909, year = {2024}, author = {Brunetta, HS and Jung, AS and Valdivieso-Rivera, F and de Campos Zani, SC and Guerra, J and Furino, VO and Francisco, A and Berçot, M and Moraes-Vieira, PM and Keipert, S and Jastroch, M and Martinez, LO and Sponton, CH and Castilho, RF and Mori, MA and Bartelt, A}, title = {IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat.}, journal = {The EMBO journal}, volume = {43}, number = {21}, pages = {4870-4891}, pmid = {39284909}, issn = {1460-2075}, support = {2022/00358-1//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; 852742//EC | European Research Council (ERC)/ ; BA4925/2-1//Deutsche Forschungsgemeinschaft (DFG)/ ; 81X3600212//Deutsches Zentrum für Herz-Kreislaufforschung (DZHK)/ ; 310287/2018-9//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/ ; 88881.143924/2017-01//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)/ ; }, mesh = {Animals ; *Thermogenesis/genetics ; Mice ; *Adipose Tissue, Brown/metabolism ; *Cold Temperature ; *ATPase Inhibitory Protein ; *Mitochondrial Proton-Translocating ATPases/metabolism/genetics ; Hydrolysis ; Mitochondria/metabolism ; Mice, Inbred C57BL ; Male ; Adipocytes, Brown/metabolism ; Membrane Potential, Mitochondrial ; Energy Metabolism ; }, abstract = {While mechanisms controlling uncoupling protein-1 (UCP1) in thermogenic adipocytes play a pivotal role in non-shivering thermogenesis, it remains unclear whether F1Fo-ATP synthase function is also regulated in brown adipose tissue (BAT). Here, we show that inhibitory factor 1 (IF1, encoded by Atp5if1), an inhibitor of ATP synthase hydrolytic activity, is a critical negative regulator of brown adipocyte energy metabolism. In vivo, IF1 levels are diminished in BAT of cold-adapted mice compared to controls. Additionally, the capacity of ATP synthase to generate mitochondrial membrane potential (MMP) through ATP hydrolysis (the so-called "reverse mode" of ATP synthase) is increased in brown fat. In cultured brown adipocytes, IF1 overexpression results in an inability of mitochondria to sustain the MMP upon adrenergic stimulation, leading to a quiescent-like phenotype in brown adipocytes. In mice, adeno-associated virus-mediated IF1 overexpression in BAT suppresses adrenergic-stimulated thermogenesis and decreases mitochondrial respiration in BAT. Taken together, our work identifies downregulation of IF1 upon cold as a critical event for the facilitation of the reverse mode of ATP synthase as well as to enable energetic adaptation of BAT to effectively support non-shivering thermogenesis.}, } @article {pmid39291629, year = {2024}, author = {Karl, MT and Kim, YD and Rajendran, K and Manger, PR and Sherwood, CC}, title = {Invariance of Mitochondria and Synapses in the Primary Visual Cortex of Mammals Provides Insight Into Energetics and Function.}, journal = {The Journal of comparative neurology}, volume = {532}, number = {9}, pages = {e25669}, pmid = {39291629}, issn = {1096-9861}, support = {R24 NS092988/NS/NINDS NIH HHS/United States ; NS092988/NH/NIH HHS/United States ; EF-2021785//National Science Foundation/ ; DRL-2219759//National Science Foundation/ ; HG011641/NH/NIH HHS/United States ; R01 HG011641/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; *Synapses/ultrastructure/metabolism ; *Mitochondria/ultrastructure/metabolism ; *Mammals ; *Primary Visual Cortex/physiology ; Energy Metabolism/physiology ; Species Specificity ; Visual Cortex/metabolism/cytology/physiology/ultrastructure ; Mice ; Humans ; }, abstract = {The cerebral cortex accounts for substantial energy expenditure, primarily driven by the metabolic demands of synaptic signaling. Mitochondria, the organelles responsible for generating cellular energy, play a crucial role in this process. We investigated ultrastructural characteristics of the primary visual cortex in 18 phylogenetically diverse mammals, spanning a broad range of brain sizes from mouse to elephant. Our findings reveal remarkable uniformity in synapse density, postsynaptic density (PSD) length, and mitochondria density, indicating functional and metabolic constraints that maintain these fundamental features. Notably, we observed an average of 1.9 mitochondria per synapse across mammalian species. When considered together with the trend of decreasing neuron density with larger brain size, we find that brain enlargement in mammals is characterized by increasing proportions of synapses and mitochondria per cortical neuron. These results shed light on the adaptive mechanisms and metabolic dynamics that govern cortical ultrastructure across mammals.}, } @article {pmid39300074, year = {2024}, author = {Gitschlag, BL and Pereira, CV and Held, JP and McCandlish, DM and Patel, MR}, title = {Multiple distinct evolutionary mechanisms govern the dynamics of selfish mitochondrial genomes in Caenorhabditis elegans.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8237}, pmid = {39300074}, issn = {2041-1723}, support = {R01 GM123260/GM/NIGMS NIH HHS/United States ; R35 GM133613/GM/NIGMS NIH HHS/United States ; F31 GM125344/GM/NIGMS NIH HHS/United States ; T32 GM008554/GM/NIGMS NIH HHS/United States ; R35 GM145378/GM/NIGMS NIH HHS/United States ; F31GM125344//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R35GM133613//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R35GM145378//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01GM123260//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, mesh = {Animals ; *Caenorhabditis elegans/genetics ; *Genome, Mitochondrial ; *DNA, Mitochondrial/genetics ; *Mutation ; *Evolution, Molecular ; Selection, Genetic ; Genetic Drift ; Models, Genetic ; Mitochondria/genetics/metabolism ; Genotype ; }, abstract = {Cells possess multiple mitochondrial DNA (mtDNA) copies, which undergo semi-autonomous replication and stochastic inheritance. This enables mutant mtDNA variants to arise and selfishly compete with cooperative (wildtype) mtDNA. Selfish mitochondrial genomes are subject to selection at different levels: they compete against wildtype mtDNA directly within hosts and indirectly through organism-level selection. However, determining the relative contributions of selection at different levels has proven challenging. We overcome this challenge by combining mathematical modeling with experiments designed to isolate the levels of selection. Applying this approach to many selfish mitochondrial genotypes in Caenorhabditis elegans reveals an unexpected diversity of evolutionary mechanisms. Some mutant genomes persist at high frequency for many generations, despite a host fitness cost, by aggressively outcompeting cooperative genomes within hosts. Conversely, some mutant genomes persist by evading inter-organismal selection. Strikingly, the mutant genomes vary dramatically in their susceptibility to genetic drift. Although different mechanisms can cause high frequency of selfish mtDNA, we show how they give rise to characteristically different distributions of mutant frequency among individuals. Given that heteroplasmic frequency represents a key determinant of phenotypic severity, this work outlines an evolutionary theoretic framework for predicting the distribution of phenotypic consequences among individuals carrying a selfish mitochondrial genome.}, } @article {pmid39303860, year = {2024}, author = {Yong, Y and Hu, S and Zhong, M and Wen, Y and Zhou, Y and Ma, R and Jiang, X and Zhang, Q}, title = {Horizontal gene transfer from chloroplast to mitochondria of seagrasses in the yellow-Bohai seas.}, journal = {Genomics}, volume = {116}, number = {5}, pages = {110940}, doi = {10.1016/j.ygeno.2024.110940}, pmid = {39303860}, issn = {1089-8646}, mesh = {*Gene Transfer, Horizontal ; Genome, Mitochondrial ; Chloroplasts/genetics ; Genome, Chloroplast ; Alismatales/genetics/metabolism ; Phylogeny ; Mitochondria/genetics/metabolism ; }, abstract = {Seagrasses are ideal for studying plant adaptation to marine environments. In this study, the mitochondrial (mt) and chloroplast (cp) genomes of Ruppia sinensis were sequenced. The results showed an extensive gene loss in seagrasses, including a complete loss of cp-rpl19 genes in Zosteraceae, most cp-ndh genes in Hydrocharitaceae, and mt-rpl and mt-rps genes in all seagrasses, except for the mt-rpl16 gene in Phyllospadix iwatensis. Notably, most ribosomal protein genes were lost in the mt and cp genomes. The deleted cp genes were not transferred to the mt genomes through horizontal gene transfer. Additionally, a significant DNA transfer between seagrass organelles was found, with the mt genomes of Zostera containing numerous sequences from the cp genome. Rearrangement analyses revealed an unreported inversion of the cp genome in R. sinensis. Moreover, four positively selected genes (atp8, nad5, atp4, and ccmFn) and five variable regions (matR, atp4, atp8, rps7, and ccmFn) were identified.}, } @article {pmid39307735, year = {2024}, author = {Zhang, YX and Fan, X and Zhang, M and Chen, YC and Zhao, YY and Jiao, HH and Zhang, G and Yuan, Y}, title = {[Influence of Tis108 on GA content and expression of key enzyme GeCYP714A1 involved in GA deactivation of Gastrodia elata].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {49}, number = {15}, pages = {4007-4014}, doi = {10.19540/j.cnki.cjcmm.20240517.101}, pmid = {39307735}, issn = {1001-5302}, mesh = {*Gastrodia/genetics/chemistry ; *Gibberellins/pharmacology/metabolism ; *Plant Proteins/genetics/metabolism/chemistry ; Gene Expression Regulation, Plant/drug effects ; Lactones/pharmacology ; Phylogeny ; Amino Acid Sequence ; }, abstract = {To investigate the influence of the strigolactone inhibitor Tis108 on the growth of Gastrodia elata, this study treated G. elata tuber with Tis108 solution of 10 μmol·L~(-1) and measured the content of endogenous hormone gibberellin(GA) in the tuber. By using reverse transcription-polymerase chain reaction(RT-PCR) technology, the key enzyme GeCYP714A1 gene involved in GA deactivation was cloned. Bioinformatics analysis on the GeCYP714A1 gene was carried out by using ExPASy, SWISS-MODEL, MEGA, etc., and its expression levels in different parts of G. elata were determined. The results showed that after Tis108 treatment, GA content in G. elata tuber was significantly increased, and the transcription level of the GeCYP714A1 gene was significantly decreased. The full length of the coding region of the GeCYP714A1 gene is 1 173 bp, encoding 390 amino acids. The protein has a molecular weight of 44.85 kDa, a theoretical isoelectric point of 9.83, an instability index of 49.20, an aliphatic index of 89.03, and a grand average of hydropathicity of-0.235, classifying it as an unstable, basic, hydrophilic protein, and the GeCYP714A1 protein was localized in the mitochondria, lacking a signal peptide and a transmembrane structure. Phylogenetic tree analysis revealed that GeCYP714A1 was most closely related to the DcCYP714C2(PKU78454.1) protein from Dendrobium candidum, with a sequence identity of 67.25%. The qRT-PCR analysis of the expression patterns of the GeCYP714A1 gene indicated that GeCYP714A1 had the highest transcription level in G. elata tuber, followed by stem and inflorescence. The study represented that Tis108 inhibited the transcription level of GeCYP714A1 involved in GA deactivation in G. elata tuber, thereby increasing the accumulation of GA and affecting the growth of G. elata tuber. These results provided a basis for further studies of strigolactone regulation of GA signal and tuber development in G. elata.}, } @article {pmid39308980, year = {2024}, author = {Mendoza, H and Lamb, EA and Thomas, J and Tavares, DG and Schroeder, LA and Müller, C and Agrawal, N and Schirawski, J and Perlin, MH}, title = {Comparative mitogenomic analysis of Sporisorium reilianum f. sp. zeae suggests recombination events during its evolutionary history.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1264359}, pmid = {39308980}, issn = {1664-042X}, abstract = {INTRODUCTION: Modern understanding of the concept of genetic diversity must include the study of both nuclear and organellar DNA, which differ greatly in terms of their structure, organization, gene content and distribution. This study comprises an analysis of the genetic diversity of the smut fungus Sporisorium reilianum f. sp. zeae from a mitochondrial perspective.

METHODS: Whole-genome sequencing data was generated from biological samples of S. reilianum collected from different geographical regions. Multiple sequence alignment and gene synteny analysis were performed to further characterize genetic diversity in the context of mitogenomic polymorphisms.

RESULTS: Mitochondria of strains collected in China contained unique sequences. The largest unique sequence stretch encompassed a portion of cox1, a mitochondrial gene encoding one of the subunits that make up complex IV of the mitochondrial electron transport chain. This unique sequence had high percent identity to the mitogenome of the related species Sporisorium scitamineum and Ustilago bromivora.

DISCUSSION: The results of this study hint at potential horizontal gene transfer or mitochondrial genome recombination events during the evolutionary history of basidiomycetes. Additionally, the distinct polymorphic region detected in the Chinese mitogenome provides the ideal foundation to develop a diagnostic method to discern between mitotypes and enhance knowledge on the genetic diversity of this organism.}, } @article {pmid39326543, year = {2025}, author = {Rodriguez, E and Peng, B and Lane, N}, title = {Anaesthetics disrupt complex I-linked respiration and reverse the ATP synthase.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1866}, number = {1}, pages = {149511}, doi = {10.1016/j.bbabio.2024.149511}, pmid = {39326543}, issn = {1879-2650}, mesh = {Animals ; *Drosophila melanogaster/metabolism ; *Electron Transport Complex I/metabolism ; *Mitochondrial Proton-Translocating ATPases/metabolism ; Isoflurane/pharmacology ; Membrane Potential, Mitochondrial/drug effects ; Sevoflurane/pharmacology ; Adenosine Triphosphate/metabolism ; Anesthetics, Inhalation/pharmacology ; Mitochondria/drug effects/metabolism/enzymology ; }, abstract = {The mechanism of volatile general anaesthetics has long been a mystery. Anaesthetics have no structural motifs in common, beyond lipid solubility, yet all exert a similar effect. The fact that the inert gas xenon is an anaesthetic suggests their common mechanism might relate to physical rather than chemical properties. Electron transfer through chiral proteins can induce spin polarization. Recent work suggests that anaesthetics dissipate spin polarization during electron transfer to oxygen, slowing respiration. Here we show that the volatile anaesthetics isoflurane and sevoflurane specifically disrupt complex I-linked respiration in the thoraces of Drosophila melanogaster, with less effect on maximal respiration. Suppression of complex I-linked respiration was greatest with isoflurane. Using high-resolution tissue fluorespirometry, we show that these anaesthetics simultaneously increase mitochondrial membrane potential, implying reversal of the ATP synthase. Inhibition of ATP synthase with oligomycin prevented respiration and increased membrane potential back to the maximal (LEAK state) potential. Magnesium-green fluorescence predicted a collapse in ATP availability following a single anaesthetic dose, consistent with ATP hydrolysis through reversal of the ATP synthase. Raised membrane potential corresponded to a rise in ROS flux, especially with isoflurane. Anaesthetic doses causing respiratory suppression were in the same range as those that induce anaesthesia, although we could not establish tissue concentrations. Our findings show that anaesthetics suppress complex I-linked respiration with concerted downstream effects. But we cannot explain why only mutations in complex I, and not elsewhere in the electron-transfer system, confer hypersensitivity to anaesthetics.}, } @article {pmid39331563, year = {2024}, author = {Kubota, K and Oishi, M and Taniguchi, E and Akazawa, A and Matsui, K and Kitazaki, K and Toyoda, A and Toh, H and Matsuhira, H and Kuroda, Y and Kubo, T}, title = {Mitochondrial phylogeny and distribution of cytoplasmic male sterility-associated genes in Beta vulgaris.}, journal = {PloS one}, volume = {19}, number = {9}, pages = {e0308551}, pmid = {39331563}, issn = {1932-6203}, mesh = {*Beta vulgaris/genetics ; *Phylogeny ; *Plant Infertility/genetics ; Mitochondria/genetics ; Polymorphism, Single Nucleotide ; Genes, Plant ; Genes, Mitochondrial ; Genome, Mitochondrial ; DNA, Mitochondrial/genetics ; }, abstract = {Cytoplasmic male sterility (CMS) is a mitochondrial-encoded trait that confers reproductive defects in males but not in females or any vegetative function. Why CMS is so often found in plants should be investigated from the viewpoint of mitochondrial phylogeny. Beta vulgaris, including the wild subspecies maritima and cultivated subspecies vulgaris (e.g., sugar beet), is known to be mitochondrially polymorphic, from which multiple CMS mitochondria have been found, but their evolutionary relationship has been obscure. We first refined the B. vulgaris reference mitochondrial genome to conduct a more accurate phylogenetic study. We identified mitochondrial single-nucleotide polymorphic sites from 600 B. vulgaris accessions. Principal component analysis, hierarchical clustering analysis, and creation of a phylogenetic tree consistently suggested that B. vulgaris mitochondria can be classified into several groups whose geographical distribution tends to be biased toward either the Atlantic or Mediterranean coasts. We examined the distribution of CMS-associated mitochondrial genes from Owen, E- and G-type CMS mitochondria. About one-third of cultivated beets had Owen-type CMS, which reflects the prevalence of using Owen-type CMS in hybrid breeding. Occurrence frequencies for each of the three CMS genes in wild beet were less than 4%. CMS genes were tightly associated with specific mitochondrial groups that are phylogenetically distinct, suggesting their independent origin. However, homologous sequences of the Owen type CMS gene occurred in several different mitochondrial groups, for which an intricate explanation is necessary. Whereas the origin of cultivated beet had been presumed to be Greece, we found an absence of Owen-type mitochondria in Greek accessions.}, } @article {pmid39334842, year = {2024}, author = {Gambino, G and Da Pozzo, E and Salvetti, A and Rossi, L}, title = {Planarian Mucus: A Novel Source of Pleiotropic Cytotoxic and Cytostatic Agents against Cancer Cells.}, journal = {Biomolecules}, volume = {14}, number = {9}, pages = {}, pmid = {39334842}, issn = {2218-273X}, mesh = {Animals ; *Planarians/drug effects/metabolism ; *Mucus/metabolism ; Humans ; *Antineoplastic Agents/pharmacology/chemistry ; Cytostatic Agents/pharmacology/chemistry ; Reactive Oxygen Species/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; }, abstract = {Biological evolution has generated a vast array of natural compounds produced by organisms across all domains. Among these, secondary metabolites, selected to enhance an organism's competitiveness in its natural environment, make them a reservoir for discovering new compounds with cytotoxic activity, potentially useful as novel anticancer agents. Slime secretions, the first barrier between epithelial surfaces and the surrounding environment, frequently contain cytotoxic molecules to limit the growth of parasitic organisms. Planarians, freshwater Triclads, continuously secrete a viscous mucus with multiple physiological functions. The chemical composition of planarian mucus has been only partially elucidated, and there are no studies reporting its cytotoxic or cytostatic effects. In this study, we developed a protocol for collecting mucus from Dugesia japonica specimens and we demonstrated that it inhibits the growth of cancer cells by activating cytostatic and ROS-dependent cytotoxic mechanisms inducing lipid droplet accumulation and mitochondrial membrane reorganization. Although further research is needed to identify the specific chemicals responsible for the anticancer activity of planarian mucus, this work opens up numerous research avenues aimed at better understanding the mechanisms of action of this product for potential therapeutic applications.}, } @article {pmid39341116, year = {2024}, author = {Yazaki, E and Uehara, T and Sakamoto, H and Inagaki, Y}, title = {Dinotoms possess two evolutionary distinct autophagy-related ubiquitin-like conjugation systems.}, journal = {Protist}, volume = {175}, number = {6}, pages = {126067}, doi = {10.1016/j.protis.2024.126067}, pmid = {39341116}, issn = {1618-0941}, mesh = {*Autophagy ; *Dinoflagellida/genetics/classification/metabolism ; *Diatoms/genetics/metabolism/classification ; Symbiosis ; Phylogeny ; Biological Evolution ; Ubiquitin/metabolism/genetics ; Autophagy-Related Proteins/genetics/metabolism ; }, abstract = {Autophagy is an intracellular degradation mechanism by which cytoplasmic materials are delivered to and degraded in the lysosome-fused autophagosome (autolysosome) and proposed to have been established at an early stage of eukaryotic evolution. Dinoflagellates harboring endosymbiotic diatoms (so-called "dinotoms"), which retain their own nuclei and mitochondria in addition to plastids, have been investigated as an intermediate toward the full integration of a eukaryotic phototroph into the host-controlled organelle (i.e., plastid) through endosymbiosis. Pioneering studies systematically evaluated the degree of host governance on several metabolic pathways in the endosymbiotic diatoms (ESDs). However, little attention has been paid to the impact of the endosymbiotic lifestyle on the autophagy operated in the ESDs. In this study, we searched for ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, and ATG12, which are required for autophagosome formation, in the RNA-seq data from dinotoms Durinskia baltica and Kryptoperidinium foliaceum. We detected two evolutionally distinct sets of the ATG proteins in the dinotom species, one affiliated with the dinoflagellate homologs and the other with the diatom homologs in phylogenetic analyses. The results suggest that the ATG proteins descended from the diatom taken up by the dinoflagellate host persist for autophagosome formation and, most likely, autophagy.}, } @article {pmid39342114, year = {2024}, author = {Ye, H and Liu, H and Li, H and Lei, D and Gao, Z and Zhou, H and Zhao, P}, title = {Complete mitochondrial genome assembly of Juglans regia unveiled its molecular characteristics, genome evolution, and phylogenetic implications.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {894}, pmid = {39342114}, issn = {1471-2164}, support = {Y23Z619F17//Qinling Hundred Talents Project of Shaanxi Academy of Science/ ; 32370386//National Natural Science Foundation of China/ ; 2023-JC-JQ-22//Science Foundation for Distinguished Young Scholars of Shaanxi Province/ ; 22JHZ005//Basic Research Project of Shaanxi Academy of Fundamental Science/ ; 2024NC-YBXM-064//Shaanxi Key Research and Development Program/ ; 2023K-49, 2023K-26, and 2019K-06//Science and Technology Program of Shaanxi Academy of Science/ ; SXLK2023-02-20//Shaanxi Forestry Science and Technology Innovation Key Project/ ; }, mesh = {*Juglans/genetics ; *Genome, Mitochondrial ; *Phylogeny ; *Evolution, Molecular ; RNA, Transfer/genetics ; Genome, Plant ; RNA Editing ; Codon Usage ; Base Composition ; }, abstract = {BACKGROUND: The Persian walnut (Juglans regia), an economically vital species within the Juglandaceae family, has seen its mitochondrial genome sequenced and assembled in the current study using advanced Illumina and Nanopore sequencing technology.

RESULTS: The 1,007,576 bp mitogenome of J. regia consisted of three circular chromosomes with a 44.52% GC content encoding 39 PCGs, 47 tRNA, and five rRNA genes. Extensive repetitive sequences, including 320 SSRs, 512 interspersed, and 83 tandem repeats, were identified, contributing to genomic complexity. The protein-coding sequences (PCGs) favored A/T-ending codons, and the codon usage bias was primarily shaped by selective pressure. Intracellular gene transfer occurred among the mitogenome, chloroplast, and nuclear genomes. Comparative genomic analysis unveiled abundant structure and sequence variation among J. regia and related species. The results of selective pressure analysis indicated that most PCGs underwent purifying selection, whereas the atp4 and ccmB genes had experienced positive selection between many species pairs. In addition, the phylogenetic examination, grounded in mitochondrial genome data, precisely delineated the evolutionary and taxonomic relationships of J. regia and its relatives. We identified a total of 539 RNA editing sites, among which 288 were corroborated by transcriptome sequencing data. Furthermore, expression profiling under temperature stress highlighted the complex regulation pattern of 28 differently expressed PCGs, wherein NADH dehydrogenase and ATP synthase genes might be critical in the mitochondria response to cold stress.

CONCLUSIONS: Our results provided valuable molecular resources for understanding the genetic characteristics of J. regia and offered novel perspectives for population genetics and evolutionary studies in Juglans and related woody species.}, } @article {pmid39343888, year = {2024}, author = {Ahmad, F and Abdullah, M and Khan, Z and Stępień, P and Rehman, SU and Akram, U and Rahman, MHU and Ali, Z and Ahmad, D and Gulzar, RMA and Ali, MA and Salama, EAA}, title = {Genome-wide analysis and prediction of chloroplast and mitochondrial RNA editing sites of AGC gene family in cotton (Gossypium hirsutum L.) for abiotic stress tolerance.}, journal = {BMC plant biology}, volume = {24}, number = {1}, pages = {888}, pmid = {39343888}, issn = {1471-2229}, support = {32130075//National Natural Science Foundation of China/ ; 32130075//National Natural Science Foundation of China/ ; 32130075//National Natural Science Foundation of China/ ; 2021AB008, 2020CB003//Science Technology and Achievement Transformation Project of the Xinjiang Production and Construction Corps/ ; 2021AB008, 2020CB003//Science Technology and Achievement Transformation Project of the Xinjiang Production and Construction Corps/ ; 2021AB008, 2020CB003//Science Technology and Achievement Transformation Project of the Xinjiang Production and Construction Corps/ ; ADP-LO21002838 Punjab, Pak//ADP Funded Project entitled National Crop Genomics and Speed Breeding Center for Agri-cultural Sustainability/ ; ADP-LO21002838 Punjab, Pak//ADP Funded Project entitled National Crop Genomics and Speed Breeding Center for Agri-cultural Sustainability/ ; ADP-LO21002838 Punjab, Pak//ADP Funded Project entitled National Crop Genomics and Speed Breeding Center for Agri-cultural Sustainability/ ; ADP-LO21002838 Punjab, Pak//ADP Funded Project entitled National Crop Genomics and Speed Breeding Center for Agri-cultural Sustainability/ ; ADP-LO21002838 Punjab, Pak//ADP Funded Project entitled National Crop Genomics and Speed Breeding Center for Agri-cultural Sustainability/ ; RSP2024R306//King Saud University, Riyadh, Saudi Arabia/ ; }, mesh = {*Gossypium/genetics/physiology ; *RNA Editing/genetics ; *Stress, Physiological/genetics ; *Phylogeny ; *Chloroplasts/genetics ; Genome, Plant ; Mitochondria/genetics ; Plant Proteins/genetics/metabolism ; Multigene Family ; Genome-Wide Association Study ; Gene Expression Regulation, Plant ; RNA, Mitochondrial/genetics ; Genes, Plant ; }, abstract = {BACKGROUND: Cotton is one of the topmost fiber crops throughout the globe. During the last decade, abrupt changes in the climate resulted in drought, heat, and salinity. These stresses have seriously affected cotton production and significant losses all over the textile industry. The GhAGC kinase, a subfamily of AGC group and member of serine/threonine (Ser/Thr) protein kinases group and is highly conserved among eukaryotic organisms. The AGC kinases are compulsory elements of cell development, metabolic processes, and cell death in mammalian systems. The investigation of RNA editing sites within the organelle genomes of multicellular vascular plants, such as Gossypium hirsutum holds significant importance in understanding the regulation of gene expression at the post-transcriptional level.

METHODS: In present work, we characterized twenty-eight GhAGC genes in cotton and constructed phylogenetic tree using nine different species from the most primitive to the most recent.

RESULTS: In sequence logos analyses, highly conserved amino acid residues were found in G. hirsutum, G. arboretum, G. raimondii and A. thaliana. The occurrence of cis-acting growth and stress-related elements in the promoter regions of GhAGCs highlight the significance of these factors in plant development and abiotic stress tolerance. Ka/Ks levels demonstrated that purifying selection pressure resulting from segmental events was applied to GhAGC with little functional divergence. We focused on identifying RNA editing sites in G. hirsutum organelles, specifically in the chloroplast and mitochondria, across all 28 AGC genes.

CONCLUSION: The positive role of GhAGCs was explored by quantifying the expression in the plant tissues under abiotic stress. These findings help in understanding the role of GhAGC genes under abiotic stresses which may further be used in cotton breeding for the development of climate smart varieties in abruptly changing climate.}, } @article {pmid39356435, year = {2024}, author = {Zouaoui, S and Rouabhi, R}, title = {Lysosomal disruption, mitochondrial impairment, histopathological and oxidative stress in rat's nervous system after exposure to a neonicotinoid (imidacloprid).}, journal = {Environmental science and pollution research international}, volume = {31}, number = {49}, pages = {59472-59489}, pmid = {39356435}, issn = {1614-7499}, mesh = {Animals ; *Oxidative Stress/drug effects ; *Rats, Wistar ; Rats ; *Lysosomes/drug effects ; *Neonicotinoids/toxicity ; *Mitochondria/drug effects ; Nitro Compounds/toxicity ; Nervous System/drug effects ; Male ; Insecticides/toxicity ; }, abstract = {Imidacloprid (IMI), a neonicotinoid pesticide, has been widely used due to its high efficiency against insect pests. However, its prolonged exposure may pose significant risks to non-target organisms, including mammals. Recent studies have raised concerns about its potential neurotoxicity, yet the underlying mechanisms remain poorly understood. This study aimed to assess the neurotoxic effects of chronic Imidacloprid exposure in Wistar rats, focusing on oxidative stress, mitochondrial dysfunction, and lysosomal disruption. Wistar rats were orally administered two doses of Imidacloprid (5 mg/kg and 50 mg/kg body weight) for three months. Neurotoxic effects were assessed by measuring key biochemical markers such as the enzymatic activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione S-transferase (GST). Non-enzymatic markers, including glutathione (GSH) levels and malondialdehyde (MDA) index, were also evaluated. Mitochondrial function was assessed by analyzing oxygen consumption, swelling, and membrane permeability and histopathological changes. Lysosomal stability was examined using the Neutral Red Retention Time (NRRT) assay. Neutral red is a dye that accumulates in the acidic environment of lysosomes. Healthy lysosomes retain the dye, while compromised lysosomes lose it, indicating destabilization. By measuring the amount of neutral red retained in lysosomes, the NRRT assay assesses lysosomal integrity. Lysosomal pH variations were also monitored to evaluate functional changes. Microscopic analysis provided insight into structural changes in lysosomes and other cell components. Lysosomal destabilization was further confirmed by morphological alterations observed through light microscopy, revealing a progressive, time-dependent degeneration of lysosomal structures, including lysosomal expansion, neutral red dye leakage, and cell rounding. These changes reflected a temporal evolution of lysosomal damage, progressing from minor structural disruptions to more severe alterations as exposure continued, observable at the microscopic level. During the study, clinical observations of intoxicated rats included symptoms such as lethargy, reduced activity levels, and impaired motor coordination. High-dose Imidacloprid exposure led to noticeable behavioral changes, including decreased exploratory behavior and altered grooming patterns. Additionally, signs of neurotoxic effects, such as tremors or ataxia, were observed in the rats exposed to the higher dose, reflecting the systemic impact of chronic pesticide exposure. The results revealed a significant decrease in the enzymatic activities of CAT, GPx, and SOD, accompanied by an increase in GST activity. A notable reduction in glutathione levels and a rise in MDA index were observed, indicating enhanced oxidative stress in the brain. Mitochondrial impairment was evidenced by disturbances in oxygen consumption, increased swelling, and altered membrane permeability. Lysosomal destabilization was confirmed by reduced retention of neutral red dye, structural changes in lysosomes, and a significant rise in lysosomal pH in the IMI-exposed groups. In addition, the histopathological features indicate that imidacloprid at the given dose and exposure duration may have caused notable neurotoxic effects in Wistar rat brain tissue. Chronic exposure to Imidacloprid induces oxidative stress, mitochondrial dysfunction, lysosomal disruption and histopathological alterations in the central nervous system of Wistar rats. These findings provide valuable insights into the neurotoxic mechanisms of neonicotinoid pesticides, highlighting the need for further research to understand the long-term effects of Imidacloprid exposure on mammalian health.}, } @article {pmid39358558, year = {2024}, author = {Tronik-Le Roux, D and Daouya, M and Poras, I and Desgrandchamps, F and Carosella, ED}, title = {HLA-G neo-expression modifies genetic programs governing tumor cell lines.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {73}, number = {12}, pages = {247}, pmid = {39358558}, issn = {1432-0851}, mesh = {Humans ; *HLA-G Antigens/genetics/metabolism/immunology ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; CRISPR-Cas Systems ; Neuropilin-1/genetics/metabolism ; Immunotherapy/methods ; }, abstract = {The development of immunotherapies has proved to be clinically encouraging to re-establish the immune function modified by the expression of immune inhibitory molecules in tumors. However, there are still patients with poor survival rates following treatment. The elucidation of molecular mechanisms triggered by the neo-expression of particular IC in tumors would constitute a major step toward better understanding tumor evolution and would help to design future clinical protocols. To this end, we investigate the modifications triggered by the neo-expression of the immune checkpoints HLA-G in ccRCC tumor cells. We demonstrate, for the first time, that HLA-G modifies key genes implicated mainly in tumor development, angiogenesis, calcium flow and mitochondria dynamics. The involvement of HLA-G on the expression of genes belonging to these pathways such as ADAM-12, NCAM1 and NRP1 was confirmed by the CRISPR/Cas9-mediated edition of HLA-G. The data reveal multifaceted roles of HLA-G in tumor cells which are far beyond the well-known function of HLA-G in the immune anti-tumor response. This warrants further investigation of HLA-G and these new partners in tumors of different origin so as to propose future new treatments to improve health patient's outcome.}, } @article {pmid39367089, year = {2025}, author = {Piselli, C}, title = {How to isolate channel-forming membrane proteins using the E. coli expression system.}, journal = {Nature protocols}, volume = {20}, number = {2}, pages = {462-479}, pmid = {39367089}, issn = {1750-2799}, mesh = {*Escherichia coli/genetics/metabolism ; Chromatography, Ion Exchange/methods ; *Membrane Proteins/isolation & purification/genetics ; Solubility ; *Escherichia coli Proteins/isolation & purification/genetics ; Recombinant Proteins/isolation & purification/genetics/metabolism ; Detergents/chemistry ; Porins/isolation & purification ; }, abstract = {The recombinant expression, isolation and characterization of pore-forming proteins is one of the most commonly used strategies for understanding the permeability properties of the biological membrane into which they are embedded. This protocol describes how to quantify the expression of your protein of interest and use this information to optimize its production using the Escherichia coli strain BL21Gold(de3)ΔABCF. It explains with a step-by-step approach how to separate the bacterial compartments according to their solubility and how to extract your protein of interest in its native conformation using detergent solutions. Finally, it describes how to improve its purity via ion-exchange chromatography and insert the purified porins into outer membrane vesicles, from which they can be copurified. The protocol is simpler and less empirical than those described for most channel-forming membrane proteins and also provides a solid foundation for the isolation of soluble proteins. Several parameters can be optimized on a case-by-case basis: expression time and temperature, concentration of the inducer, nature and concentration of the detergent, incubation time and temperature, pH and ionic strength of the purification buffers. This protocol is effective with prokaryotic channel-forming membrane proteins and can be employed for the production of pore-forming proteins from chloroplasts, mitochondria or eukaryotes in general. With minor optimization, this protocol can be adapted for the isolation of receptors, carrier, pumps or any other membrane-active proteins.}, } @article {pmid39369076, year = {2024}, author = {Tseng, WW and Chu, CH and Lee, YJ and Zhao, S and Chang, C and Ho, YP and Wei, AC}, title = {Metabolic regulation of mitochondrial morphologies in pancreatic beta cells: coupling of bioenergetics and mitochondrial dynamics.}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {1267}, pmid = {39369076}, issn = {2399-3642}, support = {MOST-109-2636-B-002-001; MOST-110-2636-B-002-017//Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan)/ ; NTU-112L900701//National Taiwan University (NTU)/ ; }, mesh = {*Insulin-Secreting Cells/metabolism ; *Mitochondrial Dynamics ; *Energy Metabolism ; *Mitochondria/metabolism ; Animals ; Models, Biological ; Mice ; Adenosine Triphosphate/metabolism ; Humans ; }, abstract = {Cellular bioenergetics and mitochondrial dynamics are crucial for the secretion of insulin by pancreatic beta cells in response to elevated levels of blood glucose. To elucidate the interactions between energy production and mitochondrial fission/fusion dynamics, we combine live-cell mitochondria imaging with biophysical-based modeling and graph-based network analysis. The aim is to determine the mechanism that regulates mitochondrial morphology and balances metabolic demands in pancreatic beta cells. A minimalistic differential equation-based model for beta cells is constructed that includes glycolysis, oxidative phosphorylation, calcium dynamics, and fission/fusion dynamics, with ATP synthase flux and proton leak flux as main regulators of mitochondrial dynamics. The model shows that mitochondrial fission occurs in response to hyperglycemia, starvation, ATP synthase inhibition, uncoupling, and diabetic conditions, in which the rate of proton leakage exceeds the rate of mitochondrial ATP synthesis. Under these metabolic challenges, the propensities of tip-to-tip fusion events simulated from the microscopy images of the mitochondrial networks are lower than those in the control group and prevent the formation of mitochondrial networks. The study provides a quantitative framework that couples bioenergetic regulation with mitochondrial dynamics, offering insights into how mitochondria adapt to metabolic challenges.}, } @article {pmid39370506, year = {2024}, author = {Zhu, L and Diao, S and Li, T and Guo, J}, title = {Deciphering the multi- partite mitochondrial genome of Crataegus pinnatifida: insights into the evolution and genetics of cultivated Hawthorn.}, journal = {BMC plant biology}, volume = {24}, number = {1}, pages = {929}, pmid = {39370506}, issn = {1471-2229}, mesh = {*Crataegus/genetics ; *Genome, Mitochondrial ; Phylogeny ; Evolution, Molecular ; Genome, Plant ; RNA Editing ; }, abstract = {Flowering plant (angiosperm) mitochondrial genomes are remarkably dynamic in their structures. We present the complete mitochondrial genome of hawthorn (Crataegus pinnatifida Bunge), a shrub that bears fruit and is celebrated for its extensive medicinal history. We successfully assembled the hawthorn mitogenome utilizing the PacBio long-read sequencing technique, which yielded 799,862 reads, and the Illumina novaseq6000 sequencing platform, which producing 6.6 million raw paired reads. The C. pinnatifida mitochondria sequences encompassed a total length of 440,295 bp with a GC content of 45.42%. The genome annotates 54 genes, including 34 that encode proteins, 17 that encode tRNA, and three genes for rRNA. A fascinating interplay was observed between the chloroplast and mitochondrial genomes, which share 17 homologous sequences sequences that rotal 1,933 bp. A total of 134 SSRs, 22 tandem repeats and 42 dispersed repeats were identified in the mitogenome. Four conformations of C. pinnatifida mitochondria sequences recombination were verified through PCR experiments and Sanger sequencing, and C. pinnatifida mitogenome is more likely to be assembled into three circular-mapping chromosomes. All the RNA editing sites that were identified C-U edits, which predominantly occurred at the first and second positions of the codons. Phylogenetic and collinearity analyses identified the evolutionary trajectory of C. pinnatifida, which reinforced the genetic identity of the hawthorn section. This unveiling of the unique multi-partite structure of the hawthorn mitogenome offers a foundational reference for future study into the evolution and genetics of C. pinnatifida.}, } @article {pmid39371131, year = {2024}, author = {Smith, TB and Kopajtich, R and Demain, LAM and Rea, A and Thomas, HB and Schiff, M and Beetz, C and Joss, S and Conway, GS and Shukla, A and Yeole, M and Radhakrishnan, P and Azzouz, H and Ben Chehida, A and Elmaleh-Bergès, M and Glasgow, RIC and Thompson, K and Oláhová, M and He, L and Jenkinson, EM and Jahic, A and Belyantseva, IA and Barzik, M and Urquhart, JE and O' Sullivan, J and Williams, SG and Bhaskar, SS and Carrera, S and Blakes, AJM and Banka, S and Yue, WW and Ellingford, JM and Houlden, H and , and Munro, KJ and Friedman, TB and Taylor, RW and Prokisch, H and O'Keefe, RT and Newman, WG}, title = {Biallelic variants in DAP3 result in reduced assembly of the mitoribosomal small subunit with altered intrinsic and extrinsic apoptosis and a Perrault syndrome-spectrum phenotype.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39371131}, support = {/WT_/Wellcome Trust/United Kingdom ; T32 DC000039/DC/NIDCD NIH HHS/United States ; Z01 DC000039/ImNIH/Intramural NIH HHS/United States ; }, abstract = {The mitoribosome synthesizes 13 protein subunits of the oxidative phosphorylation system encoded by the mitochondrial genome. The mitoribosome is composed of 12S rRNA, 16S rRNA and 82 mitoribosomal proteins encoded by nuclear genes. To date, variants in 12 genes encoding mitoribosomal proteins are associated with rare monogenic disorders, and frequently show combined oxidative phosphorylation deficiency. Here, we describe five unrelated individuals with biallelic variants in the DAP3 nuclear gene encoding mitoribosomal small subunit 29 (MRPS29), with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. Assessment of respiratory chain function and proteomic profiling of fibroblasts from affected individuals demonstrated reduced MRPS29 protein levels, and consequently decreased levels of additional protein components of the mitoribosomal small subunit, associated with a combined complex I and IV deficiency. Lentiviral transduction of fibroblasts from affected individuals with wild-type DAP3 cDNA increased DAP3 mRNA expression, and partially rescued protein levels of MRPS7, MRPS9 and complex I and IV subunits, demonstrating the pathogenicity of the DAP3 variants. Protein modelling suggested that DAP3 disease-associated missense variants can impact ADP binding, and in vitro assays demonstrated DAP3 variants can consequently reduce both intrinsic and extrinsic apoptotic sensitivity, DAP3 thermal stability and DAP3 GTPase activity. Our study presents genetic and functional evidence that biallelic variants in DAP3 result in a multisystem disorder of combined oxidative phosphorylation deficiency with pleiotropic presentations, consistent with mitochondrial dysfunction.}, } @article {pmid39378918, year = {2024}, author = {Wang, Z and Wang, R and Sang, Y and Wang, T and Su, Y and Liao, W}, title = {Comparative analysis of mitochondrial genomes of invasive weed Mikania micrantha and its indigenous congener Mikania cordata.}, journal = {International journal of biological macromolecules}, volume = {281}, number = {Pt 1}, pages = {136357}, doi = {10.1016/j.ijbiomac.2024.136357}, pmid = {39378918}, issn = {1879-0003}, mesh = {*Genome, Mitochondrial/genetics ; *Plant Weeds/classification/cytology/genetics ; *Mikania/classification/cytology/genetics ; *Introduced Species ; *Mitochondria/genetics ; Codon Usage ; RNA Editing ; Repetitive Sequences, Nucleic Acid ; Hydrophobic and Hydrophilic Interactions ; Amino Acids/chemistry/genetics/metabolism ; Synteny ; Phylogeny ; Chloroplasts/genetics ; }, abstract = {Mikania micrantha and Mikania cordata are two distinct species in China. The former is notorious as one of the top 100 worst invasive species, whereas the latter is an indigenous species harmless to native plants or the environment. They form an ideal congener pair for comparative studies aimed at deeply understanding the invasion mechanisms of the exotic weed. In this study, we have assembled and annotated the mitogenomes of both species using Illumina and PacBio sequencing data and compared their characteristic differences. The complete mitogenome of M. micrantha is a double-stranded DNA with a length of 336,564 bp, while the mitogenome of M. cordata exhibits a branching structure, consisting of two small circular molecules and six linear molecules, with a combined length totaling 335,444 bp. Compared to M. cordata, M. micrantha has less SSRs, tandem repeats, dispersed repeats, mitochondrial protein coding genes (PCGs). The two plants show similar codon usage patterns. This comparative study has revealed the structure and function of the mitogenomes of the two species and laid a solid foundation for investigating the effects of gene loss and duplication on the development of invasive traits in M. micrantha.}, } @article {pmid39386732, year = {2024}, author = {Korotkevich, E and Conrad, DN and Gartner, ZJ and O'Farrell, PH}, title = {Selection promotes age-dependent degeneration of the mitochondrial genome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39386732}, issn = {2692-8205}, support = {P30 DK026743/DK/NIDDK NIH HHS/United States ; S10 OD028511/OD/NIH HHS/United States ; R33 CA247744/CA/NCI NIH HHS/United States ; P30 CA082103/CA/NCI NIH HHS/United States ; R37 GM037193/GM/NIGMS NIH HHS/United States ; R35 GM136324/GM/NIGMS NIH HHS/United States ; }, abstract = {Somatic mutations in mitochondrial genomes (mtDNA) accumulate exponentially during aging. Using single cell sequencing, we characterize the spectrum of age-accumulated mtDNA mutations in mouse and human liver and identify directional forces that accelerate the accumulation of mutations beyond the rate predicted by a neutral model. "Driver" mutations that give genomes a replicative advantage rose to high cellular abundance and carried along "passenger" mutations, some of which are deleterious. In addition, alleles that alter mtDNA-encoded proteins selectively increased in abundance overtime, strongly supporting the idea of a "destructive" selection that favors genomes lacking function. Overall, this combination of selective forces acting in hepatocytes promotes somatic accumulation of mutations in coding regions of mtDNA that are otherwise conserved in evolution. We propose that these selective processes could contribute to the population prevalence of mtDNA mutations, accelerate the course of heteroplasmic mitochondrial diseases and promote age-associated erosion of the mitochondrial genome.}, } @article {pmid39390511, year = {2024}, author = {Li, Y and Thomas, GWC and Richards, S and Waterhouse, RM and Zhou, X and Pfrender, ME}, title = {Rapid evolution of mitochondrion-related genes in haplodiploid arthropods.}, journal = {BMC biology}, volume = {22}, number = {1}, pages = {229}, pmid = {39390511}, issn = {1741-7007}, mesh = {Animals ; *Evolution, Molecular ; *Arthropods/genetics ; *Genes, Mitochondrial/genetics ; Phylogeny ; Haploidy ; Diploidy ; Oxidative Phosphorylation ; Cell Nucleus/genetics ; }, abstract = {BACKGROUND: Mitochondrial genes and nuclear genes cooperate closely to maintain the functions of mitochondria, especially in the oxidative phosphorylation (OXPHOS) pathway. However, mitochondrial genes among arthropod lineages have dramatic evolutionary rate differences. Haplodiploid arthropods often show fast-evolving mitochondrial genes. One hypothesis predicts that the small effective population size of haplodiploid species could enhance the effect of genetic drift leading to higher substitution rates in mitochondrial and nuclear genes. Alternatively, positive selection or compensatory changes in nuclear OXPHOS genes could lead to the fast-evolving mitochondrial genes. However, due to the limited number of arthropod genomes, the rates of evolution for nuclear genes in haplodiploid species, besides hymenopterans, are largely unknown. To test these hypotheses, we used data from 76 arthropod genomes, including 5 independently evolved haplodiploid lineages, to estimate the evolutionary rates and patterns of gene family turnover of mitochondrial and nuclear genes.

RESULTS: We show that five haplodiploid lineages tested here have fast-evolving mitochondrial genes and fast-evolving nuclear genes related to mitochondrial functions, while nuclear genes not related to mitochondrion showed no significant evolutionary rate differences. Among hymenopterans, bees and ants show faster rates of molecular evolution in mitochondrial genes and mitochondrion-related nuclear genes than sawflies and wasps. With genome data, we also find gene family expansions and contractions in mitochondrion-related genes of bees and ants.

CONCLUSIONS: Our results reject the small population size hypothesis in haplodiploid species. A combination of positive selection and compensatory changes could lead to the observed patterns in haplodiploid species. The elevated evolutionary rates in OXPHOS complex 2 genes of bees and ants suggest a unique evolutionary history of social hymenopterans.}, } @article {pmid39392668, year = {2024}, author = {Princepe, D and de Aguiar, MAM}, title = {Nuclear compensatory evolution driven by mito-nuclear incompatibilities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {42}, pages = {e2411672121}, pmid = {39392668}, issn = {1091-6490}, support = {2018/11187-8//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; 2021/14335-0//ICTP South American Institute for Fundamental Research (ICTP-SAIFR)/ ; 301082/2019-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/ ; }, mesh = {*Cell Nucleus/genetics/metabolism ; *DNA, Mitochondrial/genetics ; Mutation ; Models, Genetic ; Evolution, Molecular ; Mitochondria/genetics/metabolism ; Animals ; Selection, Genetic ; Biological Evolution ; Mutation Rate ; }, abstract = {Mitochondrial function relies on the coordinated expression of mitochondrial and nuclear genes, exhibiting remarkable resilience despite high mitochondrial mutation rates. The nuclear compensation mechanism suggests deleterious mitochondrial alleles drive compensatory nuclear mutations to preserve mito-nuclear compatibility. However, prevalence and factors conditioning this phenomenon remain debated due to its conflicting evidence. Here, we investigate how mito-nuclear incompatibilities impact substitutions in a model for species radiation. Mating success depends on genetic compatibility (nuclear DNA) and spatial proximity. Populations evolve from partially compatible mito-nuclear states, simulating mitochondrial DNA (mtDNA) introgression. Mutations do not confer advantages nor disadvantages, but individual fecundity declines with increasing incompatibilities, selecting for mito-nuclear coordination. We find that selection for mito-nuclear compatibility affects each genome differently based on their initial state. In compatible gene pairs, selection reduces substitutions in both genomes, while in incompatible nuclear genes, it consistently promotes compensation, facilitated by more mismatches. Interestingly, high mitochondrial mutation rates can reduce nuclear compensation by increasing mtDNA rectification, while substitutions in initially compatible nuclear gene are boosted. Finally, the presence of incompatibilities accelerates species radiation, but equilibrium richness is not directly correlated to substitution rates, revealing the complex dynamics triggered by mitochondrial introgression and mito-nuclear coevolution. Our study provides a perspective on nuclear compensation and the role of mito-nuclear incompatibilities in speciation by exploring extreme scenarios and identifying trends that empirical data alone cannot reveal. We emphasize the challenges in detecting these dynamics and propose analyzing specific genomic signatures could shed light on this evolutionary process.}, } @article {pmid39395416, year = {2024}, author = {Greenway, R and De-Kayne, R and Brown, AP and Camarillo, H and Delich, C and McGowan, KL and Nelson, J and Arias-Rodriguez, L and Kelley, JL and Tobler, M}, title = {Integrative analyses of convergent adaptation in sympatric extremophile fishes.}, journal = {Current biology : CB}, volume = {34}, number = {21}, pages = {4968-4982.e7}, doi = {10.1016/j.cub.2024.09.027}, pmid = {39395416}, issn = {1879-0445}, mesh = {Animals ; *Hydrogen Sulfide/metabolism ; *Sympatry ; *Adaptation, Physiological/genetics ; *Extremophiles/genetics/physiology ; Biological Evolution ; Poecilia/genetics/physiology ; }, abstract = {The evolution of independent lineages along replicated environmental transitions frequently results in convergent adaptation, yet the degree to which convergence is present across multiple levels of biological organization is often unclear. Additionally, inherent biases associated with shared ancestry and variation in selective regimes across geographic replicates often pose challenges for confidently identifying patterns of convergence. We investigated a system in which three species of poeciliid fishes sympatrically occur in a toxic spring rich in hydrogen sulfide (H2S) and an adjacent nonsulfidic stream to examine patterns of adaptive evolution across levels of biological organization. We found convergence in morphological and physiological traits and genome-wide patterns of gene expression among all three species. In addition, there were shared signatures of selection on genes encoding H2S toxicity targets in the mitochondrial genomes of each species. However, analyses of nuclear genomes revealed neither evidence for substantial genomic islands of divergence around genes involved in H2S toxicity and detoxification nor substantial congruence of strongly differentiated regions across population pairs. These non-convergent, heterogeneous patterns of genomic divergence may indicate that sulfide tolerance is highly polygenic, with shared allele frequency shifts present at many loci with small effects along the genome. Alternatively, H2S tolerance may involve substantial genetic redundancy, with non-convergent, lineage-specific variation at multiple loci along the genome underpinning similar changes in phenotypes and gene expression. Overall, we demonstrate variability in the extent of convergence across organizational levels and highlight the challenges of linking patterns of convergence across scales.}, } @article {pmid39404344, year = {2024}, author = {Storer, ISR and Sastré-Velásquez, LE and Easter, T and Mertens, B and Dallemulle, A and Bottery, M and Tank, R and Offterdinger, M and Bromley, MJ and van Rhijn, N and Gsaller, F}, title = {Shining a light on the impact of antifungals on Aspergillus fumigatus subcellular dynamics through fluorescence imaging.}, journal = {Antimicrobial agents and chemotherapy}, volume = {68}, number = {11}, pages = {e0080324}, pmid = {39404344}, issn = {1098-6596}, support = {219551/Z/19/Z//Wellcome Trust (WT)/ ; P 31093/FWF_/Austrian Science Fund FWF/Austria ; P35951, P31093//Austrian Science Fund (FWF)/ ; 226408/Z/22/Z//Wellcome Trust (WT)/ ; /WT_/Wellcome Trust/United Kingdom ; MR/N013751/1//UKRI | Medical Research Council (MRC)/ ; 219551/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Aspergillus fumigatus/drug effects/metabolism ; *Antifungal Agents/pharmacology ; *Voriconazole/pharmacology ; *Amphotericin B/pharmacology ; *Optical Imaging/methods ; Hyphae/drug effects ; Spores, Fungal/drug effects ; Luminescent Proteins/metabolism/genetics ; Mitochondria/drug effects/metabolism ; Microscopy, Fluorescence/methods ; Cell Membrane/drug effects/metabolism ; }, abstract = {Fluorescent proteins (FPs) are indispensable tools used for molecular imaging, single-cell dynamics, imaging in infection models, and more. However, next-generation FPs have yet to be characterized in Aspergillus. Here, we characterize 18 FPs in the pathogenic filamentous fungus Aspergillus fumigatus spanning the visible light spectrum. We report on in vivo FP brightness in hyphal and spore morphotypes and show how a fluoropyrimidine-based selection system can be used to iteratively introduce four distinct FPs enabling the simultaneous visualization of the cell membrane, mitochondria, peroxisomes, and vacuoles. Using this strain, we describe and compare the dynamic responses of organelles to stresses induced by voriconazole, amphotericin B, and the novel antifungal drugs olorofim and manogepix. The expansion to the fluorescent genetic toolbox will overcome boundaries in research applications that involve fluorescence imaging in filamentous fungi.}, } @article {pmid39408807, year = {2024}, author = {Wang, Y and Shi, Y and Li, H and Wang, S and Wang, A}, title = {Whole Genome Identification and Biochemical Characteristics of the Tilletia horrida Cytochrome P450 Gene Family.}, journal = {International journal of molecular sciences}, volume = {25}, number = {19}, pages = {}, pmid = {39408807}, issn = {1422-0067}, support = {32001490//National Natural Science Foundation of China/ ; }, mesh = {*Cytochrome P-450 Enzyme System/genetics/metabolism ; Oryza/microbiology/genetics ; Multigene Family ; Phylogeny ; Fungal Proteins/genetics/metabolism ; Genome, Fungal ; Gene Expression Regulation, Fungal ; Basidiomycota/genetics/enzymology ; Plant Diseases/microbiology/genetics ; Promoter Regions, Genetic ; }, abstract = {Rice kernel smut caused by the biotrophic basidiomycete fungus Tilletia horrida causes significant yield losses in hybrid rice-growing areas around the world. Cytochrome P450 (CYP) enzyme is a membrane-bound heme-containing monooxygenase. In fungi, CYPs play a role in cellular metabolism, adaptation, pathogenicity, decomposition, and biotransformation of hazardous chemicals. In this study, we identified 20 CYP genes based on complete sequence analysis and functional annotation from the T. horrida JY-521 genome. The subcellular localization, conserved motifs, and structures of these 20 CYP genes were further predicted. The ThCYP genes exhibit differences in gene structures and protein motifs. Subcellular localization showed that they were located in the plasma membrane, cytoplasm, nucleus, mitochondria, and extracellular space, indicating that they had multiple functions. Some cis-regulatory elements related to stress response and plant hormones were found in the promoter regions of these genes. Protein-protein interaction (PPI) analysis showed that several ThCYP proteins interact with multiple proteins involved in the ergosterol pathway. Moreover, the expression of 20 CYP genes had different responses to different infection time points and underwent dynamic changes during T. horrida JY-521 infection, indicating that these genes were involved in the interaction with rice and their potential role in the pathogenic mechanism. These results provided valuable resources for elucidating the structure of T. horrida CYP family proteins and laid an important foundation for further research of their roles in the pathogenesis.}, } @article {pmid39409762, year = {2024}, author = {Bakhoum, AJS and Marigo, AM and Poonlaphdecha, S and Ribas, A and Morand, S and Miquel, J}, title = {Ultrastructural Characteristics of the Mature Spermatozoon of Artyfechinostomum malayanum (Digenea: Echinostomatidae), an Intestinal Parasite of Rattus norvegicus (Rodentia: Muridae) in Vietnam.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {19}, pages = {}, pmid = {39409762}, issn = {2076-2615}, abstract = {The study of sperm characteristics has proven useful for elucidating interrelationships in several groups of Platyhelminthes, such as digeneans. Thus, in the present work, the ultrastructural organization of the mature spermatozoon of the digenean Artyfechinostomum malayanum (Echinostomatidae), a parasite of Rattus norvegicus (Rodentia: Muridae) from Dong Thap Province, Vietnam, was investigated for the first time using transmission electron microscopy. The male gamete of A. malayanum exhibits two axonemes of different lengths, showing the 9 + '1' pattern of the Trepaxonemata, a nucleus, two mitochondria, two lateral expansions, two bundles of parallel cortical microtubules, external ornamentation, spine-like bodies, and granules of glycogen. Thus, the mature spermatozoon follows a Type V sperm model proposed for digeneans. We also highlight some noteworthy characteristics in Echinostomatidae with possible phylogenetic implications, such as two lateral expansions in the anterior region of the spermatozoon and two mitochondria.}, } @article {pmid39417543, year = {2025}, author = {Tu, F and Qiao, Y and Zhao, W and Wu, T}, title = {Comparative selective pressure analysis on mitochondrial protein-coding genes in flying squirrels (Pteromyini) and tree squirrels (Sciurini).}, journal = {Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis}, volume = {35}, number = {3-4}, pages = {75-83}, doi = {10.1080/24701394.2024.2416179}, pmid = {39417543}, issn = {2470-1408}, mesh = {Animals ; *Sciuridae/genetics/classification ; Phylogeny ; Genome, Mitochondrial ; *Mitochondrial Proteins/genetics ; *Selection, Genetic ; *Genes, Mitochondrial ; }, abstract = {Different animal groups with varying locomotion modes may have unique energy requirements. Mitochondria produce adenosine triphosphate (ATP) and reactive oxygen species via oxidative phosphorylation to support organisms energy requirements. The tribes Pteromyini (flying squirrels) and Sciurini (tree squirrels), two closely related taxa within the family Sciuridae, exhibit distinct locomotion modes, energy requirements, and likely face different selective pressures on mitochondrial protein-coding genes (PCGs). We analysed 13 mitochondrial genome sequences from species belonging to the tribe Pteromyini and 117 from species belonging to the tribe Sciurini. Phylogenetic analysis revealed Pteromyini and Sciurini formed a sister relationship within the family Sciuridae. Among the 13 PCGs, ATP8 exhibited the highest dN/dS values, while COX1 showed the lowest. The background selection ratio (ω2) values for six genes (ND1, ND2, ND4, ATP6, ND5, and COX3) in Pteromyini were lower than the foreground selection ratio (ω0) values observed in Sciurini. A RELAX analysis revealed that CYTB, ND4, ATP6, and COX3 genes experienced intensified in selection strength. BUSTED analysis identified stronger signatures of diversifying selection in CYTB and ATP6, highlighting amino acid changes. MEME identified episodic diversifying selection at specific sites among eight PCGs. These findings revealed distinct selective pressures on PCGs in flying and tree squirrels.}, } @article {pmid39417916, year = {2024}, author = {Stefano, GB and Weissenberger, S and Ptacek, R and Anders, M and Raboch, J and Büttiker, P}, title = {Viruses and Mitochondrial Dysfunction in Neurodegeneration and Cognition: An Evolutionary Perspective.}, journal = {Cellular and molecular neurobiology}, volume = {44}, number = {1}, pages = {68}, pmid = {39417916}, issn = {1573-6830}, mesh = {Humans ; *Mitochondria/metabolism ; Animals ; *Neurodegenerative Diseases/metabolism/pathology/physiopathology ; *Biological Evolution ; Viruses ; Cognition/physiology ; }, abstract = {Mitochondria, the cellular powerhouses with bacterial evolutionary origins, play a pivotal role in maintaining neuronal function and cognitive health. Several viruses have developed sophisticated mechanisms to target and disrupt mitochondrial function which contribute to cognitive decline and neurodegeneration. The interplay between viruses and mitochondria might be traced to their co-evolutionary history with bacteria and may reflect ancient interactions that have shaped modern mitochondrial biology.}, } @article {pmid39437314, year = {2024}, author = {Ozerova, I and Fallmann, J and Mörl, M and Bernt, M and Prohaska, SJ and Stadler, PF}, title = {Aberrant Mitochondrial tRNA Genes Appear Frequently in Animal Evolution.}, journal = {Genome biology and evolution}, volume = {16}, number = {11}, pages = {}, pmid = {39437314}, issn = {1759-6653}, support = {451363052//German Research Foundation/ ; }, mesh = {Animals ; *RNA, Transfer/genetics ; *Evolution, Molecular ; *Genome, Mitochondrial ; Phylogeny ; Genes, Mitochondrial ; Mitochondria/genetics ; RNA, Mitochondrial/genetics ; }, abstract = {Mitochondrial tRNAs have acquired a diverse portfolio of aberrant structures throughout metazoan evolution. With the availability of more than 12,500 mitogenome sequences, it is essential to compile a comprehensive overview of the pattern changes with regard to mitochondrial tRNA repertoire and structural variations. This, of course, requires reanalysis of the sequence data of more than 250,000 mitochondrial tRNAs with a uniform workflow. Here, we report our results on the complete reannotation of all mitogenomes available in the RefSeq database by September 2022 using mitos2. Based on the individual cases of mitochondrial tRNA variants reported throughout the literature, our data pinpoint the respective hotspots of change, i.e. Acanthocephala (Lophotrochozoa), Nematoda, Acariformes, and Araneae (Arthropoda). Less dramatic deviations of mitochondrial tRNAs from the norm are observed throughout many other clades. Loss of arms in animal mitochondrial tRNA clearly is a phenomenon that occurred independently many times, not limited to a small number of specific clades. The summary data here provide a starting point for systematic investigations into the detailed evolutionary processes of structural reduction and loss of mitochondrial tRNAs as well as a resource for further improvements of annotation workflows for mitochondrial tRNA annotation.}, } @article {pmid39454737, year = {2024}, author = {Liu, X and Liu, N and Jing, X and Khan, H and Yang, K and Zheng, Y and Nie, Y and Song, H and Huang, Y}, title = {Genomic and transcriptomic perspectives on the origin and evolution of NUMTs in Orthoptera.}, journal = {Molecular phylogenetics and evolution}, volume = {201}, number = {}, pages = {108221}, doi = {10.1016/j.ympev.2024.108221}, pmid = {39454737}, issn = {1095-9513}, mesh = {Animals ; *Phylogeny ; *Orthoptera/genetics/classification ; *Pseudogenes/genetics ; *DNA, Mitochondrial/genetics ; *Transcriptome ; *Evolution, Molecular ; Cell Nucleus/genetics ; Genome, Mitochondrial/genetics ; Genome, Insect/genetics ; }, abstract = {Nuclear mitochondrial pseudogenes (NUMTs) result from the transfer of mitochondrial DNA (mtDNA) to the nuclear genome. NUMTs, as "frozen" snapshots of mitochondria, can provide insights into diversification patterns. In this study, we analyzed the origins and insertion frequency of NUMTs using genome assembly data from ten species in Orthoptera. We found divergences between NUMTs and contemporary mtDNA in Orthoptera ranging from 0 % to 23.78 %. The results showed that the number of NUMT insertions was significantly positively correlated with the content of transposable elements in the genome. We found that 39.09 %-68.65 % of the NUMTs flanking regions (2,000 bp) contained retrotransposons, and more NUMTs originated from mitochondrial rDNA regions. Based on the analysis of the mitochondrial transcriptome, we found a potential mechanism of NUMT integration: mitochondrial transcripts are reverse transcribed into double-stranded DNA and then integrated into the genome. The probability of this mechanism occurring accounts for 0.30 %-1.02 % of total mitochondrial nuclear transfer events. Finally, based on the phylogenetic tree constructed using NUMTs and contemporary mtDNA, we provide insights into ancient evolutionary events such as species-specific "autaponumts" and "synaponumts" shared among different species, as well as post-integration duplication events.}, } @article {pmid39456251, year = {2024}, author = {Indo, HP and Chatatikun, M and Nakanishi, I and Matsumoto, KI and Imai, M and Kawakami, F and Kubo, M and Abe, H and Ichikawa, H and Yonei, Y and Beppu, HJ and Minamiyama, Y and Kanekura, T and Ichikawa, T and Phongphithakchai, A and Udomwech, L and Sukati, S and Charong, N and Somsak, V and Tangpong, J and Nomura, S and Majima, HJ}, title = {The Roles of Mitochondria in Human Being's Life and Aging.}, journal = {Biomolecules}, volume = {14}, number = {10}, pages = {}, pmid = {39456251}, issn = {2218-273X}, support = {Grant-in-Aid for Research Project, No. 2022-1013//Kitasato University School of Allied Health Sciences/ ; JPMXP1323015488//MEXT Promotion of Development of a Joint Usage/Research System Project: Coalition of Universities for Research Excellence Program (CURE)/ ; }, mesh = {Humans ; *Mitochondria/metabolism ; *Aging/metabolism ; Archaea/metabolism ; Bacteria/metabolism ; }, abstract = {The universe began 13.8 billion years ago, and Earth was born 4.6 billion years ago. Early traces of life were found as soon as 4.1 billion years ago; then, ~200,000 years ago, the human being was born. The evolution of life on earth was to become individual rather than cellular life. The birth of mitochondria made this possible to be the individual life. Since then, individuals have had a limited time of life. It was 1.4 billion years ago that a bacterial cell began living inside an archaeal host cell, a form of endosymbiosis that is the development of eukaryotic cells, which contain a nucleus and other membrane-bound compartments. The bacterium started to provide its host cell with additional energy, and the interaction eventually resulted in a eukaryotic cell, with both archaeal (the host cell) and bacterial (mitochondrial) origins still having genomes. The cells survived high concentrations of oxygen producing more energy inside the cell. Further, the roles of mitochondria in human being's life and aging will be discussed.}, } @article {pmid39456791, year = {2024}, author = {Li, J and Ma, M and Zeng, T and Gu, L and Zhu, B and Wang, H and Du, X and Zhu, X}, title = {Genome-Wide Identification of the Peanut ASR Gene Family and Its Expression Analysis under Abiotic Stress.}, journal = {International journal of molecular sciences}, volume = {25}, number = {20}, pages = {}, pmid = {39456791}, issn = {1422-0067}, support = {QSXM2022-B10//Xuye Du/ ; QSXM2022-B30//Xuye Du/ ; QSXM2022-15//Xuye Du/ ; }, mesh = {*Arachis/genetics/metabolism ; *Stress, Physiological/genetics ; *Gene Expression Regulation, Plant ; *Plant Proteins/genetics/metabolism ; *Multigene Family ; Phylogeny ; Abscisic Acid/metabolism/pharmacology ; Droughts ; Genome, Plant ; Gene Expression Profiling ; }, abstract = {Peanut (Arachis hypogaea L.) is one of the most important oil and food legume crops worldwide. ASR (abscisic acid, stress, ripening) plays extremely important roles in plant growth and development, fruit ripening, pollen development, and stress. Here, six ASR genes were identified in peanut. Structural and conserved motif analyses were performed to identify common ABA/WDS structural domains. The vast majority of ASR genes encoded acidic proteins, all of which are hydrophilic proteins and localized on mitochondria and nucleus, respectively. The cis-element analysis revealed that some cis-regulatory elements were related to peanut growth and development, hormone, and stress response. Under normal growth conditions, AhASR4 and AhASR5 were expressed in all tissues of peanut plants. Quantitative real-time PCR (qRT-PCR) results indicated that peanut ASR genes exhibited complex expression patterns in response to abiotic stress. Notably, under drought and cadmium (Cd) stress, the expression levels of AhASR4 and AhASR5 were significantly upregulated, suggesting that these genes may play a crucial role in the peanut plant's resistance to such stressors. These results provide a theoretical basis for studying the evolution, expression, and function of the peanut ASR gene family and will provide valuable information in the identification and screening of genes for peanut stress tolerance breeding.}, } @article {pmid39457076, year = {2024}, author = {Zhu, K and Zhang, Y and Shen, W and Yu, L and Li, D and Zhang, H and Miao, C and Ding, X and Jiang, Y}, title = {Genome-Wide Analysis and Expression Profiling of Glyoxalase Gene Families Under Abiotic Stresses in Cucumber (Cucumis sativus L.).}, journal = {International journal of molecular sciences}, volume = {25}, number = {20}, pages = {}, pmid = {39457076}, issn = {1422-0067}, support = {22ZR1460500//The Natural Science Foundation of Shanghai/ ; [2022]022//The Excellent Team Program of the Shanghai Academy of Agricultural Sciences/ ; }, mesh = {*Cucumis sativus/genetics/enzymology ; *Stress, Physiological/genetics ; *Gene Expression Regulation, Plant ; *Phylogeny ; *Lactoylglutathione Lyase/genetics/metabolism ; *Multigene Family ; Thiolester Hydrolases/genetics/metabolism ; Plant Proteins/genetics/metabolism ; Gene Expression Profiling ; Genome-Wide Association Study ; Genome, Plant ; Hydroxyacylglutathione Hydrolase ; }, abstract = {The glyoxalase pathway, consisting of glyoxalase I (GLYI) and glyoxalase II (GLYII), is an enzymatic system that converts cytotoxic methylglyoxal to non-toxic S-D-lactoylglutathione. Although the GLY gene family has been analyzed in Arabidopsis, rice, grape, cabbage, and soybean, cucumber studies are lacking. Here, we analyzed the cucumber GLY gene family, identifying 13 CsGLYI and 2 CsGLYII genes. Furthermore, we investigated the physicochemical properties, phylogenetic relationships, chromosomal localization and colinearity, gene structure, conserved motifs, cis-regulatory elements, and protein-protein interaction networks of the CsGLY family. They were primarily localized in the cytoplasm, chloroplasts, and mitochondria, with a minor presence in the nucleus. The classification of CsGLYI and CsGLYII genes into five classes closely resembled the homologous genes in Arabidopsis and soybean. Additionally, hormone-responsive elements dominated the promoter region of GLY genes, alongside light- and stress-responsive elements. The predicted interaction proteins of CsGLYIs and CsGLYIIs exerted a significant role in cellular respiration, amino acid synthesis, and metabolism, as well as methylglyoxal catabolism. In addition, the expression profiles of GLY genes were distinct in different tissues of cucumber as well as under diverse abiotic stresses. This study is conducive to the further exploration of the functional diversity among glyoxalase genes and the mechanisms of stress responses in cucumber.}, } @article {pmid39462818, year = {2025}, author = {Arce, LF and Facelli Fernández, F and Giorello, N and Butti, M and Maldonado, LL and Arrabal, JP and Natalini, MB and Kowalewski, M and Pedrassani, D and Silveira Mascarenhas, C and da Silva Rappeti, JC and Zilli, F and Beldomenico, PM and Lia, V and Franchini, GR and Kamenetzky, L}, title = {Genetic diversity of Dioctophyme renale in Southern South America.}, journal = {Parasitology}, volume = {152}, number = {8}, pages = {776-786}, pmid = {39462818}, issn = {1469-8161}, mesh = {Animals ; Animals, Wild/parasitology ; Biomarkers ; *Carnivora/parasitology ; Cyclooxygenase 1/genetics ; *Dioctophymatoidea/genetics ; *Enoplida Infections/epidemiology/transmission/veterinary ; Mitochondria/genetics ; NADH Dehydrogenase/genetics ; Phylogeny ; Phylogeography ; South America ; Male ; Female ; }, abstract = {Dioctophyme renale, the giant kidney worm, is a nematode related to Trichuris sp and is distributed worldwide. These parasites locate in the kidney of their definitive hosts (mainly belonging to the order Carnivora) and have an indirect life cycle with an annelid as the main intermediate host. Humans are rarely affected, but in those that are, 1 or both kidneys are destroyed. In South America, D. renale is widespread in riparian regions where changing climatic conditions, environmental degradation, and compromised sanitation are increasing the risk of distribution of this parasite, including humans. Here, we provide the descriptions of the genetic diversity of the parasite in the region by analysing 73 adult D. renale samples collected from domestic and wild carnivores. The most common hosts were (Canis lupus familiaris) and maned wolf (Chrysocyon brachyurus Fam. Canidae) among domestic and wild carnivores, respectively. This work shows the descriptions of the genetic diversity of this parasite complementing molecular methods and classical and probabilistic phylogeography. Our results strongly suggest that this parasite has been present on the continent long enough to develop local genetic variants. Also, the phylogenies show transmission between localities and bidirectional transmission between domestic and wild species. We now have new tools to understand the ecological dynamics of this parasite such as molecular markers to study its genetic diversity as well as for identification and reporting in cryptic cases.}, } @article {pmid39465975, year = {2024}, author = {Cheng, YK and Zhang, Y and Zhang, ZY and Cong, PK and Feng, JY and Zhang, R and Long, SR and Zhang, X and Wang, ZQ and Cui, J}, title = {Biological characteristics and functions of a novel glutamate dehydrogenase from Trichinella spiralis.}, journal = {Parasite (Paris, France)}, volume = {31}, number = {}, pages = {65}, pmid = {39465975}, issn = {1776-1042}, support = {82172300//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Glutamate Dehydrogenase/metabolism/genetics ; *Trichinella spiralis/enzymology/genetics/growth & development ; Female ; Cloning, Molecular ; Larva/enzymology/growth & development/genetics ; Amino Acid Sequence ; RNA Interference ; Phylogeny ; Male ; Helminth Proteins/genetics/metabolism ; Sequence Alignment ; }, abstract = {Glutamate dehydrogenase (GDH) plays an important role in the metabolism of organisms. Its high abundance in mitochondria in particular highlights its core role in cellular physiological processes. GDH catalyzes the mutual conversion between L-glutamic acid and α-ketoglutaric acids. At the same time, this transformation is accompanied by the oxidation-reduction of NAD(H) or NADP(H). This process not only helps to link amino acid metabolism with sugar metabolism, but also helps maintain the balance of intracellular pH and nitrogen homeostasis. In this study, a novel Trichinella spiralis glutamate dehydrogenase (TsGDH) was cloned, expressed and identified. The results revealed that TsGDH was expressed at various stages of development of the nematode T. spiralis, with higher expression levels in the adult worm stage, and was mainly localized in the cuticle, muscular layer, stichosome and female intrauterine embryos. After RNAi treatment, larval natural TsGDH enzyme activity was obviously reduced, and metabolism, molting, growth and reproduction were also significantly inhibited. The results indicate that TsGDH plays an important role in the development and survival of T. spiralis, and it may be a potential molecular target of anti-Trichinella vaccines and drugs.}, } @article {pmid39467848, year = {2024}, author = {Büttiker, P and Boukherissa, A and Weissenberger, S and Ptacek, R and Anders, M and Raboch, J and Stefano, GB}, title = {Cognitive Impact of Neurotropic Pathogens: Investigating Molecular Mimicry through Computational Methods.}, journal = {Cellular and molecular neurobiology}, volume = {44}, number = {1}, pages = {72}, pmid = {39467848}, issn = {1573-6830}, mesh = {Humans ; *Molecular Mimicry ; Computational Biology/methods ; Cognition/physiology ; Protein Binding ; Amino Acid Sequence ; Viral Proteins/metabolism/chemistry ; Models, Molecular ; }, abstract = {Neurotropic pathogens, notably, herpesviruses, have been associated with significant neuropsychiatric effects. As a group, these pathogens can exploit molecular mimicry mechanisms to manipulate the host central nervous system to their advantage. Here, we present a systematic computational approach that may ultimately be used to unravel protein-protein interactions and molecular mimicry processes that have not yet been solved experimentally. Toward this end, we validate this approach by replicating a set of pre-existing experimental findings that document the structural and functional similarities shared by the human cytomegalovirus-encoded UL144 glycoprotein and human tumor necrosis factor receptor superfamily member 14 (TNFRSF14). We began with a thorough exploration of the Homo sapiens protein database using the Basic Local Alignment Search Tool (BLASTx) to identify proteins sharing sequence homology with UL144. Subsequently, we used AlphaFold2 to predict the independent three-dimensional structures of UL144 and TNFRSF14. This was followed by a comprehensive structural comparison facilitated by Distance-Matrix Alignment and Foldseek. Finally, we used AlphaFold-multimer and PPIscreenML to elucidate potential protein complexes and confirm the predicted binding activities of both UL144 and TNFRSF14. We then used our in silico approach to replicate the experimental finding that revealed TNFRSF14 binding to both B- and T-lymphocyte attenuator (BTLA) and glycoprotein domain and UL144 binding to BTLA alone. This computational framework offers promise in identifying structural similarities and interactions between pathogen-encoded proteins and their host counterparts. This information will provide valuable insights into the cognitive mechanisms underlying the neuropsychiatric effects of viral infections.}, } @article {pmid39468759, year = {2025}, author = {Deconinck, A and Madalone, OF and Willett, CS}, title = {Absence of heterosis for hypoxia tolerance in F1 hybrids of Tigriopus californicus.}, journal = {The Journal of heredity}, volume = {116}, number = {2}, pages = {149-158}, doi = {10.1093/jhered/esae061}, pmid = {39468759}, issn = {1465-7333}, support = {IOS-2029156 and IOS-1555959//The National Science Foundation/ ; }, mesh = {*Hybrid Vigor/genetics ; Animals ; *Hybridization, Genetic ; *Hypoxia/genetics ; Mitochondria/genetics ; Male ; Female ; Genetic Fitness ; }, abstract = {Hybridization produces a range of outcomes from advantageous to disadvantageous, and a goal of genetic research is to understand the gene interactions that generate these outcomes. Interactions between cytoplasmic elements, such as mitochondria, and the nucleus may be particularly vulnerable to accruing disadvantageous combinations as a result of their different rates of evolution. Consequently, mitonuclear incompatibilities may play an important role in hybrid outcomes even if their negative impacts could be masked for some fitness measures by heterosis in first-generation (F1) hybrids. We used Tigriopus californicus, a model system for mitonuclear incompatibilities that is also known for exhibiting heterosis in the F1 generation and outbreeding depression in later generations, to test whether heterosis or outbreeding depression would occur when mitonuclear mismatch was paired with a stress that heavily impacts mitochondrial processes-specifically, hypoxia. We generated 284 parental and 436 F1 hybrids from four population crosses (720 total) and compared parental and F1 populations for hypoxia tolerance. We observed that, on average, F1 hybrids were less likely to survive a hypoxia stress test than parental populations, although we did not detect a statistically significant trend (P = 0.246 to 0.614). This suggests that hypoxia may be a particularly intense stressor for mitonuclear coordination and hybridization outcomes vary by trait.}, } @article {pmid39474867, year = {2024}, author = {Barcytė, D and Jaške, K and Pánek, T and Yurchenko, T and Ševčíková, T and Eliášová, A and Eliáš, M}, title = {A cryptic plastid and a novel mitochondrial plasmid in Leucomyxa plasmidifera gen. and sp. nov. (Ochrophyta) push the frontiers of organellar biology.}, journal = {Open biology}, volume = {14}, number = {10}, pages = {240022}, pmid = {39474867}, issn = {2046-2441}, support = {//European Regional Development Fund/ ; //Grantová Agentura České Republiky/ ; //Univerzita Karlova v Praze/ ; }, mesh = {*Plasmids/genetics ; *Phylogeny ; *Genome, Plastid ; *Plastids/genetics/metabolism ; Mitochondria/genetics/metabolism ; Genome, Mitochondrial ; Evolution, Molecular ; }, abstract = {Complete plastid loss seems to be very rare among secondarily non-photosynthetic eukaryotes. Leukarachnion sp. PRA-24, an amoeboid colourless protist related to the photosynthetic algal class Synchromophyceae (Ochrophyta), is a candidate for such a case based on a previous investigation by transmission electron microscopy. Here, we characterize this organism in further detail and describe it as Leucomyxa plasmidifera gen. et sp. nov., additionally demonstrating it is the first known representative of a broader clade of non-photosynthetic ochrophytes. We recovered its complete plastid genome, exhibiting a reduced gene set similar to plastomes of other non-photosynthetic ochrophytes, yet being even more extreme in sequence divergence. Identification of components of the plastid protein import machinery in the L. plasmidifera transcriptome assembly corroborated that the organism possesses a cryptic plastid organelle. According to our bioinformatic reconstruction, the plastid contains a unique combination of biosynthetic pathways producing haem, a folate precursor and tocotrienols. As another twist to its organellar biology, L. plasmidifera turned out to contain an unusual long insertion in its mitogenome related to a newly discovered mitochondrial plasmid exhibiting unprecedented features in terms of its size and coding capacity. Combined, our work uncovered further striking outcomes of the evolutionary course of semiautonomous organelles in protists.}, } @article {pmid39484454, year = {2024}, author = {Keeney, JG and Astling, D and Andries, V and Vandepoele, K and Anderson, N and Davis, JM and Lopert, P and Vandenbussche, J and Gevaert, K and Staes, A and Paukovich, N and Vögeli, B and Jones, KL and van Roy, F and Patel, M and Sikela, JM}, title = {Olduvai domain expression downregulates mitochondrial pathways: implications for human brain evolution and neoteny.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39484454}, issn = {2692-8205}, support = {R01 GM150642/GM/NIGMS NIH HHS/United States ; R01 MH081203/MH/NIMH NIH HHS/United States ; R01 MH108684/MH/NIMH NIH HHS/United States ; R01 NS039587/NS/NINDS NIH HHS/United States ; }, abstract = {Encoded by the NBPF gene family, Olduvai (formerly DUF1220) protein domains have undergone the largest human lineage-specific copy number expansion of any coding region in the genome. Olduvai copy number shows a linear relationship with several brain size-related measures and cortical neuron number among primates and with normal and disease-associated (micro- and macrocephaly) variation in brain size in human populations. While Olduvai domains have been shown to promote proliferation of neural stem cells, the mechanism underlying such effects has remained unclear. Here, we investigate the function of Olduvai by transcriptome and proteome analyses of cells overexpressing NBPF1, a gene encoding 7 Olduvai domains. Our results from both RNAseq and mass spectrometry approaches suggest a potential downregulation of mitochondria. In our proteomics study, a Gene Ontology (GO) enrichment analysis for the downregulated proteins revealed a striking overrepresentation of the biological process related to the mitochondrial electron transport chain (p value: 1.81e-11) and identified deregulation of the NADH dehydrogenase activity (p value: 2.43e-11) as the primary molecular function. We verify the reduction of apparent mitochondria via live-cell imaging experiments. Given these and previous Olduvai findings, we suggest that the Olduvai-mediated, dosage-dependent reduction in available energy via mitochondrial downregulation may have resulted in a developmental slowdown such that the neurogenic window among primates, and most extremely in humans, was expanded over a greater time interval, allowing for production of greater numbers of neurons and a larger brain. We further suggest that such a slowdown may extend to other developmental processes that also exhibit neotenic features.}, } @article {pmid39488375, year = {2024}, author = {Leka, KP and Wideman, JG}, title = {An introduction to comparative genomics, EukProt, and the reciprocal best hit (RBH) method for bench biologists: Ancestral phosphorylation of Tom22 in eukaryotes as a case study.}, journal = {Methods in enzymology}, volume = {707}, number = {}, pages = {209-234}, doi = {10.1016/bs.mie.2024.07.036}, pmid = {39488375}, issn = {1557-7988}, mesh = {*Genomics/methods ; Phosphorylation ; Eukaryota/genetics/metabolism ; Humans ; Animals ; Evolution, Molecular ; Databases, Protein ; Amino Acid Sequence ; }, abstract = {Comparative genomics is a useful approach for hypothesis generation for future functional investigations at the bench. However, most bench biologists shy away from computational methods. Here we reintroduce the simple but extremely effective Reciprocal Best Hit method for inferring protein orthologues. Because taxon set delimitation is perhaps the most important step in comparative genomics, we introduce The Comparative Set, a taxonomically representative subset of EukProt, a comprehensive eukaryotic predicted proteome database. After introducing the basic methods, we provide a step-by-step guide, including screen shots, for a case study on collecting Tom22 sequences from diverse eukaryotes. As an example of possible downstream analyses, we show that Tom22 proteins from diverse eukaryotes are likely regulated by conserved kinases at several sites. Though the sites evolve quickly, the processes and functions involved are likely ancestral and conserved across many eukaryotes.}, } @article {pmid39495610, year = {2024}, author = {Tian, X and Li, F and Lin, J and Xu, Y and Tian, K and Gu, L and Zhang, Y and Xu, JR and Wang, Q}, title = {Ancient duplications, multidimensional specializations, and defense role of hexokinases in wheat.}, journal = {The Plant journal : for cell and molecular biology}, volume = {120}, number = {6}, pages = {2456-2467}, doi = {10.1111/tpj.17122}, pmid = {39495610}, issn = {1365-313X}, support = {2022YFD1400100//National Key Research and Development Program of China/ ; 32072505//National Natural Science Foundation of China/ ; 32370212//National Natural Science Foundation of China/ ; }, mesh = {*Triticum/genetics/enzymology/immunology ; *Hexokinase/genetics/metabolism ; *Plant Proteins/genetics/metabolism ; *Gene Duplication ; *Phylogeny ; Gene Expression Regulation, Plant ; Plant Diseases/genetics/immunology/microbiology ; Mitochondria/genetics/enzymology/metabolism ; }, abstract = {Hexokinases (HXKs), which sense and catalyze cellular sugar, play a critical role in the growth and development of various plants, including wheat, a primary source of human calories frequently attacked by fungal pathogens. However, the evolutionary dynamics and functional diversification of HXKs in wheat, particularly their roles in plant defense, remain unclear. Here, we discovered that the wheat hexokinase gene family originated through multiple ancient gene duplications across different plant lineages and has undergone comprehensive, multidimensional functional specialization in gene expression, subcellular localization, enzyme activity, and regulation of plant defense responses. Gene expression analysis suggests that two-thirds of the TaHXK genes are responsive to fungal infection. Subcellular analysis reveals that while six TaHXKs are localized in mitochondria, three TaHXKs from different phylogenetic branches are sorted into other cellular compartments. Notably, biochemical analysis shows that TaHXKs in mitochondria differ in their glucose-catalyzing activity, with TaHXK5 and TaHXK3 exhibiting the highest and lowest enzyme activity, respectively. Consistently, transient expression analysis suggests that TaHXK5 induces various plant defense responses, while TaHXK3 is defective in activating some plant defense responses. Furthermore, inactivation of the glucokinase activity of TaHXK5 compromised its function in defense activation, suggesting that mitochondrial TaHXKs display functional divergence in both enzyme activity and defense-inducing activity that are intrinsically connected. Overall, our findings reveal that the multidimensional specialization events following the ancient duplication events may have shaped the functional diversity of HXKs in wheat, shedding light on their evolutionary dynamics and potentially contributing to the improvement of wheat defense.}, } @article {pmid39503889, year = {2024}, author = {Berrissou, C and Cognat, V and Koechler, S and Bergdoll, M and Duchêne, AM and Drouard, L}, title = {Extensive import of nucleus-encoded tRNAs into chloroplasts of the photosynthetic lycophyte, Selaginella kraussiana.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {46}, pages = {e2412221121}, pmid = {39503889}, issn = {1091-6490}, support = {ANR-10-IDEX-0002//Agence Nationale de la Recherche (ANR)/ ; ANR-17-EURE-0023//Agence Nationale de la Recherche (ANR)/ ; }, mesh = {*RNA, Transfer/genetics/metabolism ; *Chloroplasts/metabolism/genetics ; *Selaginellaceae/genetics/metabolism ; *Photosynthesis/genetics ; *Cell Nucleus/metabolism/genetics ; RNA, Plant/genetics/metabolism ; }, abstract = {Over the course of evolution, land plant mitochondrial genomes have lost many transfer RNA (tRNA) genes and the import of nucleus-encoded tRNAs is essential for mitochondrial protein synthesis. By contrast, plastidial genomes of photosynthetic land plants generally possess a complete set of tRNA genes and the existence of plastidial tRNA import remains a long-standing question. The early vascular plants of the Selaginella genus show an extensive loss of plastidial tRNA genes while retaining photosynthetic capacity, and represent an ideal model for answering this question. Using purification, northern blot hybridization, and high-throughput tRNA sequencing, a global analysis of total and plastidial tRNA populations was undertaken in Selaginella kraussiana. We confirmed the expression of all plastidial tRNA genes and, conversely, observed that nucleus-encoded tRNAs corresponding to these plastidial tRNAs were generally excluded from the chloroplasts. We then demonstrated a selective and differential plastidial import of around forty nucleus-encoded tRNA species, likely compensating for the insufficient coding capacity of plastidial-encoded tRNAs. In-depth analysis revealed differential import of tRNA isodecoders, leading to the identification of specific situations. This includes the expression and import of nucleus-encoded tRNAs expressed from plastidial or bacterial-like genes inserted into the nuclear genome. Overall, our results confirm the existence of molecular processes that enable tRNAs to be selectively imported not only into mitochondria, as previously described, but also into chloroplasts, when necessary.}, } @article {pmid39511474, year = {2024}, author = {Zhang, K and Qu, G and Zhang, Y and Liu, J}, title = {Assembly and comparative analysis of the first complete mitochondrial genome of Astragalus membranaceus (Fisch.) Bunge: an invaluable traditional Chinese medicine.}, journal = {BMC plant biology}, volume = {24}, number = {1}, pages = {1055}, pmid = {39511474}, issn = {1471-2229}, support = {2022CXY22//Scientific Research Project of Shanxi Datong University, China/ ; 2023-BSBA-286//Provincial Natural Science Foundation of Liaoning, China/ ; }, mesh = {*Astragalus propinquus/genetics ; *Genome, Mitochondrial ; *Phylogeny ; Medicine, Chinese Traditional ; Genome, Plant ; }, abstract = {BACKGROUND: Astragalus membranaceus (Fisch.) Bunge is one of the most well-known tonic herbs in traditional Chinese medicine, renowned for its remarkable medicinal value in various clinical contexts. The corresponding chloroplast (cp) and nuclear genomes have since been accordingly sequenced, providing valuable information for breeding and phylogeny studies. However, the mitochondrial genome (mitogenome) of A. membranaceus remains unexplored, which hinders comprehensively understanding the evolution of its genome.

RESULTS: For this study, we de novo assembled the mitogenome of A. membranaceus (Fisch.) Bunge var. mongholicus (Bunge) P. K. Hsiao using a strategy integrating Illumina and Nanopore sequencing technology and subsequently performed comparative analysis with its close relatives. The mitogenome has a multi-chromosome structure, consisting of two circular chromosomes with a total length of 398,048 bp and an overall GC content of 45.3%. It encodes 54 annotated functional genes, comprising 33 protein-coding genes (PCGs), 18 tRNA genes, and 3 rRNA genes. An investigation of codon usage in the PCGs revealed an obvious preference for codons ending in A or U (T) bases, given their high frequency. RNA editing identified 500 sites in the coding regions of mt PCGs that exhibit a perfect conversion of the base C to U, a process that tends to lead to the conversion of hydrophilic amino acids into hydrophobic amino acids. From the mitogenome analysis, a total of 399 SSRs, 4 tandem repeats, and 77 dispersed repeats were found, indicating that A. membranaceus possesses fewer repeats compared to its close relatives with similarly sized mitogenomes. Selection pressure analysis indicated that most mt PCGs were purifying selection genes, while only five PCGs (ccmB, ccmFc, ccmFn, nad3, and nad9) were positive selection genes. Notably, positive selection emerged as a critical factor in the evolution of ccmB and nad9 in all the pairwise species comparisons, suggesting the extremely critical role of these genes in the evolution of A. membranaceus. Moreover, we inferred that 22 homologous fragments have been transferred from cp to mitochondria (mt), in which 5 cp-derived tRNA genes remain intact in the mitogenome. Further comparative analysis revealed that the syntenic region and mt gene organization are relatively conserved within the provided legumes. The comparison of gene content indicated that the gene composition of Fabaceae mitogenomes differed. Finally, the phylogenetic tree established from analysis is largely congruent with the taxonomic relationships of Fabaceae species and highlights the close relationship between Astragalus and Oxytropis.

CONCLUSIONS: We provide the first report of the assembled and annotated A. membranaceus mitogenome, which enriches the genetic resources available for the Astragalus genus and lays the foundation for comprehensive exploration of this invaluable medicinal plant.}, } @article {pmid39516195, year = {2024}, author = {Speth, DR and Zeller, LM and Graf, JS and Overholt, WA and Küsel, K and Milucka, J}, title = {Genetic potential for aerobic respiration and denitrification in globally distributed respiratory endosymbionts.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {9682}, pmid = {39516195}, issn = {2041-1723}, mesh = {*Symbiosis ; *Phylogeny ; *Denitrification ; Metagenome ; Aerobiosis ; Ciliophora/genetics/metabolism ; Groundwater/microbiology ; Gammaproteobacteria/genetics/metabolism ; Germany ; Electron Transport Complex IV/genetics/metabolism ; California ; Genome, Bacterial ; }, abstract = {The endosymbiont Candidatus Azoamicus ciliaticola was proposed to generate ATP for its eukaryotic host, an anaerobic ciliate of the Plagiopylea class, fulfilling a function analogous to mitochondria in other eukaryotic cells. The discovery of this respiratory endosymbiosis has major implications for both evolutionary history and ecology of microbial eukaryotes. However, with only a single species described, knowledge of its environmental distribution and diversity is limited. Here we report four complete, circular metagenome assembled genomes (cMAGs) representing respiratory endosymbionts inhabiting groundwater in California, Ohio, and Germany. These cMAGs form two lineages comprising a monophyletic clade within the uncharacterized gammaproteobacterial order UBA6186, enabling evolutionary analysis of their key protein complexes. Strikingly, all four cMAGs encode a cytochrome cbb3 oxidase, which indicates that these endosymbionts have the capacity for aerobic respiration. Accordingly, we detect these respiratory endosymbionts in diverse habitats worldwide, thus further expanding the ecological scope of this respiratory symbiosis.}, } @article {pmid39518988, year = {2024}, author = {Liu, R and Ma, T and Li, Y and Lei, X and Ji, H and Du, H and Zhang, J and Cao, SK}, title = {Genomic Identification and Expression Analysis of Regulator of Chromosome Condensation 1-Domain Protein Family in Maize.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39518988}, issn = {1422-0067}, support = {2022CFB183, 2024AFB301, 2022CFA030//Hubei Natural Science Foundation/ ; }, mesh = {*Zea mays/genetics/metabolism ; *Gene Expression Regulation, Plant ; *Plant Proteins/genetics/metabolism ; *Stress, Physiological/genetics ; Phylogeny ; Multigene Family ; Chromosomes, Plant/genetics ; Promoter Regions, Genetic ; Gene Expression Profiling ; Genomics/methods ; }, abstract = {Abiotic stress affects the growth and development of maize (Zea mays). The regulator of chromosome condensation 1 (RCC1)-containing proteins (RCPs) plays crucial roles in plant growth and development and response to abiotic stresses. However, a comprehensive analysis of the maize RCP family has not been reported in detail. This study presents a systematic bioinformatics analysis of the ZmRCP family, identifying a total of 30 members distributed across nine chromosomes. The physicochemical properties and cis-acting elements in the promoters of ZmRCP members are predicted. The results of subcellular localization showed that ZmRCP3 and ZmRCP10 are targeted to mitochondria and ZmRCP2 is localized in the nucleus. A heatmap of expression levels among family members under abiotic stress conditions revealed varying degrees of induced expression, and the expression levels of 10 ZmRCP members were quantified using RT-qPCR under abiotic stress and plant hormone treatments. The results showed that ZmRCP members exhibit induced or inhibited responses to these abiotic stresses and plant hormones. These results contribute to a better understanding of the evolutionary history and potential role of the ZmRCP family in mediating responses to abiotic stress in maize.}, } @article {pmid39527633, year = {2024}, author = {Gould, SB and Magiera, J and García García, C and Raval, PK}, title = {Reliability of plastid and mitochondrial localisation prediction declines rapidly with the evolutionary distance to the training set increasing.}, journal = {PLoS computational biology}, volume = {20}, number = {11}, pages = {e1012575}, pmid = {39527633}, issn = {1553-7358}, mesh = {*Plastids/metabolism/genetics ; *Mitochondria/metabolism ; *Algorithms ; *Computational Biology/methods ; Reproducibility of Results ; Evolution, Molecular ; Arabidopsis/genetics/metabolism ; Chlamydomonas reinhardtii/metabolism/genetics ; Zea mays/genetics/metabolism ; Proteome/metabolism ; Protein Transport/physiology ; }, abstract = {Mitochondria and plastids import thousands of proteins. Their experimental localisation remains a frequent task, but can be resource-intensive and sometimes impossible. Hence, hundreds of studies make use of algorithms that predict a localisation based on a protein's sequence. Their reliability across evolutionary diverse species is unknown. Here, we evaluate the performance of common algorithms (TargetP, Localizer and WoLFPSORT) for four photosynthetic eukaryotes (Arabidopsis thaliana, Zea mays, Physcomitrium patens, and Chlamydomonas reinhardtii) for which experimental plastid and mitochondrial proteome data is available, and 171 eukaryotes using orthology inferences. The match between predictions and experimental data ranges from 75% to as low as 2%. Results worsen as the evolutionary distance between training and query species increases, especially for plant mitochondria for which performance borders on random sampling. Specificity, sensitivity and precision analyses highlight cross-organelle errors and uncover the evolutionary divergence of organelles as the main driver of current performance issues. The results encourage to train the next generation of neural networks on an evolutionary more diverse set of organelle proteins for optimizing performance and reliability.}, } @article {pmid39527645, year = {2024}, author = {Salminen, TS and Vesala, L and Basikhina, Y and Kutzer, M and Tuomela, T and Lucas, R and Monteith, K and Prakash, A and Tietz, T and Vale, PF}, title = {A naturally occurring mitochondrial genome variant confers broad protection from infection in Drosophila.}, journal = {PLoS genetics}, volume = {20}, number = {11}, pages = {e1011476}, pmid = {39527645}, issn = {1553-7404}, mesh = {Animals ; *Drosophila melanogaster/genetics/parasitology/immunology ; *Genome, Mitochondrial ; *DNA, Mitochondrial/genetics ; *Immunity, Innate/genetics ; *Hemocytes/immunology/metabolism ; Mitochondria/genetics ; Larva/genetics ; Phagocytosis/genetics ; Genetic Variation ; }, abstract = {The role of mitochondria in immunity is increasingly recognized, but it is unclear how variation in mitochondrial DNA (mtDNA) contributes to variable infection outcomes. To quantify the effect of mtDNA variation on humoral and cell-mediated innate immune responses, we utilized a panel of fruit fly Drosophila melanogaster cytoplasmic hybrids (cybrids), where unique mtDNAs (mitotypes) were introgressed into a controlled isogenic nuclear background. We observed substantial heterogeneity in infection outcomes within the cybrid panel upon bacterial, viral and parasitoid infections, driven by the mitotype. One of the mitotypes, mtKSA2, protected against bacterial, parasitoid, and to a lesser extent, viral infections. Enhanced survival was not a result of improved bacterial clearance, suggesting mtKSA2 confers increased disease tolerance. Transcriptome sequencing showed that the mtKSA2 mitotype had an upregulation of genes related to mitochondrial respiration and phagocytosis in uninfected flies. Upon infection, mtKSA2 flies exhibited infection type and duration specific transcriptomic changes. Furthermore, uninfected mtKSA2 larvae showed immune activation of hemocytes (immune cells), increased hemocyte numbers and ROS production, and enhanced encapsulation response against parasitoid wasp eggs and larvae. Our results show that mtDNA variation acts as an immunomodulatory factor in both humoral and cell-mediated innate immunity and that specific mitotypes can provide broad protection against infections.}, } @article {pmid39532882, year = {2024}, author = {Erinjeri, AP and Wang, X and Williams, R and Chiozzi, RZ and Thalassinos, K and Labbadia, J}, title = {HSF-1 promotes longevity through ubiquilin-1-dependent mitochondrial network remodelling.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {9797}, pmid = {39532882}, issn = {2041-1723}, support = {P40 OD010440/OD/NIH HHS/United States ; BB/T013273/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; 209250/Z/17/Z//Wellcome Trust (Wellcome)/ ; /WT_/Wellcome Trust/United Kingdom ; 221521/Z/20/Z//Wellcome Trust (Wellcome)/ ; }, mesh = {*Mitochondria/metabolism ; Animals ; *Longevity/genetics ; *Caenorhabditis elegans Proteins/metabolism/genetics ; *Caenorhabditis elegans/metabolism/genetics ; *Transcription Factors/metabolism/genetics ; RNA Interference ; Endoplasmic Reticulum/metabolism ; }, abstract = {Increased activity of the heat shock factor, HSF-1, suppresses proteotoxicity and enhances longevity. However, the precise mechanisms by which HSF-1 promotes lifespan are unclear. Using an RNAi screen, we identify ubiquilin-1 (ubql-1) as an essential mediator of lifespan extension in worms overexpressing hsf-1. We find that hsf-1 overexpression leads to transcriptional downregulation of all components of the CDC-48-UFD-1-NPL-4 complex, which is central to both endoplasmic reticulum and mitochondria associated protein degradation, and that this is complemented by UBQL-1-dependent turnover of NPL-4.1. As a consequence, mitochondrial network dynamics are altered, leading to increased lifespan. Together, our data establish that HSF-1 mediates lifespan extension through mitochondrial network adaptations that occur in response to down-tuning of components associated with organellar protein degradation pathways.}, } @article {pmid39535230, year = {2024}, author = {van Westerhoven, AC and Dijkstra, J and Aznar Palop, JL and Wissink, K and Bell, J and Kema, GHJ and Seidl, MF}, title = {Frequent genetic exchanges revealed by a pan-mitogenome graph of a fungal plant pathogen.}, journal = {mBio}, volume = {15}, number = {12}, pages = {e0275824}, pmid = {39535230}, issn = {2150-7511}, support = {AG-5797//Bill and Melinda Gates Foundation (GF)/ ; }, mesh = {*Genome, Mitochondrial/genetics ; *Fusarium/genetics/classification ; *Recombination, Genetic ; Evolution, Molecular ; Phylogeny ; Gene Transfer, Horizontal ; Genome, Fungal ; Plant Diseases/microbiology ; Genetic Variation ; }, abstract = {Mitochondria are present in almost all eukaryotic lineages. The mitochondrial genomes (mitogenomes) evolve separately from nuclear genomes, and they can therefore provide relevant insights into the evolution of their host species. Fusarium oxysporum is a major fungal plant pathogen that is assumed to reproduce clonally. However, horizontal chromosome transfer between strains can occur through heterokaryon formation, and recently, signs of sexual recombination have been observed. Similarly, signs of recombination in F. oxysporum mitogenomes challenged the prevailing assumption of clonal reproduction in this species. Here, we construct, to our knowledge, the first fungal pan-mitogenome graph of nearly 500 F. oxysporum mitogenome assemblies to uncover the variation and evolution. In general, the gene order of fungal mitogenomes is not well conserved, yet the mitogenome of F. oxysporum and related species are highly colinear. We observed two strikingly contrasting regions in the F. oxysporum pan-mitogenome, comprising a highly conserved core mitogenome and a long variable region (6-16 kb in size), of which we identified three distinct types. The pan-mitogenome graph reveals that only five intron insertions occurred in the core mitogenome and that the long variable regions drive the difference between mitogenomes. Moreover, we observed that their evolution is neither concurrent with the core mitogenome nor with the nuclear genome. Our large-scale analysis of long variable regions uncovers frequent recombination between mitogenomes, even between strains that belong to different taxonomic clades. This challenges the common assumption of incompatibility between genetically diverse F. oxysporum strains and provides new insights into the evolution of this fungal species.IMPORTANCEInsights into plant pathogen evolution is essential for the understanding and management of disease. Fusarium oxysporum is a major fungal pathogen that can infect many economically important crops. Pathogenicity can be transferred between strains by the horizontal transfer of pathogenicity chromosomes. The fungus has been thought to evolve clonally, yet recent evidence suggests active sexual recombination between related isolates, which could at least partially explain the horizontal transfer of pathogenicity chromosomes. By constructing a pan-genome graph of nearly 500 mitochondrial genomes, we describe the genetic variation of mitochondria in unprecedented detail and demonstrate frequent mitochondrial recombination. Importantly, recombination can occur between genetically diverse isolates from distinct taxonomic clades and thus can shed light on genetic exchange between fungal strains.}, } @article {pmid39536732, year = {2024}, author = {Xuan, D and Qiang, F and Xu, H and Wang, L and Xia, Y}, title = {Screening for Mitochondrial tRNA Variants in 200 Patients with Systemic Lupus Erythematosus.}, journal = {Human heredity}, volume = {89}, number = {1}, pages = {84-97}, pmid = {39536732}, issn = {1423-0062}, mesh = {Humans ; *Lupus Erythematosus, Systemic/genetics ; *RNA, Transfer/genetics ; Female ; Male ; Adult ; DNA, Mitochondrial/genetics ; Middle Aged ; RNA, Mitochondrial/genetics ; Reactive Oxygen Species/metabolism ; Mitochondria/genetics ; Mutation/genetics ; Case-Control Studies ; Phylogeny ; Membrane Potential, Mitochondrial/genetics ; Genetic Predisposition to Disease ; }, abstract = {INTRODUCTION: Systemic lupus erythematosus (SLE) is a common autoimmune disease with unknown etiology. Recently, a growing number of evidence suggested that mitochondrial dysfunctions played active roles in the pathogenesis of SLE, but its detailed mechanism remains largely undetermined. The aim of this study was to analyze the frequencies of mitochondrial tRNA (mt-tRNA) variants in Chinese individuals with SLE.

METHODS: We carried out a mutational screening of mt-tRNA variants in a cohort of 200 patients with SLE and 200 control subjects by PCR-Sanger sequencing. The potential pathogenicity of mt-tRNA variants was evaluated by phylogenetic conservation and haplogroup analyses. In addition, trans-mitochondrial cybrid cell lines were established, and mitochondrial functions including ATP, reactive oxygen species (ROS), mitochondrial DNA (mtDNA) copy number, mitochondrial membrane potential (MMP), superoxide dismutase (SOD), and mt-RNA transcription were analyzed in cybrids with and without these putative pathogenic mt-tRNA variants.

RESULTS: We identified five possible pathogenic variants: tRNAVal G1606A, tRNALeu(UUR) A3243G, tRNAIle A4295G, tRNAGly T9997C, and tRNAThr A15924G that only found in SLE patients but were absent in controls. Interestingly, these variants were located at extremely conserved nucleotides of the corresponding tRNAs and may alter tRNAs' structure and function. Furthermore, cells carrying these tRNA variants had much lower levels of ATP, mtDNA copy number, MMP, and SOD than controls; by contrast, the levels of ROS increased significantly (p < 0.05 for all). Furthermore, a significant reduction in mt-ND1, ND2, ND3, ND5, and A6 mRNA expression was observed in cells with these mt-tRNA variants, while compared with controls. Thus, failures in tRNA metabolism caused by these variants would impair mitochondrial translation and subsequently lead to mitochondrial dysfunction that was involved in the progression and pathogenesis of SLE.

CONCLUSIONS: Our study suggested that mt-tRNA variants were important causes for SLE, and screening for mt-tRNA pathogenic variants was recommended for early detection and prevention for this disorder.}, } @article {pmid39540328, year = {2024}, author = {Pham, LTK and Van Quyen, D and Saijuntha, W and Doan, HTT and Le, TH and Lawton, SP}, title = {Mitogenomics of the zoonotic parasite Echinostoma miyagawai and insights into the evolution of tandem repeat regions within the mitochondrial non-coding control region.}, journal = {Parasitology}, volume = {151}, number = {14}, pages = {1543-1554}, pmid = {39540328}, issn = {1469-8161}, support = {108.02-2020.07//National Foundation for Science and Technology Development/ ; }, mesh = {Animals ; *Genome, Mitochondrial/genetics ; *Echinostoma/genetics/classification ; *Tandem Repeat Sequences/genetics ; Phylogeny ; *Evolution, Molecular ; Echinostomiasis/parasitology ; Zoonoses/parasitology ; Humans ; }, abstract = {Echinostoma miyagawai is a cosmopolitan parasite within the Echinostomatidae and is a cause of human echinostomiasis. Species within the family have been a challenge to disentangle with E. miyagawai being synonyms of several other Echinostoma species. However, complete mitochondrial genomes have been shown to be vital in distinguishing echinostomatid species, but detailed comparisons of not only gene content but also structural features have been limited. Using long range sequencing techniques, the complete mitochondrial genome of E. miyagawai was sequenced and compared to other members of Echinostomatidae. In total 12 protein coding genes, 2 ribosomal RNA genes and 22 transfer RNA genes were identified, as was an extensive noncoding control region (CR), consisting of 2 types of multiple tandem repeat units. Phylogenetic analyses of complete mitochondrial genomes corresponded to previous studies on single mitochondrial genes and nuclear ribosomal nuclear markers confirmed E. miyagawai to be within in the ‘Echinostoma revolutum’ group. The tandem repeat units found in the CR contained promoter sequences containing domains typical of initiation sites for replication and transcription as well as several palindromic regions which were shared between echinostomatid species. The study illustrates not only the utility complete mitogenomes in disentangling the relationship between these parasite species, but also provides some insight into the potential adaptations and other evolutionary processes that may govern the divergence of mitochondrial genomes for the first time in echinostomatids.}, } @article {pmid39540883, year = {2024}, author = {Garcia, LE and Sanchez-Puerta, MV}, title = {Mitochondrial Splicing Efficiency Is Lower in Holoparasites Than in Free-Living Plants.}, journal = {Plant & cell physiology}, volume = {65}, number = {12}, pages = {2018-2029}, doi = {10.1093/pcp/pcae120}, pmid = {39540883}, issn = {1471-9053}, mesh = {*RNA Splicing ; *Mitochondria/genetics/metabolism ; *Introns/genetics ; Gene Transfer, Horizontal ; Magnoliopsida/genetics/parasitology ; Evolution, Molecular ; Plants/genetics/parasitology ; }, abstract = {Mitochondria play a crucial role in eukaryotic organisms, housing their own genome with genes vital for oxidative phosphorylation. Coordination between nuclear and mitochondrial genomes is pivotal for organelle gene expression. Splicing, editing and processing of mitochondrial transcripts are regulated by nuclear-encoded factors. Splicing efficiency (SEf) of the many group II introns present in plant mitochondrial genes is critical for mitochondrial function since a splicing defect or splicing deficiency can severely impact plant growth and development. This study investigates SEf in free-living and holoparasitic plants, focusing on 25 group II introns from 15 angiosperm species. Our comparative analyses reveal distinctive splicing patterns with holoparasites exhibiting significantly lower SEf, potentially linked to their unique evolutionary trajectory. Given the preponderance of horizontal gene transfer (HGT) in parasitic plants, we investigated the effect of HGT on SEf, such as the presence of foreign introns or foreign nuclear-encoded splicing factors. Contrary to expectations, the SEf reductions do not correlate with HGT events, suggesting that other factors are at play, such as the loss of photosynthesis or the transition to a holoparasitic lifestyle. The findings of this study broaden our understanding of the molecular evolution in parasitic plants and shed light on the multifaceted factors influencing organelle gene expression.}, } @article {pmid39543792, year = {2024}, author = {Jacobs, HT and Rustin, P and Bénit, P and Davidi, D and Terzioglu, M}, title = {Mitochondria: great balls of fire.}, journal = {The FEBS journal}, volume = {291}, number = {24}, pages = {5327-5341}, pmid = {39543792}, issn = {1742-4658}, support = {ALTF 1146-2018//European Molecular Biology Organization/ ; 324730//Research Council of Finland/ ; n/a//Edmond de Rothschild Foundation/ ; LT000232/2019-L//Human Frontier Science Program/ ; }, mesh = {*Mitochondria/metabolism ; Animals ; Humans ; Mitochondrial Dynamics ; Homeostasis ; Hot Temperature ; Biological Evolution ; }, abstract = {Recent experimental studies indicate that mitochondria in mammalian cells are maintained at temperatures of at least 50 °C. While acknowledging the limitations of current experimental methods and their interpretation, we here consider the ramifications of this finding for cellular functions and for evolution. We consider whether mitochondria as heat-producing organelles had a role in the origin of eukaryotes and in the emergence of homeotherms. The homeostatic responses of mitochondrial temperature to externally applied heat imply the existence of a molecular heat-sensing system in mitochondria. While current findings indicate high temperatures for the innermost compartments of mitochondria, those of the mitochondrial surface and of the immediately surrounding cytosol remain to be determined. We ask whether some aspects of mitochondrial dynamics and motility could reflect changes in the supply and demand for mitochondrial heat, and whether mitochondrial heat production could be a factor in diseases and immunity.}, } @article {pmid39547447, year = {2025}, author = {Xin, C and Wang, J and Chi, J and Xu, Y and Liang, R and Jian, L and Wang, L and Guo, J}, title = {Intragenic cytosine methylation modification regulates the response of SUCLα1 to lower temperature in Solanaceae.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {350}, number = {}, pages = {112320}, doi = {10.1016/j.plantsci.2024.112320}, pmid = {39547447}, issn = {1873-2259}, mesh = {*Cytosine/metabolism ; *Cold Temperature ; Plant Proteins/genetics/metabolism ; DNA Methylation ; Solanum tuberosum/genetics/metabolism ; Phylogeny ; Gene Expression Regulation, Plant ; Solanaceae/genetics/metabolism/physiology ; Nicotiana/genetics ; }, abstract = {The tricarboxylic acid cycle (TCAC) is a fundamental metabolic process governing matter and energy in plant cells, playing an indispensable role. However, its involvement in responding to low temperature stress in potato remains poorly understood. Previous studies have identified succinyl-CoA ligase (SUCL), which catalyzes the phosphorylation of TCAC substrates, as a gene associated with lower temperatures. Nevertheless, its function in potato's response to lower temperatures remains unclear. Phylogenetic analysis has revealed that Solanum tuberosum possesses α and β subunits of SUCL, which cluster with those of Solanum lycopersicum, Nicotiana tabacum and Nicotiana benthamiana. Further investigation has shown that StSUCLα1 is predominantly located within mitochondria. Low temperatures induce methylation modification alterations at 11 intragenic cytosine sites and lead to changes in StSUCLα1 expression levels. Correlation analysis suggests that alterations in intragenic cytosine methylation sites of SUCLα1 may be associated with MET1. Knocking down NbSUCLα1, the homologous gene of StSUCLα1 in N. benthamiana, results in increased susceptibility to low temperature stress in plants. In summary, we have confirmed that SUCLα1 is a key gene modulated by intragenic cytosine methylation in response to lower temperatures, providing a novel target for genetic breeding aimed at enhancing potato tolerance to low temperature stress.}, } @article {pmid39554026, year = {2024}, author = {Kemph, A and Kharel, K and Tindell, SJ and Arkov, AL and Lynch, JA}, title = {Novel structure and composition of the unusually large germline determinant of the wasp Nasonia vitripennis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39554026}, issn = {2692-8205}, support = {R01 GM129153/GM/NIGMS NIH HHS/United States ; }, abstract = {Specialized, maternally derived ribonucleoprotein (RNP) granules play an important role in specifying the primordial germ cells in many animal species. Typically, these germ granules are small (~100 nm to a few microns in diameter) and numerous; in contrast, a single, extremely large granule called the oosome plays the role of germline determinant in the wasp Nasonia vitripennis. The organizational basis underlying the form and function of this unusually large membraneless RNP granule remains an open question. Here we use a combination of super-resolution and transmission electron microscopy to investigate the composition and morphology of the oosome. We show that the oosome has properties of a viscous liquid or elastic solid. The most prominent feature of the oosome is a branching mesh-like network of high abundance mRNAs that pervades the entire structure. Homologs of the core polar granule proteins Vasa and Oskar do not appear to nucleate this network, but rather are distributed adjacently as separate puncta. Low abundance RNAs appear to cluster in puncta that similarly do not overlap with the protein puncta. Several membrane-bound organelles, including lipid droplets and rough ER-like vesicles, are incorporated within the oosome, whereas mitochondria are nearly entirely excluded. Our findings show that the remarkably large size of the oosome is reflected in a complex sub-granular organization and suggest that the oosome is a powerful model for probing interactions between membraneless and membrane-bound organelles, structural features that contribute to granule size, and the evolution of germ plasm in insects.}, } @article {pmid39562266, year = {2024}, author = {Povelones, ML and Ginger, ML}, title = {Bric-à-brac, an 'umbilical cord' and trypanosome kinetoplast segregation.}, journal = {Trends in parasitology}, volume = {40}, number = {12}, pages = {1072-1074}, doi = {10.1016/j.pt.2024.10.021}, pmid = {39562266}, issn = {1471-5007}, mesh = {*Protozoan Proteins/metabolism/genetics ; DNA, Kinetoplast/genetics ; Animals ; Trypanosoma brucei brucei/physiology/genetics ; }, abstract = {Cadena et al. recently discovered a conserved trypanosomatid 'nabelschnur' protein TbNAB70 from a search through the protein localization resource TrypTag, providing new insight into kinetoplast origin and evolution.}, } @article {pmid39563898, year = {2024}, author = {Jinesh, GG and Smallin, MT and Mtchedlidze, N and Napoli, M and Lockhart, JH and Flores, ER and Brohl, AS}, title = {C19MC drives nucleolar invasion of mitochondria and meiotic nuclear division in human cancers.}, journal = {iScience}, volume = {27}, number = {11}, pages = {111132}, pmid = {39563898}, issn = {2589-0042}, support = {K08 CA255933/CA/NCI NIH HHS/United States ; }, abstract = {The chromosome-19 miRNA cluster (C19MC) restricts viruses depending on the multinucleated state of placental trophoblasts. However, the relationship of C19MC to multinucleation is unknown. Here we show that C19MC is coexpressed in multiple cancer type subsets with meiosis-related genes. We discovered a novel meiosis-III that exhibits simultaneous progression of meiotic nuclear division (MND) and cytokinesis. C19MC promotes meiotic bridged-chromosomes to block MND and cytokinesis to generate multinucleated cells. MND starts with the invagination of nuclear membrane to form nucle(ol)ar invasive cytoplasm (NiC), mitochondria and protein cargoes. Aurora-B regulates the efflux of cargos from NiC, whereas C19MC, CDK1, and autophagy promote cargo influx to inflate NiC size for MND progression. Using CRISPR human genetic engineering we demonstrate that the C19MC expression is required for NiC-driven MND and multinucleation. This discovery has impacts on cancer-pathogen interactions, immunotherapy, vertical transmission of viruses, antiviral research and SpCas9-CRISPR therapeutics.}, } @article {pmid39567420, year = {2025}, author = {Yun, BH and Kim, YH and Han, HS and Bang, IC}, title = {Population genetics analysis based on mitochondrial cytochrome c oxidase subunit I (CO1) gene sequences of Cottus koreanus in South Korea.}, journal = {Genes & genomics}, volume = {47}, number = {2}, pages = {207-221}, pmid = {39567420}, issn = {2092-9293}, support = {NRF-2021R1A6A1A03039503//Ministry of Education/ ; Soonchunhyang University//Soonchunhyang University/ ; }, mesh = {*Electron Transport Complex IV/genetics ; Republic of Korea ; Animals ; Haplotypes ; Genetics, Population ; Genetic Variation ; Phylogeny ; Mitochondria/genetics ; *Fishes/genetics ; }, abstract = {BACKGROUND: The freshwater sculpin Cottus koreanus is endemic to the Korean Peninsula and has a fluvial life history. However, its population has been greatly reduced and it is now listed as an endangered class II species.

OBJECTIVE: To obtain important information for its conservation, we examine the genetic diversity, population structure, and demographic history of C. koreanus through mitochondrial cytochrome c oxidase subunit I (CO1) gene sequence analysis.

METHODS: We analyzed the CO1 gene sequences of 430 individuals of C. koreanus from 23 populations in South Korea.

RESULTS: In all, 32 haplotypes were defined by 124 variable nucleotide sites, of which 28 were unique haplotypes not shared with other regional populations. All sampled populations had high haplotype diversity (Hd = 0.941) and low nucleotide diversity (π = 0.0146). Median-joining network analysis identified two divergent clusters: cluster I that had unique haplotype patterns assigned to each population and cluster II that had a star-like pattern. Each was supported by pairwise FST values and hierarchical analysis of molecular variance. The results of the mismatch distribution, goodness-of-fit test, and extended Bayesian skyline plot analysis showed that cluster I has experienced a gradual population expansion since the last glacial maximum, while cluster II experienced a sudden one. The results of neutrality testing supported the results for cluster II but the signal was weak.

CONCLUSIONS: C. koreanus inhabits the upper reaches of rivers and has extremely low dispersal ability, resulting in unique genetic structure patterns among populations. Therefore, all populations should be managed and conserved separately.}, } @article {pmid39571164, year = {2024}, author = {Luan, T and Hu, S and Nie, W and Liu, J and Jia, L and Wang, S and Zhou, J and An, N and Duan, Y and Wang, A and Xu, M and Mao, Y}, title = {Mechanisms of the Mitochondrial Unfolded Protein Response in Caenorhabditis elegans and Mammals and Its Roles in Striated Muscles.}, journal = {Aging and disease}, volume = {16}, number = {5}, pages = {2890-2907}, pmid = {39571164}, issn = {2152-5250}, mesh = {*Unfolded Protein Response/physiology ; Animals ; *Muscle, Striated/metabolism ; *Caenorhabditis elegans/metabolism ; Humans ; *Mitochondria/metabolism ; *Aging/metabolism ; Mammals ; }, abstract = {Throughout the course of evolution, organisms and cells have evolved a suite of mechanisms to manage persistent stimuli, thereby preserving cellular and organismal homeostasis. Upon detecting stress signals, cells activate a transcriptional response termed the mitochondrial unfolded protein response (UPR[mt]). This response is crucial for maintaining protein homeostasis, facilitating mitochondrial function recovery, promoting cell survival, and ultimately influencing lifespan. Striated muscles play a pivotal role in oxygen supply, movement, and metabolism. The aging of these muscles can lead to heart failure, arrhythmias, and sarcopenia, significantly impacting quality of life and lifespan. Given the intimate connection between UPR[mt] and striated muscle aging, UPR[mt] emerges as a potential therapeutic target for mitigating the effects of striated muscle aging. In this review, we delve into the role of UPR[mt] in striated muscle aging, drawing upon the extant molecular regulatory mechanisms of UPR[mt]. This exploration may enhance our understanding of the underlying mechanisms of striated muscle aging and aid in the identification of potential drug targets.}, } @article {pmid39581968, year = {2024}, author = {Wang, Y and Chen, F and Chen, Y and Ren, K and Zhao, D and Li, K and Li, H and Wan, X and Peng, M and Xiang, Z and Tang, Q and Hou, Z and Fang, Q and Zhou, Y and Lu, Y}, title = {Identification and analysis of drought-responsive F-box genes in upland rice and involvement of OsFBX148 in ABA response and ROS accumulation.}, journal = {BMC plant biology}, volume = {24}, number = {1}, pages = {1120}, pmid = {39581968}, issn = {1471-2229}, support = {32360075//the National Natural Science Foundation of China/ ; 2022CFB694//the Scientific Research Project of Department of Science and Technology of Hubei Province/ ; SCKJ-JYRC-2023-35//"Yazhou Bay" Elite Talent Science and Technology Program of Sanya Yazhou Bay Science and Technology City/ ; PY22005//the Incubation Project of Hubei Minzu University/ ; }, mesh = {*Oryza/genetics/physiology ; Drought Resistance ; *F-Box Proteins/chemistry/genetics/metabolism ; *Plant Proteins/chemistry/genetics/metabolism ; Phylogeny ; Promoter Regions, Genetic ; Gene Expression Profiling ; Abscisic Acid/metabolism ; Stress, Physiological ; Gene Expression Regulation, Plant ; Reactive Oxygen Species/metabolism ; Ubiquitin/metabolism ; }, abstract = {BACKGROUND: Upland rice varieties exhibit significant genetic diversity and broad environmental adaptability, making them ideal candidates for identifying consistently expressed stress-responsive genes. F-box proteins typically function as part of the SKP1-CUL1-F-box protein (SCF) ubiquitin ligase complexes to precisely regulate gene expression and protein level, playing essential roles in the modulation of abiotic stress responses. Therefore, utilizing upland rice varieties for screening stress-responsive F-box genes is a highly advantageous approach.

RESULTS: Through mRNA-seq analysis in the Brazilian upland rice (cv. IAPAR9), the research identified 29 drought-responsive F-box genes. Gene distribution and duplication analysis revealed these genes are distributed on 11 of the 12 chromosomes and 10 collinear gene pairs were identified on different chromosomes. 13 cis-elements or binding sites were identified in the promoters of the 29 drought-responsive F-box genes by analysis. Protein domain, stability and subcellular localization analysis results suggest that these F-box proteins possess F-box domain and several other domains, and they are mostly unstable proteins with subcellular localization in cytoplasm, nucleus, chloroplasts, mitochondria and endoplasmic reticulum. Most of drought-responsive F-box genes exhibited expression in various tissues such as root, stem, leaf, leaf sheath and panicle except for OsFBO10 and OsFBX283. These genes exhibited various responses to abiotic stresses such as osmotic, cold, heat, and salt stresses, along with ABA treatment. Importantly, a frame-shift mutation in OsFBX148 was created in the ZH11 variety, leading to altered ABA signal transduction and ROS accumulation. The study further elucidated the interaction of OsFBX148 with SKP1 family proteins OSK4/7/17 to form the SCF complex, dependent on the F-box domain.

CONCLUSIONS: The research identified and analyzed 29 drought-responsive F-box genes in upland rice and provides valuable insights into the role of OsFBX148 in ABA and ROS responses. It establishes a basis for future exploration of F-box genes in improving resistance to abiotic stresses, especially drought.}, } @article {pmid39596001, year = {2024}, author = {Wang, H and Charagh, S and Dong, N and Lu, F and Wang, Y and Cao, R and Ma, L and Wang, S and Jiao, G and Xie, L and Shao, G and Sheng, Z and Hu, S and Zhao, F and Tang, S and Chen, L and Hu, P and Wei, X}, title = {Genome-Wide Analysis of Heat Shock Protein Family and Identification of Their Functions in Rice Quality and Yield.}, journal = {International journal of molecular sciences}, volume = {25}, number = {22}, pages = {}, pmid = {39596001}, issn = {1422-0067}, support = {2023YFF1000500//National Key Research and Development Program of China/ ; 32372099//National Natural Science Foundation of China/ ; 32188102//National Natural Science Foundation of China/ ; }, mesh = {*Oryza/genetics/metabolism/growth & development ; *Heat-Shock Proteins/genetics/metabolism ; *Plant Proteins/genetics/metabolism ; *Gene Expression Regulation, Plant ; Multigene Family ; Genome, Plant ; Phylogeny ; Chromosomes, Plant/genetics ; Genome-Wide Association Study ; }, abstract = {Heat shock proteins (Hsps), acting as molecular chaperones, play a pivotal role in plant responses to environmental stress. In this study, we found a total of 192 genes encoding Hsps, which are distributed across all 12 chromosomes, with higher concentrations on chromosomes 1, 2, 3, and 5. These Hsps can be divided into six subfamilies (sHsp, Hsp40, Hsp60, Hsp70, Hsp90, and Hsp100) based on molecular weight and homology. Expression pattern data indicated that these Hsp genes can be categorized into three groups: generally high expression in almost all tissues, high tissue-specific expression, and low expression in all tissues. Further analysis of 15 representative genes found that the expression of 14 Hsp genes was upregulated by high temperatures. Subcellular localization analysis revealed seven proteins localized to the endoplasmic reticulum, while others localized to the mitochondria, chloroplasts, and nucleus. We successfully obtained the knockout mutants of above 15 Hsps by the CRISPR/Cas9 gene editing system. Under natural high-temperature conditions, the mutants of eight Hsps showed reduced yield mainly due to the seed setting rate or grain weight. Moreover, the rice quality of most of these mutants also changed, including increased grain chalkiness, decreased amylose content, and elevated total protein content, and the expressions of starch metabolism-related genes in the endosperm of these mutants were disturbed compared to the wild type under natural high-temperature conditions. In conclusion, our study provided new insights into the HSP gene family and found that it plays an important role in the formation of rice quality and yield.}, } @article {pmid39596209, year = {2024}, author = {Wang, X and Wang, Z and Yang, F and Lin, R and Liu, T}, title = {Assembly, Annotation, and Comparative Analysis of Mitochondrial Genomes in Trichoderma.}, journal = {International journal of molecular sciences}, volume = {25}, number = {22}, pages = {}, pmid = {39596209}, issn = {1422-0067}, support = {XTCX2022NYB12//Collaborative Innovation Center Project of Hainan University/ ; }, mesh = {*Genome, Mitochondrial ; *Phylogeny ; *Trichoderma/genetics ; *Molecular Sequence Annotation ; RNA, Transfer/genetics ; Base Composition/genetics ; Evolution, Molecular ; Introns/genetics ; }, abstract = {Trichoderma is a widely studied ascomycete fungal genus, including more than 400 species. However, genetic information on Trichoderma is limited, with most species reporting only DNA barcodes. Mitochondria possess their own distinct DNA that plays a pivotal role in molecular function and evolution. Here, we report 42 novel mitochondrial genomes (mitogenomes) combined with 18 published mitogenomes of Trichoderma. These circular mitogenomes exhibit sizes of 26,276-94,608 bp, typically comprising 15 core protein-coding genes (PCGs), 2 rRNAs, and 16-30 tRNAs; however, the number of endonucleases and hypothetical proteins encoded in the introns of PCGs increases with genome size enlargement. According to the result of phylogenetic analysis of the whole mitogenome, these strains diverged into six distinct evolutionary branches, supported by the phylogeny based on 2830 single-copy nuclear genes. Comparative analysis revealed that dynamic Trichoderma mitogenomes exhibited variations in genome size, gene number, GC content, tRNA copy, and intron across different branches. We identified three mutation hotspots near the regions encoding nad3, cox2, and nad5 that caused major changes in the mitogenomes. Evolutionary analysis revealed that atp9, cob, nad4L, nad5, and rps3 have been influenced by positive selection during evolution. This study provides a valuable resource for exploring the important roles of the genetic and evolutionary dynamics of Trichoderma mitogenome in the adaptive evolution of biocontrol fungi.}, } @article {pmid39603112, year = {2024}, author = {Haro, R and Walunjkar, N and Jorapur, S and Slamovits, CH}, title = {Long-read DNA sequencing reveals the organization of the mitochondrial genome in the early-branching dinoflagellate Oxyrrhis marina.}, journal = {Protist}, volume = {175}, number = {6}, pages = {126071}, doi = {10.1016/j.protis.2024.126071}, pmid = {39603112}, issn = {1618-0941}, mesh = {*Dinoflagellida/genetics/classification ; *Genome, Mitochondrial/genetics ; Sequence Analysis, DNA ; High-Throughput Nucleotide Sequencing ; Genome, Protozoan/genetics ; DNA, Mitochondrial/genetics ; DNA, Protozoan/genetics ; }, abstract = {The mitochondrial genomes of dinoflagellate protists are remarkable for their highly fragmented and heterogeneous organization. Early attempts to determine their structure without 'next-generation' DNA sequencing failed to recover a defined genome. Still, it coincided in showing that the proteins coding genes, three in total, and parts of the ribosomal RNA genes were spread across a diffuse assortment of small linear fragments. In contrast, a recent study employed Illumina sequencing to assemble a 326 kbp long single-molecule, circular mitochondrial genome in the symbiotic dinoflagellate Breviolum minutum. Here, we used a combination of short- and long-read massively-parallel DNA sequencing to analyze further the mitochondrial DNA of the early-branching dinoflagellate Oxyrrhis marina. We found that the mitochondrial genome of O. marina consists of 3 linear chromosomes sized 15.9, 33.8 and 40.6 kbp for a total of 90.3 kbp. It contains the cox1, cox3 and cob genes, the same three proteins encoded in the mitochondrion of all myzozoans (Apicomplexa and Dinophyceae), some fragments of ribosomal RNA genes as well as many non-functional gene fragments and extensive noncoding DNA. Our analysis unveiled segments syntenic patterns and rearrangements encompassing coding and non-coding regions, suggesting that recombination is a pervasive process driving the evolution of these genomes.}, } @article {pmid39604839, year = {2024}, author = {Liao, R and Yao, J and Zhang, Y and Liu, Y and Pan, H and Han, B and Song, C}, title = {MYB transcription factors in Peucedanum Praeruptorum Dunn: the diverse roles of the R2R3-MYB subfamily in mediating coumarin biosynthesis.}, journal = {BMC plant biology}, volume = {24}, number = {1}, pages = {1135}, pmid = {39604839}, issn = {1471-2229}, support = {2023YFC3503804//National Key R&D Program of China/ ; TCMRPSU-2022-04//Open Fund of Anhui Engineering Laboratory for Conservation and Sustainable Utilization of Traditional Chinese Medicine Resource/ ; TCMADM-2023-03//Open Fund of the Anhui Dabieshan Academy of Traditional Chinese Medicine/ ; }, mesh = {*Transcription Factors/metabolism/genetics ; *Plant Proteins/genetics/metabolism ; *Apiaceae/genetics/metabolism ; *Phylogeny ; *Coumarins/metabolism ; Gene Expression Regulation, Plant ; Gene Expression Profiling ; }, abstract = {BACKGROUND: The MYB superfamily (v-myb avian myeloblastosis viral oncogene homolog) plays a role in plant growth and development, environmental stress defense, and synthesis of secondary metabolites. Little is known about the regulatory function of MYB genes in Peucedanum praeruptorum Dunn, although many MYB family members, especially R2R3-MYB genes, have been extensively studied in model plants.

RESULTS: A total of 157 R2R3-MYB transcription factors from P. praeruptorum were identified using bioinformatics analysis. Comprehensive analyses including chromosome location, microsynteny, gene structure, conserved motif, phylogenetic tree, and conserved domain were further performed. The length of the 157 transcription factors ranged from 120 to 1,688 amino acids (molecular weight between 14.21 and 182.69 kDa). All proteins were hydrophilic. Subcellular localization predictions showed that 155 PpMYB proteins were localized in the nucleus, with PpMYB12 and PpMYB157 localized in the chloroplasts and mitochondria, respectively. Ten conserved motifs were identified in the PpMYBs, all of which contained typical MYB domains. Transcriptome analysis identified 47,902 unigenes. Kyoto Encyclopedia of Genes and Genomes analysis revealed 136 pathways, of which 524 genes were associated with the phenylpropanoid pathway. Differential expressed genes (DEGs) before and after bolting showed that 11 genes were enriched in the phenylpropanoid pathway. Moreover, the expression patterns of transcription genes were further verified by qRT-PCR. With high-performance liquid chromatography (HPLC), 8 coumarins were quantified from the root, stem, and leaf tissue samples of P. praeruptorum at different stages. Praeruptorin A was found in both roots and leaves before bolting, whereas praeruptorin B was mainly concentrated in the roots, and the content of both decreased in the roots and stems after bolting. Praeruptorin E content was highest in the leaves and increased with plant growth. The correlation analysis between transcription factors and coumarin content showed that the expression patterns of PpMYB3 and PpMYB103 in roots align with the accumulation trends of praeruptorin A, praeruptorin B, praeruptorin E, scopoletin, and isoscopoletin, which declined in content after bolting, suggesting that these genes may positively regulate the biosynthesis of coumarins. Eleven distinct metabolites and 48 DEGs were identified. Correlation analysis revealed that the expression of all DEGs were significantly related to the accumulation of coumarin metabolites, indicating that these genes are involved in the regulation of coumarin biosynthesis.

CONCLUSIONS: R2R3-MYB transcription factors may be involved in the synthesis of coumarin. Our findings provide basic data and a rationale for future an in-depth studies on the role of R2R3-MYB transcription factors in the growth and regulation of coumarin synthesis.}, } @article {pmid39605599, year = {2025}, author = {Nolbrant, S and Wallace, JL and Ding, JW and Zhu, T and Sevetson, JL and Kajtez, J and Baldacci, IA and Corrigan, EK and Hoglin, K and McMullen, R and Ostrowski, MS and Schmitz, MT and Breevoort, A and Swope, D and Wu, F and Pavlovic, BJ and Salama, SR and Kirkeby, A and Huang, H and Schaefer, NK and Pollen, AA}, title = {Interspecies Organoids Reveal Human-Specific Molecular Features of Dopaminergic Neuron Development and Vulnerability.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39605599}, issn = {2692-8205}, support = {R01 MH120295/MH/NIMH NIH HHS/United States ; P51 OD011132/OD/NIH HHS/United States ; S10 OD028511/OD/NIH HHS/United States ; K12 GM139185/GM/NIGMS NIH HHS/United States ; RM1 HG011543/HG/NHGRI NIH HHS/United States ; R01 MH134981/MH/NIMH NIH HHS/United States ; R01 AG087959/AG/NIA NIH HHS/United States ; DP2 MH122400/MH/NIMH NIH HHS/United States ; T32 HD007470/HD/NICHD NIH HHS/United States ; }, abstract = {The disproportionate expansion of telencephalic structures during human evolution involved tradeoffs that imposed greater connectivity and metabolic demands on midbrain dopaminergic neurons. Despite the central role of dopaminergic neurons in human-enriched disorders, molecular specializations associated with human-specific features and vulnerabilities of the dopaminergic system remain unexplored. Here, we establish a phylogeny-in-a-dish approach to examine gene regulatory evolution by differentiating pools of human, chimpanzee, orangutan, and macaque pluripotent stem cells into ventral midbrain organoids capable of forming long-range projections, spontaneous activity, and dopamine release. We identify human-specific gene expression changes related to axonal transport of mitochondria and reactive oxygen species buffering and candidate cis- and trans-regulatory mechanisms underlying gene expression divergence. Our findings are consistent with a model of evolved neuroprotection in response to tradeoffs related to brain expansion and could contribute to the discovery of therapeutic targets and strategies for treating disorders involving the dopaminergic system.}, } @article {pmid39617091, year = {2025}, author = {Zhao, J and Liang, ZL and Fang, SL and Li, RJ and Huang, CJ and Zhang, LB and Robison, T and Zhu, ZM and Cai, WJ and Yu, H and He, ZR and Zhou, XM}, title = {Phylogenomics of Paragymnopteris (Cheilanthoideae, Pteridaceae): Insights from plastome, mitochondrial, and nuclear datasets.}, journal = {Molecular phylogenetics and evolution}, volume = {204}, number = {}, pages = {108253}, doi = {10.1016/j.ympev.2024.108253}, pmid = {39617091}, issn = {1095-9513}, mesh = {*Phylogeny ; *Pteridaceae/genetics/classification ; Evolution, Molecular ; Cell Nucleus/genetics ; }, abstract = {Previous studies have shown that at least six genera of the Cheilanthoideae, a subfamily of the fern family Pteridaceae, may not be monophyletic. In these non-monophyletic genera, the Old-World genus Paragymnopteris including approximately five species have long been controversial. In this study, with an extensive taxon sampling of Paragymnopteris, we assembled 19 complete plastomes of all recognized Paragymnopteris species, plastomes of Pellaea (3 species) and Argyrochosma (1 species), as well as transcriptomes from Paragymnopteris (6 species) and Argyrochosma (1 species). We conducted a comprehensive and systematic phylogenomic analysis focusing on the contentious relationships among the genus of Paragymnopteris through 9 plastid makers, the plastomes, mitochondria, nuclear ribosomal cistron genomes, and single-copy nuclear genes. Moreover, we further combined distribution, ploidy, and morphological features to investigate the evolution of Paragymnopteris. The backbone of Paragymnopteris was resolved consistently in the nuclear and plastid phylogenies. Our major results include: (1) Paragymnopteris is not monophyletic including two fully supported clades; (2) confirming that Paragymnopteris delavayi var. intermedia is a close relative of P. delavayi instead of P. marantae var. marantae; (3) the chromosome base number may not be a stable trait which has previously been used as an important character to divide Paragymnopteris into two groups; and (4) gene flow or introgression might be the main reason for the gene trees conflict of Paragymnopteris, but both gene flow and ILS might simultaneously and/or cumulatively act on the conflict of core pellaeids. The robust phylogeny of Paragymnopteris presented here will help us for the future studies of the arid to semi-arid ferns of Cheilanthoideae at the evolutionary, physiological, developmental, and omics-based levels.}, } @article {pmid39623304, year = {2024}, author = {Zhang, C and Rasool, A and Qi, H and Zou, X and Wang, Y and Wang, Y and Wang, Y and Liu, Y and Yu, Y}, title = {Comprehensive analysis of the first complete mitogenome and plastome of a traditional Chinese medicine Viola diffusa.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {1162}, pmid = {39623304}, issn = {1471-2164}, mesh = {*Genome, Mitochondrial ; *Medicine, Chinese Traditional ; *Viola/genetics ; Phylogeny ; Base Composition ; RNA, Transfer/genetics ; Genome, Plastid ; Codon Usage ; }, abstract = {BACKGROUND: Viola diffusa is used in the formulation of various Traditional Chinese Medicines (TCMs), including antiviral, antimicrobial, antitussive, and anti-inflammatory drugs, due to its richness in flavonoids and triterpenoids. The biosynthesis of these compounds is largely mediated by cytochrome P450 enzymes, which are primarily located in the membranes of mitochondria and the endoplasmic reticulum.

RESULTS: This study presents the complete assembly of the mitogenome and plastome of Viola diffusa. The circular mitogenome spans 474,721 bp with a GC content of 44.17% and encodes 36 unique protein-coding genes, 21 tRNA, and 3 rRNA. Except for the RSCU values of 1 observed for the start codon (AUG) and tryptophan (UGG), the mitochondrial protein-coding genes exhibited a codon usage bias, with most estimates deviating from 1, similar to patterns observed in closely related species. Analysis of repetitive sequences in the mitogenome demonstrated potential homologous recombination mediated by these repeats. Sequence transfer analysis revealed 24 homologous sequences shared between the mitogenome and plastome, including nine full-length genes. Collinearity was observed among Viola diffusa species within the other members of Malpighiales order, indicated by the presence of homologous fragments. The length and arrangement of collinear blocks varied, and the mitogenome exhibited a high frequency of gene rearrangement.

CONCLUSIONS: We present the first complete assembly of the mitogenome and plastome of Viola diffusa, highlighting its implications for pharmacological, evolutionary, and taxonomic studies. Our research underscores the multifaceted importance of comprehensive mitogenome analysis.}, } @article {pmid39623987, year = {2024}, author = {Zhang, Y and Zang, C and Pan, X and Gong, M and Liu, H}, title = {[Population genetic diversity of Culex tritaeniorhynchus in Jining City of Shandong Province based on the mitochondrial cytochrome C oxidase I gene].}, journal = {Zhongguo xue xi chong bing fang zhi za zhi = Chinese journal of schistosomiasis control}, volume = {36}, number = {5}, pages = {466-473}, doi = {10.16250/j.32.1915.2024119}, pmid = {39623987}, issn = {1005-6661}, support = {tsqn202312373//Shandong Provincial Taishan Scholar Program/ ; ZR2R2020KH001//Key Project of Natural Science Foundation t of Shandong Province/ ; 230726153807227//University-Industry Collaborative Education Program of Ministry of Education/ ; }, mesh = {Animals ; *Culex/genetics ; *Electron Transport Complex IV/genetics ; *Genetic Variation ; China ; Haplotypes ; Phylogeny ; Female ; Mitochondria/genetics ; }, abstract = {OBJECTIVE: To understand the genetic basis of the adaptation of Culex tritaeniorhynchus to different environmental ecology in Jining City, Shandong Province, so as to provide insights into understanding of the population structure or isolation pattern of Cx. tritaeniorhynchus in the city.

METHODS: Seven sampling sites were selected from urban, suburban and rural areas of Jining City, Shandong Province from June to August 2023, and mosquitoes were collected using mosquito-trapping lamps. All collected adult mosquitoes were identified morphologically. Genomic DNA was extracted from a single female Cx. tritaeniorhynchus mosquito, and the mitochondrial cytochrome C oxidase I (COI) gene was amplified using a PCR assay, sequenced and subjected to molecular identification. The number of haplotypes, haplotype diversity (Hd), nucleotide diversity (Pi), and average number of nucleotide differences (K) of Cx. tritaeniorhynchus DNA sequences were estimated among different sampling sites using the software DnaSP 6, and a neutrality test was performed. The fixation index (FST), and gene flow (number of migrants, Nm) of Cx. tritaeniorhynchus populations were calculated using the software Arlequin 3.5.2, and subjected to analysis of molecular variance (AMOVA). In addition, a haplotype network diagrams and a phylogenetic tree of Cx. tritaeniorhynchus populations were created using the software PopART and MEGA 11, respectively.

RESULTS: A total of 420 sequences were successfully amplified from the COI gene of Cx. tritaeniorhynchus samples collected from 7 sampling sites in Jining City, and a gene fragment sequence with a length of 603 bp was obtained, with 55 variable sites and 46 haplotypes and without insertion or deletion mutations. Of the 46 haplotypes, H01 was the dominant shared haplotype, and the haplotype frequency increased gradually from urban areas (34.00%) to rural areas (47.00%). The mean Hd, Pi and K values of Cx. tritaeniorhynchus COI genes were 0.814, 0.024 and 14.129, 0.489, 0.016 and 7.941 and 0.641, 0.016 and 10.393 in suburban, urban, and rural areas, respectively, with the highest population diversity of Cx. tritaeniorhynchus in suburban areas and the lowest in urban areas. Paired FST analysis among different types of sampling sites showed that the mean FST value was 0.029 between urban and suburban areas, indicating more frequent inter-population communication. AMOVA revealed that the percentage of intra-population variation (95.74%) was higher than that of inter-population variation (4.26%). Neutrality tests showed deviation from neutrality in Cx. tritaeniorhynchus populations collected from Nanyang Township (Tajima's D = 2.793, Fu's Fs = 6.429, both P values < 0.05). In addition, the mismatch distribution curves of Cx. tritaeniorhynchus COI gene appeared bimodal or multimodal patterns in Jining City, indicating a relatively stable overall population size.

CONCLUSIONS: The mitochondrial COI gene may be used as a molecular marker to investigate the population genetic diversity of Cx. tritaeniorhynchus. The population genetic diversity of Cx. tritaeniorhynchus is higher in the suburban areas of Jining City than in rural and urban areas, and there are frequent genetic exchanges between Cx. tritaeniorhynchus populations from urban and suburban areas.}, } @article {pmid39629328, year = {2024}, author = {Qi, X and Wang, Z and Lin, Y and Guo, Y and Dai, Z and Wang, Q}, title = {Elucidation and engineering mitochondrial respiratory-related genes for improving bioethanol production at high temperature in Saccharomyces cerevisiae.}, journal = {Engineering microbiology}, volume = {4}, number = {2}, pages = {100108}, pmid = {39629328}, issn = {2667-3703}, abstract = {Industrial manufacturing of bioproducts, especially bioethanol, can benefit from high-temperature fermentation, which requires the use of thermotolerant yeast strains. Mitochondrial activity in yeast is closely related to its overall metabolism. However, the mitochondrial respiratory changes in response to adaptive thermotolerance are still poorly understood and have been rarely utilized for developing thermotolerant yeast cell factories. Here, adaptive evolution and transcriptional sequencing, as well as whole-genome-level gene knockout, were used to obtain a thermotolerant strain of Saccharomyces cerevisiae. Furthermore, thermotolerance and bioethanol production efficiency of the engineered strain were examined. Physiological evaluation showed the boosted fermentation capacity and suppressed mitochondrial respiratory activity in the thermotolerant strain. The improved fermentation produced an increased supply of adenosine triphosphate required for more active energy-consuming pathways. Transcriptome analysis revealed significant changes in the expression of the genes involved in the mitochondrial respiratory chain. Evaluation of mitochondria-associated gene knockout confirmed that ADK1, DOC1, or MET7 were the key factors for the adaptive evolution of thermotolerance in the engineered yeast strain. Intriguingly, overexpression of DOC1 with TEF1 promoter regulation led to a 10.1% increase in ethanol production at 42 °C. The relationships between thermotolerance, mitochondrial activity, and respiration were explored, and a thermotolerant yeast strain was developed by altering the expression of mitochondrial respiration-related genes. This study provides a better understanding on the physiological mechanism of adaptive evolution of thermotolerance in yeast.}, } @article {pmid39633470, year = {2024}, author = {Atherton, W and Ambrose, L and Wisdom, J and Lessard, BD and Kurucz, N and Webb, CE and Beebe, NW}, title = {Nuclear and mitochondrial population genetics of the Australasian arbovirus vector Culex annulirostris (Skuse) reveals strong geographic structure and cryptic species.}, journal = {Parasites & vectors}, volume = {17}, number = {1}, pages = {501}, pmid = {39633470}, issn = {1756-3305}, support = {RG 18-19//Australian Biological Resources Study, Australia's Department of Climate Change, Energy, the Environment and Water/ ; }, mesh = {Animals ; *Culex/genetics/classification/virology ; *Microsatellite Repeats/genetics ; *Mosquito Vectors/genetics/classification/virology ; *Genetic Variation ; Australia ; *DNA, Mitochondrial/genetics ; Genetics, Population ; Arboviruses/genetics ; Australasia/epidemiology ; Papua New Guinea ; Electron Transport Complex IV/genetics ; Haplotypes ; Phylogeny ; Mitochondria/genetics ; }, abstract = {BACKGROUND: The mosquito Culex annulirostris Skuse (Diptera: Culicidae) is an important arbovirus vector in Australasia. It is part of the Culex sitiens subgroup that also includes Cx. palpalis and Cx. sitiens. Single locus mitochondrial and nuclear DNA sequencing studies suggest that Cx. annulirostris consists of a complex of at least two species. We tested this hypothesis by analysing both nuclear microsatellite data and additional mitochondrial sequence data to describe the population genetics of Cx. annulirostris through Australia, Papua New Guinea (PNG) and the Solomon Archipelago.

METHODS: Twelve novel microsatellite markers for Cx. annulirostris were developed and used on over 500 individuals identified as Cx. annulirostris by molecular diagnostics. Ten of the 12 microsatellites then used for analysis using Discriminant Analysis of Principal Components, a Bayesian clustering software, STRUCTURE, along with estimates of Jost's D statistic that is similar to FST but better suited to microsatellite data. Mitochondrial cytochrome oxidase I (COI) DNA sequence were also generated complementing previous work and analysed for sequence diversity (Haplotype diversity, Hd and Pi, π), Tadjima's D, and pairwise FST between populations. An allele specific molecular diagnostic with an internal control was developed.

RESULTS: We confirm the existence of multiple genetically and geographically restricted populations. Within mainland Australia, our findings show that Cx. annulirostris consists of two genetically and geographically distinct populations. One population extends through northern Australia and into the south-east coast of Queensland and New South Wales (NSW). The second Australian population occurs through inland NSW, Victoria, South Australia, extending west to southern Western Australia. These two Australian populations show evidence of possible admixture in central Australia and far north Queensland. Australia's Great Dividing Range that runs down southeast Australia presents a strong gene-flow barrier between these two populations which may be driven by climate, elevation or river basins. In PNG we find evidence of reproductive isolation between sympatric cryptic species occurring through PNG and Australia's northern Cape York Peninsula. A PCR-based molecular diagnostic was developed to distinguish these two cryptic species.

CONCLUSION: This study adds to the growing body of work suggesting that the taxon presently known as Cx. annulirostris now appears to consist of at least two cryptic species that co-occur in northern Australia and New Guinea and can be distinguished by a ITS1 PCR diagnostic. The Solomon Islands population may also represent a distinct species but in light its geographic isolation and lack of sympatry with other species would require further study. Additionally, the mitochondrial and nuclear DNA evidence of population structure between geographic regions within Australia appears latitudinal and elevational driven and may suggest an additional subspecies in that hybridise where they overlap.}, } @article {pmid39648544, year = {2025}, author = {Acharya, TK and Mahapatra, P and Kumar, S and Dubey, NK and Rajalaxmi, S and Ghosh, A and Kumar, A and Goswami, C}, title = {Conserved and Unique Mitochondrial Target Sequence of TRPV4 Can Independently Regulate Mitochondrial Functions.}, journal = {Proteins}, volume = {93}, number = {4}, pages = {908-919}, pmid = {39648544}, issn = {1097-0134}, support = {BT/PR8004/MED/30/988/2013//Department of Biotechnology (DBT), Ministry of science and Technology/ ; //National Institute of Science Education and Research/ ; }, mesh = {*TRPV Cation Channels/metabolism/genetics/chemistry ; *Mitochondria/metabolism/genetics ; Humans ; Animals ; Conserved Sequence ; Amino Acid Sequence ; *Mitochondrial Proteins/metabolism/genetics/chemistry ; HEK293 Cells ; }, abstract = {Though mitochondria have their own genome and protein synthesis machineries, the majority of the mitochondrial proteins are actually encoded by the nuclear genome. Most of these mitochondrial proteins are imported into specific compartments of the mitochondria due to their mitochondrial target sequence (MTS). Unlike the nuclear target sequence, the MTS of most of the mitochondrial localized proteins remain poorly understood, mainly due to their variability, heterogeneity, unconventional modes of action, mitochondrial potential-dependent transport, and other complexities. Recently, we reported that transient receptor potential vanilloid subtype 4 (TRPV4), a thermosensitive cation channel, is physically located at the mitochondria. Here we characterize a small segment (AA 592-630) located at the TM4-loop4-TM5 segment of TRPV4 that acts as a novel MTS. The same region remains highly conserved in all vertebrates and contains a large number of point mutations each of which causes an diverse spectrum of diseases in human. Using confocal and super-resolution microscopy, we show that this MTS of TRPV4 or its mutants localizes to the mitochondria independently and also induces functional and quantitative changes in the mitochondria. By using conformal microscopy, we could detect the presence of the MTS region within the isolated mitochondria. These findings may be important to understand the complexity of MTS and TRPV4-induced channelopathies better.}, } @article {pmid39658314, year = {2025}, author = {Sørensen, MES and Stiller, ML and Kröninger, L and Nowack, ECM}, title = {Protein import into bacterial endosymbionts and evolving organelles.}, journal = {The FEBS journal}, volume = {292}, number = {12}, pages = {2992-3013}, pmid = {39658314}, issn = {1742-4658}, support = {101061817//H2020 European Research Council/ ; //Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Symbiosis ; Protein Transport ; *Bacteria/metabolism/genetics ; *Organelles/metabolism/genetics ; *Bacterial Proteins/metabolism/genetics ; Mitochondria/metabolism/genetics ; Plastids/metabolism/genetics ; }, abstract = {Bacterial endosymbionts are common throughout the eukaryotic tree of life and provide a range of essential functions. The intricate integration of bacterial endosymbionts into a host led to the formation of the energy-converting organelles, mitochondria and plastids, that have shaped eukaryotic evolution. Protein import from the host has been regarded as one of the distinguishing features of organelles as compared to endosymbionts. In recent years, research has delved deeper into a diverse range of endosymbioses and discovered evidence for 'exceptional' instances of protein import outside of the canonical organelles. Here we review the current evidence for protein import into bacterial endosymbionts. We cover both 'recently evolved' organelles, where there is evidence for hundreds of imported proteins, and endosymbiotic systems where currently only single protein import candidates are described. We discuss the challenges of establishing protein import machineries and the diversity of mechanisms that have independently evolved to solve them. Understanding these systems and the different independent mechanisms, they have evolved is critical to elucidate how cellular integration arises and deepens at the endosymbiont to organelle interface. We finish by suggesting approaches that could be used in the future to address the open questions. Overall, we believe that the evidence now suggests that protein import into bacterial endosymbionts is more common than generally realized, and thus that there is an increasing number of partnerships that blur the distinction between endosymbiont and organelle.}, } @article {pmid39661651, year = {2024}, author = {Prediger, C and Ferreira, EA and Zorzato, SV and Hua-Van, A and Klasson, L and Miller, WJ and Yassin, A and Madi-Ravazzi, L}, title = {Saltational Episodes of Reticulate Evolution in the Drosophila saltans Species Group.}, journal = {Molecular biology and evolution}, volume = {41}, number = {12}, pages = {}, pmid = {39661651}, issn = {1537-1719}, support = {95/06165-1//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; 141545/2020-8//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/ ; //Excellence Eiffel Scholarship Program/ ; //Swedish National Genomics Infrastructure and Science for Life Laboratory/ ; //Swedish Research Council/ ; 2014-4353//Knut and Alice Wallenberg Foundation/ ; //CNRS/ ; ANR-11-INBS-0001//Agence Nationale de la Recherche/ ; P28255-B22//Austrian Science Fund/ ; ANR-18-CE02-0008//Richard Lounsbery Foundation/ ; }, mesh = {Animals ; *Drosophila/genetics ; *Phylogeny ; Biological Evolution ; Genome, Insect ; Synteny ; Evolution, Molecular ; }, abstract = {Phylogenomics reveals reticulate evolution to be widespread across taxa, but whether reticulation is due to low statistical power or it is a true evolutionary pattern remains a field of study. Here, we investigate the phylogeny and quantify reticulation in the Drosophila saltans species group, a Neotropical clade of the subgenus Sophophora comprising 23 species whose relationships have long been problematic. Phylogenetic analyses revealed conflicting topologies between the X chromosome, autosomes and the mitochondria. We extended the ABBA-BABA test of asymmetry in phylogenetic discordance to cases where no "true" species tree could be inferred, and applied our new test (called 2A2B) to whole genome data and to individual loci. We used four strategies, two based on our new assemblies using either conserved genes or ≥50 kb-long syntenic blocks with conserved collinearity across Neotropical Sophophora, and two consisted of windows from pseudo-reference genomes aligned to either an ingroup or outgroup species. Evidence for reticulation varied among the strategies, being lowest in the synteny-based approach, where it did not exceed ∼7% of the blocks in the most conflicting species quartets. High incidences of reticulation were restricted to three nodes on the tree that coincided with major paleogeographical events in South America. Our results identify possible technical biases in quantifying reticulate evolution and indicate that episodic rapid radiations have played a major role in the evolution of a largely understudied Neotropical clade.}, } @article {pmid39662740, year = {2025}, author = {de Quadros, T and Jaramillo, ML and Barreto, C and da Rosa, RD and de Melo, MS and Nazari, EM}, title = {Modulation of mitochondrial dynamics genes and mtDNA during embryonic development and under UVB exposure.}, journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology}, volume = {300}, number = {}, pages = {111790}, doi = {10.1016/j.cbpa.2024.111790}, pmid = {39662740}, issn = {1531-4332}, mesh = {Animals ; *Ultraviolet Rays ; *DNA, Mitochondrial/genetics ; *Embryonic Development/radiation effects/genetics ; *Mitochondrial Dynamics/radiation effects ; Palaemonidae/genetics/embryology/radiation effects ; Phylogeny ; Mitochondria/metabolism/radiation effects/genetics ; Gene Expression Regulation, Developmental/radiation effects ; Embryo, Nonmammalian/radiation effects/metabolism ; }, abstract = {Studies using the embryos of the freshwater prawn Macrobrachium olfersii have reported changes in embryonic cells after exposure to ultraviolet B (UVB) radiation, such as DNA damage and apoptosis activation. Considering the importance of mitochondria in embryonic cells, this study aimed to characterize the aspects of mitochondrial morphofunctionality in M. olfersii embryos and mitochondrial responses to UVB radiation exposure. The coding sequences of genes Tfam, Nrf1, Mfn1, and Drp1 were identified from the transcriptome of M. olfersii embryos. The phylogenetic relationship showed strong amino acid identity and a highly conserved nature of the sequences. Additionally, the number of mitochondrial DNA (mtDNA) copies were higher in the early embryonic days. The results showed that the expression of the analyzed genes was highly regulated during embryonic development, increasing their levels near hatching. Furthermore, when embryos were exposed to UVB radiation, mitochondrial biogenesis was activated, recognized by higher levels of transcripts of genes Tfam and Nrf1, accompanied by mitochondrial fission. Additionally, these mitochondrial events were supported by an increase of mtDNA copies. Our results showed that UVB radiation was able to change the mitochondrial morphofunctionality, and under the current knowledge, certainly compromise embryonic cellular integrity. Additionally, mitochondria is an important cellular target of this radiation and its responses can be used to assess environmental stress caused by UVB radiation in embryos of aquatic species.}, } @article {pmid39665281, year = {2024}, author = {Crino, OL and Wild, KH and Friesen, CR and Leibold, D and Laven, N and Peardon, AY and Recio, P and Salin, K and Noble, DWA}, title = {From eggs to adulthood: sustained effects of early developmental temperature and corticosterone exposure on physiology and body size in an Australian lizard.}, journal = {The Journal of experimental biology}, volume = {227}, number = {24}, pages = {}, pmid = {39665281}, issn = {1477-9145}, support = {DP210101152//Australian Research Council/ ; //Australian National University/ ; }, mesh = {Animals ; *Corticosterone/pharmacology ; *Lizards/physiology/growth & development ; *Body Size/drug effects ; *Temperature ; Female ; Ovum/drug effects/physiology ; Australia ; Male ; }, abstract = {Developing animals are increasingly exposed to elevated temperatures as global temperatures rise as a result of climate change. Vertebrates can be affected by elevated temperatures during development directly, and indirectly through maternal effects (e.g. exposure to prenatal glucocorticoid hormones). Past studies have examined how elevated temperatures and glucocorticoid exposure during development independently affect vertebrates. However, exposure to elevated temperatures and prenatal corticosterone could have interactive effects on developing animals that affect physiology and life-history traits across life. We tested interactions between incubation temperature and prenatal corticosterone exposure in the delicate skink (Lampropholis delicata). We treated eggs with high or low doses of corticosterone and incubated eggs at 23°C (cool) or 28°C (warm). We measured the effects of these treatments on development time, body size and survival from hatching to adulthood and on adult hormone levels and mitochondrial respiration. We found no evidence for interactive effects of incubation temperature and prenatal corticosterone exposure on phenotype. However, incubation temperature and corticosterone treatment each independently decreased body size at hatching and these effects were sustained into the juvenile period and adulthood. Lizards exposed to low doses of corticosterone during development had elevated levels of baseline corticosterone as adults. Additionally, lizards incubated at cool temperatures had higher levels of baseline corticosterone and more efficient mitochondria as adults compared with lizards incubated at warm temperatures. Our results show that developmental conditions can have sustained effects on morphological and physiological traits in oviparous lizards but suggest that incubation temperature and prenatal corticosterone do not have interactive effects.}, } @article {pmid39674307, year = {2025}, author = {Pistolesi, A and Ranieri, G and Calvani, M and Guasti, D and Chiarugi, A and Buonvicino, D}, title = {Microglial suppression by myeloperoxidase inhibitor does not delay neurodegeneration in a mouse model of progressive multiple sclerosis.}, journal = {Experimental neurology}, volume = {385}, number = {}, pages = {115095}, doi = {10.1016/j.expneurol.2024.115095}, pmid = {39674307}, issn = {1090-2430}, mesh = {Animals ; Mice ; *Microglia/drug effects ; Disease Models, Animal ; *Peroxidase/antagonists & inhibitors/metabolism ; Mice, Inbred NOD ; Female ; *Multiple Sclerosis, Chronic Progressive/pathology/drug therapy ; Disease Progression ; Reactive Oxygen Species/metabolism ; *Propionates/pharmacology/therapeutic use ; *Enzyme Inhibitors/therapeutic use/pharmacology ; Mitochondria/drug effects/metabolism ; *Nerve Degeneration/pathology/drug therapy ; Spinal Cord/pathology/drug effects ; Aminopyridines ; Pyrroles ; }, abstract = {Drugs able to efficiently counteract the progression of multiple sclerosis (MS) are still an unmet need. Numerous preclinical evidence indicates that reactive oxygen-generating enzyme myeloperoxidase (MPO), expressed by neutrophils and microglia, might play a key role in neurodegenerative disorders. Then, the MPO inhibition has been evaluated in clinical trials in Parkinson's and multiple system atrophy patients, and a clinical trial for the treatment of amyotrophic lateral sclerosis is underway. The effects of MPO inhibition on MS patients have not yet been explored. In the present study, by adopting the NOD mouse model of progressive MS (PMS), we evaluated the pharmacological effects of the MPO inhibitor verdiperstat (also known as AZD3241) on functional, immune, and mitochondrial parameters during disease evolution. We found that daily treatment with verdiperstat did not affect the pattern of progression as well as survival, despite its ability to reduce mitochondrial reactive oxygen species and microglia activation in the spinal cord of immunized mice. Remarkably, verdiperstat did not affect adaptive immunity, neutrophils invasion as well as mitochondrial derangement in the spinal cords of immunized mice. Data suggest that microglia suppression is not sufficient to prevent disease evolution, corroborating the hypothesis that immune-independent components drive neurodegeneration in progressive MS.}, } @article {pmid39676593, year = {2025}, author = {Coronel, FP and Gras, DE and Canal, MV and Roldan, F and Welchen, E and Gonzalez, DH}, title = {Cytochrome c levels link mitochondrial function to plant growth and stress responses through changes in SnRK1 pathway activity.}, journal = {The Plant journal : for cell and molecular biology}, volume = {121}, number = {2}, pages = {e17215}, doi = {10.1111/tpj.17215}, pmid = {39676593}, issn = {1365-313X}, support = {PICT-2020-0362//Fondo para la Investigación Científica y Tecnológica/ ; PICT-2021-00486//Fondo para la Investigación Científica y Tecnológica/ ; CAI+D-2020//Universidad Nacional del Litoral/ ; }, mesh = {*Protein Serine-Threonine Kinases/metabolism/genetics ; *Mitochondria/metabolism ; *Arabidopsis/genetics/physiology/metabolism/growth & development ; *Arabidopsis Proteins/metabolism/genetics ; Stress, Physiological ; *Cytochromes c/metabolism/genetics ; Gene Expression Regulation, Plant ; Signal Transduction ; Electron Transport ; }, abstract = {Energy is required for growth as well as for multiple cellular processes. During evolution, plants developed regulatory mechanisms to adapt energy consumption to metabolic reserves and cellular needs. Reduced growth is often observed under stress, leading to a growth-stress trade-off that governs plant performance under different conditions. In this work, we report that plants with reduced levels of the mitochondrial respiratory chain component cytochrome c (CYTc), required for electron transport coupled to oxidative phosphorylation and ATP production, show impaired growth and increased global expression of stress-responsive genes, similar to those observed after inhibiting the respiratory chain or the mitochondrial ATP synthase. CYTc-deficient plants also show activation of the SnRK1 pathway, which regulates growth, metabolism, and stress responses under carbon starvation conditions, even though their carbohydrate levels are not significantly different from wild-type. Notably, loss-of-function of the gene encoding the SnRK1α1 subunit restores the growth of CYTc-deficient plants, as well as autophagy, free amino acid and TOR pathway activity levels, which are affected in these plants. Moreover, increasing CYTc levels decreases SnRK1 pathway activation, reflected in reduced SnRK1α1 phosphorylation, with no changes in total SnRK1α1 protein levels. Under stress imposed by mannitol, the growth of CYTc-deficient plants is relatively less affected than that of wild-type plants, which is also related to the activation of the SnRK1 pathway. Our results indicate that SnRK1 function is affected by CYTc levels, thus providing a molecular link between mitochondrial function and plant growth under normal and stress conditions.}, } @article {pmid39677574, year = {2024}, author = {Bettinazzi, S and Liang, J and Rodriguez, E and Bonneau, M and Holt, R and Whitehead, B and Dowling, DK and Lane, N and Camus, MF}, title = {Assessing the role of mitonuclear interactions on mitochondrial function and organismal fitness in natural Drosophila populations.}, journal = {Evolution letters}, volume = {8}, number = {6}, pages = {916-926}, pmid = {39677574}, issn = {2056-3744}, abstract = {Mitochondrial function depends on the effective interactions between proteins and RNA encoded by the mitochondrial and nuclear genomes. Evidence suggests that both genomes respond to thermal selection and promote adaptation. However, the contribution of their epistatic interactions to life history phenotypes in the wild remains elusive. We investigated the evolutionary implications of mitonuclear interactions in a real-world scenario that sees populations adapted to different environments, altering their geographical distribution while experiencing flow and admixture. We created a Drosophila melanogaster panel with replicate native populations from the ends of the Australian east-coast cline, into which we substituted the mtDNA haplotypes that were either predominant or rare at each cline-end, thus creating putatively mitonuclear matched and mismatched populations. Our results suggest that mismatching may impact phenotype, with populations harboring the rarer mtDNA haplotype suffering a trade-off between aerobic capacity and key fitness aspects such as reproduction, growth, and survival. We discuss the significance of mitonuclear interactions as modulators of life history phenotypes in the context of future adaptation and population persistence.}, } @article {pmid39688736, year = {2024}, author = {Singha, D and Patidar, A and Pal, S and Tyagi, K and Kumar, V}, title = {Mitochondrial genetic diversity of pest and vector species, Frankliniella schultzei (Thripidae: Thripinae).}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {55}, pmid = {39688736}, issn = {1573-4978}, support = {CRG/2023/000498//Science and Engineering Research Board/ ; }, mesh = {Animals ; *Phylogeny ; *Genetic Variation/genetics ; *Haplotypes/genetics ; India ; *Thysanoptera/genetics/classification ; DNA Barcoding, Taxonomic/methods ; Australia ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Insect Vectors/genetics/classification ; Bayes Theorem ; Gene Flow ; }, abstract = {BACKGROUND: Frankliniella schultzei (Trybom) is a serious pest and a carrier of tospoviruses in major agricultural crops. This species is a historical and unresolved species complex that contains genetically different cryptic species across the globe.

METHODS AND RESULTS: DNA barcodes were generated from freshly collected specimens of F. schultzei from India and Australia using the sanger sequencing. Seventy-five COI sequences were generated from India and Australia. Moreover, 318 sequences were downloaded (India, Australia, Pakistan, and Africa) from the NCBI GenBank to explore the genetic diversity and phylogeny. The minimum and maximum mean interspecific distance between 393 sequences was found to be 7.97% and 21.50%, respectively. Bayesian and Neighbour joining clustering indicated the presence of five putative species within F. schultzei that had sympatry and allopatry. Moreover, 20 haplotypes and 140 polymorphic sites were identified. The African clade is unique; it does not share haplotypes with any other countries, suggesting it may represent the true F. schultzei. Haplotype network analysis showed shallow gene flow and deep genetic variation between the populations. Signatures of recent population history events were measured using Fu's Fs test and Tajima's D test. Morphometric analysis based on seven characters is also carried out.

CONCLUSION: Phylogeny and genetic distance revealed the presence of five putative species within F. schultzei. On the contrary, morphology does not unequivocally corroborate the phylogenetic results, as morphometric analysis showed overlap among these clades. To resolve F. schultzei species complex, whole genome-based sequencing data are very much necessitated.}, } @article {pmid39688921, year = {2025}, author = {Alvarenga, JP and Stata, M and Sage, RF and Patel, R and das Chagas Mendonca, AM and Della Torre, F and Liu, H and Cheng, S and Weake, S and Watanabe, EJ and Lage Viana, P and de Castro Arruda, IA and Ludwig, M and Delfino Barbosa, JPRA and Sage, TL}, title = {Evolutionary diversification of C2 photosynthesis in the grass genus Homolepis (Arthropogoninae).}, journal = {Annals of botany}, volume = {135}, number = {4}, pages = {769-788}, pmid = {39688921}, issn = {1095-8290}, support = {RGPIN-2020-05925//Natural Science and Engineering Research Council of Canada/ ; APQ-02653-18//Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Brazil (FAPEMIG) project/ ; }, mesh = {*Photosynthesis/physiology ; Phylogeny ; *Biological Evolution ; *Poaceae/physiology/genetics/metabolism ; Plant Leaves/physiology/metabolism ; Glycine Dehydrogenase (Decarboxylating)/metabolism/genetics ; Carbon Isotopes ; Plant Proteins/metabolism/genetics ; Transcriptome ; }, abstract = {BACKGROUND AND AIMS: To better understand C4 evolution in monocots, we characterized C3-C4 intermediate phenotypes in the grass genus Homolepis (subtribe Arthropogoninae).

METHODS: Carbon isotope ratio (δ13C), leaf gas exchange, mesophyll (M) and bundle sheath (BS) tissue characteristics, organelle size and numbers in M and BS tissue, and tissue distribution of the P-subunit of glycine decarboxylase (GLDP) were determined for five Homolepis species and the C4 grass Mesosetum loliiforme from a phylogenetic sister clade. We generated a transcriptome-based phylogeny for Homolepis and Mesosetum species to interpret physiological and anatomical patterns in an evolutionary context, and to test for hybridization.

KEY RESULTS: Homolepis contains two C3 species (H. glutinosa, H. villaricensis), one species with a weaker form of C2 termed sub-C2 (H. isocalycia), and two C2 species (H. longispicula, H. aturensis). Homolepis longispicula and H. aturensis express over 85 % of leaf glycine in centripetal mitochondria within the BS, and have increased fractions of leaf chloroplasts, mitochondria and peroxisomes within the BS relative to H. glutinosa. Analysis of leaf gas exchange, cell ultrastructure and transcript expression show M. loliiforme is a C4 plant of the NADP-malic enzyme subtype. Homolepis comprises two sister clades, one containing H. glutinosa and H. villaricensis and the second H. longispicula and H. aturensis. Homolepis isocalycia is of hybrid origin, its parents being H. aturensis and a common ancestor of the C3  Homolepis clade and H. longispicula.

CONCLUSIONS: Photosynthetic activation of BS tissue in the sub-C2 and C2 species of Homolepis is similar to patterns observed in C3-C4 intermediate eudicots, indicating common evolutionary pathways from C3 to C4 photosynthesis in these disparate clades. Hybridization can diversify the C3-C4 intermediate character state and should be considered in reconstructing putative ancestral states using phylogenetic analyses.}, } @article {pmid39693336, year = {2024}, author = {DeTar, RA and Chustecki, JM and Martinez-Hottovy, A and Ceriotti, LF and Broz, AK and Lou, X and Sanchez-Puerta, MV and Elowsky, C and Christensen, AC and Sloan, DB}, title = {Photosynthetic demands on translational machinery drive retention of redundant tRNA metabolism in plant organelles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {52}, pages = {e2421485121}, pmid = {39693336}, issn = {1091-6490}, support = {MCB-2322154//NSF (NSF)/ ; MCB-2048407//NSF (NSF)/ ; MCB-1933590//NSF (NSF)/ ; IOS-2208908//NSF (NSF)/ ; N/A//University of Nebraska Foundation/ ; }, mesh = {*Photosynthesis ; *Protein Biosynthesis ; *RNA, Transfer/metabolism/genetics ; *Amino Acyl-tRNA Synthetases/metabolism/genetics ; *Mitochondria/metabolism ; *Plastids/metabolism/genetics ; Organelles/metabolism ; Cytosol/metabolism ; Evolution, Molecular ; }, abstract = {Eukaryotic nuclear genomes often encode distinct sets of translation machinery for function in the cytosol vs. organelles (mitochondria and plastids). This raises questions about why multiple translation systems are maintained even though they are capable of comparable functions and whether they evolve differently depending on the compartment where they operate. These questions are particularly interesting in plants because translation machinery, including aminoacyl-transfer RNA (tRNA) synthetases (aaRS), is often dual-targeted to the plastids and mitochondria. These organelles have different functions, with much higher rates of translation in plastids to supply the abundant, rapid-turnover proteins required for photosynthesis. Previous studies have indicated that plant organellar aaRS evolve more slowly compared to mitochondrial aaRS in eukaryotes that lack plastids. Thus, we investigated the evolution of nuclear-encoded organellar and cytosolic aaRS and tRNA maturation enzymes across a broad sampling of angiosperms, including nonphotosynthetic (heterotrophic) plant species with reduced plastid gene expression, to test the hypothesis that translational demands associated with photosynthesis constrain the evolution of enzymes involved in organellar tRNA metabolism. Remarkably, heterotrophic plants exhibited wholesale loss of many organelle-targeted aaRS and other enzymes, even though translation still occurs in their mitochondria and plastids. These losses were often accompanied by apparent retargeting of cytosolic enzymes and tRNAs to the organelles, sometimes preserving aaRS-tRNA charging relationships but other times creating surprising mismatches between cytosolic aaRS and mitochondrial tRNA substrates. Our findings indicate that the presence of a photosynthetic plastid drives the retention of specialized systems for organellar tRNA metabolism.}, } @article {pmid39701103, year = {2025}, author = {Smith, TB and Kopajtich, R and Demain, LAM and Rea, A and Thomas, HB and Schiff, M and Beetz, C and Joss, S and Conway, GS and Shukla, A and Yeole, M and Radhakrishnan, P and Azzouz, H and Ben Chehida, A and Elmaleh-Bergès, M and Glasgow, RIC and Thompson, K and Oláhová, M and He, L and Jenkinson, EM and Jahic, A and Belyantseva, IA and Barzik, M and Urquhart, JE and O'Sullivan, J and Williams, SG and Bhaskar, SS and Carrera, S and Blakes, AJM and Banka, S and Yue, WW and Ellingford, JM and Houlden, H and , and Munro, KJ and Friedman, TB and Taylor, RW and Prokisch, H and O'Keefe, RT and Newman, WG}, title = {Bi-allelic variants in DAP3 result in reduced assembly of the mitoribosomal small subunit with altered apoptosis and a Perrault-syndrome-spectrum phenotype.}, journal = {American journal of human genetics}, volume = {112}, number = {1}, pages = {59-74}, pmid = {39701103}, issn = {1537-6605}, support = {MR/W019027/1/MRC_/Medical Research Council/United Kingdom ; T32 DC000039/DC/NIDCD NIH HHS/United States ; Z01 DC000039/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; Female ; *Apoptosis/genetics ; *Phenotype ; Male ; *Alleles ; *Mitochondrial Ribosomes/metabolism ; Fibroblasts/metabolism ; Child, Preschool ; Child ; Oxidative Phosphorylation ; Mitochondria/metabolism/genetics/pathology ; Mitochondrial Proteins/genetics/metabolism ; Mitochondrial Diseases/genetics/pathology ; Infant ; Ribosomal Proteins/genetics ; Ribosome Subunits, Small/genetics ; }, abstract = {The mitochondrial ribosome (mitoribosome) synthesizes 13 protein subunits of the oxidative phosphorylation system encoded by the mitochondrial genome. The mitoribosome is composed of 12S rRNA, 16S rRNA, and 82 mitoribosomal proteins encoded by nuclear genes. To date, variants in 12 genes encoding mitoribosomal proteins are associated with rare monogenic disorders and frequently show combined oxidative phosphorylation deficiency. Here, we describe five unrelated individuals with bi-allelic variants in death-associated protein 3 (DAP3), a nuclear gene encoding mitoribosomal small subunit 29 (MRPS29), with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. Assessment of respiratory-chain function and proteomic profiling of fibroblasts from affected individuals demonstrated reduced MRPS29 protein amounts and, consequently, decreased levels of additional protein components of the mitoribosomal small subunit, as well as an associated combined deficiency of complexes I and IV. Lentiviral transduction of fibroblasts from affected individuals with wild-type DAP3 cDNA increased DAP3 mRNA expression and partially rescued protein levels of MRPS7, MRPS9, and complex I and IV subunits, demonstrating the pathogenicity of the DAP3 variants. Protein modeling suggested that DAP3 disease-associated missense variants can impact ADP binding, and in vitro assays demonstrated that DAP3 variants can consequently reduce both intrinsic and extrinsic apoptotic sensitivity, DAP3 thermal stability, and DAP3 GTPase activity. Our study presents genetic and functional evidence that bi-allelic variants in DAP3 result in a multisystem disorder of combined oxidative phosphorylation deficiency with pleiotropic presentations, consistent with mitochondrial dysfunction.}, } @article {pmid39703908, year = {2024}, author = {Li, W and Yang, Z and Yan, C and Chen, S and Zhao, X}, title = {The relationship between mitochondrial DNA haplotype and its copy number on body weight and morphological traits of Wuliangshan black-bone chickens.}, journal = {PeerJ}, volume = {12}, number = {}, pages = {e17989}, pmid = {39703908}, issn = {2167-8359}, mesh = {Animals ; *Chickens/genetics/anatomy & histology ; *Haplotypes/genetics ; *DNA, Mitochondrial/genetics ; *Body Weight/genetics ; Female ; *DNA Copy Number Variations ; Phylogeny ; Phenotype ; }, abstract = {Mitochondria play a pivotal role as carriers of genetic information through their circular DNA molecules. The rapid evolution of the D-loop region in mitochondria makes it an ideal molecular marker for exploring genetic differentiation among individuals within species and populations with close kinship. However, the influence of mtDNA D-loop region haplotypes and mtDNA copy numbers on phenotypic traits, particularly production traits in chickens, remains poorly understood. In this comprehensive study, we conducted D-loop region amplification and sequencing in the blood mitochondria of 232 female Wuliangshan black-bone chickens. Our investigation identified a total of 38 haplotypes, with a focus on 10 haplotypes that included more than five individuals. We meticulously analyzed the correlations between these haplotypes and a range of traits, encompassing body weight, tibial length, tibial circumference, body oblique length, chest width, and chest depth. The results unveiled significant disparities in specific tested traits across different haplotypes, indicating a tangible association between mtDNA haplotypes and traits in chickens. These findings underscore the potential impact of mitochondrial DNA variations on energy metabolism, ultimately leading to divergent chicken phenotypes. Furthermore, our examination revealed positive correlations between mtDNA copy numbers and tested traits for select haplotypes, while other haplotypes exhibited non-uniform relationships between traits and mtDNA copy numbers. In addition, phylogenetic analysis disclosed the involvement of two subspecies of red jungle chicken in the origin of Wuliangshan black-bone chickens. Consequently, our research contributes novel insights into mitochondrial genomic selection, augments comprehension of the roles played by haplotypes and mtDNA copy numbers in chicken population genetics and phylogenetic analysis, and furnishes fundamental data crucial for the preservation and provenance determination of black-bone chickens.}, } @article {pmid39732307, year = {2025}, author = {Wang, Z and Sun, W and Zhang, K and Ke, X and Wang, Z}, title = {New insights into the relationship of mitochondrial metabolism and atherosclerosis.}, journal = {Cellular signalling}, volume = {127}, number = {}, pages = {111580}, doi = {10.1016/j.cellsig.2024.111580}, pmid = {39732307}, issn = {1873-3913}, mesh = {Humans ; *Atherosclerosis/metabolism/pathology ; *Mitochondria/metabolism ; Animals ; Muscle, Smooth, Vascular/metabolism ; Mitochondrial Dynamics ; }, abstract = {Atherosclerotic cardiovascular and cerebrovascular diseases are the number one killer of human health. In view of the important role of mitochondria in the formation and evolution of atherosclerosis, our manuscript aims to comprehensively elaborate the relationship between mitochondria and the formation and evolution of atherosclerosis from the aspects of mitochondrial dynamics, mitochondria-organelle interaction (communication), mitochondria and cell death, mitochondria and vascular smooth muscle cell phenotypic switch, etc., which is combined with genome, transcriptome and proteome, in order to provide new ideas for the pathogenesis of atherosclerosis and the diagnosis and treatment of related diseases.}, } @article {pmid39732540, year = {2025}, author = {Golomb, R and Dahan, O and Dahary, D and Pilpel, Y}, title = {Cell-autonomous adaptation: an overlooked avenue of adaptation in human evolution.}, journal = {Trends in genetics : TIG}, volume = {41}, number = {1}, pages = {12-22}, doi = {10.1016/j.tig.2024.10.009}, pmid = {39732540}, issn = {0168-9525}, mesh = {Animals ; Humans ; *Adaptation, Physiological/genetics ; *Biological Evolution ; Evolution, Molecular ; Mitochondria/genetics/metabolism ; Selection, Genetic/genetics ; }, abstract = {Adaptation to environmental conditions occurs over diverse evolutionary timescales. In multi-cellular organisms, adaptive traits are often studied in tissues/organs relevant to the environmental challenge. We argue for the importance of an underappreciated layer of evolutionary adaptation manifesting at the cellular level. Cell-autonomous adaptations (CAAs) are inherited traits that boost organismal fitness by enhancing individual cell function. For instance, the cell-autonomous enhancement of mitochondrial oxygen utilization in hypoxic environments differs from an optimized erythropoiesis response, which involves multiple tissues. We explore the breadth of CAAs across challenges and highlight their counterparts in unicellular organisms. Applying these insights, we mine selection signals in Andean highlanders, revealing novel candidate CAAs. The conservation of CAAs across species may reveal valuable insights into multi-cellular evolution.}, } @article {pmid39738580, year = {2025}, author = {Ahmed, S and Nadeem, MS and Johansson, AM and Jonas, E and Muhammad, K and Mehmood, SA}, title = {Molecular diversity and phylogenetic analysis of ten sheep breeds from Khyber Pakhtunkhwa, Pakistan, based on mitochondrial D-loop sequences.}, journal = {Mammalian genome : official journal of the International Mammalian Genome Society}, volume = {36}, number = {1}, pages = {129-139}, pmid = {39738580}, issn = {1432-1777}, mesh = {Animals ; *Phylogeny ; Pakistan ; *DNA, Mitochondrial/genetics/chemistry ; Sheep/genetics/classification ; *Genetic Variation ; Haplotypes ; Female ; Breeding ; *Mitochondria/genetics ; }, abstract = {Livestock farming has a key role in many rural communities both economically and culturally. It plays an important role in overcoming the deficiencies of meat, milk, wool and various by-products. Pakistan has a large number of livestock, well-adapted to local conditions. and has some of the best tropical dairy breeds. Native sheep breeds stand a vital asset to the country's livestock sector because of their adaptability and unique genetic traits. However, knowledge of the genetic diversity of these sheep breeds remains limited. This study aims to investigate the genetic diversity of 10 local sheep breeds from Khyber Pakhtunkhwa by analyzing the mitochondrial D-loop from 159 individual samples of females. The sequenced data from the mtDNA D-loop showed 106 different haplotypes, with a haplotype diversity of 0.9854 ± 0.0041. Analysis of the mitochondrial D-loop revealed three distinct haplogroups (HapA, HapB, and HapC). Out of the 159 sequences, 125 (77.99%) grouped with HapA, 30 (18.87%) with HapB, and 5 (3.14%) with HapC. While HapA and HapB are commonly found in sheep breeds worldwide, the identification of 5 sequences belonging to HapC was unexpected. This haplogroup was seen in four sheep breeds: Afghani, Australian, Gauder and Waziri. Most interestingly, the two Pakistani-origin breeds, the Waziri sheep breed, from South of Waziristan and the Gauder, a crossbreed, have been identified with HapC haplogroup. This indicates that the sheep breeds of Khyber Pakhtunkhwa belong to three distinct phylogenetic lineages, suggesting a probable gene flow from the southwest to the northeast regions of the province.}, } @article {pmid39748539, year = {2025}, author = {Delmore, KE and DaCosta, JM and Winker, K}, title = {Thrushes in Love: Extensive Gene Flow, With Differential Resistance and Selection, Obscures and Reveals the Evolutionary History of a Songbird Clade.}, journal = {Molecular ecology}, volume = {34}, number = {22}, pages = {e17635}, doi = {10.1111/mec.17635}, pmid = {39748539}, issn = {1365-294X}, support = {R35 GM151012/GM/NIGMS NIH HHS/United States ; 1R35GM151012/GM/NIGMS NIH HHS/United States ; IOS-2143004//Division of Integrative Organismal Systems/ ; 1R35GM151012/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Gene Flow ; *Phylogeny ; *Songbirds/genetics/classification ; *Selection, Genetic ; Animal Migration ; *Biological Evolution ; DNA, Mitochondrial/genetics ; Recombination, Genetic ; Genetics, Population ; *Evolution, Molecular ; Sex Chromosomes/genetics ; }, abstract = {The application of high-throughput sequencing to phylogenetic analyses is allowing authors to reconstruct the true evolutionary history of species. This work can illuminate specific mechanisms underlying divergence when combined with analyses of gene flow, recombination and selection. We conducted a phylogenomic analysis of Catharus, a songbird genus with considerable potential for gene flow, variation in migratory behaviour and genomic resources. We documented discordance among trees constructed for mitochondrial, autosomal and sex (Z) chromosome partitions. Two trees were recovered on the Z. Both trees differed from the autosomes, one matched the mitochondria, and the other was unique to the Z. Gene flow with one species likely generated much of this discordance; substantial admixture between ustulatus and the remaining species was documented and linked to at least two historic events. The tree unique to the Z likely reflects the true history of Catharus; local genomic analyses recovered the same tree in autosomal regions with reduced admixture and recombination. Genes previously connected to migration were enriched in these regions suggesting transitions between migratory and non-migratory states helped generate divergence. Migratory (vs. nonmigratory) Catharus formed a monophyletic clade in a subset of genomic regions. Gene flow was elevated in some of these regions suggesting adaptive introgression may have occurred, but the dominant pattern was of balancing selection maintaining ancestral polymorphisms important for olfaction and perhaps, by extension, adaptation to temperate climates. This work illuminates the evolutionary history of an important model in speciation and demonstrates how differential resistance to gene flow can affect local genomic patterns.}, } @article {pmid39759086, year = {2024}, author = {Zou, J and Liu, Y and Tian, C and Wang, L and Li, S and Ran, J and Yang, X and Nie, G and Peng, W}, title = {Understanding the Complexity of Hypertension with Sarcopenia by Scientometric Analysis.}, journal = {Journal of multidisciplinary healthcare}, volume = {17}, number = {}, pages = {6211-6228}, pmid = {39759086}, issn = {1178-2390}, abstract = {OBJECTIVE: The scientometric analysis was aim to focus on recent studies and clarify new research directions on hypertension with sarcopenia. We hope to provide comprehensive insights or actionable recommendations for clinicians or policymakers.

METHODS: The Web of Science Core Collection database (WoSCC) from 2004 to 2023 for analysis was used. And VOSviewer, CiteSpace, and Origin software were utilized for scientometric analyses.

RESULTS: The United States was the primary contributor to 1,994 studies on hypertension with sarcopenia. The University of São Paulo emerged as the most prolific institution, with Morrell Nicholas W. being the most influential scholar and Cruz-Jentoft A.J. being the most co-cited author. PLoS One was the most prolific journal, whereas Circulation was the most relevant journal. Research has focused not only on physiological, biochemical, and cell biological mechanisms but also on sarcopenia associated with other diseases and involved in various fields, highlighting the complexity of the area and the need for integrative treatment. Keyword analysis revealed that, in addition to hypertension and sarcopenia, other topics such as obesity, pulmonary hypertension, old age, metabolic syndrome, inflammation, hypoxia, exercise, insulin resistance, and revascularization attracted attention. In recent years, COVID-19, mitochondria, handgrip strength, etc. have been hot topics, but aging, skeletal muscle, weight loss, diabetes, obesity, metabolic syndrome, insulin resistance, heart failure, mitochondria, mortality, exercise, and physical activity seems to bridge hypertension and sarcopenia research.

CONCLUSION: This study highlights the distribution of fields, the structure of knowledge and the evolution of major research topics related to hypertension in patients with sarcopenia. Identifying keyword hotspots enhanced the comprehension of occurrence, development, and future research trends related to the topic.}, } @article {pmid39775223, year = {2025}, author = {de Oliveira, EC and Tibúrcio, R and Duarte, G and Lago, A and de Melo, L and Nunes, S and Davanzo, GG and Martins, AJ and Ribeiro, BV and Mothé, D and Menezes, JBP and Veras, P and Tavares, N and Moraes-Vieira, PM and Brodskyn, CI}, title = {Pharmacological inhibition of key metabolic pathways attenuates Leishmania spp infection in macrophages.}, journal = {PLoS neglected tropical diseases}, volume = {19}, number = {1}, pages = {e0012763}, pmid = {39775223}, issn = {1935-2735}, mesh = {*Macrophages/parasitology/metabolism/drug effects ; Animals ; Mice ; Mitochondria/metabolism/drug effects ; *Metabolic Networks and Pathways/drug effects ; *Leishmania/drug effects ; Mice, Inbred C57BL ; Glycolysis/drug effects ; *Antiprotozoal Agents/pharmacology ; Energy Metabolism/drug effects ; *Leishmaniasis/parasitology/drug therapy ; Adenosine Triphosphate/metabolism ; }, abstract = {Macrophages represent a fundamental component of the innate immune system that play a critical role in detecting and responding to pathogens as well as danger signals. Leishmania spp. infections lead to a notable alteration in macrophage metabolism, whereby infected cells display heightened energy metabolism that is linked to the integrity of host mitochondria. However, little is known about how different species of Leishmania manipulate host metabolism. Here, we demonstrate that despite differences in their mechanisms for evading host immune responses, L. amazonensis and L. braziliensis induce comparable disruptions in key metabolic pathways. We found that infected macrophages exhibited an overall elevation in energy metabolism regardless of the parasite strain, evidenced by the elevation in glycolysis and oxygen consumption rates, along with increased proton leak and decreased ATP production. We also analyzed the effects of both Leishmania spp. strain infection on mitochondria function, further revealing that infected cells display heightened mitochondrial mass and membrane potential. To investigate the metabolic pathways required for Leishmania amastigotes to persist in BMDMs, we pre-treated cells with small molecule drugs that target major metabolic pathways, revealing that perturbations in several metabolic processes affected parasite survival in a strain-independent manner. Treatments with inhibitors of the oxidative phosphorylation and glycolysis substantially reduced parasite loads. Collectively, our findings suggest that L.amazonensis and L.braziliensis exploit host cell metabolic pathways similarly to survive in macrophages.}, } @article {pmid39796122, year = {2024}, author = {Queiroz, ALF and Garcia, CB and Silva, JPMO and Cavalini, DFA and Alexandrino, AV and Cunha, AF and Vercesi, AE and Castilho, RF and Shiguemoto, GE}, title = {Preventive Effects of Resistance Training on Hemodynamics and Kidney Mitochondrial Bioenergetic Function in Ovariectomized Rats.}, journal = {International journal of molecular sciences}, volume = {26}, number = {1}, pages = {}, pmid = {39796122}, issn = {1422-0067}, mesh = {Animals ; Female ; Ovariectomy ; *Mitochondria/metabolism ; *Kidney/metabolism ; *Energy Metabolism ; Rats ; Rats, Wistar ; *Resistance Training ; *Hemodynamics ; Physical Conditioning, Animal ; Oxidative Phosphorylation ; Hypertension/prevention & control ; }, abstract = {Menopause occurs due to the depletion of the ovarian reserve, leading to a progressive decline in estrogen (E2) levels. This decrease in E2 levels increases the risk of developing several diseases and can coexist with chronic kidney disease (CKD). Arterial hypertension (AH) is another condition associated with menopause and may either contribute to or result from CKD. Ovariectomy (OVX) induces hypoestrogenism, which can lead to mitochondrial bioenergetic dysfunction in the kidneys. Previous studies have suggested that exercise training has beneficial effects on adults with CKD and AH. To investigate the effects of OVX and resistance training (RT) on hemodynamic parameters and mitochondrial bioenergetic function of the kidney, female Wistar rats were divided into ovariectomized (OVX) and intact (INT) groups. These rats were either kept sedentary (SED) or subjected to RT for thirteen weeks. The RT involved climbing a vertical ladder with a workload apparatus. Hemodynamic parameters were assessed via tail plethysmography. Mitochondrial respiratory function was evaluated with high-resolution respirometry. Gene expression related to the electron transport chain (ETC) and oxidative phosphorylation (OXPHOS) was evaluated by real-time qPCR. At week 13, key hemodynamic parameters (systolic blood pressure and mean arterial pressure) were significantly elevated in the OVX-SED group. Compared with those in the other groups, mitochondrial bioenergetics were impaired in the OVX-SED group. In contrast, the trained groups presented improved mitochondrial bioenergetic function compared with the sedentary groups. OVX led to reduced gene expression related to the mitochondrial ETC and OXPHOS, whereas RT both prevented this reduction and increased gene expression in the trained groups. Our results indicate that hypoestrogenism significantly decreases OXPHOS and ETC capacity in the kidneys of sedentary animals. However, RT effectively increased the expression of genes related to mitochondrial ETC and OXPHOS, thereby counteracting the effects of OVX.}, } @article {pmid39798085, year = {2025}, author = {Martell, E and Kuzmychova, H and Senthil, H and Chawla, U and Kaul, E and Grewal, A and Banerji, V and Anderson, CM and Venugopal, C and Miller, D and Werbowetski-Ogilvie, TE and Singh, SK and Sharif, T}, title = {Disease stage-specific role of the mitochondrial pyruvate carrier suppresses differentiation in temozolomide and radiation-treated glioblastoma.}, journal = {Neuro-oncology}, volume = {27}, number = {5}, pages = {1193-1209}, pmid = {39798085}, issn = {1523-5866}, support = {/CAPMC/CIHR/Canada ; //Natural Sciences and Engineering Research Council/ ; //Manitoba Medical Services Foundation/ ; }, mesh = {Humans ; *Glioblastoma/pathology/metabolism/therapy/drug therapy/radiotherapy ; *Temozolomide/pharmacology/therapeutic use ; Animals ; *Brain Neoplasms/pathology/metabolism/therapy/drug therapy ; Mice ; Antineoplastic Agents, Alkylating/pharmacology/therapeutic use ; Mitochondria/metabolism/drug effects ; *Cell Differentiation/drug effects ; Xenograft Model Antitumor Assays ; *Mitochondrial Membrane Transport Proteins/metabolism ; Tumor Cells, Cultured ; Neoplasm Staging ; *Monocarboxylic Acid Transporters/metabolism ; }, abstract = {BACKGROUND: The mitochondrial pyruvate carrier (MPC), a central metabolic conduit linking glycolysis and mitochondrial metabolism, is instrumental in energy production. However, the role of the MPC in cancer is controversial. In particular, the importance of the MPC in glioblastoma (GBM) disease progression following standard temozolomide (TMZ) and radiation therapy (RT) remains unexplored.

METHODS: Leveraging in vitro and in vivo patient-derived models of TMZ-RT treatment in GBM, we characterize the temporal dynamics of MPC abundance and downstream metabolic consequences using state-of-the-art molecular, metabolic, and functional assays.

RESULTS: Our findings unveil a disease stage-specific role for the MPC, where in posttreatment GBM, but not therapy-naïve tumors, the MPC acts as a central metabolic regulator that suppresses differentiation. Temporal profiling reveals a dynamic metabolic rewiring where a steady increase in MPC abundance favors a shift towards enhanced mitochondrial metabolic activity across patient GBM samples. Intriguingly, while overall mitochondrial metabolism is increased, acetyl-CoA production is reduced in posttreatment GBM cells, hindering histone acetylation and silencing neural differentiation genes in an MPC-dependent manner. Finally, the therapeutic translations of these findings are highlighted by the successful pre-clinical patient-derived orthotopic xenograft trials utilizing a blood-brain-barrier permeable MPC inhibitor, MSDC-0160, which augments standard TMZ-RT therapy to mitigate disease relapse and prolong animal survival.

CONCLUSION: Our findings demonstrate the critical role of the MPC in mediating GBM aggressiveness and molecular evolution following standard TMZ-RT treatment, illuminating a therapeutically-relevant metabolic vulnerability to potentially improve survival outcomes for GBM patients.}, } @article {pmid39804925, year = {2025}, author = {Ricou, A and Simon, M and Duflos, R and Azzopardi, M and Roux, F and Budar, F and Camilleri, C}, title = {Identification of novel genes responsible for a pollen killer present in local natural populations of Arabidopsis thaliana.}, journal = {PLoS genetics}, volume = {21}, number = {1}, pages = {e1011451}, pmid = {39804925}, issn = {1553-7404}, mesh = {*Arabidopsis/genetics ; *Pollen/genetics ; *Arabidopsis Proteins/genetics/metabolism ; CRISPR-Cas Systems ; Mitochondria/genetics ; Alleles ; Genes, Plant ; }, abstract = {Gamete killers are genetic loci that distort segregation in the progeny of hybrids because the killer allele promotes the elimination of the gametes that carry the sensitive allele. They are widely distributed in eukaryotes and are important for understanding genome evolution and speciation. We had previously identified a pollen killer in hybrids between two distant natural accessions of Arabidopsis thaliana. This pollen killer involves three genetically linked genes, and we previously reported the identification of the gene encoding the antidote that protects pollen grains from the killer activity. In this study, we identified the two other genes of the pollen killer by using CRISPR-Cas9 induced mutants. These two genes are necessary for the killer activity that we demonstrated to be specific to pollen. The cellular localization of the pollen killer encoded proteins suggests that the pollen killer activity involves the mitochondria. Sequence analyses reveal predicted domains from the same families in the killer proteins. In addition, the C-terminal half of one of the killer proteins is identical to the antidote, and one amino acid, crucial for the antidote activity, is also essential for the killer function. Investigating more than 700 worldwide accessions of A. thaliana, we confirmed that the locus is subject to important structural rearrangements and copy number variation. By exploiting available de novo genomic sequences, we propose a scenario for the emergence of this pollen killer in A. thaliana. Furthermore, we report the co-occurrence and behavior of killer and sensitive genotypes in several local populations, a prerequisite for studying gamete killer evolution in the wild. This highlights the potential of the Arabidopsis model not only for functional studies of gamete killers but also for investigating their evolutionary trajectories at complementary geographical scales.}, } @article {pmid39806272, year = {2025}, author = {Mazzocca, A and Ferraro, G and Misciagna, G}, title = {The systemic evolutionary theory of the origin of cancer (SETOC): an update.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {31}, number = {1}, pages = {12}, pmid = {39806272}, issn = {1528-3658}, mesh = {Animals ; Humans ; *Biological Evolution ; Cell Transformation, Neoplastic/genetics/metabolism ; *Neoplasms/metabolism/pathology/genetics ; Tumor Microenvironment ; }, abstract = {The Systemic Evolutionary Theory of the Origin of Cancer (SETOC) is a recently proposed theory founded on two primary principles: the cooperative and endosymbiotic process of cell evolution as described by Lynn Margulis, and the integration of complex systems operating in eukaryotic cells, which is a core concept in systems biology. The SETOC proposes that malignant transformation occurs when cells undergo a continuous adaptation process in response to long-term injuries, leading to tissue remodeling, chronic inflammation, fibrosis, and ultimately cancer. This process involves a maladaptive response, wherein the 'endosymbiotic contract' between the nuclear-cytoplasmic system (derived from the primordial archaeal cell) and the mitochondrial system (derived from the primordial α-proteobacterium) gradually breaks down. This ultimately leads to uncoordinated behaviors and functions in transformed cells. The decoupling of the two cellular subsystems causes transformed cells to acquire phenotypic characteristics analogous to those of unicellular organisms, as well as certain biological features of embryonic development that are normally suppressed. These adaptive changes enable cancer cells to survive in the harsh tumor microenvironment characterized by low oxygen concentrations, inadequate nutrients, increased catabolic waste, and increased acidity. De-endosymbiosis reprograms the sequential metabolic functions of glycolysis, the TCA cycle, and oxidative phosphorylation (OxPhos). This leads to increased lactate fermentation (Warburg effect), respiratory chain dysfunction, and TCA cycle reversal. Here, we present an updated version of the SETOC that incorporates the fundamental principles outlined by this theory and integrates the epistemological approach used to develop it.}, } @article {pmid39819387, year = {2025}, author = {Li, H and Liu, L and Qiu, Z and He, F and Dong, W}, title = {Complete mitochondrial genome assembly and comparative analysis of Colocasia esculenta.}, journal = {BMC plant biology}, volume = {25}, number = {1}, pages = {67}, pmid = {39819387}, issn = {1471-2229}, support = {2021GXNSFBA196012, 2022GXNSFAA035493//Natural Science Foundation of Guangxi/ ; TS202113//the Lipu C. esculenta Test Station Project of Guangxi/ ; Gui nongke 2023YM91, Gui nongke 2024YP081//Basic Scientific Research Business Project of Guangxi Academy of Agricultural Sciences/ ; }, mesh = {*Colocasia/genetics ; *Genome, Mitochondrial/genetics ; Phylogeny ; *Genome, Plant ; RNA Editing ; }, abstract = {Colocasia esculenta ranks as the fifth most important tuber crop and is known for its high nutritional and medicinal value. However, there is no research on its mitochondrial genome, hindering in-depth exploration of its genomic resources and genetic relationships. Using second- and third-generation sequencing technologies, we assembled and annotated the mitogenome of C. esculenta. Its mitogenome mainly consists of five circular DNA molecules, with a total length of 594,811 bp and a GC content of 46.25%. A total of 55 genes, 157 simple sequence repeats, 29 tandem repeat sequences, 202 dispersed repeat sequences, and 625 RNA editing sites were detected. Most protein-coding genes use ATG as the start codon, and the third position of the codon tends to be A or T (U). GAA, AUU, and UUU are the most common codons in C. esculenta mitochondria. Finally, based on 28 representative plant species, a phylogenetic tree was constructed, revealing a close relationship between C. esculenta and Araceae. This study provides comprehensive information on C. esculenta, laying a foundation for crop genetics and molecular breeding.}, } @article {pmid39833664, year = {2025}, author = {Tan, S and Wang, W and Li, J and Sha, Z}, title = {Comprehensive analysis of 111 Pleuronectiformes mitochondrial genomes: insights into structure, conservation, variation and evolution.}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {50}, pmid = {39833664}, issn = {1471-2164}, mesh = {Animals ; *Genome, Mitochondrial ; *Flatfishes/genetics/classification ; Phylogeny ; *Evolution, Molecular ; *Genetic Variation ; Codon Usage ; Genomics/methods ; RNA, Transfer/genetics ; Conserved Sequence ; }, abstract = {BACKGROUND: Pleuronectiformes, also known as flatfish, are important model and economic animals. However, a comprehensive genome survey of their important organelles, mitochondria, has been limited. Therefore, we aim to analyze the genomic structure, codon preference, nucleotide diversity, selective pressure and repeat sequences, as well as reconstruct the phylogenetic relationship using the mitochondrial genomes of 111 flatfish species.

RESULTS: Our analysis revealed a conserved gene content of protein-coding genes and rRNA genes, but varying numbers of tRNA genes and control regions across species. Various gene rearrangements were found in flatfish species, especially for the rearrangement of nad5-nad6-cytb block in Samaridae family, the swapping rearrangement of nad6 and cytb gene in Bothidae family, as well as the control region translocation and tRNA-Gln gene inversion in the subfamily Cynoglossinae, suggesting their unique evolutionary history and/or functional benefit. Codon usage showed obvious biases, with adenine being the most frequent nucleotide at the third codon position. Nucleotide diversity and selective pressure analysis suggested that different protein-coding genes underwent varying degrees of evolutionary pressure, with cytb and cox genes being the most conserved ones. Phylogenetic analysis using both whole mitogenome information and concatenated independently aligned protein-coding genes largely mirrored the taxonomic classification of the species, but showed different phylogeny. The identification of simple sequence repeats and various long repetitive sequences provided additional complexity of genome organization and offered markers for evolutionary studies and breeding practices.

CONCLUSIONS: This study represents a significant step forward in our comprehension of the flatfish mitochondrial genomes, providing valuable insights into the structure, conservation and variation within flatfish mitogenomes, with implications for understanding their evolutionary history, functional genomics and fisheries management. Future research can delve deeper into conservation biology, evolutionary biology and functional usages of variations.}, } @article {pmid39834790, year = {2025}, author = {Arias, E and Crawford, AJ and Hertz, A and Parra Olea, G}, title = {Deep cryptic diversity in the Craugastor podiciferus Species Group (Anura: Craugastoridae) of Isthmian Central America revealed by mitochondrial and nuclear data.}, journal = {PeerJ}, volume = {13}, number = {}, pages = {e18212}, pmid = {39834790}, issn = {2167-8359}, mesh = {Animals ; Phylogeny ; *Anura/genetics/classification ; *DNA, Mitochondrial/genetics ; Central America ; Panama ; *Cell Nucleus/genetics ; *Genetic Variation ; *Mitochondria/genetics ; }, abstract = {The Craugastor podiciferus Species Group contains eleven species of terraranan frogs distributed from eastern Honduras to eastern Panama. All species have remarkable color pattern polymorphisms, which may contribute to potential taxonomic problems. We performed exhaustive sampling throughout the geographic distribution of the group to evaluate the phylogenetic relationships and biogeographic history of all named species based on two mitochondrial markers and nuclear ddRAD loci. We also implemented various species delimitation methods to test for the presence of unconfirmed candidate species within the group. Molecular phylogenetic analyses showed that the group contains four major clades. All currently named species are supported by molecular data, yet species richness within the group is clearly underestimated. Species delimitation was discordant between the mitochondrial and nuclear datasets and among analytical methods. Adopting a conservative approach, we propose that the C. podiciferus species group contains at least 12 unconfirmed candidate species. Ancestral area reconstruction showed that the group originated and diversified in the highlands of the Talamancan montane forest ecoregion of Costa Rica and western Panama.}, } @article {pmid39843848, year = {2025}, author = {Luo, L and Wang, M and Liu, Y and Li, J and Bu, F and Yuan, H and Tang, R and Liu, C and He, G}, title = {Sequencing and characterizing human mitochondrial genomes in the biobank-based genomic research paradigm.}, journal = {Science China. Life sciences}, volume = {68}, number = {6}, pages = {1610-1625}, pmid = {39843848}, issn = {1869-1889}, mesh = {Humans ; *DNA, Mitochondrial/genetics ; *Genome, Mitochondrial/genetics ; *Genomics/methods ; *Biological Specimen Banks ; Genetic Variation ; Mutation ; Haplotypes ; Sequence Analysis, DNA/methods ; Mitochondria/genetics ; Heteroplasmy ; }, abstract = {Human mitochondrial DNA (mtDNA) harbors essential mutations linked to aging, neurodegenerative diseases, and complex muscle disorders. Due to its uniparental and haploid inheritance, mtDNA captures matrilineal evolutionary trajectories, playing a crucial role in population and medical genetics. However, critical questions about the genomic diversity patterns, inheritance models, and evolutionary and medical functions of mtDNA remain unresolved or underexplored, particularly in the transition from traditional genotyping to large-scale genomic analyses. This review summarizes recent advancements in data-driven genomic research and technological innovations that address these questions and clarify the biological impact of nuclear-mitochondrial segments (NUMTs) and mtDNA variants on human health, disease, and evolution. We propose a streamlined pipeline to comprehensively identify mtDNA and NUMT genomic diversity using advanced sequencing and computational technologies. Haplotype-resolved mtDNA sequencing and assembly can distinguish authentic mtDNA variants from NUMTs, reduce diagnostic inaccuracies, and provide clearer insights into heteroplasmy patterns and the authenticity of paternal inheritance. This review emphasizes the need for integrative multi-omics approaches and emerging long-read sequencing technologies to gain new insights into mutation mechanisms, the influence of heteroplasmy and paternal inheritance on mtDNA diversity and disease susceptibility, and the detailed functions of NUMTs.}, } @article {pmid39847448, year = {2025}, author = {Wang, S and Luo, H}, title = {Dating the Bacterial Tree of Life Based on Ancient Symbiosis.}, journal = {Systematic biology}, volume = {74}, number = {4}, pages = {639-655}, pmid = {39847448}, issn = {1076-836X}, support = {14116922//Hong Kong Research Grants Council General Research Fund/ ; 42293294//Natural Science Foundation of China/ ; AoE/M-403/16//Hong Kong Research Grants Council Area of Excellence Scheme/ ; }, mesh = {*Symbiosis ; *Phylogeny ; *Bacteria/classification/genetics ; Fossils ; *Classification/methods ; }, abstract = {Obtaining a timescale for bacterial evolution is crucial to understand early life evolution but is difficult owing to the scarcity of bacterial fossils. Here, we introduce multiple new time constraints to calibrate bacterial evolution based on ancient symbiosis. This idea is implemented using a bacterial tree constructed with genes found in the mitochondrial lineages phylogenetically embedded within Proteobacteria. The expanded mitochondria-bacterial tree allows the node age constraints of eukaryotes established by their abundant fossils to be propagated to ancient co-evolving bacterial symbionts and across the bacterial tree of life. Importantly, we formulate a new probabilistic framework that considers uncertainty in inference of the ancestral lifestyle of modern symbionts to apply 19 relative time constraints each informed by host-symbiont association to constrain bacterial symbionts no older than their eukaryotic host. Moreover, we develop an approach to incorporating substitution mixture models that better accommodate substitutional saturation and compositional heterogeneity for dating deep phylogenies. Our analysis estimates that the last bacterial common ancestor occurred approximately 4.0-3.5 billion years ago (Ga), followed by rapid divergence of major bacterial clades. It is generally robust to alternative root ages, root positions, tree topologies, fossil ages, ancestral lifestyle reconstruction, gene sets, among other factors. The obtained timetree serves as a foundation for testing hypotheses regarding bacterial diversification and its correlation with geobiological events across different timescales.}, } @article {pmid39847522, year = {2025}, author = {Weinstein, B and Wang, Z and Zhou, Q and Roy, SW}, title = {ZW Sex Chromosome Differentiation in Palaeognathous Birds Is Associated with Mitochondrial Effective Population Size but Not Mitochondrial Genome Size or Mutation Rate.}, journal = {Genome biology and evolution}, volume = {17}, number = {2}, pages = {}, pmid = {39847522}, issn = {1759-6653}, support = {1616878//National Science Foundation/ ; }, mesh = {Animals ; *Genome, Mitochondrial ; *Mutation Rate ; *Sex Chromosomes/genetics ; Genome Size ; *Birds/genetics ; Population Density ; Female ; Evolution, Molecular ; Male ; }, abstract = {Eukaryotic genome size varies considerably, even among closely related species. The causes of this variation are unclear, but weak selection against supposedly costly "extra" genomic sequences has been central to the debate for over 50 years. The mutational hazard hypothesis, which focuses on the increased mutation rate to null alleles in superfluous sequences, is particularly influential, though challenging to test. This study examines the sex chromosomes and mitochondrial genomes of 15 flightless or semiflighted palaeognathous bird species. In this clade, the nonrecombining portion of the W chromosome has independently expanded stepwise in multiple lineages. Given the shared maternal inheritance of the W chromosome and mitochondria, theory predicts that mitochondrial effective population size (Ne) should decrease due to increased Hill-Robertson interference in lineages with expanded nonrecombining W regions. Our findings support the extent of the nonrecombining W region with three indicators of reduced selective efficiency: (i) the ratio of nonsynonymous to synonymous nucleotide changes in the mitochondrion, (ii) the probability of radical amino acid changes, and (iii) the number of ancient, W-linked genes lost through evolution. Next, we tested whether reduced Ne affects mitochondrial genome size, as predicted by weak selection against genome expansion. We find no support for a relationship between mitochondrial genome size and expanded nonrecombining W regions, nor with increased mitochondrial mutation rates (predicted to modulate selective costs). These results highlight the utility of nonrecombining regions and mitochondrial genomes for studying genome evolution and challenge the general idea of a negative relation between the efficacy of selection and genome size.}, } @article {pmid39848024, year = {2025}, author = {Gureev, AP and Nesterova, VV and Sadovnikova, IS}, title = {Long-range PCR as a tool for evaluating mitochondrial DNA damage: Principles, benefits, and limitations of the technique.}, journal = {DNA repair}, volume = {146}, number = {}, pages = {103812}, doi = {10.1016/j.dnarep.2025.103812}, pmid = {39848024}, issn = {1568-7856}, mesh = {*DNA, Mitochondrial/genetics/metabolism ; Humans ; *DNA Damage ; Animals ; *Polymerase Chain Reaction/methods ; DNA Repair ; Mitochondria/genetics/metabolism ; }, abstract = {Mitochondrial DNA (mtDNA) is often more susceptible to damage compared to nuclear DNA. This is due to its localization in the mitochondrial matrix, where a large portion of reactive oxygen species are produced. Mitochondria do not have histones and mtDNA is only slightly protected by histone-like proteins and is believed to have less efficient repair mechanisms. In this review, we discuss the long-range PCR method, which allows for the effective detection of mtDNA damage. The method is based on the assumption that various types of DNA lesions can interfere the progress of DNA polymerase, resulting in reduced amplification efficiency. It can be used to estimate the number of additional (above background) lesions in mtDNA. The review outlines the evolution of the methodology, its variations, applications in a wide range of model organisms, the advantages of the method and its limitations, as well as ways to overcome these limitations. Over the past two decades, the use of long-range PCR has allowed the study of mtDNA repair mechanisms, the characteristics of mitochondrial genome damage in various neurodegenerative diseases, aging, ischemic and oncological processes, as well as in anticancer therapy. The assessment of mtDNA damage has also been proposed for use in environmental biomonitoring. This review provides a critical evaluation of the various variations of this method, summarizes the accumulated data, and discusses the role of mtDNA damage in different organs at the organismal level.}, } @article {pmid39859262, year = {2025}, author = {Cui, J and Yang, Q and Zhang, J and Ju, C and Cui, S}, title = {Mitochondrial Genome Insights into Evolution and Gene Regulation in Phragmites australis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {2}, pages = {}, pmid = {39859262}, issn = {1422-0067}, support = {31170784, 31972934//National Natural Science Foundation of China/ ; 19530050183//special fund from Capital Normal University/ ; }, mesh = {*Genome, Mitochondrial ; *Evolution, Molecular ; Phylogeny ; *Poaceae/genetics ; *Gene Expression Regulation ; }, abstract = {As a globally distributed perennial Gramineae, Phragmites australis can adapt to harsh ecological environments and has significant economic and environmental values. Here, we performed a complete assembly and annotation of the mitogenome of P. australis using genomic data from the PacBio and BGI platforms. The P. australis mitogenome is a multibranched structure of 501,134 bp, divided into two circular chromosomes of 325,493 bp and 175,641 bp, respectively. A sequence-simplified succinate dehydrogenase 4 gene was identified in this mitogenome, which is often translocated to the nuclear genome in the mitogenomes of gramineous species. We also identified tissue-specific mitochondrial differentially expressed genes using RNAseq data, providing new insights into understanding energy allocation and gene regulatory strategies in the long-term adaptive evolution of P. australis mitochondria. In addition, we studied the mitogenome features of P. australis in more detail, including repetitive sequences, gene Ka/Ks analyses, codon preferences, intracellular gene transfer, RNA editing, and multispecies phylogenetic analyses. Our results provide an essential molecular resource for understanding the genetic characterisation of the mitogenome of P. australis and provide a research basis for population genetics and species evolution in Arundiaceae.}, } @article {pmid39860980, year = {2024}, author = {Han, L and Yang, Y and Lu, M and Yu, H and Lu, Y and Zhou, M and Liu, T and Zhang, R and Chen, B and Hou, Z}, title = {Mitogenome Phylogenetics of Spiruromorpha Porpoise Parasite: Insights Into Phylogeny of Crassicauda magna.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {39860980}, issn = {2076-0817}, support = {415471//the Postdoctoral Funding Program of Heilongjiang Province, China/ ; GZC20230394//the State-sponsored Postdoctoral Researcher program/ ; }, mesh = {Animals ; *Phylogeny ; *Genome, Mitochondrial ; *Porpoises/parasitology ; }, abstract = {(1) Background: Crassicauda magna is a major parasite of large porpoises and whales and has been classified in the Habronematoidea family. However, there has been a great controversy regarding its classification. Mitochondria have an important function in revealing taxonomic and evolutionary history. (2) Methods: In this study, we sequenced the mitochondrial genome of C. magna and conducted a phylogenetic analysis with the mitochondrial sequences of species belonging to the Habronematoidea family. (3) Results: The complete mitochondrial genome was 13,604 bp and it has an AT-rich sequence and one non-coding region (NCR). The reconstruction of the ancestral state showed that the gene orders of all species in Spirurina were conserved. The phylogenetic tree indicates that C. magna is closer to Heliconema longissimum (Physalopteroidea) than Tetrameres grusi (Habronematoidea). (4) Conclusions: This study provides new evidence that C. magna is phylogenetically closer to Physalopteroidea at the molecular taxonomic level.}, } @article {pmid39863913, year = {2025}, author = {Komza, M and Khatun, J and Gelles, JD and Trotta, AP and Abraham-Enachescu, I and Henao, J and Elsaadi, A and Kotini, AG and Clementelli, C and Arandela, J and Ghaity-Beckley, SE and Barua, A and Chen, Y and Berisa, M and Marcellino, BK and Papapetrou, EP and Poyurovsky, MV and Chipuk, JE}, title = {Metabolic adaptations to acute glucose uptake inhibition converge upon mitochondrial respiration for leukemia cell survival.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {47}, pmid = {39863913}, issn = {1478-811X}, support = {R01 CA237264/CA/NCI NIH HHS/United States ; R01 CA267696/CA/NCI NIH HHS/United States ; R01 CA271346/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Glucose/metabolism ; *Mitochondria/metabolism/drug effects ; Cell Survival/drug effects ; Cell Line, Tumor ; Cell Respiration/drug effects ; Oxidative Phosphorylation/drug effects ; Glycolysis/drug effects ; *Adaptation, Physiological/drug effects ; *Leukemia/metabolism/pathology ; *Leukemia, Myeloid, Acute/metabolism/pathology ; }, abstract = {One hallmark of cancer is the upregulation and dependency on glucose metabolism to fuel macromolecule biosynthesis and rapid proliferation. Despite significant pre-clinical effort to exploit this pathway, additional mechanistic insights are necessary to prioritize the diversity of metabolic adaptations upon acute loss of glucose metabolism. Here, we investigated a potent small molecule inhibitor to Class I glucose transporters, KL-11743, using glycolytic leukemia cell lines and patient-based model systems. Our results reveal that while several metabolic adaptations occur in response to acute glucose uptake inhibition, the most critical is increased mitochondrial oxidative phosphorylation. KL-11743 treatment efficiently blocks the majority of glucose uptake and glycolysis, yet markedly increases mitochondrial respiration via enhanced Complex I function. Compared to partial glucose uptake inhibition, dependency on mitochondrial respiration is less apparent suggesting robust blockage of glucose uptake is essential to create a metabolic vulnerability. When wild-type and oncogenic RAS patient-derived induced pluripotent stem cell acute myeloid leukemia (AML) models were examined, KL-11743 mediated induction of mitochondrial respiration and dependency for survival associated with oncogenic RAS. Furthermore, we examined the therapeutic potential of these observations by treating a cohort of primary AML patient samples with KL-11743 and witnessed similar dependency on mitochondrial respiration for sustained cellular survival. Together, these data highlight conserved adaptations to acute glucose uptake inhibition in diverse leukemic models and AML patient samples, and position mitochondrial respiration as a key determinant of treatment success.}, } @article {pmid39870744, year = {2025}, author = {Tan, I and Chothani, S and Lim, HH and Lam, KP}, title = {Alu-Sc-mediated exonization generated a mitochondrial LKB1 gene variant found only in higher order primates.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {3360}, pmid = {39870744}, issn = {2045-2322}, mesh = {Animals ; *Alu Elements/genetics ; Humans ; *Exons/genetics ; *Protein Serine-Threonine Kinases/genetics ; *Primates/genetics ; AMP-Activated Protein Kinase Kinases ; Alternative Splicing ; *Mitochondria/genetics ; Introns ; Evolution, Molecular ; }, abstract = {The tumor suppressor LKB1/STK11 plays important roles in regulating cellular metabolism and stress responses and its mutations are associated with various cancers. We recently identified a novel exon 1b within intron 1 of human LKB1/STK11, which generates an alternatively spliced, mitochondria-targeting LKB1 isoform important for regulating mitochondrial oxidative stress. Here we examined the formation of this novel exon 1b and uncovered its relatively late emergence during evolution. Analyses of putative exon 1b genomic sequences within the primate superfamily indicated that the exonization of LKB1/STK11 exon 1b was mediated by the conserved retrotransposable element Alu-Sc. While putative exon 1b sequences are recognizable in most members of the primate family from New World Monkeys onwards, characteristically functional LKB1/STK11 exon 1b, with translation start and 5' and 3' splice sites, could only be found in greater apes and human, and interestingly, correlates with their increased body mass and longevity development.}, } @article {pmid39871928, year = {2022}, author = {Li, J and Cui, J and Tian, Y}, title = {Neuron-periphery mitochondrial stress communication in aging and diseases.}, journal = {Life medicine}, volume = {1}, number = {2}, pages = {168-178}, pmid = {39871928}, issn = {2755-1733}, abstract = {The nervous system is the central hub of the body, detecting environmental and internal stimuli to regulate organismal metabolism via communications to the peripheral tissues. Mitochondria play an essential role in neuronal activity by supplying energy, maintaining cellular metabolism, and buffering calcium levels. A variety of mitochondrial conditions are associated with aging and age-related neurological disorders. Beyond regulating individual neuron cells, mitochondria also coordinate signaling in tissues and organs during stress conditions to mediate systemic metabolism and enable organisms to adapt to such stresses. In addition, peripheral organs and immune cells can also produce signaling molecules to modulate neuronal function. Recent studies have found that mitokines released upon mitochondrial stresses affect metabolism and the physiology of different tissues and organs at a distance. Here, we summarize recent advances in understanding neuron-periphery mitochondrial stress communication and how mitokine signals contribute to the systemic regulation of metabolism and aging with potential implications for therapeutic strategies.}, } @article {pmid39878681, year = {2025}, author = {Zhao, K and Zhang, H and Ding, W and Yu, X and Hou, Y and Liu, X and Li, X and Wang, X}, title = {Adipokines regulate the development and progression of MASLD through organellar oxidative stress.}, journal = {Hepatology communications}, volume = {9}, number = {2}, pages = {}, pmid = {39878681}, issn = {2471-254X}, mesh = {Humans ; *Oxidative Stress/physiology ; *Adipokines/metabolism/physiology ; Disease Progression ; Endoplasmic Reticulum Stress ; *Fatty Liver/metabolism/etiology ; Reactive Oxygen Species/metabolism ; Animals ; Mitochondria/metabolism ; Adipose Tissue/metabolism ; }, abstract = {The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), which is increasingly being recognized as a leading cause of chronic liver pathology globally, is increasing. The pathophysiological underpinnings of its progression, which is currently under active investigation, involve oxidative stress. Human adipose tissue, an integral endocrine organ, secretes an array of adipokines that are modulated by dietary patterns and lifestyle choices. These adipokines intricately orchestrate regulatory pathways that impact glucose and lipid metabolism, oxidative stress, and mitochondrial function, thereby influencing the evolution of hepatic steatosis and progression to metabolic dysfunction-associated steatohepatitis (MASH). This review examines recent data, underscoring the critical interplay of oxidative stress, reactive oxygen species, and redox signaling in adipokine-mediated mechanisms. The role of various adipokines in regulating the onset and progression of MASLD/MASH through mitochondrial dysfunction and endoplasmic reticulum stress and the underlying mechanisms are discussed. Due to the emerging correlation between adipokines and the development of MASLD positions, these adipokines are potential targets for the development of innovative therapeutic interventions for MASLD management. A comprehensive understanding of the pathogenesis of MASLD/MASH is instrumental for identifying therapies for MASH.}, } @article {pmid39888573, year = {2025}, author = {Brzezniakiewicz-Janus, K and Jarczak, J and Konopko, A and Ratajczak, J and Kucia, M and Ratajczak, MZ}, title = {Mitochondria Express Functional Signaling Ligand-Binding Receptors that Regulate their Biological Responses - the Novel Role of Mitochondria as Stress-Response Sentinels.}, journal = {Stem cell reviews and reports}, volume = {21}, number = {3}, pages = {597-604}, pmid = {39888573}, issn = {2629-3277}, support = {UMO-2022/45/B/NZ6/00475//Narodowe Centrum Nauki/ ; }, mesh = {Humans ; *Mitochondria/metabolism ; *Signal Transduction ; Animals ; *Stress, Physiological ; Ligands ; }, abstract = {Evidence accumulated mitochondria, as the "powerplants of the cell," express several functional receptors for external ligands that modify their function and regulate cell biology. This review sheds new light on the role of these organelles in sensing external stimuli to facilitate energy production for cellular needs. This is possible because mitochondria express some receptors on their membranes that are responsible for their autonomous responses. This is not surprising given the widely accepted hypothesis that these intracellular organelles originated from prokaryotic ancestors that fused with eukaryotic cells during early evolution. It has been reported that mitochondria express functional estrogen, androgen, glucocorticoid, 5-hydroxytryptamine, melatonin, and cannabinoid receptors. What is intriguing is recent evidence showing that mitochondria could also be directly regulated by active mediators of intracellular complement (complosome) and intrinsic mediators of purinergic signaling. Accordingly, they express receptors for intracellular complement cleavage fragments (C5a and C3a) as well as for adenosine triphosphate (ATP), which, besides its crucial role in transferring energy in the cells, is also an important signaling molecule interacting with P2X7 receptor expressed not only on the cell surface but also on the mitochondria membrane. Based on this, intrinsic complosome and purinergic signaling mediators emerge as important cooperating regulators of reactive oxygen species (ROS) release from mitochondria and activators of intracellular pattern recognition receptor Nlrp3 inflammasome. This activation within the beneficial "hormetic zone response" regulates cell metabolism, proliferation, migration, and adaptation to the surrounding challenges of the microenvironment in a favorable way.}, } @article {pmid39892609, year = {2025}, author = {Liu, K and Zhang, L and Xu, X and Song, M and Ding, H and Xiao, L and Wen, J and Zhou, C and Bai, J and Liu, Y}, title = {Lactational high weight loss impairs follicular development by causing mitochondrial dysfunction of ovarian cells in sows and mitigated by butyrate supplement.}, journal = {Journal of advanced research}, volume = {78}, number = {}, pages = {11-28}, pmid = {39892609}, issn = {2090-1224}, mesh = {Animals ; Female ; Swine ; *Mitochondria/metabolism/drug effects/pathology ; *Butyrates/pharmacology ; *Lactation/physiology ; Mice ; *Ovarian Follicle/drug effects/metabolism ; *Weight Loss/physiology ; Dietary Supplements ; Ovary/metabolism/drug effects ; Granulosa Cells/metabolism/drug effects ; }, abstract = {INTRODUCTION: In modern sows, lactational high weight loss (HWL), caused by the large litter size and inadequate feed intake, has a negative effect on follicular development after weaning, resulting in poor reproductive performance in the subsequent parity. However, the underlying mechanism remains unclear.

OBJECTIVES: This research aimed to explore the mechanism that sows HWL during lactation damages follicular development and attempt to improve the reproductive function by treating with butyrate.

METHOD: Four multiparous sister sows were chosen to build a HWL model for lactating sows through feed restriction during the final week of a 21-day lactation. Spatially transcriptomics (ST) and tissue immunofluorescent staining were then utilized for the antral follicles in the ovarian surface to search for differentially expressed genes and proteins among different cell types. Subsequently, the mouse assay, including immunofluorescent staining, transmission electron microscopy, hormone detection and western blot, were conducted to verify the findings in sows and investigate the effect of butyrate on the follicular development in HWL mice.

RESULTS: Based on the transcriptomic analysis, differentially expressed genes in granulosa cells, theca cells, and ovarian stromal cells were examined. The findings revealed that HWL disturbs the mitochondrial electron transport chain and steroidogenesis in all three cell types by downregulating the expression of NDUFB3, SDHB, CYCS, COX8A and CYP19A1, as well as upregulating the expression of STAR, CYP11A1 and CYP17A1. Furthermore, results from mouse assays demonstrated that HWL causes apoptosis and alters sex hormone secretion by impairing mitochondrial function and disordering the expression of steroidogenesis key enzymes in ovarian cells, while these effects were partially mitigated by butyrate treatment.

CONCLUSION: The mitochondrial dysfunction and abnormal steroidogenesis induced by HWL during lactation in ovarian cells harm the follicular development of weaning sows, which could be alleviated by butyrate treatment.}, } @article {pmid39892694, year = {2025}, author = {Uzoigwe, CE}, title = {Nuclear quantum effects explain chemiosmosis: The power of the proton.}, journal = {Bio Systems}, volume = {251}, number = {}, pages = {105407}, doi = {10.1016/j.biosystems.2025.105407}, pmid = {39892694}, issn = {1872-8324}, mesh = {Humans ; *Adenosine Triphosphate/metabolism ; Hydrogen/chemistry/metabolism ; Hydrogen Bonding ; Mitochondria/metabolism ; *Protons ; *Quantum Theory ; Thermodynamics ; Water/chemistry/metabolism ; }, abstract = {ATP is a universal bio-currency, with chemiosmosis the metabolic mint by which currency is printed. Chemiosmosis leverages a membrane potential and ion gradient, typically a proton gradient, to generate ATP. The current chemiosmotic hypothesis is both cannon and dogma. However, there are obstacles to the unqualified and uncritical acceptance of this model. Intriguingly the proton is sufficiently small to exhibit quantum phenomena of wave-particle duality, often thought the exclusive prerogative of smaller subcellular particles. Evidence shows that chemiosmosis is by necessity critically dependent upon these nuclear quantum effects (NQE) of hydrogen, most notably as a proton. It is well established scientific orthodoxy that protons in water and hydrogen atoms of water molecules exhibit quantum phenomena. The effect is amplified by the hydrogen bonding and juxta-membrane location of protons in mitochondria and chloroplasts. NQE explains the otherwise inexplicable features of chemiosmosis, including the paucity of protons, the rate of proton movement and ATP genesis in otherwise subliminal proton motive forces and thus functionality of alkaliphiles. It also accounts for the efficiencies of chemiosmosis reported at greater than 100% in certain contexts, which violates the second law of thermodynamics under the paradigm of classical physics. Mitochondria may have evolved to exploit quantum biology with notable features such as dimeric ATP synthases adumbrating the first double-slip experiment with the protons. The dramatic global deceleration of mitochondrial chemiosmosis and all cellular function following proton substitution with its heavier isotopes, deuterium and tritium: "deuteruction", is testimony to the primacy of nuclear quantum effects in this Quantum Chemiosmosis. Indeed the speed of evolution itself and its inexorable route to homeothermy may be due to the power of nuclear quantum effects of the smallest nucleus, the proton. The atom that is almost nothing was selected to bring about the most important processes and complex manifestations of life.}, } @article {pmid39893444, year = {2025}, author = {Hao, J and Liang, Y and Wang, T and Su, Y}, title = {Correlations of gene expression, codon usage bias, and evolutionary rates of the mitochondrial genome show tissue differentiation in Ophioglossum vulgatum.}, journal = {BMC plant biology}, volume = {25}, number = {1}, pages = {134}, pmid = {39893444}, issn = {1471-2229}, support = {31872670//National Natural Science Foundation of China/ ; 32071781//National Natural Science Foundation of China/ ; }, mesh = {*Codon Usage ; *Evolution, Molecular ; *Genome, Mitochondrial/genetics ; *Lamiales/genetics/growth & development ; Gene Expression Regulation, Plant ; Codon ; }, abstract = {BACKGROUND: Mitochondria are crucial for energy production in plant tissues, but their quantity and activity vary in different tissues and developmental processes. Determining the factors underlying differential molecular evolutionary rates has long been a central question in evolutionary biology, with expression level emerging as the prime predictor. Although we have previously observed an anti-correlation between expression level (E) and evolutionary rate (R) in chloroplast genes, it remains unclear whether such an anti-correlation exists in plant mitochondrial genes. Ophioglossum vulgatum is a typical plant belonging to the Ophioglossaceae, characterized by its unique morphology with only a single leaf above ground. It holds significant scientific and medicinal value. Using the mitochondrial genome and transcriptome data of O. vulgatum, we first analyzed the correlation between mitochondrial gene expression, codon usage bias, and evolutionary rates in different tissues.

RESULTS: Our findings indicated that mitochondrial gene expression level was the strongest between stem and leaf, while the weakest was between sporangium and root. Kruskal-Wallis tests revealed significant differences across various tissue types. Codon usage bias was influenced by both mutation and selection, with selection exerting a greater impact. The Spearman's rank correlation coefficients between codon adaptation index and expression levels of sporangium, stem, leaf, and root were 0.1178, 0.3926, 0.4463, and 0.2945, respectively, with significance in stem and leaf (P < 0.05). The correlation coefficients between the nonsynonymous substitution rate (dN) and expression levels in sporangium, stem, leaf, and root were -0.0840, -0.1786, -0.1714, and -0.0857, respectively, yet none are statistically significant. The correlation coefficient between the synonymous substitution rate (dS) and expression levels in sporangium was negative, whereas those between dS and the stem, leaf, and root were positive, although they were not significant. The dN/dS ratio exhibited a significant negative correlation with expression levels in both leaf and root (P < 0.05).

CONCLUSIONS: For the first time, our study revealed differences in the correlation between mitochondrial gene expression and codon usage bias, as well as evolutionary rates, across various tissues of O. vulgatum. Moreover, we also provide novel insights into understanding the effects of plant mitochondrial gene expression on evolutionary patterns.}, } @article {pmid39893979, year = {2025}, author = {Duan, C and Zhao, Y and Xiao, Y and Hou, Y and Gong, W and Zhang, H and Wang, Y and Nie, X}, title = {Lithium with environmentally relevant concentrations interferes with mitochondrial function, antioxidant response, and autophagy processes in Daphnia magna, leading to changes in life-history traits and behavior.}, journal = {Journal of hazardous materials}, volume = {488}, number = {}, pages = {137420}, doi = {10.1016/j.jhazmat.2025.137420}, pmid = {39893979}, issn = {1873-3336}, mesh = {Animals ; *Daphnia/drug effects/physiology/metabolism ; Autophagy/drug effects ; *Water Pollutants, Chemical/toxicity ; *Mitochondria/drug effects/metabolism ; *Lithium/toxicity ; *Antioxidants/metabolism ; Behavior, Animal/drug effects ; Life History Traits ; Oxidative Stress/drug effects ; Reactive Oxygen Species/metabolism ; Daphnia magna ; }, abstract = {With the increasing production and use of lithium-based products, concerns over lithium pollution in aquatic ecosystems are increasing, whereas research on its toxicity mechanisms in aquatic organisms remains limited. The main objective of the present study was to explore the effects of environmentally relevant concentrations of lithium exposure on the life-history strategy, behavior, antioxidant system, and autophagy process of Daphnia magna. Acute (24-96 h) and chronic (21 days) exposure experiments under three lithium treatments (low: 8.34 μg/L, medium: 83.44 μg/L, and high: 834.41 μg/L) were conducted. The results indicated that exposure to medium and high lithium concentrations led to eye and tail deformities in D. magna. Furthermore, developmental and reproductive parameters such as body length, total neonates per female, and average neonates per time were negatively influenced. Lithium also interfered with energy metabolism to cause the decreasing swimming speed and the reduction in the swimming range. In addition, lithium exposure affected the expression of gsk-3β, further disrupting the dynamic balance of mitochondrial fission, fusion, and regeneration, which caused ROS accumulation and induced oxidative stress. D. magna attenuated the stress by activating the FoxO/SESN and Nrf2/Keap1 pathways, synergistically enhancing downstream antioxidant enzymes expression. Concurrently, D. magna also mitigated oxidative stress and mitochondrial damage by promoting autophagy and inhibiting apoptosis. In summary, lithium harmed the physiological and biochemical functions of D. magna through multiple mechanisms, suggesting that environmental lithium pollution may pose a potential threat to aquatic organisms.}, } @article {pmid39901091, year = {2025}, author = {Park, S and Hwang, Y and Kim, H and Choi, K}, title = {Insights into the nuclear-organelle DNA integration in Cicuta virosa (Apiaceae) provided by complete plastid and mitochondrial genomes.}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {102}, pmid = {39901091}, issn = {1471-2164}, mesh = {*Genome, Mitochondrial ; *Cell Nucleus/genetics ; *Genome, Plastid ; Phylogeny ; *Plastids/genetics ; Genome, Plant ; Evolution, Molecular ; DNA, Plant/genetics ; }, abstract = {BACKGROUND: Gene transfer between the organelles and the nucleus plays a central role in shaping plant genome evolution. The identification and analysis of nuclear DNA of plastid (NUPTs) and mitochondrial (NUMTs) origins are important for exploring the extent of intracellular DNA transfer in genomes.

RESULTS: We report the complete plastid and mitochondrial genomes (plastome and mitogenome) of Cicuta virosa (Apiaceae) as well as a draft nuclear genome using high-fidelity (HiFi) PacBio sequencing technologies. The C. virosa plastome (154,449 bp) is highly conserved, with a quadripartite structure, whereas the mitogenome (406,112 bp) exhibits two chromosomes (352,718 bp and 53,394 bp). The mitochondrial-encoded genes (rpl2, rps14, rps19, and sdh3) were successfully transferred to the nuclear genome. Our findings revealed extensive DNA transfer from organelles to the nucleus, with 6,686 NUPTs and 6,237 NUMTs detected, covering nearly the entire plastome (99.93%) and a substantial portion of the mitogenome (77.04%). These transfers exhibit a range of sequence identities (80-100%), suggesting multiple transfer events over evolutionary timescales. Recent DNA transfer between organelles and the nucleus is more frequent in mitochondria than that in plastids.

CONCLUSIONS: This study contributes to the understanding of ongoing genome evolution in C. virosa and underscores the significance of the organelle-nuclear genome interplay in plant species. Our findings provide valuable insights into the evolutionary processes that shape organelle genomes in Apiaceae, with implications for broader plant genome evolution.}, } @article {pmid39903101, year = {2025}, author = {Iliushchenko, D and Efimenko, B and Mikhailova, AG and Shamanskiy, V and Saparbaev, MK and Matkarimov, BT and Mazunin, I and Voronka, A and Knorre, D and Kunz, WS and Kapranov, P and Denisov, S and Fellay, J and Khrapko, K and Gunbin, K and Popadin, K}, title = {Deciphering the Foundations of Mitochondrial Mutational Spectra: Replication-Driven and Damage-Induced Signatures Across Chordate Classes.}, journal = {Molecular biology and evolution}, volume = {42}, number = {2}, pages = {}, pmid = {39903101}, issn = {1537-1719}, support = {//Federal Academic Leadership Program Priority 2030/ ; //Immanuel Kant Baltic Federal University/ ; 21-75-20143//Russian Science Foundation/ ; 075-15-2021-1084//Ministry of Science and Higher Education of the Russian Federation/ ; KU 911/22-1//Deutsche Forschungsgemeinschaft/ ; AP23485899//Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; }, mesh = {*DNA, Mitochondrial/genetics ; DNA Replication ; Animals ; *Mutation ; DNA Damage ; Mutagenesis ; DNA Repair ; DNA Polymerase gamma ; Mitochondria/genetics ; DNA Mismatch Repair ; DNA-Directed DNA Polymerase/genetics ; }, abstract = {Mitochondrial DNA (mtDNA) mutagenesis remains poorly understood despite its crucial role in disease, aging, and evolutionary tracing. In this study, we reconstructed a comprehensive 192-component mtDNA mutational spectrum for chordates by analyzing 118,397 synonymous mutations in the CytB gene across 1,697 species and five classes. This analysis revealed three primary forces shaping mtDNA mutagenesis: (i) symmetrical, replication-driven errors by mitochondrial polymerase (POLG), resulting in C > T and A > G mutations that are highly conserved across classes; (ii) asymmetrical, damage-driven C > T mutations on the single-stranded heavy strand with clock-like dynamics; and (iii) asymmetrical A > G mutations on the heavy strand, with dynamics suggesting sensitivity to oxidative damage. The third component, sensitive to oxidative damage, positions mtDNA mutagenesis as a promising marker for metabolic and physiological processes across various classes, species, organisms, tissues, and cells. The deconvolution of the mutational spectra into mutational signatures uncovered deficiencies in both base excision repair (BER) and mismatch repair (MMR) pathways. Further analysis of mutation hotspots, abasic sites, and mutational asymmetries underscores the critical role of single-stranded DNA damage (components ii and iii), which, uncorrected due to BER and MMR deficiencies, contributes roughly as many mutations as POLG-induced errors (component i).}, } @article {pmid39906580, year = {2025}, author = {Erkosar, B and Dupuis, C and Savary, L and Kawecki, TJ}, title = {Shared genetic architecture links energy metabolism, behavior and starvation resistance along a power-endurance axis.}, journal = {Evolution letters}, volume = {9}, number = {1}, pages = {150-162}, pmid = {39906580}, issn = {2056-3744}, abstract = {Shared developmental, physiological, and molecular mechanisms can generate strong genetic covariances across suites of traits, constraining genetic variability, and evolvability to certain axes in multivariate trait space ("variational modules" or "syndromes"). Such trait suites will not only respond jointly to selection; they will also covary across populations that diverged from one another by genetic drift. We report evidence for such a genetically correlated trait suite that links traits related to energy metabolism along a "power-endurance" axis in Drosophila melanogaster. The "power" pole of the axis is characterized by high potential for energy generation and expenditure-high expression of glycolysis and TCA cycle genes, high abundance of mitochondria, and high spontaneous locomotor activity. The opposite "endurance" pole is characterized by high triglyceride (fat) reserves, locomotor endurance, and starvation resistance (and low values of traits associated with the "power" pole). This trait suite also aligns with the first principal component of metabolome; the "power" direction is characterized by low levels of trehalose (blood sugar) and high levels of some amino acids and their derivatives, including creatine, a compound known to facilitate energy production in muscles. Our evidence comes from six replicate "Selected" populations adapted to a nutrient-poor larval diet regime during 250 generations of experimental evolution and six "Control" populations evolved in parallel on a standard diet regime. We found that, within each of these experimental evolutionary regimes, the above traits strongly covaried along this "power-endurance" axis across replicate populations which diversified by drift, indicating a shared genetic architecture. The two evolutionary regimes also drove divergence along this axis, with Selected populations on average displaced towards the "power" direction compared to Controls. Aspects of this "power-endurance" axis resemble the "pace of life" syndrome and the "thrifty phenotype"; it may have evolved as part of a coordinated organismal response to nutritional conditions.}, } @article {pmid39913674, year = {2025}, author = {Lavrov, DV and Turner, TL and Vicente, J}, title = {Pervasive Mitochondrial tRNA Gene Loss in Clade B of Haplosclerid Sponges (Porifera, Demospongiae).}, journal = {Genome biology and evolution}, volume = {17}, number = {3}, pages = {}, pmid = {39913674}, issn = {1759-6653}, support = {2048457//National Science Foundation/ ; }, mesh = {Animals ; *Porifera/genetics/classification ; *RNA, Transfer/genetics ; Phylogeny ; Genome, Mitochondrial ; Evolution, Molecular ; *Genes, Mitochondrial ; Mitochondria/genetics ; }, abstract = {Mitochondrial tRNA gene loss and cytosolic tRNA import are two common phenomena in mitochondrial biology, but their importance is often under-appreciated in animals. This is because the mitochondrial DNA (mtDNA) of most bilaterally symmetrical animals (Bilateria) encodes a complete set of tRNAs required for mitochondrial translation. By contrast, the mtDNA of nonbilaterian animals (phyla Cnidaria, Ctenophora, Porifera, and Placozoa) often contains a reduced set of tRNA genes, necessitating tRNA import from the cytosol. Interestingly, in many nonbilaterian lineages, tRNA gene content appears to be set early in evolution and remains conserved thereafter. Here, we report that Clade B of haplosclerid sponges (CBHS) represents an exception to this pattern, displaying considerable variation in tRNA gene content even among relatively closely related species. We determined mt-genome sequences for eight CBHS species and analyzed them in conjunction with six previously available sequences. Additionally, we sequenced mt-genomes for two species of haplosclerid sponges outside the CBHS and used them with eight previously available sequences as outgroups. We found that tRNA gene content varied widely within CBHS, ranging from three in an undescribed Haliclona species (Haliclona sp. TLT785) to 25 in Xestospongia muta and X. testudinaria. Furthermore, we found that all CBHS species outside the genus Xestospongia lacked the atp9 gene, with some also lacking atp8. Analysis of nuclear sequences from Niphates digitalis revealed that both atp8 and atp9 had transferred to the nuclear genome, while the absence of mt-tRNA genes indicated their genuine loss. We argue that CBHS can serve as a valuable system for studying mt-tRNA gene loss, mitochondrial import of cytosolic tRNAs, and the impact of these processes on mitochondrial evolution.}, } @article {pmid39921600, year = {2025}, author = {Shi, X and Ma, C and Chen, N and Xu, MM and Kambal, S and Cai, ZF and Yang, Q and Adeola, AC and Liu, LS and Wang, J and Lu, WF and Li, Y and Msalya, GM and Lei, C and Mwacharo, JM and Han, JL and Hanotte, O and Zhang, YP and Peng, MS}, title = {Selection Increases Mitonuclear DNA Discordance but Reconciles Incompatibility in African Cattle.}, journal = {Molecular biology and evolution}, volume = {42}, number = {2}, pages = {}, pmid = {39921600}, issn = {1537-1719}, support = {2023YFF1001000//National Key Research and Development Program of China/ ; NSFC32388102//National Natural Science Foundation of China/ ; SAJC202103//Sino-Africa Joint Research Center, Chinese Academy of Sciences/ ; }, mesh = {Animals ; Cattle/genetics ; *DNA, Mitochondrial/genetics ; *Selection, Genetic ; Cell Nucleus/genetics ; Female ; Male ; DNA Copy Number Variations ; Hybridization, Genetic ; Mitochondria/genetics ; }, abstract = {Mitochondrial function relies on the coordinated interactions between genes in the mitochondrial DNA and nuclear genomes. Imperfect interactions following mitonuclear incompatibility may lead to reduced fitness. Mitochondrial DNA introgressions across species and populations are common and well documented. Various strategies may be expected to reconcile mitonuclear incompatibility in hybrids or admixed individuals. African admixed cattle (Bos taurus × B. indicus) show sex-biased admixture, with taurine (B. taurus) mitochondrial DNA and a nuclear genome predominantly of humped zebu (B. indicus). Here, we leveraged local ancestry inference approaches to identify the ancestry and distribution patterns of nuclear functional genes associated with the mitochondrial oxidative phosphorylation process in the genomes of African admixed cattle. We show that most of the nuclear genes involved in mitonuclear interactions are under selection and of humped zebu ancestry. Variations in mitochondrial DNA copy number may have contributed to the recovery of optimal mitochondrial function following admixture with the regulation of gene expression, alleviating or nullifying mitochondrial dysfunction. Interestingly, some nuclear mitochondrial genes with enrichment in taurine ancestry may have originated from ancient African aurochs (B. primigenius africanus) introgression. They may have contributed to the local adaptation of African cattle to pathogen burdens. Our study provides further support and new evidence showing that the successful settlement of cattle across the continent was a complex mechanism involving adaptive introgression, mitochondrial DNA copy number variation, regulation of gene expression, and selection of ancestral mitochondria-related genes.}, } @article {pmid39932860, year = {2025}, author = {Zhao, S and Hou, J and Deng, L and Qi, Z and Tao, N and Ruan, W and Zheng, J and Wang, W and Xu, Q and Saiding, Q and Kong, N and Liu, YN and Tao, W}, title = {Lactate-Modulating Nanozyme-Mediated Mitochondrial Respiration Block for Tumor Immunosuppression Remodeling.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {64}, number = {17}, pages = {e202422203}, doi = {10.1002/anie.202422203}, pmid = {39932860}, issn = {1521-3773}, support = {22238013//National Natural Science Foundation of China/ ; 22178393//National Natural Science Foundation of China/ ; 2019TP1001//Hunan Provincial Science and Technology Plan Project/ ; 2020JJ3044//Hunan Provincial Science and Technology Plan Project/ ; //High-Performance Computing Center of Central South University/ ; 2024M764247//China Postdoctoral Science Foundation/ ; LCD1034625//American Lung Association Cancer Discovery award/ ; 2022A017206//American Lung Association Courtney Cox Cole Lung Cancer Research award/ ; 2023A004452//Harvard/Brigham Health & Technology Innovation Fund/ ; 2022A002721//Nanotechnology Foundation/ ; 018129//Distinguished Chair Professorship Foundation/ ; }, mesh = {Humans ; *Lactic Acid/metabolism ; *Mitochondria/metabolism/drug effects ; Tumor Microenvironment/drug effects ; *Neoplasms/metabolism/immunology ; Mixed Function Oxygenases/metabolism ; Copper/chemistry ; Cell Line, Tumor ; }, abstract = {Abnormal lactate metabolism in tumor cells leads to immune escape in the tumor microenvironment. Intervening in specific lactate metabolic pathways while blocking downstream pyruvate influx holds great promise for overcoming conventional lactate-targeted therapy limitations such as short half-life, insufficient lactate consumption, and pathological microenvironment elasticity. Herein, a nanocatalytic medicine based on carbondoping engineered copper nitride enzyme (Cu3N-C NE) with enhanced lactate oxidase (LOX) activity was carefully designed. Computational results revealed that the introduction of C favors activation of the hydroxyalkyl C-H bond in lactate by the polarization of adjacent hydroxyl groups, correspondingly facilitating the abstraction of hydrogen atoms from the desired α-C-H and α-C-O-H groups in lactate via the hydrogen atom-transfer (HAT) process. The Cu3N-C NEs could downregulate lactate levels in tumor cells for robust remodeling of the immunosuppressive microenvironment and further block as-generated pyruvate to influx into the mitochondrial respiration, achieving lactate homeostasis reprogramming. Our study provides a proof-of-concept design of next-generation lactate-modulation nanomedicine via heteroatom-doping and evolution with the additional potential to expedite the industrial production of lactate to pyruvate.}, } @article {pmid39933620, year = {2025}, author = {Tatarczuch, A and Gogola-Mruk, J and Kotarska, K and Polański, Z and Ptak, A}, title = {Mitochondrial activity and steroid secretion in mouse ovarian granulosa cells are suppressed by a PFAS mixture.}, journal = {Toxicology}, volume = {512}, number = {}, pages = {154083}, doi = {10.1016/j.tox.2025.154083}, pmid = {39933620}, issn = {1879-3185}, mesh = {Female ; Animals ; *Fluorocarbons/toxicity ; *Granulosa Cells/drug effects/metabolism ; *Mitochondria/drug effects/metabolism ; Mice ; *Steroids/metabolism ; Progesterone/metabolism ; Reactive Oxygen Species/metabolism ; Cells, Cultured ; Estradiol/metabolism ; Alkanesulfonic Acids/toxicity ; Membrane Potential, Mitochondrial/drug effects ; Endocrine Disruptors/toxicity ; }, abstract = {The accumulation of a number of per- and polyfluoroalkyl substances (PFASs) in ovarian follicular fluid (FF) has been documented, raising serious questions about their impact on female fertility. Here, we tested the hypothesis that a mixture of PFASs acts in a paracrine manner on granulosa cells (GCs) as a metabolism-disrupting chemical. We selected perfluorooctane sulfonate (PFOS; 22.4 ng/mL), perfluorooctanoic acid (PFOA; 14.5 ng/mL), perfluorohexane sulfonate (PFHxS; 21.3 ng/mL), perfluorodecanoic acid (PFDA; 0.9 ng/mL), perfluoroheptane sulphonate (PFHpA; 0.6 ng/mL), perfluoroundecanoic acid (PFUnDA; 0.4 ng/mL), and perfluorononanoic acid (PFNA; 2 ng/mL), which were the most commonly detected PFASs in FF of women undergoing assisted reproductive technology treatment. Exposure of mouse GCs to the PFAS mixture decreased the amount of active mitochondria and the mitochondrial membrane potential, which correlated with a reduction in ATP production and inhibition of oxidative phosphorylation (OXPHOS). At the same time, expression of the mitochondrial membrane-associated steroidogenic enzyme 3-beta-hydroxysteroid dehydrogenase (3βHSD) and production of the major steroids progesterone and estradiol were decreased. In addition, expression and activity of superoxide dismutase 1 (SOD1), an enzyme that neutralizes reactive oxygen species (ROS), were decreased while ROS levels and lipid peroxidation were increased without cell death, indicating that the PFAS mixture had subtoxic effects. Our results show that PFAS mixtures, at concentrations similar to those found in human FF led to GC dysfunction by impairing mitochondrial function and steroid secretions and therefore may have implications for reproductive health.}, } @article {pmid39936990, year = {2025}, author = {Zhang, Y and Sun, J and Li, S and Wang, L and Song, L}, title = {The Potential Mechanism of Cuproptosis in Hemocytes of the Pacific Oyster Crassostrea gigas upon Elesclomol Treatment.}, journal = {Cells}, volume = {14}, number = {3}, pages = {}, pmid = {39936990}, issn = {2073-4409}, support = {32222086, 32230110//National Natural Science Foundation of China/ ; CARS-49//the fund for China Agriculture Research System/ ; No//Outstanding Talents and Innovative Teams of Agricultural Scientific Research in MARA/ ; LT202009//innovation team of Aquaculture Environment Safety from Liaoning Province/ ; XLYC2203087//Liaoning Revitalization Talents Program/ ; 2022RG14//Dalian High Level Talent Innovation Support Program/ ; 2022RY01//Dalian Outstanding Young Scientific and Technological Talent/ ; }, mesh = {Animals ; *Hemocytes/drug effects/metabolism ; *Crassostrea/drug effects/metabolism/cytology ; Mitochondria/metabolism/drug effects ; *Copper/metabolism ; *Hydrazines/pharmacology ; }, abstract = {Cuproptosis is a novel cell death dependent on mitochondrial respiration and regulated by copper. While the study of it is mainly focused on tumor therapy, in the present study, two key cuproptosis-related genes, ferredoxin (FDX1) and dihydrolipoamide S-acetyltransferase (DLAT) homologs (designated as CgFDX1 and CgDLAT), were identified from Crassostrea gigas. CgFDX1 has a Fer2 domain with a 2Fe-2S cluster forming a unique ferredoxin. CgDLAT is composed of a biotin_lipoyl domain, an E3-binding domain, and a 2-oxoacid_dh domain. CgFDX1 and CgDLAT mRNA were expressed in all the examined tissues. After elesclomol treatment, both mRNA and protein expressions of them were reduced in the hemocytes. The mortality rate of the hemocytes increased significantly, and the hemocytes were accompanied with noticeable adhesive abnormalities and heightened secretion after elesclomol treatment. Additionally, the accumulation or depletion of actin was observed in the hemocytes. The integrity of the double membrane structure of the mitochondria was compromised, and the organization of mitochondrial cristae was disrupted. The contents of copper, malondialdehyde (MDA), pyruvic acid and mitoSOX as well as the ratio of cells with low mitochondrial potential increased significantly in the hemocytes upon elesclomol treatment and the content of citric acid decreased significantly. These findings suggest the potential presence of cuproptosis in oysters and its activation mechanism is relatively conserved in evolution.}, } @article {pmid39940743, year = {2025}, author = {Zeng, Q and Yu, Q and Mo, Y and Liang, H and Chen, B and Meng, J}, title = {Genome-Wide Identification and Functional Characterization of the Acyl-CoA Dehydrogenase (ACAD) Family in Fusarium sacchari.}, journal = {International journal of molecular sciences}, volume = {26}, number = {3}, pages = {}, pmid = {39940743}, issn = {1422-0067}, support = {31960031//National Natural Science Foundation of China/ ; 2024GXNSFAA010041//Guangxi Natural Science Foundation/ ; }, mesh = {*Fusarium/genetics/enzymology/pathogenicity ; Phylogeny ; Fatty Acids/metabolism ; *Acyl-CoA Dehydrogenase/genetics/metabolism ; *Genome, Fungal ; Gene Expression Regulation, Fungal ; *Fungal Proteins/genetics/metabolism ; Plant Diseases/microbiology ; Multigene Family ; }, abstract = {Fusarium sacchari is one of the primary causal agents of Pokkah boeng disease (PBD), an important disease of sugarcane worldwide. The acyl-CoA dehydrogenases (ACADs) constitute a family of flavoenzymes involved in the β-oxidation of fatty acids and amino acid catabolism in mitochondria. However, the role of ACADs in the pathogenesis of F. sacchari is unclear. Here, 14 ACAD-encoding genes (FsACAD-1-FsACAD-14) were identified by screening the entire genome sequence of F. sacchari. The FsACAD genes are distributed across seven chromosomes and were classified into seven clades based on phylogenetic analysis of the protein sequences. In vivo mRNA quantification revealed that the FsACAD genes are differentially expressed during sugarcane infection, and their expression patterns differ significantly in response to the in vitro induction of fatty acids of different classes. Fatty acid utilization assays of the FsACAD-deletion mutants revealed that the FsACADs varied in their preference and ability to break down different fatty acids and amino acids. There was variation in the adverse impact of FsACAD-deletion mutants on fungal traits, including growth, conidiation, stress tolerance, and virulence. These findings provide insights into the roles of FsACADs in F. sacchari, and the identification of FsACADs offers potential new targets for the improved control of PBD.}, } @article {pmid39944804, year = {2024}, author = {Vorozheykin, PS and Titov, II}, title = {Computer analysis shows differences between mitochondrial miRNAs and other miRNAs.}, journal = {Vavilovskii zhurnal genetiki i selektsii}, volume = {28}, number = {8}, pages = {834-842}, doi = {10.18699/vjgb-24-91}, pmid = {39944804}, issn = {2500-0462}, abstract = {A subclass of miRNAs with as yet unknown specific functions is mitomiRs - mitochondrial miRNAs that are mainly derived from nuclear DNA and are imported into mitochondria; moreover, changes in the expression levels of mitomiRs are associated with some diseases. To identify the most pronounced characteristics of mitochondrial miRNAs that distinguish them from other miRNAs, we classified mitomiR sequences using the Random Forest algorithm. The analysis revealed, for the first time, a significant difference between mitomiRs and other microRNAs by the following criteria (in descending order of importance in the classification): mitomiRs are evolutionarily older (have a lower phylostratigraphic age index, PAI); have more targets and disease associations, including mitochondrial ones (two-sided Fisher's exact test, average p-values 1.82 × 10-89/1.13 × 10-96 for all mRNA/diseases and 6.01 × 10-22/1.09 × 10-9 for mitochondria, respectively); and are in the class of "circulating" miRNAs (average p- value 1.20 × 10-56). The identified differences between mitomiRs and other miRNAs may help uncover the mode of miRNA delivery into mitochondria, indicate the evolutionary conservation and importance of mitomiRs in the regulation of mitochondrial function and metabolism, and generally show that mitomiRs are not randomly encountered miRNAs. Information on 1,312 experimentally validated mitomiR sequences for three organisms (Homo sapiens, Mus musculus and Rattus norvegicus) is collected in the mitomiRdb database (https://mitomiRdb.org).Key words: mitomiR; mitochondria; miRNA; evolution; database.}, } @article {pmid39944907, year = {2025}, author = {Ruiz, E and Leprieur, F and Sposito, G and Lüthi, M and Schmidlin, M and Panfili, J and Pellissier, L and Albouy, C}, title = {Environmental DNA Epigenetics Accurately Predicts the Age of Cultured Fish Larvae.}, journal = {Ecology and evolution}, volume = {15}, number = {2}, pages = {e70645}, pmid = {39944907}, issn = {2045-7758}, abstract = {While acquiring age information is crucial for efficient stock management and biodiversity conservation, traditional aging methods fail to offer a universal, non-invasive, and precise way of estimating a wild animal's age. DNA methylation from tissue DNA (tDNA) was recently proposed as a method to overcome these issues and showed more accurate results than telomere-length-based age assessments. Here, we used environmental DNA (eDNA) for the first time as a template for age estimation, focusing on the larval phase (10-24 days post-hatch) of cultured Dicentrarchus labrax (seabass), a species of major economic and conservation interest. Using third-generation sequencing, we were able to directly detect various modification types (e.g., cytosine and adenosine methylation in all contexts) across the whole genome using amplification-free nanopore sequencing. However, aging sites were only present in the mitogenome, which could be a specific feature of eDNA methylation or the consequence of better DNA protection within mitochondria. By considering qualitative and quantitative information about aging sites according to an objective model selection framework, our epigenetic clock reached a cross-validated accuracy of 2.6 days (Median Absolute Error). Such performances are higher than those of previous clocks, notably for adult seabass even when scaling MAE to the age range, which could be linked to a more dynamic epigenome during early life stages. Overall, our pilot study proposes new methods to determine the potential of eDNA for simultaneous age and biodiversity assessments, although robust validation of our preliminary results along with methodological developments are needed before field applications can be envisaged.}, } @article {pmid39945506, year = {2026}, author = {Van Gaever, M and Dupuy, O and Dupont, E and Canu, MH and Daussin, F}, title = {Early sensorimotor restriction in rats induces age-dependent mitochondrial alterations in skeletal muscles and brain structures.}, journal = {The Journal of physiology}, volume = {604}, number = {6}, pages = {2512-2524}, pmid = {39945506}, issn = {1469-7793}, mesh = {Animals ; *Muscle, Skeletal/metabolism/physiology ; Male ; Rats ; Rats, Wistar ; *Brain/metabolism ; Citrate (si)-Synthase/metabolism ; *Mitochondria/metabolism/physiology ; *Aging/physiology ; *Mitochondria, Muscle/metabolism/physiology ; Female ; }, abstract = {A sedentary lifestyle can lead to motor and cognitive deficits, increasing the risk of neurodegenerative diseases in ageing. Emerging hypotheses suggest that these functional alterations may be related to energy metabolism. Indeed, ATP produced by mitochondria is essential for muscle contraction, neurotransmission and brain plasticity processes. Although a sedentary lifestyle has been associated with mitochondrial alterations in skeletal muscle, the potential effects on brain structures have yet to be investigated. The present study aimed to determine whether early sensorimotor restriction (SMR) alters mitochondrial metabolism in rat muscles and brain structures. Enzyme activities of citrate synthase (CS) and respiratory chain complexes I, II and IV were measured using a spectrophotometric technique and mitochondrial respiration was assessed using high-resolution respirometry in two hind limb muscles [soleus and extensor digitorum longus (EDL)] and four brain structures (sensorimotor cortex, striatum, prefrontal cortex and hippocampus) in control rats and rats experiencing early SMR from birth to day 28. Mitochondrial enzyme activities decreased in the soleus (complexes I and II), in the EDL (complex I) and in the hippocampus (complexes I and IV) in an age-dependent manner, whereas no effect was observed in other brain structures. CS activity decreases in the soleus and increases transiently in the striatum and sensorimotor cortex at postnatal day 15. Mitochondrial respiration was reduced in the soleus and in the sensorimotor cortex (CI and CI+CII). Early SMR appears to induce quantitative and qualitative mitochondrial alterations in skeletal muscles and certain brain structures involved in cognitive and motor processes. KEY POINTS: Early sensorimotor restriction (SMR) alters mitochondrial enzyme activities and mitochondrial respiration in skeletal muscles and brain. Mitochondrial alterations induced by early SMR are age-dependent, structure-dependent and complex-dependent. Mitochondrial enzyme activities increase during development and the evolution pattern is specific to the different structures.}, } @article {pmid39946260, year = {2025}, author = {Waneka, G and Broz, AK and Wold-McGimsey, F and Zou, Y and Wu, Z and Sloan, DB}, title = {Disruption of recombination machinery alters the mutational landscape in plant organellar genomes.}, journal = {G3 (Bethesda, Md.)}, volume = {15}, number = {4}, pages = {}, pmid = {39946260}, issn = {2160-1836}, support = {R35 GM148134/GM/NIGMS NIH HHS/United States ; NIGMS R35GM148134/NH/NIH HHS/United States ; }, mesh = {*Recombination, Genetic ; *Arabidopsis/genetics ; *Genome, Plant ; *Mutation ; Arabidopsis Proteins/genetics ; Genome, Plastid ; Genome, Mitochondrial ; Point Mutation ; Genomic Instability ; }, abstract = {Land plant organellar genomes have extremely low rates of point mutation yet also experience high rates of recombination and genome instability. Characterizing the molecular machinery responsible for these patterns is critical for understanding the evolution of these genomes. While much progress has been made toward understanding recombination activity in land plant organellar genomes, the relationship between recombination pathways and point mutation rates remains uncertain. The organellar-targeted mutS homolog MSH1 has previously been shown to suppress point mutations as well as non-allelic recombination between short repeats in Arabidopsis thaliana. We therefore implemented high-fidelity Duplex Sequencing to test if other genes that function in recombination and maintenance of genome stability also affect point mutation rates. We found small to moderate increases in the frequency of single nucleotide variants (SNVs) and indels in mitochondrial and/or plastid genomes of A. thaliana mutant lines lacking radA, recA1, or recA3. In contrast, osb2 and why2 mutants did not exhibit an increase in point mutations compared to wild-type (WT) controls. In addition, we analyzed the distribution of SNVs in previously generated Duplex Sequencing data from A. thaliana organellar genomes and found unexpected strand asymmetries and large effects of flanking nucleotides on mutation rates in WT plants and msh1 mutants. Finally, using long-read Oxford Nanopore sequencing, we characterized structural variants in organellar genomes of the mutant lines and show that different short repeat sequences become recombinationally active in different mutant backgrounds. Together, these complementary sequencing approaches shed light on how recombination may impact the extraordinarily low point mutation rates in plant organellar genomes.}, } @article {pmid39949038, year = {2025}, author = {Ratajczak, MZ and Thetchinamoorthy, K and Wierzbicka, D and Konopko, A and Ratajczak, J and Kucia, M}, title = {Extracellular microvesicles/exosomes-magic bullets in horizontal transfer between cells of mitochondria and molecules regulating mitochondria activity.}, journal = {Stem cells (Dayton, Ohio)}, volume = {43}, number = {3}, pages = {}, pmid = {39949038}, issn = {1549-4918}, support = {R01 DK074720/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Mitochondria/metabolism ; Animals ; *Exosomes/metabolism ; *Extracellular Vesicles/metabolism ; }, abstract = {Extracellular microvesicles (ExMVs) were one of the first communication platforms between cells that emerged early in evolution. Evidence indicates that all types of cells secrete these small circular structures surrounded by a lipid membrane that plays an important role in cellular physiology and some pathological processes. ExMVs interact with target cells and may stimulate them by ligands expressed on their surface and/or transfer to the target cells their cargo comprising various RNA species, proteins, bioactive lipids, and signaling nucleotides. These small vesicles can also hijack some organelles from the cells and, in particular, transfer mitochondria, which are currently the focus of scientific interest for their potential application in clinical settings. Different mechanisms exist for transferring mitochondria between cells, including their encapsulation in ExMVs or their uptake in a "naked" form. It has also been demonstrated that mitochondria transfer may involve direct cell-cell connections by signaling nanotubules. In addition, evidence accumulated that ExMVs could be enriched for regulatory molecules, including some miRNA species and proteins that regulate the function of mitochondria in the target cells. Recently, a new beneficial effect of mitochondrial transfer has been reported based on inducing the mitophagy process, removing damaged mitochondria in the recipient cells to improve their energetic state. Based on this novel role of ExMVs in powering the energetic state of target cells, we present a current point of view on this topic and review some selected most recent discoveries and recently published most relevant papers.}, } @article {pmid39950816, year = {2025}, author = {Guo, B and Guo, G and Qi, W and Aizezi, M and Wu, C and Tian, M and Casulli, A and Zhang, W and Li, J}, title = {The genetic variation of mitochondrial sequences and pathological differences of Echinococcus multilocularis strains from different continents.}, journal = {Microbiology spectrum}, volume = {13}, number = {4}, pages = {e0131824}, pmid = {39950816}, issn = {2165-0497}, support = {2023TSYCTD0017//Tianshan talent training program/ ; 32072886,U1803282//MOST | National Natural Science Foundation of China (NSFC)/ ; 81830066//MOST | National Natural Science Foundation of China (NSFC)/ ; SKLHIDCA-2022-BC4//State Key Laboratory/ ; }, mesh = {Animals ; *Echinococcus multilocularis/genetics/classification/pathogenicity/isolation & purification ; *Genetic Variation ; Phylogeny ; *Echinococcosis/parasitology/pathology ; Mice ; Japan ; *DNA, Mitochondrial/genetics ; *Mitochondria/genetics ; Disease Models, Animal ; Liver/parasitology/pathology ; }, abstract = {Alveolar echinococcosis is a lethal zoonotic disease caused by the fox tapeworm Echinococcus multilocularis. The parasite is widely distributed in the Northern Hemisphere and exhibits low genetic diversity among populations. To compare the differences among four E. multilocularis strains from different geographical locations, namely, Alaska (EM-AK), Japan (EM-JP), Xinjiang (EM-XJ), and Ningxia (EM-NX), their complete mitochondrial (mt) sequences were compared, and their induced pathological lesions were analyzed in mouse models. The complete mt sequence of EM-AK resulted in 0.84%-0.86% variation as compared with the other strains, which had a lower variation. Phylogenetic analysis and parsimony network indicated that EM-AK resulted in 30,000 years of evolutionary distance from the other three strains. EM-AK induced more pathological damage than the other three strains, which was likely to induce more host cell infiltration and acute granuloma in the liver. More importantly, EM-AK produced more protoscoleces than the other three strains, which may impact the transmission dynamics of the parasite. Given the geographical location of four strains, which is far from each other, and also the pathological differences, the strains of E. multilocularis are likely models for addressing the relationship and interfacial immune response between the host and the helminth.IMPORTANCEEchinococcus multilocularis is the causative agent of alveolar echinococcosis, which is considered the most serious parasitic disease in the Northern Hemisphere. There are many genotypes, but the pathogenic and mitochondria sequence and differences are still unclear. Therefore, this study showed both pathological and genetic differences between the four strains of E. multilocularis. EM-AK induced more severe immune responses and especially induced more host cell infiltration, which resulted in more severe granuloma in the liver. EM-JP has metacestode lesions morphologically closer to those of E. granulosus with clear cyst fluid. However, this strain produced much fewer protoscoleces (PSCs). Genetically, EM-AK is more distant from other strains.}, } @article {pmid39961891, year = {2025}, author = {Larkum, AWD and Falkowski, PG and Edwards, D and Osmond, CB and Lambers, H and Sanchez-Baracaldo, P and Ritchie, RJ and Runcie, JW and Ralph, PJ and Westoby, M and Maberly, S and Griffiths, H and Smith, FA and Beardall, J}, title = {John Raven, FRS, FRSE: a truly great innovator in plant physiology, photosynthesis and much more.}, journal = {Photosynthesis research}, volume = {163}, number = {2}, pages = {18}, pmid = {39961891}, issn = {1573-5079}, mesh = {*Photosynthesis/physiology ; History, 20th Century ; *Plant Physiological Phenomena ; History, 21st Century ; *Botany/history ; }, abstract = {This is a tribute to a truly inspirational plant biologist, Prof. John A. Raven, FRS, FRSE (25th June 1941- 23rd May 2024), who died at the age of 82. He was a leader in the field of evolution and physiology of algae and land plants. His research touched on many areas including photosynthesis, ion transport, carbon utilisation, mineral use, such as silicon, iron and molybdenum, the evolution of phytoplankton, the evolution of root systems, the impact of global change, especially on the acidification of the oceans, carbon gain and water use in early land plants, and ways of detecting extraterrestrial photosynthesis. Beginning his research career in the Botany School, University of Cambridge, John studied ion uptake in a giant algal cell. This was at the time of great strides brought about by Peter Mitchell (1920-1992) in elucidating the role of energy generation in mitochondria and chloroplasts and the coupling of ion transport systems to energy generation. With Enid MacRobbie and Andrew Smith, John pioneered early work on the involvement of ion transport in the growth and metabolism of plant cells.On leaving Cambridge John took up a lectureship at the University of Dundee in 1971, where he was still attached upon his death. His primary focus over the years, with one of us (Paul Falkowski), was on phytoplankton, the photosynthetic microalgae of the oceans. Still, his publication list of 5 books and over 600 scientific papers spans a very broad range. The many highly cited papers (see Table 1) attest to an outstanding innovator, who influenced a multitude of students and coworkers and a very wide readership worldwide. At the personal level, John Raven was a wonderful human being; he had an extraordinary memory, dredging up facts and little-known scientific papers, like a scientific magician, but at the same time making humorous jokes and involving his colleagues in fun and sympathetic appreciation. Table 1 Ten best cited articles (from google scholar) Citations Date Aquatic Photosynthesis, 3rd Edition P.G. Falkowski & J.A. Raven Princeton University Press, 2013 3854 2013 The evolution of modern eukaryotic phytoplankton P.G. Falkowski, M.E. Katz, A.H. Knoll, A. Quigg, J.A. Raven, et al Science 305, 354-360 1790 2004 CO2 concentrating mechanisms in algae: mechanisms, environmental modulation, and evolution M. Giordano, J. Beardall & J.A. Raven Annu. Rev. Plant Biol. 56 (1), 99-131 1648 2005 Algae as nutritional food sources: revisiting our understanding M.L. Wells, P. Potin, J.S. Craigie, J.A. Raven, S.S. Merchant, et al Journal of applied phycology 29, 949-982 1527 2017 Plant Nutrient acquisition strategies change with soil age H. Lambers, J.A. Raven, G.R. Shaver & S.E. Smith Trends in ecology & evolution 23, 95-103 1488 2008 Ocean acidification due to increasing atmospheric carbon dioxide J. Raven, K. Caldeira, H. Elderfield, O. Hoegh-Guldberg, P. Liss, et al The Royal Society, Policy Document, June 2005 1470 2005 Phytoplankton in a changing world: cell size and elemental stoichiometry Z.V. Finkel, J. Beardall, K.J. Flynn, A. Quigg, T.A.V. Rees & J.A. Raven Journal of plankton research 32, 119-137 1198 2010 Opportunities for improving phosphorus efficiency in crop plants E.J. Veneklaas, H. Lambers, J. Bragg, P.M. Finnegan, C.E. Lovelock, et al New phytologist 195, 306-320 951 2012 Adaptation of unicellular algae to irradiance: an analysis of strategies K. Richardson, J. Beardall & J.A. Raven New Phytologist 93, 157-191 914 1983 Nitrogen assimilation and transport in vascular land plants in relation to Intracellular pH regulation J.A. Raven & F.A. Smith New Phytologist 76, 415-431 893 1976 Temperature and algal growth J.A. Raven & R.J. Geider New phytologist 110, 441-461 867 1988 The role of trace metals in photosynthetic electron transport in O2 -evolving organisms J.A. Raven, M.C.W. Evans & R.E. Korb Photosynthesis Research 60, 111-150 840 1999.}, } @article {pmid39962375, year = {2025}, author = {Kim, SC and Kang, ES and Kim, TH and Choi, YR and Kim, HJ}, title = {Report on the complete organelle genomes of Orobanche Filicicola Nakai ex Hyun, Y. S. Lim & H. C. Shin (Orobanchaceae): insights from comparison with Orobanchaceae plant genomes.}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {157}, pmid = {39962375}, issn = {1471-2164}, mesh = {Phylogeny ; *Genome, Mitochondrial ; *Genome, Chloroplast ; Base Composition ; *Orobanche/genetics/classification ; *Genome, Plant ; *Orobanchaceae/genetics/classification ; Genomics ; Evolution, Molecular ; RNA, Transfer/genetics ; Microsatellite Repeats ; }, abstract = {BACKGROUND: Orobanche is a parasitic plant distributed in the temperate zone of Northern Hemisphere, with approximately 200 species found worldwide. In the Republic of Korea, two species of Orobanche, namely O. coerulescens Stephan ex Willd. and O. filicicola Nakai ex Hyun, Y. S. Lim & H. C. Shin, are present, with O. filicicola being endemic. Genome analysis of this species has not yet been performed, and characterizing its complete organelle genome will provide valuable insights into the phylogeny and genome evolution of parasitic plants.

RESULTS: The chloroplast and mitochondrial genomes were analyzed, revealing distinct characteristics. The chloroplast genome is 91,529 bp long with a GC content of 33.6%, containing 33 protein-coding, 30 tRNA, and 4 rRNA genes. In contrast, the mitochondrial genome is 1,058,991 bp long with a GC content of 45.5%, featuring 31 protein-coding, 16 tRNA, and 3 rRNA genes. The mitochondrial genome has over three times more simple sequence repeats and longer long repeats than the chloroplast genome. Analysis of synonymous codon usage in protein-coding genes from nine Orobanchaceae species revealed significant differences between chloroplasts and mitochondria, with codons ending in A or T exhibiting higher coding rates. Ka/Ks ratio calculations indicated that psbI and atpB had the smallest and largest ratios in chloroplasts, respectively, while ccmFC was identified as the only gene under positive selection in mitochondria genomes. Sequence alignment identified 30 homologous fragments between the two genomes, totaling 7,247 bp. Comparison of O. filicicola's chloroplast genome with related species showed gene loss and conserved inverted repeat sequences. Numerous homologous collinear blocks were found in mitochondrial genomes of related species, but some regions lacked homology. Phylogenetic analysis indicated identical topologies for chloroplasts and mitochondria, with Orobanchaceae forming a strong monophyletic group.

CONCLUSIONS: Characterizing the complete organelle genome of O. filicicola enabled a comprehensive analysis of the Orobanchaceae organelle genome, providing important baseline data for its structure and evolution.}, } @article {pmid39972273, year = {2025}, author = {Zhou, B and Sui, R and Yu, L and Qi, D and Fu, S and Luo, Y and Qi, H and Li, X and Zhao, K and Liu, S and Tian, F}, title = {Transcriptomics and proteomics provide insights into the adaptative strategies of Tibetan naked carps (Gymnocypris przewalskii) to saline-alkaline variations.}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {162}, pmid = {39972273}, issn = {1471-2164}, support = {32071489//National Natural Science Foundation of China/ ; 32401305//National Natural Science Foundation of China/ ; LHZX-2021-03//Joint Foundation from the Chinese Academy of Sciences -People's Government of Qinghai Province on Sanjiangyuan National Park/ ; }, mesh = {Animals ; *Proteomics ; Gills/metabolism ; *Salinity ; *Carps/genetics/physiology/metabolism ; *Gene Expression Profiling ; *Adaptation, Physiological/genetics ; *Transcriptome ; Kidney/metabolism ; Fish Proteins/genetics/metabolism ; Lakes ; Fresh Water ; Osmoregulation ; Proteome ; Tibet ; }, abstract = {Gymnocypris przewalskii is an exclusively cyprinid fish that inhabits Lake Qinghai, which is characterized by high salinity and alkalinity. To elucidate the molecular basis of the adaptation of G. przewalskii to a wide range of salinity‒alkalinity conditions, we performed morphological, biochemical, transcriptomic and proteomic analyses of the major osmoregulatory organs of the gills and kidney. Morphological examination revealed that mitochondria-rich cells were replaced by mucus cells in the gills during the transition of G. przewalskii from freshwater to lake water. In the kidney, the tight junction formed dense structure in the renal tubules under lake water condition compared with the loose structure in freshwater. The results of the biochemical assays revealed an increased content of total amino acids, indicating their potential roles as osmolytes and energy supplies in freshwater. The decreased urea concentration suggested that urea synthesis might not be involved in the detoxicity of ammonia. The transcriptomic and proteomic data revealed that genes involved in ion absorption and ammonia excretion were activated in freshwater and that genes involved in cell junction and glutamine synthesis were induced in lake water, which was consistent with the morphological and biochemical observations. Together with the higher levels of glutamine and glutamate, we proposed that G. przewalskii alleviated the toxic effect of ammonia direct excretion through gills under freshwater and the activation of the conversion of glutamate to glutamine under high saline-alkaline condition. Our results revealed different expression profiles of genes involved in metabolic pathways, including the upregulation of genes involved in energy production in freshwater and the induction of genes involved in the synthesis of acetylneuramic acid and sphingolipid in soda lake water. In conclusion, the appearance of mitochondria-rich cells and increased energy production might contribute to ion absorption in G. przewalskii to maintain ion and solute homeostasis in freshwater. The existence of mucus cells and dense junctions, which are associated with increased gene expression, might be related to the adaptation of G. przewalskii to high salinity-alkalinity.}, } @article {pmid39977315, year = {2025}, author = {Elling, FJ and Pierrel, F and Chobert, SC and Abby, SS and Evans, TW and Reveillard, A and Pelosi, L and Schnoebelen, J and Hemingway, JD and Boumendjel, A and Becker, KW and Blom, P and Cordes, J and Nathan, V and Baymann, F and Lücker, S and Spieck, E and Leadbetter, JR and Hinrichs, KU and Summons, RE and Pearson, A}, title = {A novel quinone biosynthetic pathway illuminates the evolution of aerobic metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {8}, pages = {e2421994122}, pmid = {39977315}, issn = {1091-6490}, support = {1702262//NSF (NSF)/ ; 1843285//NSF (NSF)/ ; NA//Gordon and Betty Moore Foundation (GBMF)/ ; 441217575//Deutsche Forschungsgemeinschaft (DFG)/ ; ANR-21-CE02-0018//Agence Nationale de la Recherche (ANR)/ ; ANR-15-IDEX-02//Agence Nationale de la Recherche (ANR)/ ; IDEX-IRS 2020//Grenoble-Alpes University/ ; EXC-2077-390741603//Deutsche Forschungsgemeinschaft (DFG)/ ; NA//Alexander von Humboldt-Stiftung (AvH)/ ; 016.Vidi.189.050//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)/ ; 18-EXXO18-0039//NASA | NASA Astrobiology Institute (NAI)/ ; 946150//EC | European Research Council (ERC)/ ; 80NSSC19K0480//NASA | NASA Astrobiology Institute (NAI)/ ; }, mesh = {Aerobiosis ; *Biosynthetic Pathways ; Plastoquinone/metabolism/chemistry/analogs & derivatives ; *Quinones/metabolism ; Phylogeny ; Oxidation-Reduction ; *Biological Evolution ; *Evolution, Molecular ; *Bacteria/metabolism/genetics ; }, abstract = {The dominant organisms in modern oxic ecosystems rely on respiratory quinones with high redox potential (HPQs) for electron transport in aerobic respiration and photosynthesis. The diversification of quinones, from low redox potential (LPQ) in anaerobes to HPQs in aerobes, is assumed to have followed Earth's surface oxygenation ~2.3 billion years ago. However, the evolutionary origins of HPQs remain unresolved. Here, we characterize the structure and biosynthetic pathway of an ancestral HPQ, methyl-plastoquinone (mPQ), that is unique to bacteria of the phylum Nitrospirota. mPQ is structurally related to the two previously known HPQs, plastoquinone from Cyanobacteriota/chloroplasts and ubiquinone from Pseudomonadota/mitochondria, respectively. We demonstrate a common origin of the three HPQ biosynthetic pathways that predates the emergence of Nitrospirota, Cyanobacteriota, and Pseudomonadota. An ancestral HPQ biosynthetic pathway evolved ≥ 3.4 billion years ago in an extinct lineage and was laterally transferred to these three phyla ~2.5 to 3.2 billion years ago. We show that Cyanobacteriota and Pseudomonadota were ancestrally aerobic and thus propose that aerobic metabolism using HPQs significantly predates Earth's surface oxygenation. Two of the three HPQ pathways were later obtained by eukaryotes through endosymbiosis forming chloroplasts and mitochondria, enabling their rise to dominance in modern oxic ecosystems.}, } @article {pmid39980242, year = {2025}, author = {Yonemitsu, MA and Sevigny, JK and Vandepas, LE and Dimond, JL and Giersch, RM and Gurney-Smith, HJ and Abbott, CL and Supernault, J and Withler, R and Smith, PD and Weinandt, SA and Garrett, FES and Child, ZJ and Sigo, RLW and Unsell, E and Crim, RN and Metzger, MJ}, title = {Multiple Lineages of Transmissible Neoplasia in the Basket Cockle (C. nuttallii) With Repeated Horizontal Transfer of Mitochondrial DNA.}, journal = {Molecular ecology}, volume = {34}, number = {6}, pages = {e17682}, doi = {10.1111/mec.17682}, pmid = {39980242}, issn = {1365-294X}, support = {//National Research Council/ ; 2208081//Division of Ocean Sciences/ ; A19AP00215//Bureau of Indian Affairs/ ; }, mesh = {Animals ; *DNA, Mitochondrial/genetics ; Washington ; *Cardiidae/genetics ; *Neoplasms/genetics ; *Gene Transfer, Horizontal/genetics ; Phylogeny ; }, abstract = {Transmissible cancers are clonal lineages of neoplastic cells able to infect multiple hosts, spreading through populations in the environment as an infectious disease. Transmissible cancers have been identified in Tasmanian devils, dogs, and bivalves. Several lineages of bivalve transmissible neoplasias (BTN) have been identified in multiple bivalve species. In 2019 in Puget Sound, Washington, USA, disseminated neoplasia was observed in basket cockles (Clinocardium nuttallii), a species that is important to the culture and diet of the Suquamish Tribe as well as other tribes with traditional access to the species. To test whether disseminated neoplasia in cockles is a previously unknown lineage of BTN, a nuclear locus was amplified from cockles from Agate Pass, Washington, and sequences revealed evidence of transmissible cancer in several individuals. We used a combination of cytology and quantitative PCR to screen collections of cockles from 11 locations in Puget Sound and along the Washington coastline to identify the extent of contagious cancer spread in this species. Two BTN lineages were identified in these cockles, with one of those lineages (CnuBTN1) being the most prevalent and geographically widespread. Within the CnuBTN1 lineage, multiple nuclear loci support the conclusion that all cancer samples form a single clonal lineage. However, the mitochondrial alleles in each cockle with CnuBTN1 are different from each other, suggesting mitochondrial genomes of this cancer have been replaced multiple times during its evolution, through horizontal transmission. The identification and analysis of these BTNs are critical for broodstock selection, management practices, and repopulation of declining cockle populations, which will enable continued cultural connection and dietary use of the cockles by Coast Salish Tribes.}, } @article {pmid39980249, year = {2025}, author = {de Bont, L and Donnay, N and Favier, F and Couturier, J and Didierjean, C and Rouhier, N}, title = {Novel atypical thioredoxins with potential redox activity in eukaryote photosynthetic organisms.}, journal = {Journal of experimental botany}, volume = {76}, number = {13}, pages = {3834-3850}, doi = {10.1093/jxb/eraf066}, pmid = {39980249}, issn = {1460-2431}, support = {//Nationale de la Recherche/ ; }, mesh = {Oxidation-Reduction ; *Thioredoxins/metabolism/genetics/chemistry ; *Photosynthesis ; *Arabidopsis/metabolism/genetics ; Amino Acid Sequence ; *Arabidopsis Proteins/metabolism/genetics/chemistry ; Phylogeny ; }, abstract = {Photosynthetic organisms have a high diversity of proteins belonging to the thioredoxin (TRX) superfamily. It comprises more than 150 proteins distributed in different families and classes, including thioredoxins, glutaredoxins, protein disulfide isomerases, thiol peroxidases, and glutathione transferases, which all share the thioredoxin structural fold. Many of them have one or two redox-active cysteines and a characteristic cis-proline at specific positions, and additional domains or secondary structures at either end or inserted into the protein core. With the aim of further describing the TRX family in plants, we have identified a set of 17 atypical TRX-like proteins from Arabidopsis, which have not been considered before despite having both a TRX fold and the CxxC/S signature typical of redox-active TRXs. In silico sequence and structure analyses revealed that they are divided into eight distinct classes with unique active-site signatures and structures, some with disulfide bond-forming protein A (DsbA) and peroxiredoxin-like folds. Their distinct subcellular localizations (plastids, mitochondria, extracellular space) and gene expression profiles suggest that these proteins are involved in diverse cellular processes, further expanding the set of proteins involved in redox regulation and/or stress adaptation. Our results reveal additional diversity in the structure and function of atypical TRXs in plants.}, } @article {pmid39985363, year = {2025}, author = {Ganetzky, R and Stanley, KD and MacMullen, LE and George-Sankoh, I and Wang, J and Goldstein, A and Xiao, R and Falk, MJ}, title = {Recognizing the evolution of clinical syndrome spectrum progression in individuals with single large-scale mitochondrial DNA deletion syndromes (SLSMDS).}, journal = {Genetics in medicine : official journal of the American College of Medical Genetics}, volume = {27}, number = {5}, pages = {101386}, doi = {10.1016/j.gim.2025.101386}, pmid = {39985363}, issn = {1530-0366}, mesh = {Humans ; Female ; Male ; *Mitochondrial Diseases/genetics/pathology ; *DNA, Mitochondrial/genetics ; Child ; *Kearns-Sayre Syndrome/genetics/pathology ; Adult ; Adolescent ; Quality of Life ; Retrospective Studies ; Phenotype ; Child, Preschool ; Disease Progression ; Middle Aged ; Young Adult ; Sequence Deletion/genetics ; *Lipid Metabolism, Inborn Errors/genetics/pathology ; Syndrome ; Ophthalmoplegia, Chronic Progressive External/genetics/pathology ; Acyl-CoA Dehydrogenase, Long-Chain/genetics/deficiency ; Mitochondria/genetics ; Congenital Bone Marrow Failure Syndromes ; Muscular Diseases ; }, abstract = {PURPOSE: Single large-scale mtDNA deletions (SLSMD) result in single large-scale deletion syndromes (SLSMDS). SLSMDS presentations have classically been recognized to encompass at least 3 distinct clinical phenotypes: Pearson syndrome (PS), Kearns-Sayre syndrome (KSS), and chronic progressive ophthalmoplegia.

METHODS: A facilitated review of electronic medical records, manual charts, and Research Electronic Data Capture research databases was performed to complete a retrospective natural history study of 30 participants with SLSMDS in a single health system between 2002 and 2020. The evaluated characteristics included genetic and clinical laboratory test values, growth parameters, signs and symptoms, demographics, and patient-reported outcome measures of fatigue, quality of life, and overall function.

RESULTS: Detailed cohort characterization highlighted that a recurrent deleted region involving MT-ND5 (HGNC:7641) occurs in 96% of participants with SLSMDS regardless of the clinical phenotype, which tends to evolve over time. Higher blood heteroplasmy correlated with an earlier age of onset. Growth differentiation factor 15 levels were elevated in all participants with SLSMDS. A history of PS was associated with poor survival prognosis. Furthermore, increased fatigue and decreased quality of life have been reported in patients with SLSMD with advanced age.

CONCLUSION: A retrospective natural history study of patients with SLSMDS demonstrated the evolution of classically considered PS, Kearns-Sayre syndrome, and chronic progressive ophthalmoplegia clinical presentations in affected individuals, which may inform future clinical trial developments.}, } @article {pmid39988053, year = {2025}, author = {Monesi, N and Fernandes, GM and Valer, FB and Uliana, JVC and Trinca, V and Azzolini, AECS and Gorab, E and Alberici, LC}, title = {Identification and characterization of a laterally transferred alternative oxidase (AOX) in a terrestrial insect, the dipteran Pseudolycoriella hygida.}, journal = {Biochimie}, volume = {233}, number = {}, pages = {60-74}, doi = {10.1016/j.biochi.2025.02.007}, pmid = {39988053}, issn = {1638-6183}, mesh = {Animals ; *Mitochondrial Proteins/genetics/metabolism/antagonists & inhibitors ; *Oxidoreductases/genetics/metabolism/antagonists & inhibitors ; *Plant Proteins/genetics/metabolism ; *Diptera/enzymology/genetics ; Mitochondria/enzymology/metabolism ; *Gene Transfer, Horizontal ; *Insect Proteins/genetics/metabolism ; Phylogeny ; Salicylamides ; Alternative Oxidase ; }, abstract = {Alternative oxidase (AOX) (EC 1.10.3.11) is a terminal oxidase in the mitochondrial inner membrane that branches the canonical electron transport system (ETS). AOX is ubiquitous in plants, frequently found in fungi and protists and presents a more sporadic distribution in metazoans. More recently, AOX has gained attention due to its potential application in gene therapy for treatment of mitochondrial diseases. Here we characterized the AOX in the basal Dipteran, Pseudolycoriella hygida using a combination of genomic analyses, molecular, functional and in vivo survival assays. AOX is a single copy gene that encodes three developmental stage specific protein isoforms. AOX localizes to the mitochondria in adult thoracic muscles, which present cyanide-resistant respiration that is sensitive to the AOX inhibitor salicylhydroxamic acid (SHAM). Both the cyanide-resistant respiration and AOX levels gradually increase during aging, but are not influenced by thermal stress. Thoracic mitochondria respire using substrates derived from several metabolic routes, such as pyruvate, proline, acylcarnitine, NADH and glycerol-3P, and present values of oxidative phosphorylation capacity ((P-L)/E = 0.70) and coupling (P/L = 4.35; L/E = 0.21). Adult flies exhibit a high survival resistance for SHAM-sensitive complex III inhibition. Together, our results demonstrate the presence of a functional AOX in a terrestrial arthropod and provide insights regarding AOX function in animals and evolution of respiratory systems in metazoans. Psl. hygida emerges as a natural and valuable model for comprehensive AOX research at the whole-organism level which complements models expressing the heterologous enzyme.}, } @article {pmid39990427, year = {2025}, author = {Cai, L and Havird, JC and Jansen, RK}, title = {Recombination and retroprocessing in broomrapes reveal a universal roadmap for mitochondrial evolution in heterotrophic plants.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39990427}, issn = {2692-8205}, support = {R35 GM142836/GM/NIGMS NIH HHS/United States ; }, abstract = {The altered life history strategies of heterotrophic organisms often leave a profound genetic footprint on energy metabolism related functions. In parasitic plants, the reliance on host-derived nutrients and loss of photosynthesis in holoparasites have led to highly degraded to absent plastid genomes, but its impact on mitochondrial genome (mitogenome) evolution has remained controversial. By examining mitogenomes from 45 Orobanchaceae species including three independent transitions to holoparasitism and key evolutionary intermediates, we identified measurable and predictable genetic alterations in genomic shuffling, RNA editing, and intracellular (IGT) and horizontal gene transfer (HGT) en route to a nonphotosynthetic lifestyle. In-depth comparative analyses revealed DNA recombination and repair processes, especially RNA-mediated retroprocessing, as significant drivers for genome structure evolution. In particular, we identified a novel RNA-mediated IGT and HGT mechanism, which has not been demonstrated in cross-species and inter-organelle transfers. Based on this, we propose a generalized dosage effect mechanism to explain the biased transferability of plastid DNA to mitochondria across green plants, especially in heterotrophic lineages like parasites and mycoheterotrophs. Evolutionary rates scaled with these genomic changes, but the direction and strength of selection varied substantially among genes and clades, resulting in high contingency in mitochondrial genome evolution. Finally, we describe a universal roadmap for mitochondrial evolution in heterotrophic plants where increased recombination and repair activities, rather than relaxed selection alone, lead to differentiated genome structure compared to free-living species.}, } @article {pmid39993485, year = {2025}, author = {Li, W and Yang, G and Fan, Y and Yan, X and Li, Z and Guo, Y and Wang, Q and Li, X and Gu, W and Ning, M and Zhou, J and Meng, Q}, title = {Eriocheir sinensis CD63 activate mitochondria-mediated apoptosis to resist Spiroplasma eriocheiris infection.}, journal = {Fish & shellfish immunology}, volume = {161}, number = {}, pages = {110227}, doi = {10.1016/j.fsi.2025.110227}, pmid = {39993485}, issn = {1095-9947}, mesh = {Animals ; *Spiroplasma/physiology ; *Tetraspanin 30/genetics/immunology/chemistry ; *Apoptosis ; *Brachyura/immunology/genetics/microbiology ; Mitochondria ; *Arthropod Proteins/genetics/immunology/chemistry ; *Immunity, Innate/genetics ; Hemocytes/immunology ; Phylogeny ; Amino Acid Sequence ; Sequence Alignment ; }, abstract = {CD63, a member of the tetraspanins, is involved in cell movement, adhesion, immune response. Nevertheless, the role of CD63 in combating pathogen infections in invertebrates remains largely unclear. Tremor disease, whose pathogen is Spiroplasma eriocheiris, is one of the most prevalent illnesses affecting Eriocheir sinensis. EsCD63 is 1474 bp, with a 756 bp open reading frame that encodes for 252 amino acids. The qPCR data demonstrated that gills showed significant levels of transcription for EsCD63, followed by hemocytes, hepatopancreas, intestines and nerves, while showing low levels of transcription in the heart and muscles. After infection with S. eriocheiris, an obvious drop in the transcription level of EsCD63 was observed. Both the amount of S. eriocheiris copies in hemocytes and the mortality of E. sinensis significantly increased after the injection of chemically synthesized EsCD63 siRNA and stimulation with S. eriocheiris. After EsCD63 interference, the phagocytosis of hemocytes to S. eriocheiris, the apoptosis of hemocytes, and reactive oxygen species level of hemocytes were all decreased significantly, by laser scanning confocal microscopy and flow cytometry analysis. Meanwhile, the mitochondrial membrane potential of hemocytes was increased after EsCD63 interference. These findings indicated that EsCD63 was crucial for E. sinensis immunity and defense mechanisms against infection of S. eriocheiris.}, } @article {pmid39993486, year = {2025}, author = {He, M and Li, S and Sun, J and Lv, X and Li, Y and Song, L}, title = {CgVDAC2 participated in haemocyte mitophagy induced by Vibrio splendidus in the Pacific oyster Crassostrea gigas.}, journal = {Fish & shellfish immunology}, volume = {160}, number = {}, pages = {110226}, doi = {10.1016/j.fsi.2025.110226}, pmid = {39993486}, issn = {1095-9947}, mesh = {Animals ; *Crassostrea/immunology/genetics/microbiology ; *Vibrio/physiology ; *Mitophagy/genetics ; Hemocytes/immunology ; *Immunity, Innate/genetics ; *Voltage-Dependent Anion Channel 2/genetics/immunology/chemistry ; Phylogeny ; *Gene Expression Regulation/immunology ; Sequence Alignment ; Amino Acid Sequence ; }, abstract = {VDAC2 (Voltage dependent anion channel 2) is a highly conserved pore-forming protein expressed in the outer membrane of eukaryotic mitochondria. In the present study, CgVDAC2 identified from Crassostrea gigas regulated the mitophagy of haemocytes induced by Vibrio splendidus. CgVDAC2 was distributed in the cytoplasm of three subpopulations of haemocytes. After V. splendidus stimulation, the mRNA and protein expressions of CgVDAC2 were induced in haemocytes. Furthermore, the green signals of CgVDAC2 were colocalized with the red signals of mitochondria and Mtphagy Dye, respectively. And their co-localization values were both increased significantly in haemocytes at 12 h after V. splendidus stimulation, respectively. In siCgVDAC2-treated oysters, the mRNA expressions of mitophagy-related genes (CgLC3, CgPINK1, CgParkin1, CgPHB2, and CgATG16L) and the levels of mitophagy decreased significantly in haemocytes after V. splendidus stimulation. In addition, both the fluorescence intensities of the JC-1 monomer/aggregate ratio (Q4/Q2) and mitochondrial reactive oxygen species (mtROS) increased significantly. Collectively, all the results indicated that CgVDAC2 participated in oyster antibacterial immune response through regulating the haemocyte mitophagy.}, } @article {pmid39997180, year = {2025}, author = {Luccarini, A and Marcheggiani, F and Galeazzi, R and Zuccarotto, A and Castellano, I and Damiani, E}, title = {Characterizing the Ultraviolet (UV) Screening Ability of L-5-Sulfanylhistidine Derivatives on Human Dermal Fibroblasts.}, journal = {Marine drugs}, volume = {23}, number = {2}, pages = {}, pmid = {39997180}, issn = {1660-3397}, support = {2022MJBEK9, CUP E53D23009970006//Next Generation Europe/ ; }, mesh = {Humans ; *Ultraviolet Rays/adverse effects ; *Fibroblasts/drug effects/radiation effects/metabolism ; *Histidine/pharmacology/analogs & derivatives/chemistry ; *Sunscreening Agents/pharmacology/chemistry ; Cell Survival/drug effects/radiation effects ; Reactive Oxygen Species/metabolism ; Apoptosis/drug effects/radiation effects ; Skin/drug effects/radiation effects/cytology ; Antioxidants/pharmacology ; Mitochondria/drug effects/metabolism ; }, abstract = {Using sunscreens is one of the most widespread measures to protect human skin from sun ultraviolet radiation (UVR) damage. However, several studies have highlighted the toxicity of certain inorganic and organic UV filters used in sunscreens for the marine environment and human health. An alternative strategy may involve the use of natural products of marine origin to counteract UVR-mediated damage. Ovothiols are sulfur-containing amino acids produced by marine invertebrates, microalgae, and bacteria, endowed with unique antioxidant and UV-absorption properties. This study aimed to evaluate the protective effect of synthetic L-5-sulfanyl histidine derivatives, inspired by natural ovothiols, on human dermal fibroblasts (HDFs) upon UVA exposure. By using a custom-made experimental set-up to assess the UV screening ability, we measured the levels of cytosolic and mitochondrial reactive oxygen species (ROS), as well as cell viability and apoptosis in HDFs, in the presence of tested compounds, after UVA exposure, using flow cytometry assays with specific fluorescent probes. The results show that L-5-sulfanyl histidine derivatives display a UV screening capacity and prevent loss in cell viability, the production of cytosolic and mitochondrial ROS induced by UVA exposure in HDFs, and subsequent apoptosis. Overall, this study sheds light on the potential applications of marine-inspired sulfur-containing amino acids in developing alternative eco-safe sunscreens for UVR skin protection.}, } @article {pmid39998089, year = {2025}, author = {Lan, X and Yang, M and Wang, J and Huang, C and Wu, A and Cui, L and Guo, Y and Zeng, L and Guo, X and Zhang, Y and Xiang, Y and Wang, Q}, title = {Pore-Forming Protein LIN-24 Enhances Starvation Resilience in Caenorhabditis elegans by Modulating Lipid Metabolism and Mitochondrial Dynamics.}, journal = {Toxins}, volume = {17}, number = {2}, pages = {}, pmid = {39998089}, issn = {2072-6651}, support = {82471591, 82460283, 32360136//National Natural Science Foundation of China/ ; 2023YFC3603300, 2023YFF1001000//National Key R&D Program, Ministry of Science and Technology of China/ ; 2024SSY07161 and 20221ZDG020070//Natural Science Foundation of Jiangxi Province/ ; 28740105//Foundation of Nanchang University/ ; }, mesh = {Animals ; *Caenorhabditis elegans/genetics/metabolism ; *Caenorhabditis elegans Proteins/genetics/metabolism ; *Lipid Metabolism ; *Mitochondrial Dynamics ; *Starvation/metabolism ; *Pore Forming Cytotoxic Proteins/genetics/metabolism ; Mitochondria/metabolism ; }, abstract = {The ability to survive starvation is a critical evolutionary adaptation, yet the molecular mechanisms underlying this capability remain incompletely understood. Pore-forming proteins (PFPs) are typically associated with immune defense, where they disturb the membranes of target cells. However, the role of PFPs in non-immune functions, particularly in metabolic and structural adaptations to starvation, is less explored. Here, we investigate the aerolysin-like PFP LIN-24 in Caenorhabditis elegans and uncover its novel function in enhancing starvation resistance. We found that LIN-24 expression is upregulated during starvation, leading to increased expression of the lipase-encoding gene lipl-3. This upregulation accelerates the mobilization and degradation of lipid stores, thereby sustaining energy levels. Additionally, LIN-24 overexpression significantly preserves muscle integrity, as evidenced by the maintenance of muscle structure compared to wild-type worms. Furthermore, we demonstrate that LIN-24 induces the formation of donut-shaped mitochondria, a structural change likely aimed at reducing ATP production to conserve energy during prolonged nutrient deprivation. This mitochondrial remodeling depends on genes involved in mitochondrial dynamics, including mff-1, mff-2, drp-1, and clk-1. Collectively, these findings expand our understanding of PFPs, demonstrating their multifaceted role in stress resistance beyond immune defense. LIN-24's involvement in regulating metabolism, preserving muscle structure, and remodeling mitochondria highlights its crucial role in the adaptive response to starvation, offering novel insights into the evolution of stress resistance mechanisms and potential therapeutic targets for conditions related to muscle preservation and metabolic regulation.}, } @article {pmid40000832, year = {2025}, author = {Du, W and Sun, Q and Hu, S and Yu, P and Kan, S and Zhang, W}, title = {Equus mitochondrial pangenome reveals independent domestication imprints in donkeys and horses.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {6803}, pmid = {40000832}, issn = {2045-2322}, support = {ZR2023QC278//Natural Science Foundation of Shandong Province/ ; 2022YFC3341002-2//National Key Research and Development Program of China/ ; }, mesh = {Animals ; Horses/genetics ; *Equidae/genetics ; *Genome, Mitochondrial ; Phylogeny ; *Domestication ; Genetic Variation ; *Mitochondria/genetics ; China ; }, abstract = {Mitochondria are semi-autonomous organelles that play a crucial role in the energy budget of animal cells and are closely related to the locomotor abilities of animals. Equidae is renowned for including two domesticated species with distinct purposes: the endurance-oriented donkey and the power-driven horse, making it an ideal system for studying the relationship between mitochondria and locomotor abilities. In this study, to cover the genetic diversity of donkeys, we sequenced and assembled six new mitochondrial genomes from China. Meanwhile, we downloaded the published mitochondrial genomes of all species within Equus and conducted a comprehensive pan-mitochondrial genome analysis. We found that the mitochondrial genomes of Equus are highly conserved, each encoding 37 genes, including 13 protein-coding genes (PCGs). Phylogenetic analysis based on mitochondrial genomes supports previous research, indicating that the extant species in Equus are divided into three main branches: horses, donkeys, and zebras. Specifically, 761 genetic variants were identified between donkeys and horses, 68 of which were non-synonymous mutations in PCGs, potentially linked to their different locomotor abilities. Structural protein modeling indicated that despite genetic differences, the overall protein structures between donkeys and horses remain similar. This study revealed the mitochondrial genome variation patterns of domesticated animals, offering novelty perspectives on domestication imprints. Additionally, it provides reliable candidate molecular markers for the identification of donkeys and horses.}, } @article {pmid40002411, year = {2025}, author = {Peña, FJ and Martín-Cano, FE and Becerro-Rey, L and da Silva-Álvarez, E and Gaitskell-Phillips, G and Aparicio, IM and Gil, MC and Ortega-Ferrusola, C}, title = {Redox Regulation and Glucose Metabolism in the Stallion Spermatozoa.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {2}, pages = {}, pmid = {40002411}, issn = {2076-3921}, abstract = {Stallion spermatozoa are cells which exhibit intense metabolic activity, where oxidative phosphorylation in the mitochondria is the primary ATP generator. However, metabolism must be viewed as a highly interconnected network of oxidation-reduction reactions that generate the energy necessary for life. An unavoidable side effect of metabolism is the generation of reactive oxygen species, leading to the evolution of sophisticated mechanisms to maintain redox homeostasis. In this paper, we provide an updated overview of glucose metabolism in stallion spermatozoa, highlighting recent evidence on the role of aerobic glycolysis in these cells, and the existence of an intracellular lactate shuttle that may help to explain the particular metabolism of the stallion spermatozoa in the context of their redox regulation.}, } @article {pmid40006901, year = {2025}, author = {Stefano, GB and Kream, RM}, title = {Primordial Biochemicals Within Coacervate-Like Droplets and the Origins of Life.}, journal = {Viruses}, volume = {17}, number = {2}, pages = {}, pmid = {40006901}, issn = {1999-4915}, mesh = {*Mitochondria/metabolism/genetics ; *Origin of Life ; *Viruses/genetics/metabolism ; Humans ; Animals ; Energy Metabolism ; Biological Evolution ; Reactive Oxygen Species/metabolism ; }, abstract = {An organism is considered "alive" if it can grow, reproduce, respond to external stimuli, metabolize nutrients, and maintain stability. By this definition, both mitochondria and viruses exhibit the key characteristics of independent life. In addition to their capacity for self-replication under specifically defined conditions, both mitochondria and viruses can communicate via shared biochemical elements, alter cellular energy metabolism, and adapt to their local environment. To explain this phenomenon, we hypothesize that early viral prototype species evolved from ubiquitous environmental DNA and gained the capacity for self-replication within coacervate-like liquid droplets. The high mutation rates experienced in this environment streamlined their acquisition of standard genetic codes and adaptation to a diverse set of host environments. Similarly, mitochondria, eukaryotic intracellular organelles that generate energy and resolve oxygen toxicity, originally evolved from an infectious bacterial species and maintain their capacity for active functionality within the extracellular space. Thus, while mitochondria contribute profoundly to eukaryotic cellular homeostasis, their capacity for freestanding existence may lead to functional disruptions over time, notably, the overproduction of reactive oxygen species, a phenomenon strongly linked to aging-related disorders. Overall, a more in-depth understanding of the full extent of the evolution of both viruses and mitochondria from primordial precursors may lead to novel insights and therapeutic strategies to address neurodegenerative processes and promote healthy aging.}, } @article {pmid40008059, year = {2025}, author = {Nielsen, TL and Nielsen, SH and Novosolov, M and Gravlund, P and Allentoft, ME}, title = {Deeply Diverged but Morphologically Conserved Lineages in Tornier's Cat Snake (Crotaphopeltis tornieri) of the Eastern Arc Mountains.}, journal = {Ecology and evolution}, volume = {15}, number = {2}, pages = {e70452}, pmid = {40008059}, issn = {2045-7758}, abstract = {The Eastern Arc Mountain (EAM) forests in Tanzania have remarkably high endemism. Closely-related forest-adapted species are found isolated on different "sky islands" testifying to allopatry as a major driver for speciation in this region. However, some species defy this pattern. Tornier's cat snake (Crotaphopeltis tornieri) occupies most of the isolated mountain rainforest, despite presumably not being able to move across the arid savannah landscape that separates them. To test contrasting hypotheses of recent dispersal vs morphological conservatism we examined scale characters of 218 C. tornieri individuals and sequenced 80 full mitochondrial genomes covering populations from eight mountain blocks across the EAM and Southern Highlands of Tanzania (SHT). The morphological examination revealed no differentiation between populations except the Usambara Mountain populations showing significant differences in some scale characters. This was in stark contrast to the genetic analyses showing very high divergence between mountain populations. On average the mitochondrial genome showed > 12% genetic differentiation with cytB and COI showing interpopulation distances of up to 28.5% and 15.1%, respectively. Both Bayesian coalescent and maximum-likelihood based phylogenies, uncovered a highly distinct clade structure in C. tornieri defined by the mountains. Divergence times were estimated at c. 21 million years for the split between the EAM and SHT populations and 5.4-1.4 millions years for population splits within EAM. Our results point towards old isolation events but with a highly conserved morphology resulting in just one recognized species. By including presumed outgroups of C. degeni and C. hotamboeia in the phylogeny we found C. tornieri to be paraphyletic. These results have implications for understanding evolution in the EAM and warrant a revision of the number of species in this genus.}, } @article {pmid40021962, year = {2025}, author = {Dong, S and Li, X and Liu, Q and Zhu, T and Tian, A and Chen, N and Tu, X and Ban, L}, title = {Comparative genomics uncovers evolutionary drivers of locust migratory adaptation.}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {203}, pmid = {40021962}, issn = {1471-2164}, support = {2022YFD1400500//National Key Research and Development Program of China/ ; }, mesh = {Animals ; *Animal Migration ; *Grasshoppers/genetics/physiology ; *Genomics/methods ; *Evolution, Molecular ; Selection, Genetic ; *Adaptation, Physiological/genetics ; Phylogeny ; Phenotype ; }, abstract = {BACKGROUND: Locust migration is one of the main causes of locust plagues. While existing research has highlighted the adaptive migratory capabilities of locusts, the evolutionary patterns of their migration remain elusive. This study aims to explore these evolutionary patterns of locust migratory behavior at the genomic level. To achieve this, we conducted comparative genomics analysis using genomic data from 10 locust species with diverse migratory tendencies.

RESULTS: We identified 1064 genes showing signatures of positive selection in five migratory locust species using a dN/dS model. The BUSTED-PH model revealed 116 genes associated with migratory phenotypes. Gene ontology enrichment analysis indicated that these genes were predominantly related to metabolism and mitochondria-related pathways through both methods. Additionally, the evolutionary rate (RER) analysis between migratory and non-migratory locusts revealed significant divergence in energy metabolism pathways. Notably, of the genes analyzed, the SETX gene consistently showed evidence of positive selection across all five migratory species.

CONCLUSIONS: The findings suggest that the evolution of migratory behavior is associated with increased selective pressure on metabolism and mitochondria-related pathways. Hundreds of genes undergo selective changes during repetitive transitions to migratory behavior. These findings enhance our understanding of the genetic and phenotypic relationships underlying different locust migratory behaviors, providing important data for understanding the biological mechanisms behind locust outbreaks.}, } @article {pmid40022150, year = {2025}, author = {Shalata, A and Saada, A and Mahroum, M and Hadid, Y and Furman, C and Shalata, ZE and Desnick, RJ and Lorber, A and Khoury, A and Higazi, A and Shaag, A and Barash, V and Spiegel, R and Vlodavsky, E and Rustin, P and Pietrokovski, S and Manov, I and Gieger, D and Tal, G and Salzberg, A and Mandel, H}, title = {Sengers syndrome caused by biallelic TIMM29 variants and RNAi silencing in Drosophila orthologue recapitulates the human phenotype.}, journal = {Human genomics}, volume = {19}, number = {1}, pages = {21}, pmid = {40022150}, issn = {1479-7364}, mesh = {Animals ; Humans ; Male ; Phenotype ; Female ; Drosophila melanogaster/genetics ; *Cataract/genetics/pathology/congenital ; Alleles ; *Drosophila Proteins/genetics ; RNA Interference ; Mutation ; Pedigree ; *Cardiomyopathy, Hypertrophic/genetics/pathology ; *Acidosis, Lactic/genetics/pathology ; Disease Models, Animal ; Adult ; Mitochondria/pathology/genetics ; }, abstract = {PURPOSE: Sengers-syndrome (S.S) is a genetic disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy and lactic acidosis. All reported cases were genetically caused by biallelic mutations in the AGK gene. We herein report a pathogenic variant in TIMM29 gene, encoding Tim29 protein, as a novel cause of S.S. Notably, AGK and Tim29 proteins are components of the TIM22 complex, which is responsible for importing carrier proteins into the inner mitochondrial membrane.

METHOD: Clinical data of 17 consanguineous patients featuring S.S was obtained. Linkage analysis, and sequencing were used to map and identify the disease-causing gene. Tissues derived from the study participants and a Drosophila melanogaster model were used to evaluate the effects of TIMM29 variant on S.S.

RESULTS: The patients presented with a severe phenotype of S.S, markedly elevated serum creatine-phosphokinase, combined mitochondrial-respiratory-chain-complexes deficiency, reduced pyruvate-dehydrogenase complex activity, and reduced adenine nucleotide translocator 1 protein. Histopathological studies showed accumulation of abnormal mitochondria. Homozygosity mapping and gene sequencing revealed a biallelic variant in TIMM29 NM_138358.4:c.514T > C NP_612367.1:p.(Trp172Arg). The knockdown of the Drosophila TIMM29 orthologous gene (CG14270) recapitulated the phenotype and pathology observed in the studied cohort. We expand the clinical phenotype of S.S and provide substantial evidence supporting TIMM29 as the second causal gene of a severe type of S.S, designated as S.S- TIMM29.

CONCLUSION: The present study uncovers several biochemical differences between the two S.S types, including the hyperCPKemia being almost unique for S.S-TIMM29 cohort, the different frequency of MMRCC and PDHc deficiencies among the two S.S types. We propose to designate the S.S associated with TIMM29 homozygous variant as S.S-TIMM29.}, } @article {pmid40027321, year = {2025}, author = {Zhang, T and Fu, J and Li, C and Gong, R and Al-Rasheid, KAS and Stover, NA and Shao, C and Cheng, T}, title = {Novel findings on the mitochondria in ciliates, with description of mitochondrial genomes of six representatives.}, journal = {Marine life science & technology}, volume = {7}, number = {1}, pages = {79-95}, pmid = {40027321}, issn = {2662-1746}, support = {P40 OD010964/OD/NIH HHS/United States ; }, abstract = {UNLABELLED: Determining and comparing mitochondrial genomes (mitogenomes) are essential for assessing the diversity and evolution of mitochondria. Ciliates are ancient and diverse unicellular eukaryotes, and thus are ideal models for elucidating the early evolution of mitochondria. Here, we report on six new mitogenomes of spirotrichs, a dominant ciliate group, and perform comparative analyses on 12 representative species. We show that: (1) the mitogenomes of spirotrichs are linear structures with high A+T contents (61.12-81.16%), bidirectional transcription, and extensive synteny (except for the nad5, ccmf and cob genes in Euplotia); (2) the non-split of NADH dehydrogenase subunit 2 gene (nad2) is a plesiomorphy of ciliates, whereas it has evolved into a split gene in Spirotrichea (apart from Euplotes taxa), Oligohymenophorea, and Armophorea; (3) the number of small subunit ribosomal proteins (rps) encoded in mitogenomes increases in the later branching classes of ciliates, whereas rps8 shows a loss trend during the evolution of Euplotes taxa; (4) the mitogenomes of spirotrichs exhibit A/T codon bias at the third position, and the codon bias is mainly due to DNA mutation in oligotrichs, hypotrichs and Diophrys appendiculata; (5) the phylogenetic position of D. appendiculata is unstable and controversial based on both phylogenetic analyses and mitogenome evidence. In summary, we investigated the mitogenome diversity of spirotrichs and broadened our understanding of the evolution of mitochondria in ciliates.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42995-024-00249-7.}, } @article {pmid40027421, year = {2025}, author = {Bagdonaitė, L and Mauvisseau, Q and Johnsen, A and Lifjeld, JT and Leder, EH}, title = {Sperm mtDNA Copy Number Is Not Associated With Midpiece Size Among Songbirds.}, journal = {Ecology and evolution}, volume = {15}, number = {3}, pages = {e71055}, pmid = {40027421}, issn = {2045-7758}, abstract = {Tremendous variation in sperm morphology is observed across the animal kingdom. Within avian taxa, the songbirds (infraorder Passerides) have the largest variation in sperm morphology. Their spermatozoa move by using energy generated in the midpiece, which is formed by multiple mitochondria fusing together during spermatogenesis. However, very little is known regarding the number of mitochondria required to form the songbird midpiece. Based on previous research showing an association of midpiece length and mitochondrial DNA (mtDNA) copy number in the zebra finch Taeniopygia guttata, we hypothesize that songbird species with longer sperm midpieces have more copies of mtDNA. We estimated the sperm mtDNA copy number in 19 species from 10 families within Passerides, covering a broad range of midpiece sizes. Mitochondrial and nuclear DNA abundance were determined using droplet digital PCR (ddPCR) and the ratio between mitochondrial and single-copy nuclear genes was used to estimate mtDNA copy number per spermatozoon. We found that species differ in their average mtDNA copy number, but the variation was small and not significantly related to midpiece length. A possible explanation is that mitochondrial genomes are eliminated in the spermatids during spermatogenesis.}, } @article {pmid40029892, year = {2025}, author = {Paul, SK and Islam, MSU and Akter, N and Zohra, FT and Rashid, SB and Ahmed, MS and Rahman, SM and Sarkar, MAR}, title = {Genome-wide identification and characterization of FORMIN gene family in cotton (Gossypium hirsutum L.) and their expression profiles in response to multiple abiotic stress treatments.}, journal = {PloS one}, volume = {20}, number = {3}, pages = {e0319176}, pmid = {40029892}, issn = {1932-6203}, mesh = {*Gossypium/genetics/metabolism ; *Stress, Physiological/genetics ; Phylogeny ; *Gene Expression Regulation, Plant ; *Formins/genetics ; *Plant Proteins/genetics/metabolism ; *Multigene Family ; Gene Expression Profiling ; Genome, Plant ; }, abstract = {FORMIN proteins distinguished by FH2 domain, are conserved throughout evolution and widely distributed in eukaryotic organisms. These proteins interact with various signaling molecules and cytoskeletal proteins, playing crucial roles in both biotic and abiotic stress responses. However, the functions of FORMINs in cotton (Gossypium hirsutum L.) remain uncovered. In this study, 46 FORMIN genes in G. hirsutum (referred to as GhFH) were systematically identified. The gene structures, conserved domains, and motifs of these GhFH genes were thoroughly explored. Phylogenetic and structural analysis classified these 46 GhFH genes into five distinct groups. In silico subcellular localization, prediction suggested that GhFH genes are distributed across various cellular compartments, including the nucleus, extracellular space, cytoplasm, mitochondria, cytoskeleton, plasma membrane, endoplasmic reticulum, and chloroplasts. Evolutionary and functional diversification analyses, based on on-synonymous (Ka) and synonymous (Ks) ratios and gene duplication events, indicated that GhFH genes have evolved under purifying selection. The analysis of cis-acting elements suggested that GhFH genes may be involved in plant growth, hormone regulation, light response, and stress response. Results from transcriptional factors TFs and gene ontology analysis indicate that FORMIN proteins regulate cell wall structure and cytoskeleton dynamics by reacting to hormone signals associated with environmental stress. Additionally, 45 putative ghr-miRNAs were identified from 32 families targeting 33 GhFH genes. Expression analysis revealed that GhFH1, GhFH10, GhFH20, GhFH24, and GhFH30 exhibited the highest levels of expression under red, blue, and white light conditions. Further, GhFH9, GhFH20, and GhFH30 displayed higher expression levels under heat stress, while GhFH20 and GhFH30 showed increased expression under salt stress compared to controls. The result suggests that GhFH20 and GhFH30 genes could play significant roles in the development of G. hirsutum under heat and salt stresses. Overall these findings enhance our understanding of the biological functions of the cotton FORMIN family, offering prospects for developing stress-resistant cotton varieties through manipulation of GhFH gene expression.}, } @article {pmid40037840, year = {2025}, author = {Medini, H and Mishmar, D}, title = {Vertebrates show coordinated elevated expression of mitochondrial and nuclear genes after birth.}, journal = {Genome research}, volume = {35}, number = {3}, pages = {459-474}, pmid = {40037840}, issn = {1549-5469}, mesh = {Animals ; *Gene Expression Regulation, Developmental ; *Vertebrates/genetics/growth & development ; *Genes, Mitochondrial ; *Mitochondria/genetics/metabolism ; *Cell Nucleus/genetics ; Oxidative Phosphorylation ; Transcription Factors/genetics ; Chickens/genetics ; Zebrafish/genetics ; }, abstract = {Interactions between mitochondrial and nuclear factors are essential to life. Nevertheless, the importance of coordinated regulation of mitochondrial-nuclear gene expression (CMNGE) to changing physiological conditions is poorly understood and is limited to certain tissues and organisms. We hypothesized that CMNGE is important for development across vertebrates and, hence, should be conserved. As a first step, we analyzed more than 1400 RNA-seq experiments performed during prenatal development, in neonates, and in adults across vertebrate evolution. We find conserved sharp elevation of CMNGE after birth, including oxidative phosphorylation (OXPHOS) and mitochondrial ribosome genes, in the heart, hindbrain, forebrain, and kidney across mammals, as well as in Gallus gallus and in the lizard Anolis carolinensis This is accompanied by elevated expression of TCA cycle enzymes and reduction in hypoxia response genes, suggesting a conserved cross-tissue metabolic switch after birth/hatching. Analysis of about 70 known regulators of mitochondrial gene expression reveals consistently elevated expression of PPARGC1A (also known as Pgc-1alpha) and CEBPB after birth/hatching across organisms and tissues, thus highlighting them as candidate regulators of CMNGE upon transition to the neonate. Analyses of Danio rerio, Xenopus tropicalis, Caenorhabditis elegans, and Drosophila melanogaster reveal elevated CMNGE prior to hatching in X. tropicalis and in D. melanogaster, which is associated with the emergence of muscle activity. Lack of such an ancient pattern in mammals and in chickens suggests that it was lost during radiation of terrestrial vertebrates. Taken together, our results suggest that regulated CMNGE after birth reflects an essential metabolic switch that is under strong selective constraints.}, } @article {pmid40043708, year = {2025}, author = {Thomas, HB and Demain, LAM and Cabrera-Orefice, A and Schrauwen, I and Shamseldin, HE and Rea, A and Bharadwaj, T and Smith, TB and Oláhová, M and Thompson, K and He, L and Kaur, N and Shukla, A and Abukhalid, M and Ansar, M and Rehman, S and Riazuddin, S and Abdulwahab, F and Smith, JM and Stark, Z and Mancilar, H and Tumer, S and Esen, FN and Uctepe, E and Topcu, V and Yesilyurt, A and Afzal, E and Salari, M and Carroll, C and Zifarelli, G and Bauer, P and Kor, D and Bulut, FD and Houlden, H and Maroofian, R and Carrera, S and Yue, WW and Munro, KJ and Alkuraya, FS and Jamieson, P and Ahmed, ZM and Leal, SM and Taylor, RW and Wittig, I and O'Keefe, RT and Newman, WG}, title = {Bi-allelic variants in MRPL49 cause variable clinical presentations, including sensorineural hearing loss, leukodystrophy, and ovarian insufficiency.}, journal = {American journal of human genetics}, volume = {112}, number = {4}, pages = {952-962}, pmid = {40043708}, issn = {1537-6605}, support = {R01 HD109342/HD/NICHD NIH HHS/United States ; R01 NS107428/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Female ; *Hearing Loss, Sensorineural/genetics/pathology ; *Primary Ovarian Insufficiency/genetics/pathology ; Child ; Alleles ; Child, Preschool ; Pedigree ; Male ; *Ribosomal Proteins/genetics ; *Mitochondrial Proteins/genetics ; Oxidative Phosphorylation ; Adolescent ; Phenotype ; Adult ; *Gonadal Dysgenesis, 46,XX/genetics ; Mutation ; Infant ; }, abstract = {Combined oxidative phosphorylation deficiency (COXPD) is a rare multisystem disorder that is clinically and genetically heterogeneous. Genome sequencing identified bi-allelic MRPL49 variants in individuals from nine unrelated families with presentations ranging from Perrault syndrome (primary ovarian insufficiency and sensorineural hearing loss) to severe childhood onset of leukodystrophy, learning disability, microcephaly, and retinal dystrophy. Complexome profiling of fibroblasts from affected individuals revealed reduced levels of the small mitochondrial ribosomal subunits and a more pronounced reduction of the large mitochondrial ribosomal subunits. There was no evidence of altered mitoribosomal assembly. The reductions in levels of oxidative phosphorylation (OXPHOS) enzyme complexes I and IV are consistent with a form of COXPD associated with bi-allelic MRPL49 variants, expanding the understanding of how disruption of the mitochondrial ribosomal large subunit results in multisystem phenotypes.}, } @article {pmid40043709, year = {2025}, author = {Ping, J and Liu, X and Lu, Y and Quan, C and Fan, P and Lu, H and Li, Q and Wang, C and Zhang, Z and Liu, M and Chen, S and Chang, L and Jiang, Y and Huang, Q and Liu, J and Wuren, T and Liu, H and Hao, Y and Kang, L and Liu, G and Lu, H and Wei, X and Wang, Y and Li, Y and Guo, H and Cui, Y and Zhang, H and Zhang, Y and Zhai, Y and He, Y and Zheng, W and Qi, X and Ouzhuluobu, and Ma, H and Yang, L and Wang, X and Jin, W and Cui, Y and Ge, R and Wu, S and Wei, Y and Su, B and He, F and Zhang, H and Zhou, G}, title = {A highland-adaptation variant near MCUR1 reduces its transcription and attenuates erythrogenesis in Tibetans.}, journal = {Cell genomics}, volume = {5}, number = {3}, pages = {100782}, pmid = {40043709}, issn = {2666-979X}, mesh = {Humans ; Tibet ; *Erythropoiesis/genetics ; Altitude ; Calcium/metabolism ; Mitochondria/metabolism ; Quantitative Trait Loci/genetics ; Polymorphism, Single Nucleotide/genetics ; *Adaptation, Physiological/genetics ; Male ; Transcription, Genetic ; Female ; East Asian People ; }, abstract = {To identify genomic regions subject to positive selection that might contain genes involved in high-altitude adaptation (HAA), we performed a genome-wide scan by whole-genome sequencing of Tibetan highlanders and Han lowlanders. We revealed a collection of candidate genes located in 30 genomic loci under positive selection. Among them, MCUR1 at 6p23 was a novel pronounced candidate. By single-cell RNA sequencing and comprehensive functional studies, we demonstrated that MCUR1 depletion leads to impairment of erythropoiesis under hypoxia and normoxia. Mechanistically, MCUR1 knockdown reduced mitochondrial Ca[2+] uptake and then concomitantly increased cytosolic Ca[2+] levels, which thereby reduced erythropoiesis via the CAMKK2-AMPK-mTOR axis. Further, we revealed rs61644582 at 6p23 as an expression quantitative trait locus for MCUR1 and a functional variant that confers an allele-specific transcriptional regulation of MCUR1. Overall, MCUR1-mediated mitochondrial Ca[2+] homeostasis is highlighted as a novel regulator of erythropoiesis, deepening our understanding of the genetic mechanism of HAA.}, } @article {pmid40056111, year = {2025}, author = {Sun, A and Wang, WX}, title = {Photodegradation Controls of Potential Toxicity of Secondary Sunscreen-Derived Microplastics and Associated Leachates.}, journal = {Environmental science & technology}, volume = {59}, number = {10}, pages = {5223-5236}, pmid = {40056111}, issn = {1520-5851}, mesh = {*Microplastics/toxicity ; *Sunscreening Agents ; Photolysis ; Water Pollutants, Chemical/toxicity ; }, abstract = {The escalating environmental concern over secondary microplastics (SMPs) stems from their physicochemical evolution from primary microplastics (PMPs), yet the contribution of varying physicochemical transformations to the ultimate environmental risks remains unknown. In this study, a photomechanical degradation process was employed to convert the primary sunscreen-derived microplastics (SDMPs) into secondary SDMPs. While mechanical degradation caused physical fragmentation, photodegradation induced both physical and chemical alterations, introducing surface oxidation, chemical bond scission, and cross-linking to the secondary SDMPs. Employing a combination of alkaline digestion and pyrolysis GC-MS techniques, it was observed that both physical fragmentation and photooxidation led to heightened intracellular sequestration of MPs. Although the bioaccumulated SDMPs could be indicated by the enlarged lysosomes and fragmented mitochondria, toxicity of secondary SDMPs at the cellular level was primarily driven by chemical transformations post-photodegradation. A nontargeted analysis employing high-resolution mass spectrometry identified 46 plastic-associated compounds in the leachate, with photodegradation-induced chemical transformations playing a crucial role in the dissociation of hydrophobic additives and oxidative conversion of leached compounds. The toxicity of the leachate was exacerbated by photodegradation, with mitochondrial fragmentation serving as the primary subcellular biomarker, indicative of leachate toxicity. This study elucidates the pivotal role of photodegradation in augmenting the cytotoxicity of secondary SDMPs, shedding light on the intricate interplay between physicochemical transformations and environmental risks.}, } @article {pmid40072502, year = {2025}, author = {Kemph, A and Kharel, K and Tindell, SJ and Arkov, AL and Lynch, JA}, title = {Novel structure and composition of the unusually large germline determinant of the wasp Nasonia vitripennis.}, journal = {Molecular biology of the cell}, volume = {36}, number = {5}, pages = {ar55}, pmid = {40072502}, issn = {1939-4586}, support = {P20 GM103436/GM/NIGMS NIH HHS/United States ; R01 GM129153/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Wasps/metabolism ; *Germ Cells/metabolism/ultrastructure ; Ribonucleoproteins/metabolism ; Female ; Insect Proteins/metabolism ; RNA, Messenger/metabolism ; Cytoplasmic Granules/metabolism/ultrastructure ; Microscopy, Electron, Transmission ; }, abstract = {Specialized, maternally derived ribonucleoprotein (RNP) granules play an important role in specifying the primordial germ cells in many animal species. Typically, these germ granules are small (∼100 nm to a few microns in diameter) and numerous; in contrast, a single, extremely large granule called the oosome plays the role of germline determinant in the wasp Nasonia vitripennis. The organizational basis underlying the form and function of this unusually large membraneless RNP granule remains an open question. Here we use a combination of super-resolution and transmission electron microscopy (TEM) to investigate the composition and morphology of the oosome. We show evidence which suggests the oosome has properties of a viscous liquid or elastic solid. The most prominent feature of the oosome is a branching mesh-like network of high abundance mRNAs that pervades the entire structure. Homologues of the core germ granule proteins Vasa and Oskar do not appear to nucleate this network but rather are distributed adjacently as separate puncta. Low abundance RNAs appear to cluster in puncta that similarly do not overlap with the protein puncta. Several membrane-bound organelles, including lipid droplets and rough endoplasmic reticulum (ER)-like vesicles, are incorporated within the oosome, whereas mitochondria are nearly entirely excluded. Our findings show that the remarkably large size of the oosome is reflected in a complex subgranular organization and suggest that the oosome is a powerful model for probing interactions between membraneless and membrane-bound organelles, structural features that contribute to granule size, and the evolution of germ plasm in insects.}, } @article {pmid40075306, year = {2025}, author = {Zhou, N and Wang, X and Xia, Y and Liu, Z and Luo, L and Jin, R and Tong, X and Shi, Z and Wang, Z and Sui, H and Ma, Y and Li, Y and Cao, Z and Zhang, Y}, title = {Comparatively profiling the transcriptome of human, Porcine and mouse oocytes undergoing meiotic maturation.}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {236}, pmid = {40075306}, issn = {1471-2164}, support = {2020LCX015//Anhui Province Innovation and Entrepreneurship Support Program for Returnee Scholar/ ; 2021YFA0805905//Sub-project of National Key Research and Development Program of China/ ; AHCYJSTX-04//Special Fund for Anhui Agriculture Research System/ ; }, mesh = {Animals ; *Oocytes/metabolism/cytology ; Mice ; *Meiosis/genetics ; Humans ; Swine ; *Gene Expression Profiling ; *Transcriptome ; Female ; Species Specificity ; }, abstract = {BACKGROUND: Oocyte maturation is a critical process responsible for supporting preimplantation embryo development and full development to term. Understanding oocyte gene expression is relevant given the unique molecular mechanism present in this gamete. Comparative transcriptome analysis across species offers a powerful approach to uncover conserved and species-specific genes involved in the molecular regulation of oocyte maturation throughout evolution.

RESULTS: Transcriptome analysis identified 4,625, 3,824, 4,972 differentially expressed genes (DEGs) between the germinal vesicle (GV) and metaphase II (MII) stage in human, porcine and mouse oocytes respectively. These DEGs showed dynamic changes associated with oocyte maturation. Functional enrichment analysis revealed that the DEGs in all three species were mainly involved in DNA replication, cell cycle and redox regulation. Comparative transcriptome analysis identified 551 conserved DEGs in the three species with significant enrichment in mitochondria and mitochondrial intima.

CONCLUSIONS: This study provides a systematic comparative analysis of oocyte meiotic maturation in humans, pigs and mice identifying both conserved and species-specific patterns during oocyte meiosis. Our findings also implied that the selection of oocyte expressed genes among these three species could form a basis for further exploring their functional roles in human oocyte maturation.}, } @article {pmid40076588, year = {2025}, author = {Zhou, W and Cao, X and Li, H and Cui, X and Diao, X and Qiao, Z}, title = {Genomic Analysis of Hexokinase Genes in Foxtail Millet (Setaria italica): Haplotypes and Expression Patterns Under Abiotic Stresses.}, journal = {International journal of molecular sciences}, volume = {26}, number = {5}, pages = {}, pmid = {40076588}, issn = {1422-0067}, mesh = {*Setaria Plant/genetics/enzymology ; Phylogeny ; *Gene Expression Regulation, Plant ; *Stress, Physiological/genetics ; *Haplotypes ; *Hexokinase/genetics/metabolism ; *Plant Proteins/genetics/metabolism ; Genomics/methods ; Evolution, Molecular ; }, abstract = {Hexokinases (HXKs) in plants are multifunctional enzymes that not only phosphorylate hexose but also function as glucose sensors, integrating nutrient, light, and hormone signaling networks to regulate cell metabolism and signaling pathways, thereby controlling growth and development in response to environmental changes. To date, limited information is available regarding the HXKs of foxtail millet (Setaria italica L.). In this study, six HXK genes were identified and characterized in foxtail millet. Phylogenetic analysis revealed that the foxtail millet hexokinases were classified into three subfamilies, corresponding to the two types (B-type and C-type) of hexokinases in plants. Gene structure and conserved motif analysis showed that the SiHXKs exhibited varying numbers of introns and exons, with proteins in each subfamily showing similar motif organization. Evolutionary divergence analysis indicated that the foxtail millet HXK and green foxtail HXK genes families underwent both positive and negative selection and experienced a large-scale duplication event approximately 1.18-154.84 million years ago. Expression analysis revealed that these genes are widely expressed in roots, stems, leaves, panicles, anthers, and seeds, with most genes showing significantly increased expression in roots under abiotic stress conditions, including 20% PEG 6000 (drought stress), 200 μmol/L NaCl (salt stress), and 1 μmol/L BR (brassinosteroid-mediated stress response). These results suggest that these genes may play a pivotal role in enhancing stress tolerance. Subcellular localization assay showed that SiHXK5 and SiHXK6 were predominantly localized in mitochondria. Haplotype analysis revealed that SiHXK3-H1 was associated with higher plant height and grain yield. These findings provide valuable insights into the functional characteristics of HXK genes, especially in the context of marker-assisted selection and the pyramiding of advantageous haplotypes in foxtail millet breeding programs.}, } @article {pmid40081380, year = {2025}, author = {Morel, CA and Asencio, C and Moreira, D and Blancard, C and Salin, B and Gontier, E and Duvezin-Caubet, S and Rojo, M and Bringaud, F and Tetaud, E}, title = {A new member of the dynamin superfamily modulates mitochondrial membrane branching in Trypanosoma brucei.}, journal = {Current biology : CB}, volume = {35}, number = {6}, pages = {1337-1352.e5}, doi = {10.1016/j.cub.2025.02.033}, pmid = {40081380}, issn = {1879-0445}, mesh = {*Trypanosoma brucei brucei/genetics/metabolism/physiology ; *Mitochondrial Membranes/metabolism ; *Dynamins/metabolism/genetics ; *Protozoan Proteins/metabolism/genetics ; Mitochondrial Dynamics ; Mitochondria/metabolism ; Phylogeny ; }, abstract = {Unlike most other eukaryotes, where mitochondria continuously fuse and divide, the mitochondrion of trypanosome cells forms a single and continuously interconnected network that divides only during cytokinesis. However, the machinery governing mitochondrial remodeling and interconnection of trypanosome mitochondrion remain largely unknown. We functionally characterize a new member of the dynamin superfamily protein (DSP) from T. brucei (TbMfnL), which shares similarity with a family of homologs present in various eukaryotic and prokaryotic phyla but not in opisthokonts like mammals and budding yeast. The sequence and domain organization of TbMfnL is distinct, and it is phylogenetically very distant from the yeast and mammalian dynamin-related proteins involved in mitochondrial fusion/fission dynamics, such as optic atrophy 1 (Opa1) and mitofusin (Mfn). TbMfnL localizes to the inner mitochondrial membrane facing the matrix and, upon overexpression, induces a strong increase in the interconnection and branching of mitochondrial filaments in a GTPase-dependent manner. TbMfnL is a component of a novel membrane remodeling machinery with an unprecedented matrix-side localization that is able to modulate the degree of inter-mitochondrial connections.}, } @article {pmid40107618, year = {2025}, author = {Thalhofer, V and Doktor, C and Philipp, L and Betat, H and Mörl, M}, title = {An alternative adaptation strategy of the CCA-adding enzyme to accept noncanonical tRNA substrates in Ascaris suum.}, journal = {The Journal of biological chemistry}, volume = {301}, number = {4}, pages = {108414}, pmid = {40107618}, issn = {1083-351X}, mesh = {*Ascaris suum/enzymology/genetics ; Animals ; *RNA, Transfer/metabolism/chemistry/genetics ; *RNA Nucleotidyltransferases/metabolism/genetics/chemistry ; Substrate Specificity ; *Helminth Proteins/metabolism/genetics/chemistry ; Peptide Elongation Factor Tu/metabolism/genetics/chemistry ; }, abstract = {Playing a central role in translation, tRNAs act as an essential adapter linking the correct amino acid to the corresponding mRNA codon in translation. Due to this function, all tRNAs exhibit a typical secondary and tertiary structure to be recognized by the tRNA maturation enzymes as well as many components of the translation machinery. Yet, there is growing evidence for structurally deviating tRNAs in metazoan mitochondria, requiring a coevolution and adaptation of these enzymes to the unusual structures of their substrates. Here, it is shown that the CCA-adding enzyme of Ascaris suum carries such a specific adaptation in form of a C-terminal extension. The corresponding enzymes of other nematodes also carry such extensions, and many of them have an additional adaptation in a small region of their N-terminal catalytic core. Thus, the presented data indicate that these enzymes evolved two distinct strategies to tolerate noncanonical tRNAs as substrates for CCA incorporation. The identified C-terminal extension represents a surprising case of convergent evolution in tRNA substrate adaptation, as the nematode mitochondrial translation factor EF-Tu1 carries a similar extension that is essential for efficient binding to such structurally deviating tRNAs.}, } @article {pmid40107722, year = {2025}, author = {Dondi, A and Borgsmüller, N and Ferreira, PF and Haas, BJ and Jacob, F and Heinzelmann-Schwarz, V and , and Beerenwinkel, N}, title = {De novo detection of somatic variants in high-quality long-read single-cell RNA sequencing data.}, journal = {Genome research}, volume = {35}, number = {4}, pages = {900-913}, pmid = {40107722}, issn = {1549-5469}, support = {U24 CA180922/CA/NCI NIH HHS/United States ; 766030/ERC_/European Research Council/International ; }, mesh = {Humans ; *Single-Cell Analysis/methods ; *Polymorphism, Single Nucleotide ; DNA Copy Number Variations ; Female ; *Ovarian Neoplasms/genetics/pathology ; *Sequence Analysis, RNA/methods ; *Neoplasms/genetics ; Computational Biology/methods ; }, abstract = {In cancer, genetic and transcriptomic variations generate clonal heterogeneity, leading to treatment resistance. Long-read single-cell RNA sequencing (LR scRNA-seq) has the potential to detect genetic and transcriptomic variations simultaneously. Here, we present LongSom, a computational workflow leveraging high-quality LR scRNA-seq data to call de novo somatic single-nucleotide variants (SNVs), including in mitochondria (mtSNVs), copy number alterations (CNAs), and gene fusions, to reconstruct the tumor clonal heterogeneity. Before somatic variant calling, LongSom reannotates marker gene-based cell types using cell mutational profiles. LongSom distinguishes somatic SNVs from noise and germline polymorphisms by applying an extensive set of hard filters and statistical tests. Applying LongSom to human ovarian cancer samples, we detected clinically relevant somatic SNVs that were validated against matched DNA samples. Leveraging somatic SNVs and fusions, LongSom found subclones with different predicted treatment outcomes. In summary, LongSom enables de novo variant detection without the need for normal samples, facilitating the study of cancer evolution, clonal heterogeneity, and treatment resistance.}, } @article {pmid40112915, year = {2026}, author = {Park, YJ and Pang, WK and Ryu, DY and Rahman, MS and Pang, MG}, title = {Spatiotemporal translation of sperm acrosome associated proteins during early capacitation modulates sperm fertilizing ability.}, journal = {Journal of advanced research}, volume = {79}, number = {}, pages = {313-329}, pmid = {40112915}, issn = {2090-1224}, mesh = {Male ; *Sperm Capacitation/physiology ; Animals ; Cattle ; *Spermatozoa/metabolism ; *Protein Biosynthesis ; *Fertilization/physiology ; *Acrosome/metabolism ; Fertility/physiology ; Proteome/metabolism ; }, abstract = {INTRODUCTION: Despite the lack of essential cytoplasmic organelles in mature spermatozoa, which creates unfavorable conditions for transcription and translation, the presence of various mRNA and proteins during capacitation suggests potential for de novo protein synthesis.

OBJECTIVES: We applied a metabolic labeling method using a fluorescent noncanonical amino acid tagging system (FUNCAT) and proximity ligation method (PLA) in normal and reduced fertility spermatozoa to detect different translation phenomena during sperm capacitation according to their fertility.

METHODS: We explored different proteome changes in spermatozoa according to the time-sequential capacitation process (0, 20, 40, 60, and 120 min) between normal [average fertility rate (FR) = 77.44 % ± 1.51] and reduced fertility (average FR = 58.57 % ± 1.64) spermatozoa bull spermatozoa, as the representative male fertility models owing to their broad spectrum of fertility phenotypes. Moreover, the FUNCAT/PLA method was used to detect and visualize different translation phenomena during sperm capacitation according to fertility.

RESULTS: We found that sperm-associated protein (SPACA) 1 and SPACA5 were newly synthesized in the head of normal-fertility spermatozoa, whereas a lack of newly synthesized proteins in the head and a relatively earlier loss of SPACA1 and SPACA5 were observed in the reduced-fertility spermatozoa. Moreover, the mitochondrial translation inhibitor, chloramphenicol, partially inhibited sperm translation and delayed translocation, suggesting that mitochondria participate in sperm translation.

CONCLUSION: Our results unveil time-sequential microenvironmental changes in sperm proteomes during capacitation, which lead to the orchestra of proteins that complete fertilization. Fertile spermatozoa are selected through inter-competition during the journey of fertilization in the female reproductive tract. This study provides an overview of how translation dynamics acts on the sperm selection and influence the evolution of sperm fertility.}, } @article {pmid40114504, year = {2025}, author = {Iverson, ENK and Criswell, A and Havird, JC}, title = {Stronger Evidence for Relaxed Selection Than Adaptive Evolution in High-elevation Animal mtDNA.}, journal = {Molecular biology and evolution}, volume = {42}, number = {4}, pages = {}, pmid = {40114504}, issn = {1537-1719}, support = {R35 GM142836/GM/NIGMS NIH HHS/United States ; 1R35GM142836/NH/NIH HHS/United States ; //Stengl-Wyer Endowment/ ; }, mesh = {Animals ; *Selection, Genetic ; *DNA, Mitochondrial/genetics ; *Evolution, Molecular ; Altitude ; Genome, Mitochondrial ; Fishes/genetics ; Vertebrates/genetics ; Arthropods/genetics ; Adaptation, Biological/genetics ; Biological Evolution ; Adaptation, Physiological/genetics ; }, abstract = {Mitochondrial (mt) genes are the subject of many adaptive hypotheses due to the key role of mitochondria in energy production and metabolism. One widespread adaptive hypothesis is that selection imposed by life at high elevation leads to the rapid fixation of beneficial alleles in mtDNA, reflected in the increased rates of mtDNA evolution documented in many high-elevation species. However, the assumption that fast mtDNA evolution is caused by positive selection, rather than relaxed purifying selection, has rarely been tested. Here, we calculated the dN/dS ratio, a metric of nonsynonymous substitution bias, and explicitly tested for relaxed selection in the mtDNA of over 700 species of terrestrial vertebrates, freshwater fishes, and arthropods, with information on elevation and latitudinal range limits, range sizes, and body sizes. We confirmed that mitochondrial genomes of high-elevation taxa have slightly higher dN/dS ratios compared to low-elevation relatives. High-elevation species tend to have smaller ranges, which predict higher dN/dS ratios and more relaxed selection across species and clades, while absolute elevation and latitude do not predict higher dN/dS. We also find a positive relationship between body mass and dN/dS, supporting a role for small effective population size leading to relaxed selection. We conclude that higher mt dN/dS among high-elevation species is more likely to reflect relaxed selection due to smaller ranges and reduced effective population size than adaptation to the environment. Our results highlight the importance of rigorously testing adaptive stories against non-adaptive alternative hypotheses, especially in mt genomes.}, } @article {pmid40119623, year = {2025}, author = {Tamburino, R and D'Agostino, N and Aufiero, G and Nicolia, A and Facchiano, A and Giordano, D and Sannino, L and Paparo, R and Arimura, SI and Scotti, N and Cardi, T}, title = {Mitochondrial gene editing and allotopic expression unveil the role of orf125 in the induction of male fertility in some Solanum spp. hybrids and in the evolution of the common potato.}, journal = {Plant biotechnology journal}, volume = {23}, number = {5}, pages = {1862-1875}, pmid = {40119623}, issn = {1467-7652}, support = {//European Commission/ ; }, mesh = {*Plant Infertility/genetics ; *Gene Editing ; *Solanum/genetics/physiology ; *Solanum tuberosum/genetics/physiology ; Plant Proteins/genetics/metabolism ; Genome, Mitochondrial/genetics ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; }, abstract = {Genic-cytoplasmic male sterility (CMS) due to interactions between nuclear and cytoplasmic genomes is a well-known phenomenon in some Solanum spp. hybrids, but genes involved are not known. In this study, the chondriomes of two isonuclear male-fertile and sterile somatic hybrids (SH9A and SH9B, respectively) between the common potato (S. tuberosum Group Tuberosum, tbr) and the wild species S. commersonii were sequenced and compared to those of parental species to identify mitochondrial genes involved in the expression of male sterility. A putative novel gene (orf125) was found only in tbr and in male-sterile hybrids. Physical or functional deletion of orf125 by mtDNA editing in SH9B and its allotopic expression in SH9A clearly demonstrated that orf125 affects male fertility. Besides knockout mutants induced by mitoTALEN and DddA-derived cytosine base editing, specific orf125 missense mutations generated by the latter approach also induced reversion to male fertility in edited SH9B plants, prompting further studies on ORF125 structure-function relationship. The organization of the mitochondrial genome region implicated in CMS was found to be conserved across all common potato accessions, while an identical copy of tbr orf125 was detected in accessions belonging to the S. berthaultii species complex (ber). Such findings corroborate the hypothesis that ber accessions with T/β cytoplasm outcrossed as female with Andean potato, giving rise to the differentiation of the Chilean potato, and highlight the origin of mitochondrial factors contributing to genic-cytoplasmic male sterility in some tuber-bearing Solanum hybrids. Our results contribute to the development of innovative breeding approaches in potato.}, } @article {pmid40123256, year = {2025}, author = {Richmond, JQ and Gottscho, AD and Jockusch, EL and Leaché, AD and Fisher, RN and Reeder, TW}, title = {Genomic discordance throws a wrench in the parallel speciation hypothesis for scincid lizards.}, journal = {Evolution; international journal of organic evolution}, volume = {79}, number = {7}, pages = {1386-1399}, doi = {10.1093/evolut/qpaf059}, pmid = {40123256}, issn = {1558-5646}, mesh = {Animals ; *Lizards/genetics/classification/anatomy & histology ; *Genetic Speciation ; Hybridization, Genetic ; Reproductive Isolation ; Phylogeny ; Female ; Male ; DNA, Mitochondrial/genetics ; }, abstract = {Parallel evolution of the same reproductive isolation barrier within a taxon is an indicator of ecology's role in speciation (i.e., parallel speciation), yet spatiotemporal variability in the efficacy of the barrier can present challenges to retracing how it evolved. Here, we revisit the evidence for a candidate example of parallel speciation in a clade of scincid lizards (the Plestiodon skiltonianus complex) using genomic data, with emphasis on determining whether hybridization may have confounded the phylogenetic signals of parallelism for this group. Our results show a striking case of genealogical discordance, in which mitochondrial loci support multiple origins of a derived large-bodied morphotype (Plestiodon gilberti) within a small-bodied ancestor (Plestiodon skiltonianus), whereas nuclear loci indicate a single origin. We attribute the discordance to separate, temporally-spaced hybridization events that led to asymmetric capture of P. skiltonianus mitochondria in different regional lineages of P. gilberti. Nuclear introgression showed a similar directional bias but was less pervasive. We demonstrate how a mechanical reproductive barrier previously identified for this group explains the asymmetry of mitochondrial introgression, given that hybrid matings are most likely when the male is P. gilberti and the female is P. skiltonianus. We then use permutation tests of morphological data to provide evidence that the mechanical barrier is less stringent in areas where hybridization is inferred to have occurred. Our results demonstrate how biased hybridization can dictate which genetic variants are transmitted between species and emphasize the importance of accounting for introgression and deep coalescence in identifying phyletic signatures of parallel speciation.}, } @article {pmid40127832, year = {2025}, author = {Liu, Q and Mao, W and Wang, Y and Xiao, J and Saha, S and Gao, T and Liu, F}, title = {Whole genome sequencing and phylogenetic analyses of the Sillaginidae family fish.}, journal = {Molecular phylogenetics and evolution}, volume = {207}, number = {}, pages = {108340}, doi = {10.1016/j.ympev.2025.108340}, pmid = {40127832}, issn = {1095-9513}, mesh = {Animals ; *Phylogeny ; Whole Genome Sequencing ; Evolution, Molecular ; *Fishes/genetics/classification ; Genome, Mitochondrial ; }, abstract = {For a long time, the taxonomic study of the Sillaginidae family of fish has been relatively slow, leaving the evolutionary relationships among species unclear. Previous research has mainly relied on morphological characteristics, with molecular studies limited primarily to mitochondrial genomics, including analyses of gene fragments and whole mitochondrial genomic sequence. This approach resulted in less precise and comprehensive species identification. In this study, we employed high-depth whole-genome sequencing (WGS) and genome surveys on 13 specimens representing 9 species of Sillaginidae fish collected from the wild. Our analysis included a thorough genomic survey and the assembly of draft genomes for each specimen. The genome sizes of Sillaginidae species are highly similar, ranging from 511.71 Mb to 578.27 Mb, with most individuals exhibiting repeat sequences content below 34.69 %. After the genome draft assembly of each sample, we identified conserved genes and shared consistent sequences among individuals and constructed a species phylogenetic tree based on these data. The results revealed that Sillago ingenua occupies the basal branch, followed by S. maculata and S. aeolus, then Sillaginopsis panijus, S. japonica and S. asiatica, and finally S. nigrofasciata and S. cf. sihama. Subsequently, we validated the phylogenetic tree using genome-wide single nucleotide variations, and the results were highly consistent. This research provides, for the first time, a whole-genome perspective on the evolutionary relationships among Sillaginidae species, offering valuable insights into their taxonomy and historical evolution.}, } @article {pmid40128668, year = {2025}, author = {Song, S and Cao, J and Xiang, H and Liu, Z and Jiang, W}, title = {Comparative mitogenomic analysis of Chinese cavefish Triplophysa (Cypriniformes: Nemacheilidae): novel gene tandem duplication and evolutionary implications.}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {293}, pmid = {40128668}, issn = {1471-2164}, support = {32060128//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Cypriniformes/genetics/classification ; *Genome, Mitochondrial ; *Evolution, Molecular ; *Gene Duplication ; Phylogeny ; China ; RNA, Transfer/genetics ; *Genomics/methods ; }, abstract = {BACKGROUND: Cavefish exhibit significant morphological changes that result in trade-offs in metabolic requirements and energy utilization in perpetual darkness. As cellular "powerhouses", mitochondria play crucial roles in energy metabolism, suggesting that mitochondrial genes have likely experienced selective pressures during cavefish evolution.

RESULTS: This study presents the first assembly of the complete mitogenome of Triplophysa yangi, a typical cavefish species in China. The mitogenome is 17,068 bp long, marking the longest recorded for the genus Triplophysa, and includes 13 protein-coding genes (PCGs), 2 rRNAs, 25 tRNAs, and a noncoding control region. An ~ 500 bp insertion between ND2 and WANCY regions was observed, comprising a large intact tandem repeat unit (A'-N'-OL'-C') flanked by two unannotated sequences (U1/U2). The evolutionary origin of this repeat unit may involve either in situ duplication events with subsequent functional divergence-where neofunctionalization, subfunctionalization, or pseudogenization drove differential mutation rates between paralogs-or alternatively, horizontal acquisition from exogenous genetic material that became functionally integrated into the ancestral T. yangi mitogenome through co-option mechanisms. Phylogenetic analyses revealed two major clades within Triplophysa-epigean and hypogean lineages-consistent with previous classifications, while cave-restricted species exhibited signs of parallel evolution within the hypogean lineage. Selective pressure analysis indicated that the hypogean lineage (cave-dwelling groups, II & III) have a significantly increased ratio of nonsynonymous to synonymous substitution rates (ω) compared to the epigean lineage (surface-dwelling group, I), suggesting a combination of adaptive selection and relaxed functional constraints in cave-dwelling species.

CONCLUSIONS: The duplication of tRNAs in T. yangi and the potential positive selection sites identified in Triplophysa cavefish further indicated adaptive evolution in mitochondrial PCGs in response to extreme subterranean conditions.}, } @article {pmid40141318, year = {2025}, author = {Prado-Souza, LFLD and Ferraz, LS and Citrangulo Tortelli, T and Ribeiro, CAJ and Amaral, DTD and Arruda, DC and Oliveira, ÉA and Chammas, R and Maria-Engler, SS and Rodrigues, T}, title = {Exploiting Paradoxical Activation of Oncogenic MAPK Signaling by Targeting Mitochondria to Sensitize NRAS Mutant-Melanoma to Vemurafenib.}, journal = {International journal of molecular sciences}, volume = {26}, number = {6}, pages = {}, pmid = {40141318}, issn = {1422-0067}, support = {2021/14650-3//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 306681/2023-4//Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico/ ; 001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, mesh = {Humans ; *Melanoma/genetics/drug therapy/metabolism/pathology ; *Vemurafenib/pharmacology ; *Mitochondria/metabolism/drug effects ; Cell Line, Tumor ; *GTP Phosphohydrolases/genetics/metabolism ; *Membrane Proteins/genetics ; *Mutation ; *MAP Kinase Signaling System/drug effects ; Mitochondrial Dynamics/drug effects ; Dynamins/metabolism/genetics ; Mitochondrial Proteins/metabolism/genetics ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/drug effects ; }, abstract = {Vemurafenib is a BRAF (rapidly accelerated fibrosarcoma B-type)-targeted therapy used to treat patients with advanced, unresectable melanoma. It inhibits the MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinase) pathway and tumor proliferation in BRAF[V600E]-mutated melanoma cells. Resistance to vemurafenib has been reported in melanoma patients due to secondary NRAS (neuroblastoma RAS viral oncogene homolog) mutations, which lead to paradoxical MAPK pathway activation and tumor proliferation. However, the impact of this paradoxical activation on mitochondrial dynamics and function in NRAS-mutated melanoma is unclear. Here, we investigated the effects of vemurafenib on NRAS[Q61R]-mutated melanoma cells, focusing on mitochondrial dynamics and function. As expected, vemurafenib did not exhibit cytotoxicity in SK-MEL-147 NRAS[Q61R]-mutated melanoma cells, even after 72 h of incubation. However, it significantly enhanced the MAPK/ERK signaling through paradoxical activation, accompanied by decreased expression of mitochondrial fusion proteins and activation of the fission protein DRP1 (dynamin-related protein 1), leading to small, rounded mitochondrial morphology. These observations were corroborated by transcriptome data obtained from NRAS-mutated melanoma patients, showing MFN1 (mitofusin 1) and OPA1 (optic atrophy 1) downregulation and DNM1L (DRP1 gene) upregulation. Interestingly, inhibition of mitochondrial fission with mdivi-1 or modulation of oxidative phosphorylation via respiratory chain inhibition or uncoupling significantly sensitized NRAS[Q61R]-mutated melanoma cells to vemurafenib. Despite vemurafenib's low cytotoxicity in NRAS-mutated melanoma, targeting mitochondrial dynamics and/or oxidative phosphorylation may offer a promising strategy for combined therapy.}, } @article {pmid40167337, year = {2025}, author = {Koch, RE and Truong, CN and Reeb, HR and Joski, BH and Hill, GE and Zhang, Y and Toomey, MB}, title = {Multiple Pathways to Red Carotenoid Coloration: House Finches (Haemorhous mexicanus) Do Not Use CYP2J19 to Produce Red Plumage.}, journal = {Molecular ecology}, volume = {34}, number = {9}, pages = {e17744}, pmid = {40167337}, issn = {1365-294X}, support = {NSF-IOS-2037735//Directorate for Biological Sciences/ ; NSF-IOS-2037739//Directorate for Biological Sciences/ ; NSF-IOS-2037741//Directorate for Biological Sciences/ ; NSF-IOS-2224556//Directorate for Biological Sciences/ ; }, mesh = {Animals ; *Feathers/metabolism ; *Finches/genetics/metabolism/physiology ; *Carotenoids/metabolism ; *Pigmentation/genetics ; *Cytochrome P-450 Enzyme System/genetics/metabolism ; }, abstract = {The carotenoid-based colours of birds are a celebrated example of biological diversity and an important system for the study of evolution. Recently, a two-step mechanism, with the enzymes cytochrome P450 2J19 (CYP2J19) and 3-hydroxybutyrate dehydrogenase 1-like (BDH1L), was described for the biosynthesis of red ketocarotenoids from yellow dietary carotenoids in the retina and plumage of birds. A common assumption has been that all birds with ketocarotenoid-based plumage coloration used this CYP2J19/BDH1L mechanism to produce red feathers. We tested this assumption in house finches (Haemorhous mexicanus) by examining the catalytic function of the house finch homologues of these enzymes and tracking their expression in birds growing new feathers. We found that CYP2J19 and BDH1L did not catalyse the production of 3-hydroxy-echinenone (3-OH-echinenone), the primary red plumage pigment of house finches, when provided with common dietary carotenoid substrates. Moreover, gene expression analyses revealed little to no expression of CYP2J19 in liver tissue or growing feather follicles, the putative sites of pigment metabolism in moulting house finches. Finally, although the hepatic mitochondria of house finches have high concentrations of 3-OH-echinenone, observations using fluorescent markers suggest that both CYP2J19 and BDH1L localise to the endomembrane system rather than the mitochondria. We propose that house finches and other birds that deposit 3-OH-echinenone as their primary red plumage pigment use an alternative enzymatic pathway to produce their characteristic red ketocarotenoid-based coloration.}, } @article {pmid40174813, year = {2025}, author = {Xu, J and Shen, Z and Hao, T and Su, H and Chen, M and Pan, X and Yi, Z}, title = {Exploring the evolution of anaerobes within ciliate class Prostomatea by transcriptomics.}, journal = {Molecular phylogenetics and evolution}, volume = {207}, number = {}, pages = {108345}, doi = {10.1016/j.ympev.2025.108345}, pmid = {40174813}, issn = {1095-9513}, mesh = {*Phylogeny ; *Ciliophora/genetics/classification/metabolism ; Anaerobiosis ; *Transcriptome ; *Evolution, Molecular ; Mitochondria/genetics/metabolism ; Biological Evolution ; }, abstract = {Mitochondrion-related organelles (MROs) enable anaerobic eukaryotes to thrive in anoxic environments, and the independent ciliate lineages of anaerobes serve as excellent candidates for investigating the convergent evolutionary transition from mitochondria to MROs. Previous studies have demonstrated that the adaptations of ciliates to anaerobic conditions may be lineage-specific. However, our understanding of the diverse metabolic peculiarities of MROs is limited to a few ciliate lineages. In this study, we sequenced the transcriptomes of four anaerobic species from two genera (Apolagynus and Holophrya), which are classified within the predominantly aerobic class Prostomatea, and predicted their mitochondrial metabolisms. The ecological niches of prostomatean anaerobes were mapped onto newly constructed phylogenomic trees and small subunit (SSU) rDNA trees. Results showed that paraphyletic class Prostomatea containing six clades (Clade Ⅰ-Ⅵ) has a close relationship with Oligohymenophorea and Plagiopylea. Notably, all prostomatean species within Clade Ⅱ are anaerobic, while anaerobes are only sporadically present in other clades. The MROs of anaerobic prostomatean species display at least two distinct phenotypes. Holophrya ovum in Clade Ⅰ produces ATP by oxidative phosphorylation under aerobic conditions and via substrate-level phosphorylation via acetate: succinate CoA transferase (ASCT) and succinyl CoA synthetase (SCS) as well as adenylate kinase (AK) under anaerobic conditions. In contrast, three species of Apolagynus in Clade Ⅱ possess reduced electron transport chain (ETC), and are capable of ATP generation via substrate-level phosphorylation mediated by ASCT/SCS and propionyl-CoA. Additionally, these three Apolagynus species possess [FeFe] hydrogenase probably producing H2. A comparison of the ETC pathways among various anaerobic ciliates further showed that the MROs of these organisms have originated from repeated convergent evolution. Our findings shed lights on evolutionary history of anaerobes within the ciliate class Prostomatea.}, } @article {pmid40174913, year = {2025}, author = {Rubens, P and Mayeur, A and Chatzovoulou, K and Gigarel, N and Monnot, S and Rötig, A and Munnich, A and Frydman, N and Steffann, J}, title = {Profiling mitochondrial DNA variant segregation during human preimplantation development: a prerequisite to preimplantation genetic testing for mitochondrial DNA-related disorders.}, journal = {Human reproduction (Oxford, England)}, volume = {40}, number = {5}, pages = {956-961}, doi = {10.1093/humrep/deaf050}, pmid = {40174913}, issn = {1460-2350}, support = {//Association Française contre les Myopathies/ ; //Université Paris Cité/ ; }, mesh = {Humans ; *DNA, Mitochondrial/genetics ; *Preimplantation Diagnosis/methods ; Female ; *Blastocyst/metabolism ; *Embryonic Development/genetics ; *Mitochondrial Diseases/genetics/diagnosis ; *Genetic Testing/methods ; Pregnancy ; Heteroplasmy ; Blastomeres ; }, abstract = {STUDY QUESTION: Is preimplantation genetic testing for mitochondrial DNA (mtDNA) disorders (PGT-mt) feasible at early compaction and blastocyst stages?

SUMMARY ANSWER: Pathogenic mtDNA variants segregate evenly among cell types and various lineages of a given embryo during preimplantation development, supporting the relevance of genetic analyses performed on Day 4 blastomere and on Day 5 or 6 trophectoderm (TE) samples.

WHAT IS KNOWN ALREADY: PGT-mt is validated at cleavage stage (Day 3 of development). However, its feasibility at later stages is questionable, as little is known regarding the segregation of pathogenic mtDNA variants during preimplantation development. Since mtDNA replication is silenced until the blastocyst stage (Day 5 or 6), uneven mtDNA segregation between preimplantation embryo cellular lineages known as a 'bottleneck' effect, cannot be excluded, posing a challenge for PGT-mt.

STUDY DESIGN, SIZE, DURATION: We analyzed 112 'mito' embryos carrying pathogenic mtDNA variants and 28 control embryos with mtDNA polymorphism. Heteroplasmy levels were assessed in single cells of the TE, in different parts of blastocysts (inner cell mass and TE), and at three time points of development, namely cleavage (Day 3), early compaction (Day 4), and blastocyst stages (Day 5 or 6).

As part of clinical PGT, a blastomere biopsy was performed at cleavage or early compaction stages (Day 3 or 4) on 112 'mito' and 21/28 control embryos. Further analysis was carried out at Day 5 or 6 on 51 embryos deemed unsuitable for uterine transfer and donated to research. Heteroplasmy levels were determined by semi-quantitative PCR amplification of (i) the mtDNA pathogenic variants with additional enzymatic digestion or (ii) the mtDNA polymorphic hypervariable region 2.

Here, we first show that mtDNA variants segregate evenly among blastomeres during early compaction (Day 4), supporting the feasibility of PGT-mt at this stage. We also found that mtDNA ratios remain stable between cleavage and blastocyst stages. Yet, the substantial variation of heteroplasmy levels occurring among single TE cells in 1/8 embryos suggests that PGT is only feasible when at least 5-10 cells are collected by standard TE biopsy.

This study sheds light on mtDNA segregation in human preimplantation embryo development. Its limitation lies in the scarcity of the material and the small number of embryos carrying a specific pathogenic mtDNA variant. Furthermore, the study of single cells from TE was performed on control embryos only.

By supporting the relevance of blastocyst biopsy in the context of PGT for pathogenic mtDNA variants, this study contributes to the general trend of postponing the biopsy to later stages of embryonic development. However, particular attention should be paid to the number of TE cells tested. Due to the potential variation of mutant load during in utero development, a control amniocentesis for evolutive pregnancies following the transfer of heteroplasmic embryos is still recommended.

This work was funded by 'Association Française contre les Myopathies/AFM Téléthon' (22112, 24317, 28525); and EUR G.E.N.E. (No. ANR-17-EURE-0013). The authors have no competing interests to declare.

TRIAL REGISTRATION NUMBER: N/A.}, } @article {pmid40181281, year = {2025}, author = {Degnan, PH and Percy, DM and Hansen, AK}, title = {Coupled evolutionary rates shape a Hawaiian insect-symbiont system.}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {336}, pmid = {40181281}, issn = {1471-2164}, support = {DEB 1241253//NSF/ ; 2019-70016-29066//National Institute of Food and Agriculture/ ; }, mesh = {Animals ; *Symbiosis/genetics ; *Evolution, Molecular ; Phylogeny ; Hawaii ; *Hemiptera/genetics/microbiology/classification ; Genome, Mitochondrial ; Genome, Insect ; }, abstract = {BACKGROUND: The Hawaiian Pariaconus psyllid radiation represents a unique system to study the co-evolution of nuclear, mitochondrial, and endosymbiont genomes. These psyllids, which diversified across the Hawaiian Islands during the last 3-3.5 million years vary with their ecological niches on their plant host 'Ōhi'a lehua (Metrosideros polymorpha) (free-living, open-gall, and closed-gall lifestyles) and harbor one to three beneficial bacterial endosymbionts. Co-evolutionary studies of other multi-endosymbiont insect systems have shown decoupled rates of sequence evolution between mitochondria and endosymbionts. Here we examine the evolutionary trends in Pariaconus psyllids, their mitochondria and their endosymbionts to determine if they fit this paradigm.

RESULTS: We sequenced a new Carsonella genome from the ohialoha species group (closed-gall, one symbiont), revealing a remarkable degree of gene conservation between two of the most divergent species from this diverse species group that has dispersed across multiple islands. Further, despite the rapid radiation of psyllid species, we observed complete synteny among mitochondrial genomes from all six Pariaconus species in this study, suggesting the preservation of genome structure due to strong purifying selection. Phylogenetic analyses of the nuclear, mitochondrial, and endosymbiont genomes across these six Pariaconus species revealed correlated rates of substitutions, contrary to prior reports of decoupling between mitochondrial and endosymbiont genomes in other insect systems with multiple symbiont partners. Finally, we found that free-living psyllids with three symbionts exhibited elevated mutation rates (~ 1.2-1.6x) across all genomes and elevated rates of fixation of nonsynonymous substitutions in the insect nuclear genome and one of the endosymbionts.

CONCLUSIONS: This study highlights the interplay between ecological diversification and genomic evolution in Pariaconus. Further, these data indicate that multiple endosymbiont partners alone are not sufficient to result in decoupling rates of sequence evolution. Future work on basal members of this species radiation will refine our understanding of the mechanisms shaping this dynamic insect-symbiont system and its implications for genome evolution.}, } @article {pmid40183649, year = {2025}, author = {Zielenkiewicz, U and Kaushal, V and Kaczanowski, S}, title = {On the origins and evolution of apoptosis: the predator-mitochondrial prey hypothesis.}, journal = {Journal of evolutionary biology}, volume = {38}, number = {8}, pages = {1031-1040}, doi = {10.1093/jeb/voaf039}, pmid = {40183649}, issn = {1420-9101}, support = {2017/27/B/NZ8/02502//Polish National Science Centre/ ; }, mesh = {Animals ; *Apoptosis/physiology/genetics ; *Biological Evolution ; *Mitochondria/physiology ; Models, Biological ; Phylogeny ; }, abstract = {Different types of programmed cell death (PCD) have been described both in unicellular and multicellular organisms. The fundamental mode of eukaryotic cell death is PCD initiated by mitochondria, which is frequently referred to as apoptosis (or mitochondrial apoptosis). It is initiated by mitochondria through mitochondrial permeability transition and the release of apoptotic factors. It is widely thought that mitochondrial apoptosis evolved concurrently with mitochondrial domestication. PCD initiated by mitochondria is observed in various multicellular and unicellular eukaryotes. We discuss key hypotheses-namely, the "pleiotropy," "addiction," "immunological," and our "predator-mitochondrial prey" hypotheses-to explain the mechanisms of mitochondrial domestication that lead to apoptosis. In this perspective paper, we present evidence from various phylogenetic and experimental studies that strongly indicate our hypothesis is the most plausible. For the first time, we also present evidence that challenges the assumptions underlying all other hypotheses.}, } @article {pmid40185233, year = {2025}, author = {Zhao, HF and Wang, Y and Liu, XH and Liu, XH and Geng, Z and Gao, ZQ and Huang, L and Weng, CJ and Dong, YH and Zhang, H}, title = {Structure-function insights into the dual role of African swine fever virus pB318L: A typical geranylgeranyl-diphosphate synthase and a nuclear import protein.}, journal = {Virologica Sinica}, volume = {40}, number = {2}, pages = {236-246}, pmid = {40185233}, issn = {1995-820X}, mesh = {*African Swine Fever Virus/genetics/enzymology/physiology ; Animals ; *Viral Proteins/genetics/metabolism/chemistry ; Structure-Activity Relationship ; Swine ; Phylogeny ; Virus Replication ; Active Transport, Cell Nucleus ; Cell Nucleus/metabolism ; Nuclear Localization Signals/genetics ; }, abstract = {African swine fever virus (ASFV) pB318L is an important protein for viral replication that acts as a membrane-bound trans-geranylgeranyl-diphosphate synthase (GGPPS) catalyzing the condensation of isopentenyl diphosphate (IPP) with allylic diphosphates. Recently we solved the crystal structure pB318L lacking N-terminal transmembrane region and performed a preliminary structural analysis. In this study, structure-based mutagenesis study and geranylgeranyl pyrophosphate (GGPP) production assay further revealed the key residues for the GGPPS activity. Structural comparison showed pB318L displays a strong similarity to typical GGPPSs instead of protein prenyltransferases. The phylogenetic analysis indicated pB318L may share a common ancestor with the GGPPSs from Brassicaceae plants rather than from its natural host. The subcellular localization analysis showed pB318L is localized in both nucleus and cytoplasm (including the endoplasmic reticulum membrane and mitochondria outer membrane). A unique N-terminal nuclear localization signal (NLS) following the transmembrane region was discovered in pB318L and the NLS was confirmed to be required for the nuclear import. We further revealed the NLS plays an essential role in the interaction with nuclear transporter karyopherin subunit alpha 1 (KPNA1). Their interaction may suppress signal transducers and activators of transcription 1 (STAT1) translocation and subsequently competitively inhibit nuclear import of IFN-stimulated gene factor 3 (ISGF3) complex. Our biochemical, structural and cellular analyses provide novel insights to pB318L that acts as an essential GGPPS that promotes viral replication and as a nuclear import protein that may be involved in immune evasion of ASFV.}, } @article {pmid40188039, year = {2025}, author = {Liang, H and Deng, J and Wang, Y and Gao, G and Yang, R}, title = {The first complete mitochondrial genome of Curcuma amarissima (Zingiberaceae): insights into multi-branch structure, codon usage, and phylogenetic evolution.}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {343}, pmid = {40188039}, issn = {1471-2164}, support = {ITH2024ZD02//Basic scientific research business expenses of HAAS/ ; 32001390//Natural Science Foundation of Shenyang Municipality/ ; }, mesh = {*Phylogeny ; *Codon Usage ; *Curcuma/genetics/classification ; *Genome, Mitochondrial ; *Evolution, Molecular ; Base Composition ; RNA, Transfer/genetics ; }, abstract = {BACKGROUND: As a key genus in Zingiberaceae, Curcuma is widely studied for its taxonomic diversity, the presence of bioactive curcuminoids and volatile oils, and its extensive applications in traditional medicine and economic products such as spices and cosmetics. Although chloroplast genomes have been assembled and published for over 20 Curcuma species, mitochondrial genomic data remain limited.

RESULTS: We successfully sequenced, assembled, and annotated the mitogenome of Curcuma amarissima (C. amarissima) using both Illumina short reads and Nanopore long reads, achieving the first complete mitogenome characterization in the Zingiberaceae family. The C. amarissima mitogenome features a unique multi-branched structure, spanning 6,505,655 bp and consisting of 39 distinct segments. It contains a total of 43 protein-coding genes, 63 tRNA genes, and 4 rRNA genes, with a GC content of 44.04%. Codon usage analysis indicated a weak bias, with neutrality plot analysis suggesting natural selection as a key factor shaping mitochondrial codon usage in C. amarissima. The mitogenome provides valuable insights into genome size, coding genes, structural features, RNA editing, repetitive sequences, and sequence migration, enhancing our understanding of the evolution and molecular biology of multi-branched mitochondria in Zingiberaceae. The high frequency of repeat sequences may contribute to the structural stability of the mitochondria. Comparing chloroplast genome, phylogenetic analysis based on the mitochondrial genome establishes a foundation for further exploration of evolutionary relationships within Zingiberaceae.

CONCLUSIONS: In short, the mitochondrial genome characterized here advances our understanding of multi-branched mitogenome organization in Zingiberaceae and offers useful genomic resources that may support future breeding, germplasm conservation, and phylogenetic studies, though further research is necessary.}, } @article {pmid40196624, year = {2025}, author = {Ly, J and Tao, YF and Di Bernardo, M and Khalizeva, E and Giuliano, CJ and Lourido, S and Fleming, MD and Cheeseman, IM}, title = {Alternative start codon selection shapes mitochondrial function during evolution, homeostasis, and disease.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40196624}, issn = {2692-8205}, support = {R01 AI144369/AI/NIAID NIH HHS/United States ; R01 AI158501/AI/NIAID NIH HHS/United States ; R35 GM126930/GM/NIGMS NIH HHS/United States ; R24 DK094746/DK/NIDDK NIH HHS/United States ; T32 GM087237/GM/NIGMS NIH HHS/United States ; R01 DK087992/DK/NIDDK NIH HHS/United States ; }, abstract = {Mitochondrial endosymbiosis was a pivotal event in eukaryotic evolution, requiring core proteins to adapt to function both within the mitochondria and in the host cell. Here, we systematically profile the localization of protein isoforms generated by alternate start codon selection during translation. We identify hundreds of pairs of differentially-localized protein isoforms, many of which affect mitochondrial targeting and are essential for mitochondrial function. The emergence of dual-localized mitochondrial protein isoforms coincides with mitochondrial acquisition during early eukaryotic evolution. We further reveal that eukaryotes use diverse mechanisms-such as leaky ribosome scanning, alternative transcription, and paralog duplication-to maintain the production of dual-localized isoforms. Finally, we identify multiple isoforms that are specifically dysregulated by rare disease patient mutations and demonstrate how these mutations can help explain unique clinical presentations. Together, our findings illuminate the evolutionary and pathological relevance of alternative translation initiation, offering new insights into the molecular underpinnings of mitochondrial biology.}, } @article {pmid40197538, year = {2025}, author = {Zhao, P and Tian, R and Song, D and Zhu, Q and Ding, X and Zhang, J and Cao, B and Zhang, M and Xu, Y and Fang, J and Tan, J and Yi, C and Xia, H and Liu, W and Zou, W and Sun, Q}, title = {Rab GTPases are evolutionarily conserved signals mediating selective autophagy.}, journal = {The Journal of cell biology}, volume = {224}, number = {5}, pages = {}, pmid = {40197538}, issn = {1540-8140}, support = {92254307//National Natural Science Foundation of China/ ; 2024YFA1803003//Ministry of Science and Technology of the People's Republic of China/ ; }, mesh = {*rab GTP-Binding Proteins/metabolism/genetics ; Humans ; *Autophagy ; Animals ; *Signal Transduction ; HeLa Cells ; Mitochondria/metabolism ; Mitophagy ; *Evolution, Molecular ; }, abstract = {Selective autophagy plays a crucial role in maintaining cellular homeostasis by specifically targeting unwanted cargo labeled with "autophagy cues" signals for autophagic degradation. In this study, we identify Rab GTPases as a class of such autophagy cues signals involved in selective autophagy. Through biochemical and imaging screens, we reveal that human Rab GTPases are common autophagy substrates. Importantly, we confirm the conservation of Rab GTPase autophagic degradation in different model organisms. Rab GTPases translocate to damaged mitochondria, lipid droplets, and invading Salmonella-containing vacuoles (SCVs) to serve as degradation signals. Furthermore, they facilitate mitophagy, lipophagy, and xenophagy, respectively, by recruiting receptors. This interplay between Rab GTPases and receptors may ensure the de novo synthesis of isolation membranes around Rab-GTPase-labeled cargo, thereby mediating selective autophagy. These processes are further influenced by upstream regulators such as LRRK2, GDIs, and RabGGTase. In conclusion, this study unveils a conserved mechanism involving Rab GTPases as autophagy cues signals and proposes a model for the spatiotemporal control of selective autophagy.}, } @article {pmid40199161, year = {2025}, author = {Xia, J and Ma, R and Cai, Y and Xie, T and Zhang, Y and Lv, M and Liu, Y and You, H and Zhang, C and Yu, D and Hua, X}, title = {The functional conservation of SSR1 homologs in plants.}, journal = {Plant physiology and biochemistry : PPB}, volume = {223}, number = {}, pages = {109855}, doi = {10.1016/j.plaphy.2025.109855}, pmid = {40199161}, issn = {1873-2690}, mesh = {*Arabidopsis Proteins/metabolism/genetics/chemistry ; *Arabidopsis/metabolism/genetics ; *Mitochondrial Proteins/metabolism/genetics/chemistry ; Amino Acid Sequence ; Phylogeny ; Mitochondria/metabolism ; Plant Proteins/metabolism/genetics ; Bryopsida/genetics/metabolism ; }, abstract = {AtSSR1 (Arabidopsis thaliana short and swollen root 1) is a plant-specific gene that encodes a mitochondrial protein containing TPR (tetratricopeptide repeat) domains, and was shown to be required for maintaining mitochondrial function. However, the evolution of its function in the plant lineage is not known. In this paper, SSR1 homologs were cloned from seven representative plant species ranging from lower to higher plants. Their structural and functional conservation were characterized in detail. The results demonstrated that most of the SSR1 homologs are predicted to have mitochondrial localization except for the one from Physcomitrella patens and all of them possess various numbers of TPR domains. Upon introduction into the Arabidopsis ssr1-2 knock-out mutant, all SSR1 homologs were capable of fully rescuing the short-root and stress hypersensitive phenotype of the mutant. In addition, in vitro pull-down analysis showed that similar to AtSSR1, the selected SSR1 homologs were also able to interact with AtHSCA2 and AtISU1, two components of mitochondrial iron-sulfur cluster assembly pathway, suggesting that SSR1 homologs from various plant species are functionally conserved. Despite the conserved function, different SSR1 homologs shared relatively low sequence identity with AtSSR1. Instead, their 3D structures display a common feature of a globular shape, mainly dominated by α-helices and two β-sheets embedded in the center. Taken together, our results suggest that SSR1, as a plant-specific mitochondrial protein, might have complete functionality in plant development and stress response already in the early stage of plant evolution.}, } @article {pmid40205193, year = {2025}, author = {Lu, Q and Luo, W}, title = {Comparative analysis of the complete mitochondrial genomes of Firmiana danxiaensis and F. kwangsiensis (Malvaceae), two endangered Firmiana species in China.}, journal = {Planta}, volume = {261}, number = {5}, pages = {107}, pmid = {40205193}, issn = {1432-2048}, support = {31960083//National Natural Science Foundation of China/ ; }, mesh = {*Genome, Mitochondrial/genetics ; Endangered Species ; China ; Phylogeny ; RNA, Transfer/genetics ; Genome, Chloroplast/genetics ; }, abstract = {We reported the mitogenomes of F. danxiaensis and F. kwangsiensis for the first time. Mitogenome size and structure differ significantly between them. Firmiana danxiaensis and F. kwangsiensis belong to the Firmiana genus and are distributed in the Danxia and Karst regions of southern China. Both species have been designated as endangered. Currently, the chloroplast genomes of F. danxiaensis and F. kwangsiensis have been sequenced, but the mitochondrial genome (mitogenome) of these two species has not been reported. To further understand the mitogenome characteristics, evolution, and phylogeny of F. danxiaensis and F. kwangsiensis, we assembled the mitogenomes of these two species based on a combination of Illumina and Nanopore sequencing methods. The mitogenome of F. danxiaensis exhibits a branching structure consisting of nine circular molecules with a total length of 938,890 bp, while the F. kwangsiensis has a circular structure with a length of 736,334 bp. Compared to F. kwangsiensis, F. danxiaensis has more tRNA genes, SSRs, tandem repeats, and dispersed repeats, while the codon use patterns are similar in these two species. There were 24 and 23 homologous sequences between mitogenome and chloroplast genome of F. danxiaensis and F. kwangsiensis, accounting for 0.37% and 0.49% of the mitogenome, respectively. In addition, the Ka/Ks ratio and the nucleic acid diversity analysis revealed that most of the mitochondria protein-coding genes in F. danxiaensis and F. kwangsiensis are highly conserved and may have undergone purifying selection. Furthermore, the collinear and comparative analysis showed that extensive genomic rearrangement events existed among the Malvaceae species. Lastly, a phylogenetic tree based on shared mitochondrial PCGs of 29 species revealed that F. danxiaensis and F. kwangsiensis form a sister group with high support values. Overall, the current study reports two mitogenomes (F. danxiaensis and F. kwangsiensis) in the Firmiana genus for the first time, which will help enhance comprehension of the mitogenome evolutionary patterns within Firmiana and promote the evolutionary and comparative genomic analyses within Malvaceae species.}, } @article {pmid40207624, year = {2025}, author = {Mathieu, S and Lesch, E and Garcia, S and Graindorge, S and Schallenberg-Rüdinger, M and Hammani, K}, title = {De novo RNA base editing in plant organelles with engineered synthetic P-type PPR editing factors.}, journal = {Nucleic acids research}, volume = {53}, number = {7}, pages = {}, pmid = {40207624}, issn = {1362-4962}, support = {ANR-18-CE20-0013//Agence National de la Recherche/ ; //Centre National de la Recherche Scientifique/ ; SCHA 1952/2-2//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*RNA Editing ; Nicotiana/genetics/metabolism ; Chloroplasts/genetics/metabolism ; Mitochondria/genetics/metabolism ; Escherichia coli/genetics ; *Plant Proteins/genetics/metabolism ; Cytidine Deaminase/genetics/metabolism ; }, abstract = {In plant mitochondria and chloroplasts, cytidine-to-uridine RNA editing is necessary for the production of functional proteins. While natural PLS-type PPR proteins are specialized in this process, synthetic PPR proteins offer significant potential for targeted RNA editing. In this study, we engineered chimeric editing factors by fusing synthetic P-type PPR guides with the DYW cytidine deaminase domain of a moss mitochondrial editing factor, PPR56. These designer PPR editors (dPPRe) elicited efficient and precise de novo RNA editing in Escherichia coli as well as in the chloroplasts and mitochondria of Nicotiana benthamiana. Chloroplast transcriptome-wide analysis of the most efficient dPPRe revealed minimal off-target effects, with only three nontarget C sites edited due to sequence similarity with the intended target. This study introduces a novel and precise method for RNA base editing in plant organelles, paving the way for new approaches in gene regulation applicable to plants and potentially other organisms.}, } @article {pmid40214180, year = {2025}, author = {Takahashi, K and Lum, WM and Hehenberger, E and Iwataki, M}, title = {Kapelodiniopsis flava n. g., n. sp. (Dinophyceae), a new katodinioid with haptophyte-derived plastids of multiple origins: Implications for the plastid integration process.}, journal = {The Journal of eukaryotic microbiology}, volume = {72}, number = {3}, pages = {e13082}, doi = {10.1111/jeu.13082}, pmid = {40214180}, issn = {1550-7408}, support = {LQ200962204//The Czech Academy of Sciences, Lumina Quaeruntur fellowship/ ; 19KK0160//Japan Society for the Promotion of Science/ ; 21K15150//Japan Society for the Promotion of Science/ ; }, mesh = {*Plastids/genetics/ultrastructure ; Phylogeny ; *Dinoflagellida/genetics/classification/ultrastructure/isolation & purification ; *Haptophyta/genetics/ultrastructure ; DNA, Protozoan/genetics/chemistry ; Japan ; DNA, Ribosomal/genetics/chemistry ; RNA, Ribosomal, 18S/genetics ; Sequence Analysis, DNA ; }, abstract = {An autotrophic unarmored dinoflagellate species with haptophyte-derived plastids, Kapelodiniopsis flava n. g., n. sp., was described as a sister taxon of Kapelodinium vestifici, which was formerly well characterized by its low-positioned cingulum and heterotrophic nature. The isolates from several Japanese coastal locations were observed using light microscopy, scanning and transmission electron microscopy, and their phylogeny was inferred from nuclear-encoded rRNA genes and multiple plastid-encoded genes. To date of this publication, a representative culture of Ks. flava has grown autotrophically for 98 months in the absence of prey or organic matter. This dinoflagellate lacked nonplastid haptophyte cell components (e.g. nucleus or mitochondria). In the host dinoflagellate phylogeny, Ks. flava was distantly related to the other two dinoflagellate lineages known to be associated with haptophyte-derived plastids, thus representing the third of such lineage. Plastid origins differed among Ks. flava strains (>99.8% 18S rRNA gene identity), with plastids being derived from at least three haptophytes and an especially strong genetic similarity to two distantly related extant haptophytes (>99.9% 16S rRNA gene identity). This indicates that Ks. flava recently integrated plastids from multiple haptophyte lineages to an extent that allows the host to replicate the plastids without other haptophyte components.}, } @article {pmid40225169, year = {2023}, author = {Lazarian, G and Leroy, B and Theves, F and Hormi, M and Letestu, R and Eclache, V and Tueur, G and Ameur, A and Bidet, A and Cornillet-Lefebvre, P and Davi, F and Delabesse, E and Estienne, MH and Etancelin, P and Kosmider, O and Laibe, S and Muller, M and Nadal, N and Naguib, D and Pastoret, C and Poulain, S and Sujobert, P and Veronese, L and Imache, S and Lefebvre, V and Cymbalista, F and Baran-Marszak, F and Soussi, T and , }, title = {The Broad Spectrum of TP53 Mutations in CLL: Evidence of Multiclonality and Novel Mutation Hotspots.}, journal = {Human mutation}, volume = {2023}, number = {}, pages = {4880113}, pmid = {40225169}, issn = {1098-1004}, mesh = {Humans ; *Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; *Tumor Suppressor Protein p53/genetics ; *Mutation ; }, abstract = {TP53 aberrations are a major predictive factor of resistance to chemoimmunotherapy in chronic lymphocytic leukemia (CLL), and an assessment of them before each line of treatment is required for theranostic stratification. Acquisition of subclonal TP53 abnormalities underlies the evolution of CLL. To better characterize the distribution, combination, and impact of TP53 variants in CLL, 1,056 TP53 variants collected from 683 patients included in a multicenter collaborative study in France were analyzed and compared to UMD_CLL, a dataset built from published articles collectively providing 5,173 TP53 variants detected in 3,808 patients. Our analysis confirmed the presence of several CLL-specific hotspot mutations, including a two-base pair deletion in codon 209 and a missense variant at codon 234, the latter being associated with alkylating treatment. Our analysis also identified a novel CLL-specific variant in the splice acceptor signal of intron 6 leading to the use of a cryptic splice site, similarly utilized by TP53 to generate p53psi, a naturally truncated p53 isoform localized in the mitochondria. Examination of both UMD_CLL and several recently released large-scale genomic analyses of CLL patients confirmed that this splice variant is highly enriched in this disease when compared to other cancer types. Using a TP53-specific single-nucleotide polymorphism, we also confirmed that copy-neutral loss of heterozygosity is frequent in CLL. This event can lead to misinterpretation of TP53 status. Unlike other cancers, CLL displayed a high proportion of patients harboring multiple TP53 variants. Using both in silico analysis and single molecule smart sequencing, we demonstrated the coexistence of distinct subclones harboring mutations on distinct alleles. In summary, our study provides a detailed TP53 mutational architecture in CLL and gives insights into how treatments may shape the genetic landscape of CLL patients.}, } @article {pmid40229603, year = {2025}, author = {Li, X and Hu, L and Hu, Q and Jin, H}, title = {Research dynamics and drug treatment of renal fibrosis from a mitochondrial perspective: a historical text data analysis based on bibliometrics.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {398}, number = {10}, pages = {13843-13856}, pmid = {40229603}, issn = {1432-1912}, support = {82274307//National Natural Science Foundation of China/ ; 2023CXMMTCM018//Research Funds of Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM/ ; }, mesh = {Humans ; Bibliometrics ; Fibrosis/drug therapy ; *Mitochondria/drug effects/metabolism/pathology ; *Kidney Diseases/drug therapy/pathology/metabolism ; Animals ; *Kidney/pathology/drug effects ; *Biomedical Research/trends ; }, abstract = {Renal fibrosis (RF) represents a significant public health challenge, necessitating the urgent identification of effective and safe therapeutic agents. Mitochondrial-targeted strategies have demonstrated considerable promise in restoring renal function and mitigating fibrosis. This study aims to examine the evolution of research and therapeutic interventions for RF from a mitochondrial perspective through bibliometric analysis. Literature retrieval was primarily conducted using the Web of Science Core Collection. Visual analysis was performed utilizing the Bibliometrix package (R- 4.4.2), CiteSpace 6.3.R1, and VOSviewer 1.6.19. A total of 819 documents were included for analysis. Significant contributions were made by researchers from China and the USA, with Nanjing Medical University leading in publication volume. Zhang Aihua and Huang Songming emerge as key scholars in the field, while the International Journal of Molecular Sciences is the journal with the highest publication output. Key research themes include oxidative stress, expression, injury, activation, mechanisms, and mitochondrial dysfunction. Mitochondrial-targeted approaches for treating RF can be categorized into six main strategies: mitochondrial biogenesis regulators, mitochondrial dynamics modulators, mitophagy inducers, oxidative stress regulators, NLRP3 inhibitors, and other mitochondrial-targeted therapeutic approaches. This study comprehensively examines the current state of RF research from a mitochondrial standpoint, summarizing key drugs and potential mechanisms of mitochondrial regulation. The findings aim to enhance scholarly understanding of the ongoing research trends and provide valuable insights for the development of targeted therapeutic agents.}, } @article {pmid40229680, year = {2025}, author = {Liu, M and Fan, R and Wang, C and Dai, L and Chu, S}, title = {Complete analysis and phylogenetic analysis of Polygonatum sibiricum mitochondria.}, journal = {BMC plant biology}, volume = {25}, number = {1}, pages = {471}, pmid = {40229680}, issn = {1471-2229}, mesh = {*Polygonatum/genetics/classification ; *Phylogeny ; *Genome, Mitochondrial/genetics ; RNA, Transfer/genetics ; Base Composition ; RNA, Ribosomal/genetics ; }, abstract = {In this project, we studied the complete mitogenome of the liliaceae medicinal plant Polygonatum sibiricum. The genome is represented by a circular ring molecule with a length of 691,910 bp and a GC content of 46.33%. Mitochondrial genome composition is slightly biased towards A+T, with AT accounting for 53.67%, and AT skewness slightly positive (0.092%). The complete mitogenome has a total of sixty-three unique genes, including thirty-nine protein-coding genes, twenty-one transfer RNAs (tRNAs) and three ribosomal RNAs (rRNAs). We examined codon use, repeat sequence, RNA editing in the mitogenome of P. sibiricum, and elucidated species classification based on phylogenetic trees of mitogenome of twenty-three species. Our results provide comprehensive information on the mitogenome of P. sibiricum and show for the first time the evolutionary relationship between the mitogenome of P. sibiricum and Chlorophytum comosum in the Asparagales family.}, } @article {pmid40231068, year = {2025}, author = {Bagdonaitė, L and Leder, EH and Lifjeld, JT and Johnsen, A and Mauvisseau, Q}, title = {Assessing reliability and accuracy of qPCR, dPCR and ddPCR for estimating mitochondrial DNA copy number in songbird blood and sperm cells.}, journal = {PeerJ}, volume = {13}, number = {}, pages = {e19278}, pmid = {40231068}, issn = {2167-8359}, mesh = {Animals ; Male ; *DNA, Mitochondrial/genetics/blood/analysis ; *Spermatozoa/chemistry ; Reproducibility of Results ; *DNA Copy Number Variations ; *Songbirds/genetics/blood ; *Polymerase Chain Reaction/methods ; *Real-Time Polymerase Chain Reaction/methods ; }, abstract = {Mitochondrial DNA (mtDNA) copy number varies across species, individuals, and cell types. In birds, there are two types of cells with a relatively low number of mitochondria: red blood cells and spermatozoa. Previous studies investigating variation of mitochondrial abundance in animal sperm have generally used quantitative PCR (qPCR), but this method shows potential limitations when quantifying targets at low abundance. To mitigate such issues, we investigated and compared the reliability and accuracy of qPCR, digital PCR (dPCR) and droplet digital PCR (ddPCR) to quantify high and low concentration DNA. We used synthetic DNA targets, to calculate the limit of detection and the limit of quantification and found that with both dPCR and ddPCR, these limits were lower than with qPCR. Then, to compare quantification accuracy and repeatability, we used DNA extracted from blood and sperm cells of Eurasian siskin. We found that qPCR, dPCR and ddPCR all reliably quantified mitochondrial DNA in sperm samples but showed significant differences when analyzing the typically lower levels of mtDNA in blood, with ddPCR consistently showing lower variation among replicates. Our study provides critical insights and recommendations for future studies aiming to quantify target mtDNA and indicates that dPCR and ddPCR are the preferred methods when working with samples with low abundance of mtDNA.}, } @article {pmid40237040, year = {2025}, author = {Kervella, M and Bertile, F and Bouillaud, F and Criscuolo, F}, title = {The cell origin of reactive oxygen species and its implication for evolutionary trade-offs.}, journal = {Open biology}, volume = {15}, number = {4}, pages = {240312}, pmid = {40237040}, issn = {2046-2441}, support = {//Centre National de la Recherche Scientifique/ ; }, mesh = {*Reactive Oxygen Species/metabolism ; Animals ; *Mitochondria/metabolism ; Humans ; *Biological Evolution ; Oxidative Stress ; Energy Metabolism ; Homeostasis ; Antioxidants/metabolism ; Oxidation-Reduction ; }, abstract = {The allocation of resources in animals is shaped by adaptive trade-offs aimed at maximizing fitness. At the heart of these trade-offs, lies metabolism and the conversion of food resources into energy, a process mostly occurring in mitochondria. Yet, the conversion of nutrients to utilizable energy molecules (adenosine triphosphate) inevitably leads to the by-production of reactive oxygen species (ROS) that may cause damage to important biomolecules such as proteins or lipids. The 'ROS theory of ageing' has thus proposed that the relationship between lifespan and metabolic rate may be mediated by ROS production. However, the relationship is not as straightforward as it may seem: not only are mitochondrial ROS crucial for various cellular functions, but mitochondria are also actually equipped with antioxidant systems, and many extra-mitochondrial sources also produce ROS. In this review, we discuss how viewing the mitochondrion as a regulator of cellular oxidative homeostasis, not merely a ROS producer, may provide new insights into the role of oxidative stress in the reproduction-survival trade-off. We suggest several avenues to test how mitochondrial oxidative buffering capacity might complement current bioenergetic and evolutionary studies.}, } @article {pmid40238856, year = {2025}, author = {Lawson, LP and Bittencourt-Silva, GB and Conradie, W and Portik, DM and Loader, SP}, title = {A phylogenomic perspective reveals mitochondrial-nuclear discordance and previously undescribed species nested within a widespread East African Reed frog species (Hyperolius substriatus Ahl, 1931).}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0318951}, pmid = {40238856}, issn = {1932-6203}, mesh = {Animals ; Female ; Africa, Eastern ; *Anura/genetics/classification ; *Cell Nucleus/genetics ; *DNA, Mitochondrial/genetics ; *Mitochondria/genetics ; *Phylogeny ; Phylogeography ; }, abstract = {The sub-montane East African Reed Frog, Hyperolius substriatus Ahl, 1931 (Spotted Reed Frog) has a fragmented highland distribution throughout East Africa. Previous studies show extensive mitochondrial divergence between four lineages of African Spotted Reed Frogs that roughly correspond to previously-recognized subspecies. These may have conservation implications if formally described. However, as mitochondrial-based population models only track maternal patterns, further genomic datasets are necessary to assess the distinctness of these lineages in relation to historically recognized morphological subspecies. In this study, we expanded sampling to newly discovered localities and assessed mitochondrial and genomic data to better understand phylogeography and landscape genomics of this species. We found that genomic clades (biparentally inherited) confirm some of the mitochondrial structure (female inherited), but also revealed multiple cases of mitonuclear discordance particularly within the Udzungwa Mountain block, which may have two separate founding events based on peripatric mitochondrial lineages and panmictic genomic signals. Taken together, the three clades within the geographical range of H. substriatus through Tanzania, Malawi, and Mozambique correspond to three previously-identified subspecies and lineages, and have both spatially cohesive and population-specific patterns of geneflow and isolation with neighboring highland locations.}, } @article {pmid40239883, year = {2025}, author = {Wallnoefer, O and Formaggioni, A and Plazzi, F and Passamonti, M}, title = {Convergent evolution in nuclear and mitochondrial OXPHOS subunits underlies the phylogenetic discordance in deep lineages of Squamata.}, journal = {Molecular phylogenetics and evolution}, volume = {208}, number = {}, pages = {108358}, doi = {10.1016/j.ympev.2025.108358}, pmid = {40239883}, issn = {1095-9513}, mesh = {*Phylogeny ; Animals ; *Oxidative Phosphorylation ; *Evolution, Molecular ; Cell Nucleus/genetics ; *Lizards/genetics/classification ; Mitochondria/genetics ; Snakes/genetics/classification ; Genome, Mitochondrial ; }, abstract = {The order Squamata is a good candidate for detecting unusual patterns of mitochondrial evolution. The lineages leading to the snake and agamid clades likely experienced convergent evolution in mitochondrial OXidative PHOSphorylation (OXPHOS) genes, which provides strong support for the sister relationship of these two groups. The OXPHOS subunits are encoded by both the nuclear and mitochondrial genomes, which are subject to distinct evolutionary pressures. Nevertheless, the cooperation between OXPHOS subunits is essential for proper OXPHOS function, as incompatibilities between subunits can be highly deleterious. In the present study, we annotated OXPHOS genes of 56 Squamata species. The nuclear OXPHOS subunits that physically interact with mitochondrial proteins also support the clade sister relationship between snakes and agamids. Additionally, we found a significant number of convergent amino acid changes between agamids and snakes, not only in mitochondrial OXPHOS genes, but also in nuclear ones, with a higher rate of convergence in the nuclear OXPHOS subunits that play central roles in the OXPHOS complexes, like COX4 and NDUFA4. Overall, the common selective pressures in two distinct lineages can lead two sets of genes, encoded by two different genomes, to exhibit similar patterns of convergent evolution, as well as similar evolutionary rates. As a consequence, the coevolution of interdependent subunits and their adaptation to specific evolutionary pressures can heavily influence the molecular structure of cytonuclear enzyme complexes and blur phylogenetic signals.}, } @article {pmid40250433, year = {2025}, author = {Rao, AK and Yee, D and Chevalier, F and LeKieffre, C and Pavie, M and Olivetta, M and Dudin, O and Gallet, B and Hehenberger, E and Seifi, M and Jug, F and Deschamps, J and Wu, TD and Gast, R and Jouneau, PH and Decelle, J}, title = {Hijacking and integration of algal plastids and mitochondria in a polar planktonic host.}, journal = {Current biology : CB}, volume = {35}, number = {11}, pages = {2509-2523.e7}, doi = {10.1016/j.cub.2025.03.076}, pmid = {40250433}, issn = {1879-0445}, mesh = {*Plastids/physiology ; *Dinoflagellida/physiology ; *Symbiosis/physiology ; *Mitochondria/physiology ; Photosynthesis/physiology ; *Microalgae/physiology ; }, abstract = {In oceanic plankton, various hosts are capable of engulfing and temporarily integrating microalgae (photosymbiosis) or just their photosynthetic plastids (kleptoplastidy) from the environment. These cellular interactions have been hypothesized to be representative of evolutionary steps in plastid acquisition in eukaryotes, but the underlying mechanisms are not fully understood. Here, we studied a polar kleptoplastidic dinoflagellate, which is known to steal plastids of the microalga Phaeocystis antarctica. We tracked the morphology and activity of stolen plastids over several months by combining multimodal subcellular imaging and photophysiology. Upon integration inside a host vacuole, the volume of plastids and pyrenoids significantly increased, and photosynthetic activity was boosted. This may be supported by the retention of a 50-fold larger algal nucleus for ∼1 week. Once the algal nucleus was lost, there was a decrease in plastid volume and photosynthesis, but nucleus- and plastid-encoded photosystem subunits were still detected. Carbon fixation and transfer to the host were also maintained after >2 months. We also showed that the algal mitochondrion was stolen and retained for several months, transforming into an extensive network interacting with plastids. This highlights a complex strategy in plankton along the continuum of plastid symbioses, where both plastids and mitochondria of a microalga are hijacked by a host for several months without the algal nucleus. This association, which we found to be widely distributed in polar regions, suggests that plastid-mitochondrion interaction may have played a role in the evolution of plastid acquisition and opens new questions about host control and organelle maintenance.}, } @article {pmid40252292, year = {2025}, author = {Cournoyer, JE and De, BC and Mehta, AP}, title = {Molecular and biochemical insights from natural and engineered photosynthetic endosymbiotic systems.}, journal = {Current opinion in chemical biology}, volume = {87}, number = {}, pages = {102598}, pmid = {40252292}, issn = {1879-0402}, support = {R01 GM139949/GM/NIGMS NIH HHS/United States ; }, mesh = {*Symbiosis ; *Photosynthesis ; Chloroplasts/metabolism/genetics ; *Bacteria/metabolism/genetics ; Mitochondria/metabolism/genetics ; }, abstract = {Mitochondria and chloroplasts evolved through the transformation of bacterial endosymbionts established within the host cells. Studies on these organelles have provided several phylogenetic and biochemical insights related to this remarkable evolutionary transformation. Additionally, comparative studies between naturally existing endosymbionts and present-day organelles have allowed us to identify important common features of endosymbiotic evolution. In this review, we discuss hallmarks of photosynthetic endosymbiotic systems, particularly focusing on some of the fascinating molecular changes that occur in the endosymbiont and the host as the endosymbiont/host chimera evolves and transforms endosymbionts into organelles; these include the following: (i) endosymbiont genome minimization and host/endosymbiont gene transfer, (ii) protein import/export systems, (iii) metabolic crosstalk between the endosymbiont, (iv) alterations to the endosymbiont peptidoglycan, and (v) host-controlled replication of endosymbionts/organelles. We discuss these hallmarks in the context of naturally existing photosynthetic endosymbiotic systems and present-day chloroplasts. Further, we also briefly discuss laboratory efforts to engineer endosymbiosis between photosynthetic bacteria and host cells, the lessons learned from these studies, future directions of these studies, and their implications on evolutionary biology and synthetic biology.}, } @article {pmid40265287, year = {2025}, author = {Davanzo, GG and Castelucci, BG and de Souza, GF and Muraro, SP and Menezes Dos Reis, L and de Oliveira, IB and Fachi, JL and Virgilio-da-Silva, JV and Berçot, MR and Fernandes, MF and de Oliveira, S and Araujo, NVP and Ribeiro, G and de Castro, G and Costa, WLG and Santoro, AL and Rodrigues-Luiz, GF and do Carmo, HRP and Breder, I and Mori, MA and Farias, AS and Martins-de-Souza, D and Guarnieri, JW and Wallace, DC and Vinolo, MAR and Proença-Módena, JL and Beheshti, A and Sposito, AC and Moraes-Vieira, PM}, title = {Obesity-Induced Metabolic Priming Exacerbates SARS-CoV-2 Inflammation.}, journal = {Immunology}, volume = {175}, number = {3}, pages = {323-338}, pmid = {40265287}, issn = {1365-2567}, support = {//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 21/08354-2//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 13/07607-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2016/18031-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; P30 DK019525/DK/NIDDK NIH HHS/United States ; 2015/15626-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 18/15313-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 20/04579-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2274/20//Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas/ ; 406974/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 20/16030-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Humans ; *COVID-19/immunology/metabolism/complications ; *Obesity/immunology/metabolism/complications ; *SARS-CoV-2/immunology/physiology ; *Monocytes/immunology/metabolism/virology ; *Inflammation/immunology/metabolism ; *Fatty Acids, Nonesterified/metabolism ; Male ; Female ; Interleukin-6/metabolism/genetics ; Adult ; Middle Aged ; Mitochondria/metabolism ; Viral Load ; }, abstract = {Despite the early recognition that individuals living with obesity are more prone to develop adverse outcomes during COVID-19, the mechanisms underlying these conditions are still unclear. During obesity, an accumulation of free fatty acids (FFAs) in the circulation promotes low-grade inflammation. Here, we show that FFAs induce epigenetic reprogramming of monocytes, exacerbating their inflammatory profile after SARS-CoV-2 infection, a mechanism named metabolic-primed immunity. Monocytes from people with obesity or primed with palmitate, a central component of circulating FFAs, presented elevated viral load and higher gene expression of IL-6. Palmitate-primed monocytes upregulate fatty acid oxidation and FFAs entry into the mitochondria. FFA-derived acetyl-CoA is then converted into citrate, exiting the mitochondria and is used to support H3K18 histone acetylation, which regulates IL-6 accessibility. Ingestion of palm oil by lean and healthy individuals increased circulating FFAs levels and was sufficient to exacerbate the inflammatory profile of monocytes upon SARS-CoV-2 infection. Our findings demonstrate that obesity-derived FFAs induce the metabolic priming of monocytes, which exacerbates the inflammatory response observed in people with severe COVID-19.}, } @article {pmid40265338, year = {2025}, author = {Venkatraman, K and Lipp, NF and Budin, I}, title = {Origin and evolution of mitochondrial inner membrane composition.}, journal = {Journal of cell science}, volume = {138}, number = {9}, pages = {}, pmid = {40265338}, issn = {1477-9137}, support = {GBMF9734//Gordon and Betty Moore Foundation/ ; //University of California/ ; GM142960/NH/NIH HHS/United States ; R35 GM142960/GM/NIGMS NIH HHS/United States ; T32 GM008326/GM/NIGMS NIH HHS/United States ; }, mesh = {*Mitochondrial Membranes/metabolism/chemistry ; *Mitochondria/metabolism/genetics ; Humans ; Animals ; Mitochondrial Proteins/metabolism ; *Evolution, Molecular ; }, abstract = {Unique membrane architectures and lipid building blocks underlie the metabolic and non-metabolic functions of mitochondria. During eukaryogenesis, mitochondria likely arose from an alphaproteobacterial symbiont of an Asgard archaea-related host cell. Subsequently, mitochondria evolved inner membrane folds known as cristae alongside a specialized lipid composition supported by metabolic and transport machinery. Advancements in phylogenetic methods and genomic and metagenomic data have suggested potential origins for cristae-shaping protein complexes, such as the mitochondrial contact site and cristae-organizing system (MICOS). MICOS protein homologs function in the formation of cristae-like intracytoplasmic membranes (ICMs) in diverse extant alphaproteobacteria. The machinery responsible for synthesizing key mitochondrial phospholipids - which cooperate with cristae-shaping proteins to establish inner membrane architecture - could have also evolved from a bacterial ancestor, but its origins have been less explored. In this Review, we examine the current understanding of mitochondrial membrane evolution, highlighting distinctions between prokaryotic and eukaryotic mitochondrial-specific proteins and lipids and their differing roles in shaping cristae and ICM architecture, and propose a model explaining the concurrent specialization of the mitochondrial lipidome and inner membrane structure in eukaryogenesis. We discuss how advancements across a range of disciplines are shedding light on how multiple membrane components co-evolved to support the central functions of eukaryotic mitochondria.}, } @article {pmid40267584, year = {2025}, author = {Costa, JAS and da Silva Medeiros, C and Furtado, LFV and Rabelo, ÉML}, title = {From selection to resistance: Mitochondrial findings in hookworm evolution under drug pressure.}, journal = {Veterinary parasitology}, volume = {337}, number = {}, pages = {110470}, doi = {10.1016/j.vetpar.2025.110470}, pmid = {40267584}, issn = {1873-2550}, mesh = {Animals ; *Selection, Genetic ; *Drug Resistance/genetics ; Phylogeny ; *Anthelmintics/pharmacology ; *Ancylostoma/genetics/drug effects ; Albendazole/pharmacology ; Mitochondria/genetics ; Polymorphism, Single Nucleotide ; Evolution, Molecular ; Electron Transport Complex IV/genetics ; Genetic Variation ; NADH Dehydrogenase/genetics ; }, abstract = {Single nucleotide polymorphisms (SNPs) in codons 134, 167, 198, and 200 of the β-tubulin isotype 1 gene are associated with benzimidazole resistance in nematodes. Our group previously selected an Ancylostoma ceylanicum strain resistant to albendazole through drug-induced selective pressure, derived from a wild-type strain maintained under laboratory conditions for over 15 years. This study aimed to investigate mitochondrial genetic variability in the resistant strain compared to its wild-type counterpart. A total of 151 worms from both strains, collected during and 42 months after the selection process, were analyzed for partial sequences of the mitochondrial COI and NAD1 genes. Nucleotide variations were detected exclusively in the resistant strain, with low divergence levels of 0.16 % (1/612 bp) in COI and 0.25 % (1/398 bp) in NAD1. All COI substitutions were synonymous, while NAD1 presented one nonsynonymous mutation. Phylogenetic analyses based on Maximum Likelihood and Bayesian inference revealed strong clustering between resistant and wild-type laboratory samples (COI: 99 % bootstrap; NAD1: 96 %), distinct from field-derived sequences. These findings suggest that genetically homogeneous populations, resulting from isolation and restricted gene flow, may be more susceptible to genetic pressures, including selection, potentially leading to the establishment of resistant parasites. This study underscores the role of population genetics in the evolution of drug resistance and emphasizes the importance of managing genetic diversity to mitigate resistance development.}, } @article {pmid40271811, year = {2025}, author = {Bravo-Arévalo, JE}, title = {Tracing the evolutionary pathway: on the origin of mitochondria and eukaryogenesis.}, journal = {The FEBS journal}, volume = {292}, number = {19}, pages = {5026-5041}, pmid = {40271811}, issn = {1742-4658}, support = {CF-2023-I-1545//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; PAPIIT: IN218424//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; }, mesh = {Animals ; Humans ; *Biological Evolution ; *Eukaryota/genetics/metabolism ; *Eukaryotic Cells/metabolism ; *Evolution, Molecular ; Gene Transfer, Horizontal ; *Mitochondria/genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; Phylogeny ; Protein Transport ; Symbiosis/genetics ; }, abstract = {The mito-early hypothesis posits that mitochondrial integration was a key driver in the evolution of defining eukaryotic characteristics (DECs). Building on previous work that identified endosymbiotic selective pressures as central to eukaryotic cell evolution, this study examines how endosymbiotic gene transfer (EGT) and the resulting genomic and bioenergetic constraints shaped mitochondrial protein import systems. These systems were crucial for maintaining cellular function in early eukaryotes and facilitated their subsequent diversification. A primary focus is the co-evolution of mitochondrial import mechanisms and eukaryotic endomembrane complexity. Specifically, I investigate how the necessity for nuclear-encoded mitochondrial protein import drove the adaptation of bacterial secretion components, alongside eukaryotic innovations, to refine translocation pathways. Beyond enabling bioenergetic expansion, mitochondrial endosymbiosis played a fundamental role in the emergence of compartmentalisation and cellular complexity in LECA, driving the evolution of organellar networks. By integrating genomic, structural and phylogenetic evidence, this study aimed to contribute to the mito-early framework, clarifying the mechanisms that linked mitochondrial acquisition to the origin of eukaryotic cells.}, } @article {pmid40272291, year = {2025}, author = {Liu, X and Yan, Y}, title = {Advances in origin, evolution, and pathogenesis of optic disc drusen: A narrative review.}, journal = {Indian journal of ophthalmology}, volume = {73}, number = {5}, pages = {637-647}, pmid = {40272291}, issn = {1998-3689}, mesh = {Humans ; *Optic Disk Drusen/etiology/diagnosis ; *Tomography, Optical Coherence/methods ; *Optic Disk/pathology/diagnostic imaging ; *Visual Fields ; *Retinal Ganglion Cells/pathology ; }, abstract = {Optic disc drusen (ODD) is acellular calcified deposits found mainly in front of the lamina cribrosa within the optic nerve. It can cause chronic or acute vision loss. There has been progress in clinical diagnosis using ophthalmic multimodal imaging in recent years. We conducted a database search on PubMed and Google Scholar (April 2023) with no restrictions on publication year or language. We used the terms: ("optic disc drusen") OR ("optic nerve head drusen") OR ("drusen of optic nerve head"). Other terms included gene, mutation, scleral canal, axonal transport, calcinosis, mitochondria, blood vessel, vasculature, visual field, vision, and optical coherence tomography to identify publications. Etiologically, ODD may stem from congenital genetic defects, aberrant axoplasmic transport, anatomical abnormalities, and mechanical factors during ocular duction. Clinically, ODD is linked to progressive visual field defects and vascular complications. Detection of deeply buried ODD can be challenging, but advances in optical coherence tomography make early identification possible. Structural changes, including retinal nerve fiber layer thinning, can be monitored. Increasing reports indicate vascular complications, including anterior ischemic optic neuropathy, in ODD patients. Currently, ODD-related visual field defects are not effectively treated, and observation remains the primary management approach. Future pathological discoveries or the establishment of animal models may provide new evidence for revealing the pathogenesis of ODD.}, } @article {pmid40283904, year = {2025}, author = {Sakrajda, K and Rybakowski, JK}, title = {The Mechanisms of Lithium Action: The Old and New Findings.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {4}, pages = {}, pmid = {40283904}, issn = {1424-8247}, abstract = {Despite lithium's presence in modern psychiatry for three-quarters of a century, the mechanisms of its therapeutic action have not been fully elucidated. This article presents the evolution of the views on these mechanisms, and both the old and new findings are discussed. Among the old mechanisms, lithium's effect on the purinergic system; electrolyte metabolism; membrane transport; and second messenger systems, namely, cyclic nucleotide and phosphatidylinositol (PI), glycogen synthase kinase-3beta (GSK-3β), brain-derived neurotrophic factor, and neurotransmitters, are discussed. The new data were obtained from in vitro studies, molecular biology, and genetic research. They showed the effects of lithium on the immune system, biological rhythms, telomere functions, and mitochondria. In this article, each lithium mechanism is considered in the light of its association with the pathogenesis of bipolar disorder or/and as a marker of the lithium response. Although not exhaustive, this review elucidates the multiple potential mechanisms of lithium action. It was also observed that many seemingly "old" mechanisms have experienced a resurgence in research conducted during the 21st century. Additionally, many studies converged on the previously postulated mechanisms of lithium inhibiting GSK-3β and PI.}, } @article {pmid40290089, year = {2025}, author = {Reumann, S and Parasyri, A}, title = {Protein acetylation as a novel post-translational modification of plant peroxisomal proteins.}, journal = {Journal of experimental botany}, volume = {76}, number = {12}, pages = {3311-3323}, doi = {10.1093/jxb/eraf089}, pmid = {40290089}, issn = {1460-2431}, support = {//University of Hamburg/ ; }, mesh = {Acetylation ; *Protein Processing, Post-Translational ; *Peroxisomes/metabolism ; *Arabidopsis/metabolism ; *Plant Proteins/metabolism ; Arabidopsis Proteins/metabolism ; }, abstract = {Plant peroxisomes compartmentalize many important metabolic functions, but little is known about how these pathways are regulated at the post-translational level. A few plant peroxisomal proteins have been shown to be subjected to reversible phosphorylation or ubiquitination, but other post-translational modifications are hardly known for peroxisomes from animals, fungi, and plants. We here address the question of whether plant peroxisomal metabolism might be regulated by protein acetylation. We summarize available knowledge on protein acetylation in plastids and mitochondria, focusing on the catalytic machinery and the regulation of target enzymes. We screened global acetylome studies of Arabidopsis for known proteins of peroxisomes that are N-terminally or Lys-acetylated. For selected matrix proteins, we mapped the acetylated Lys sites onto their AlphaFold 3D models to predict their effect on enzyme activity and oligomerization. We also summarize knowledge on two Arabidopsis acetyl transferases that have recently been identified as novel peroxisomal matrix proteins. We deduce their evolution in peroxisomes and partially their functions, as far as they can be predicted from available structural models. This information allows us to identify experimental strategies to define the postulated new regulatory mechanism of protein acetylation for plant peroxisomes in the near future.}, } @article {pmid40300602, year = {2025}, author = {Baumann, N and Wagener, RJ and Javed, A and Conti, E and Abe, P and Lopes, A and Sansevrino, R and Lavalley, A and Magrinelli, E and Szalai, T and Fuciec, D and Ferreira, C and Fièvre, S and Fouassier, A and D'Amico, D and Harschnitz, O and Jabaudon, D}, title = {Regional differences in progenitor metabolism shape brain growth during development.}, journal = {Cell}, volume = {188}, number = {13}, pages = {3567-3582.e20}, doi = {10.1016/j.cell.2025.04.003}, pmid = {40300602}, issn = {1097-4172}, mesh = {Animals ; Mice ; *Neurogenesis ; *Brain/metabolism/growth & development/embryology ; Mitochondria/metabolism ; *Neural Stem Cells/metabolism/cytology ; Cell Proliferation ; Neurons/metabolism/cytology ; Single-Cell Analysis ; Mice, Inbred C57BL ; Female ; Male ; }, abstract = {Mammals have particularly large forebrains compared with other brain parts, yet the developmental mechanisms underlying this regional expansion remain poorly understood. Here, we provide a single-cell-resolution birthdate atlas of the mouse brain (www.neurobirth.org), which reveals that while hindbrain neurogenesis is transient and restricted to early development, forebrain neurogenesis is temporally sustained through reduced consumptive divisions of ventricular zone progenitors. This atlas additionally reveals region-specific patterns of direct and indirect neurogenesis. Using single-cell RNA sequencing, we identify evolutionarily conserved cell-cycle programs and metabolism-related molecular pathways that control regional temporal windows of proliferation. We identify the late neocortex-enriched mitochondrial protein FAM210B as a key regulator using in vivo gain- and loss-of-function experiments. FAM210B elongates mitochondria and increases lactate production, which promotes progenitor self-replicative divisions and, ultimately, the larger clonal size of their progeny. Together, these findings indicate that spatiotemporal heterogeneity in mitochondrial function regulates regional progenitor cycling behavior and associated clonal neuronal production during brain development.}, } @article {pmid40302930, year = {2025}, author = {Scheckhuber, CQ and Maciver, SK and de Obeso Fernandez Del Valle, A}, title = {Unveiling the molecular architecture of the mitochondrial respiratory chain of Acanthamoeba castellanii.}, journal = {Microbial cell (Graz, Austria)}, volume = {12}, number = {}, pages = {65-75}, pmid = {40302930}, issn = {2311-2638}, abstract = {Acanthamoeba castellanii is a ubiquitous free-living amoeba that can cause severe infections in humans. Unlike most other organisms, A. castellanii possesses a "complete" mitochondrial respiratory chain, meaning it con-tains several additional enzymes that contribute to its metabolic versa-tility and survival in diverse environments. This review provides a com-prehensive overview of the mitochondrial respiratory chain in A. castellanii, focusing on the key alternative components in-volved in oxidative phosphorylation and their roles in energy metabo-lism, stress response, and adaptation to various conditions. The func-tional characterization of the alternative oxidase (AOX), uncoupling pro-tein (UCP), and alternative NAD(P)H dehydrogenases, highlight their roles in reducing oxidative stress, modulating proton gradients, and adapting to changes in temperature and nutrient availability. These pro-teins and systems serve a role in the survival of A. castel-lanii under stressful conditions such as starvation and cold con-ditions. Further knowledge of the respiratory chain of the amoeba has potential implications for understanding the evolution of mitochondrial respiration and developing new therapies for treating Acanthamoeba infections.}, } @article {pmid40305847, year = {2025}, author = {Sarkar, M and Pucadyil, TJ}, title = {Division of Labor among Fission Dynamins Based on Substrate Size.}, journal = {Biochemistry}, volume = {64}, number = {10}, pages = {2117-2122}, doi = {10.1021/acs.biochem.4c00862}, pmid = {40305847}, issn = {1520-4995}, mesh = {Humans ; *Dynamins/metabolism/chemistry ; Animals ; Guanosine Triphosphate/metabolism ; Organelles/metabolism ; }, abstract = {Membrane fission is necessary for the formation of vesicles in the endolysosomal system and for the division of organelles like peroxisomes, mitochondria, and chloroplasts. In these processes, fission is managed by certain members of the dynamin superfamily of proteins (DSPs). These DSPs are soluble proteins that self-assemble into helical scaffolds that hydrolyze GTP and force the constriction of tubular membrane substrates, leading to their fission. Based on where they function, fission DSPs can be operationally categorized into vesicle dynamins (VDs) or organelle dynamins (ODs). Even though they share conserved domains and display largely similar enzymatic properties, recent results reveal fundamental differences with respect to the size of the tubular membrane substrate that certain VDs and ODs can sever. Substrate sizes encountered during vesicle formation and organelle division are quite different and could have served as physical constraints that forced the evolution of VDs and ODs. Here, we briefly review and rationalize mechanisms for the division of labor among DSPs.The structural basis for substrate size-dependent fission activity among VDs and ODs remains unclear and represents an attractive area for future research.}, } @article {pmid40307667, year = {2025}, author = {Koch, RE and Toomey, MB and Zhang, Y and Hill, GE}, title = {Mechanisms of Carotenoid Metabolism: Understanding the Links between Red Coloration, Cellular Respiration, and Individual Quality.}, journal = {Integrative and comparative biology}, volume = {65}, number = {2}, pages = {496-506}, doi = {10.1093/icb/icaf022}, pmid = {40307667}, issn = {1557-7023}, support = {NSF-IOS-2037741//National Science Foundation/ ; NSF-IOS-2037735//National Science Foundation/ ; NSF-IOS-2224556//National Science Foundation/ ; NSF-IOS-2037739//National Science Foundation/ ; }, mesh = {Animals ; *Carotenoids/metabolism ; *Pigmentation/physiology ; *Birds/physiology/metabolism/genetics ; Cell Respiration ; Feathers ; }, abstract = {In many species of birds, red carotenoid coloration serves as an honest signal of individual quality, but the mechanisms that link carotenoid coloration to animal performance remain poorly understood. Most birds that display red carotenoid coloration of feathers, bills, or legs ingest yellow carotenoids and metabolically convert the yellow pigments to red. Here, we review two lines of investigation that have rapidly advanced understanding of the production of red carotenoid coloration in birds, potentially providing an explanation for how red coloration serves as a signal of quality: the identification of the genes that enable birds to be red and the confirmation of links between production of red pigments and core cellular function. CYP2J19 and BDH1L were identified as key enzymes that catalyze the conversion of yellow carotenoids to red carotenoids both in the retinas of birds for enhanced color vision and in the feathers and bills of birds for ornamentation. This CYP2J19 and BDH1L pathway was shown to be the mechanism for production of red coloration in diverse species of birds and turtles. In other studies, it was shown that male House Finches (Haemorhous mexicanus) have high concentrations of red carotenoids within liver mitochondria and that redness is positively associated with mitochondrial function. These observations suggested that the CYP2J19 and BDH1L pathway might be tightly associated with mitochondrial function. However, it was subsequently discovered that male House Finches do not use the CYP2J19 and BDH1L pathway to produce red pigments and that both CYP2J19 and BDH1L localize in the endoplasmic reticulum, not the mitochondria. Thus, we have the most detailed understanding of links between cellular function and redness in a bird species for which the enzymes to convert yellow to red pigments remain unknown, while we have the best understanding of the enzymatic pathways to red in species for which links to cellular function are largely unstudied. Deducing whether and how signals of quality arise from these distinct mechanisms of ornamental coloration is a current challenge for scientists interested in the evolution of honest signaling.}, } @article {pmid40313116, year = {2026}, author = {Li, C and Luo, Y and Li, S}, title = {Mechanistic insights of neuronal death and neuroprotective therapeutic approaches in stroke.}, journal = {Neural regeneration research}, volume = {21}, number = {3}, pages = {869-886}, pmid = {40313116}, issn = {1673-5374}, abstract = {Stroke, particularly ischemic stroke, is the leading cause of long-term disability and mortality worldwide. It occurs due to the occlusion of the cerebral arteries, which significantly reduces the delivery of blood, oxygen, and essential nutrients to brain tissues. This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death. Recent studies have clarified the multifactorial pathogenesis of ischemic stroke, highlighting the roles of energy failure, excitotoxicity, oxidative stress, neuroinflammation, and apoptosis. This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke. Additionally, we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke, including the interplay of apoptosis, autophagy, pyroptosis, ferroptosis, and necrosis, which collectively influence neuronal fate. We also discussed advancements in neuroprotective therapeutics, encompassing a range of interventions from pharmacological modulation to stem cell-based therapies, aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke. Despite these advancements, challenges remain in translating mechanistic insights into effective clinical therapies. Although neuroprotective strategies have shown promise in preclinical models, their efficacy in human trials has been inconsistent, often due to the complex pathology of ischemic stroke and the timing of interventions. In conclusion, this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia. It sheds light on cutting-edge advancements in potential neuroprotective therapeutics, underscores the promise of regenerative medicine, and offers a forward-looking perspective on potential clinical breakthroughs. The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.}, } @article {pmid40323724, year = {2025}, author = {Sloan, DB}, title = {Can transcriptome size and off-target effects explain the contrasting evolution of mitochondrial vs nuclear RNA editing?.}, journal = {Journal of evolutionary biology}, volume = {38}, number = {12}, pages = {1573-1577}, pmid = {40323724}, issn = {1420-9101}, support = {R35 GM148134/GM/NIGMS NIH HHS/United States ; R35GM148134/NH/NIH HHS/United States ; MCB-2048407//National Science Foundation/ ; }, mesh = {*RNA Editing ; *Evolution, Molecular ; *Transcriptome ; *Genome, Mitochondrial ; *Genetic Drift ; Humans ; Animals ; }, abstract = {Mitochondrial RNA editing has evolved independently in numerous eukaryotic lineages, where it generally restores conserved sequences and functional reading frames in mRNA transcripts derived from altered or disrupted mitochondrial protein-coding genes. In contrast to this "restorative" RNA editing in mitochondria, most editing of nuclear mRNAs introduces novel sequence variants and diversifies the proteome. This Perspective addresses the hypothesis that these completely opposite effects of mitochondrial vs. nuclear RNA editing arise from the enormous difference in gene number between the respective genomes. Because mitochondria produce a much smaller transcriptome, they likely create less opportunity for off-target editing, which has been supported by recent experimental work expressing mitochondrial RNA editing machinery in foreign contexts. In addition, there is recent evidence that the size and complexity of RNA targets may slow the kinetics and reduce efficiency of on-target RNA editing. These findings suggest that efficient targeting and a low risk of off-target editing have facilitated the repeated emergence of disrupted mitochondrial genes and associated restorative RNA editing systems via (potentially non-adaptive) evolutionary pathways that are not feasible in larger nuclear transcriptomes due to lack of precision.}, } @article {pmid40329166, year = {2025}, author = {Zhong, T and Huang, S and Liu, R and Zhuo, J and Lu, H and Gan, C and Fu, J and Qian, Q}, title = {The complete mitochondrial genome of Sinojackia microcarpa: evolutionary insights and gene transfer.}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {446}, pmid = {40329166}, issn = {1471-2164}, support = {SRSJJD2024005//Off-campus practice education base for design majors of Zhejiang Shuren University/ ; SRSJJD2024005//Off-campus practice education base for design majors of Zhejiang Shuren University/ ; SRSJJD2024005//Off-campus practice education base for design majors of Zhejiang Shuren University/ ; SRSJJD2024005//Off-campus practice education base for design majors of Zhejiang Shuren University/ ; SXSZY202412//Key Specialty Project of Ordinary Colleges and Universities/ ; SXSZY202412//Key Specialty Project of Ordinary Colleges and Universities/ ; SXSZY202412//Key Specialty Project of Ordinary Colleges and Universities/ ; SXSZY202412//Key Specialty Project of Ordinary Colleges and Universities/ ; LGN21C160015//the Basic Public Welfare Research Projects of Zhejiang province/ ; LGN21C160015//the Basic Public Welfare Research Projects of Zhejiang province/ ; LGN21C160015//the Basic Public Welfare Research Projects of Zhejiang province/ ; LGN21C160015//the Basic Public Welfare Research Projects of Zhejiang province/ ; }, mesh = {*Genome, Mitochondrial ; *Evolution, Molecular ; Phylogeny ; RNA, Transfer/genetics ; Genomics ; }, abstract = {BACKGROUND: As a dicotyledonous plant within the Styracaceae family, Sinojackia microcarpa (S. microcarpa) is notable for its library-shaped fruit and sparse distribution, serving as a model system for studying the entire tree family. However, the scarcity of genomic data, particularly concerning the mitochondrial and nuclear sequences of S. microcarpa, has substantially impeded our understanding of its evolutionary traits and fundamental biological mechanisms.

RESULTS: This study presents the first complete mitochondrial genome sequence of S. microcarpa and conducts a comparative analysis of its protein-encoding genes across eight plant species. Our analysis revealed that the mitochondrial genome of S. microcarpa spans 687,378 base pairs and contains a total of 59 genes, which include 37 protein-coding genes (PCGs), 20 transfer RNA (tRNA) genes, and 2 ribosomal RNA (rRNA) genes. Sixteen plastid-derived fragments strongly linked with mitochondrial genes, including one intact plastid-related gene (rps7), were identified. Additionally, Ka/Ks ratio analysis revealed that most mitochondrial genes are under purifying selection, with a few genes, such as nad9 and ccmB, showing signs of relaxed or adaptive evolution. An analysis of twenty-nine protein-coding genes from twenty-four plant species reveals that S. microcarpa exhibits a closer evolutionary relationship with species belonging to the genus Camellia. The findings of this study provide new genomic data that enhance our understanding of S. microcarpa, and reveal its mitochondrial genome's evolutionary proximity to other dicotyledonous species.

CONCLUSIONS: Overall, this research enhances our understanding of the evolutionary and comparative genomics of S. microcarpa and other plants in the Styracaceae family and lays the foundation for future genetic studies and evolutionary analyses in the Styracaceae family.}, } @article {pmid40338339, year = {2025}, author = {Li, X and Liu, D and Han, B and Huang, S and Deng, H}, title = {Genome-wide identification of CYP450 in Ganoderma lucidum and expression analysis of genes related to ganoderic acid synthesis.}, journal = {Archives of microbiology}, volume = {207}, number = {6}, pages = {137}, pmid = {40338339}, issn = {1432-072X}, support = {2023YFC3503804//The National Key Research and Development Program of China/ ; 2023AH052637//Special Funds for Anhui Dabie Mountain Institute of Traditional Chinese Medicine/ ; Anhui [2023] TG07//the 2023 Central Finance Forestry Science and Technology Promotion Demonstration Funds Project/ ; }, mesh = {*Cytochrome P-450 Enzyme System/genetics/metabolism ; *Reishi/genetics/enzymology/metabolism ; *Triterpenes/metabolism ; *Fungal Proteins/genetics/metabolism ; *Genome, Fungal ; Gene Expression Profiling ; Gene Expression Regulation, Fungal ; Phylogeny ; Transcriptome ; }, abstract = {The biosynthesis mechanism of ganoderic acid, a class of secondary metabolites of Ganoderma lucidum, is currently unknown. Members of G. lucidum's CYP450 gene family were found in this study by genome-wide analysis. Determination of ganoderic acid content in Jilin, Zhejiang, Jinzhai, Fujian, Yunnan and Shandong regions was performed using high performance liquid chromatography. Expression of CYP450 gene of G. lucidum from Jilin, Jinzhai and Shandong origins was analyzed by transcriptome sequencing. The findings indicated that, through comprehensive sequence analysis and functional annotation, 189 CYP450 genes were detected in the G. lucidum genome, among which 34 CYP450 genes were significantly differentially expressed in transcriptome analysis, and the gene expression was positively correlated with ganoderic acid content. Bioinformatics analysis predicted the conserved motifs, structural features, and subcellular localization of 189 CYP genes, revealing significant differences in gene structure and protein motif composition among GlCYP450 family members. Subcellular localization revealed that they are located in the plasma membrane, cytoplasm, nucleus, mitochondria, peroxisome, endoplasmic reticulum, extracellular space, and cytoskeleton, suggesting that they have multiple functions. A number of cis-regulatory elements associated with stress responses and phytohormones were identified in the promoter regions of these genes. It demonstrates that ganoderic acid production has been significantly controlled by these P450 genes. These findings offer a crucial theoretical foundation for a thorough comprehension of the process of ganoderic acid production, the bioinformatics role of CYP450 genes in G. lucidum, and the selection and breeding of superior G. lucidum resources.}, } @article {pmid40343117, year = {2025}, author = {Meng, D and Lu, T and He, M and Ren, Y and Fu, M and Zhang, Y and Yang, P and Lin, X and Yang, Y and Zhang, Y and Yang, Y and Jin, X}, title = {Organelle genomes of two Scaevola species, S. taccada and S. hainanensis, provide new insights into evolutionary divergence between Scaevola and its related species.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1587750}, pmid = {40343117}, issn = {1664-462X}, abstract = {Chloroplast and mitochondrial genomes harbor crucial information that can be utilized for elucidating plant evolution and environmental adaptation. The organellar genomic characteristics of Goodeniaceae, a sister family to Asteraceae, remain unexplored. Here, using a combination of short-read and long-read sequencing technologies, we successfully assembled the complete organellar genomes of two Goodeniaceae species native to China, Scaevola taccada and S. hainanensis. Chloroplast genome collinearity analysis revealed that Scaevola expanded its genome length through inverted repeat expansion and large single copy fragment duplication, resulting in 181,022 bp (S. taccada) and 182,726 bp (S. hainanensis), ~30 kb increase compared to its related species. Mitochondrial genomes of two Scaevola species exhibit multi-ring topology, forming dual mitochondrial chromosomes of 314,251 bp (S. taccada) and 276,175 bp (S. hainanensis). Sequence variation analysis demonstrated substantial chloroplast sequence divergence (Pi = 0.45) and an increase in gene copy number within the genus. Relative synonymous codon usage (RSCU) analysis revealed that Scaevola chloroplast has a higher bias for A/U-ending codons than mitochondria, with chloroplasts RSCU values ranging from 0.32 to 1.94, whereas mitochondrial RSCU values ranging from 0.38 to 1.62. Phylogenetic analyses support the monophyly of the Asteraceae-Goodeniaceae sister group, whereas the extended evolutionary branches of Scaevola, coupled with mitochondrial collinearity analysis, indicate rapid organellar genome evolution of Scaevola. Organellar-nuclear horizontal gene transfer analysis identified specific increased in the copy numbers of photosynthesis-related genes and chloroplast-nuclear transfer events in S. taccada. Our study not only provides insights for understanding environmental adaptation mechanisms of coastal plants, but also contributes to elucidating organellar genome evolution in Scaevola and Goodeniaceae.}, } @article {pmid40359151, year = {2025}, author = {Garlovsky, MD and Dobler, R and Guo, R and Voigt, S and Dowling, DK and Reinhardt, K}, title = {Testing for age- and sex-specific mitonuclear epistasis in Drosophila.}, journal = {Evolution; international journal of organic evolution}, volume = {79}, number = {8}, pages = {1568-1582}, doi = {10.1093/evolut/qpaf096}, pmid = {40359151}, issn = {1558-5646}, support = {RE 1666/9-1//Deutsche Forschungsgemeinschaft/ ; //Australian Research Council/ ; //China Scholarship Council/ ; }, mesh = {Animals ; Male ; Female ; *Drosophila melanogaster/genetics/physiology ; *Epistasis, Genetic ; Genetic Fitness ; Aging ; Cell Nucleus/genetics ; Mitochondria/genetics ; Fertility ; }, abstract = {The need for efficient ATP production is predicted to result in the evolution of cooperation between the mitochondrial and nuclear encoded components of the electron transport system. Genotypes where mitochondrial and nuclear genomes from different geographic populations are combined (mismatched) are therefore predicted to result in negative fitness consequences. Such negative fitness effects are expected to be prominent in males, since maternal inheritance of mitochondria can lead to accumulation of male-harming mutations (the mother's curse hypothesis), and they may become more prevalent with aging. To test these predictions, we measured fertility traits of females and males at different ages using a genetically diverse panel of 27 mitonuclear populations of Drosophila melanogaster with matched or experimentally mismatched mitonuclear genomes. We found no evidence that novel mitonuclear combinations had reduced fitness in females. In males, we found limited evidence of mitonuclear interactions affecting fitness in old age, however, not in the direction predicted. Novel mitonuclear combinations were associated with males that sired more offspring. Sex-specific advantages of mismatched males might arise if novel nuclear alleles compensate for deleterious mitochondrial alleles that have accumulated. If such compensatory effects of novel mitonuclear combinations increasing fitness occur in nature, they could represent a possible counterforce to the mother's curse.}, } @article {pmid40359376, year = {2025}, author = {Belinchon-Moreno, J and Berard, A and Canaguier, A and Le-Clainche, I and Rittener-Ruff, V and Lagnel, J and Hinsinger, D and Boissot, N and Faivre-Rampant, P}, title = {Nuclear and organelle genome assemblies of 5 Cucumis melo L. accessions, Ananas, Canton, PI 414723, Vedrantais, and Zhimali, belonging to diverse botanical groups.}, journal = {G3 (Bethesda, Md.)}, volume = {15}, number = {7}, pages = {}, pmid = {40359376}, issn = {2160-1836}, support = {//French National Research Institute for Agriculture, Food and Environment (INRAE)/ ; //Avignon University/ ; }, mesh = {*Cucumis melo/genetics/classification ; *Genome, Plant ; *Genomics/methods ; *Cell Nucleus/genetics ; Molecular Sequence Annotation ; *Genome, Chloroplast ; Genome, Mitochondrial ; Genetic Variation ; Chromosomes, Plant ; }, abstract = {The construction of accurate whole genome sequences is pivotal for characterizing the genetic diversity of plant species, identifying genes controlling important traits, or understanding their evolutionary dynamics. Here, we generated the nuclear, mitochondrial, and chloroplast high-quality assemblies of 5 melon (Cucumis melo L.) accessions representing 5 botanical groups, using the Oxford Nanopore sequencing technology. The accessions here studied included varied origins, fruit shapes, sizes, and resistance traits, providing a holistic view of melon genomic diversity. The final chromosome-level genome assemblies ranged in size from 359 to 365 Mb, with approximately 25× coverage for 4 of them multiplexed in half of a PromethION flowcell, and 48× coverage for the fifth, sequenced individually in another half of a PromethION flowcell. Contigs N50 ranged from 7 to 15 Mb for all the assemblies, and very long contigs reaching sizes of 20-25 Mb, almost compatible with complete chromosomes, were assembled in all the accessions. Quality assessment through Benchmarking Universal Single-Copy Orthologs (BUSCO) and Merqury indicated the high completeness and accuracy of the assemblies, with BUSCO values exceeding 96% for all accessions, and Merqury QV values ranging between 41 and 47. We focused on the complex NLR resistance gene regions to validate the accuracy of the assemblies in highly complex and repetitive regions. Through Nanopore adaptive sampling, we generated accurately targeted assemblies of these regions with significantly higher coverage, enabling the comparison to our whole genome assemblies. Overall, these chromosome-level assembled genomes constitute a valuable resource for research focused on melon diversity, disease resistance, evolution, and breeding applications.}, } @article {pmid40373020, year = {2025}, author = {Mu, W and Liu, J and Zhang, H}, title = {Characterization of the complete mitochondrial genomes of two sea cucumbers, Deima validum and Oneirophanta mutabilis (Holothuroidea, Synallactida, Deimatidae): Insight into deep-sea adaptive evolution of Deimatidae.}, journal = {PloS one}, volume = {20}, number = {5}, pages = {e0323612}, pmid = {40373020}, issn = {1932-6203}, mesh = {Animals ; *Genome, Mitochondrial ; *Sea Cucumbers/genetics/classification ; Phylogeny ; *Evolution, Molecular ; RNA, Transfer/genetics ; *Adaptation, Physiological/genetics ; }, abstract = {The deep-sea is the largest and most extensive ecosystem on our planet with limited food availability, extreme pressure reaching hundreds of bars, perpetual darkness, frigid temperatures, and minimal oxygen levels. Mitochondria plays a key role in energy metabolism and oxygen usage, thus it may undergo adaptive evolution in response to pressures from extreme harsh environments. In this study, we present the mitochondrial genome sequences of the sea cucumbers Deima validum and Oneirophanta mutabilis collected from the South China Sea. To our knowledge, they are the first reported mitogenomes from the family Deimatidae. Similar to other sea cucumbers, both mitogenomes contain 13 PCGs, 2 rRNA genes, 22 tRNA genes (including duplication of trnS and trnL) and 1 non-coding regions. The genes in both species are distributed on the positive and negative strands, with six genes encoded on the L-strand and 31 genes encoded on the H-strand. We compared the order of genes from the 13 available holothurian mitogenomes and found a novel gene arrangement in D. validum. Phylogenetic analysis revealed that D. validum clustered with O. mutabilis, forming the deep-sea Deimatidae clade. The analysis of individual genes revealed the presence of three sites (90 L, 147 S, 192 V) in nad2 and one site (28 S) in nad5 with high posterior probabilities indicating positive selection. By comparing these features with those of shallow sea cucumbers, we predict that nad2 and nad5 may provide valuable insights into the molecular mechanisms at the mitochondrial level involved in Deimatidae's adaptation to the deep-sea habitat.}, } @article {pmid40381604, year = {2025}, author = {He, Q and Cao, S and Yu, W and Li, Z and Liu, W and Tian, C and Li, D and Zou, Y and Yu, B and Zhan, Y and Jiang, Y and Wu, J and Yang, Y and Wang, N}, title = {hnRNP K regulates mitochondrial apoptosis induced by porcine circovirus type 3 capsid protein.}, journal = {Veterinary microbiology}, volume = {306}, number = {}, pages = {110557}, doi = {10.1016/j.vetmic.2025.110557}, pmid = {40381604}, issn = {1873-2542}, mesh = {*Circovirus/genetics ; *Apoptosis ; Animals ; *Capsid Proteins/genetics/metabolism ; Swine ; *Mitochondria/metabolism ; *Heterogeneous-Nuclear Ribonucleoprotein K/metabolism/genetics ; Cell Line ; Circoviridae Infections/virology/veterinary ; Molecular Docking Simulation ; }, abstract = {Porcine circovirus type 3 (PCV3) is a globally emerging circovirus affecting pigs and other animals. The capsid protein (Cap) is the sole structural protein of PCV, with a crucial role in virus evolution and pathogenesis. Through interactions with host factors, Cap enables viral entry, transport, and replication while modifying various cellular processes. Cap protein-induced apoptosis has important implications for viral pathogenesis, but remains poorly defined. Herein, we demonstrated for the first time that PCV3 Cap induced cell cycle arrest of PK-15 cells in S-phase and initiated apoptosis via a mitochondrial Caspase-9-dependent pathway. Truncation analysis localized the apoptotic determinant to the N-terminal 1-34 aa of PCV3 Cap and heterogeneous nuclear ribonucleoprotein K (hnRNP K) was identified as a host protein that binds to PCV3 Cap. Overexpression of hnRNP K reduced PCV3 Cap-induced release of Cyt-c into the cytoplasm, implying a regulatory role in apoptosis. Based on structural modelling and molecular docking, amino acids at sites 24 and 27 of Cap from PCV3 variants, which define genotypes (PCV3a/b/c), affected binding with hnRNP K. Specifically, PCV3c Cap (V24/K27 and V24/R27) had higher affinity than PCV3a Cap (A24/R27) or PCV3b Cap (A24/K27), consistent with its superior apoptosis-inducing capacity compared to PCV3a/b variants, highlighting the importance of Cap interactions with hnRNP K. In summary, we identified novel molecular determinants of PCV3 pathogenesis that will inform development of vaccines and diagnostics.}, } @article {pmid40384044, year = {2025}, author = {Harada, R and Shiratori, T and Yabuki, A and Inagaki, Y and Roger, AJ and Kamikawa, R}, title = {Complete Mitochondrial Genomes of Ancyromonads Provide Clues for the Gene Content and Genome Structures of Ancestral Mitochondria.}, journal = {The Journal of eukaryotic microbiology}, volume = {72}, number = {3}, pages = {e70012}, pmid = {40384044}, issn = {1550-7408}, support = {18J02091//Japan Society for the Promotion of Science/ ; 22KJ0401//Japan Society for the Promotion of Science/ ; 24K21929//Japan Society for the Promotion of Science/ ; 23K27226//Japan Society for the Promotion of Science/ ; BPI06050//Japan Society for the Promotion of Science/ ; RGPIN-2022-05430//Natural Sciences and Engineering Research Council of Canada/ ; G-2024-1-011//Institute for Fermentation, Osaka/ ; //World Premier International Research Center Initiative/ ; }, mesh = {*Genome, Mitochondrial ; Phylogeny ; Evolution, Molecular ; *Mitochondria/genetics ; Eukaryota/genetics ; }, abstract = {Mitochondria of eukaryotic cells are direct descendants of an endosymbiotic bacterium related to Alphaproteobacteria. These organelles retain their own genomes, which are highly reduced and divergent when compared to those of their bacterial relatives. To better understand the trajectory of mitochondrial genome evolution from the last eukaryotic common ancestor (LECA) to extant species, mitochondrial genome sequences from phylogenetically diverse lineages of eukaryotes-particularly protists-are essential. For this reason, we focused on the mitochondrial genomes of Ancyromonadida, an independent and understudied protist lineage in the eukaryote tree of life. Here we report the mitochondrial genomes from three Ancyromonadida: Ancyromonas sigmoides, Nutomonas longa, and Fabomonas tropica. Our analyses reveal that these mitochondrial genomes are circularly mapping molecules with inverted repeats that carry genes. This inverted repeat structure has been observed in other mitochondrial genomes but is patchily distributed over the tree of eukaryotes. Ancyromonad mitochondrial genomes possess several protein-coding genes, which have not been detected from any other mitochondrial genomes of eukaryotes sequenced to date, thereby extending the known mitochondrial gene repertoire of ancestral eukaryotes, including LECA. These findings significantly expand our understanding of mitochondrial genome diversity across eukaryotes, shedding light on the early phases of mitochondrial genome evolution.}, } @article {pmid40388856, year = {2025}, author = {Liu, J and Pan, L and Cheng, Y and Ruan, M and Ye, Q and Wang, R and Yao, Z and Zhou, G and Liu, C and Wan, H}, title = {Evolution and functional roles of neutral/alkaline invertases in plant growth, development, and stress response.}, journal = {Plant physiology and biochemistry : PPB}, volume = {225}, number = {}, pages = {110011}, doi = {10.1016/j.plaphy.2025.110011}, pmid = {40388856}, issn = {1873-2690}, mesh = {*Plant Development ; *Stress, Physiological ; *beta-Fructofuranosidase/metabolism/genetics ; *Plants/enzymology/genetics ; *Plant Proteins/metabolism/genetics ; *Evolution, Molecular ; }, abstract = {Neutral/alkaline invertases (N/A-Invs) are crucial enzymes in sucrose metabolism, playing essential roles in plant growth, development, and stress responses. Unlike acidic invertases, N/A-Invs are localized in various subcellular compartments, including the cytoplasm, mitochondria, chloroplasts, and plastids, with distinct functions in each organelle. These enzymes regulate sugar homeostasis and are involved in key processes such as root development, carbon partitioning, and osmotic stress responses. Recent studies have identified two subfamilies of N/A-Invs, α and β, with the β subfamily being more conserved and primarily localized in the cytoplasm, whereas the α subfamily is associated with mitochondria and plastids. Despite significant advances, many aspects of N/A-Invs remain unclear, particularly their interaction with signaling pathways and their differential roles across plant species. Future research should focus on understanding the molecular mechanisms underlying N/A-Invs' regulation, their evolutionary history, and their potential applications in improving crop resilience and productivity. This growing body of knowledge promises to enhance our understanding of plant physiology and offer insights into agricultural biotechnology.}, } @article {pmid40389310, year = {2025}, author = {Nosek, J and Tomáška, Ľ}, title = {Hidden Treasures of the Genetic Systems in Yeast Mitochondria.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {17}, number = {12}, pages = {}, pmid = {40389310}, issn = {1943-0264}, mesh = {*Mitochondria/genetics ; Protein Biosynthesis ; *Saccharomyces cerevisiae/genetics ; Evolution, Molecular ; Open Reading Frames ; Genome, Mitochondrial ; *Genes, Mitochondrial ; Gene Expression Regulation, Fungal ; Ribosomes/metabolism ; *Yeasts/genetics ; }, abstract = {Mitochondria are the masters of evolutionary tinkering, which can be exemplified by both the remarkable variability of the mitochondrial genome architectures and numerous noncanonical features involved in the mitochondrial gene expression. Evolutionary experimentation in these living test tubes is facilitated by their polyploid nature and resulted in a number of surprising oddities identified in various eukaryotic lineages. Excellent examples of these peculiarities are provided by mitochondrial genetic systems of unicellular fungi classified as the budding yeasts. Perhaps the most perplexing eccentricity found in yeast mitochondria are the bypassing elements (byps) residing in the reading frames of protein-coding genes. Ribosomes ignore byps during translation by means of programmed translational bypassing. Massive occurrence of these coding gaps in certain yeast species raises the questions on their evolutionary origin and mobility as well as the molecular mechanism of translational bypassing.}, } @article {pmid40392717, year = {2025}, author = {Bryner, J}, title = {Hopeful Sunshine and Quantum Bubbles: The June 2025 issue of Scientific American is packed with exciting features, from magnificent mitochondria and a plan to refreeze the Arctic to the universe's first light and recent human evolution.}, journal = {Scientific American}, volume = {332}, number = {6}, pages = {4}, doi = {10.1038/scientificamerican062025-YZxzd1kSxUa63TFsqt7QZ}, pmid = {40392717}, issn = {0036-8733}, } @article {pmid40394395, year = {2025}, author = {Sekine, H and Akaike, T and Motohashi, H}, title = {Oxygen needs sulfur, sulfur needs oxygen: a relationship of interdependence.}, journal = {The EMBO journal}, volume = {44}, number = {12}, pages = {3307-3326}, pmid = {40394395}, issn = {1460-2075}, support = {18H05277//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 23H02672//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H05263//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K19397//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 23K20040//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 24H00063//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H04799//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H05258//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H05264//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 24H00605//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JPMJCR2024//MEXT | JST | Core Research for Evolutional Science and Technology (CREST)/ ; JP24gm6710026//Japan Agency for Medical Research and Development (AMED)/ ; }, mesh = {*Sulfur/metabolism ; *Oxygen/metabolism ; Humans ; Oxidation-Reduction ; Energy Metabolism ; Animals ; Bacteria/metabolism ; }, abstract = {Oxygen and sulfur, both members of the chalcogen group (group 16 elements), play fundamental roles in life. Ancient organisms primarily utilized sulfur for energy metabolism, while the rise in atmospheric oxygen facilitated the evolution of aerobic organisms, enabling highly efficient energy production. Nevertheless, all modern organisms, both aerobes and anaerobes, must protect themselves from oxygen toxicity. Interestingly, aerobes still rely on sulfur for survival. This dependence has been illuminated by the recent discovery of supersulfides, a novel class of biomolecules, made possible through advancements in technology and analytical methods. These breakthroughs are reshaping our understanding of biological processes and emphasizing the intricate interplay between oxygen and sulfur in regulating essential redox reactions. This review summarizes the latest insights into the biological roles of sulfur and oxygen, their interdependence in key processes, and their contributions to adaptive responses to environmental stressors. By exploring these interactions, we aim to provide a comprehensive perspective on how these elements drive survival strategies across diverse life forms, highlighting their indispensable roles in both human health and the sustenance of life.}, } @article {pmid40394897, year = {2025}, author = {Macdonald, JE and Ashby, PD}, title = {The molecular mechanism of ATP synthase constrains the evolutionary landscape of chemiosmosis.}, journal = {Biophysical journal}, volume = {124}, number = {13}, pages = {2103-2119}, pmid = {40394897}, issn = {1542-0086}, mesh = {Adenosine Triphosphate/metabolism ; *Proton-Translocating ATPases/metabolism/chemistry ; *Evolution, Molecular ; Models, Molecular ; Hydrolysis ; }, abstract = {ATP synthase, the enzyme responsible for regenerating adenosine triphosphate (ATP) in the cell, comprises a proton-translocating motor in the cell membrane (labeled FO in bacteria, mitochondria, and chloroplasts), coupled by a common stalk to a catalytic motor F1 that synthesizes or hydrolyzes ATP, depending on the direction of rotation. The detailed mechanisms of FO, F1 and their coupling in ATP synthase have been elucidated through structural studies, single-molecule experiments, and molecular modeling. The outcomes of this body of work are reviewed with a particular focus on the features of the mechanism that enable the high energy efficiency and reversibility of ATP synthase. Models for the origin of chemiosmosis involve either ATP synthesis (driven by the proton gradient across the membrane) or ATP hydrolysis (for pumping protons out of the cell) as a primary function, the other function being a later development enabled by the coupled nature of the two motors. The mechanism of ATP synthase and the stringent requirements on efficiency to maintain life constrain existing models and the search for the origin of chemiosmosis.}, } @article {pmid40396044, year = {2022}, author = {Kato, S and Tagaya, M}, title = {STX17: an ancient SNARE protein whose roles have not been conserved.}, journal = {Autophagy reports}, volume = {1}, number = {1}, pages = {14-16}, pmid = {40396044}, issn = {2769-4127}, abstract = {Mammalian STX17 (syntaxin 17) plays different cellular roles, including in mitochondrial fission, lipid droplet expansion and macroautophagy/autophagy, depending on the nutritional status. STX17 has a long C-terminal hydrophobic domain (CHD) with a hairpin-like structure, flanked by a basic amino acid-enriched C-terminal tail (C-tail). STX17 is present in a wide variety of eukaryotes, but has been lost in several lineages during evolution. Moreover, the structure of its C-tail remarkably varies, although the CHD is highly conserved. Recently, we compared the localization and function of fly and nematode Syx17/SYX-17 proteins expressed in mammalian cells with that of human STX17. Fly Syx17 expressed in mammalian cells localizes almost exclusively to the cytosol and translocates to autophagosomes upon starvation, whereas nematode SYX-17 is mainly distributed to mitochondria and promotes mitochondrial fission, but does not participate in autophagy. In vivo experiments showed that fly and nematode STX17 homologs are not involved in mitochondrial fission and autophagy, respectively. These results provide important insights into the localization and function of STX17, which acts as a molecular sensor for different nutritional conditions.}, } @article {pmid40398836, year = {2025}, author = {Chen, X and Chen, Z and Xu, Y and Zou, P and Shen, W and Zhang, Z and Wang, Y}, title = {Genome-wide identification of heat shock protein 90 family in Larimichthys crocea and expression analysis in response to thermal stress and Vibrio parahaemolyticus infection.}, journal = {Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology}, volume = {279}, number = {}, pages = {111112}, doi = {10.1016/j.cbpb.2025.111112}, pmid = {40398836}, issn = {1879-1107}, mesh = {Animals ; *Vibrio parahaemolyticus/physiology ; *HSP90 Heat-Shock Proteins/genetics/metabolism ; *Vibrio Infections/genetics/veterinary/metabolism ; *Perciformes/genetics/microbiology/metabolism ; *Fish Proteins/genetics/metabolism ; *Fish Diseases/genetics/microbiology/metabolism ; *Heat-Shock Response ; Gene Expression Regulation ; Phylogeny ; }, abstract = {Members of the heat shock protein 90 family (HSP90s) are evolutionarily conserved and play crucial roles in protein transport, immune regulation and antigen presentation. In this study, five hsp90s were identified from the genome of large yellow croaker (Larimichthys crocea) and analyzed using bioinformatics. All five identified hsp90s encode proteins with HATPase_c and HSP90 domains, and are mainly localized in the cytoplasm, mitochondria and endoplasmic reticulum. Chromosomal mapping revealed their distribution across three distinct chromosomes. Quantitative real-time PCR (qPCR) analysis showed differential expression patterns of the five hsp90s in 11 tissues. Additionally, their expression dynamics in the liver, spleen, head kidney, gill and blood were analyzed at 3 h, 12 h, 24 h and 48 h post thermal stress, Vibrio parahaemolyticus infection or under a combination of these two stressors. Results showed that the L. crocea hsp90s exhibited distinct expression patterns in response to the above three stimuli in different immune tissues. Notably, hsp90s in the spleen were most responsive. This study systematically clarified for the first time the gene structure characteristics, tissue expression patterns, and environmental stress response mechanisms of the HSP90 family in L. crocea. It confirmed that hsp90s show significant functional differentiation and synergy in response to biotic (pathogen infection) and abiotic (thermal stress) stresses, and provides important clues for a deeper understanding of the genetic basis of environmental adaptation in L. crocea.}, } @article {pmid40406718, year = {2025}, author = {Zhang, R and Liu, S and Liu, Y and Wei, P and Xiang, N and Zhao, Y and Gao, X and Yin, Y and Qin, L and Yuan, T}, title = {Comparative analysis of the organelle genomes of seven Rosa species (Rosaceae): insights into structural variation and phylogenetic position.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1584289}, pmid = {40406718}, issn = {1664-462X}, abstract = {INTRODUCTION: The genus Rosa belongs to the family Rosaceae within the order Rosales, which is one of the more ancient plant lineages. At present, the complete mitochondrial genome of Rosa spp. is still rarely reported, and studies on the mitochondrial genome of Rosa spp. are limited.

METHODS: In this study, the R. laevigata mitochondrial genome was sequenced using both Pacbio Sequel II and DNB-SEQ-T7 platforms. The second- and third-generation data for the other five Rosa species were downloaded from the NCBI database. Genome annotation was performed using Geneious, with structural visualization via CPGview. In-depth analyses were conducted, including assessments of non-synonymous/synonymous mutation ratios (Ka/Ks), codon usage bias, collinearity, and the identification of homologous fragments between chloroplast and mitochondrial genomes. Finally, we employed the maximum likelihood (ML) methods to analyze the phylogenetic relationships among R. laevigata and other Rosa species.

RESULTS: The chloroplast genome sizes ranged from 156,342 bp (R. laevigata) to 157,214 bp (R. agrestis). The GC content varied from 37.2% to 37.3%, and the number of genes ranged from 129 to 131. The mitochondrial genomes were all circular, with lengths between 271,191 bp and 338,975 bp, containing 52 to 59 genes. Codon usage analysis indicated a preference for A/T-ending codons in both chloroplast and mitochondrial genes. Four highly differentiated regions (rps19, ndhF, ycf1, and psbM-trnD-GUC) in the plastomes of the 7 Rosa species were identified, which can serve as molecular markers for future species identification and studies of genetic diversity. Compared to PCGs of plastome, mitochondrial PCGs displayed a higher non-synonymous to synonymous ratio. We also observed extensive gene transfer between the mitochondria and chloroplasts, particularly with the rrn16 and rpl23 genes, which are commonly found in Rosa species. These gene transfer events likely occurred in the ancestor of Rosa around 4.46 Mya. Estimates of divergence events indicate that rapid differentiation among Rosa species took place around 4.46 Mya, potentially influenced by the uplift of the Qinghai-Tibet Plateau during the Late Miocene.

DISCUSSION: This study enriches the genetic resources of the Rosa genus and lays the groundwork for the development of molecular markers, phylogenetic analyses, and research into the evolution of organelle genomes.}, } @article {pmid40419126, year = {2025}, author = {Bernier, D and Grafl, N and Gnauck, J and Betat, H and Dengler, S and Huc, I and Mörl, M}, title = {Armless hairpin-like tRNAs in Romanomermis culicivorax: Evolutionary adaptation of a mitochondrial elongation factor EF-Tu.}, journal = {The Journal of biological chemistry}, volume = {301}, number = {7}, pages = {110294}, pmid = {40419126}, issn = {1083-351X}, mesh = {*Peptide Elongation Factor Tu/metabolism/genetics/chemistry ; Animals ; *Evolution, Molecular ; *RNA, Transfer/chemistry/metabolism/genetics ; Nucleic Acid Conformation ; *Mitochondria/metabolism/genetics ; Mitochondrial Proteins/metabolism/genetics/chemistry ; }, abstract = {tRNAs are central players in translation, delivering cognate amino acids to the ribosome. To fulfill this essential function, secondary and tertiary structures of tRNAs are highly conserved. In metazoan, however, several mitochondrial tRNAs show strong structural deviations and lack D- or T-arms. As these elements are important for the interaction with tRNA-binding proteins, these proteins are adapted to recognize such unusual targets. A prominent example is mitochondrial EF-Tu, delivering aminoacylated tRNAs to the ribosome. In nematode mitochondria, two variants of mt-EF-Tu exist. While mt-EF-Tu2 is specific for D-armless mt-tRNA[Ser], mt-EF-Tu1 recognizes the remaining 20 tRNAs. The most bizarre mt-tRNAs are found in Romanomermis culicivorax, where hairpin-like structures were described lacking both D- and T-arm. To ensure functional translation with such extremely reduced tRNAs, the corresponding mt-EF-Tu1 must have undergone a further adaptation. In a comparative analysis, the tRNA-binding behavior of recombinant mitochondrial EF-Tu1 versions from several nematodes was investigated. They all carry a C-terminal extension that is required for an efficient interaction with non-canonical tRNAs. Furthermore, in mt-EF-Tu1 from R. culicivorax and Caenorhabditis elegans, a basic residue in domain III was identified that represents an additional adaptation in the transition from canonical towards hairpin-like tRNA substrates. The results indicate that nematode mt-EF-Tu1 proteins are in principle able to interact with hairpin-like tRNAs, although such transcripts are only found in some of these species. Hence, concerning mt-EF-Tu, the evolutionary stage is set for a further truncation of mitochondrial tRNAs towards armless structures.}, } @article {pmid40427588, year = {2025}, author = {Luo, Y and Bähler, J and Huang, Y}, title = {The Insertion Domain of Mti2 Facilitates the Association of Mitochondrial Initiation Factors with Mitoribosomes in Schizosaccharomyces pombe.}, journal = {Biomolecules}, volume = {15}, number = {5}, pages = {}, pmid = {40427588}, issn = {2218-273X}, support = {302608/Z/23/Z//Wellcome Discovery Award/ ; }, mesh = {*Schizosaccharomyces/metabolism/genetics ; *Schizosaccharomyces pombe Proteins/metabolism/genetics/chemistry ; *Mitochondrial Proteins/metabolism/genetics/chemistry ; *Mitochondrial Ribosomes/metabolism ; *Mitochondria/metabolism/genetics ; Protein Domains ; *Peptide Initiation Factors/metabolism/genetics/chemistry ; }, abstract = {Translation initiation in mitochondria involves unique mechanisms distinct from those in the cytosol or in bacteria. The Schizosaccharomyces pombe mitochondrial translation initiation factor 2 (Mti2) is the ortholog of human MTIF2, which plays a vital role in synthesizing proteins in mitochondria. Here, we investigate the insertion domain of Mti2, which stabilizes its interaction with the ribosome and is crucial for efficient translation initiation. Our results show that the insertion domain is critical for the proper folding and function of Mti2. The absence of the insertion domain disrupts cell growth and affects the expression of genes encoded by mitochondrial DNA. Additionally, we show that Mti2 physically interacts with the small subunits of mitoribosomes (mtSSU), and deletion of the insertion domain dissociates mitochondrial initiation factors from the mitoribosome, reducing the efficiency of mitochondrial translation. Altogether, these findings highlight the conserved role of the insertion domain in facilitating translation initiation in fission yeast and thus reveal shared principles of mitochondrial translation initiation in both fission yeast and humans.}, } @article {pmid40432501, year = {2025}, author = {Macdonald, JR and Arnold, MS and Luth, MR and Cihalova, D and Quinn, RJ and Winzeler, EA and Lee, MC and van Dooren, GG and Maier, AG and Skinner-Adams, TS and Andrews, KT and Fisher, GM}, title = {Inner-mitochondrial membrane protein PfMPV17 is linked to P. falciparum in vitro resistance to the indoloquinolizidine alkaloid alstonine.}, journal = {The Journal of antimicrobial chemotherapy}, volume = {80}, number = {7}, pages = {1869-1877}, pmid = {40432501}, issn = {1460-2091}, support = {T32 GM008666MRL//National Institute for General Medical Sciences/ ; //Commonwealth Government Research Training programme/ ; //Ruth L. Kirschstein Institutional National Research Award/ ; R01 AI152533/AI/NIAID NIH HHS/United States ; //Griffith University GRIDD ECR/ ; GNT1182369//National Health and Medical Research Council/ ; INV-039628//Bill & Melinda Gates Foundation/ ; //Griffith University Postgraduate Research Scholarship/ ; R01 AI169892/AI/NIAID NIH HHS/United States ; /NH/NIH HHS/United States ; T32 GM008666/GM/NIGMS NIH HHS/United States ; 1R01AI152533//Bill & Melinda Gates Foundation/ ; }, mesh = {*Plasmodium falciparum/drug effects/genetics ; *Drug Resistance/genetics ; *Antimalarials/pharmacology ; *Protozoan Proteins/genetics/metabolism ; Mitochondria/metabolism/drug effects ; Humans ; *Quinolizidines/pharmacology ; *Mitochondrial Proteins/genetics/metabolism ; Whole Genome Sequencing ; Alkaloids/pharmacology ; Mutation ; }, abstract = {BACKGROUND: There are an estimated 260 million malaria cases and ∼600 000 deaths annually. Challenges to malaria eradication include the lack of highly effective and broadly applicable vaccines and parasite drug resistance. This is driving the need for new tools, including novel drugs and drug targets. The indoloquinolizidine alkaloid alstonine was previously shown to have in vitro activity against Plasmodium falciparum malaria parasites and a slow-action activity that is different from other slow-action antiplasmodial compounds such as clindamycin.

OBJECTIVES: To investigate the action of the antiplasmodial compound alstonine by validating a putative resistance mutation and determining whether the activity of alstonine is linked to the mitochondrial electron transport chain.

MATERIALS AND METHODS: In vitro evolution of resistance was used to generate alstonine-resistant P. falciparum, followed by whole-genome sequencing and CRISPR/Cas9 gene editing of wildtype parasites to validate a putative resistance-associated mutation. Links to mitochondrial function were assessed using oxygen consumption rate measurements and activity of alstonine in P. falciparum expressing the yeast dihydroorotate dehydrogenase.

RESULTS: P. falciparum parasites were selected with ∼20-fold reduced sensitivity to alstonine compared to wild-type parasites. Whole-genome sequencing of alstonine-resistant P. falciparum sub-clones identified several mutations including a copy number variation and point mutation (A318P) in a gene encoding a putative inner-mitochondrial membrane protein (PfMPV17). Introduction of the A318P mutation into the PfMPV17 gene in wild-type P. falciparum yielded parasites with reduced alstonine sensitivity. While a direct link between alstonine action and mitochondrial respiratory function was not found, a transgenic P. falciparum line resistant to the cytochrome bc1 inhibitor atovaquone and pyrimidine synthesis inhibitor DSM265 had reduced sensitivity to alstonine.

CONCLUSIONS: These data demonstrate that PfMPV17 is linked to alstonine resistance and suggest that alstonine action is linked to the mitochondria and/or pyrimidine biosynthesis pathways.}, } @article {pmid40441921, year = {2025}, author = {Liu, F and Zhao, Z and Fernie, AR and Zhang, Y}, title = {Towards establishing functional nitrogenase activities within plants.}, journal = {Trends in biotechnology}, volume = {43}, number = {11}, pages = {2698-2708}, doi = {10.1016/j.tibtech.2025.04.020}, pmid = {40441921}, issn = {1879-3096}, mesh = {*Nitrogenase/metabolism/genetics ; Nitrogen Fixation ; *Plants/enzymology ; Synthetic Biology ; Nitrogen/metabolism ; *Protein Engineering/methods ; }, abstract = {Biological nitrogen fixation, catalyzed by nitrogenase, can convert atmospheric N2 into NH3 for plant growth. Legumes form symbioses with nitrogen-fixing bacteria, but non-legumes rely on excessive nitrogen fertilizers. Efforts to engineer nitrogenase in non-legumes face major challenges, including oxygen sensitivity, metal cluster assembly complexity, and high energy demands. Nonetheless, advances in synthetic biology, and artificial intelligence (AI)-driven design - shown by partial nitrogenase reconstitution in Escherichia coli and yeast - offer promising solutions. Engineering nitrogenase in yeast mitochondria under low-oxygen conditions also helps circumvent oxygen constraints. Fully overcoming energy costs and feedback loops responsive to nitrogen levels could yield nitrogen-fixing crops, transforming sustainable agriculture and ensuring global food security. Such breakthroughs would reduce fertilizer dependence, cut pollution, and stabilize yields in diverse farming systems.}, } @article {pmid40444636, year = {2025}, author = {Tanouti, Y and Roovers, M and Wolff, P and Lechner, A and Van Elder, D and Feller, A and Soin, R and Gueydan, C and Kruys, V and Droogmans, L and Labar, G}, title = {Structural insight into the novel Thermus thermophilus SPOUT methyltransferase RlmR catalysing Um2552 formation in the 23S rRNA A-loop: a case of convergent evolution.}, journal = {Nucleic acids research}, volume = {53}, number = {10}, pages = {}, pmid = {40444636}, issn = {1362-4962}, support = {//Fonds de la Recherche Scientifique - FNRS/ ; //Fonds Jean Brachet/ ; //French National Program Investissement d'Avenir/ ; ANR-10-LABX-0036_NETRNA//Agence Nationale de la Recherche/ ; //Interdisciplinary Thematic Institute IMCBio/ ; //University of Strasbourg/ ; ANR-10-IDEX-0002//IdEx Unistra/ ; ANR-20-SFRI-0012//IdEx Unistra/ ; ANR-17-EURE-750023//IdEx Unistra/ ; 20210875//French Investments for the Future Program/ ; 20232022//French Investments for the Future Program/ ; //Institut de Recherche LABIRIS-Commission communautaire française-COCOF/ ; }, mesh = {*Thermus thermophilus/enzymology/genetics ; *RNA, Ribosomal, 23S/chemistry/metabolism/genetics ; *Methyltransferases/chemistry/metabolism/genetics ; Evolution, Molecular ; Humans ; Nucleic Acid Conformation ; Escherichia coli/genetics ; Models, Molecular ; *Bacterial Proteins/chemistry/metabolism/genetics ; Crystallography, X-Ray ; Methylation ; }, abstract = {The A-loop of the 23S ribosomal RNA is a critical region of the ribosome involved in stabilizing the CCA-end of A-site-bound transfer RNA. Within this loop, nucleotide U2552 is frequently 2'-O-methylated (Um2552) in various organisms belonging to the three domains of life. Until now, two enzymatic systems are known to modify this position, relying on either a Rossmann fold-like methyltransferase (RFM) or a small RNA-guided system. Here, we report the identification of a third system involved in Um2552 formation, consisting of a methyltransferase of the SPOUT (SpoU-TrmD) superfamily encoded by the ttc1712 open reading frame of Thermus thermophilus, herein renamed RlmR. In Escherichia coli and human mitochondria, the absence of the RFM enzyme responsible for Um2552 formation is known to cause severe defects in ribogenesis and ribosome function. In contrast, no comparable effect was observed upon ttc1712 gene invalidation in T. thermophilus. We also report the high-resolution crystal structure of RlmR in complex with a 59-mer substrate RNA. The structure highlights significant conformational rearrangements of the A-loop and provides a new insight into the catalytic mechanism, revealing structural features that may be generalized to other SpoU methyltransferases.}, } @article {pmid40451764, year = {2025}, author = {Zhu, W and Wu, J and Kang, Y and Xue, P}, title = {Cu2O/CuVO3 Nano-Heterojunction as a Highly Active Therapeutic Catalyst for Aggravating Redox Dyshomeostasis of Neoplastic Cells.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {37}, number = {33}, pages = {e2502407}, doi = {10.1002/adma.202502407}, pmid = {40451764}, issn = {1521-4095}, support = {2024YFFK0249//Key Research and Development Project of Sichuan Provincial Science and Technology Plan/ ; KFKT202405//Open Research Project from Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment/ ; 2023YFF0713900//National Key Research and Development Program of China/ ; XNDX2022020013//Shuangcheng Cooperative Agreement Research Grant of Yibin/ ; KJQN202400202//Scientific and Technological Research Program of Chongqing Municipal Education Commission/ ; }, mesh = {*Copper/chemistry/pharmacology ; Oxidation-Reduction/drug effects ; Humans ; Catalysis ; Animals ; Mice ; Cell Line, Tumor ; *Homeostasis/drug effects ; *Antineoplastic Agents/chemistry/pharmacology/therapeutic use ; *Neoplasms/drug therapy/pathology/metabolism ; Reactive Oxygen Species/metabolism ; Apoptosis/drug effects ; Mitochondria/drug effects/metabolism ; Hydroxyl Radical/metabolism ; Density Functional Theory ; }, abstract = {Redox dyshomeostasis is both a hallmark and a vulnerability of cancer cells, offering multiple avenues for therapeutic intervention. Herein, a belt-like nano-heterojunction Cu2O/CuVO3 (CVO) is developed as a potential redox dyshomeostasis inducer by exacerbating ROS levels and compromising antioxidant defense without the need of exogenous stimulations. Steady-state analysis reveals that CVO exhibits extraordinary reaction velocity and catalytic efficiency (Vmax = 2.32 µm s[-1], Kcat = 0.49 s[-1]) in the production of hydroxyl radicals (·OH). Likewise, density functional theory (DFT) calculations indicate that the superb charge-transferring properties in the heterojunction structure and unique surface coverage rate of CVO primarily dominate the high-efficient catalytic reactions. Noteworthy, CVO is capable of inducing mitochondria dysfunction by aggravating the cellular redox imbalance, thereby triggering multiple cell death pathways and generating synergistic effects. Transcriptomics analysis outcomes further demonstrate that CVO exerts significant and distinct effects on key biological processes in tumor cells, encompassing but not limited to canonical pathways such as apoptosis, ferroptosis, and cuprotosis. Both in vitro and in vivo studies demonstrate the pronounced tumor-inhibitory efficacy of CVO, which paves a promising pathway for the development of novel nanocatalysts that effectively target cancer through the amplification of redox dyshomeostasis.}, } @article {pmid40456292, year = {2025}, author = {Dormegny-Jeanjean, LC and Lenoir, S and Humbert, I and Mainberger, OAE and Lozere, C and Meyer, C and Geny, B and Michel, B and Foucher, JR and de Crespin de Billy, C}, title = {Cardiovascular Effects of Non-Selective Monoamine Oxidase Inhibitors and Intranasal Esketamine Combination in Depression - A Quasi-Experimental Design with Bayesian Analyses.}, journal = {Pharmacopsychiatry}, volume = {58}, number = {6}, pages = {273-283}, doi = {10.1055/a-2590-3469}, pmid = {40456292}, issn = {1439-0795}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Administration, Intranasal ; *Antidepressive Agents/administration & dosage/adverse effects ; Bayes Theorem ; *Blood Pressure/drug effects ; *Depressive Disorder, Treatment-Resistant/drug therapy ; Drug Therapy, Combination ; Heart Rate/drug effects ; *Ketamine/administration & dosage/adverse effects/pharmacology/therapeutic use ; *Monoamine Oxidase Inhibitors/administration & dosage/adverse effects/pharmacology/therapeutic use ; }, abstract = {Ketamine and esketamine (ESK) offer new treatment options for resistant depression. Unlike traditional antidepressants, they can be used in combination with non-selective monoamine oxidase inhibitors (NS-MAOI) without the risk of serotonergic syndrome. However, potential sympathomimetic synergy may lead to elevated blood pressure (BP). This series investigates whether cardiovascular parameters (heart rate, systolic [SP], and diastolic [DP] pressures) increase during ESK sessions and whether the ESK+NS-MAOI combination is associated with BP elevations.We collected cardiovascular parameters for ESK sessions conducted between 2018 and 2022. These parameters were measured at baseline and every 30 min for 2 h. Patients were categorized into two non-equivalent groups: those receiving ESK alone and those receiving ESK+NS-MAOI. A Bayesian random model was used to estimate the evolution of these parameters, while a Bayesian hierarchical model assessed factors contributing to BP elevation.ESK sessions (n=193), of which 116 involved NS-MAOI, were performed in 13 patients. SP, DP, and heart rate showed peak increases during sessions, but these changes were not clinically significant (SP+8.68 mmHg, DP+6.57 mmHg, and heart rate+3.5 bpm). No significant differences were found between the ESK-alone and ESK+NS-MAOI groups. The combination was not identified as a factor linked to BP elevations.These findings align with previous research on ketamine derivatives and suggest minimal peripheric sympathomimetic synergy with NS-MAOI. Bayesian models were used to account for biases intrinsically related to these ecological data and provide a foundation for future open adversarial collaborations. Registration NCT05530668.}, } @article {pmid40461783, year = {2026}, author = {Chen, L and Hong, M and Luan, C and Yuan, M and Wang, Y and Guo, X and Fang, Y and Huang, H and Dong, X and Gao, H and Zhang, D and Chen, X and Meng, D and Huang, M and Yi, Z and Liu, M and Wei, W and Gao, L and Song, G and Zhou, X and Li, D}, title = {Efficient mitochondrial A-to-G base editors for the generation of mitochondrial disease models.}, journal = {Nature biotechnology}, volume = {44}, number = {3}, pages = {418-429}, pmid = {40461783}, issn = {1546-1696}, support = {No.32025023//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; Humans ; *DNA, Mitochondrial/genetics ; Rats ; *Gene Editing/methods ; *Mitochondrial Diseases/genetics ; *Mitochondria/genetics ; Disease Models, Animal ; }, abstract = {Existing A-to-G base editors for mitochondrial DNA (mtDNA) are limited by low efficiency. We used directed evolution to discover variants of the TadA-8e base editors that have substantially increased activity and expanded targeting compatibility for both nuclear and mitochondrial adenine base editing, especially in previously unfavored sequence contexts. The engineered mtDNA editors (eTd-mtABEs) showed up to 87% editing efficiency in human cells, with greatly reduced DNA and RNA off-target effects. Strand-selective A-to-G editing was enhanced by an average of 3.2-fold with substitution of DddA to DNA nickases in eTd-mtABE backbones compared to mitochondrial ABEs. In rat cells, editing efficiencies of eTd-mtABEs were up to 145-fold higher compared to split DddA transcription activator-like effector-linked deaminase. We also generated rats with sensorineural hearing loss by installing targeted mutations with frequencies of up to 44% through embryonic injection. The developed eTd-mtABEs are efficient and precise mtDNA-engineering tools for basic research and translational studies.}, } @article {pmid40463036, year = {2025}, author = {Xu, P and Mancuso, RI and Leonzino, M and Zeiss, CJ and Krause, DS and De Camilli, P}, title = {Defect in hematopoiesis and embryonic lethality at midgestation of Vps13a/Vps13c double knockout mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40463036}, issn = {2692-8205}, support = {P30 DA018343/DA/NIDA NIH HHS/United States ; U54 DK106857/DK/NIDDK NIH HHS/United States ; R01 NS036251/NS/NINDS NIH HHS/United States ; S10 OD030363/OD/NIH HHS/United States ; R37 NS036251/NS/NINDS NIH HHS/United States ; }, abstract = {VPS13 is the founding member of a family of proteins that mediate lipid transfer at intracellular membrane contact sites by a bridge-like mechanism. Mammalian genomes comprise 4 VPS13 genes encoding proteins with distinct localizations and function. The gene duplication resulting in VPS13A and VPS13C is the most recent in evolution and, accordingly, these two proteins are the most similar to each other. However, they have distinct subcellular localizations and their loss of function mutations in humans are compatible with life but result in two different age-dependent neurodegenerative diseases, chorea-acanthocytosis and Parkinson's disease, respectively. Thus, it remains unclear whether these two proteins have overlapping functions. Here, we show that while Vps13a KO and Vps13c KO mice are viable, embryonic development of Vps13a/Vps13c double knockout (DKO) mice is arrested at midgestation. Prior to death, DKO embryos were smaller than controls, were anemic and had a smaller liver, the key erythropoietic site at this developmental stage. Further analyses of erythroid precursor cells showed that their differentiation was impaired and that this defect was accompanied by activation of innate immunity as revealed by upregulation of interferon stimulated genes (ISGs). Additionally, the RIG-I and MDA5 components of dsRNA triggered innate immunity were found upregulated in the DKO fetal liver. Activation of innate immunity may result from loss of integrity of the membranes of intracellular organelles, such as mitochondria and autophagic lysosomes, due to the absence of these lipid transport proteins. The surprising and striking synthetic effect resulting for the combined loss of VPS13A and VPS13C suggests that despite of the different localization of these two proteins, the lipid fluxes that they mediate are partially redundant.}, } @article {pmid40464854, year = {2025}, author = {Gruber, A and Vohnoutová, M and McKay, C and Rocap, G and Oborník, M}, title = {ASAFind 2.0: multi-class protein targeting prediction for diatoms and algae with complex plastids.}, journal = {The Plant journal : for cell and molecular biology}, volume = {122}, number = {5}, pages = {e70138}, pmid = {40464854}, issn = {1365-313X}, support = {//Parazitologický ústav, Akademie Věd České Republiky/ ; //National Science Foundation/ ; LM2023055//Ministry of Education, Youth and Science/ ; 21-26115S//Czech Science Foundation/ ; 23-06203S//Czech Science Foundation/ ; }, mesh = {*Diatoms/metabolism/genetics ; *Plastids/metabolism ; Proteome ; Rhodophyta/metabolism ; *Algal Proteins/metabolism ; *Software ; *Computational Biology/methods ; }, abstract = {Plastids of diatoms and related algae with complex plastids of red algal origin are surrounded by four membranes, which also define the periplastidic compartment (PPC), the space between the second and third membranes. Metabolic reactions as well as cell biological processes take place in the PPC; however, genome-wide predictions of the proteins targeted to this compartment were so far based on manual annotation work. Using published experimental protein localizations as reference data, we developed the first automatic prediction method for PPC proteins, which we included as a new feature in an updated version of the plastid protein predictor ASAFind. With our method, at least a subset of the PPC proteins can be predicted with high specificity, with an estimate of at least 81 proteins (0.7% of the predicted proteome) targeted to the PPC in the model diatom Phaeodactylum tricornutum. The proportion of PPC proteins varies, since 180 PPC proteins (1.3% of the predicted proteome) were predicted in the genome of the diatom Thalassiosira pseudonana. The new ASAFind version can also generate a newly designed graphical output that visualizes the contribution of each position in the sequence to the score and accepts the output of the recent versions of SignalP (5.0) and TargetP (2.0) as input data. Furthermore, we release a script to calculate custom scoring matrices that can be used for predictions in a simplified score cut-off mode. This allows for adjustments of the method to other groups of algae.}, } @article {pmid40471698, year = {2025}, author = {Eddo, D and Hodur, Z and Wang, S}, title = {The Hidden Figures at Species Boundaries: The Mitochondrial Energetics Behind Mating Signal Divergence.}, journal = {Integrative and comparative biology}, volume = {65}, number = {2}, pages = {472-480}, doi = {10.1093/icb/icaf058}, pmid = {40471698}, issn = {1557-7023}, support = {//SUNY Research Foundation/ ; }, mesh = {Animals ; *Mitochondria/genetics/physiology/metabolism ; *Energy Metabolism ; *Genetic Speciation ; *Sexual Behavior, Animal ; Gene Flow ; Hybridization, Genetic ; *Animal Communication ; }, abstract = {The energy expenditures of mating signals are often divergent between species and influence heterospecific mating, thus mediating the direction of gene flow across the species boundaries. The relative energetics of the mating signals can be underpinned by mitochondrial haplotype divergence between species, which contributes to hybrid mitonuclear incompatibility and speciation. Here, we discuss the connection between mitochondrial variation, mating signal energetics, and their impact on gene flow across the species boundaries. Using multiple case studies, we highlighted the connections between mitochondrial functions, mating signal energetics, and hybridization across visual, acoustic, kinesthetic, and chemosensory signaling modalities. Integrating mitochondrial functions and mating signal energetics at the species boundaries will illuminate the organismal mechanisms underlying the formation and maintenance of species boundaries.}, } @article {pmid40474826, year = {2025}, author = {Yang, X and Zhou, Y and Zhang, B and Tao, X and Qi, W and Wu, H}, title = {Irradiation-induced increase in nuclear p62 levels contributes to chromosomal fragmentation and chromothripsis.}, journal = {International journal of surgery (London, England)}, volume = {111}, number = {8}, pages = {5660-5663}, doi = {10.1097/JS9.0000000000002643}, pmid = {40474826}, issn = {1743-9159}, mesh = {Humans ; *Chromothripsis/radiation effects ; *Chromosomal Instability/radiation effects ; *Neoplasms/radiotherapy/genetics ; *Cell Nucleus/radiation effects/metabolism ; *Sequestosome-1 Protein/metabolism ; }, abstract = {Chromosomal instability (CIN) is a hallmark of cancer, closely associated with tumor evolution, metastasis, immune evasion, and resistance to treatment. CIN is driven by persistent chromosome missegregation, resulting in abnormal chromosomal copy numbers and promoting tumor progression through mitotic errors, faulty chromosome segregation, and the formation of micronuclei or chromosome bridges. Previous studies have demonstrated that p62 localizes to micronuclei, where it interacts with mitochondria, enhancing reactive oxygen species-mediated cysteine oxidation and promoting p62 homo-oligomerization. This disrupts repair by recruiting CHMP7 and other ESCRT-III components, impairing their function in restoring the micronuclear envelope. Notably, we observed a time-dependent increase in nuclear p62 levels following radiation therapy, which correlated with enhanced chromatin fragmentation and chromothripsis. While p62 inhibits homologous recombination repair and promotes non-homologous end joining, we hypothesize that radiation-induced nuclear p62 accumulation impairs nuclear envelope resealing by inhibiting ESCRT-III components, thereby contributing to chromosomal fragmentation and chromothripsis. These chromosomal alterations may play a significant role in tumor evolution and treatment resistance. Our findings suggest that irradiation-induced p62 accumulation is crucial for chromothripsis and may affect nuclear repair processes, impacting chromosomal stability. Future research will focus on elucidating how p62 contributes to these abnormalities and their implications for tumor progression and treatment resistance.}, } @article {pmid40481010, year = {2025}, author = {Tao, A and Tao, J and Gan, Z and Zhang, Y and Yin, C and Jiang, G}, title = {The characterisation of the complete mitochondrial genome of Polygonatum Kingianum reveals recombination mediated by repeats associated with DNA replication.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {19980}, pmid = {40481010}, issn = {2045-2322}, support = {NO. 202301AT070898, NO. 202101AT070001//Ai-en Tao/ ; }, mesh = {*Genome, Mitochondrial ; *DNA Replication/genetics ; *Polygonatum/genetics ; DNA, Mitochondrial/genetics ; Phylogeny ; *Recombination, Genetic ; RNA, Transfer/genetics ; *Repetitive Sequences, Nucleic Acid ; }, abstract = {Polygonatum kingianum Coll et Hemsl (P. kingianum) is recognized as one of the most valuable medicinal species, demonstrating a diverse range of bioactivities, including antidiabetic effects, reduction of blood lipids, anti-tumor properties, and hyperglycemic activity. However, the mitochondrial genome of P. kingianum has not yet been reported. Therefore, we sequenced and assembled the mitochondrial DNA (mtDNA) of P. kingianum. The results indicate that the mitochondrial genome possesses a multi-branched conformational structure. Further annotation of the mitochondrial genome reveals that it is 647,110 bp in length, containing a total of 35 distinct protein-coding genes, 22 tRNA genes, and 4 rRNA genes. The analysis of gene loss revealed that a total of seven genes were absent in the mitochondrial genome of P. kingianum. This includes six ribosomal protein genes (rpl2, rpl6, rpl10, rps7, rps8, rps11) and two succinate dehydrogenase genes (sdh3 and sdh4), as well as one pseudogene. Furthermore, Analysis of mitochondrial genome coding sequences of ten closely related species revealed a total of 24 shared genes. The Ka/Ks values of all shared coding protein genes are less than 1, indicating that these genes have undergone purification selection during evolution and their protein functions are relatively stable. In addition, codon studies on P. kingianum mitochondria showed 29 high-frequency codons (RSCU > 1). The preference for codon usage is influenced by mutations and natural selection, but mainly determined by natural selection. Furthermore, we identified 31 homologous fragments spanning both chloroplast and mitochondrial genomes and 585 C-to-U RNA editing sites were predicted in mitochondrial PCGs. The phylogenetic tree established a close relationship between P. kingianum and the 27 closely related species. To sum up, this study will contribute to the application of population genetics and evolutionary research in the genus Polygonatum and other genera in the Asparagales family.}, } @article {pmid40490602, year = {2025}, author = {Lerouley, O and Larrieu, I and Ducrocq, TL and Pinson, B and Giraud, MF and Mourier, A}, title = {An alternative mechanism by which If1 prevents ATP hydrolysis by the ATP synthase subcomplex in S. cerevisiae.}, journal = {EMBO reports}, volume = {26}, number = {13}, pages = {3305-3326}, pmid = {40490602}, issn = {1469-3178}, support = {ANR-22-CE14-0040//Agence Nationale de la Recherche (ANR)/ ; AAPPF2021-2020-12000110//Region Nouvelle Aquitaine/ ; MetabOptic 2022-24564910//Region Nouvelle Aquitaine/ ; COMUNCAN//SIRIC BRIO/ ; SBM-AAPG-2024//Université de Bordeaux (University of Bordeaux)/ ; }, mesh = {*Adenosine Triphosphate/metabolism ; Hydrolysis ; *Saccharomyces cerevisiae/metabolism/genetics/enzymology ; *Saccharomyces cerevisiae Proteins/metabolism/genetics ; Mitochondria/metabolism ; *Mitochondrial Proton-Translocating ATPases/metabolism/genetics ; Hydrogen-Ion Concentration ; }, abstract = {The mitochondrial F1F0-ATP synthase is crucial for maintaining the ATP/ADP balance which is critical for cell metabolism, ion homeostasis and cell proliferation. This enzyme, conserved across evolution, is found in the mitochondria or chloroplasts of eukaryotic cells and the plasma membrane of bacteria. In vitro studies have shown that the mitochondrial F1F0-ATP synthase is reversible, capable of hydrolyzing instead of synthesizing ATP. In vivo, its reversibility is inhibited by the endogenous peptide If1 (Inhibitory Factor 1), which specifically prevents ATP hydrolysis in a pH-dependent manner. Despite its presumed importance, the loss of If1 in various model organisms does not cause severe phenotypes, suggesting its role may be confined to specific stress or metabolic conditions yet to be discovered. Our analyses indicate that inhibitory peptides are crucial in mitigating mitochondrial depolarizing stress under glyco-oxidative metabolic conditions. Additionally, we found that the absence of If1 destabilizes the nuclear-encoded free F1 subcomplex. This mechanism highlights the role of If1 in preventing harmful ATP wastage, offering new insights into its function under physiological and pathological conditions.}, } @article {pmid40494286, year = {2025}, author = {Sprecher, BN and Johnson, MD}, title = {Kleptoplasty: Letting the cart lead the horse.}, journal = {Current biology : CB}, volume = {35}, number = {11}, pages = {R414-R417}, doi = {10.1016/j.cub.2025.04.068}, pmid = {40494286}, issn = {1879-0445}, mesh = {*Dinoflagellida/physiology/genetics ; Animals ; *Chloroplasts/physiology/metabolism ; *Plastids/physiology ; Photosynthesis/genetics ; Mitochondria ; Biological Evolution ; }, abstract = {Some chloroplast-stealing dinoflagellates remodel their kleptoplastids, form an extensive network with stollen mitochondria, and likely benefit from photosynthetic genes that they inherited or acquired from prey. These adaptations allow these protists to exploit kleptoplastids for months and shed light on past plastid acquisitions.}, } @article {pmid40509562, year = {2025}, author = {Terraza-Silvestre, E and Bandera-Linero, J and Oña-Sánchez, D and Pimentel-Muiños, FX}, title = {Unconventional role of ATG16L1 in the control of ATP compartmentalization during apoptosis.}, journal = {Autophagy}, volume = {21}, number = {9}, pages = {2085-2087}, pmid = {40509562}, issn = {1554-8635}, mesh = {*Autophagy-Related Proteins/metabolism ; *Apoptosis/physiology ; Humans ; *Adenosine Triphosphate/metabolism ; Autophagy ; Animals ; Autophagosomes/metabolism ; }, abstract = {The autophagy mediator ATG16L1 forms part of a complex that is essential for MAP1LC3/LC3 lipidation and autophagosome formation in the canonical macroautophagic/autophagic pathway. However, ATG16L1 is also involved in unconventional activities where LC3 becomes lipidated in single-membrane structures unrelated to double-membrane autophagosomes. Such atypical activities usually require the C-terminal domain of the molecule that includes 7 WD40-type repetitions (WD40 domain, WDD). The WDD acts as a docking site for upstream inducers that engage the LC3 lipidation ability of ATG16L1 in alternative membrane compartments. Given that this domain is absent in the yeast Atg16 ortholog, an intriguing idea proposes that it was added to the primitive protein during evolution to perform new physiological roles required by the appearance of multicellularity. Identification of such atypical activities and their physiological implications at the organismal level are important issues that remain to be clarified. In a recent report we describe an unconventional autophagic pathway that restrains the immunogenic potential of apoptosis, a key feature of homeostatic and developmentally regulated cell death in multicellular organisms. This signaling route emanates from apoptotic mitochondria and induces the formation of single-membrane, LC3-positive vesicles through a mechanism that requires the WDD of ATG16L1. The induced vesicles sequester ATP to inhibit the amount of ATP released from apoptotic cells and, consequently, prevent the activation of co-cultured phagocytes. Thus, this is a pathway that contributes to maintain the immunosilent nature of apoptotic cell death.}, } @article {pmid40509913, year = {2025}, author = {Gonçalves, LT and Pezzi, PH and Deprá, M and Françoso, E}, title = {Mitonuclear Coevolution in Bumblebees (Bombus): Genomic Signatures and Its Role in Climatic Niche Adaptation.}, journal = {Genome biology and evolution}, volume = {17}, number = {7}, pages = {}, pmid = {40509913}, issn = {1759-6653}, support = {//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; //Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; //CAPES/PRINT/ ; }, mesh = {Animals ; Bees/genetics/physiology ; *Evolution, Molecular ; Cell Nucleus/genetics ; *Mitochondria/genetics ; DNA, Mitochondrial/genetics ; Phylogeny ; Adaptation, Physiological/genetics ; Climate ; }, abstract = {Mitochondria play a central role in cellular respiration, but require close coevolution with the nuclear genome for proper function. This process, termed mitonuclear coevolution, is poorly understood on species-level evolutionary timescales, despite its role in speciation. Here, we investigate mitonuclear coevolution in bumblebees (Bombus), a group of ecologically diverse pollinators with rapid mitochondrial (mt) DNA evolution. Leveraging genomic data from a comprehensive set of 55 bumblebee species, we quantified the evolutionary rate correlation (ERC) between mt genes and nuclear genes that interact with mitochondria (N-mt). We found a strong ERC between mt and N-mt genes, but not among mt genes and random nuclear genes, supporting the mitonuclear coevolution hypothesis. Additionally, we found the strength of mitonuclear ERC seems to be consistent across bumblebee lineages, contrasting with observations in other taxa. Finally, bumblebee species from colder environments showed increased mt evolutionary rates relative to both N-mt genes and random nuclear genes. This suggests potential implications to bumblebee climatic niche adaptation and the thermoregulation of cold-adapted species, possibly driven by selection for enhanced mt function to sustain thermogenesis and flight in low-temperature environments. Our findings are discussed considering the dynamics of mitonuclear coevolution in bumblebees and its potential role in shaping their adaptation to diverse ecological niches.}, } @article {pmid40517085, year = {2025}, author = {Schoenle, A and Francis, O and Archibald, JM and Burki, F and de Vries, J and Dumack, K and Eme, L and Florent, I and Hehenberger, E and Hoffmeyer, TT and Irisarri, I and Lara, E and Leger, MM and Lukeš, J and Massana, R and Mathur, V and Nitsche, F and Strassert, JFH and Worden, AZ and Yurchenko, V and Del Campo, J and Waldvogel, AM}, title = {Protist genomics: key to understanding eukaryotic evolution.}, journal = {Trends in genetics : TIG}, volume = {41}, number = {10}, pages = {868-882}, doi = {10.1016/j.tig.2025.05.004}, pmid = {40517085}, issn = {0168-9525}, mesh = {*Evolution, Molecular ; *Genomics/methods ; Biological Evolution ; Genome ; *Eukaryota/genetics ; Humans ; Animals ; Ecosystem ; Mitochondria/genetics ; Single-Cell Analysis ; }, abstract = {All eukaryotes other than animals, plants, and fungi are protists. Protists are highly diverse and found in nearly all environments, with key roles in planetary health and biogeochemical cycles. They represent the majority of eukaryotic diversity, making them essential for understanding eukaryotic evolution. However, these mainly unicellular, microscopic organisms are understudied and the generation of protist genomes lags far behind most multicellular lineages. Current genomic methods, which are primarily designed for animals and plants, are poorly suited for protists. Advancing protist genome research requires reevaluating plant- and animal-centric genomic standards. Future efforts must leverage emerging technologies and bioinformatics tools, ultimately enhancing our understanding of eukaryotic molecular and cell biology, ecology, and evolution.}, } @article {pmid40523936, year = {2025}, author = {Muthukumar, G and Weissman, JS}, title = {Shaping the composition of the mitochondrial outer membrane.}, journal = {Nature cell biology}, volume = {27}, number = {6}, pages = {890-901}, pmid = {40523936}, issn = {1476-4679}, support = {T32GM007287//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; }, mesh = {*Mitochondrial Membranes/metabolism/chemistry ; Humans ; Animals ; *Mitochondria/metabolism ; *Mitochondrial Proteins/metabolism/chemistry/genetics ; Endoplasmic Reticulum/metabolism ; }, abstract = {Mitochondria are critical double-membraned organelles that act as biosynthetic and bioenergetic cellular factories, with the outer membrane providing an interface with the rest of the cell. Mitochondrial outer membrane proteins regulate a variety of processes, including metabolism, innate immunity and apoptosis. Although the biophysical and functional diversity of these proteins is highly documented, the mechanisms of their biogenesis and the integration of that into cellular homeostasis are just starting to take shape. Here, focusing on α-helical outer membrane proteins, we review recent insights into the mechanisms of synthesis and cytosolic chaperoning, insertion and assembly in the lipid bilayer, and quality control of unassembled or mislocalized transmembrane domains. We further discuss the role convergent evolution played in this process, comparing key biogenesis players from lower eukaryotes, including yeast and trypanosomes, with multicellular metazoan systems, and draw comparisons with the endoplasmic reticulum biogenesis system, in which membrane proteins face similar challenges.}, } @article {pmid40527445, year = {2026}, author = {Fan, Y and Wang, N and Wang, S and Yang, Z and Chen, X and Lu, X and Huang, H and Chen, X and Zhao, L and Zhang, M and Sun, Y and Wang, J and Guo, L and Wang, L and Song, R and Wang, J and Zhang, X and Yu, X and Liu, Y and Zhou, XR and Meng, J and Feng, K and Dai, M and Ye, W}, title = {GhGLDH35A gene-mediated ROS homeostasis and stomatal movement via the ascorbic acid pathway confers alkaline stress tolerance.}, journal = {Journal of advanced research}, volume = {81}, number = {}, pages = {75-94}, pmid = {40527445}, issn = {2090-1224}, mesh = {*Ascorbic Acid/metabolism ; *Reactive Oxygen Species/metabolism ; Homeostasis ; *Plant Stomata/physiology/metabolism ; *Stress, Physiological/genetics ; Arabidopsis/genetics/metabolism ; Gene Expression Regulation, Plant ; *Plant Proteins/genetics/metabolism ; *Alcohol Oxidoreductases/genetics/metabolism ; Phylogeny ; Plants, Genetically Modified ; Oxidoreductases Acting on CH-CH Group Donors ; }, abstract = {INTRODUCTION: Ascorbic acid (AsA) is involved in plant responses to various abiotic stresses. However, its specific function in alkaline stress tolerance remains poorly understood. The L-galactono-1,4-lactone dehydrogenase (GLDH) gene is crucial for AsA synthesis, yet the precise role of GLDH in modulating plant resistance to alkaline stress has not been comprehensively characterized.

OBJECTIVES: To investigate the role of GLDH genes in enhancing tolerance to alkaline stress.

METHODS: Bioinformatics analysis of the GLDH gene family members was conducted, and an evolutionary tree was constructed using MEGA software. Cis-acting elements and gene structures were analyzed using TBtools. Gene expression levels were quantified by qRT-PCR, while the function of the GhGLDH35A gene was validated through VIGS (Virus-induced gene silencing) in cotton, heterologous overexpression in Arabidopsis thaliana, and complementation assays in yeast.

RESULTS: Our study investigated the effects of salt-alkaline stress on cotton and found that alkaline stress caused significantly more severe damage than salt stress. The GLDH family genes were identified and analyzed, revealing a high degree of evolutionary conservation. Most GhGLDH genes exhibited a positive response to alkaline stress and were regulated by light. Among them, GhGLDH35A, which is highly expressed within the GLDH family, was found to play a key role in conferring tolerance to alkaline stress. Subcellular localization analysis indicated that GhGLDH35A is localized in the mitochondria. Silencing of GhGLDH35A in cotton resulted in reduced tolerance to alkaline stress, disruption of ROS homeostasis, and impairment of photosynthesis and stomatal function. Conversely, overexpression of GhGLDH35A in Arabidopsis enhanced alkaline stress resistance by elevating AsA levels, increasing antioxidant enzyme activities to enhance ROS scavenging, sustaining photosynthesis, and promoting stomatal closure. Furthermore, heterologous expression of GhGLDH35A in yeast also improved its tolerance to alkaline stress.

CONCLUSIONS: GhGLDH35A positively regulates alkaline stress tolerance by enhancing antioxidant defenses and regulating stomatal movement.}, } @article {pmid40527924, year = {2025}, author = {Cal, K and Leyva, A and Rodríguez-Duarte, J and Ruiz, S and Santos, L and Garat, MP and Colella, L and Ingold, M and Benitez-Rosendo, A and Pérez-Torrado, V and Vilaseca, C and Galliussi, G and Ziegler, L and Peclat, TR and Bresque, M and Handy, RM and King, R and Menezes Dos Reis, L and Alves, JM and Espasandín, C and de la Sovera, V and Breining, P and Dapueto, R and Lopez, A and Thompson, KL and Lino, CA and França, JV and Vieira, TS and Rattan, R and Agorrody, G and DeVallance, E and Haag, J and Meadows, E and Lewis, SE and Santana Barbosa, GC and Lai de Souza, LO and Chichierchio, MS and Valez, V and Aicardo, A and Contreras, P and Vendelbo, MH and Jakobsen, S and Kamaid, A and Porcal, W and Calliari, A and Verdes, JM and Du, J and Wang, Y and Hollander, JM and White, TA and Radi, R and Moyna, G and Quijano, C and O'Doherty, R and Moraes-Vieira, P and Giri, S and Holloway, GP and Festuccia, WT and Leiria, LO and Leonardi, R and Mori, MA and Camacho-Pereira, J and Kelley, EE and Duran, R and López, GV and Chini, EN and Batthyány, C and Escande, C}, title = {A nitroalkene derivative of salicylate, SANA, induces creatine-dependent thermogenesis and promotes weight loss.}, journal = {Nature metabolism}, volume = {7}, number = {8}, pages = {1550-1569}, pmid = {40527924}, issn = {2522-5812}, support = {R01 HL-168290//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 19TPA34850089//American Heart Association (American Heart Association, Inc.)/ ; R01 AG026094/AG/NIA NIH HHS/United States ; R01 HL128485/HL/NHLBI NIH HHS/United States ; R01DK124510-01//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 ES034628/ES/NIEHS NIH HHS/United States ; R01 HL153532/HL/NHLBI NIH HHS/United States ; R35 GM119528/GM/NIGMS NIH HHS/United States ; R01 CA233790/CA/NCI NIH HHS/United States ; R01 HL168290/HL/NHLBI NIH HHS/United States ; R35GM119528//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 AG058812/AG/NIA NIH HHS/United States ; R01 AI144004/AI/NIAID NIH HHS/United States ; NS 112727//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL153532//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 HL-128485//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; NS AI144004//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 NS112727/NS/NINDS NIH HHS/United States ; R01 DK124510/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Male ; Double-Blind Method ; Adult ; *Thermogenesis/drug effects ; *Creatine/metabolism ; Female ; *Weight Loss/drug effects ; Obesity/drug therapy/metabolism ; *Salicylates/pharmacology/chemistry/therapeutic use ; Middle Aged ; Energy Metabolism/drug effects ; Animals ; Insulin Resistance ; *Alkenes/chemistry/pharmacology ; }, abstract = {The emergence of glucagon-like peptide-1 agonists represents a notable advancement in the pharmacological treatment of obesity, yet complementary approaches are essential. Through phenotypic drug discovery, we developed promising nitroalkene-containing small molecules for obesity-related metabolic dysfunctions. Here, we present SANA, a nitroalkene derivative of salicylate, demonstrating notable efficacy in preclinical models of diet-induced obesity. SANA reduces liver steatosis and insulin resistance by enhancing mitochondrial respiration and increasing creatine-dependent energy expenditure in adipose tissue, functioning effectively in thermoneutral conditions and independently of uncoupling protein 1 and AMPK activity. Finally, we conducted a randomized, double-blind, placebo-controlled phase 1A/B clinical trial, which consisted of two parts, each with four arms: (A) single ascending doses (200-800 mg) in healthy lean volunteers; (B) multiple ascending doses (200-400 mg per day for 15 days) in healthy volunteers with overweight or obesity. The primary endpoint assessed safety and tolerability. Secondary and exploratory endpoints included pharmacokinetics, tolerability, body weight and metabolic markers. SANA shows good safety and tolerability, and demonstrates beneficial effects on body weight and glucose management within 2 weeks of treatment. Overall, SANA appears to be a first-in-class activator of creatine-dependent energy expenditure and thermogenesis, highlighting its potential as a therapeutic candidate for 'diabesity'. Australian New Zealand Clinical Trials Registry registration: ACTRN12622001519741 .}, } @article {pmid40531408, year = {2026}, author = {Modeel, S and Chaurasia, M and Siwach, S and Dolkar, P and Negi, RK and Negi, RK}, title = {Mitochondrial Perspective on Species Complexes and Evolutionary Dynamics Within Genus Channa.}, journal = {Biochemical genetics}, volume = {64}, number = {2}, pages = {2697-2721}, pmid = {40531408}, issn = {1573-4927}, support = {F. No. EEQ/2019/000214//Science and Engineering Research Board/ ; }, mesh = {Animals ; Phylogeny ; Haplotypes ; *Evolution, Molecular ; Genetic Variation ; *DNA, Mitochondrial/genetics ; DNA Barcoding, Taxonomic ; *Mitochondria/genetics ; *Fishes/genetics/classification ; }, abstract = {The genus Channa, commonly known as Snakeheads comprises a diverse variety of species that hold great significance in the commercial sectors. Their complexity and genetic variety show how adaptable they are to different environmental settings and shed light on their evolutionary history. To delve into the genetic intricacies of the genus Channa, we analyzed mitochondrial genetic diversity using 1372 COI sequences obtained from the Barcode of Life Data System (BOLD) database. The metadata and phylogenetic analysis revealed the presence of species complex within C. gachua and C. marulius, suggesting the potential existence of intra and inter-clades within one species group. Further, we selected four ecologically and economically important taxonomic groups to study their haplotype diversity and genetic differentiation. These species/taxonomic groups include C. striata, C. punctata, gachua species complex, and marulius species complex. The analysis indicated a substantial level of genetic differentiation and haplotype diversity in species groups indicating high gene flow within populations. Mitochondrial introgression and species complexes account for a significant section of errors in DNA barcodes, which are two of the primary challenges associated with employing DNA barcoding to identify species. Highlighting these challenges and ongoing uncertainties in specific taxonomic groups of genus Channa, the study argues that the efficacy of DNA barcoding and the genetic integrity of wild variation may be weakened when speciation results in the establishment of numerous cryptic taxa in a species complex.}, } @article {pmid40536996, year = {2026}, author = {Yañez, IM and Torres-Cuevas, I and Corral-Debrinski, M}, title = {Neuroglobin: A promising candidate to treat neurological diseases.}, journal = {Neural regeneration research}, volume = {21}, number = {4}, pages = {1292-1303}, pmid = {40536996}, issn = {1673-5374}, abstract = {Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide. Altogether, the burden of neurological disorders has increased considerably over the past 30 years because of population aging. Overall, neurological diseases significantly impair cognitive and motor functions and their incidence will increase as societies age and the world's population continues to grow. Autism spectrum disorder, motor neuron disease, encephalopathy, epilepsy, stroke, ataxia, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Parkinson's disease represent a non-exhaustive list of neurological illnesses. These affections are due to perturbations in cellular homeostasis leading to the progressive injury and death of neurons in the nervous system. Among the common features of neurological handicaps, we find protein aggregation, oxidative stress, neuroinflammation, and mitochondrial impairment in the target tissues, e.g., the brain, cerebellum, and spinal cord. The high energy requirements of neurons and their inability to produce sufficient adenosine triphosphate by glycolysis, are responsible for their dependence on functional mitochondria for their integrity. Reactive oxygen species, produced along with the respiration process within mitochondria, can lead to oxidative stress, which compromises neuronal survival. Besides having an essential role in energy production and oxidative stress, mitochondria are indispensable for an array of cellular processes, such as amino acid metabolism, iron-sulfur cluster biosynthesis, calcium homeostasis, intrinsic programmed cell death (apoptosis), and intraorganellar signaling. Despite the progress made in the last decades in the understanding of a growing number of genetic and molecular causes of central nervous diseases, therapies that are effective to diminish or halt neuronal dysfunction/death are rare. Given the genetic complexity responsible for neurological disorders, the development of neuroprotective strategies seeking to preserve mitochondrial homeostasis is a realistic challenge to lastingly diminish the harmful evolution of these pathologies and so to recover quality of life. A promising candidate is the neuroglobin, a globin superfamily member of 151 amino acids, which is found at high levels in the brain, the eye, and the cerebellum. The protein, which localizes to mitochondria, is involved in electron transfer, oxygen storage and defence against oxidative stress; hence, possessing neuroprotective properties. This review surveys up-to-date knowledge and emphasizes on existing investigations regarding neuroglobin physiological functions, which remain since its discovery in 2000 under intense debate and the possibility of using neuroglobin either by gene therapy or its direct delivery into the brain to treat neurological disorders.}, } @article {pmid40542427, year = {2025}, author = {Katsafadou, AI and Nebert, DW and Krupenko, SA and Thompson, DC and Vasiliou, V}, title = {Update of the sideroflexin (SLC56) gene family.}, journal = {Human genomics}, volume = {19}, number = {1}, pages = {69}, pmid = {40542427}, issn = {1479-7364}, support = {ES033815/NH/NIH HHS/United States ; }, mesh = {Humans ; Mitochondria/metabolism/genetics ; *Multigene Family ; Iron/metabolism ; Animals ; *Mitochondrial Membrane Transport Proteins/genetics ; *Mitochondrial Proteins/genetics/metabolism ; Evolution, Molecular ; }, abstract = {The human sideroflexin (SFXN) gene family, also classified as solute carrier family 56 (SLC56), encodes a group of five mitochondrial transmembrane proteins (SFXN1-SFXN5) involved in key aspects of mitochondrial metabolism, cellular homeostasis, and development. SFXNs are highly conserved across eukaryotic species, with evolutionary the origin traced back to the earliest metazoans. Functionally, each of the five family members exhibits distinct functional specialization. Particularly, SFXN1 and SFXN3 facilitate mitochondrial serine transport, supporting one-carbon metabolism. SFXN2 and SFXN4 are implicated in mitochondrial iron regulation, heme biosynthesis, and iron-sulfur cluster assembly. SFXN5, predominantly expressed in the brain, is proposed to regulate citrate metabolism and immune cell functions. Mutations or dysregulation of SFXN genes have been linked to certain human diseases, including congenital sideroblastic anemia, oxidative phosphorylation disorders, neurodegenerative conditions, and cancers. Structurally, SFXNs share conserved transmembrane domains and key motifs critical for substrate transport, mitochondrial iron homeostasis, and overall mitochondrial function. The evolutionary trajectory of the SFXN family-from amino acid transport to functionally specialized roles in higher organisms-highlights their biological and clinical significance. Comparative studies across model organisms reveal both conserved and divergent functions, emphasizing their importance in health and disease. A comprehensive understanding of the SFXN family not only advances fundamental mitochondrial research but also opens avenues for novel therapeutic interventions.}, } @article {pmid40545685, year = {2025}, author = {Benning, FMC and Bell, TA and Nguyen, TH and Syau, D and Connell, LB and Liao, YT and Keating, MP and Coughlin, M and Nordstrom, AEH and Ericsson, M and daCosta, CJB and Chao, LH}, title = {Ancestral sequence reconstruction of the Mic60 Mitofilin domain reveals residues supporting respiration in yeast.}, journal = {Protein science : a publication of the Protein Society}, volume = {34}, number = {7}, pages = {e70207}, pmid = {40545685}, issn = {1469-896X}, support = {R35 GM142553/GM/NIGMS NIH HHS/United States ; //Keystone Future of Science Fund/ ; P180777//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; RGPIN-2016-04801//Natural Sciences and Engineering Research Council of Canada/ ; R35GM142553/NH/NIH HHS/United States ; 9736//Simons Foundation/ ; 377068/CAPMC/CIHR/Canada ; //Helen Hay Whitney Foundation/ ; //Gordon and Betty Moore Foundation/ ; 34475//Canada Foundation for Innovation/ ; NFRFE-2018-00064//New Frontiers in Research Fund/ ; }, mesh = {*Saccharomyces cerevisiae/metabolism/genetics ; *Mitochondrial Proteins/genetics/chemistry/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/chemistry/metabolism ; Protein Domains ; Evolution, Molecular ; Phylogeny ; }, abstract = {In eukaryotes, cellular respiration takes place in the cristae of mitochondria. The mitochondrial inner membrane protein Mic60, a core component of the mitochondrial contact site and cristae organizing system, is crucial for the organization and stabilization of crista junctions and its associated functions. While the C-terminal Mitofilin domain of Mic60 is necessary for cellular respiration, the sequence determinants for this function have remained unclear. Here, we used ancestral sequence reconstruction to generate Mitofilin ancestors up to and including the last opisthokont common ancestor (LOCA). We found that yeast-lineage derived Mitofilin ancestors as far back as the LOCA rescue respiration. By comparing Mitofilin ancestors, we identified four residues sufficient to explain the respiratory difference between yeast- and animal-derived Mitofilin ancestors. Our results provide a foundation for investigating the conservation of Mic60-mediated cristae junction interactions.}, } @article {pmid40546076, year = {2025}, author = {Liu, S and Powell, V and Yang, SM and Lam, F and Bowler, C and Obornik, M and Dorrell, RG}, title = {Dynamic Relocalization and Divergent Expression of a Major Facilitator Carrier Subfamily in Diatoms.}, journal = {Physiologia plantarum}, volume = {177}, number = {3}, pages = {e70355}, doi = {10.1111/ppl.70355}, pmid = {40546076}, issn = {1399-3054}, support = {101039760/ERC_/European Research Council/International ; 835067/ERC_/European Research Council/International ; CZ.02.2.69/0.0/0.0/18_054/0014649//Jihočeská Univerzita v Českých Budějovicích/ ; ANR-10-INBS-09-08//Agence Nationale de la Recherche/ ; ANR-10-LABX-54//Agence Nationale de la Recherche/ ; ANR-11-BTBR-0008//Agence Nationale de la Recherche/ ; ANR-11-IDEX-0001-02//Agence Nationale de la Recherche/ ; ANR-19-CE20-0020//Agence Nationale de la Recherche/ ; 23-06203S//Grantová Agentura České Republiky/ ; }, mesh = {*Diatoms/metabolism/genetics ; Phylogeny ; Mitochondria/metabolism ; }, abstract = {Eukaryotic organisms, including microbial members such as protists and green algae, utilize suites of transporter proteins to move essential metabolites across cell organelle membranes. Amongst these different transporter families, the mitochondrial carrier family (MCF) is one of the most diverse, encompassing essential NAD+ and ADP/ATP translocators, as well as amino acid, sugar and cofactor transporters. They are typically associated with the mitochondrial inner membrane, but some display more dynamic localization. Here, we perform a census of predicted MCF domains in the genome of the model diatom alga Phaeodactylum tricornutum, identifying a new family of three proteins (termed here and elsewhere "MCFc") with strong internal sequence conservation but limited similarity to other MCF proteins encoded in its genome. Considering both phylogenetic data and experimental localization, we posit that MCFc is widespread across algae with complex red chloroplasts alongside some primary green algae, and contains multiple subfamilies targeted to diatom mitochondria, plastids, and endomembranes. Finally, using data from Tara Oceans, we identify putative roles for MCFc in diatom cells, including a possible association of the plastid-targeted Phatr3_J46742 subfamily in cellular nitrate assimilation. Our data provide insights into the evolutionary diversification of the membrane transport mechanisms associated with diatoms and other eukaryotic algae.}, } @article {pmid40547468, year = {2025}, author = {Panagopoulos, DJ and Yakymenko, I and De Iuliis, GN and Chrousos, GP}, title = {A comprehensive mechanism of biological and health effects of anthropogenic extremely low frequency and wireless communication electromagnetic fields.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1585441}, pmid = {40547468}, issn = {2296-2565}, mesh = {*Electromagnetic Fields/adverse effects ; Humans ; *Wireless Technology ; *Environmental Exposure/adverse effects ; Oxidative Stress ; DNA Damage ; Microwaves/adverse effects ; }, abstract = {Exposure to anthropogenic electromagnetic fields (EMFs), especially those of wireless communications (WC) has increased tremendously. This is an unprecedented phenomenon throughout biological evolution because, all anthropogenic EMFs, being fully polarized, coherent, and, especially WC EMFs, highly variable, differ substantially from the natural EMFs. WC EMFs consist of Microwave (MW) carrier waves, modulated, by Extremely Low Frequency (ELF) signals, and included in on/off pulses repeated at various ELF rates. Moreover, they exhibit intense random variability, mainly in the Ultra Low Frequency (ULF) band. Thus, WC EMFs are a combination of MW and ELF/ULF EMFs. The combination of polarization/coherence and intense low-frequency (ELF/ULF) variability seems to be the key to EMF-bioactivity. Epidemiological and laboratory studies highlight a connection between ELF or WC EMF exposure and cancer, infertility, electro-hypersensitivity, and various other pathologies. Studies also find DNA damage and Oxidative Stress (OS) which explain these pathologies. While man-made EMFs cannot directly ionize molecules, they are capable of doing this indirectly in biological tissue, by triggering the biosynthesis of Reactive Oxygen Species (ROS) which can damage biomolecules, including DNA. The (over)production of ROS and the consequent OS are triggered by irregular gating of Voltage-Gated Ion Channels (VGICs) in the cell membranes as described by the Ion Forced Oscillation (IFO)-VGIC mechanism: Mobile ions within VGICs forced to oscillate by the applied ELF/ULF EMFs exert forces on the voltage sensors of the VGICs, similar to or greater than the forces that physiologically gate those channels, resulting in their irregular gating (dysfunction). Dysfunction of ion channels disrupts intracellular ionic concentrations. This triggers ROS overproduction and OS by the ROS-generating systems/enzymes in the cells, such as the electron transport chain (ETC) in the mitochondria, or the NADPH/NADH oxidases (NOXs), the Nitric Oxide synthases (NOS), etc. The IFO-VGIC mechanism and the consequent OS constitute a comprehensive mechanism that explains all known adverse biological and health effects reported to be induced by anthropogenic EMFs.}, } @article {pmid40549685, year = {2025}, author = {Yu, X and Hu, J and Tan, Y and Pan, M and Zhang, H and Li, B}, title = {MitoTracer facilitates the identification of informative mitochondrial mutations for precise lineage reconstruction.}, journal = {PLoS computational biology}, volume = {21}, number = {6}, pages = {e1013090}, pmid = {40549685}, issn = {1553-7358}, support = {R01 CA245318/CA/NCI NIH HHS/United States ; R01 CA258524/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Mutation/genetics ; Algorithms ; Computational Biology/methods ; *Mitochondria/genetics ; Single-Cell Analysis/methods ; *Cell Lineage/genetics ; Neoplasms/genetics ; *DNA, Mitochondrial/genetics ; Proto-Oncogene Proteins B-raf/genetics ; }, abstract = {Mitochondrial (MT) mutations serve as natural genetic markers for inferring clonal relationships using single cell sequencing data. However, the fundamental challenge of MT mutation-based lineage tracing is automated identification of informative MT mutations. Here, we introduced an open-source computational algorithm called "MitoTracer", which accurately identified clonally informative MT mutations and inferred evolutionary lineage from scRNA-seq or scATAC-seq samples. We benchmarked MitoTracer using the ground-truth experimental lineage sequencing data and demonstrated its superior performance over the existing methods measured by high sensitivity and specificity. MitoTracer is compatible with multiple single cell sequencing platforms. Its application to a cancer evolution dataset revealed the genes related to primary BRAF-inhibitor resistance from scRNA-seq data of BRAF-mutated cancer cells. Overall, our work provided a valuable tool for capturing real informative MT mutations and tracing the lineages among cells.}, } @article {pmid40550401, year = {2025}, author = {Daplan, E and Rodriguez, E and Lane, N and Turin, L}, title = {A chance insight into phosgene toxicity.}, journal = {Free radical biology & medicine}, volume = {238}, number = {}, pages = {113-122}, doi = {10.1016/j.freeradbiomed.2025.06.033}, pmid = {40550401}, issn = {1873-4596}, mesh = {Animals ; *Superoxide Dismutase/metabolism/genetics ; Electron Spin Resonance Spectroscopy ; *Phosgene/toxicity ; Oxidative Stress/drug effects ; Drosophila melanogaster/drug effects/metabolism/genetics ; *Mitochondria/drug effects/metabolism ; Oxidation-Reduction ; Manganese/metabolism/chemistry ; Hydrogen Peroxide/metabolism ; Drosophila Proteins/genetics/metabolism ; Superoxide Dismutase 2 ; }, abstract = {It has long been known that phosgene, a war gas and an industrial reagent, causes intense oxidative stress, but how it does so remains unclear. Here we report an accidental discovery: Electron spin resonance spectroscopy (ESR) of live fruit flies reveals that phosgene exposure results in a distinctive manganese (Ⅱ) hyperfine structure. After exposure to phosgene, every batch of flies consistently displays the Mn (Ⅱ) signal. Regardless of the aftercare provided, these flies inevitably perish, making the signal a diagnostic of phosgene poisoning in flies. The intensity of the signal is dependent on both exposure time and concentration, resembling the kinetics of phosgene poisoning. The signal of Mn (Ⅱ) correlates with the presence of a functional superoxide dismutase Sod2. After exposure, heterozygous Sod2 mutants have a markedly lower intensity of Mn (Ⅱ) in their ESR spectrum. We suggest that phosgene disturbs Mn redox cycling between ESR-silent Mn (Ⅲ) and ESR-active Mn (Ⅱ) that is required for superoxide dismutation. Accordingly, mitochondria of phosgene-treated flies show reduced rates of hydrogen peroxide production, and severely compromised complex I-linked respiration. It is likely that phosgene damages mitochondria through MnSOD and complex I, which contributes to its toxicity. This work uses Drosophila melanogaster for the first time in phosgene research.}, } @article {pmid40562331, year = {2025}, author = {Martin, WF}, title = {ATP requirements for growth reveal the bioenergetic impact of mitochondrial symbiosis.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1866}, number = {4}, pages = {149564}, pmid = {40562331}, issn = {1879-2650}, support = {101018894/ERC_/European Research Council/International ; }, mesh = {*Adenosine Triphosphate/metabolism ; *Symbiosis ; *Energy Metabolism ; *Mitochondria/metabolism ; Humans ; Animals ; Amino Acids/metabolism ; }, abstract = {Studies by microbiologists in the 1970s provided robust estimates for the energy supply and demand of a prokaryotic cell. The amount of ATP needed to support growth was calculated from the chemical composition of the cell and known enzymatic pathways that synthesize its constituents from known substrates in culture. Starting in 2015, geneticists and evolutionary biologists began investigating the bioenergetic role of mitochondria at eukaryote origin and energy in metazoan evolution using their own, widely trusted-but hitherto unvetted-model for the costs of growth in terms of ATP per cell. The more recent model contains, however, a severe and previously unrecognized error that systematically overestimates the ATP cost of amino acid synthesis up to 200-fold. The error applies to all organisms studied by such models and leads to conspicuously false inferences, for example that the synthesis of an average amino acid in humans requires 30 ATP, which no biochemistry textbook will confirm. Their ATP 'cost' calculations would require that E. coli obtains ~100 ATP per glucose and that mammals obtain ~240 ATP per glucose, untenable propositions that invalidate and void all evolutionary inferences so based. By contrast, established methods for estimating the ATP cost of microbial growth show that the first mitochondrial endosymbionts could have easily doubled the host's available ATP pool, provided (i) that genes for growth on environmental amino acids were transferred from the mitochondrial symbiont to the archaeal host, and (ii) that the host for mitochondrial origin was an autotroph using the acetyl-CoA pathway. Stated in simple terms, the significance of these findings are this: Life is a chemical reaction. It requires energy release in order to proceed. The currency of energy in cells is adenosine triphosphate, ATP. Five decades ago, microbiologists were able to measure and understand the amount of ATP that cells require to grow. New studies by evolutionary biologists have appeared in the meantime that brush aside the older microbiological findings, using their own methods to calculate the ATP cost of growth instead. Science is, however, an imperfect undertaking. The new studies contain a major error, similar to conflating centimeters with yards. The error affects many publications and their conclusions. Using the old methods, we can still meaningfully study the role of energy in evolution, including the origin of complex, nucleus-bearing cells.}, } @article {pmid40564954, year = {2025}, author = {Stefano, GB and Buttiker, P and Michaelsen, MM and Esch, T}, title = {The Anatomical and Evolutionary Impact of Pain, Pleasure, Motivation, and Cognition: Integrating Energy Metabolism and the Mind-Body BERN (Behavior, Exercise, Relaxation, and Nutrition) Framework.}, journal = {International journal of molecular sciences}, volume = {26}, number = {12}, pages = {}, pmid = {40564954}, issn = {1422-0067}, mesh = {Humans ; *Energy Metabolism ; *Exercise/physiology ; *Cognition/physiology ; Mitochondria/metabolism ; *Motivation ; *Pain/metabolism/physiopathology ; Animals ; *Pleasure/physiology ; Biological Evolution ; }, abstract = {In this manuscript, we highlight the evolutionary origins of mitochondria from bacterial endosymbionts and explore their contributions to health, energy metabolism, and neural-immune communication. Mitochondrial adaptability and the roles played by these organelles in promoting oxygen-dependent ATP production provide critical regulation of cognition, motivation, and inflammation. Hypoxia has been identified as an important initiator of inflammation, neurodegeneration, and mitochondrial dysfunction, emphasizing the overall importance of oxygen homeostasis to health and well-being. The Behavior, Exercise, Relaxation, and Nutrition framework highlights these observations as tools that can be used to optimize mitochondrial efficiency. Interestingly, mitochondrial dysfunction may also be linked to psychiatric disorders (e.g., schizophrenia), a hypothesis that focuses on energy dynamics, a proposal that may extend our understanding of these disorders beyond traditional neurotransmitter-focused concepts. Collectively, these perspectives underscore the critical contributions of mitochondria to health and disease and offer a novel framework that may help to explain the connections featured in mind-body medicine.}, } @article {pmid40570835, year = {2025}, author = {Allard, CAH and Thies, AB and Mitra, R and Vaelli, PM and Leto, OD and Walsh, BL and Laetz, EMJ and Tresguerres, M and Lee, ASY and Bellono, NW}, title = {A host organelle integrates stolen chloroplasts for animal photosynthesis.}, journal = {Cell}, volume = {188}, number = {19}, pages = {5266-5277.e13}, pmid = {40570835}, issn = {1097-4172}, support = {R35 GM142527/GM/NIGMS NIH HHS/United States ; R35 GM142697/GM/NIGMS NIH HHS/United States ; }, mesh = {*Chloroplasts/metabolism ; *Photosynthesis/physiology ; Animals ; *Gastropoda/metabolism/physiology ; *Organelles/metabolism ; Symbiosis ; Biological Evolution ; }, abstract = {Eukaryotic life evolved over a billion years ago when ancient cells engulfed and integrated prokaryotes to become modern mitochondria and chloroplasts. Sacoglossan "solar-powered" sea slugs possess the ability to acquire organelles within a single lifetime by selectively retaining consumed chloroplasts that remain photosynthetically active for nearly a year. The mechanism for this "animal photosynthesis" remains unknown. Here, we discovered that foreign chloroplasts are housed within novel, host-derived organelles we term "kleptosomes." Kleptosomes use ATP-sensitive ion channels to maintain a luminal environment that supports chloroplast photosynthesis and longevity. Upon slug starvation, kleptosomes digest stored chloroplasts for additional nutrients, thereby serving as a food source. We leveraged this discovery to find that organellar retention and digestion of photosynthetic cargo has convergently evolved in other photosynthetic animals, including corals and anemones. Thus, our study reveals mechanisms underlying the long-term acquisition and evolutionary incorporation of intracellular symbionts into organelles that support complex cellular function.}, } @article {pmid40580793, year = {2025}, author = {Nishu, and Sharma, Y and Deepika, and Kaur, A and Upadhyay, SK}, title = {Exploration of mitochondrial calcium uniporters suggested their role in abiotic stress response in bread wheat.}, journal = {Plant physiology and biochemistry : PPB}, volume = {227}, number = {}, pages = {110180}, doi = {10.1016/j.plaphy.2025.110180}, pmid = {40580793}, issn = {1873-2690}, mesh = {*Triticum/genetics/metabolism/physiology ; *Stress, Physiological/genetics ; *Calcium Channels/metabolism/genetics ; *Plant Proteins/genetics/metabolism ; Gene Expression Regulation, Plant ; Phylogeny ; Mitochondria/metabolism ; MicroRNAs/genetics/metabolism ; }, abstract = {Mitochondrial calcium uniporters (MCUs) play a crucial role in calcium transport, signaling, and homeostasis, which is vital for plant growth, development, and stress responses. In this study, we identified 17 TaMCU genes classified into seven homoeologous groups with conserved gene architecture in the bread wheat genome. The structural analysis revealed the presence of MCU domain, DVME motif, transmembrane helices, and various key amino acid residues, which are conserved across all TaMCU proteins. Each TaMCU protein consisted of a mitochondrial targeting peptide and predicted to be localized in the mitochondria. The phylogenetic and synteny analyses provided insights into their evolutionary diverged and conserved nature. Cis-regulatory element analysis suggested that TaMCU genes are involved in abiotic stress responses, involving key transcription factors such as MYB, MBS, W-box, and ERF. Protein-protein interaction study suggested that TaMCUs interact with other mitochondrial and stress-related proteins, such as MICU, PHB, and FREE1. Additionally, six miRNAs related to plant development and stress-response such as miR5384-3p, tae-miR5050 etc., exhibited interactions with a few TaMCU transcripts. RNA-seq expression profiling revealed differential expression of various TaMCU genes in tissue developmental stages and under various stress conditions. qRT-PCR under salinity and drought treatments confirmed the involvement of TaMCU1-D, TaMCU3-A, and TaMCU5-B genes in these stress conditions. These findings provide insights into the potential roles of TaMCU genes and suggest their future applications in the development of abiotic stress-resilient crop plants.}, } @article {pmid40581121, year = {2025}, author = {Rabinowitz, J and Vila, IK and Luchsinger, C and Bertelli, C and Schüssler, M and Taffoni, C and Cui, B and Dai, AZ and Rashid, MM and Cisneros, WJ and Cornish, D and Redondo, J and Jackson-Jones, KA and Simons, LM and Lorenzo-Redondo, R and Laguette, N and Hultquist, JF and Diaz-Griffero, F}, title = {The ability of SAMHD1-deficient monocytes to trigger the Type I IFN response depends on cGAS and mitochondrial DNA.}, journal = {The Journal of biological chemistry}, volume = {301}, number = {8}, pages = {110430}, pmid = {40581121}, issn = {1083-351X}, support = {R01 AI165236/AI/NIAID NIH HHS/United States ; R01 AI167778/AI/NIAID NIH HHS/United States ; R01 AI150455/AI/NIAID NIH HHS/United States ; P30 AI117943/AI/NIAID NIH HHS/United States ; T32 AI007501/AI/NIAID NIH HHS/United States ; R01 MH125778/MH/NIMH NIH HHS/United States ; P01 AI169600/AI/NIAID NIH HHS/United States ; R01 AI150998/AI/NIAID NIH HHS/United States ; U54 AI170792/AI/NIAID NIH HHS/United States ; }, mesh = {*SAM Domain and HD Domain-Containing Protein 1/genetics/deficiency/metabolism ; *Nucleotidyltransferases/metabolism/genetics ; Humans ; *Monocytes/metabolism ; *Interferon Type I/metabolism/genetics ; *DNA, Mitochondrial/metabolism/genetics ; Signal Transduction ; Autoimmune Diseases of the Nervous System/genetics/metabolism ; Nervous System Malformations/genetics/metabolism ; Interferon-Induced Helicase, IFIH1/metabolism/genetics ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; }, abstract = {In humans, mutations in sterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) lead to the development of a type I interferonopathy known as Aicardi-Goutières syndrome (AGS). AGS can present with a variety of severe phenotypes in patients, and a hallmark of this disease is chronic activation of type I interferon (IFN) signaling. However, the mechanism through which type I IFN signaling is activated in the absence of functional SAMHD1 is not known. Here, we investigated the molecular pathways that lead to type I IFN signaling activation in the absence of SAMHD1. Our investigations revealed that chronic activation of type I IFN signaling in SAMHD1-knockout (KO) monocytes is cyclic GMP-AMP synthase (cGAS)-dependent. Analysis of other nucleic acid sensors showed that type I IFN signaling in SAMHD1-KO cells is not dependent on melanoma differentiation-associated protein 5 (MDA5) or retinoic acid-inducible gene I (RIG-I). In agreement with our observation that type I IFN signaling is dependent on cGAS, two inhibitors of the cGAS-stimulator of IFN genes pathway, G140 and H151, effectively prevented type I IFN activation in SAMHD1-KO monocytes. We also found that type I IFN signaling in SAMHD1-KO monocytes is dependent on type I IFN receptor expression. Further exploration revealed mitochondrial malfunction in SAMHD1-KO monocytes that is likely to leak mitochondrial components into the cytoplasm. Overall, our work suggests that genetic knock out of SAMHD1 leads to mitochondrial disfunction, resulting in the presence of mitochondrial DNA in the cytoplasm, which triggers cGAS and the type I IFN response.}, } @article {pmid40581570, year = {2025}, author = {Lai, LB and Jackman, JE and Daniels, CJ and Gopalan, V}, title = {Mitochondrial tRNA processing: a neutral evolutionary ratchet innovation.}, journal = {Trends in biochemical sciences}, volume = {50}, number = {10}, pages = {842-844}, pmid = {40581570}, issn = {0968-0004}, support = {23IPA1054097/AHA/American Heart Association-American Stroke Association/United States ; R01 CA260414/CA/NCI NIH HHS/United States ; R01 GM130135/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Evolution, Molecular ; *Mitochondria/metabolism/genetics ; *RNA Processing, Post-Transcriptional ; RNA, Mitochondrial ; *RNA, Transfer/metabolism/genetics ; }, abstract = {Mitochondrial tRNA processing is a chronicle of molecular adaptability. The processing of structurally compromised tRNAs is unexpectedly rescued by a multienzyme complex shaped by constructive neutral evolution. This striking example of biological complexity arising from nonadaptive mechanisms showcases how a potential vulnerability is transformed into a robust, if precarious, innovation.}, } @article {pmid40584852, year = {2025}, author = {Chen, Z and Wang, Z and Zhou, W and Liu, S and Xiao, Y and Gong, Y}, title = {Complete sequencing of the mitochondrial genome of tea plant Camellia sinensis cv. 'Baihaozao': multichromosomal structure, phylogenetic relationships, and adaptive evolutionary analysis.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1604404}, pmid = {40584852}, issn = {1664-462X}, abstract = {INTRODUCTION: This study reports for the first time the complete sequence characteristics of the mitochondrial genome of the tea plant cultivar Camellia sinensis cv. 'Baihaozao'. It systematically unveils its multi-chromosomal structure, RNA editing patterns, and adaptive evolutionary mechanisms, providing critical theoretical insights into the structural complexity and evolutionary mechanisms of the tea plant mitochondrial genome.

METHODS: The mitochondrial genome was fully analyzed using genome sequencing and annotation techniques. RNA editing sites were predicted to evaluate editing patterns. Codon usage bias analysis was conducted to identify high-frequency codons. Repeat sequence analysis was used to characterize dispersed and tandem repeats. Adaptive evolutionary analysis, based on Ka/Ks ratios, was performed to investigate gene selection pressures.

RESULTS: The mitochondrial genome consists of 11 linear chromosomes, with a total length of 909,843 bp and a GC content of 45.62%. A total of 73 functional genes were annotated, among which 14 variable genes (e.g., ribosomal protein coding genes) retain intact functions without pseudogenization, which is rare among Theaceae plants. RNA editing site prediction revealed significant spatial heterogeneity, with the cox1 gene being a hotspot containing 19 editing sites. Approximately 58.49% of editing events were concentrated on the second base of codons, and 48.61% of the sites resulted in amino acid changes from hydrophilic to hydrophobic. Codon usage bias analysis showed significant enrichment of high-frequency codons, including UUU (phenylalanine), AUU (isoleucine), and UUC (phenylalanine). The genome's repeat sequences were predominantly dispersed repeats (70.6%), with forward and palindromic repeats of 30-40 bp being dominant. Tandem repeats exhibited significant distribution heterogeneity among chromosomes. Adaptive evolution analysis showed that most PCGs (protein-coding genes) had Ka/Ks ratios below 1 (ranging from 0.07 to 0.78), with the atp9 gene showing the lowest ratio (0.07), while the mttB gene exhibited a significantly higher Ka/Ks ratio of 3.48. Additionally, 1.62% of the mitochondrial genome sequence was homologous to the chloroplast genome, carrying 26 complete functional genes, including 15 tRNA and 2 rRNA genes.

DISCUSSION: Codon usage bias may be related to mutation pressure due to the high AT content of the genome or reflect adaptive selection pressures for translational efficiency. The Ka/Ks results align with the widespread purifying selection observed in mitochondrial genomes, while the high Ka/Ks ratio of the mttB gene suggests it might be under positive selection to adapt to environmental pressures. The evolutionary evidence of inter-organelle gene transfer highlights the homologous sequences between mitochondria and chloroplasts. Overall, these findings systematically elucidate the adaptive evolutionary mechanisms and functional regulation of the tea plant mitochondrial genome.}, } @article {pmid40587584, year = {2025}, author = {Broz, AK and Hodous, MM and Zou, Y and Vail, PC and Wu, Z and Sloan, DB}, title = {Flipping the switch on some of the slowest mutating genomes: Direct measurements of plant mitochondrial and plastid mutation rates in msh1 mutants.}, journal = {PLoS genetics}, volume = {21}, number = {6}, pages = {e1011764}, pmid = {40587584}, issn = {1553-7404}, support = {R35 GM148134/GM/NIGMS NIH HHS/United States ; }, mesh = {*Arabidopsis/genetics ; *MutS DNA Mismatch-Binding Protein/genetics ; *Genome, Plastid/genetics ; *Genome, Mitochondrial/genetics ; *Arabidopsis Proteins/genetics ; *Mutation Rate ; Plastids/genetics ; Mitochondria/genetics ; Genome, Plant ; Mutation ; Evolution, Molecular ; }, abstract = {Plant mitochondrial and plastid genomes have exceptionally slow rates of sequence evolution, and recent work has identified an unusual member of the MutS gene family ("plant MSH1") as being instrumental in preventing point mutations in these genomes. However, the effects of disrupting MSH1-mediated DNA repair on "germline" mutation rates have not been quantified. Here, we used Arabidopsis thaliana mutation accumulation (MA) lines to measure mutation rates in msh1 mutants and matched wild type (WT) controls. We detected 124 single nucleotide variants (SNVs: 49 mitochondrial and 75 plastid) and 668 small insertions and deletions (indels: 258 mitochondrial and 410 plastid) in msh1 MA lines at a heteroplasmic frequency of ≥ 20%. In striking contrast, we did not find any organelle mutations in the WT MA lines above this threshold, and reanalysis of data from a much larger WT MA experiment also failed to detect any variants. The observed number of SNVs in the msh1 MA lines corresponds to estimated mutation rates of 6.1 × 10-7 and 3.2 × 10-6 per bp per generation in mitochondrial and plastid genomes, respectively. These rates exceed those of species known to have very high mitochondrial mutation rates (e.g., nematodes and fruit flies) by an order of magnitude or more and are on par with estimated rates in humans despite the generation times of A. thaliana being nearly 100-fold shorter. Therefore, disruption of a single plant-specific genetic factor in A. thaliana is sufficient to erase or even reverse the enormous difference in organelle mutation rates between plants and animals.}, } @article {pmid40592454, year = {2025}, author = {Bradshaw, SL and Rodríguez, E and Wang, H and Yu, CT and De Villiers De La Noue, C and Hafezjee, A and Pomiankowski, A and Camus, MF}, title = {The metabolic costs of meiotic drive.}, journal = {Proceedings. Biological sciences}, volume = {292}, number = {2050}, pages = {20250779}, pmid = {40592454}, issn = {1471-2954}, support = {//Engineering and Physical Sciences Research Council/ ; //Leverhulme Trust/ ; //Natural Environment Research Council/ ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Male ; Female ; *Meiosis/genetics ; *Diptera/genetics/metabolism ; Sex Ratio ; X Chromosome/genetics ; Adenosine Triphosphate/biosynthesis/metabolism ; Basal Metabolism ; }, abstract = {Selfish genetic elements, such as meiotic drive genes, disrupt Mendel's law of equal segregation by biasing their own transmission, often at a detriment to the rest of the genome. Metabolic costs of the X-linked sex ratio (SR) meiotic drive were investigated in stalk-eyed flies (Teleopsis dalmanni). The experiments demonstrate that individuals with SR have reduced capacity for ATP synthesis. The disruption in mitochondrial function leads to compensation exhibited in increased basal metabolic rate and greater food consumption across a range of diets. The range of metabolic costs of drive was evident in males and females at a similar magnitude. The likely cause lies in the accumulation of deleterious mutations within the series of large inversions on the drive X chromosome, subject to low recombination and weak natural selection. In females, the drive chromosome had a dominant effect, with a single copy causing substantial metabolic compromise. There was little evidence of male-specific metabolic costs, nor evidence of greater effects of drive chromosomes on female metabolism. This suggests that direct metabolic costs from meiotic drive on spermatogenesis and from sexually antagonistic selection are relatively weak. Our results underscore the broad physiological impacts that selfish genetic elements have on host metabolism and fitness.}, } @article {pmid40594503, year = {2025}, author = {Li, XY and Wang, JQ and Zheng, KW and Li, YT}, title = {Characterization of glutamine synthetase involved in the fecundity of Rhopalosiphum padi.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {20461}, pmid = {40594503}, issn = {2045-2322}, support = {31801733//National Natural Science Foundation of China/ ; 31801733//National Natural Science Foundation of China/ ; 31801733//National Natural Science Foundation of China/ ; S202110157032//College Students' Innovation and Entrepreneurship Program of Liaoning Province/ ; S202110157032//College Students' Innovation and Entrepreneurship Program of Liaoning Province/ ; }, mesh = {Animals ; *Aphids/enzymology/genetics/physiology/microbiology ; *Glutamate-Ammonia Ligase/genetics/metabolism ; Fertility/genetics ; *Insect Proteins/genetics/metabolism ; Buchnera/physiology ; Phylogeny ; Symbiosis ; Amino Acid Sequence ; Cloning, Molecular ; }, abstract = {Glutamine synthetase (GS) is a pivotal enzyme crucial for the synthesis of glutamine (Gln), an important precursor in amino acid biosynthesis, essential for the growth, development, and reproduction of insects through its involvement in nitrogen metabolism. Despite its recognized significance in insect biology, the specific functions of GS in aphids have not been fully elucidated. Here, we cloned and characterized two GS genes, RpGS1 and RpGS2, from Rhopalosiphum padi and analyzed their expression profiles and explored the contribution of RpGS to aphid fecundity. The two isoforms, which are predicted to localize in the mitochondria and cytoplasm respectively, were successfully cloned and heterologously expressed in Escherichia coli. Despite exhibiting 92% amino acid similarity, the isoforms displayed distinct enzymatic kinetic properties and demonstrated variations in mRNA expression levels across developmental stages and tissues. Notably, RpGS1 was highly expressed in the head, whereas RpGS2 was highly expressed in the intestine. Both RpGS genes were significantly expressed in alate adult aphids. Treatment with the specific inhibitor L-methionine S-sulfoximine (MSX) not only suppressed enzyme activity but also downregulated gene expression. Furthermore, inhibition of RpGS led to a marked decrease in the abundance of the obligate symbiont Buchnera and reduced the fecundity of R. padi. The transcript levels of RpVg and RpGT were also downregulated. These findings underscore the significant role of RpGS in regulating fecundity, suggesting its potential as a target for insecticide development in pest management strategies.}, } @article {pmid40595321, year = {2025}, author = {Yu, R and Liu, L and Jost, M and Zhao, R and Wanke, S and Jiao, Y}, title = {Evolution of mitochondrial RNA editing sites and stop codon-lacking transcripts in angiosperms.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {977}, pmid = {40595321}, issn = {2399-3642}, support = {32221001//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {*RNA Editing ; *Magnoliopsida/genetics ; *Evolution, Molecular ; *Codon, Terminator/genetics ; *RNA, Mitochondrial/genetics ; Gene Expression Regulation, Plant ; Mitochondria/genetics ; RNA, Plant/genetics ; }, abstract = {While the evolution of mitochondrial protein-coding genes in angiosperms has been extensively studied, the post-transcriptional RNA processing remains under-explored. Leveraging newly generated and public RNA-seq data from twenty representative angiosperms, we systematically inferred the gain-and-loss dynamics of RNA editing sites within mitochondrial protein-coding genes. Our findings reveal magnoliids retain more ancestral RNA editing sites compared to monocots and eudicots. Furthermore, we uncovered contrasting correlations between gene expression levels and RNA editing density: negative in core mitochondrial genes but positive in variable genes. We also identified widespread occurrence of stop codon-lacking transcripts of four genes (ccmC, nad6, sdh3 and sdh4) across angiosperms, a phenomenon mainly reported in Arabidopsis thaliana. Besides the known t-element previously identified in A. thaliana, we revealed another distinct motif that may contribute to the post-transcriptional processing of nad6 transcripts. Novel stem-loop motifs that may mediate the formation of stop codon-lacking transcripts of ccmC, sdh3 and sdh4 genes were also identified. Collectively, our study sheds light on the ancestral RNA editing characteristics of angiosperm mitochondrial genes, and provides evidence that the processing-derived stop codon-lacking transcripts predate the divergence of angiosperms.}, } @article {pmid40602500, year = {2025}, author = {Wang, Q and You, C and Qu, X and Zhang, Y and Bai, Y and Lin, X and Wang, Z and Fang, H and Lyu, J and Jiang, M and Wang, Y}, title = {Mitochondrial DNA genotypes modify m.3243A>G-associated mitochondrial disease via the 15-HETE/Akt/FoxO1 pathway.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {1872}, number = {7}, pages = {120012}, doi = {10.1016/j.bbamcr.2025.120012}, pmid = {40602500}, issn = {1879-2596}, mesh = {Humans ; *DNA, Mitochondrial/genetics ; *Proto-Oncogene Proteins c-akt/metabolism/genetics ; *Forkhead Box Protein O1/metabolism/genetics ; *Mitochondrial Diseases/genetics/metabolism/pathology ; Genotype ; Signal Transduction ; Mitochondria/genetics/metabolism ; Oxidative Phosphorylation ; Haplotypes ; Apoptosis/genetics ; Mutation ; }, abstract = {Mitochondrial disease caused by mitochondrial DNA (mtDNA) 3243A>G mutation is characterized by high levels of clinical heterogeneity. Varied m.3243A>G mutation loads among patients are used to, but cannot fully explain, disease heterogeneity. Here, we found that mtDNA genotypes (haplogroups) modify m.3243A>G-associated natural selection and cell fate determination. mtDNA haplogroup M7 was less prevalent in a multi-center m.3243A>G disease cohort. Further functional studies using cybrids showed that M7 accelerated cell proliferation and shortened G0/G1 cell cycle when compared with cybrid carrying a non-M7 haplogroup (D5). However, mitochondrial function and cell viability were even worse in M7 cybrid than D5 cybrid when treated with mitochondrial oxidative phosphorylation (OXPHOS) inhibitors, indicating that M7 drives negative selection in patients with m.3243A>G during evolution. By adopting multi-omics strategies, we showed a lesser increase of 15-hydroxyeicosatetraenoic acid (15-HETE) levels in M7 cybrid owing to OXPHOS inhibition, leading to insufficient Akt/FoxO1 activation and increased apoptosis. Notably, 15-HETE administration activated Akt/FoxO1 phosphorylation and abolished apoptosis difference between M7 and D5 cybrids, suggesting that augmented 15-HETE was vital to protect cells from death. Collectively, our work identified a genetic modifier of m.3243A>G-associated mitochondrial disease and demonstrated that the mitochondrial retrograde 15-HETE/Akt/FOXO1 signaling cascade plays an important role in protecting cells from OXPHOS dysfunction-induced cell death.}, } @article {pmid40603484, year = {2025}, author = {Gardellin, JV and Gestich, CC and Galetti, PM and Portela, L and Guimarães, VY and de Melo, FR and Goldberg, A and de Freitas, PD}, title = {Genetic diversity and structure of red handed howler monkeys assessed by mitochondrial and genotyping by sequencing analyses.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {23418}, pmid = {40603484}, issn = {2045-2322}, support = {CEPID-CBioClima 2021/10639-5//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; R35 GM133481/GM/NIGMS NIH HHS/United States ; 303524/2019-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 2021/05923-6//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; R01 AI175622/NH/NIH HHS/United States ; R01 AI175622/AI/NIAID NIH HHS/United States ; 150808/2019-4//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 317345/2021-4//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Animals ; *Genetic Variation ; *Alouatta/genetics/classification ; Phylogeny ; Haplotypes ; *DNA, Mitochondrial/genetics ; Genotype ; Brazil ; *Mitochondria/genetics ; Sequence Analysis, DNA ; Genotyping Techniques ; }, abstract = {The red-handed howler monkey, Alouatta belzebul, has an uncertain taxonomy complex that includes A. belzebul, A. discolor and A. ululata. These primates are endemic to Brazil and are classified as vulnerable or endangered by the IUCN Red List due to population declines over the past 40 years. Damming by hydroelectric power plants is the greatest threat to the taxa. The recent implantation of the fourth largest dam worldwide (Belo Monte Hydroelectric Dam, UHBM) threatens their populations, because its flooding zone covers areas where A. belzebul and A. discolor may co-occur. Determining species classification is crucial for conservation efforts. Here, we characterized the genetic diversity and structure of howler monkeys rescued before the flooding. We performed Genotyping by Sequencing (GBS) analyses and constructed a mitochondrial-based phylogenetic tree and a haplotype network in specimens identified as A. belzebul, based on their coat color, from both banks of the Xingu River and three islands. The study revealed the occurrence of both taxa, indicating high genetic diversity. These findings are valuable for understanding group diversity, providing reference data for monitoring populations in the region and implementing conservation actions, as well as serving as a model for similar studies of other taxa.}, } @article {pmid40604449, year = {2025}, author = {Chen, L and Yan, RR and Yang, CY and Ling, LZ and Bai, XX and Ren, QF and Hu, GX}, title = {Mitochondrial genome analysis of the endangered Oreocharis esquirolii: insights into evolutionary adaptation and conservation.}, journal = {BMC plant biology}, volume = {25}, number = {1}, pages = {827}, pmid = {40604449}, issn = {1471-2229}, support = {Qiankehefuqi [2024]013//special fund for innovation capacity construction of Guizhou research institution/ ; QKY-R[2021]08//Guizhou Academy of Science/ ; Qiankehezhongyindi [2023] 029//Natural Science Foundation of Guizhou Province/ ; }, abstract = {BACKGROUND: Oreocharis esquirolii H. Lév., a member of the Gesneriaceae family with an actinomorphic corolla, is evaluated as vulnerable and classified as a National Grade I Protected Plant. The species is endemic to Guizhou Province in southwestern China, restricted to the Longtoudashan Nature Reserve. Current research on mitochondrial genomes (mitogenomes) in Gesneriaceae plants is limited to only three species. Given the crucial role of mitochondria in plant energy metabolism and stress responses, mitogenome analyses may offer novel insights into the genetic basis of adaptive traits and contribute to understanding evolutionary processes. Therefore, in this study, we assembled and annotated the mitogenome of O. esquirolii, and performed comparative analyses to investigate structural features and variation across mitogenomes.

RESULTS: The mitogenome of O. esquirolii exhibited a linear structure, consisting of 36 protein-coding genes (PCGs), 23 tRNA genes, three rRNA genes, and one pseudogene. A total of 158 repeat sequences were identified, with the majority located in intergenic regions, while a smaller fraction appeared in coding regions. Homology analysis revealed 58 plastid-derived fragments, spanning 52,103 bp and accounting for 11.45% of the mitogenome. Collinearity analysis demonstrated extensive genomic rearrangements between O. esquirolii and its close relatives, implying structural divergence during evolution. Positive selection signals were detected in seven coding genes of the O. esquirolii mitogenome, with a potential impact on environmental adaptation. Phylogenetic analysis inferred from shared mitochondrial genes presented a well-supported topology, in which O. esquirolii was closely related with Primulina hunanensis K. M. Liu & X. Z. Cai.

CONCLUSION: Overall, this study presents the first report of the complete mitogenome of O esquirolii, revealing a linear structure, extensive genomic rearrangements, and frequent plastid-derived DNA insertions. Despite structural variation, the mitogenomes of O. esquirolii remains relatively conserved at the sequence level, particularly in terms of gene content, GC content, and codon usage bias. These findings highlight dynamic genomic evolution and provide critical molecular resources for future studies on plant adaptation and species conservation.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12870-025-06838-7.}, } @article {pmid40613303, year = {2025}, author = {Stefano, GB}, title = {Mitochondria: A Covert Chronic Infection Masquerading as a Symbiotic Partner?.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {30}, number = {6}, pages = {42854}, doi = {10.31083/FBL42854}, pmid = {40613303}, issn = {2768-6698}, mesh = {*Symbiosis ; *Mitochondria/physiology/microbiology/metabolism/ultrastructure ; Humans ; Animals ; *Persistent Infection/microbiology ; Host-Pathogen Interactions ; Bacteria/metabolism ; Chronic Disease ; }, abstract = {Mitochondria, ubiquitous in eukaryotic cells, evolved from an ancestral aerobic alpha-proteobacterium that had been phagocytosed by a primordial archaeal cell. Numerous factors link mitochondria to current-day bacteria, notably the facultative pathogens that are phagocytosed and survive within the host as a chronic infection. Despite these parallels, we typically refer to mitochondria as "symbionts" and rarely consider them as perhaps the most successful example of long-term chronic infection. Here, we will explore critical aspects of mitochondrial structure and function and consider what we might learn by refocusing our attention on mitochondria as bacteria that are uniquely adapted to their host cell, i.e., as a chronic infection tolerated by its eukaryotic host.}, } @article {pmid40619778, year = {2025}, author = {Bhide, AJ}, title = {Redefining the nitroplast: Recent insights into the endosymbiontto- organelle transition.}, journal = {Journal of biosciences}, volume = {50}, number = {}, pages = {}, pmid = {40619778}, issn = {0973-7138}, mesh = {*Symbiosis/genetics ; Gene Transfer, Horizontal ; Photosynthesis/genetics ; *Plastids/genetics ; Cyanobacteria/genetics ; Rhodophyta/genetics ; Mitochondria/genetics ; Chlorophyta/genetics ; Alphaproteobacteria/genetics ; Biological Evolution ; Evolution, Molecular ; Dinoflagellida/genetics ; }, abstract = {One of the most remarkable events in cellular evolution is the endosymbiosis of α-proteobacteria with a single archaean host cell, a rare evolutionary process, which eventually led to the transformation of symbionts into fully functional mitochondrial organelles in eukaryotes. Evolutionary events related to plants occurred almost 1.6 billion years ago, when eukaryotic heterotrophs acquired a β-cyanobacterium (containing 1B RUBISCO) in what is termed as primary endosymbiosis. Further, this composite cell lineage evolved into three photosynthetic lineages: green algae (plants), red algae and the glaucophytes. Thereafter, a secondary, and tertiary endosymbiosis event occurred giving rise to distinct kinds of green and red-derived photosynthetic plastids, which can be observed in a few haptophytes and dinoflagellates respectively. Eventually, these endosymbionts acquired characteristic cellular properties such as two/multiple envelope membranes and reduction of their genomes through either loss or concerted endosymbiotic gene transfer (EGT) into the nucleus, which ultimately led to the decline of more than three quarters of coding capacity and complete loss of several metabolic pathways. This loss, however, is partly compensated by import of nuclearencoded proteins as well as proteins acquired by horizontal gene transfer (HGT). For most proteins, specific transport mechanisms from nucleus/cytoplasm to organelle exist. The proteins are typically translated as a preprotein with specific signal sequences targeted to the organelle membrane. These membranes harbour receptors, in some cases soluble receptors, for recognition of these signal sequences. Proteins are then internalised using a set of translocation machineries (Gould et al. 2006).}, } @article {pmid40625319, year = {2025}, author = {Cai, L and Jansen, RK and Havird, JC}, title = {Altered Mitochondrial Respiration Is Associated With Loss of Nuclear-Encoded OXPHOS Genes in Parasitic Broomrapes.}, journal = {Ecology and evolution}, volume = {15}, number = {7}, pages = {e71737}, pmid = {40625319}, issn = {2045-7758}, abstract = {Parasitic plants, characterized by their dependency on host organisms for nutrients, have displayed far-reaching alterations in physiology and genetics. While significant gene losses and relaxed selection have been documented in the nuclear and plastid genomes, how parasitism impacts the molecular evolution and function of mitochondria has remained controversial. One of the main culprits hindering our understanding in this area is the lack of knowledge on nuclear-encoded mitochondrial-targeted genes (N-mt), which encode most mitochondrial oxidative phosphorylation (OXPHOS) proteins. By conducting a comprehensive survey of N-mt genes across angiosperms, we demonstrated significant gene losses and occasional horizontal transfers associated with relaxed selection unique to holoparasitic Orobanchaceae. These putative losses and transfers have the potential to affect mitochondrial function directly and cause cytonuclear incompatibility because of breakdown between co-evolved protein complexes from mitochondrial and nuclear genomes. Our physiological assessments using high-resolution respirometry revealed that despite genetic alterations, holoparasitic Orobanchaceae maintained OXPHOS capacity but relied more on the fully nuclear-encoded succinate dehydrogenase (complex II). Our results document the first example of biased loss of nuclear-encoded OXPHOS genes without accompanying mitochondrial-encoded gene loss in parasitic plants, expanding on previous studies and elucidating the mechanisms underlying the preservation of OXPHOS function despite genomic reduction.}, } @article {pmid40650192, year = {2025}, author = {Pierro, F and Fazio, M and Murdaca, G and Stagno, F and Gangemi, S and Allegra, A}, title = {Oxidative Stress and Mitochondrial Dysfunction in Myelodysplastic Syndrome: Roles in Development, Diagnosis, Prognosis, and Treatment.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40650192}, issn = {1422-0067}, mesh = {Humans ; *Myelodysplastic Syndromes/diagnosis/metabolism/therapy/pathology ; *Oxidative Stress ; *Mitochondria/metabolism/pathology ; Reactive Oxygen Species/metabolism ; Prognosis ; Animals ; }, abstract = {Myelodysplastic syndromes are a group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenia, and dysplasia in one or more myeloid lineages, with a variable risk of progression to acute myeloid leukemia. In addition to well-characterized genetic and epigenetic abnormalities, oxidative stress has emerged as a critical contributor to the pathophysiology of myelodysplastic syndrome. Reactive oxygen species and reactive nitrogen species can induce cumulative DNA damage, mitochondrial dysfunction, and altered redox homeostasis, promoting genomic instability and clonal evolution. Elevated oxidative stress in patients with myelodysplastic syndromes has been linked to increased apoptosis of hematopoietic stem and progenitor cells, disruption of the bone marrow microenvironment, and progression toward leukemic transformation. Moreover, ROS-related pathways, such as TP53 mutations and epigenetic dysregulation, interact with the key molecular drivers of myelodysplastic syndrome. Given these findings, oxidative stress is now recognized not only as a hallmark of disease biology but also as a potential therapeutic target. Antioxidant-based strategies and agents that modulate redox signaling are being investigated for their ability to restore hematopoietic function and enhance treatment efficacy. This review provides an overview of the current biology of myelodysplastic syndrome, highlights the connections between oxidative stress and disease mechanisms, and explores emerging redox-targeted therapeutic approaches.}, } @article {pmid40652880, year = {2025}, author = {Zhang, X and Lu, X and Dai, M and Fan, Y and Yang, Z and Sun, Y and Yu, X and Song, R and Zhang, M and Lan, H and Chen, X and Wang, S and Wang, J and Guo, L and Li, L and Li, Y and Zhao, L and Hao, F and Ye, W}, title = {Citrate accumulation mediated through GhCS6 enhances antioxidant modulation under Cd[2+] stress in cotton.}, journal = {Plant physiology and biochemistry : PPB}, volume = {228}, number = {}, pages = {110226}, doi = {10.1016/j.plaphy.2025.110226}, pmid = {40652880}, issn = {1873-2690}, mesh = {*Cadmium/toxicity/metabolism ; *Gossypium/metabolism/genetics/drug effects ; *Antioxidants/metabolism ; *Plant Proteins/metabolism/genetics ; *Citric Acid/metabolism ; *Citrate (si)-Synthase/metabolism/genetics ; Gene Expression Regulation, Plant/drug effects ; Reactive Oxygen Species/metabolism ; Oxidative Stress/drug effects ; *Stress, Physiological/drug effects ; Hydrogen Peroxide/metabolism ; Phylogeny ; }, abstract = {Citrate synthase (CS) catalyzes the biosynthesis of citrate (CA), a tricarboxylic acid metabolite that serves as a pivotal biochemical regulator in plant cellular metabolism. This investigation conducted systematic genome-wide identification of CS family, integrating structural, phylogenetic relationships, collinearity analysis, cis-acting elements and expression analysis. GhCS6 protein is localized in the mitochondria. The pivotal cadmium-responsive regulatory candidate gene GhCS6 was identified, followed by its silencing mediation through virus-induced gene silencing (VIGS), silenced plants displaying phenotypic evidence of enhanced Cd[2+] susceptibility. Simultaneously, CA content in the silenced plants was also significantly decreased, which reduced the chelating capacity for Cd[2+] and consequently exacerbates the accumulation of Cd[2+]. The silenced plants showed an imbalance in the reactive oxygen species (ROS) scavenging system, as evidenced by lower superoxide dismutase (SOD) activity and a marked increase in H2O2 content, causing increased oxidative damage. This oxidative stress further compromised the integrity of cellular membranes, resulting in elevated malondialdehyde (MDA) content and compromised cellular structure. These changes ultimately impaired photosynthetic efficiency and plant growth and development. This study contributes significantly to understanding the function of the GhCS6 in plant Cd[2+] tolerance, and identifies potential gene targets for breeding Cd[2+] tolerant cotton varieties.}, } @article {pmid40654039, year = {2025}, author = {Saha, S and Hearn-Thomas, B and Marisa, V and Depiazzi, K and Schaefer, M and Murcha, MW}, title = {Structural and Functional Perspectives on Mitochondrial LYR-Domain Proteins in Plants.}, journal = {Physiologia plantarum}, volume = {177}, number = {4}, pages = {e70393}, pmid = {40654039}, issn = {1399-3054}, support = {DP210103258//Australian Research Council/ ; //Australian Government's Research Training Program/ ; //University of Western Australia/ ; }, mesh = {*Arabidopsis/metabolism/genetics ; *Mitochondrial Proteins/metabolism/genetics/chemistry ; *Arabidopsis Proteins/metabolism/genetics/chemistry ; *Mitochondria/metabolism ; Gene Expression Regulation, Plant ; Protein Domains ; Phylogeny ; }, abstract = {Arabidopsis thaliana contains 12 nuclear-encoded mitochondrial LYR (leucine/tyrosine/arginine) motif-containing proteins (LYRMs). Four of these proteins have been previously characterized in plants and were found to be involved in iron-sulfur cluster biogenesis and/or respiratory complex assembly. The function of the remaining eight is yet to be determined. Evolutionary analysis revealed that several LYRM proteins are unique to plants, while others share evolutionary ties with metazoans and fungi. Protein localization studies confirmed mitochondrial targeting for all 12 proteins, and expression profiles indicated high transcript abundance during germination and in developing tissues. Structural modeling highlighted the potential role of the LYR domain in protein-protein interactions with mitochondrial acyl carrier proteins, subunits of respiratory complexes, and chaperones. These findings enhance our understanding of the diverse roles of LYRM proteins in mitochondrial function in plants.}, } @article {pmid40660128, year = {2025}, author = {Miyata, M and Nomura, M and Kageyama, D}, title = {Elusive origin of mitochondria shared by two sister species of Eurema butterflies.}, journal = {BMC ecology and evolution}, volume = {25}, number = {1}, pages = {71}, pmid = {40660128}, issn = {2730-7182}, support = {18J21090//JSPS KAKENHI/ ; 23K26922//JSPS KAKENHI/ ; }, mesh = {Animals ; *Butterflies/genetics/microbiology/classification ; *Wolbachia/genetics/physiology ; Phylogeny ; DNA, Mitochondrial/genetics ; *Mitochondria/genetics ; Haplotypes ; Japan ; Symbiosis ; }, abstract = {BACKGROUND: Wolbachia are maternally inherited arthropod endosymbionts known for their diverse effects on host reproduction, which serve to increase their prevalence in host populations. As Wolbachia spreads, the frequency of the associated mitochondrial DNA (mtDNA) haplotypes tends to increase within the host population. Two distinct Wolbachia strains, wCI and wFem, are shared by two pierid butterfly sister species: Eurema mandarina and Eurema hecabe. The congruence of mtDNA phylogeny and Wolbachia infection status suggests hybrid introgression of mtDNA from E. hecabe to E. mandarina. This inference is based on the observation that uninfected E. mandarina have unique mtDNA haplotypes, distinct from the mtDNA haplotypes found in Wolbachia-infected E. mandarina and E. hecabe. In E. hecabe, Wolbachia infection has been considered fixed, with no expectation of uninfected individuals.

RESULTS: Unexpectedly, Wolbachia-free E. hecabe individuals were discovered on the Yonaguni Island of Japan. We included these individuals in the phylogenetic analyses to reassess the impact of Wolbachia infection on Eurema butterflies. The nuclear Triosephosphate isomerase gene-based phylogenetic tree formed two discrete clades corresponding to E. mandarina and E. hecabe. Contrastingly, the mitochondrial cytochrome c oxidase subunit I gene-based tree consisted of three clades, Wolbachia-free E. mandarina, Wolbachia-free E. hecabe, and a clade consisting of Wolbachia-infected E. mandarina and E. hecabe, as well as two other Eurema species, Eurema ada and Eurema lacteola.

CONCLUSIONS: Our findings indicate that the mitochondria shared by E. mandarina and E. hecabe likely originate from a different species of Eurema (E. ada, E. lacteola, or others). Although the origin was not identified, our results indicate that Wolbachia provides significant evolutionary advantages to the associated mtDNA haplotypes across multiple Eurema species, leading to a complex mtDNA phylogeny.}, } @article {pmid40661768, year = {2025}, author = {Zhang, S and Zhang, Y and Luo, S and Gao, J and Hu, H and Liu, J and Wu, W and Wang, J and Huang, X and Lai, H and Huang, D}, title = {Mitochondrial genome assembly and comparative analysis of decaploid Camellia hainanica.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1556379}, pmid = {40661768}, issn = {1664-462X}, abstract = {INTRODUCTION: Decaploid Camellia hainanica is a new tea oil Camellia species discovered in recent years that is unique to Hainan. This species has high nutritional and medicinal value and shows strong adaptability in the growth process. Mitochondria play an important role in plant cells and have an independent genetic system. Therefore, assembling and annotating the mitochondrial genome function of decaploid C. hainanica is of great significance.

METHODS: This study successfully assembled the mitochondrial genome of decaploid C. hainanica and comprehensively annotated its functional genes using the Nanopore sequencing platform.

RESULTS: Results showed that the mitochondrial genome is 902,617 bp in length, with a typical circular structure and a guanine-cytosine content of 45.79%. The genome encodes 64 protein-coding genes and contains a total of 76 genes, including 40 mRNA, 32 tRNA, 3 rRNA, and 1 pseudogene. Tetranucleotide repeats accounted for 38.60% of the simple sequence repeats. Only two genes, atp6 and sdh4, had a Ka/Ks ratio <1, whereas the Pi value of the sdh3 gene had a maximum of 0.00374 in these regions, suggesting that the sdh3 gene can be used as a molecular marker for the analysis of the mitochondrial genome of C. hainanica. From the relative synonymous codon usage (RSCU) analysis, 29 codons had RSCU values >1, 27 of which (93%) ended in A or U, indicating a bias for A/U endings is present in C. hainanica. During RNA editing, 48.24% (260 loci) of amino acids were changed from hydrophilic to hydryophobic, resulting in an increase in the hydrophobicity of the protein. Comparative analysis identified 34 homologous fragments between the mitochondrial and chloroplast genomes, with the longest fragment being 9,572 bp in length. Phylogenetic analysis of the genomes showed that the Hainanese and Vietnamese varieties of tea oil Camellia are sister species.

DISCUSSION: Results confirmed that the mitochondrial genomes of Hainanese and Vietnamese tea oil Camellia underwent gene rearrangement. Results also provided key data support for the utilization and conservation of tea oil germplasm resources and the breeding of varieties and are of great significance for promoting genetic evolution research, genetic breeding, and identification of tea oil Camellia.}, } @article {pmid40667285, year = {2025}, author = {Robles, NV and Moran, BM and Rodríguez-Barrera, MJ and Jofre, GI and Gunn, T and Iverson, ENK and Beskid, S and Baczenas, JJ and Sedghifar, A and Andolfatto, P and Powell, DL and Brandvain, Y and Havird, JC and Rosenthal, GG and Schumer, M}, title = {Admixture mapping reveals evidence for multiple mitonuclear incompatibilities in swordtail fish hybrids.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.01.30.635158}, pmid = {40667285}, issn = {2692-8205}, support = {R01 GM115523/GM/NIGMS NIH HHS/United States ; R35 GM133774/GM/NIGMS NIH HHS/United States ; R35 GM142836/GM/NIGMS NIH HHS/United States ; }, abstract = {How barriers to gene flow arise between closely related species is one of the oldest questions in evolutionary biology. Classic models in evolutionary biology predict that negative epistatic interactions between variants in the genomes of diverged lineages, known as hybrid incompatibilities, will reduce viability or fertility in hybrids. The genetic architecture of these interactions and the evolutionary paths through which they arise have profound implications for the efficacy of hybrid incompatibilities as barriers to gene flow between species. While these questions have been studied using theoretical approaches for several decades, only recently has it become possible to genetically map larger numbers of hybrid incompatibilities. Here, we use admixture mapping in natural hybrid populations of swordtail fish (Xiphophorus) to identify hybrid incompatibilities involving genetic interactions between the mitochondrial and nuclear genomes. We find that at least nine regions of the genome are involved in mitonuclear incompatibilities. These incompatibilities involve interactions between the nuclear genome and the X. malinche mitochondria, the X. birchmanni mitochondria, or both. Moreover, they vary in the strength of selection they experience, and the degree to which they limit gene flow in natural hybrid populations. Our results build a deeper understanding of the complex architecture of selection against incompatibilities in naturally hybridizing species and highlight an important role of mitonuclear interactions in the evolution of reproductive barriers between closely related species.}, } @article {pmid40668421, year = {2025}, author = {Rocamontes-Morales, JA and Baeza, JA and Martínez-Cárdenas, A and Ortega, J and Castellanos-Morales, G}, title = {Mitochondrial selection and evolutionary insights into nectarivory in Glossophaginae (New world leaf-nosed bats).}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {720}, pmid = {40668421}, issn = {1573-4978}, support = {700958//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; 15307//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; 15307//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; }, mesh = {Animals ; *Chiroptera/genetics/physiology/classification ; Phylogeny ; Genome, Mitochondrial/genetics ; *Selection, Genetic ; *Evolution, Molecular ; *Mitochondria/genetics ; Feeding Behavior ; }, abstract = {BACKGROUND: The family Phyllostomidae, encompassing a wide range of feeding strategies, is one of the most ecologically diverse groups of bats in the Americas. Within this family, nectarivorous bats of the subfamily Glossophaginae play a significant ecological role as pollinators. This study investigated the mitochondrial genome evolution of species in the Glossophaginae subfamily, focusing on selective pressures acting on their mitochondrial protein-coding genes (PCGs) compared with those of closely related frugivorous and insectivorous species in the family Phyllostomidae.

METHODS AND RESULTS: We sequenced the complete mitochondrial genomes of Glossophaga morenoi and Glossophaga mutica, revealing typical features such as AT-rich nucleotide composition and conserved gene order. Phylogenetic analyses based on PCGs confirmed the relationships of G. morenoi and G. mutica within the genus Glossophaga. We analyzed signals of selective pressures across mitochondrial PCGs using Ka/Ks (ω) values among species in the genus Glossophaga. Ka/Ks (ω) values were consistently < 1 across all studied genes, suggesting that signals of purifying selection act in the mitochondrial genome. Moreover, with RELAX analysis, we found signals of a shift in selection pressures in ATP8, COX1, CYTB, and ND5 PCGs of the subfamily Glossophaginae in comparison to those of Stenodermatinae (frugivorous) and Lonchorhininae (insectivorous) bats. Additionally, MEME selection analysis of these four genes, with a focus on the subfamily Glossophaginae, revealed signatures of positive selection in individual sites of PCGs, which could be associated with adaptations to their nectarivorous diet.

CONCLUSIONS: We found conserved mitogenomes in the genus Glossophaga, yet our results reveal significant signatures of selection that may reflect adaptations to the metabolic demands of a nectarivorous lifestyle in Glossophaginae bats.}, } @article {pmid40670931, year = {2025}, author = {Chen, J and Jakovlić, I and Sablin, M and Xia, S and Xu, Z and Guo, Y and Kuang, R and Zhong, J and Jia, Y and Tran, NTT and Yang, H and Ma, H and Šprem, N and Han, J and Liu, D and Zhao, Y and Zhao, S}, title = {Positive selection on rare variants of IGF1R and BRD4 underlying the cold adaptation of wild boar.}, journal = {Genetics, selection, evolution : GSE}, volume = {57}, number = {1}, pages = {40}, pmid = {40670931}, issn = {1297-9686}, support = {31961143020//nsfc/ ; 2021-YF05-01331-SN//Fifth Batch of Technological Innovation Research Projects in Chengdu/ ; 2020HXBH087//Postdoctoral Research and Development Fund of West China Hospital/ ; 139190032//Short-Term Expert Fund of West China Hospital/ ; 122031100282-2//ZIN RAS/ ; 2019-04-4096//Croatian Science Foundation/ ; }, mesh = {Animals ; *Transcription Factors/genetics ; *Selection, Genetic ; *Sus scrofa/genetics/physiology ; Swine/genetics ; Cold Temperature ; *Receptor, IGF Type 1/genetics ; *Adaptation, Physiological/genetics ; Polymorphism, Single Nucleotide ; *Acclimatization/genetics ; *Cell Cycle Proteins/genetics ; }, abstract = {BACKGROUND: Domestic piglets often die of hypothermia, whereas Eurasian wild boar (Sus scrofa) thrives from tropical lowlands to subarctic forests. The thermoregulation of wild boar offers a natural experiment to uncover the genetic basis of cold adaptation.

METHODS: We conducted whole-genome resequencing on wild populations from cold regions (northern and northeastern Asia, with six samples) and warm regions (southeastern Asia and southern China, with five samples). By integrating publicly available data, we compiled a core dataset of 48 wild boar samples and an extended dataset of 445 wild boar and domestic pig samples to identify candidate genes related to cold adaptation. To investigate the functional effects of two candidate variants under positive selection, we performed CUT&Tag and RNA-seq using the northeastern Asian Min pig breed as a proxy for a cold-adapted population.

RESULTS: Our study identified candidate genes associated with cold adaptation, which are significantly enriched in thermogenesis, fat cell development, and adipose tissue pathways. We discovered two enhancer variants under positive selection: an intronic variant of IGF1R (rs341219502) and an exonic variant of BRD4 (rs327139795). These variants exhibited the highest differentiation between populations of wild boar and domestic pigs in cold and warm region populations. Furthermore, these rare variants were absent in outgroup species and warm-region wild boars but were nearly fixed in cold-region populations. The H3K27ac CUT&Tag profiling revealed that the rs341219502 variant of IGF1R is linked to the gain of novel binding sites for three transcription factors involving regulatory changes in enhancer function. In contrast, the rs327139795 variant of BRD4 may result in the loss of a phosphorylation site due to an alteration in the amino acid sequence.

CONCLUSION: Our study identified candidate genes for cold adaptation in wild boar. The variant rs341219502 in the IGF1R enhancer and the variant rs327139795 in the BRD4 exon, both of which were under positive selection and nearly fixed in populations from cold regions, suggest they may have originated de novo in these populations. Further analysis indicated that rs341219502 could influence enhancer function, while rs327139795 may affect amino acid alterations. Overall, our study highlights the adaptive evolution of genomic molecules that contribute to the remarkable environmental flexibility of wild boar.}, } @article {pmid40674831, year = {2025}, author = {Shimomura, M and Hurd, TR}, title = {Why and how paternal mitochondrial DNA gets cut out of the inheritance.}, journal = {Current opinion in genetics & development}, volume = {94}, number = {}, pages = {102381}, doi = {10.1016/j.gde.2025.102381}, pmid = {40674831}, issn = {1879-0380}, mesh = {*DNA, Mitochondrial/genetics ; Humans ; Animals ; *Mitochondria/genetics ; *Paternal Inheritance/genetics ; Male ; Maternal Inheritance/genetics ; Evolution, Molecular ; Spermatozoa/metabolism/growth & development ; Female ; Autophagy/genetics ; }, abstract = {Mitochondrial DNA (mtDNA) is inherited maternally across animals, yet the evolutionary rationale behind this unusual mode of inheritance remains a longstanding mystery. Understanding the processes that prevent the transmission of paternal mtDNA and thus ensure maternal-only inheritance is crucial to uncovering the evolutionary significance of this widespread phenomenon. Historically, research has focused on mechanisms that act within eggs to destroy sperm mitochondria via autophagy and the ubiquitin-proteasome degradation system. However, recent discoveries across multiple animal species, including humans, reveal a surprising twist: paternal mtDNA is actively degraded within mitochondria independently of and prior to the complete breakdown of the organelle itself, often even prior to fertilization. Only a few studies have begun to illuminate the molecular machinery responsible for this early mtDNA elimination. In this review, we explore the emerging landscape of paternal mtDNA elimination mechanisms across species, highlighting newly discovered pathways, evolutionary implications, and open questions that are furthering our understanding of mitochondrial inheritance.}, } @article {pmid40685983, year = {2025}, author = {Recio, P and Leibold, DC and Crino, OL and Friesen, CR and Noble, DWA}, title = {Prenatal conditions do not affect brain physiology and learning in a lizard.}, journal = {The Journal of experimental biology}, volume = {228}, number = {15}, pages = {}, pmid = {40685983}, issn = {1477-9145}, support = {PhD Scholarship//Australian National University/ ; DP210101152//Australian Research Council/ ; //National Australian University/ ; //The Australian National University/ ; }, mesh = {Animals ; *Lizards/physiology/embryology ; *Brain/physiology ; *Corticosterone/pharmacology ; Female ; Mitochondria/physiology/metabolism ; *Spatial Learning ; Temperature ; Learning ; Male ; }, abstract = {Early environmental factors such as heat or stress hormones can impair learning through brain metabolic function, which is crucial for neural development and synaptic plasticity. However, whether early environments always result in cognitive impairment through changes in neural physiology is not well established outside of a few model systems. Here, we investigated the effects of prenatal temperature and corticosterone (CORT) on brain mitochondrial activity and spatial learning in the delicate skink (Lampropholis delicata). We treated eggs with either CORT or a control vehicle and incubated at cold (23±3°C) or hot (28±3°C) temperatures. Juveniles were tested in a spatial learning task over 40 days after which mitochondrial function in the medial cortex was assessed. Despite among-individual variation in learning ability, mitochondrial physiology and spatial learning in L. delicata remained robust to prenatal temperature and CORT exposure. No significant relationship was found between mitochondrial function and cognitive performance, contrary to predictions. Increased metabolic capacity correlated with higher production of reactive oxygen species but did not affect oxidative damage, possibly as a result of protective mechanisms. These findings highlight the physiological and cognitive resilience of L. delicata to early-life challenges. Future research should explore whether this robustness extends to other brain regions, cognitive domains and life stages.}, } @article {pmid40701395, year = {2025}, author = {Yang, FG and Liang, YL and Wang, X and Wang, JT and Gao, W and Ye, QY and Li, XY and Yang, Y and Li, HL}, title = {The evolution of Alzheimer's disease: From mitochondria to microglia.}, journal = {Ageing research reviews}, volume = {111}, number = {}, pages = {102838}, doi = {10.1016/j.arr.2025.102838}, pmid = {40701395}, issn = {1872-9649}, mesh = {*Alzheimer Disease/metabolism/pathology ; Humans ; *Microglia/metabolism/pathology ; *Mitochondria/metabolism/pathology ; Animals ; Oxidative Stress/physiology ; }, abstract = {Alzheimer's disease (AD) represents the most prevalent neurodegenerative disorder worldwide. Recent studies highlights that mitochondrial dysfunction drives alterations in microglial function, serving as a pivotal mechanism in the pathogenesis and progression of AD. Increasingly, there is evidence that mitochondrial dysfunction encompasses energy metabolism deficits, heightened oxidative stress, impaired mitochondrial dynamics, disrupted autophagy, and calcium homeostasis imbalances. These impairments modulate microglial activation states, precipitating exacerbated neuroinflammation, altered phagocytic capacity, and increased cellular apoptosis, collectively contributing to microglial dysfunction. This paper presents a narrative review on the relationship between mitochondrial dysfunction and AD, elucidating the impact of mitochondrial impairment on microglia. It summarizes therapeutic strategies that target mitochondria to modulate microglial function, aiming to prevent and treat AD. The goal is to provide new perspectives and insights for AD research and treatment, contributing to improving patients' quality of life and prognosis.}, } @article {pmid40705423, year = {2025}, author = {Lareau, CA and Maschmeyer, P and Yin, Y and Gutierrez, JC and Dhindsa, RS and Gribling-Burrer, AS and Zielinski, S and Hsieh, YH and Nitsch, L and Dimitrova, V and Nalbant, B and Buquicchio, FA and Abay, T and Stickels, RR and Ulirsch, JC and Yan, P and Wang, F and Miao, Z and Sandor, K and Daniel, B and Liu, V and Mendez, PL and Knaus, P and Meyer, M and Greenleaf, WJ and Kundaje, A and Smyth, RP and Munschauer, M and Ludwig, LS and Satpathy, AT}, title = {Cell type-specific purifying selection of synonymous mitochondrial DNA variation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {30}, pages = {e2505704122}, pmid = {40705423}, issn = {1091-6490}, support = {UM1 HG012076/HG/NHGRI NIH HHS/United States ; T32 AI007290/AI/NIAID NIH HHS/United States ; R00 HG012579/HG/NHGRI NIH HHS/United States ; U01 AT012984/AT/NCCIH NIH HHS/United States ; P30CA008748//HHS | NIH | National Cancer Institute (NCI)/ ; P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *DNA, Mitochondrial/genetics ; *Electron Transport Complex IV/genetics ; *Selection, Genetic ; Mitochondria/genetics/metabolism ; CD8-Positive T-Lymphocytes/metabolism/immunology ; *Genetic Variation ; Alleles ; RNA, Transfer/genetics ; }, abstract = {While somatic variants are well-characterized drivers of tumor evolution, their influence on cellular fitness in nonmalignant contexts remains understudied. We identified a mosaic synonymous variant (m.7076A > G) in the mitochondrial DNA (mtDNA)-encoded cytochrome c-oxidase subunit 1 (MT-CO1, p.Gly391=), present at homoplasmy in 47% of immune cells from a healthy donor. Single-cell multiomics revealed strong, lineage-specific selection against the m.7076G allele in CD8[+] effector memory T cells, but not other T cell subsets, mirroring patterns of purifying selection of pathogenic mtDNA alleles. The limited anticodon diversity of mitochondrial tRNAs forces m.7076G translation to rely on wobble pairing, unlike the Watson-Crick-Franklin pairing used for m.7076A. Mitochondrial ribosome profiling confirmed stalled translation of the m.7076G allele. Functional analyses demonstrated that the elevated translational and metabolic demands of short-lived effector T cells (SLECs) amplify dependence on MT-CO1, driving this selective pressure. These findings suggest that synonymous variants can alter codon syntax, impacting mitochondrial physiology in a cell type-specific manner.}, } @article {pmid40714961, year = {2025}, author = {Ball, M and van Bergen, NJ and Compton, AG and Thorburn, DR and Rahman, S and Christodoulou, J}, title = {Therapies for Mitochondrial Disease: Past, Present, and Future.}, journal = {Journal of inherited metabolic disease}, volume = {48}, number = {4}, pages = {e70065}, pmid = {40714961}, issn = {1573-2665}, support = {//Victorian Government's Operational Infrastructure Support Program/ ; //Royal Children's Hospital Foundation/ ; //Mito Foundation, PhD Top Up Scholarship/ ; //Melbourne Academic Centre for Health, Clinician-Researcher Scholarship/ ; //VESKI Near-miss Award Pilot/ ; //Australian National Health and Medical Research Council/ ; //Medical Research Future Fund/ ; //Horizon Medicine/ ; //Innovate UK/ ; //Great Ormond Street Hospital Charity/ ; //Freya Foundation/ ; //Lily Foundation/ ; //National Institute of Health Research Great Ormond Street Hospital Biomedical Research Centre/ ; }, mesh = {Humans ; *Mitochondrial Diseases/therapy/genetics ; Genetic Therapy/methods ; Mitochondria/metabolism/genetics ; DNA, Mitochondrial/genetics ; }, abstract = {Mitochondrial disease is a diverse group of clinically and genetically complex disorders caused by pathogenic variants in nuclear or mitochondrial DNA-encoded genes that disrupt mitochondrial energy production or other important mitochondrial pathways. Mitochondrial disease can present with a wide spectrum of clinical features and can often be difficult to recognize. These conditions can be devastating; however, for the majority, there is no targeted treatment. In the last 60 years, mitochondrial medicine has experienced significant evolution, moving from the pre-molecular era to the Age of Genomics in which considerable gene discovery and advancement in our understanding of the pathophysiology of mitochondrial disease have been made. In the last decade, in response to the urgent need for effective treatments, a wide range of emerging therapies have been developed, driven by innovative approaches addressing both the genetic and cellular mechanisms underpinning the diseases. Emerging therapies include dietary intervention, small molecule therapies aimed to restore mitochondrial function, stem cell or liver transplantation, and gene or RNA-based therapies. However, despite these advances, translation to clinical practice is complicated by the sheer genetic and clinical complexity of mitochondrial disease, difficulty in efficient and precise delivery of therapies to affected tissues, rarity of individual genetic conditions, lack of reliable biomarkers and clinically relevant outcome measures, and the dearth of natural history data. This review examines the latest developments in the pursuit to identify effective treatments for mitochondrial disease and discusses the barriers impeding their success in translation to clinical practice. While treatment for mitochondrial disease may be on the horizon, many challenges must be addressed before it can become a reality.}, } @article {pmid40715117, year = {2025}, author = {Takeda, H and Shinoda, S and Goto, C and Tsutsumi, A and Sakaue, H and Zhang, C and Hirashima, T and Konishi, Y and Ono, H and Yamamori, Y and Tomii, K and Shiino, H and Tamura, Y and Zuttion, S and Senger, B and Friant, S and Becker, HD and Araiso, Y and Kobayashi, N and Kodera, N and Kikkawa, M and Endo, T}, title = {Oligomer-based functions of mitochondrial porin.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {6854}, pmid = {40715117}, issn = {2041-1723}, support = {2222703//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JPMJCR12M1//MEXT | JST | Core Research for Evolutional Science and Technology (CREST)/ ; 21gm1410002h0002//Japan Agency for Medical Research and Development (AMED)/ ; }, mesh = {*Saccharomyces cerevisiae Proteins/metabolism/genetics/chemistry/ultrastructure ; *Saccharomyces cerevisiae/metabolism/genetics ; Cryoelectron Microscopy ; *Mitochondria/metabolism ; Mitochondrial Membranes/metabolism ; *Porins/metabolism/genetics/chemistry ; Models, Molecular ; Mitochondrial Precursor Protein Import Complex Proteins ; Mitochondrial Membrane Transport Proteins/metabolism ; Mutation ; Protein Multimerization ; Voltage-Dependent Anion Channels/metabolism/genetics ; Protein Transport ; }, abstract = {Porin, or the voltage-dependent anion channel (VDAC), is a primary β-barrel channel in the mitochondrial outer membrane. It transports small metabolites and ions through its β-barrel pore and plays key roles in apoptosis and inflammatory response. Here we report the cryo-electron microscopy structure of yeast porin (Por1) in its hexameric form at 3.2 Å resolution. This structure allows us to introduce various mutations at the protomer interfaces, uncovering three critical functions of Por1 assembly beyond transport. Por1 binds unassembled Tom22, a subunit of the mitochondrial protein import gate (the TOM complex), to facilitate protein import into the intermembrane space, maintains proper mitochondrial lipid composition in the outer membrane through lipid scramblase activity, and contributes to the retention and regulated loss of mitochondrial DNA, in cooperation with nucleases identified through screening enabled by the obtained Por1 mutant.}, } @article {pmid40722904, year = {2025}, author = {Meza-Torres, C and Reyes-Torres, I and Bui Thanh, T and Campos-Silva, C and Rodriguez-Bies, E and Navas, P and López-Lluch, G}, title = {Evolution of COQ-Synthome Transcripts and CoQ Levels in Mice Tissues Along Aging: Effect of Resveratrol and Exercise.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {40722904}, issn = {2076-3921}, support = {DEP2012-39985//Ministerio de Economía y Competitividad, Spanish Government/ ; BIO-177//Junta de Andalucía/ ; }, abstract = {The balanced control of the synthesis of CoQ along the life of the organism is essential to maintain the respiratory capacity at the mitochondria and the antioxidant protection of cell membranes and plasma lipoproteins. For this reason, we determined the levels of the transcripts of the CoQ-synthome along the life of mice in comparison with the levels of antioxidant enzymes and the levels of CoQ in these animals. Surprisingly, we found that some organs such as liver, kidney and heart show great differences in mRNA levels of some COQ-genes along life whereas others such as the brain or gastrocnemius muscle do not show differences. Interestingly, these differences were not related to the total amount of CoQ in these tissues, indicating a discrepancy between the transcript activity of the CoQ-synthome and the level of the product, CoQ. This likely responds to different regulatory levels including mRNA lifespan and CoQ turnover. Further, resveratrol and physical activity in old animals can modulate some transcripts but many of them are in an organ-dependent effect, indicating a different response to the regulators.}, } @article {pmid40725489, year = {2025}, author = {Shi, SL and Li, DT and Liu, YQ}, title = {Patchy Phylogenetic Distribution and Poor Translational Adaptation of a Nested ORF in the Mammalian Mitochondrial cytb Gene.}, journal = {Genes}, volume = {16}, number = {7}, pages = {}, pmid = {40725489}, issn = {2073-4425}, mesh = {Animals ; Phylogeny ; *Open Reading Frames/genetics ; Humans ; *Cytochromes b/genetics ; *Protein Biosynthesis ; *Mitochondria/genetics ; Primates/genetics ; Genome, Mitochondrial/genetics ; Evolution, Molecular ; Mammals/genetics ; Rodentia/genetics ; }, abstract = {BACKGROUND: The mammalian mitochondrial genome has long been considered to encode only 13 proteins. However, a recent study identified a nested alternative open reading frame (nAltORF) within the primate mitochondrial cytb gene, which we designate ncytb, that is reportedly translated in the cytosol using the standard genetic code. This discovery challenges conventional understanding and raises questions about the prevalence, conservation, and translational adaptation of such ORFs.

METHODS: This study conducted a comprehensive bioinformatic analysis of nested ncytb genes in 289 primate and 380 rodent mitochondrial cytb sequences.

RESULTS: Nested ncytb genes meeting the criteria (>150 codons, standard genetic code) were identified in only 10.73% of primate and 20.53% of rodent species, suggesting a patchy phylogenetic distribution. While their encoded proteins showed homology to the previously reported protein encoded by the Homo sapiens nested ncytb gene, overall amino acid conservation was low, and characteristic protein domains or signal peptides were generally not predicted. Crucially, the Kozak consensus sequences surrounding the putative start codons of these ncytb genes were exclusively "weak" or "adequate", with none classified as "strong" or "optimal". Codon Adaptation Index (CAI) and Relative Codon Deoptimization Index (RCDI) analyses of the nested ncytb genes revealed neither significant adaptation nor deoptimization to the codon usage of nuclear and mitochondrial genes. Furthermore, cosine similarity analysis indicated that ncytb genes exhibit significantly lower codon usage similarity to both nuclear and mitochondrial gene sets compared to their host cytb genes.

CONCLUSIONS: These findings collectively suggest that while ncytb genes exist in some mammals, their inconsistent presence, weak translational initiation signals, and lack of adaptation to cytosolic codon usage characterize them as dispensable genetic elements rather than core functional genes.}, } @article {pmid40725502, year = {2025}, author = {Hu, T and Zhou, F and Wang, L and Hu, X and Li, Z and Li, X and Zhou, D and Wang, H}, title = {Mitogenome Characteristics and Intracellular Gene Transfer Analysis of Four Adansonia Species.}, journal = {Genes}, volume = {16}, number = {7}, pages = {}, pmid = {40725502}, issn = {2073-4425}, support = {No. 25L193//Integration and Optimization of Ancient Tree and Famous Tree Protection and Rural Tourism Development in Zhumadian City/ ; }, mesh = {*Genome, Mitochondrial/genetics ; Phylogeny ; Evolution, Molecular ; *Gene Transfer, Horizontal ; }, abstract = {Adansonia L. (1753) belongs to the family Malvaceae and is commonly known as the baobab tree. This species holds significant cultural and ecological value and is often referred to as the 'tree of life.' Although its nuclear genome has been reported, the mitogenome has not yet been studied. Mitogenome research is crucial for understanding the evolution of the entire genome. In this study, we assembled and analyzed the mitogenomes of four Adansonia species by integrating short-read and long-read data. The results showed that the mitogenomes of all four Adansonia species were resolved as single circular sequences. Their total genome lengths ranged from 507,138 to 607,344 bp and contained a large number of repetitive sequences. Despite extensive and complex rearrangements between the mitogenomes of Adansonia and other Malvaceae species, a phylogenetic tree constructed based on protein-coding genes clearly indicated that Adansonia is more closely related to the Bombax. Selection pressure analysis suggests that the rps4 gene in Adansonia may have undergone positive selection compared to other Malvaceae species, indicating that this gene may play a significant role in the evolution of Adansonia. Additionally, by analyzing intracellular gene transfer between the chloroplast, mitochondria, and nuclear genomes, we found that genes from the chloroplast and mitochondria can successfully transfer to each chromosome of the nuclear genome, and the psbJ gene from the chloroplast remains intact in both the mitochondrial and nuclear genomes. This study enriches the genetic information of Adansonia and provides important evidence for evolutionary research in the family Malvaceae.}, } @article {pmid40728102, year = {2025}, author = {Hou, T and Xu, Y and Dong, Y and Yao, J and Zhang, T and Zhou, L and Su, X and Zhang, Y and Zhang, Y and Chen, C and Shi, X and Liu, Y and Li, J and Du, M and Fang, X and Yan, S and Yang, S and Wang, W and Chen, Z and Qiao, S and Ahmad, B and Xu, X and Peng, Y and Xiao, H and Jin, Z and Leng, X and Tan, C and Tian, L and Li, C and Zhou, Y}, title = {The cytonuclear interactions during grapevine domestication.}, journal = {Journal of integrative plant biology}, volume = {67}, number = {10}, pages = {2686-2703}, pmid = {40728102}, issn = {1744-7909}, support = {No. 2023YFD2200700//National Key Research and Development Program of China/ ; 32372662//National Natural Science Foundation of China/ ; 6024330001K//Shenzhen Polytechnic University Research Project/ ; No. 32372662//National Natural Science Foundation of China/ ; No. 6024330001K//Shenzhen Polytechnic University Research Project/ ; }, mesh = {*Vitis/genetics ; *Domestication ; *Cell Nucleus/genetics/metabolism ; Genome-Wide Association Study ; Genome, Plant/genetics ; Genome, Mitochondrial/genetics ; }, abstract = {DNAs from the cytoplasmic genomes often communicate with the nuclear genome during regulation, development, and evolution. However, the dynamics of cytonuclear interaction during crop domestication have still been rarely investigated. Here, we examine cytonuclear interactions during grapevine domestication using pan-mitogenome, pan-plastome, and haplotype-resolved nuclear genomes, all assembled from long-read sequences across 33 wild and domesticated grapevine accessions. Structural variation shaped the mitogenomic variation in gene contents, leading to duplications of three specific genes during grapevine domestication (one cox and two rpl genes). Extensive genomic signals of cytonuclear interactions were detected, including a total of 212-431 nuclear-mitochondrial segments (NUMTs) and 95-205 nuclear-plastid segments (NUPTs). These results showed that NUMTs were under strong selection and were more abundant in cultivated grapes, whereas NUPTs dominated in wild grapes, indicating the evolutionary trajectories of cytonuclear interactions during grape domestication. Through Genome-Wide Association Study (GWAS), we identified 84 candidate genes associated with mitochondrial-nuclear genome interactions. Among these, the PFD1 gene acts as a signaling regulator, modulating specific signaling pathways regulated by the mitochondria. Interestingly, there are significantly more cytonuclear interaction genes near NUMTs than in other genomic regions, suggesting NUMT-mediated interactions between the nuclear and mitochondrial genomes. Overall, our study provides evidence that NUMTs promote cytonuclear interaction during grapevine domestication, offering new insight into the impact of cytonuclear interactions on plant evolution, genetics, and breeding.}, } @article {pmid40736517, year = {2025}, author = {Bettinazzi, S}, title = {Digest: Sex-specific benefits of mitochondrial introgression.}, journal = {Evolution; international journal of organic evolution}, volume = {79}, number = {10}, pages = {2333-2334}, doi = {10.1093/evolut/qpaf152}, pmid = {40736517}, issn = {1558-5646}, mesh = {Animals ; Male ; Female ; *Drosophila/genetics/physiology ; *Mitochondria/genetics ; *Genetic Fitness ; *Genetic Introgression ; Reproduction ; *Drosophila melanogaster/genetics ; }, abstract = {Disrupting mitochondrial and nuclear co-adaptation is expected to reduce fitness, especially in males and with age. But is that always true? Garlovsky et al. (2025) tested this in a panel of Drosophila lines, assessing reproductive success across sex and age. Unexpectedly, new mitonuclear combinations had limited impact on reproduction and even conferred a fitness advantage to some males. These findings challenge current views, suggesting that mitochondrial replacement can sometimes enhance fitness.}, } @article {pmid40739154, year = {2025}, author = {González-Orozco, E and Martínez-Guerrero, CE and Montiel, R}, title = {Genome-wide analysis in human populations reveals mitonuclear disequilibrium in genes related to neurological function.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {27794}, pmid = {40739154}, issn = {2045-2322}, support = {FC-2015-2/967//Consejo Nacional de Humanidades Ciencias y Tecnologías/ ; Reg. No. 746997//Consejo Nacional de Humanidades Ciencias y Tecnologías/ ; 612583-DEANN//FP7 People/ ; }, mesh = {Humans ; *Genome, Human ; *Linkage Disequilibrium ; *Mitochondria/genetics ; Genome-Wide Association Study ; *Cell Nucleus/genetics ; Evolution, Molecular ; Genetics, Population ; Selection, Genetic ; }, abstract = {Mitonuclear disequilibrium (MTD), defined as the non-random association of nuclear and mitochondrial alleles, is a form of gametic disequilibrium that may arise from coevolutionary adaptation between nuclear and mitochondrial genes interacting to maintain the efficiency of mitochondrial function. Intrinsic and extrinsic factors influence the outcome of this evolutionary process in which compatible alleles of the nuclear and mitochondrial counterparts are co-selected during population divergence. In humans, MTD has not been investigated deeply. Here, we present a genome-wide high-resolution analysis of 2,490 previously published human genomes from the 1000 Genomes Project database. By combining formal testing and simulations to discard random and population effects, we identified 669 nuclear protein-coding genes under MTD. In this set, we found enrichment in functional characteristics, indicating the biological meaningfulness of these genes. Genes with predicted signal peptides for mitochondrial import and genes with directional selection signals were overrepresented. Most genes were population-specific, suggesting a rapid and flexible mechanism of mitonuclear adaptation. The enriched GO terms were related to neurological function, highlighting the significant role and plasticity of neurological genes in the relatively rapid adaptation of mitochondrial function in human evolution.}, } @article {pmid40739537, year = {2025}, author = {Feng, G and Jiao, Y and Wang, Y and He, D and Liu, Q and Linchen, R and Gao, Y and Wang, J and Wang, X and Huang, T and Nie, G and Huang, L and Zhou, M and Zhang, X}, title = {Complete mitochondrial genome assembly and comparative analysis of Fagopyrum dibotrys (Golden Buckwheat).}, journal = {BMC plant biology}, volume = {25}, number = {1}, pages = {985}, pmid = {40739537}, issn = {1471-2229}, support = {202410626020//the National Undergraduate Innovation Program/ ; NSFC 32101422//the National Natural Science Foundation of China/ ; 2021YFD1200105//the National Key R&D Program of China/ ; No. CARS-34//the earmarked fund for Modern Agro-industry Technology Research System/ ; }, mesh = {*Fagopyrum/genetics ; *Genome, Mitochondrial/genetics ; Phylogeny ; *Genome, Plant ; Genes, Plant ; Evolution, Molecular ; }, abstract = {BACKGROUND: Mitochondria and chloroplasts are crucial plant organelles that harbor valuable genetic information. Fagopyrum dibotrys, commonly known as golden buckwheat, is an economically significant plant with diverse pharmacological properties, including antioxidant, antitumor, and anti-inflammatory activities. However, the mitochondrial genome (mt genome) for golden buckwheat has not yet been sequenced, limiting our understanding of its evolutionary characteristics. To address this, we employed a hybrid assembly strategy to assemble the first mt genome sequence of F. dibotrys.

RESULTS: In this study, we sequenced and assembled a mt genome of F. dibotrys (370,284 bp), which exhibited a distinctive multi-branched conformation. The genome comprises 69 genes, including 34 protein-coding genes (PCGs), six rRNAs, 28 tRNAs, and one pseudogene (rpl16). A comprehensive analysis of the PCGs and a comparison with seven closely related species indicated that the mt genomes have undergone adaptive evolution. Notably, five genes (atp4, ccmFn, nad1, nad3, and nad4) exhibited signs of positive selection. We also identified 12 homologous fragments between the chloroplast (cp.) and mt genomes, with a cumulative length of 33,984 bp. Phylogenetic analysis indicated that F. dibotrys was most closely associated with Fallopia aubertii and Fallopia multiflora.

CONCLUSIONS: The present study highlights the reliability of mt genes in revealing the phylogenetic relationships of the Polygonaceae family. Moreover, our research provides a crucial foundation for further exploration of the genetic diversity in the genus Fagopyrum and facilitates the utilization of golden buckwheat.}, } @article {pmid40757463, year = {2025}, author = {Elwan, MM and Madkour, FA and Salem, MM and El-Nahass, EE}, title = {Kidney Morphology in Marine and Terrestrial Birds and Its Phylogenetic Links to Mammals via Aquaporin (AQP) Genome Sequences.}, journal = {Journal of experimental zoology. Part A, Ecological and integrative physiology}, volume = {343}, number = {9}, pages = {1072-1089}, doi = {10.1002/jez.70018}, pmid = {40757463}, issn = {2471-5646}, support = {//The authors received no specific funding for this work./ ; }, mesh = {Animals ; *Phylogeny ; *Kidney/anatomy & histology/ultrastructure ; *Chickens/anatomy & histology/genetics ; *Ducks/anatomy & histology/genetics ; *Aquaporins/genetics ; Genome ; }, abstract = {The kidney is the main osmoregulatory organ in terrestrial vertebrates and depends on water conservation for survival. Only birds, among vertebrates other than mammals, can concentrate their urine as an adaptation to live in terrestrial environments. The water inflow of collecting duct epithelial cells is controlled by aquaporin 2 (AQP2) and an arginine vasotocin (AVT)-sensitive water channel expressed along cortical and medullary collecting ducts. This study aims to examine the anatomical, histological, histochemical, and ultrastructural variations in the kidneys of two avian species: marine birds, mallard duck (Anas platyrhynchos), and terrestrial birds, domestic chicken (Gallus gallus domesticus). Furthermore, phylogenetic relationships have been used to compare the AQP2 genome sequences of these two species with those of mammalian vertebrates. Histologically, the kidneys of the two studied species did not differ in structure. In the mallard, the renal lobule was comparatively divided into an elongated medulla (30%) and cortex (70%) and had more abundant cortical reptilian nephrons. However, the chicken renal lobule was a larger cortical region (85%) than the medullary region (15%) and had more mammalian nephrons. The brush border of the proximal convoluted tubules and the basement membrane of the nephron lining cells were positive for PAS stain but negative for AB, whereas the collecting ducts and the luminal surfaces of the distal convoluted tubules were positive for AB. Glomeruli and proximal convoluted tubules were more likely to react with bromophenol blue stain in chicken than in duck. TEM revealed that the cells lining the proximal, distal, and collecting renal tubules, as well as collecting ducts in duck, contained active and hypertrophied mitochondria, so the kidneys were more active in duck than in chicken. Multiple sequence alignment and phylogenetic tree analysis revealed that the anticipated genomic sequences of AQP2 are relatively conserved among avian species. In conclusion, studies of nephrons have identified both interspecies similarities and intraspecies differences among avian species.}, } @article {pmid40759308, year = {2025}, author = {Capodifoglio, KRH and Schneberger, F and Maia, AAM and Ranzani-Paiva, MJT}, title = {Mitochondrial dynamics and description of a novel Myxobolus species infecting Piaractus mesopotamicus in Brazil.}, journal = {Acta tropica}, volume = {269}, number = {}, pages = {107767}, doi = {10.1016/j.actatropica.2025.107767}, pmid = {40759308}, issn = {1873-6254}, mesh = {Brazil ; Animals ; *Myxobolus/classification/isolation & purification/genetics/cytology/ultrastructure ; Phylogeny ; *Fish Diseases/parasitology ; *Parasitic Diseases, Animal/parasitology ; *Mitochondria/ultrastructure ; Sequence Analysis, DNA ; DNA, Ribosomal/genetics/chemistry ; Gills/parasitology ; Characiformes/parasitology ; }, abstract = {A new Myxobolus species was identified infecting the gill arch of Piaractus mesopotamicus from a fish farm in São Paulo State, Brazil, and is described based on morphological, molecular, and biological data. Mature myxospores of Myxobolus naldonensis n.sp. were round in frontal view, with a length of 9.0 ± 0.3 µm, a width of 5.9 ± 0.3 µm, and a thickness of 5.2 ± 0.1 µm in the lateral view. Its polar capsules were elongated and equal size, occupying more than half of the myxospore, measuring 4.4 ± 0.2 µm in length, 1.7 ± 0.1 µm in width, and the polar tubules had 5 - 7 coils. Ultrastructural analysis revealed that the plasmodial wall was composed of a single membrane and that the sporogenesis process was asynchronous, with early developmental stages of myxospores in the periphery of the plasmodia and mature myxospores in the central part. Numerous mitochondria and pinocytotic channels were observed in the ectoplasm. Confocal analysis showed labeling of the nuclei of the sporoplasm, as well as of the valves and polar capsules. In mature myxospores a volume mitochondrial could be detected, but no labeling indicative of mitochondrial activity was observed. Molecular analysis based on the amplification and sequencing of small subunit ribosomal DNA (SSU rDNA) resulted in a 1968 bp sequence. Phylogenetic analysis grouped Myxobolus naldonensis n. sp. as sister species of Myxobolus tambaquiensis, which infects Colossoma macropomum, a fish belonging to the family Serrasalmidae.}, } @article {pmid40770694, year = {2025}, author = {Ha, YH and Cho, A and Kim, TH and Gil, HY}, title = {De Novo assembly and characterization of Aria alnifolia Chloroplast and mitochondrial genomes reveal homologous conformational changes mediated by repeat regions and gene transfer.}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {730}, pmid = {40770694}, issn = {1471-2164}, support = {KNA 1-1-13, 14-1//Korea National Arboretum/ ; KNA 1-1-13, 14-1//Korea National Arboretum/ ; KNA 1-1-13, 14-1//Korea National Arboretum/ ; KNA 1-1-13, 14-1//Korea National Arboretum/ ; }, mesh = {Phylogeny ; *Genome, Chloroplast ; *Genome, Mitochondrial ; *Repetitive Sequences, Nucleic Acid ; Gene Transfer, Horizontal ; Evolution, Molecular ; *Rosaceae/genetics/classification ; Base Composition ; Chloroplasts/genetics ; }, abstract = {BACKGROUND: Aria alnifolia is an ornamental landscape species widely distributed in East Asia. However, its mitochondrial genome remains largely unexplored. We used PacBio long reads and Illumina short reads to sequence and assemble the organelle genomes, aiming to understand the evolutionary relationship between the plastids and mitochondria of A. alnifolia. This study focused on the homologous conformational changes mediated by repeat regions and gene transfer between organelle genomes. We also conducted comparative genomic and phylogenetic analyses with other Rosaceae species to clarify the evolutionary placement of A. alnifolia within the family.

RESULTS: The mitochondrial genome is 455,361 bp long with a GC content of 45.2%, while the chloroplast genome is 160,303 bp long with a GC content of 36.5%. The mitochondrial genome contains 59 genes, including 35 protein-coding genes, 4 rRNA genes, and 20 tRNA genes. The chloroplast genome comprises 128 genes, with 84 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. The subcircular structure of the mitochondrial genome was inferred from two double-branch structures (DBSs) among 12 identified DBSs in A. alnifolia using a combination of long and short reads. In the mitochondrial genome, 128 simple sequence repeats were identified, compared to 69 in the chloroplast genome. Additionally, both organelles contained 239 dispersed repeats of at least 30 bp. We also confirmed gene transfer between the chloroplasts and mitochondria through shared repeats. Furthermore, we observed a region in the mitochondrial genome with high similarity to the chloroplast-encoded psaA gene, suggesting a possible inter-organellar gene transfer event. Phylogenetic analysis of the mitochondrial genomes revealed that A. alnifolia is closely related to Pyrus communis, albeit with low resolution.

CONCLUSION: This study provides one of the first comprehensive analyses of the organelle genomes (chloroplast and mitochondria) in the genus Aria. These results serve as a valuable reference for future taxonomic and molecular evolutionary studies of the Rosaceae family.}, } @article {pmid40773917, year = {2025}, author = {Richard, CMC and Renault, D and Cadot, C and Colinet, H and Derocles, SAP and Peraza Ku, SA and Salin, K and Boël, M}, title = {No evidence for behavioral or physiological effects of nanoplastics ingestion in the fruit fly Drosophila melanogaster.}, journal = {Ecotoxicology and environmental safety}, volume = {303}, number = {}, pages = {118811}, doi = {10.1016/j.ecoenv.2025.118811}, pmid = {40773917}, issn = {1090-2414}, mesh = {Animals ; *Drosophila melanogaster/drug effects/physiology ; *Microplastics/toxicity ; *Behavior, Animal/drug effects ; Locomotion/drug effects ; *Environmental Pollutants/toxicity ; }, abstract = {Plastic pollution increases worldwide, releasing small plastic particles into the environment, such as nanoplastics (NP) that affect living organisms. NP can penetrate biological membranes and interact with cellular components such as mitochondria. However, the effects of NP on terrestrial insects, the most diverse and abundant taxa, remains poorly studied compared to aquatic species. Our study assesses the effect of nanoplastics on the emergence rate, mitochondrial activity, metabolism, body mass, and locomotor activity in Drosophila melanogaster (Meigen, 1830, Diptera: Drosophilidae), a terrestrial insect. Three experimental groups were compared: a control group (C) with flies fed food without NP, a low contamination group (LOW) with flies fed food containing 1 µg/g of NP of different sizes (20, 80 and 200 nm), and a high contamination group (HIGH) with flies fed food containing 500 µg/g of NP of the same classes of sizes. Low and High groups were exposed to polystyrene NP for their entire development cycle. NP ingestion did not affect the number of pupae and adults, emergence rate, mitochondrial activity, metabolism and body mass. The locomotor activity of the flies was also unaffected by ingestion of NP. These results, compared with those reported in the literature, showed that the effect of nanoplastics on living organisms might depend on the species and polymer nature. The absence of detectable effects on flies is positive for the ecology of the species, constantly exposed to plastic pollution. Further studies in this area are still needed to fully determine the effects of NP on Drosophila biology and behavior.}, } @article {pmid40782022, year = {2025}, author = {Dimogkioka, AR and Rapaport, D}, title = {Conserved function, divergent evolution: mitochondrial outer membrane insertases across eukaryotes.}, journal = {Biological chemistry}, volume = {406}, number = {10-12}, pages = {423-429}, pmid = {40782022}, issn = {1437-4315}, mesh = {Animals ; *Mitochondrial Membranes/metabolism/enzymology ; Humans ; *Evolution, Molecular ; *Eukaryota/metabolism/enzymology ; *Mitochondrial Proteins/metabolism ; Mitochondria/metabolism ; }, abstract = {Mitochondrial function relies heavily on the proper targeting and insertion of nuclear-encoded proteins into the outer mitochondrial membrane (OMM), a process mediated by specialised biogenesis factors known as insertases. These insertases are essential for the membrane integration of α-helical OMM proteins, which contain one or multiple hydrophobic transmembrane segments. While the general mechanisms of mitochondrial protein import are well established, recent research has shed light on the diversity and evolutionary conservation of OMM insertases across eukaryotic lineages. In Saccharomyces cerevisiae, the mitochondrial import (MIM) complex, composed of Mim1 and Mim2, facilitates the integration of various α-helical OMM proteins, often in cooperation with import receptors such as Tom20 and Tom70. In Trypanosoma brucei, the functional MIM counterpart pATOM36 performs a similar role despite lacking sequence and structural homology, reflecting a case of convergent evolution. In mammals, MTCH2 has emerged as the principal OMM insertase, with MTCH1 playing a secondary, partially redundant role. This review provides a comparative analysis of these insertases, emphasising their conserved functionality, species-specific adaptations, and mechanistic nuances.}, } @article {pmid40795046, year = {2025}, author = {Shirsath, A and Khairnar, SV and Anand, A and Prabhakaran, DM and Anand, A}, title = {Hidden Markov Model-Based Prokaryotic Genome Space Mining Reveals the Widespread Pervasiveness of Complex I and Its Potential Evolutionary Scheme.}, journal = {Genome biology and evolution}, volume = {17}, number = {8}, pages = {}, pmid = {40795046}, issn = {1759-6653}, support = {19P0120//DAE-Tata Institute of Fundamental Research/ ; 21X432//DBT-Ramalingaswami Fellowship/ ; //Amitesh Anand/ ; }, mesh = {*Hidden Markov Models ; *Quinone Reductases/chemistry/genetics/metabolism ; *Prokaryotic Cells/metabolism ; Genome ; Datasets as Topic ; Molecular Sequence Annotation ; Protein Subunits ; *Evolution, Molecular ; Phylogeny ; Humans ; Mitochondria ; }, abstract = {Most cellular reactions are interdependent; however, a subset of reactions often associate more closely to form a defined reaction pathway. An extreme arrangement of interdependent reactions occurs when the cognate proteins physically associate to constitute a complex. Respiratory Complex I (C-I) is one of the largest membrane-resident protein assemblies. Besides being a hallmark of bioenergetics, this enzyme complex is critical for maintaining redox homeostasis and facilitating transport. However, its evolutionary origins are unclear due to challenges in identifying close homologs and subunit ancestry. Using custom hidden Markov model (HMM) profiles, we analyzed the prokaryotic genome space to trace the distribution of 14 core C-I or NADH-quinone oxidoreductase (Nuo) subunits. Our findings include (i) a sensitive HMMER-based workflow for comprehensively annotating and analyzing the Nuo subunits, adaptable for similar analyses; (ii) the first species-level distribution of Nuo subunits; (iii) multiple C-I variants across ∼11,000 species, with 51.2% having a complete complex; (iv) C-I variants on plasmids, aiding evolutionary spread; and (v) extending our workflow to study mitochondrial C-I accessory subunits in prokaryotes, revealing their evolutionary roots. We also developed a web application to share our resources. Together, we comprehensively account for the distribution and probable evolutionary scheme of C-I subunits among prokaryotes.}, } @article {pmid40795994, year = {2025}, author = {Janowicz, N and Dohnálek, V and Zítek, J and Peña-Diaz, P and Pyrihová, E and King, MS and Husová, M and Žárský, V and Kunji, E and Zikova, A and Hampl, V and Dolezal, P}, title = {Selective loss of ATP carriers in favour of SLC25A43 orthologues in metamonad mitochondria adapted to anaerobiosis.}, journal = {Open biology}, volume = {15}, number = {8}, pages = {240202}, pmid = {40795994}, issn = {2046-2441}, support = {//Grantová Agentura, Univerzita Karlova/ ; //European Regional Development Fund 'Centre for research of pathogenicity and virulence of parasites'/ ; //Grantová Agentura České Republiky/ ; //Ministerstvo Školství, Mládeže a Tělovýchovy/ ; /ERC_/European Research Council/International ; //Gordon and Betty Moore Foundation/ ; }, mesh = {*Adenosine Triphosphate/metabolism ; *Mitochondria/metabolism ; Anaerobiosis ; Humans ; Phylogeny ; *Mitochondrial Proteins/metabolism/genetics ; *Mitochondrial ADP, ATP Translocases/metabolism/genetics ; }, abstract = {Metamonada is a eukaryotic supergroup of free-living and parasitic anaerobic protists. Their characteristic feature is the presence of highly reduced mitochondria that have lost the ability to produce ATP by oxidative phosphorylation and in some cases even by substrate phosphorylation, with all ATP being imported from the cytosol. Given this striking difference in cellular ATP metabolism when compared to aerobic mitochondria, we studied the presence of mitochondrial carrier proteins (MCPs) mediating the transport of ATP across the inner mitochondrial membrane. Our bioinformatic analyses revealed remarkable reduction of MCP repertoire in Metamonada with striking loss of the major ADP/ATP carrier (AAC). Instead, nearly all species retained carriers orthologous to human SLC25A43 protein, a little-characterized MCP. Heterologous expression of metamonad SLC25A43 carriers confirmed their mitochondrial localization, and functional analysis revealed that SLC25A43 orthologues represent a distinct group of ATP transporters, which we designate as ATP-importing carriers (AIC). Together, our findings suggest that AIC facilitate the ATP import into highly reduced anaerobic mitochondria, compensating for their diminished or absent energy metabolism.}, } @article {pmid40806670, year = {2025}, author = {Jaeken, L and Manoj, KM}, title = {Murburn Bioenergetics and "Origins-Sustenance-Termination-Evolution of Life": Emergence of Intelligence from a Network of Molecules, Unbound Ions, Radicals and Radiations.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806670}, issn = {1422-0067}, mesh = {*Energy Metabolism ; Humans ; Animals ; Ions/metabolism ; *Origin of Life ; Free Radicals/metabolism ; }, abstract = {The paradigm-shift idea of murburn concept is no hypothesis but developed directly from fundamental facts of cellular/ecological existence. Murburn involves spontaneous and stochastic interactions (mediated by murzymes) amongst the molecules and unbound ions of cells. It leads to effective charge separation (ECS) and formation/recruitment of diffusible reactive species (DRS, like radicals whose reactions enable ATP-synthesis and thermogenesis) and emission of radiations (UV/Vis to ELF). These processes also lead to a chemo-electromagnetic matrix (CEM), ascertaining that living cell/organism react/function as a coherent unit. Murburn concept propounds the true utility of oxygen: generating DRS (with catalytic and electrical properties) on the way to becoming water, the life solvent, and ultimately also leading to phase-based macroscopic homeostatic outcomes. Such a layout enables cells to become simple chemical engines (SCEs) with powering, coherence, homeostasis, electro-mechanical and sensing-response (PCHEMS; life's short-term "intelligence") abilities. In the current review, we discuss the coacervate nature of cells and dwell upon the ways and contexts in which various radiations (either incident or endogenously generated) could interact in the new scheme of cellular function. Presenting comparative evidence/arguments and listing of systems with murburn models, we argue that the new perceptions explain life processes better and urge the community to urgently adopt murburn bioenergetics and adapt to its views. Further, we touch upon some distinct scientific and sociological contexts with respect to the outreach of murburn concept. It is envisaged that greater awareness of murburn could enhance the longevity and quality of life and afford better approaches to therapies.}, } @article {pmid40812757, year = {2025}, author = {Xi, K and Jin, Y and Lin, L and Fang, J and Wei, W and Lin, J and Huang, X and Huang, Y and Zhang, Y and Qin, Q}, title = {Grouper SPL promotes STING- and IRF3-mediated antiviral immune response against iridovirus infection.}, journal = {Fish & shellfish immunology}, volume = {166}, number = {}, pages = {110654}, doi = {10.1016/j.fsi.2025.110654}, pmid = {40812757}, issn = {1095-9947}, mesh = {Animals ; *Fish Diseases/immunology/virology ; *Immunity, Innate/genetics ; *DNA Virus Infections/immunology/veterinary ; Fish Proteins/genetics/immunology/chemistry ; Ranavirus/physiology ; *Bass/immunology/genetics ; *Gene Expression Regulation/immunology ; Interferon Regulatory Factor-3/genetics/immunology ; Phylogeny ; Gene Expression Profiling/veterinary ; Sequence Alignment/veterinary ; }, abstract = {Sphingosine-1-phosphate (S1P) lyase (SPL) was an intracellular enzyme that catalyzes the degradation of the bioactive lipid S1P. Singapore grouper iridovirus (SGIV), a highly pathogenic large cytoplasmic dsDNA virus, had caused significant economic losses in aquaculture and threatened biodiversity. Though SPL had been reported to be crucial for several crucial cellular functions due to its roles in S1P metabolism, the roles of SPL in fish virus infection remained poorly understood. Herein, we found the positive regulatory role of grouper SPL (EcSPL) on the host's innate immune responses against SGIV infection. EcSPL encoded a 563 amino acid protein, containing one DOPA domain (140-502 aa). Quantitative real time PCR (qPCR) analysis showed that EcSPL was constitutively expressed in all examined tissues, and the expression of EcSPL was induced by SGIV infection in a time dependent manner. Subcellular localization revealed that EcSPL was distributed in the cytoplasm, and partly colocalized with the endoplasmic reticulum, mitochondria, and lysosomes. Overexpression of EcSPL significantly reduced the transcription and protein expression of the viral genes, as well as the severity of the cytopathic effects (CPEs) caused by SGIV, thereby suppressing SGIV replication. Meanwhile, EcSPL overexpression potently increased the promoter activity of interferon1 (IFN1), interferon3 (IFN3), and nuclear factor kappa-B (NF-κB), as well as the expression of pro-inflammatory cytokines and interferon related genes. Furthermore, EcSPL overexpression further augmented the promoter activity of IFN1, IFN3, and NF-κB triggered by STING (stimulator of interferon genes) and IRF3 (interferon regulatory factor 3), but not TBK1 (TANK-binding kinase 1). Mechanistically, EcSPL interacted with EcSTING and EcIRF3. Consistently, these key adaptors were found to be co-located with EcSPL. The study provided the first evidence that EcSPL as an antiviral host factor, restricted SGIV replication by directly enhancing EcSTING- or EcIRF3-mediated antiviral immune response. Our findings revealed a novel role for EcSPL in teleost immune defense against viral infection.}, } @article {pmid40813934, year = {2025}, author = {Gamero-Mora, E and Muhlia-Almazán, A}, title = {The mitochondrial uncoupling proteins in early-branching animals: comparative analysis and transcriptional response to temperature in the jellyfish Stomolophus sp.2.}, journal = {Journal of bioenergetics and biomembranes}, volume = {57}, number = {4-5}, pages = {199-214}, pmid = {40813934}, issn = {1573-6881}, support = {171862//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; }, mesh = {Animals ; *Mitochondrial Uncoupling Proteins/genetics/metabolism ; Temperature ; Cnidaria/genetics ; Scyphozoa ; }, abstract = {Uncoupling proteins (UCPs) are mitochondrial membrane proteins involved in metabolite transportation and proton translocation to the mitochondrial matrix. Seven UCP homologs have been reported in bilaterians; however, UCPs of early-branching animals (i.e., members of Cnidaria, Ctenophora, Placozoa, and Porifera) remain understudied. The presence of UCPs in the cnidarian jellyfish Stomolophus sp.2. was investigated, and its UCP homologs were compared with data from 49 other early-branching species to provide insights into their evolution. Three UCPs were identified in Stomolophus sp.2: UCP4, UCP5, and a novel cnidarian-specific homolog (cnUCP). In addition to cnidarians, placozoans and sponges share UCP4 and UCP5 homologs, while ctenophores lack these but possess three distinct UCPs, two of them related to UCP5. Results suggest that since UCP4 and UCP5 originated at least at the Animalia-Choanoflagellata node and considering the evolutionary gains of UCPs in Cnidaria and Ctenophora, the relevance of these proteins in mitochondrial functions deserves attention. Moreover, to infer the role of UCPs in Stomolophus sp.2 mitochondria, their structural characteristics were identified, and the temperature effect on their gene expression was evaluated. Whereas UCP4 and UCP5 genes showed higher expression at 23 °C, cnUCP was highly expressed at 33 °C, suggesting a potential role in the jellyfish thermal stress response. Besides their role in mitochondrial uncoupling and energy balance, the bilaterian UCPs may mitigate reactive oxygen species production during thermal stress. However, their role in early-branching lineages remains unclear. This study provides key data for future functional research on UCPs in early-branching animals under climate change.}, } @article {pmid40846044, year = {2025}, author = {Hartung, J}, title = {Cancer as a failed response to renegade mitochondria.}, journal = {Experimental cell research}, volume = {451}, number = {2}, pages = {114721}, doi = {10.1016/j.yexcr.2025.114721}, pmid = {40846044}, issn = {1090-2422}, mesh = {Humans ; *Mitochondria/genetics/metabolism/pathology ; *Neoplasms/genetics/pathology/metabolism ; Animals ; Mutation ; }, abstract = {In 1948, before the word 'mitochondrion' gained common parlance in the lexicon of cell biologists, Cyril Darlington published The Plasmagene Theory of the Origin of Cancer without referring to mitochondria per se. Reconsideration of Darlington's theory is warranted today because discoveries about the extraordinary capacities of mitochondria - the organelles that house Darlington's "plasmagenes" - have grown exponentially. If Darlington was right, if intracellular competition between mutant and wild-type mitochondria is the first cause of cancer, it may be the case that a general cure for cancer will include injection of: (A) nanoparticles carrying wild-type mitochondrial genes, and (B) copious amounts of wild-type mitochondria.}, } @article {pmid40855301, year = {2025}, author = {Jian, Y and Dong, S and Liu, W and Li, G and Lian, X and Wang, Y}, title = {Mapping the evolving trend of research on efferocytosis: a comprehensive data-mining-based study.}, journal = {BioData mining}, volume = {18}, number = {1}, pages = {58}, pmid = {40855301}, issn = {1756-0381}, abstract = {BACKGROUND: Efferocytosis, the process by which apoptotic cells are recognized and removed by phagocytes, plays a critical role in maintaining tissue homeostasis and modulating inflammatory responses. Over recent decades, an increasing number of studies have investigated the molecular mechanisms and clinical implications of efferocytosis. This bibliometric analysis aims to map the evolving trends, identify key contributors, and outline emerging research themes in this field.

METHODS: A comprehensive search was conducted in Web of Science database, to collect literature related to efferocytosis from 2006 to 2024. The dataset was analyzed using several tools such as CiteSpace and VOSviewer. Analyses included evaluation of publication trends, citation networks, keyword co-occurrence, and co-cited references. Key metrics such as the most prolific authors, top contributing countries, and major research clusters were identified to understand the field's evolution and interdisciplinary collaborations.

RESULTS: The final dataset comprised 1549 scholarly works, consisting of 1166 original research articles and 383 review papers. The analysis revealed a steady increase in the number of publications concerning efferocytosis, particularly in the past decade. Geographically, China and the United States emerged as dominant contributors, representing over 64.4% of total publications. Among institutions, Harvard University demonstrated the highest research output in this field. Keyword analysis demonstrated the current research focus including molecular mechanisms and signaling regulation of efferocytosis, macrophage polarization and inflammatory modulation, pathological implications and therapeutic potential of efferocytosis in diseases. Inflammation, atherosclerosis, cardiovascular disease, myocardial infarction, and COPD are diseases that has received the most attention in this field. Several research topics including nanoparticle, neuroinflammation, fibrosis, immunometabolism, exosomes, apoptotic bodies, mesenchymal stem cells, aging, microglia, reactive oxygen species, CD47, lipid metabolism, immunotherapy, mitochondria, ferroptosis, may have great potential to be hot topics in the near future. Gene-focused investigations identified TNF, MERTK, IL10, LI6, and IL1b as the most extensively studied genetic elements in efferocytosis research.

CONCLUSIONS: This bibliometric study provides a comprehensive overview of the evolving research landscape in efferocytosis. These insights not only highlight the current milestones but also serve as a valuable guide for future research and policy-making aimed at harnessing efferocytosis for therapeutic innovations.}, } @article {pmid40858263, year = {2025}, author = {Mueller, RL and Li Puma, LC and Itgen, MW and Chicco, AJ}, title = {Evolutionary diversity of muscle OXPHOS efficiency in vitro across ectothermic vertebrates.}, journal = {Proceedings. Biological sciences}, volume = {292}, number = {2053}, pages = {20250374}, pmid = {40858263}, issn = {1471-2954}, support = {//NSF/ ; }, mesh = {Animals ; *Lizards/metabolism/physiology ; *Biological Evolution ; *Oxidative Phosphorylation ; Oxygen Consumption ; Reactive Oxygen Species/metabolism ; *Caudata/metabolism/physiology ; Adenosine Triphosphate/metabolism ; *Muscle, Skeletal/metabolism ; *Anura/metabolism/physiology ; Mitochondria, Muscle/metabolism ; }, abstract = {Oxidative metabolism meets the majority of vertebrate energy demands through the coupling of mitochondrial respiration to ATP production (OXPHOS). In endotherms, variations in OXPHOS coupling efficiency influence metabolic thermogenesis, locomotor economy and reactive oxygen species (ROS) generation. However, the extent of these variations and their functional implications in ectotherms are less clear. We measured mitochondrial oxygen consumption, ATP production and ROS production in permeabilized skeletal muscle fibres from salamanders, frogs and lizards representing ectotherm clades with low, medium and high standard metabolic rates (SMRs), respectively. Consistent with predicted associations with SMR, lizards had the highest capacities for muscle mitochondrial ATP production, while salamanders had the lowest. Unexpectedly, corresponding rates of oxygen consumption followed an opposite trend, reflecting 8.5-fold variations in OXPHOS coupling efficiency between salamanders (the lowest) and lizards (the highest). Intrinsic proton permeability of the inner mitochondrial membrane was the primary source of OXPHOS coupling variation across species, being highest in salamanders and lowest in lizards. Basal proton leak mediated by uncoupling proteins and the adenine nucleotide translocase was only seen in lizards, where it limits mitochondrial ROS production. We infer that diverse evolutionary selection pressures drive unexpectedly wide variations in muscle OXPHOS efficiency with different functional implications across ectotherm clades.}, } @article {pmid40862124, year = {2025}, author = {Lin, Y and Tian, J}, title = {Research on podocyte injury mechanisms in diabetic nephropathy: a bibliometric and knowledge-map analysis from 2000 to 2024.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1578045}, pmid = {40862124}, issn = {1664-2392}, mesh = {Animals ; Humans ; *Bibliometrics ; *Diabetic Nephropathies/pathology ; *Podocytes/pathology/metabolism ; }, abstract = {OBJECTIVES: A bibliometric and knowledge-map analysis is used to explore hotspots evolution and development trends in the Podocyte Injury Mechanisms in Diabetic Nephropathy. By looking for research hotspots and new topics, we can provide new clues and ideas for researchers in this field.

METHODS: The articles and reviews regarding Podocyte were retrieved and obtained from the Web of Science Core Collection (WOSCC) on September 1st, 2024. CtieSpace [version 6.2.4R (64-bit)] and VOSviewer (version 1.6.18) were used to conduct the bibliometric and knowledge-map analysis.

RESULTS: 12086 authors from 2394 institutions in 69 countries/regions published 3239 papers in academic journals. PEOPLES R CHINA and THE USA were absolutely in the leading position in this research field. The institution that contributed the most publications was the Shandong University. Kidney International (130 articles) is the journal with the most published records and the highest number of co-citations. The author with the highest number of co citations is Mundel p. However, there was little cooperation between countries. After 2012, cooperation among various institutions was also small. Autophagy, mitochondria, and epigenetics are hot topics and trends in this field. The most influential research hotspots were the research of podocyte autophagy and metabolism, the related research of SIRT1, VEGF. The latest hotspots and topics included the study of nlrp3 inflammasome and signaling pathway in podocyte injury. The research of Podocyte in Diabetic Nephropathy was a rapidly developing hot field.

CONCLUSION: The damage mechanism of podocytes is a very important factor in the occurrence and progress of diabetes nephropathy. Early intervention of podocyte damage is a very potential preventive measure for diabetes nephropathy, which has clinical application prospects and is currently being rapidly developed.}, } @article {pmid40869971, year = {2025}, author = {Gargus, JJ}, title = {Genetic Dissection of Energy Deficiency in Autism Spectrum Disorder.}, journal = {Genes}, volume = {16}, number = {8}, pages = {}, pmid = {40869971}, issn = {2073-4425}, mesh = {*Autism Spectrum Disorder/genetics/metabolism/pathology ; Animals ; Humans ; Mice ; Mitochondria/metabolism/genetics/pathology ; *Energy Metabolism/genetics ; Disease Models, Animal ; Calcium Signaling/genetics ; Inositol 1,4,5-Trisphosphate Receptors/genetics/metabolism ; Endoplasmic Reticulum/metabolism ; Brain/metabolism ; Calcium/metabolism ; }, abstract = {Background/Objectives: An important new consideration when studying autism spectrum disorder (ASD) is the bioenergetic mechanisms underlying the relatively recent rapid evolutionary expansion of the human brain, which pose fundamental risks for mitochondrial dysfunction and calcium signaling abnormalities and their potential role in ASD, as recently highlighted by insights from the BTBR mouse model of ASD. The rapid brain expansion taking place as Homo sapiens evolved, particularly in the parietal lobe, led to increased energy demands, making the brain vulnerable to such metabolic disruptions as are seen in ASD. Methods: Mitochondrial dysfunction in ASD is characterized by impaired oxidative phosphorylation, elevated lactate and alanine levels, carnitine deficiency, abnormal reactive oxygen species (ROS), and altered calcium homeostasis. These dysfunctions are primarily functional, rather than being due to mitochondrial DNA mutations. Calcium signaling plays a crucial role in neuronal ATP production, with disruptions in inositol 1,4,5-trisphosphate receptor (ITPR)-mediated endoplasmic reticulum (ER) calcium release being observed in ASD patient-derived cells. Results: This impaired signaling affects the ER-mitochondrial calcium axis, leading to mitochondrial energy deficiency, particularly in high-energy regions of the developing brain. The BTBR mouse model, with its unique Itpr3 gene mutation, exhibits core autism-like behaviors and metabolic syndromes, providing valuable insights into ASD pathophysiology. Conclusions: Various interventions have been tested in BTBR mice, as in ASD, but none have directly targeted the Itpr3 mutation or its calcium signaling pathway. This review presents current genetic, biochemical, and neurological findings in ASD and its model systems, highlighting the need for further research into metabolic resilience and calcium signaling as potential diagnostic and therapeutic targets for ASD.}, } @article {pmid40874342, year = {2025}, author = {Shahbazi, M and Kneřová, J and Kubíková, D and Doležalová, A and Szecówka, M and Santos, YD and Wendel, JF and Sharbrough, J and Kopecký, D}, title = {Restoring cytonuclear harmony: Distinct strategies in Arabidopsis auto- and allopolyploids.}, journal = {The Plant journal : for cell and molecular biology}, volume = {123}, number = {4}, pages = {e70451}, pmid = {40874342}, issn = {1365-313X}, support = {22-03731S//Grantová Agentura České Republiky/ ; CZ.02.01.01/00/22_008/0004581//ERDF Programme Johannes Amos Comenius/ ; }, mesh = {*Arabidopsis/genetics ; *Polyploidy ; Chloroplasts/genetics ; *Cell Nucleus/genetics ; Mitochondria/genetics/metabolism ; Genome, Plant/genetics ; Gene Expression Regulation, Plant ; DNA, Mitochondrial/genetics ; DNA, Chloroplast/genetics ; Genome, Chloroplast/genetics ; }, abstract = {Plants rely on tight coordination between nuclear, mitochondrial, and chloroplast genomes to form essential multi-enzyme cytonuclear complexes. Whole-genome duplication (WGD) doubles the nuclear genome, potentially disrupting cytonuclear stoichiometry unless organellar genomes respond accordingly. Targeted analyses of chloroplasts and mitochondria enabled us to dissect the extent and mechanisms of adjustments in both organelles immediately after WGD and across generations in Arabidopsis auto- and allopolyploids. We observed a substantial overcompensation of organellar genome copies in both organelles in early-generation autotetraploids primarily through multiplication of DNA copies within organelles rather than increasing the number of organelles. Despite higher DNA content, mitochondria maintained their volume, and chloroplasts were even smaller. In successive generations, chloroplast DNA copy numbers continued to rise, whereas mitochondrial DNA copies declined. Gene expression patterns also differed between chloroplasts and mitochondria and between auto- and allopolyploids. In autopolyploids, immediate transcriptional changes were minimal, but by the fourth generation after WGD, nuclear genes involved in mitochondria-nuclear complexes were downregulated. In allopolyploids, transcriptional changes appeared immediately in the first generation (chloroplast genes were upregulated and mitochondrial genes were downregulated). Our findings demonstrate that cytonuclear balance is restored through dynamic, organelle-specific, and polyploid-type-specific mechanisms. These insights advance our understanding of the evolution of polyploid genomes.}, } @article {pmid40875506, year = {2025}, author = {Cahoon, AB and Maggard, IJ and Pathan, WN}, title = {Mitochondrial mRNA oligocitydylation occurs in Chlorophyceae and Ulvales but not Bryopsidales or Trebouxiophyceae.}, journal = {Journal of phycology}, volume = {61}, number = {5}, pages = {1195-1205}, pmid = {40875506}, issn = {1529-8817}, mesh = {*RNA, Messenger/metabolism/genetics ; *Chlorophyceae/genetics/metabolism ; RNA, Mitochondrial ; *Chlorophyta/genetics/metabolism ; *Mitochondria/genetics/metabolism ; *Ulva/genetics ; }, abstract = {Mitochondrial mRNAs in the green algal class Chlorophyceae have non-template 3' oligo-cytosine-rich additions, also known as oligo(C), polycitydylation, or poly(C) "tails." These oligonucleotide additions are believed to be unique to green algal mitochondria, as none have been observed in any other organism. Among algae, oligocitydylation had only been observed in species within the Chlorophyceae, with no evidence of it occurring in other taxonomic classes. In this study, evidence is presented that mitochondrial mRNA oligocitydylation occurs in the genus Ulva, demonstrating its presence in the Class Ulvophyceae and Order Ulvales. Two other species in Ulvophyceae, Bryopsis plumosa and Codium fragile, from the Order Bryopsidales were also screened, but no evidence of oligonucleotide additions was observed. This demonstrates that oligocitydylation occurs in Ulvophyceae but suggests it may be limited to the Ulvales. Three species from Trebouxiophyceae were also screened, and there was no evidence of oligonucleotide additions, suggesting it does not occur in this clade. These results demonstrate that oligocitydylation does occur outside of the Chlorophyceae but only in the closely related Ulvales clade, suggesting this could be a biochemical synapomorphy shared by these groups.}, } @article {pmid40876762, year = {2025}, author = {Sena, F and Couture, C and Berais-Rubio, A and Millar, AH and Signorelli, S}, title = {Liquid-phase determination of Arabidopsis respiration and photosynthesis using Clark-type O2 electrodes.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {360}, number = {}, pages = {112735}, doi = {10.1016/j.plantsci.2025.112735}, pmid = {40876762}, issn = {1873-2259}, mesh = {*Arabidopsis/physiology/metabolism ; *Photosynthesis/physiology ; Cell Respiration ; Electrodes ; *Oxygen/metabolism ; Mitochondria/metabolism ; Seedlings/metabolism/physiology ; }, abstract = {Photosynthesis and respiration are fundamental metabolic processes in plants, tightly connected through shared substrates, energy dynamics, and redox balance. Arabidopsis is the key genetic model for plants but monitoring these sorts of physiological processes presents significant challenges using traditional gas-exchange or fluorescence-based techniques due to the small size of intact Arabidopsis thaliana (arabidopsis) seedlings. Here, we validate and characterize the use of Clark-type oxygen electrodes, specifically the Hansatech Oxytherm+P system, to quantify both photosynthetic and respiratory activity in intact arabidopsis seedlings. By monitoring oxygen evolution in dark and light phases, we demonstrate that oxygen consumption and production correspond to mitochondrial respiration and photosynthesis, respectively. These processes were modulated by tissue biomass, light intensity, developmental stage, and stress conditions. Specific inhibitors such as potassium cyanide and DCMU confirmed that the recorded changes in oxygen concentrations reflected mitochondrial cytochrome oxidase activity and photosystem electron transport-dependent oxygen production, respectively. Moreover, oxygen evolution increased significantly with bicarbonate supplementation, validating the system's sensitivity to carbon fixation. We further showed that photosynthetic activity measured with this method correlates with a quantitative green index and responds dynamically to de-etiolation, abiotic stress (salt, osmotic, oxidative), and temperature shifts. Our study lays the groundwork for measuring photosynthesis based on oxygen evolution and respiration in arabidopsis knockout mutants, CRISPR lines, overexpression lines, and ecotypes using Clark-type oxygen electrodes and highlights key considerations and limitations to consider when applying this approach. This platform could also be adapted for many other small tissue plant samples.}, } @article {pmid40879183, year = {2025}, author = {Kohzuma, K and Muraoka, S and Kumazawa, M and Ifuku, K}, title = {Evolution and regulatory diversification of plastid F1FO-ATP synthase.}, journal = {Plant & cell physiology}, volume = {66}, number = {11}, pages = {1619-1632}, doi = {10.1093/pcp/pcaf100}, pmid = {40879183}, issn = {1471-9053}, support = {25KJ0007//KAKENHI/ ; 22KJ2017//KAKENHI/ ; 24H02080//KAKENHI/ ; 22K06258//KAKENHI/ ; 21KK0264//KAKENHI/ ; MJFR2276//JST FORESTO Program/ ; }, mesh = {*Plastids/enzymology/genetics/metabolism ; Phylogeny ; *Evolution, Molecular ; Adenosine Triphosphate/metabolism ; *Proton-Translocating ATPases/metabolism/genetics ; *Chloroplast Proton-Translocating ATPases/metabolism/genetics ; }, abstract = {F1FO-ATP synthase, the enzyme complex responsible for adenosine triphosphate (ATP) production, is universally conserved and central to cellular energy metabolism in bacteria as well as in mitochondria and plastids-organelles derived from ancestral bacteria. Although its basic structure and rotational catalytic mechanism are conserved, F1FO-ATP synthase exhibits remarkable regulatory diversity, which is evident in its structural variations, tissue-specific isoforms, and ATP synthesis and hydrolysis mechanisms, reflecting the metabolic demands and environmental contexts of different organisms and organelles. Among the diverse F1FO-ATP synthase isoforms, the plastid F1FO-ATP synthase exhibits unique regulatory features, including redox-dependent modulation, which adjusts enzyme activity in response to light availability. Certain angiosperms possess two isoforms of the γ subunit, encoded by ATPC1 and ATPC2, which give rise to redox-sensitive and redox-insensitive forms of the enzyme, respectively. The latter is active in the dark and may contribute to the maintenance of the proton motive force regulation, thereby supporting stress adaptation in non-photosynthetic tissues. In this review, through a phylogenetic analysis of the γ subunit, we integrate structural, physiological, and evolutionary aspects of plastid F1FO-ATP synthase and discuss how the diversification of ATP synthases, especially within plastid, underpins their broader physiological significance beyond ATP production. Furthermore, we discuss why the chloroplast ATP synthase must be redox-regulated.}, } @article {pmid40880097, year = {2025}, author = {Schalkowski, R and Cutter, AD}, title = {Divergent organelle allocation in the evolution of sperm gigantism revealed from subcellular quantification of nematode sperm with electron microscopy.}, journal = {Evolution; international journal of organic evolution}, volume = {79}, number = {11}, pages = {2503-2515}, doi = {10.1093/evolut/qpaf172}, pmid = {40880097}, issn = {1558-5646}, support = {RGPIN-2024-03772//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Animals ; Male ; *Spermatozoa/ultrastructure/cytology/physiology ; *Biological Evolution ; *Caenorhabditis/ultrastructure/genetics/physiology ; *Organelles/ultrastructure ; Cell Size ; Microscopy, Electron, Transmission ; }, abstract = {Sperm gigantism has evolved multiple times independently, raising the question of whether intracellular allocation strategies evolved in concert with cell size. Allocation to intracellular components might evolve from direct selection on specific subcellular constituents that affect cell size indirectly, or instead as a byproduct of selection on cell size per se. We used transmission electron microscopy of nematode spermatozoa to quantify investment in pseudopods, mitochondria, and membranous organelles (MOs) from Caenorhabditis macrosperma and C. nouraguensis, related species divergent in sperm size. We demonstrate that C. macrosperma allocates more to mitochondria, in both total and relative terms, consistent with larger sperm cells having greater energetic demands associated with longevity, adhesion, and motility functions. Similar relative pseudopod sizes between species, however, are consistent with an optimal pseudopod : cell body ratio. MO size and distribution patterns within cells implicate C. macrosperma having lower relative investment in MO contributions to seminal fluid, thus excluding increased investment in MOs and pseudopod as drivers of sperm gigantism in C. macrosperma. We conclude that cell size per se likely represents the primary target of selection in the evolution of sperm gigantism, with mitochondrial traits likely evolving as a consequence of increased energetic demands of giant sperm cells.}, } @article {pmid40897671, year = {2025}, author = {Meyer, EH and Lopez-Lopez, A and Keech, O and Rouhier, N}, title = {The Expanded LYR Motif-Containing Protein Family in Archaeplastida.}, journal = {Physiologia plantarum}, volume = {177}, number = {5}, pages = {e70482}, doi = {10.1111/ppl.70482}, pmid = {40897671}, issn = {1399-3054}, support = {FFF20-0008//Swedish Foundation for Strategic Research/ ; ME 4174/3-1//Deutsche Forschungsgemeinschaft/ ; ANR-11-LABX-0002-01//Agence Nationale de la Recherche/ ; //Lorraine University of Excellence (LUE)/ ; //Knut and Alice Wallenberg Foundation/ ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Arabidopsis/genetics/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Phylogeny ; Plant Proteins/genetics/metabolism ; *Eukaryota/genetics/metabolism ; Plants/genetics/metabolism ; }, abstract = {The LYR motif (LYRM)-containing proteins are small eukaryote-specific proteins that have been defined based on the presence of a Lys-Tyr-Arg amino acid motif and a conserved triplet of α-helices. Twelve LYRM proteins were described in humans. They are involved in core mitochondrial processes as subunits or assembly/stabilising factors of mitochondrial complexes. Their function depends on their ability to interact with the acylated form of acyl-carrier proteins (mtACPs), which places these proteins as direct contributors to two intertwined functional processes, energy metabolism and mitochondrial biogenesis. To gain insight into LYRM proteins in Archaeplastida, we first analyzed the Arabidopsis thaliana genome and then a set of organisms representing the different groups of the Archaeplastida clade. This analysis revealed the existence of 17 classes encompassing 10 of the 12 LYRM classes found in humans. Eleven classes exist in Arabidopsis, and six additional classes are present in some organisms but not in Arabidopsis, thus expanding previous observations. Subsequent data mining based on literature, gene expression, and in silico analyses allowed us to speculate about the possible molecular function of some currently uncharacterised LYRMs in plants. Altogether, this study revealed the diversification of the LYRM protein family in Archaeplastida and more globally among eukaryotes, in which the LYRM-mtACP associations represent central molecular systems to regulate mitochondrial biogenesis upon fluctuating growth conditions.}, } @article {pmid40911529, year = {2025}, author = {Adler, MJ and Martin, MM and Rozo-Lopez, P and Parker, BJ}, title = {A novel mitovirus associated with the fungal entomopathogen Zoophthora radicans.}, journal = {PloS one}, volume = {20}, number = {9}, pages = {e0331239}, pmid = {40911529}, issn = {1932-6203}, mesh = {Animals ; *Aphids/microbiology/virology ; *Entomophthorales/virology/genetics ; Phylogeny ; Genome, Viral ; *RNA Viruses/genetics ; }, abstract = {Metatranscriptome sequencing has emerged as a powerful tool for uncovering viral diversity in insects and their associated microbes. To explore viruses linked to the pea aphid (Acyrthosiphon pisum), we performed metatranscriptome sequencing on field-collected samples. In addition to several known plant viruses, we assembled the genome of a new virus homologous to species in the family Mitoviridae, which are positive-sense single-stranded RNA viruses that encode only an RNA-dependent RNA polymerase and typically replicate in mitochondria. Given the frequent association of mitoviruses with fungi and the presence of entomopathogenic fungal reads in our dataset, we conducted 18S amplicon sequencing and PCR screening on individual aphids. These analyses identified two fungal entomopathogens and uncovered an association between the mitovirus and Zoophthora radicans, a generalist aphid pathogen. Our findings shed light on the hidden microbial diversity in natural pea aphid populations and emphasize the utility of metatranscriptomics in identifying novel virus-host associations.}, } @article {pmid40911664, year = {2025}, author = {Domer, A and Misraje, TR and Xing, D and Arango, BG and Selleghin-Veiga, G and Corl, A and Bowie, RCK and McGuire, JA and Sweazea, KL and Vázquez-Medina, JP and Dudley, R}, title = {Myo-inositol is a key regulator of avian metabolism: From mechanisms to seasonal behavior.}, journal = {Science advances}, volume = {11}, number = {36}, pages = {eadv2794}, pmid = {40911664}, issn = {2375-2548}, mesh = {Animals ; *Inositol/metabolism ; *Birds/metabolism ; *Seasons ; Fatty Acids/metabolism ; Oxidation-Reduction ; Mitochondria/metabolism ; }, abstract = {Being naturally hyperglycemic and insulin insensitive, birds maintain plasma glucose levels twice as high as mammals of similar size. Recent evidence suggests that perturbation of myo-inositol (MI) plays a role in mammalian hyperglycemic regulation. Using an integrative approach, we identify a fundamental role of MI in avian metabolism. We show that MI transporters are highly conserved across birds and that dietary MI reduces fat accumulation in Anna's hummingbirds. MI consumption by hummingbirds varies with seasonal changes in body mass, consistent with a regulatory role. Furthermore, MI enhances fatty acid oxidation in avian cells, via effects on pyruvate-dehydrogenase complexes, indicating a role in mitochondrial fuel selection. Our findings underscore the importance of MI in avian metabolism, offering insights into their evolutionary adaptations in the context of insulin insensitivity.}, } @article {pmid40913463, year = {2025}, author = {Kamal, MM and Cheng, YH and Chu, LW and Nguyen, PT and Liu, CJ and Liao, CW and Posch, T and Leu, JY}, title = {Environment-dependent mutualism-parasitism transitions in the incipient symbiosis between Tetrahymena utriculariae and Micractinium tetrahymenae.}, journal = {The ISME journal}, volume = {19}, number = {1}, pages = {}, pmid = {40913463}, issn = {1751-7370}, support = {NSTC 113-2811-B-001-065//National Science and Technology Council of Taiwan/ ; NSTC 113-2326-B-001-002//National Science and Technology Council of Taiwan/ ; AS-GCS-113-L03//Academia Sinica of Taiwan/ ; AS-IA-110-L01//Academia Sinica of Taiwan/ ; }, mesh = {*Symbiosis ; Phylogeny ; DNA, Mitochondrial/genetics ; Mitochondria/metabolism/genetics ; Photosynthesis/genetics ; Biological Evolution ; Gene Expression Profiling ; }, abstract = {Mutualistic endosymbiosis is a cornerstone of evolutionary innovation, enabling organisms to exploit diverse niches unavailable to individual species. However, our knowledge about the early evolutionary stage of this relationship remains limited. The association between the ciliate Tetrahymena utriculariae and its algal endosymbiont Micractinium tetrahymenae indicates an incipient stage of photoendosymbiosis. Although T. utriculariae cells rely on endosymbiotic algae to grow in low-oxygen conditions, they gradually lose the endosymbionts in oxic conditions. In this study, comparative phylogenomics revealed accelerated evolution in mitochondrial DNA and nucleus-encoded mitochondrial genes in T. utriculariae. Symbiotic cells displayed elongated mitochondria that interacted intimately with endosymbionts. Inhibition of mitochondrial fatty acid oxidation reduced host fitness but increased the endosymbiont population. Time-series transcriptomics revealed physiological fine-tuning of the host across day-night cycles, highlighting symbiosis-associated regulatory adjustments. Endosymbiotic algae downregulated photosynthesis-related genes compared with free-living cells, which correlated with reduced chlorophyll content, suggesting a shift toward host resource exploitation to compensate for diminished photosynthetic capacity. Under oxic conditions, symbiotic T. utriculariae cells exhibited lower fitness than aposymbiotic cells. Our results demonstrate that incipient endosymbioses employ mitochondrial remodeling and endosymbiont metabolic reprogramming to actively regulate transitions between mutualistic and parasitic states, revealing how symbiotic partnerships navigate environmental pressures during their incipient stage of evolutionary establishment.}, } @article {pmid40914435, year = {2026}, author = {Yang, X and Li, X and Li, H and Yu, Y and Qin, C}, title = {MdBACT5 and MdBACT8 contribute to the formation of branched-chain volatiles in apple.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {362}, number = {}, pages = {112742}, doi = {10.1016/j.plantsci.2025.112742}, pmid = {40914435}, issn = {1873-2259}, mesh = {*Malus/genetics/metabolism/enzymology ; *Plant Proteins/genetics/metabolism ; *Volatile Organic Compounds/metabolism ; Phylogeny ; *Transaminases/genetics/metabolism ; Gene Expression Regulation, Plant ; *Amino Acids, Branched-Chain/metabolism ; }, abstract = {Branched-chain amino acid aminotransferases (BCATs) catalyze both the final anabolic step and the initial catabolic step of branched-chain amino acids (BCAAs), which are pivotal for the formation of plant branched-chain volatiles (BCVs). However, the members of BCAT family in apple (Malus domestica Borkh.) remain poorly characterized. In the current study, we identified nine BCAT genes in the apple genome. Phylogenetic analysis classified these MdBCATs into two groups distributed across five chromosomes, with conserved gene structures within each group. Physicochemical analysis revealed coding sequence (CDS) lengths ranging from 852 to 1248 bp, encoding proteins with molecular weights of 31.13 45-41 kDa and isoelectric points (pI) of 5.86-8.35. Collinearity analysis indicated that segmental duplication predominantly drove the expansion of the apple BCAT family. Promoter regions of MdBCATs harbored cis-acting elements associated with growth and development, stress responses, and hormone signaling. RT-qPCR analysis demonstrated differential expression patterns of MdBCATs in the peel tissue of 'Oregon Spur II' apples during ambient storage. Subcellular localization revealed plastid- and mitochondrial-targeting of specific MdBCATs. Notably, transient overexpression of mitochondrially-localized MdBACT5 and MdBACT8 significantly enhanced BCV biosynthesis. Taken together, this study provides critical insights into the role of BCATs in apple fruit aroma quality.}, } @article {pmid40919755, year = {2025}, author = {Xu, L and Guo, P and Kuang, Y and Su, K and Hu, K and Gan, D}, title = {Characteristics of the MAPK gene family in Zizania latifolia and MAPK3 role in response to fungal pathogen infection.}, journal = {Journal of genetics}, volume = {104}, number = {}, pages = {}, pmid = {40919755}, issn = {0973-7731}, mesh = {*Plant Diseases/microbiology/genetics ; Gene Expression Regulation, Plant ; Disease Resistance/genetics ; *Mitogen-Activated Protein Kinases/genetics/metabolism ; *Poaceae/genetics/microbiology ; *Plant Proteins/genetics/metabolism ; Phylogeny ; Multigene Family ; Ustilago/pathogenicity ; Host-Pathogen Interactions/genetics ; Arabidopsis/genetics/microbiology ; }, abstract = {The stems of Zizania latifolia, an important vegetable in China, are targeted by the pathogen Ustilago esculenta, triggering a response through the mitogen-activated protein kinase (MAPK) signalling pathway. To investigate the characteristics and the role of MAPK gene family in the biological stress response, a bioinformatics-based analysis was performed, and the expression patterns of ZlMPKs and MAPK-infection pathway-related genes were detected in male plants inoculated with U. esculenta. Twenty-five ZlMPK genes were identified and divided into four subgroups A, B, C and D: carried a conserved TEY motif, while D had a conserved TDY motif. The ZlMPKs were located in the nucleus, cytoplasm, chloroplast, mitochondria, and peroxisome, and most exhibited evidence of gene duplication events. The relative expression of most ZlMPKs was the highest at 3 h after inoculation with U. esculenta, with 21 ZlMPKs being upregulated and four being downregulated. Additionally, nine of 11 MAPK-infection pathway-related genes were upregulated at 3 h after inoculation. ZlMPK3 was cloned and transformed into Arabidopsis thaliana, and two overexpression lines were identified by resistance screening and molecular detection. Their responses to Botrytis cinerea infection were studied. The leaf inoculation sites of ZlMPK3-overexpression plants revealed damage, while those of wild-type plants did not. The relative expression of MAPK pathogen related genes was altered after inoculation. Specifically, the expression levels of the ethylene biosynthetic pathway gene AtACS6 and five cysteine-rich secretory protein CAP genes were significantly upregulated, while those of systemic acquired resistance marker gene, pathogenesis-related 1 AtPR1 and early defense signalling gene AtFRK1 were significantly downregulated, indicating that resistance to B. cinerea was weakened in the ZlMPK3-overexpression lines.}, } @article {pmid40925877, year = {2025}, author = {Peters, L and Wagner, VC and Schoeller, T and Dwiani, S and Schallenberg-Rüdinger, M and Meyer, EH and Kühn, K}, title = {PPR596 Is Required for nad2 mRNA Splicing and Complex I Biogenesis in Mitochondria of Arabidopsis thaliana.}, journal = {Physiologia plantarum}, volume = {177}, number = {5}, pages = {e70507}, pmid = {40925877}, issn = {1399-3054}, support = {400681449/GRK2498//Deutsche Forschungsgemeinschaft/ ; ME 4174/3-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Arabidopsis/genetics/metabolism/growth & development ; *Arabidopsis Proteins/metabolism/genetics ; *RNA Splicing/genetics ; *Mitochondria/metabolism/genetics ; *Electron Transport Complex I/metabolism/genetics ; RNA, Messenger/genetics/metabolism ; Introns/genetics ; *RNA-Binding Proteins/metabolism/genetics ; Gene Expression Regulation, Plant ; RNA Editing/genetics ; Mutation ; *Mitochondrial Proteins/metabolism/genetics ; *NADH Dehydrogenase/genetics/metabolism ; }, abstract = {Several genes in the mitochondria of angiosperms are interrupted by introns, and their posttranscriptional excision involves numerous nucleus-encoded auxiliary factors. Most of these factors are of eukaryotic origin, among them members of the pentatricopeptide-repeat (PPR) family of RNA-binding proteins. This family divides into the PLS and P classes, with PLS-class proteins typically participating in C-to-U mRNA editing and P-class members contributing to transcript stabilization and intron splicing. The P-class protein PPR596 was previously described to be involved in mitochondrial RNA editing, with the ppr596 mutant showing moderately elevated editing of a specific, partially edited site within the rps3 mRNA. PPR596 disruption led to a substantial delay in plant development. Because the moderate change in RNA editing in the ppr596 mutant is unlikely to be the cause of its severe developmental retardation, we re-investigated mitochondrial gene expression and found that PPR596 is specifically required for the efficient excision of the third intron from the nad2 pre-mRNA. Insufficient splicing of this intron in ppr596 impairs respiratory-chain complex I biogenesis at the step of the insertion of the Nad2 subunit, thus perturbing plant development.}, } @article {pmid40930487, year = {2025}, author = {Portillo, AM and García-Velasco, JA and Varela, E}, title = {Influence of oxidative stress on women's fertility: A model with a generational age Caputo's fractional derivative.}, journal = {Bio Systems}, volume = {257}, number = {}, pages = {105577}, doi = {10.1016/j.biosystems.2025.105577}, pmid = {40930487}, issn = {1872-8324}, mesh = {Female ; Humans ; *Oxidative Stress/physiology ; *Fertility/physiology ; *Aging/physiology ; *Models, Biological ; Adult ; Telomere Shortening/physiology ; *Cellular Senescence/physiology ; Telomere/metabolism ; Granulosa Cells/metabolism ; Middle Aged ; Antioxidants ; }, abstract = {Cellular aging associated with telomeric shortening plays an important role in female fertility. In addition to natural decline, due to the loss of telomeric repeats during cell division, other factors such oxidative stress (OS), accelerate telomere shortening by causing a dramatic loss of telomeric repeats. Thus, mathematical models to better understand the accelerated aging leading to infertility are lacking in the literature. An initial and boundary value problem (IBVP) with a diffusion-advection equation was considered to describe the evolution of a cell population undergoing a gradual decrease of the proliferation potential due to the end-replication problem (Olovnikov, 1973). In this paper we propose a continuum model that attempts to capture the random telomere shortening caused by OS, replacing the advection term with a Caputo's fractional derivative of order β, 0<β<1, with respect to the generational age. The distance between the order of the Caputo derivative and 1 was considered the oxidation parameter. The mathematical model was applied to the human follicular growth from preantral to pre-ovulatory follicle, in young and older women to study the influence of oxidation and low telomerase activity on the aging rate of the pre-ovulatory follicle. We observed that as OS increases, the generational age of granulosa cells (GCs) increases as well, suggesting that telomeres of these GCs will be aged. Although middle-aged women treated with antioxidants could reduce the negative effects of OS on telomeres, antioxidants in combination with good levels of telomerase activity yield the best results regarding the reduction of generational aging of GCs.}, } @article {pmid40931882, year = {2025}, author = {Chen, L and Yang, G and Chai, S}, title = {Comparative mitogenomics of the eulipotyphlan species (Mammalia, Eulipotyphla) provides novel insights into the molecular evolution of hibernation.}, journal = {Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis}, volume = {35}, number = {5-6}, pages = {184-196}, doi = {10.1080/24701394.2025.2558619}, pmid = {40931882}, issn = {2470-1408}, mesh = {Animals ; *Hibernation/genetics ; *Evolution, Molecular ; *Genome, Mitochondrial ; Phylogeny ; *Hedgehogs/genetics ; *Eulipotyphla/genetics ; }, abstract = {Hibernation is an elaborate response strategy employed by numerous mammals to survive in cold conditions that involves active suppression of metabolism. Despite the role of mitochondria as energy metabolism centers during hibernation, the adaptive and evolutionary mechanisms of mitochondrial genes in hibernating animals, like hedgehogs in eulipotyphlan species, are not yet fully understood. In this study, we sequenced and assembled mitochondrial genomes of the hibernating four-toed hedgehog (Atelerix albiventris) and the non-hibernating Asian house shrew (Suncus murinus). While no significant positive selection was detected, we identified unique amino acid substitutions and accelerated evolutionary rates of mitochondrial proteins and the encoding genes in hibernating hedgehogs. Moreover, the distinctive evolutionary patterns indicated a potential link among the adaptive evolution of mitochondrial genes (such as ATP6, CYTB, and ND6), the phenotypes of hibernation and longevity in eulipotyphlan species. These three genes evolved rapidly in hibernating Erinaceidae species and exhibited significant correlations with the two distinct phenotypes, indicating their pivotal roles in the evolution of hibernation and longevity. These findings provide insights into the genetic mechanisms responsible for metabolic plasticity and longevity in eulipotyphlan hibernators, with implications for other mammalian taxa.}, } @article {pmid40933545, year = {2025}, author = {West, SL and Wardill, TJ}, title = {Diverse musculature layers in three species of octopus support precise motor control yet lack smooth muscle.}, journal = {Royal Society open science}, volume = {12}, number = {9}, pages = {250684}, pmid = {40933545}, issn = {2054-5703}, abstract = {Octopus intrinsic arm musculature is often referred to as entirely obliquely striated muscle. However, only three muscle layers have been systematically shown as striated muscle. Because molluscan muscle control can vary greatly (i.e. smooth versus striated types), a systematic examination of each arm muscle layer is necessary to understand its neuromuscular control. Here, we use two-photon microscopy to determine if striations are present in the eight layers and trabeculae of intrinsic arm muscle in Octopus bimaculoides (California two-spot octopus) and Abdopus aculeatus ('prickly octopus'). We also use scanning electron microscopy to examine the arm of Octopus bocki (Bock's pygmy octopus). We confirm for the first time, to our knowledge, that each intrinsic arm muscle layer from multiple octopus species is obliquely striated. Furthermore, we find that the two layers of longitudinal muscle-divided by the median oblique layer-exhibit different morphology. This occurs in all three species examined, with significantly lower muscle fibre density in the internal longitudinal layer of O. bimaculoides and A. aculeatus, and smaller internal mitochondria cores (with larger muscle area) compared with the external longitudinal layer in O. bocki. This suggests additional functional muscle layers that would give octopuses even greater precision in motor control of their arms.}, } @article {pmid40943134, year = {2025}, author = {Lin, D and Zhao, X and Hu, Q and Wang, S and Zhang, Y and Xu, Z}, title = {Genome-Wide Identification, Phylogenetic Analysis, and Expression Pattern of Polyamine Biosynthesis Gene Family in Pepper.}, journal = {International journal of molecular sciences}, volume = {26}, number = {17}, pages = {}, pmid = {40943134}, issn = {1422-0067}, support = {2024LZGC013//Key R&D Program of Shandong Province/ ; 25-1-5-xdny-13-nsh//Science & Technology for Public Benefit Demonstration Project of Qingdao/ ; 2024TZXD019//Sci-Tech Innovation Action Plan for Rural Vitalization of Shandong Province/ ; SDAIT0507//Vegetable Industrial Technology System of Shandong Province/ ; 24-4-4-zrjj-27-jch//Natural Science Foundation of Qingdao/ ; }, mesh = {*Capsicum/genetics/metabolism ; *Polyamines/metabolism ; *Gene Expression Regulation, Plant ; Phylogeny ; Stress, Physiological/genetics ; Multigene Family ; *Plant Proteins/genetics/metabolism ; *Genome, Plant ; Plant Growth Regulators/metabolism ; Promoter Regions, Genetic ; }, abstract = {Polyamines (PAs), including putrescine, spermidine, spermine, and thermospermine, play essential roles in plant growth, development, and responses to stress. However, the structure and function of PA biosynthetic genes in pepper remain poorly characterized. This study aimed to identify PA biosynthesis genes in the pepper genome using bioinformatics approaches and to assess their expression under various stress conditions. A total of 16 PA biosynthesis-related genes were identified, representing members of the arginine decarboxylase (ADC), ornithine decarboxylase (ODC), agmatine iminohydrolase (AIH), N-carbamoylputrescine amidohydrolase (CPA), S-adenosylmethionine decarboxylase (SAMDC), spermidine synthase (SPDS), spermine synthase (SPMS), and ACAULIS5 (ACL5) gene families. These genes encode proteins with an average molecular weight of approximately 40 kDa, primarily localized in the mitochondria and cytoplasm. Promoter analysis revealed multiple cis-acting elements associated with stress and phytohormone responsiveness. Gene expression was induced by various abiotic stresses, including saline-alkaline, drought, heat, cold, and hydrogen peroxide, as well as by phytohormones such as abscisic acid, ethylene, salicylic acid, auxin, and gibberellin. Overall, this study provides a comprehensive analysis of PA biosynthesis genes in pepper and highlights their potential roles in stress adaptation and hormone signalling, offering a foundation for further exploration of PA-mediated stress tolerance mechanisms.}, } @article {pmid40948565, year = {2025}, author = {Zlatogursky, V and Boscaro, V and Lax, G and Wanntorp, M and Pohl, N and Burki, F and Keeling, PJ}, title = {Phylogenetic position and mitochondrial genome evolution of "orphan" eukaryotic lineages.}, journal = {iScience}, volume = {28}, number = {8}, pages = {113184}, pmid = {40948565}, issn = {2589-0042}, abstract = {The phylogenetic tree of eukaryotes is divided into a handful of highly diverse "'supergroups"; only a few so-called "orphan" lineages branch in uncertain positions outside of these large clades. We found that the mitochondrial genome of one such lineage, the telonemids, is considerably gene-rich, a feature observed in other "orphans" as well, raising the possibility that these organisms share a common history. On the contrary, our phylogenomic analyses show that "orphans" with gene-rich mitochondria branch into two different positions: telonemids actually belong to the established supergroup Haptista, while provorans and meteorids form a strongly supported clade with hemimastigophorans, in a previously unrecognized ancient supergroup that we dub here Promethea. Comparative genomics shows that this split reflects differences between mitochondrial gene sets. Thanks to the increased number of available representatives analyzed together, our results further simplify and illuminate the evolutionary relationships between eukaryotes.}, } @article {pmid40956846, year = {2025}, author = {Xu, P and Mancuso, RI and Leonzino, M and Zeiss, CJ and Krause, DS and De Camilli, P}, title = {Impaired hematopoiesis and embryonic lethality at midgestation of mice lacking both lipid transfer proteins VPS13A and VPS13C.}, journal = {PLoS biology}, volume = {23}, number = {9}, pages = {e3003393}, pmid = {40956846}, issn = {1545-7885}, support = {P30 DA018343/DA/NIDA NIH HHS/United States ; U54 DK106857/DK/NIDDK NIH HHS/United States ; R01 NS036251/NS/NINDS NIH HHS/United States ; S10 OD030363/OD/NIH HHS/United States ; R37 NS036251/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Mice, Knockout ; Mice ; *Vesicular Transport Proteins/genetics/metabolism/deficiency ; *Hematopoiesis/genetics/physiology ; *Embryo Loss/genetics ; Embryonic Development/genetics ; *Carrier Proteins/genetics/metabolism ; Female ; Erythropoiesis/genetics ; Autophagy ; Mice, Inbred C57BL ; Embryo, Mammalian ; }, abstract = {VPS13 is the founding member of a family of proteins that mediate lipid transfer at intracellular membrane contact sites by a bridge-like mechanism. Mammalian genomes comprise 4 VPS13 genes encoding proteins with distinct localizations and function. The gene duplication resulting in VPS13A and VPS13C is the most recent in evolution and, accordingly, these two proteins are the most similar to each other. However, they have distinct subcellular localizations and their loss of function mutations in humans are compatible with life but result in two different age-dependent neurodegenerative diseases, chorea-acanthocytosis and Parkinson's disease, respectively. Thus, it remains unclear whether these two proteins have overlapping functions. Here, we show that while Vps13a KO and Vps13c KO mice are viable, embryonic development of Vps13a/Vps13c double knockout (DKO) mice is arrested at midgestation. Prior to death, DKO embryos were smaller than controls, were anemic and had a smaller liver, most likely reflecting defective embryonic erythropoiesis which at this developmental stage occurs primarily in this organ. Further analyses of erythroid precursor cells showed that their differentiation was impaired and that this defect was accompanied by activation of innate immunity as revealed by upregulation of interferon stimulated genes (ISGs). Additionally, the RIG-I and MDA5 components of dsRNA triggered innate immunity were found upregulated in the DKO fetal liver. Activation of innate immunity may result from loss of integrity of the membranes of intracellular organelles, such as mitochondria and autophagic lysosomes, or to impaired autophagy, due to the absence of these lipid transport proteins. The surprising and striking synthetic effect resulting for the combined loss of VPS13A and VPS13C suggests that despite of the different localization of these two proteins, the lipid fluxes that they mediate are partially redundant.}, } @article {pmid40958577, year = {2025}, author = {Robles, NV and Moran, BM and Rodríguez Barrera, MJ and Jofre, GI and Gunn, T and Iverson, ENK and Beskid, S and Baczenas, JJ and Sedghifar, A and Andolfatto, P and Powell, DL and Brandvain, Y and Havird, JC and Rosenthal, GG and Schumer, M}, title = {Admixture Mapping Reveals Evidence for Multiple Mitonuclear Incompatibilities in Swordtail Fish Hybrids.}, journal = {Molecular ecology}, volume = {34}, number = {22}, pages = {e70106}, pmid = {40958577}, issn = {1365-294X}, support = {R35GM133774/GM/NIGMS NIH HHS/United States ; R01 GM115523/GM/NIGMS NIH HHS/United States ; R35 GM142836/GM/NIGMS NIH HHS/United States ; R01GM115523/GM/NIGMS NIH HHS/United States ; IOS-1755327//Division of Integrative Organismal Systems/ ; R35GM142836/GM/NIGMS NIH HHS/United States ; Y81//Human Frontiers in Science Program/ ; IOS-2421661//Division of Integrative Organismal Systems/ ; R35 GM133774/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Hybridization, Genetic ; Gene Flow ; *Cell Nucleus/genetics ; *Cyprinodontiformes/genetics ; *Genetics, Population ; Genome, Mitochondrial ; Mitochondria/genetics ; }, abstract = {How barriers to gene flow arise between closely related species is one of the oldest questions in evolutionary biology. Classic models in evolutionary biology predict that negative epistatic interactions between variants in the genomes of diverged lineages, known as hybrid incompatibilities, will reduce viability or fertility in hybrids. The genetic architecture of these interactions and the evolutionary paths through which they arise have profound implications for the efficacy of hybrid incompatibilities as barriers to gene flow between species. While these questions have been studied using theoretical approaches for several decades, only recently has it become possible to genetically map larger numbers of hybrid incompatibilities. Here, we use admixture mapping in natural hybrid populations of swordtail fish (Xiphophorus) to identify hybrid incompatibilities involving genetic interactions between the mitochondrial and nuclear genomes. We find that at least nine regions of the genome are involved in mitonuclear incompatibilities. These incompatibilities involve interactions between the nuclear genome and the X. malinche mitochondria, the X. birchmanni mitochondria, or both. Moreover, they vary in the strength of selection they experience and the degree to which they limit gene flow in natural hybrid populations. Our results build a deeper understanding of the complex architecture of selection against incompatibilities in naturally hybridising species and highlight an important role of mitonuclear interactions in the evolution of reproductive barriers between closely related species.}, } @article {pmid40959572, year = {2025}, author = {Chuang, CC and Chen, YH and Chu, FY and Yang, CP and Ho, HL and Chang, FP and Lo, YL and Chen, CJ and Chang, YH}, title = {Temporal Effects of Lipid Oversupply on Energy Metabolism and Mitochondrial Homeostasis in Hepatocytes.}, journal = {International journal of medical sciences}, volume = {22}, number = {14}, pages = {3664-3681}, pmid = {40959572}, issn = {1449-1907}, mesh = {*Hepatocytes/metabolism/pathology ; Humans ; *Energy Metabolism ; *Non-alcoholic Fatty Liver Disease/pathology/metabolism ; Homeostasis ; Animals ; Fatty Acids/metabolism ; Lipid Metabolism ; Male ; Mice ; Epithelial-Mesenchymal Transition ; Mitochondria/metabolism ; Glucose/metabolism ; *Mitochondria, Liver/metabolism/pathology ; }, abstract = {Obesity is closely associated with multiple metabolic disorders such as non-alcoholic fatty liver disease (NAFLD). Patients with NAFLD are susceptible to develop irreversible life-threatening diseases, however, the evolution concerning mitochondrial and metabolic alterations during NAFLD development and progression remain elusive. This study focused on uncovering the sequential events of energy metabolism and mitochondrial homeostasis of hepatocytes under the environment of lipid oversupply by in vitro and in vivo strategies. Long-chain fatty acid (FA) synthesis and lipid storage were first induced by providing hepatocytes with sufficient energy source, followed by suppressed glucose metabolic efficiency and decreased mitochondrial mass. Intriguingly, distinctive features of hepatic cancer cells in response to FA oversupply were characterized. Insulin signaling and glucose uptake were rapidly deterred while lipid β-oxidation was significantly boosted. Enhanced mitochondrial biogenesis was identified as compensatory feedback for mitochondrial dysfunction. FA-induced mitophagy, cell morphological transition and higher N-cadherin expression potentiates epithelial-mesenchymal transition (EMT) which confers the cells with higher plasticity and accelerates NAFLD progression to irreversible hepatic diseases. This study provides evidence elucidating the temporal events caused by FA oversupply, moreover, delineates the facilitative role of excess nutrients in shaping the environment for lipid-laden hepatocytes to acquire malignant traits. Given the rapidly increasing global prevalence of metabolic disorders and the heterogeneous manifestations exhibited by NAFLD during disease progression, better understanding of the sequential events caused by FA overload aids in identifying promising targets and developing tailor-made treatment protocol according to individual disease status and conditions.}, } @article {pmid40972592, year = {2025}, author = {Liu, H and Liu, Y and Hu, Y}, title = {Mitochondrial Impostors: Prevalence and Impacts of NUMTs on Genetic and Evolutionary Studies in Carnivora.}, journal = {Genome biology and evolution}, volume = {17}, number = {10}, pages = {}, pmid = {40972592}, issn = {1759-6653}, mesh = {Animals ; *Carnivora/genetics/classification ; *Pseudogenes ; Phylogeny ; *Evolution, Molecular ; *DNA, Mitochondrial/genetics ; Genome, Mitochondrial ; *Mitochondria/genetics ; }, abstract = {Nuclear mitochondrial pseudogenes are mitochondria-derived DNA sequences integrated into the nuclear genome, which can introduce errors in species identification, phylogenetic inference, and population genetics. Although nuclear mitochondrial pseudogene contamination has been reported in some Carnivora species, a systematic investigation into the prevalence and impacts of nuclear mitochondrial pseudogenes across an order is still lacking. In this study, 22,102 mitochondrial DNA sequences of 80 Carnivora species from 14 families and 54 genera were retrieved from the public National Center for Biotechnology Information database and further analyzed. Using alignment-based methods, 158 problematic sequences/sequence groups were identified and categorized into four types: nuclear mitochondrial pseudogenes, species misidentification or mislabeling, sequence errors, and anomalous sites. Among families, Felidae exhibited the highest rate of nuclear mitochondrial pseudogene contamination, particularly in species of the genus Panthera. In contrast, no nuclear mitochondrial pseudogene contamination was detected in members of Ursidae and Ailuridae. Phylogenetic analysis revealed multiple independent origins of nuclear mitochondrial pseudogene, with some tracing back to the common ancestor of Carnivora. To mitigate nuclear mitochondrial pseudogene-related errors, rigorous sequence verification strategies, such as sequence alignment and phylogenetic validation, should be implemented. In conclusion, our findings highlight the necessity of nuclear mitochondrial pseudogene awareness in genetic and evolutionary studies of Carnivora and other taxa.}, } @article {pmid40974057, year = {2025}, author = {Zhang, X and An, P and Zhang, Z and Hao, Y and Guo, X and Zhu, Y and Gu, Z and Luo, Y and Luo, J}, title = {Single-cell Omics Assessment of Mitochondrial Function: Current Status and Future Perspectives.}, journal = {Genomics, proteomics & bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1093/gpbjnl/qzaf081}, pmid = {40974057}, issn = {2210-3244}, abstract = {In recent years, single-cell omics technologies have seen significant advancements, offering new insights into the study of mitochondria. These technologies are particularly suitable for investigating mitochondria due to their capacity to address intracellular and intercellular heterogeneity. In this review, we categorize the mitochondrial dysfunction and variability identified in both pathological and physiological contexts through single-cell omics assessments. We examine the cutting-edge single-cell omics technologies and track the evolution of studies on mitochondria, highlighting the transition from low-throughput to high-throughput capabilities and from single data types to the integration of multiple genomic and phenomic profiles. Furthermore, we emphasize the applications of single-cell mitochondrial assessment methods in exploring mechanisms, disease screening and prevention, and their potential impacts on lineage tracing, drug discovery, and genetic counseling. Insights gained from single-cell technologies may lead to the development of novel therapeutic strategies, offering promising avenues for addressing diseases associated with mitochondrial dysfunction. Lastly, we identify the limitations of current methodologies and propose areas of focus for future research.}, } @article {pmid40980060, year = {2025}, author = {Russell, JE and Mizera, N and Brown, CG and Chuang, A and Coyle, DR and Nelsen, DR}, title = {Mitochondrial and Wolbachia phylogenetics of the introduced Jorō spider, Trichonephila clavata (Araneae: Araneidae) in North America.}, journal = {PeerJ}, volume = {13}, number = {}, pages = {e19952}, pmid = {40980060}, issn = {2167-8359}, mesh = {Animals ; *Wolbachia/genetics/classification ; *Phylogeny ; *Spiders/microbiology/genetics ; Genetic Variation ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/genetics ; *Mitochondria/genetics ; Sequence Analysis, DNA ; North America ; Georgia ; }, abstract = {The introduction of Trichonephila clavata (L. Koch, 1878) (Araneae: Araneidae: subfamily Nephilinae) in the United States was first recorded in Georgia in 2014. Since its introduction, T. clavata has become a prominent feature of the arthropod fauna in several southeastern US states. Many questions regarding the introduction event(s) remain unanswered; for instance, was the introduction a single discrete event followed by rapid spread, or were there multiple introductions? The mitochondrial cytochrome c oxidase subunit one gene region (COI), which was used to characterize the initial T. clavata observation in the US, has also been used to characterize within- and between-population genetic variation. One confounding factor for COI as a population genetic molecular marker, though, is the presence of cytoplasmic agents of selection such as intracellular bacteria in the genus Wolbachia. Given that Wolbachia infections have been detected in potential source populations of T. clavata, the present study sought to characterize mitochondrial genetic diversity and the status of Wolbachia infection in the North American population(s) closest to the originally proposed introduction site in Georgia. DNA sequencing revealed no mitochondrial genetic variation in the T. clavata population sampled in North America, and an exact sequence match to the previously reported T. clavata in Georgia and a sequence sample from Yunnan, China. Wolbachia was detected in the North American samples. However, phylogenetic analysis on a concatenated multi-locus type sequence suggested two distinct Wolbachia clades, one represented by samples collected in Georgia and another represented by a single sample collected in South Carolina. Sequence analyses of the multi-locus gene regions suggested that the Georgia T. clavata may be infected with two strains of Wolbachia (super-infection), and the South Carolina sample represented a separate single infection. The study's results emphasize the need for further research, including expanded sampling in the introduced and potential source population regions, as well as a more detailed molecular characterization of the populations.}, } @article {pmid40986664, year = {2025}, author = {Raval, PK and García García, C and Sanchez, MS and Gould, SB}, title = {Evolutionary Refinement of Mitochondrial and Plastid Targeting Sequences Coincides with the Late Diversification of Land Plants.}, journal = {Molecular biology and evolution}, volume = {42}, number = {10}, pages = {}, pmid = {40986664}, issn = {1537-1719}, support = {SFB 1208-2672 05415//Deutsche Forschungsgemeinschaft/ ; SPP2237-440043394//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Plastids/genetics/metabolism ; *Mitochondria/metabolism/genetics ; *Embryophyta/genetics/metabolism ; *Evolution, Molecular ; Protein Transport ; Biological Evolution ; Plant Proteins/genetics/metabolism ; Marchantia/genetics/metabolism ; }, abstract = {Plastids and mitochondria are key to plant survival and adaptation. The evolutionary progress of land plants (embryophytes) witnessed gene and genome duplications, and the expansion of organelle-localized proteins. To deal with the increase of nuclear-encoded proteins, targeting to and import by the mitochondrion and plastid are known to have adapted in multiple ways. It included the addition of entirely new import channels and lineage-specific import receptors. Through comparative genomics and experimental biology, we uncover further changes in the organelle import machineries. Their evolution likely served to enhance the rate of protein import and improve its physiological regulation, e.g. via interactions between the import channel and respiratory complex. On the cargo side, nuclear-encoded N-terminal targeting sequences of mitochondrial targeting peptide (TP) and plastidal (pTPs) proteins have diverged in their charge via a preference for phosphorylatable amino acids (AA) (adding negative charges after phosphorylation) and an avoidance of positive charges in the pTPs, which is most evident in eudicots. Using Chlamydomonas and Marchantia, we experimentally underscore that the evolved TP divergence prevents mis-sorting between mitochondria and plastids. In accordance with the increase in phosphorylatable AA in the pTPs, we pinpoint the embryophytic origin of a membrane-anchored phosphatase, PAP2, which is associated with targeting sequence processing. On the whole, we propose a revised model for the evolution of plant organelle protein import from algae to angiosperms, which facilitated the flourishing of this lineage on land.}, } @article {pmid40986928, year = {2025}, author = {Fang, Y and Dou, A and Zhang, Y and Zhang, Y and Gao, Y and Xie, K}, title = {Research on Sepsis and Metabolic Reprogramming from 1998 to 2025: A Bibliometric and Visualized Analysis.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000002714}, pmid = {40986928}, issn = {1540-0514}, abstract = {BACKGROUND: Metabolic reprogramming has emerged as a central mechanism in sepsis pathogenesis, influencing immune responses, organ dysfunction, and therapeutic outcomes. This study conducts a comprehensive bibliometric analysis to map the research landscape, identify key trends, and highlight future directions in this field.

METHODS: Based on the Science Citation Index Expanded database in Web of Science Core Collection (WOSCC) database, we retrieved and analyzed 672 English-language original research articles and reviews. Using R-bibliometrix, VOSviewer, and CiteSpace we performed a multidimensional analysis of academic output trends, geographical distribution, institutional and author collaboration networks, burst detection and the evolution of research hotspots.

RESULTS: The analysis reveals a consistent upward trend in both publication output and citation frequency within this research domain. The United States (24.3% of total publications) and China (23.4%) have emerged as the most productive contributing nations. Notably, the United States maintains superior academic influence as evidenced by its highest citation frequency. Among institutions, Wake Forest University in the United States holds a preeminent position, having published 54 high-impact articles in this field. The journals Frontiers in Immunology, Shock, and Critical Care, represent the premier academic platforms in this research domain. Immunometabolism, mitochondrial regulation, gut microbiota imbalance, epigenetic modifications, along with the mTOR/AMPK/HIF-1α axis and the Sirtuin family pathway has been identified as the key research hotspots. Novel therapeutic approaches targeting metabolic regulation are rapidly emerging, including pharmacological agents, natural compounds, stem cell-based therapies, and non-coding RNA interventions.

CONCLUSION: Research on metabolic reprogramming in sepsis shows promising prospects, with investigations into key mechanisms focusing on current research hotspots and the development of metabolism-targeted interventions emerging as critical priorities for future sepsis prevention and treatment strategies.}, } @article {pmid40990941, year = {2025}, author = {Glastad, RC and Johnston, IG}, title = {Convergent pathways of reductive mitochondrial evolution characterized with hypercubic inference.}, journal = {Journal of evolutionary biology}, volume = {38}, number = {12}, pages = {1590-1600}, doi = {10.1093/jeb/voaf111}, pmid = {40990941}, issn = {1420-9101}, support = {805046/ERC_/European Research Council/International ; TMS2021TMT09//Trond Mohn Foundation/ ; }, mesh = {*Mitochondria/metabolism/genetics ; *Biological Evolution ; Animals ; *Evolution, Molecular ; *Eukaryota/genetics ; }, abstract = {For a striking example of mitochondrial behaviour beyond adenosine triphosphate (ATP) generation, consider mitochondrion-related organelles (MROs). Hydrogenosomes, mitosomes, and other reduced mitochondrial forms have evolved through the loss of physical and functional features, from individual electron transport chain complexes to oxidative phosphorylation and the very ability to produce ATP (and further). Reduction of mitochondria is a dramatic example of convergent evolution, occuring in every eukaryotic kingdom and many parallel times. Here, we use hypercubic inference, a class of methods from evolutionary accumulation modelling, to explore the pathways of convergent mitochondrial reduction across eukaryotes. We find that most MRO diversity can be explained by small variations on two distinct pathways, starting with either the loss of Complex I or the loss of Complexes III/IV or TCA cycle steps, which tend to proceed over different characteristic timescales. We show that different clades, including ciliates and apicomplexans, reflect particular instances of these pathways. Using metabolic modelling, we connect the structure of these evolutionary pathways to the metabolic impact of the changes involved, suggesting a plausible explanation for the dramatically convergent nature of reductive evolution. We discuss this approach in connection with related theory on the genetic and functional reduction of mitochondria across organisms.}, } @article {pmid40995854, year = {2026}, author = {Wang, H and Yuan, H and Wang, Y and Xi, W and Wang, X and Tang, R and Xu, Q and Li, J and Liu, D and Yang, Q and Wang, X and Kong, F and Liu, B and Li, X and Wang, Z}, title = {Natural Variation of a PPR Coding Gene SST1 Confers Salt Tolerance During Soybean Domestication.}, journal = {Plant biotechnology journal}, volume = {24}, number = {2}, pages = {831-855}, pmid = {40995854}, issn = {1467-7652}, support = {2023YFD1200600//National Key Research and Development Program of China/ ; 2023ZD040710505//Biological Breeding-National Science and Technology Major Project/ ; }, mesh = {*Glycine max/genetics/physiology ; *Salt Tolerance/genetics ; Domestication ; *Plant Proteins/genetics/metabolism ; Genome-Wide Association Study ; Gene Expression Regulation, Plant ; Genes, Plant ; Genetic Variation ; }, abstract = {Soil salinity is one of the constraints that adversely affect seedling growth and limit soybean yield. Identifying salt tolerance genes and profiling their allele variants are crucial for elucidating the mechanisms underlying salt tolerance in soybean and enabling the genetic improvement of salt-tolerant cultivars. Here, we developed a salt-induced leaf senescence-based screening system to assess salt tolerance and identified a key salt tolerance gene, SST1, which encodes a pentatricopeptide repeat (PPR) protein, via genome-wide association analysis. We showed that the truncated allele SST1[HapT], which has a nonsense mutation, increases salt tolerance in soybean, whereas the full-length allele SST1[HapC] does not. Located in mitochondria, SST1 regulates RNA editing of the mitochondrial genes cob, nad3 and atp6-1, thereby influencing mitochondrial morphology and H2O2 homeostasis in root cells. SST1 is an adaptive domestication-related gene; the truncated SST1[HapT] allele is exclusively fixed in cultivated soybean but absent in wild soybean, indicating selection under increasing soil salinity during domestication. Furthermore, our results revealed that SST1 regulates salt tolerance by synergistic interaction with GmCHX1, a pivotal salt tolerance gene unselected during domestication. Our findings provide valuable insights into soybean domestication and offer targets for enhancing soybean salt tolerance.}, } @article {pmid40996337, year = {2025}, author = {Lee, S and Jung, SY and Kuś, P and Bondaruk, J and Lee, JG and Jaksik, R and Putluri, N and Dinh, KN and Cogdell, D and Chen, H and Wang, Y and Chen, J and Navai, N and Dinney, C and Mendelsohn, C and McConkey, D and Behringer, RR and Guo, CC and Wei, P and Kimmel, M and Czerniak, B}, title = {Dysregulated mitochondrial energy metabolism drives the progression of mucosal field effects to invasive bladder cancer.}, journal = {The Journal of pathology}, volume = {267}, number = {3}, pages = {329-346}, pmid = {40996337}, issn = {1096-9896}, support = {//MD Anderson Donor Funds/ ; RP210227//Cancer Prevention and Research Institute of Texas/ ; //Dan L. Duncan Comprehensive Cancer Center funds/ ; P30CA125123/NH/NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; 2021/41/B/NZ2/04134//National Science Centre (Krakow, Poland)/ ; RP230166//Cancer Prevention and Research Institute of Texas/ ; //MD Anderson Nathan W. Lassiter Endowment/ ; RP220021//Cancer Prevention and Research Institute of Texas/ ; }, mesh = {Humans ; Disease Progression ; *Energy Metabolism ; Epithelial-Mesenchymal Transition ; *Mitochondria/metabolism/pathology/genetics ; Mutation ; Neoplasm Invasiveness ; *Urinary Bladder Neoplasms/pathology/genetics/metabolism ; }, abstract = {Multiplatform mutational and gene expression profiling complemented with proteomic and metabolomic spatial mapping were used on the whole-organ scale to identify the molecular profile of bladder cancer evolution from field effects. Analysis of the mutational landscape identified three types of mutations, referred to as α, β, and γ. Time modeling of the mutations revealed that carcinogenesis may span 30 years and can be divided into dormant and progressive phases. The α mutations developed in the dormant phase. The progressive phase lasted 5 years and was signified by expanding β mutations, but it was driven to invasive cancer by γ mutations. The mutational landscape emerged on a background of disorganized urothelial differentiation, activated epithelial-mesenchymal transition, and enhanced immune infiltration with T-cell exhaustion. Complex dysregulation of mitochondrial energy metabolism with downregulation of oxidative phosphorylation emerged as the leading mechanism driving the progression of mucosal field effects to invasive cancer. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.}, } @article {pmid40996803, year = {2025}, author = {Song, J and Qi, Z and He, C and Luo, G and Yuan, B and Xiao, S and Yang, Y and Wang, F and Ye, G and Fang, Q and Yan, Z}, title = {Duplication of a conserved mitochondrial enzyme gene arms parasitoid wasps with venom cytotoxicity and oogenesis regulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {39}, pages = {e2512820122}, pmid = {40996803}, issn = {1091-6490}, support = {32330085//MOST | NSFC | Key Programme/ ; 2023YFD1400600//MOST | National Key Research and Development Program of China (NKPs)/ ; 2022YFD1401102//MOST | National Key Research and Development Program of China (NKPs)/ ; 226-2024-00070//MOE | Fundamental Research Funds for the Central Universities (Fundamental Research Fund for the Central Universities)/ ; }, mesh = {Animals ; *Wasps/genetics/enzymology ; *Gene Duplication ; *Oogenesis/genetics ; Evolution, Molecular ; Phylogeny ; *Wasp Venoms/genetics ; Female ; *Mitochondria/enzymology/genetics ; Insect Proteins/genetics/metabolism ; *Genes, Mitochondrial ; }, abstract = {Gene duplication, followed by neofunctionalization, is a key mechanism driving the emergence of evolutionary novelties. Despite its significance, the molecular and functional processes underlying this phenomenon remain incompletely understood. By tracing the evolutionary history of cysteine-S-conjugate beta-lyase genes within the kynurenine aminotransferase family, we identified a gene duplication event in parasitoid wasps of the Chalcidoidea superfamily. Notably, a single-copy, highly conserved mitochondria-localized physiological gene underwent a significant duplication, resulting in one copy being recruited into the venom system and acquired cytotoxicity against wasps' hosts. Through this neofunctionalization process, we observed several key evolutionary changes, including loss of ancestral mitochondrial localization and enzyme activity, acquisition of a secretory signal peptide, shift in expression pattern, positive selection, and the establishment of evolutionary acquired protein-protein interactions. Additionally, we found that another duplicate copy was specialized in wasps' ovary and repurposed for oogenesis regulation. Our study offers a detailed insight into the genetic and molecular mechanisms that drive functional diversification during the evolution of gene families.}, } @article {pmid41007366, year = {2025}, author = {Xiong, Y and Xiong, Y and Yu, Q and Ma, X and Lei, X}, title = {Organelle Genomes of Nardostachys jatamansi Offer New Perspectives into the Evolutionary Dynamics of Caprifoliaceae.}, journal = {Biology}, volume = {14}, number = {9}, pages = {}, pmid = {41007366}, issn = {2079-7737}, support = {32271753//National Natural Science Foundation of China/ ; 2022YFQ0076//Sichuan Province regional innovation cooperation project/ ; 2023YFSY0012//Cooperation project of provincial college, and provincial school/ ; }, abstract = {The organelle genomes of N. jatamansi were sequenced and examined to explore their structure, evolution, and possible functional implications. The chloroplast genome was constructed as a singular circular entity of 155,225 bp, whereas the mitochondrial genome exhibited considerable complexity, divided into 14 contigs totaling 1,229,747 bp, along with several sub-circular formations. Comparative analysis within the Caprifoliaceae family revealed that four genes (rps19, rpl22, rpl20, and matK) exhibited high sequence variability, suggesting their potential as molecular markers for the identification of species. In addition, three genes (clpP, ycf1, and ycf2) exhibited ka/ks ratios greater than one, which implies positive selection. Intracellular (between chloroplast and mitochondria) gene transfer analysis revealed the integration of six chloroplast-derived genes, and repeat analysis identified 47,980 repeat pairs in the mitochondrial genome, which spans 2.64 Mb. It is likely that these traits add to the structural complexity of the mitochondrial genome. Predictions based on climate show that N. jatamansi may be able to find more ideal habitat over the next 60 years. These results give us a useful genetic resource for studying evolution and set the stage for future research into how the species can be used in medicinal applications.}, } @article {pmid41009599, year = {2025}, author = {Gong, Y and Chen, R and Yang, C and Lu, Y and Fu, Z and Feng, Y and Li, X and Li, L and Li, X}, title = {Genomic-Encoded Mitovirus RdRp Is Required for Embryo Development and Maintaining Mitochondrial Dynamics in Arabidopsis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {18}, pages = {}, pmid = {41009599}, issn = {1422-0067}, support = {No.32171920//National Natural Science Foundation of China/ ; }, mesh = {*Arabidopsis/genetics/virology/embryology/growth & development/metabolism ; *RNA-Dependent RNA Polymerase/genetics/metabolism ; *Mitochondrial Dynamics/genetics ; Mitochondria/metabolism/genetics ; Phylogeny ; *Seeds/genetics/growth & development ; *Arabidopsis Proteins/genetics/metabolism ; *Viral Proteins/genetics/metabolism ; Gene Expression Regulation, Plant ; }, abstract = {Mitoviral-derived sequences are frequently detected in plant genomes, encoding an RNA-dependent RNA polymerase (RdRp). These sequences share many similarities with mitoviruses that are known to commonly infect plant mitochondria. However, the functional characterization of nuclear-encoded mitoviral-RdRp remains unclear. This study elucidates the critical role of mRdRp (AT2G07749) in maintaining mitochondrial homeostasis and embryo viability, highlighting the dual role of viral-derived genes in plant development and stress response. Phylogenetic analysis reveals that mRdRp shares 96.8% identity with the mitoviral RdRp encoded by mitochondrial-genomes, suggesting that this nuclear mRdRp gene originated from horizontal transfer events following ancestral plant-mitovirus infections. To dissect mRdRp function, we generated a mRdRp knockout mutant via CRISPR-Cas9 or knockdown mutant by RNA interference (RNAi). These mRdRp mutants exhibited severe developmental defects, including dwarfism, embryo lethality, and sterility. Phenotypic assays further showed that mRdRp mutants displayed heightened susceptibility to ABA and rotenone, indicating impaired adaptive capacity to both hormonal and metabolic stress. Loss of mRdRp led to fragmented mitochondrial networks and a significant reduction in mitochondrial abundance in both leaf protoplasts and root meristematic cells. Additionally, mitochondrial-derived small RNA (sRNA) aberrantly accumulated in mRdRp mutants, which potentially disrupts endogenous RNA-silencing pathways that rely on sRNA-mediated gene regulation. Collectively, these results provide mechanistic insights into the function integration of a virus-derived gene into plant cellular networks, advancing our understanding of host-virus coevolution and the role of horizontally transferred viral genes in shaping plant physiology.}, } @article {pmid41009722, year = {2025}, author = {Greco, S and Assalve, G and Lunetti, P and Kayentao, K and Dara, A and Scaramuzzi, D and Zara, V and Ferramosca, A}, title = {Targeting Mitochondrial Function in Plasmodium falciparum: Insight into Antimalarial Drugs and the Emerging Role of Saccharomyces cerevisiae as a Model System.}, journal = {International journal of molecular sciences}, volume = {26}, number = {18}, pages = {}, pmid = {41009722}, issn = {1422-0067}, support = {Mission 4, Component 2 - Investment 3.3 "Introduction of innovative PhD programs addressing the innovation needs of enterprises and promoting the employment of researchers by companies" - Fellowship ID 14230//Italian National Recovery and Resilience Plan (PNRR)/ ; }, mesh = {*Saccharomyces cerevisiae/drug effects/metabolism/genetics ; *Plasmodium falciparum/drug effects/metabolism ; *Mitochondria/drug effects/metabolism ; *Antimalarials/pharmacology/therapeutic use ; Humans ; *Malaria, Falciparum/drug therapy/parasitology ; Animals ; }, abstract = {Malaria remains a major global health threat, particularly in low- and middle-income countries, where children under five and pregnant women are most vulnerable. Despite notable progress in reducing malaria-related morbidity and mortality, the rise of drug-resistant Plasmodium falciparum strains continues to undermine eradication efforts. In this context, the parasite's mitochondrion has emerged as a promising target for novel antimalarial therapies due to its essential role in parasite viability throughout all life cycle stages and its marked structural and biochemical differences from the human counterpart. This review highlights recent advances in the development of compounds targeting mitochondrial function in P. falciparum and discusses the utility of Saccharomyces cerevisiae as a powerful model organism for antimalarial drug discovery. Owing to its shared eukaryotic features, genetic tractability, and capacity for heterologous expression of parasite mitochondrial proteins, S. cerevisiae offers a cost-effective and experimentally accessible platform for elucidating drug mechanisms and accelerating therapeutic development.}, } @article {pmid41009977, year = {2025}, author = {Zhou, B and Guan, C and Guan, M}, title = {Genome-Wide Identification of the BnaRFS Gene Family and Functional Characterization of BnaRFS6 in Brassica napus.}, journal = {Genes}, volume = {16}, number = {9}, pages = {}, pmid = {41009977}, issn = {2073-4425}, support = {HARS-03//Hunan Agriculture Research System/ ; }, mesh = {*Brassica napus/genetics/metabolism/growth & development ; *Plant Proteins/genetics/metabolism ; Phylogeny ; Gene Expression Regulation, Plant ; Multigene Family ; *Galactosyltransferases/genetics/metabolism ; }, abstract = {BACKGROUND: Raffinose synthase (RFS) plays a crucial role in plant growth and development, as well as in responses to biotic and abiotic stresses. However, its functions in Brassica napus remain poorly understood.

METHODS: To investigate the characteristics of the RFS gene family in B. napus (rapeseed), five Arabidopsis thaliana RFS gene sequences were used as references to identify thirteen RFS genes in B. napus, four in Brassica rapa, and six in Brassica oleracea. A comprehensive analysis was conducted, including molecular characteristics, phylogenetic relationships, conserved protein motifs, gene structures, and chromosomal localization.

RESULTS: BnaC02G0100500ZS was selected as a candidate gene due to its unique expression profile. Sequence alignment identified it as BnaRFS6, and subcellular localization revealed that its encoded protein is localized in the mitochondria. Overexpression of BnaRFS6 in rapeseed significantly affected the soluble sugar and starch content in the stalks, resulting in increased levels of fructose, glucose, and raffinose, and a decreased starch content.

CONCLUSIONS: These findings highlight the role of BnaRFS6 in enhancing sugar metabolism in B. napus, particularly in relation to fructose, glucose, and raffinose accumulation. Understanding its potential function provides a foundation for improving the sugar content and taste of rapeseed stalks through genetic engineering in the future.}, } @article {pmid41011480, year = {2025}, author = {Mpakosi, A and Kaliouli-Antonopoulou, C and Cholevas, V and Cholevas, S and Tzouvelekis, I and Mironidou-Tzouveleki, M and Tsantes, EA and Tsakri, D and Vlachaki, M and Baliou, S and Ioannou, P and Sokou, R and Bonovas, S and Tsantes, AG}, title = {From Ancient Philosophy to Endosymbiotic Theory: The Bacterial Origin and Key Role of Mitochondria in Immune Responses.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, pmid = {41011480}, issn = {2076-2607}, abstract = {The endosymbiotic theory, which is the crucial starting point of eukaryogenesis, was first mentioned in the philosophy of the pre-Socratic Greek philosopher Empedocles. According to him, everything merges into units with differential survival. Similarly, during eukaryogenesis, the fusion of two distinct units resulted in the creation of a new cell type that possessed a newly formed organelle, the mitochondrion. Since then, the mitochondrion has been a key regulator of health and immunity. Furthermore, many of its characteristics and functions are due to its endosymbiotic bacterial origin. For example, it possesses damage-associated molecular patterns that can activate inflammatory signaling pathways, has circular DNA with CpG-rich motifs, as well as a double phospholipid membrane, and divides by fission. Mitochondrial function plays a critical role in maintaining cellular homeostasis, as they meet the cell's energy needs and regulate many of its functions. However, after cellular damage due to infection, radiation, or toxins, mitochondrial stress and dysfunction can occur and mitochondrial DNA can be released into the cytosol. Cytosolic mitochondrial DNA can then activate proinflammatory signaling pathways, mediated by TLR9 and cGAS, as well as inflammasomes, triggering inflammation and autoimmunity.}, } @article {pmid41012037, year = {2025}, author = {Teixeira, SP and Silva, JV and Santos, VC and Mazzeo, L and Correa, RCC and Pereira, RAS}, title = {Fig Macula as a Key Multifunctional Structure Mediating the Fig-Fig Wasp Mutualism.}, journal = {Plants (Basel, Switzerland)}, volume = {14}, number = {18}, pages = {}, pmid = {41012037}, issn = {2223-7747}, support = {2018/03691-8 and 2022/12533-2//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 303986/2023-9 and 304029/2023-8//National Council for Scientific and Technological Development/ ; Finance Code 001//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; }, abstract = {Plant-insect mutualisms often drive the evolution of adaptive morphological and physiological traits, enabling ecological specialization and diversification. Fig trees (Ficus spp., Moraceae) and their pollinating wasps (Agaonidae) are engaged in a brood-site pollination mutualism that exemplifies such adaptive specializations. This study investigates the morphological and ecological roles of maculae, characterized as distinct-pigmented regions on the fig surface, in the mutualistic interaction between Ficus citrifolia and fig wasps. Through morphological analyses using light and electron microscopy, we demonstrated that maculae concentrate numerous stomata and exhibit secretory activity. This activity is evidenced by the exudation of a sugary-like solution and by the presence of epidermal and subepidermal cells with features consistent with sugar- and terpene-secreting cells, such as abundant starch reserves, numerous mitochondria, plastids containing osmiophilic droplets, a Golgi complex with dilated cisternae, oil bodies, and extensive endoplasmic reticulum. Histochemical tests confirmed a terpenic-sugary secretion in the macula cells. We demonstrated that non-pollinating fig wasps avoid ovipositing through macular regions. This behavior may reflect a selective pressure to prevent structural damage to maculae caused by ovipositor insertion, thus preserving their functional integrity. Temperature measurements revealed that figs are up to 10% cooler on average than the ambient air. Therefore, our findings suggest that fig maculae are multifunctional structures, simultaneously performing the roles of extrafloral nectaries, gas exchange, and thermal regulation, which are crucial for maintaining suitable internal conditions for wasp larval development. These results provide novel insights into previously underexplored plant adaptations supporting specialized brood-site pollination mutualisms.}, } @article {pmid41023160, year = {2025}, author = {Brocklebank, JW and Davies, L and Hancock, J and Metta, M and Juani, K and Engkias, J and Goossens, B and Orozco-terWengel, P}, title = {Maternal origins and genetic diversity of Sabahan swamp buffalo using mitochondrial cytochrome b gene.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {33685}, pmid = {41023160}, issn = {2045-2322}, support = {NE/X016714/1//Natural Environment, Biotechnology and Biological Sciences and Medical Research Councils/ ; NE/X016714/1//Natural Environment, Biotechnology and Biological Sciences and Medical Research Councils/ ; NE/X016714/1//Natural Environment, Biotechnology and Biological Sciences and Medical Research Councils/ ; NE/X016714/1//Natural Environment, Biotechnology and Biological Sciences and Medical Research Councils/ ; }, mesh = {Animals ; *Buffaloes/genetics ; *Cytochromes b/genetics ; *Genetic Variation ; Haplotypes ; Phylogeny ; Malaysia ; Female ; Genetics, Population ; DNA, Mitochondrial/genetics ; *Mitochondria/genetics ; }, abstract = {The swamp buffalo (Bubalus bubalis carabanensis) plays a crucial role in agriculture across Southeast Asia but is increasingly underutilized in regions like Sabah, Malaysia. This study presents the first comprehensive statewide genetic assessment of Sabahan swamp buffalo using mitochondrial cytochrome b (cytb) gene sequences to investigate maternal origins and assess genetic diversity. Blood samples were collected from 211 individuals across eight locations in Sabah. DNA extraction and PCR amplification successfully yielded 198 high-quality cytb sequences. Comparative analysis with 1745 publicly available sequences revealed that 197 Sabahan buffalo belong to the SA1 haplogroup, which is common across Southeast Asia. Only four haplotypes were identified, with one dominant haplotype found in 190 individuals, indicating remarkably low genetic diversity (haplotype diversity = 0.088; nucleotide diversity = 0.00031). An additional river buffalo haplotype detected in one phenotypically swamp buffalo suggests introgression from Murrah buffalo. Analysis of molecular variance (AMOVA) showed that 96.29% of genetic variation occurred within populations, with minimal differentiation among them. ΦST comparisons suggest Sabah's buffalo are genetically closer to Chinese swamp buffalo populations than those from South Asia, supporting a maternal lineage via the China-Taiwan-Philippines dispersal route. Spatial autocorrelation analysis indicated localized gene flow, while demographic reconstruction via Bayesian Skyline Plot suggested long-term population stability with recent expansion. These findings highlight the limited maternal genetic variation within Sabahan swamp buffalo, likely stemming from a founder effect during introduction to Borneo and minimal subsequent genetic inflow. The study provides critical insight into the evolutionary history and population structure of Sabah's swamp buffalo, with implications for conservation and livestock improvement strategies aimed at bolstering genetic diversity and productivity in the region.}, } @article {pmid41024490, year = {2025}, author = {Speijer, D}, title = {Eukaryogenesis From FECA to LECA: Radical Steps Along the Way.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {47}, number = {11}, pages = {e70063}, pmid = {41024490}, issn = {1521-1878}, mesh = {Symbiosis ; Gene Transfer, Horizontal ; Phylogeny ; Archaea/genetics ; *Eukaryota/genetics ; Reactive Oxygen Species/metabolism ; *Biological Evolution ; Mitochondria/metabolism/genetics ; *Eukaryotic Cells ; Adenosine Triphosphate/metabolism ; }, abstract = {The characteristics of the last eukaryotic common ancestor (LECA) population and the root of the eukaryotic tree have been coming into focus lately. However, the trajectory taking the host, related to present-day Asgard archaea and the endosymbiont, related to present-day alphaproteobacteria, toward such fully integrated and complex organisms is still unclear. Here I marshal recent evidence supporting the early arrival of the "mitochondrion-to-be", setting up the evolutionary dynamic for a series of mutual adaptations leading to eukaryotes. Upon critical analysis of some presuppositions in phylogenomic reconstructions of eukaryogenesis, I again propose that pre-symbiosis, efficient ATP generation, internal reactive oxygen species (ROS) formation and enhanced retention of genes supplied by horizontal gene transfer (HGT) interdependently allowed this unique transformation to occur.}, } @article {pmid41024750, year = {2025}, author = {Kwok van der Giezen, FM and McDowell, R and Duncan, O and Zumkeller, S and Colas des Francs-Small, C and Small, I}, title = {High Conservation of Translation-Enabling RNA Editing Sites in Hyper-editing Ferns Implies They Are Not Selectively Neutral.}, journal = {Molecular biology and evolution}, volume = {42}, number = {10}, pages = {}, pmid = {41024750}, issn = {1537-1719}, support = {DP200102981//Australian Research Council/ ; }, mesh = {*RNA Editing ; *Ferns/genetics ; Protein Biosynthesis ; Chloroplasts/genetics ; Genome, Chloroplast ; }, abstract = {RNA editing is essential for processing transcripts in plant chloroplasts and mitochondria. Levels of RNA editing vary between lineages, but some hornworts, lycophytes, and ferns have an extraordinary abundance of RNA editing. A feature of "hyper-editing" species is the prevalence of RNA editing events that promote translation by creating start codons or removing stop codons via C-to-U or U-to-C editing, respectively. These "translation-enabling" RNA editing events may play roles in regulating organelle gene expression. To investigate the importance of translation-enabling RNA editing events, we generated DNA and RNA sequence libraries for four Salviniales water ferns: Azolla rubra, Azolla pinnata, Marsilea mutica, and Salvinia molesta. We assembled chloroplast genomes, mitochondrial genes, and transcriptomes and identified RNA editing sites and candidate RNA editing factors. We reanalyzed sequence data of Azolla filiculoides and conducted a comparative analysis of RNA editing in chloroplasts and mitochondrial transcripts. Estimates of pyrimidine transition rates show that translation-enabling RNA editing sites are more conserved than other nonsynonymous editing sites, suggesting an emergent role in organelle gene expression that is not selectively neutral. This makes these events rare examples of RNA editing conferring adaptive advantage, in contrast to the prevailing view that RNA editing arises via constructive neutral evolutionary processes. Shotgun proteomics of M. mutica chloroplast thylakoid fractions verified the expected consequences of RNA editing on translation of chloroplast transcripts and implies that mechanisms exist to avoid translation of partially edited transcripts. Start codon editing may be one of those mechanisms.}, } @article {pmid41037994, year = {2025}, author = {Fraj, M and Khemaissia, H and Nasri-Ammar, K and Ghemari, C and Souty-Grosset, C and Raimond, M and Jelassi, R}, title = {Histopathological and physiological response to zinc exposure in Orchestia species from a Tunisian lagoon.}, journal = {Marine environmental research}, volume = {212}, number = {}, pages = {107583}, doi = {10.1016/j.marenvres.2025.107583}, pmid = {41037994}, issn = {1879-0291}, abstract = {The Bizerte lagoon is a highly productive coastal ecosystem, yet it faces constant pressure from human activities and exposure to Zinc. This study compared Zn bioaccumulation in three Orchestia species (Orchestia gammarellus, Orchestia montagui, and Orchestia mediterranea) collected from the lagoon's banks. Individuals were exposed to contaminated soil with three different zinc concentrations, and their biological and physiological responses were assessed. Body zinc concentrations were measured using flame atomic emission spectrometry. Results showed a significant increase in mortality by the second week of exposure, alongside notable differences in body mass variations between species. O. mediterranea exhibited greater resilience to zinc exposure. Zinc accumulation in the Orchestia species was considerably higher than in the surrounding sediment, classifying all three species as macroconcentrators of zinc. Additionally, zinc-contaminated substrates induced structural changes in the amphipods' hepatopancreas, considered as the efficient storage organ, with the most pronounced alterations occurring at the highest zinc concentrations. In O. gammarellus, ultrastructural changes included lipid granules of varying shapes and sizes, while O. montagui and O. mediterranea displayed disrupted cell borders and swollen mitochondria. This study highlights the sensitivity of Orchestia species to zinc contamination, confirming their potential as bioindicators of metal pollution in coastal environments.}, } @article {pmid41047525, year = {2026}, author = {Wang, Q and Xiong, S and Zhao, R and Chen, J and Li, S and Jiang, W and Zhang, L}, title = {Organ-Targeted and Organelle-Targeted Liposome Gene Vector Construction.}, journal = {Advanced healthcare materials}, volume = {15}, number = {4}, pages = {e02254}, doi = {10.1002/adhm.202502254}, pmid = {41047525}, issn = {2192-2659}, support = {82273479//National Natural Science Foundation of China/ ; 20240305079YY//Research Fund of Jilin Provincial Science and Technology Department/ ; }, mesh = {*Liposomes/chemistry ; Humans ; *Genetic Vectors/genetics/chemistry ; *Genetic Therapy/methods ; *Organelles/metabolism ; Animals ; *Gene Transfer Techniques ; }, abstract = {The objective of this study is to systematically evaluate the advantages and disadvantages of liposomes as gene delivery agents, highlighting the importance of targeting in improving the efficiency and specificity of gene delivery. Systematic examination of these factors results in a robust theoretical underpinning and practical directives for the development of high-performance liposome vectors designed for targeted organ and organelle delivery. The research findings are poised to substantially bolster the evolution and practical deployment of gene therapy across various disease treatments. The research findings are poised to substantially bolster the evolution and practical deployment of gene therapy across various disease treatments. Comprehensive details on the production methods and regulatory aspects of targeted liposomes are presented, covering major organs like the liver, kidney, spleen, and lung, as well as pivotal organelles such as the nucleus, mitochondria, and lysosome. To target liposomes precisely, surface modification, composition and structure optimization, and physical variable control are utilized. The method demonstrates considerable therapeutic efficacy in gene editing, metabolic disorder treatment, and lysosomal storage disease management. Innovative strategies for optimizing liposome delivery systems are delineated in this study, emphasizing their revolutionary role in gene therapy.}, } @article {pmid41050429, year = {2025}, author = {Meroni, M and Paolini, E and Longo, M and Battistin, M and Dondossola, D and Ripolone, M and Napoli, L and Mosca, E and Corti, S and Dongiovanni, P}, title = {Exploring multiorgan mitochondrial dysfunction in the switch toward progressive MASLD in AMLN mice.}, journal = {iScience}, volume = {28}, number = {9}, pages = {113449}, pmid = {41050429}, issn = {2589-0042}, abstract = {Hepatic mitochondrial maladaptation features the transition from metabolic dysfunction-associated steatotic liver disease (MASLD) to Steatohepatitis (MASH) up to fibrosis/cirrhosis. However, it is still unexplored whether mitochondrial alterations also affect adipose tissue, muscle and heart during disease progression. C57Bl/6 mice were fed an AMLN diet to recapitulate the human MASLD spectrum. In the liver, TEM depicted a progressive morphologic dysfunction of mitochondria, which appeared swollen in MASH, with disorganized cristae/matrix loss in MASH-fibrosis. The mitophagy pathway was reduced in MASH-fibrosis, thus explaining the accumulation of damaged mitochondria, whereas mitochondrial complexes activities alongside OXPHOS protein levels and ATP production were dampened across the disease in liver, adipose, muscle, and cardiac tissues. Finally, the release of cell-free circulating mitochondrial DNA into the bloodstream reflected tissue mitochondrial impairment. In sum, we demonstrated that alterations in mitochondrial morphology, life cycle, and activity feature all disease stages in the liver but also in other tissues engaged in MASLD evolution.}, } @article {pmid41055410, year = {2026}, author = {Larson, DA and Itgen, MW and Denton, RD and Hahn, MW}, title = {Reconsidering cytonuclear discordance in the genomic age.}, journal = {Evolution; international journal of organic evolution}, volume = {80}, number = {1}, pages = {1-14}, doi = {10.1093/evolut/qpaf201}, pmid = {41055410}, issn = {1558-5646}, support = {IOS-2109716//National Science Foundation/ ; DBI-2305732//National Science Foundation/ ; DEB-2045704//National Science Foundation/ ; DEB-1936187//National Science Foundation/ ; }, mesh = {*Phylogeny ; *Cell Nucleus/genetics ; *Evolution, Molecular ; Genomics ; *Cytoplasm/genetics ; }, abstract = {Historically, phylogenetic datasets had relatively few loci but were over-represented for cytoplasmic sequences (mitochondria and chloroplast) because of their ease of amplification and large numbers of informative sites. Under those circumstances, it made sense to contrast individual gene tree topologies obtained from cytoplasmic loci and nuclear loci, with the goal of detecting differences between them-so-called cytonuclear discordance. In the current age of phylogenomics and ubiquitous gene tree discordance among thousands of loci, it is important to distinguish between simply observing discordance between cytoplasmic trees and a species tree inferred from many nuclear loci and identifying the cause of discordance. Here, we examine what inferences one can make from trees representing different genomic compartments. While topological discordance can be caused by multiple factors, the end goal of many studies is to determine whether the compartments have different evolutionary histories: what we refer to as "cytonuclear dissonance." Answering this question is more complex than simply asking whether there is discordance, requiring additional analyses to determine whether genetic exchange has affected only (or mostly) one compartment. Furthermore, even when these histories differ, expectations about why they differ are not always clear. We conclude by pointing to current research and future opportunities that may help to shed light on topological variation across the multiple genomes contained within a single eukaryotic cell.}, } @article {pmid41066576, year = {2025}, author = {Frison, M and Lockey, BS and Nie, Y and Golder, Z and Theiaspra, E and Ryall, CD and Lyons, C and Burr, SP and Prater, M and Bozhilova, LV and Glynos, A and Stewart, JB and Jones, NS and Chiaratti, MR and Chinnery, PF}, title = {Ubiquitin-mediated mitophagy regulates the inheritance of mitochondrial DNA mutations.}, journal = {Science (New York, N.Y.)}, volume = {390}, number = {6769}, pages = {156-163}, doi = {10.1126/science.adr5438}, pmid = {41066576}, issn = {1095-9203}, mesh = {Animals ; Female ; Humans ; Mice ; *DNA, Mitochondrial/genetics ; Heteroplasmy ; *Mitochondria/genetics/metabolism ; Mitochondrial Diseases/genetics ; *Mitophagy/genetics ; *Mutation ; Proteasome Endopeptidase Complex/metabolism ; *Thiolester Hydrolases/metabolism/antagonists & inhibitors/genetics ; *Ubiquitin/metabolism ; Zygote ; *Mitochondrial Proteins/genetics/metabolism ; }, abstract = {Mitochondrial synthesis of adenosine triphosphate is essential for eukaryotic life but is dependent on the cooperation of two genomes: nuclear and mitochondrial DNA (mtDNA). mtDNA mutates ~15 times as fast as the nuclear genome, challenging this symbiotic relationship. Mechanisms must have evolved to moderate the impact of mtDNA mutagenesis but are poorly understood. Here, we observed purifying selection of a mouse mtDNA mutation modulated by Ubiquitin-specific peptidase 30 (Usp30) during the maternal-zygotic transition. In vitro, Usp30 inhibition recapitulated these findings by increasing ubiquitin-mediated mitochondrial autophagy (mitophagy). We also found that high mutant burden, or heteroplasmy, impairs the ubiquitin-proteasome system, explaining how mutations can evade quality control to cause disease. Inhibiting USP30 unleashes latent mitophagy, reducing mutant mtDNA in high-heteroplasmy cells. These findings suggest a potential strategy to prevent mitochondrial disorders.}, } @article {pmid41070827, year = {2026}, author = {Shin, DW and Chen, T and Letts, JA}, title = {Mapping the evolution of mitochondrial complex I through structural variation.}, journal = {FEBS letters}, volume = {600}, number = {10}, pages = {1491-1518}, doi = {10.1002/1873-3468.70181}, pmid = {41070827}, issn = {1873-3468}, support = {R35GM137929/GM/NIGMS NIH HHS/United States ; DE-SC0022293//Basic Energy Sciences/ ; R35GM137929/GM/NIGMS NIH HHS/United States ; }, mesh = {*Electron Transport Complex I/chemistry/genetics/metabolism ; *Evolution, Molecular ; Animals ; Humans ; Protein Subunits/genetics/chemistry/metabolism ; *Mitochondria/genetics/metabolism ; Phylogeny ; Oxidative Phosphorylation ; }, abstract = {Respiratory complex I (CI) is a multi-subunit membrane protein complex important for the production of ATP via the oxidative phosphorylation pathway. The structure of CI is roughly conserved across species and is composed of subunits that are either embedded in the membrane or are exposed to the aqueous environment that together form an overall L-shaped 'boot'. The conserved core of CI is generally composed of 14 subunits. Across species, various less conserved 'supernumerary' or 'accessory' subunits have been added. Accessory subunits vary in number across species and can include proteins that are unique to specific lineages. Additionally, there are structural variations in the core subunits between clades. In this Review, we compare seven representative CI structures from divergent eukaryotic lineages to identify what aspects of the CI core subunits are susceptible to variation and classify eukaryotic accessory subunits into those conserved from the last eukaryotic common ancestor (LECA) or those that are lineage specific. Impact statement Understanding the biodiversity and evolution of mitochondrial complex I will reveal patterns that may reflect metabolic niche and can be used to constrain quantitative models of molecular evolution.}, } @article {pmid41078958, year = {2026}, author = {Huang, C and Xie, Z and Li, J and Zhang, C}, title = {Mitochondria and tumorigenesis: Molecular basis and therapeutic implications.}, journal = {Genes & diseases}, volume = {13}, number = {1}, pages = {101806}, pmid = {41078958}, issn = {2352-3042}, abstract = {Mitochondria, vital organelles within cells, govern energy metabolism. They play a pivotal role in maintaining redox homeostasis and are instrumental in the initiation and transmission of cell death signals, along with the synthesis of biological macromolecules. The role of mitochondria in tumor evolution and treatment has recently been the focus of extensive research. Studies indicate that the quality and biogenesis of mitochondria, along with their structure, functions, and macromolecule synthesis relevant to it, are intimately linked to tumorigenesis and the prognostic outcomes of clinical treatments. As such, therapies targeting mitochondria offer promising avenues to augment the efficacy of tumor treatment. We summarized the inherent links between mitochondrial structure, mitochondrial genes, metabolism of mitochondrial-related biological macromolecules, and mitochondria-regulated cell death in relation to tumorigenesis and progression. Furthermore, we reviewed the latest research progress in targeting mitochondria for tumor therapy. This study suggests that targeting mitochondria could open new avenues for developing tumor therapy.}, } @article {pmid41081364, year = {2025}, author = {Barrinha, A and Loyola-Machado, AC and Mariano Dos Santos, MD and Carvalho, PC and de Souza, W and Valente, AP and Galina, A and Motta, MCM}, title = {Endosymbiosis in trypanosomatids: the bacterium regulates the intermediate and oxidative metabolism of the host cell.}, journal = {mSphere}, volume = {10}, number = {11}, pages = {e0045725}, pmid = {41081364}, issn = {2379-5042}, support = {305299/2022-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; E-26/201.011/2021//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; }, mesh = {*Symbiosis ; *Trypanosomatina/microbiology/metabolism ; Oxidative Phosphorylation ; Oxidation-Reduction ; Proteomics ; Glycolysis ; }, abstract = {UNLABELLED: Endosymbiosis in trypanosomatids involves a mutualistic association between a symbiotic bacterium and a host protozoan and represents an excellent model for studying metabolic coevolution and the origin of organelles. This work investigated the influence of the symbiont on the metabolism of Angomonas deanei by comparing wild-type and aposymbiotic strains under different nutritional conditions. The presence of the symbiont enhanced cell proliferation in the medium containing a single carbon source and increased O2 consumption. Wild-type cells utilized oxidative phosphorylation to produce ATP, whereas aposymbiotic cells relied on substrate-level glycolysis, resulting in the excretion of greater amounts of fermentative products, such as acetate, succinate, and ethanol. Proteomic analysis revealed an increased expression of glycolytic and fermentative enzymes by the aposymbiotic strain and oxidative phosphorylation enzymes by symbiont-harboring cells. These findings highlight the role of the symbiotic bacterium in optimizing host metabolism and provide insights into the evolution of parasitism in trypanosomatids when A. deanei is compared with pathogenic species.

IMPORTANCE: This work provides groundbreaking insights into the metabolic and evolutionary dynamics of endosymbiosis, a topic of central importance to cellular evolution. Angomonas deanei, a trypanosomatid species, has become a paradigm for investigating the evolution of eukaryotic cells and the origin of organelles through endosymbiosis. Harbored in the cytoplasm of this protozoan, the symbiont engages in intricate metabolic exchanges, offering a time window to analyze the processes and evolutionary history that underlie the establishment of permanent endosymbiotic relationships. By employing a multidisciplinary approach, we have uncovered how the symbiotic bacterium regulates the oxidative metabolism of the trypanosomatid, integrating glucose catabolism and optimizing energy production. Our discoveries have broad implications for understanding the metabolic integration of organelles, such as mitochondria and glycosomes, with the bacterial endosymbiont. Beyond unravelling the complexities of metabolic adaptations during symbiosis, our work may contribute to the general understanding of the evolutionary dynamics of parasitism within the Trypanosomatidae family.}, } @article {pmid41081732, year = {2026}, author = {Alves-Lima, C and Montecinos, G and Escalona, M and Calhoun, S and Marimuthu, M and Nguyen, O and Beraut, E and Lipzen, A and Grigoriev, IV and Raimondi, P and Nuzhdin, S and Alberto, F}, title = {The reference genome for the northeastern Pacific bull kelp, Nereocystis luetkeana.}, journal = {The Journal of heredity}, volume = {117}, number = {3}, pages = {478-491}, doi = {10.1093/jhered/esaf077}, pmid = {41081732}, issn = {1465-7333}, support = {DE-FOA-0001726-1513//Macroalgae Research Inspiring Novel Energy Resources at the Advanced Research Projects Agency-Energy at the Department of Energy/ ; C0874002//CA Sea/ ; RSI-19-690224//State of California/ ; }, mesh = {*Kelp/genetics ; *Genome ; California ; Phylogeny ; Genomics ; Molecular Sequence Annotation ; }, abstract = {Bull kelp, Nereocystis luetkeana, is a northeastern Pacific kelp with a broad distribution from Alaska to central California. Its population declines have caused severe concerns in northern California, the Salish Sea in Washington, and recently in some populations in Oregon. Despite bull kelp's accumulated ecological and physiological studies, an assembled and annotated genomic reference was still unavailable. Here, we report the complete and annotated genome of N. luetkeana, produced by the California Conservation Genomics Project (CCGP), which aims to reveal genomic diversity patterns across California by sequencing the complete genomes of approximately 150 carefully selected species. The genome was assembled into 1,562 scaffolds with 449.82 Mb, 80× of coverage, and 22,952 gene models. BUSCO assembly showed a completeness score of 72% for the stramenopiles gene set. The mitochondria and chloroplast genome sequences have 37 Kb and 131 Mb, respectively. The orthology analysis between 10 Phaeophycean genomes showed 1,065 expanded and 286 unique orthogroups for this species. Pairwise comparisons showed 542 orthogroups present only in N. luetkeana and Macrocystis pyrifera, another large-body kelp. The enrichment analysis of these orthogroups showed important functions related to central metabolism and signaling due to ATPase enrichment in these two species. This genome assembly will provide an essential resource for the ecology, evolution, conservation, and breeding of bull kelp.}, } @article {pmid41091018, year = {2026}, author = {Fang, Y and Zhang, FC and He, JY and Liu, Y and Chen, LZ and Yu, C and Zhang, YX and He, Z and Wu, F}, title = {ζTrypsin is required for spermatid elongation and individualization in Drosophila spermatogenesis.}, journal = {Insect molecular biology}, volume = {35}, number = {2}, pages = {151-165}, doi = {10.1111/imb.70014}, pmid = {41091018}, issn = {1365-2583}, support = {//Natural Science Foundation of Hubei Province (2024AFC007)/ ; //China Agriculture Research System of MOF and MARA (CARS-18-SYZ10)/ ; //Hubei Province Agricultural Science and Technology Innovation Center Project (2024-620-000-001-009)/ ; //Hubei Province Key Research and Development Project (2024BBB013 and 2022BBA0079)/ ; //Opening Foundation of Guangxi Key Laboratory of Sericultural Genetic Improvement and Efficient Breeding (2024GXKLSK0101)/ ; }, mesh = {Animals ; *Drosophila/enzymology/genetics/physiology ; Spermatogenesis ; *Trypsin/genetics ; Male ; Gene Knockdown Techniques ; Seminal Vesicles/growth & development/physiology ; *Spermatids/physiology ; Fertility ; Gene Expression Regulation ; }, abstract = {During Drosophila spermatogenesis, mitochondria undergo elongation along the entire length of the spermatid tail, thereby establishing a structural framework that facilitates microtubule reorganization and the synchronized individualization of spermatids. This process ultimately culminates in the production of functional, mature sperm. Despite this understanding, the regulatory mechanisms governing elongation and individualization remain largely unexplored. The gene ζTrypsin encodes a member of the serine protease enzyme family. However, its molecular function remains to be elucidated. In this study, we elucidated the critical role of ζTrypsin in the process of spermatid individualization. In ζTrypsin knockdown testes, spermatid individualization complexes with F-actin cones were either entirely absent or disrupted, leading to an absence of mature sperm in the seminal vesicle and resulting in reduced male fertility. The most significant effects included reduced tubulin polyglycylation and disrupted mitochondrial function. Transcriptome analysis identified 1878 differentially expressed genes, with 814 genes upregulated and 1064 genes downregulated. These findings suggest that ζTrypsin is essential for spermatid maturation by influencing mitochondrial morphogenesis.}, } @article {pmid41091849, year = {2025}, author = {Bettinazzi, S and Ghirardello, M and Combeaud, A and Fan, J and Bonneau, M and Fowler, K and Dowling, DK and Camus, MF}, title = {Mitonuclear interactions and early-life diet shape adult nutritional behaviour.}, journal = {Journal of evolutionary biology}, volume = {38}, number = {12}, pages = {1601-1611}, doi = {10.1093/jeb/voaf123}, pmid = {41091849}, issn = {1420-9101}, support = {101030803//European Union/ ; NE/V014307/1//UKRI/ ; RPG-2023-198//Leverhulme Trust/ ; DP200100892//Australian Research Council/ ; DP210102931//Australian Research Council/ ; }, mesh = {Animals ; *Drosophila melanogaster/genetics/physiology/growth & development ; Female ; Male ; *Diet ; *Feeding Behavior ; Genotype ; Larva/growth & development ; }, abstract = {Mitochondrial function relies on close coordination between the mitochondrial and nuclear genomes. Disruption to this coordination-via mitonuclear mismatch-can impair metabolic efficiency, particularly under energetically demanding conditions such as during development. The nutritional environment further modulates mitochondrial demands, suggesting that mitonuclear genotype and diet may interact to shape life-history traits and behaviour. Here, we investigate how early-life diet and mitonuclear genotype jointly influence development time, adult body size, and nutritional preference in Drosophila melanogaster. Using a full-factorial panel of putatively matched and mismatched combinations (cybrids) of mitonuclear genotype derived from natural Australian populations, we reared flies on diets varying in their ratio of macronutrients and assessed how this influenced larval development and subsequent adult diet preference. Developmental rate was significantly influenced by mitonuclear coevolution and diet, with cybrids showing delayed development under all conditions, with dietary extremes exacerbating this effect. Despite this, egg-to-adult viability remained unaffected. Adult nutritional behaviour exhibited clear genotype- and diet-dependent effects. Flies reared on high-protein diets increased carbohydrate intake as adults, while those reared on high-carbohydrate diets increased protein intake, suggesting compensatory feeding responses. Mitonuclear mismatch further modulated nutrient consumption, particularly in females, whose carbohydrate intake was influenced by intergenomic compatibility and early-life dietary conditions. Males' protein consumption was also impacted by mitonuclear coevolution across all developmental diets. Finally, body size was also shaped by interactions between mitonuclear genotype and diet. Together, our findings demonstrate that mitonuclear compatibility and the composition of the early nutritional environment interact to shape developmental and behavioural phenotypes. These results support a role for mitonuclear coadaptation in mediating metabolic plasticity, highlighting the evolutionary and physiological significance of genotype-specific mitonuclear coordination.}, } @article {pmid41092398, year = {2025}, author = {Haltom, JA and Trovao, NS and Guarnieri, JW and Pan, V and Singh, U and Tsoy, S and O'Leary, CA and Bram, Y and Widjaja, GA and Cen, Z and Meller, R and Baylin, SB and Moss, WN and Nikolau, BJ and Enguita, FJ and Wallace, DC and Beheshti, A and Schwartz, RE and Wurtele, ES}, title = {Importance of De Novo Gene Evolution to Emerging Viral Threats: The ORF10 Strain-Restricted Orphan Gene of SARS-CoV-2 Promotes Pathogenesis.}, journal = {Molecular biology and evolution}, volume = {42}, number = {10}, pages = {}, pmid = {41092398}, issn = {1537-1719}, support = {ACI-1548562//National Science Foundation/ ; INV-046722//Bill & Melinda Gates Foundation/ ; W81XWH-21-1-0128//DOD/ ; NIAID 2R01AI107301/GF/NIH HHS/United States ; R01 GM133810/GM/NIGMS NIH HHS/United States ; NIDDK R01DK121072/GF/NIH HHS/United States ; R01GM133810//NIH/NIGMS/ ; }, mesh = {Humans ; *SARS-CoV-2/genetics/pathogenicity ; *COVID-19/virology/genetics ; *Evolution, Molecular ; Mutation ; *Viral Proteins/genetics ; HEK293 Cells ; Genome, Viral ; A549 Cells ; }, abstract = {Orphan genes, which encode species-specific proteins, are common but are rarely investigated. The SARS-CoV-2 orphan gene, ORF10, has been understudied; in vitro work suggests it may modulate innate immunity. Whether ORF10 influences COVID-19 outcomes in humans remained unknown. Here, analyzing millions of SARS-CoV-2 genomes, we find ORF10 sequences are identical to ancestral Wuhan-Hu-1 haplotype. In all variants of concern, <5% of genomes carry any ORF10 mutation. Despite limited statistical power due to the sparsity of mutated sequences, four ORF10 mutations were associated with less severe clinical outcomes in COVID-19 patients: three affect protein structure, one alters RNA structural dynamics. No mutations were linked to increased severity. ORF10 transcript levels in humans and human models are conditionally discordant from other SARS-CoV-2 genes. ORF10 expression in A549 and 293T cells significantly perturbs oxidative phosphorylation gene expression, disrupts immune gene networks, and shifts expression of 14 novel human transcripts. ORF10 is present in multiple Betacoronavirus pandemicum strains, but absent from SARS-CoV-1-like strains. We propose that this strain-restricted orphan gene contributes to severe COVID-19 in humans, with implications for future therapeutic strategies. These findings underscore the importance of studying recently evolved, potentially overlooked, viral orphan genes as a standard approach in pandemic preparedness.}, } @article {pmid41102174, year = {2025}, author = {Dramé, M and Garcia-Rodriguez, FJ and Ershov, D and Martyn, JE and Tinevez, JY and Buchrieser, C and Escoll, P}, title = {Backtracking metabolic dynamics in single cells predicts bacterial replication in human macrophages.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {9189}, pmid = {41102174}, issn = {2041-1723}, support = {ANR-21-CE15-0038-01//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-10-LABX-62-IBEID//Agence Nationale de la Recherche (French National Research Agency)/ ; PTR-651//Institut Pasteur/ ; EQU201903007847//Fondation pour la Recherche Médicale (Foundation for Medical Research in France)/ ; }, mesh = {Humans ; *Legionella pneumophila/growth & development/physiology ; *Macrophages/microbiology/metabolism ; Membrane Potential, Mitochondrial ; Reactive Oxygen Species/metabolism ; Mitochondria/metabolism ; Single-Cell Analysis/methods ; Host-Pathogen Interactions ; *Legionnaires' Disease/microbiology/metabolism ; Machine Learning ; }, abstract = {Accurately tracking dynamic state transitions is crucial for modeling and predicting biological outcomes, as it captures heterogeneity of cellular responses. To build a model to predict bacterial infection in single cells, we have monitored in parallel infection progression and metabolic parameters in thousands of human primary macrophages infected with the intracellular pathogen Legionella pneumophila. By combining live-cell imaging with a tool for classifying cells based on infection outcomes, we were able to trace the specific evolution of metabolic parameters linked to distinct outcomes, such as bacterial replication or cell death. Our findings revealed that early changes in mitochondrial membrane potential (Δψm) and in the production of mitochondrial Reactive Oxygen Species (mROS) are associated with macrophages that will later support bacterial growth. We used these data to train an explainable machine-learning model and achieved 83% accuracy in predicting L. pneumophila replication in single, infected cells before bacterial replication starts. Our results highlight backtracking as a valuable tool to gain new insights in host-pathogen interactions and identify early mitochondrial alterations as key predictive markers of success of bacterial infection.}, } @article {pmid41105886, year = {2025}, author = {Brieske, SD and Irving, BA and Rees, BB}, title = {The Contribution of Tissue-Specific Mitochondrial Respiration to Individual Variation in Oxygen Uptake during Rest and Exercise by the Gulf Killifish, Fundulus grandis.}, journal = {Ecological and evolutionary physiology}, volume = {98}, number = {4}, pages = {244-259}, doi = {10.1086/737167}, pmid = {41105886}, issn = {2993-7973}, mesh = {*Fundulidae/physiology/metabolism ; *Oxygen Consumption/physiology ; Animals ; Muscle, Skeletal/metabolism ; Swimming/physiology ; *Mitochondria/metabolism ; Liver/metabolism ; Brain/metabolism ; *Physical Conditioning, Animal/physiology ; *Rest/physiology ; Male ; Glycolysis ; }, abstract = {AbstractVariation in rates of oxygen uptake (Ṁo2) among individuals within a species is widespread and observed during both rest and activity. Such variation is expected to be important in animal physiology, ecology, and evolution, yet the mechanistic bases for this variation are incompletely understood. In the present study, we asked whether interindividual variation in Ṁo2 at rest (standard Ṁo2 [Ṁo2,standard]) and during an incremental swim test (peak swimming Ṁo2 [peak Ṁo2,swim]) in Gulf killifish (Fundulus grandis) is related to variation in mitochondrial Ṁo2 in five tissues: heart, oxidative skeletal muscle, glycolytic skeletal muscle, liver, and brain. After accounting for the effects of body mass, Ṁo2,standard was positively related to liver mass and its maximum capacity for oxygen flux by the electron transport system (ETS). Peak Ṁo2,swim was positively related to ETS respiration by heart ventricle and mitochondrial respiration required to offset the dissipation of the proton gradient in the absence of ATP synthesis (LEAK) by glycolytic skeletal muscle. The relationship between peak Ṁo2,swim and glycolytic muscle LEAK respiration prompted us to examine the relationship between the aerobic cost of transport and mitochondrial phosphorylation efficiency in glycolytic skeletal muscle. We found that individuals with a lower phosphorylation efficiency consumed more oxygen to travel a given distance (i.e., had a higher aerobic cost of transport). This result supports the idea that LEAK respiration represents an energetic cost during activity, which might be partially offset if higher LEAK results in less reactive oxygen species formation.}, } @article {pmid41105913, year = {2026}, author = {Ohno, H and Nishimura, T and Kainoh, K and Ohashi, Y and Onodera, N and Kano, M and Sari, LN and Masuda, M and Tamura, Y and Nishino, T and Hayashi, Y and Yamamoto, Y and Takahashi, SI and Mishima, Y and Yoneyama, Y and Takeuchi, Y and Sekiya, M and Matsuzaka, T and Miyamoto, T and Shimano, H}, title = {Label-free imaging of intracellular structures in living mammalian cells via external apodization phase-contrast microscopy.}, journal = {The FEBS journal}, volume = {293}, number = {4}, pages = {1127-1149}, pmid = {41105913}, issn = {1742-4658}, support = {JPMJCR1927//Core Research for Evolutional Science and Technology/ ; JPMJPF2017//Japan Science and Technology Agency/ ; DGM06005J//Takeda Science Foundation/ ; KAKENHI (22H02296)//Japan Society for the Promotion of Science/ ; //Cabinet Office, Government of Japan/ ; }, mesh = {Microscopy, Phase-Contrast/methods ; Humans ; *Lipid Droplets/ultrastructure/metabolism ; Microscopy, Fluorescence/methods ; Mitochondria/ultrastructure/metabolism ; Animals ; HeLa Cells ; Biomolecular Condensates/ultrastructure ; }, abstract = {Developing techniques to visualize intracellular structures, which influence the spatiotemporal functionality of biomolecules, is essential for elucidating mechanisms governing cellular behavior. In this study, we demonstrate that label-free external apodized phase-contrast (ExAPC) microscopy serves as a valuable tool for the simultaneous observation of various intracellular structures with high spatiotemporal resolution, while successfully mitigating halo artifacts. Additionally, through quantitative analysis of images obtained by combining ExAPC microscopy with fluorescence microscopy, we identified distinct heterogeneities in biomolecular condensates, lipid droplets, and mitochondria. Our findings highlight the potential of ExAPC microscopy to provide detailed insights into alterations in intracellular structures associated with diverse cellular processes, corroborating the existing knowledge and potentially contributing to the discovery of previously unknown cellular mechanisms.}, } @article {pmid41124226, year = {2025}, author = {Barcytė, D and Žihala, D and Eliáš, M}, title = {Expanded diversity of pedinophytes provides a window into the evolution of the genetic code in organelles.}, journal = {PLoS genetics}, volume = {21}, number = {10}, pages = {e1011901}, pmid = {41124226}, issn = {1553-7404}, mesh = {Phylogeny ; *Evolution, Molecular ; *Genetic Code/genetics ; *Chlorophyta/genetics/classification ; Plastids/genetics ; *Dinoflagellida/genetics/classification ; Mitochondria/genetics ; *Organelles/genetics ; Codon/genetics ; }, abstract = {Mitochondria and plastids of various lineages exhibit genetic code alterations. However, the knowledge of the diversity and occurrence, mechanistic underpinnings, and evolutionary origins of codon reassignments in organelles remains incomplete. To address this gap, we focused on organelles of the neglected green algal class Pedinophyceae, as well as pedinophyte-derived secondary plastids of green-coloured dinoflagellates (peDinoflagellates). We isolated and characterized a novel pedinophyte, herein formally described as Oistococcus okinawensis gen. et sp. nov., and phenotypically documented the previously sequenced but morphologically uncharacterized strain YPF-701, herein described as Akinorimonas japonica gen. et sp. nov. Based on phylogenetic analyses, both new taxa were classified into the expanded family Resultomonadaceae. We sequenced the organellar genomes of O. okinawensis, and utilizing existing raw (meta)genomic data we assembled organellar genome sequences from other previously unexplored pedinophyte lineages. Bioinformatic analyses of the expanded set of pedinophyte organellar genomes painted a complex picture of their genetic code landscape. Concerning mitochondria, the stop-to-Trp reassignment of the UGA codon turned out to have evolved multiple times in pedinophytes, and the Arg-to-Ala reassignment of AGA/AGG codons was shown to be apomorphic for the whole order Marsupiomonadales. The latter has additionally converted UUA and UUG into termination codons, relying on specific mutations in the mtRF1a protein. All pedinophyte mitochondria seem to decode AUA as methionine rather than the standard isoleucine, and an analogous reassignment seems to be evolving also in plastids of two separate pedinophyte lineages. Finally, apart from the previously reported Ile-to-Met AUA reassignment, peDinoflagellate plastids have switched the meaning of the AGA/AGG codons from arginine to another amino acid (most likely alanine), and have modified their pRF2 protein to mediate translation termination at UUA/UCA codons. Pedinophyte(-derived) organelles present a broad spectrum of codon reassignments and provide important insights into the emergence and mechanisms of non-standard codon translation.}, } @article {pmid41126044, year = {2025}, author = {You, K and Kong, J and Gu, X and Nie, L and Kan, J and Wang, J and Zhao, Y and Zhang, S and Tembrock, LR and Lin, S and Wang, X and Jia, M and Wu, Z}, title = {The cucumber (Cucumis sativus L.) mitochondrial genome: intraspecific structural variation, repetitive architecture, and comparative evolutionary dynamics.}, journal = {BMC plant biology}, volume = {25}, number = {1}, pages = {1430}, pmid = {41126044}, issn = {1471-2229}, support = {32170238//National Natural Science Foundation of China/ ; 32170238//National Natural Science Foundation of China/ ; 32170238//National Natural Science Foundation of China/ ; 32170238//National Natural Science Foundation of China/ ; 32170238//National Natural Science Foundation of China/ ; 32170238//National Natural Science Foundation of China/ ; 32170238//National Natural Science Foundation of China/ ; 110243160001007//Chinese Academy of Agricultural Sciences Elite Youth Program/ ; 110243160001007//Chinese Academy of Agricultural Sciences Elite Youth Program/ ; 110243160001007//Chinese Academy of Agricultural Sciences Elite Youth Program/ ; 110243160001007//Chinese Academy of Agricultural Sciences Elite Youth Program/ ; 110243160001007//Chinese Academy of Agricultural Sciences Elite Youth Program/ ; 110243160001007//Chinese Academy of Agricultural Sciences Elite Youth Program/ ; JCYJ20220818103212025//Shenzhen Fundamental Research Program/ ; JCYJ20220818103212025//Shenzhen Fundamental Research Program/ ; JCYJ20220818103212025//Shenzhen Fundamental Research Program/ ; 2021QN02N792//Guangdong Pearl River Talent Program/ ; 2021QN02N792//Guangdong Pearl River Talent Program/ ; 2021QN02N792//Guangdong Pearl River Talent Program/ ; 2021QN02N792//Guangdong Pearl River Talent Program/ ; 2021QN02N792//Guangdong Pearl River Talent Program/ ; 2021QN02N792//Guangdong Pearl River Talent Program/ ; 2021QN02N792//Guangdong Pearl River Talent Program/ ; }, mesh = {*Cucumis sativus/genetics ; *Genome, Mitochondrial/genetics ; *Evolution, Molecular ; Phylogeny ; Genome, Plant ; Genetic Variation ; Repetitive Sequences, Nucleic Acid ; }, abstract = {BACKGROUND: Mitochondria are essential organelles with complex mitochondrial genomes (mitogenomes) that challenge conventional assembly and analysis. Compared to plastid and nuclear genomes, plant mitochondrial genomes (mitogenomes) exhibit immense structural complexity and low nucleotide substitution rates. Cucumber (Cucumis sativus L.) is a vital crop and a key model for studying its rare paternal mitogenome inheritance. However, a comprehensive understanding of intraspecific mitogenomic diversity in cucumber has been hindered by the limitations of short-read sequencing, which fails to resolve its complex, repeat-rich architecture.

RESULTS: Here, by leveraging long-read sequencing, we assembled the complete mitogenomes of 12 diverse cucumber accessions. The assemblies revealed massive mitogenomes (1.49-1.61 Mb) with highly reticulate, graph-based structures, moving beyond the simplistic"master-circle" model. We discovered that this profound structural diversity is driven by a small number of large, recombinationally active repeats, which allowed us to classify the mitogenomes into six distinct structural types. Phylogenetic analyses of the plastid (maternal) and mitochondrial (paternal) genomes revealed strikingly discordant evolutionary histories, reflecting their different inheritance modes and evolutionary rates. Analysis of intracellular DNA transfer showed that mitochondrial-to-nuclear transfers (NUMTs) have declined over evolutionary time, whereas plastid-to-nuclear transfers (NUPTs) are more recent and ongoing. Furthermore, the synonymous substitution rate in cucumber mitogenomes was 8-10 times lower than in plastomes, underscoring their extreme sequence conservation.

CONCLUSIONS: Our study demonstrates that cucumber mitogenomes are not static but are highly dynamic mosaics shaped by repeat-mediated recombination, resulting in extensive structural variation even within a single species. These findings highlight the power of long-read assembly for studying complex organellar genomes and establish the paternally inherited mitogenome as a valuable resource for tracing paternal lineages and developing novel strategies for crop improvement.}, } @article {pmid41129220, year = {2025}, author = {Charara, S and Choy, J and Cauwenberghs, K and Vijayakumar, P and Ng, R and Kim, KY and Weng, SC and Akbari, OS and Ellisman, MH and Rifkin, SA and Su, CY}, title = {Morphological specializations of mosquito CO2-sensing olfactory receptor neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {43}, pages = {e2514666122}, pmid = {41129220}, issn = {1091-6490}, support = {R21DC020536//HHS | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)/ ; T32 GM133351/GM/NIGMS NIH HHS/United States ; R01 DC021551/DC/NIDCD NIH HHS/United States ; R21 AI169343/AI/NIAID NIH HHS/United States ; R01DC016466//HHS | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)/ ; R01 AI148300/AI/NIAID NIH HHS/United States ; R01GM138780//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; U24 NS120055/NS/NINDS NIH HHS/United States ; R01DC021551//HHS | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)/ ; R01 AI175152/AI/NIAID NIH HHS/United States ; R01AI175152//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R21AI169343//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; U24NS120055//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R21 DC020536/DC/NIDCD NIH HHS/United States ; R01 GM138780/GM/NIGMS NIH HHS/United States ; R01 DC016466/DC/NIDCD NIH HHS/United States ; R01AI148300//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; T32GM133351//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, mesh = {Animals ; *Carbon Dioxide/metabolism ; *Olfactory Receptor Neurons/ultrastructure/metabolism/physiology/cytology ; *Aedes/physiology/metabolism/ultrastructure ; Microscopy, Electron, Scanning ; Dendrites/ultrastructure ; Sensilla/ultrastructure ; }, abstract = {Hematophagous mosquitoes use CO2 as a key arousal signal that gates behavioral responses to host-derived cues. In Aedes aegypti, CO2 is detected by olfactory receptor neurons (ORNs) housed in the sensory hairs (sensilla) on the maxillary palp. While the molecular mechanism and behavioral significance of CO2 sensing have been well studied in mosquitoes, the nanoscale three-dimensional structures of their CO2-sensing ORNs and associated cells have remained unclear. Using serial block-face scanning electron microscopy, we characterize the CO2-sensing cpA neuron and its odor-sensitive neighbors, cpB and cpC, within the capitate sensilla of A. aegypti. Notably, cpA neurons are significantly larger, with an outer dendritic surface area 8 to 12 times greater than that of cpB and cpC neurons. This expanded CO2-sensing surface arises from its unique architecture, consisting of numerous flattened dendritic sheets folded into intricate lamellae. In contrast, cpB and cpC dendrites exhibit sparse, narrow cylindrical branches. Moreover, the cpA axon displays a prominent pearls-on-a-string morphology, with numerous mitochondria-rich, nonsynaptic varicosities connected by thin cables. Remarkably, a glial cell and an auxiliary cell together ensheathe the cpA soma but not cpB or cpC, suggesting a specialized role in supporting cpA function. Compared to Drosophila CO2-sensitive ORNs, a larger portion of the cpA outer dendrite is embedded within the sensillum cuticle, potentially improving access to environmental CO2. These findings reveal key morphological specializations of cpA neurons, thereby advancing our understanding of mosquito sensory biology and laying the groundwork for future studies on the molecular basis and functional ramifications of these anatomical adaptations.}, } @article {pmid41130487, year = {2025}, author = {Hu, Y and Chen, S and Sun, Q and Song, L and Liu, L and Zhang, D and Liu, H and Wang, S}, title = {HSP70-mediated survival mechanisms and thermotolerance plasticity in the corn aphid, Rhopalosiphum maidis, across developmental stages.}, journal = {International journal of biological macromolecules}, volume = {331}, number = {Pt 2}, pages = {148462}, doi = {10.1016/j.ijbiomac.2025.148462}, pmid = {41130487}, issn = {1879-0003}, mesh = {Animals ; *Aphids/genetics/growth & development/physiology/metabolism ; *HSP70 Heat-Shock Proteins/genetics/metabolism/chemistry ; *Thermotolerance/genetics ; *Insect Proteins/genetics/metabolism ; Heat-Shock Response ; Phylogeny ; Gene Expression Regulation, Developmental ; }, abstract = {Heat shock proteins (HSPs) play a fundamental role in mediating thermotolerance in insects; however, their stage-specific contributions to thermal adaptation in the corn aphid, Rhopalosiphum maidis, remain poorly characterized. Here, we systematically characterized Hsp70-mediated thermotolerance mechanisms across the developmental stages of this devastating maize pest. A total of 15 Hsp70 genes were identified, each containing conserved functional domains such as EEVD and GIDLGTTYS motifs, ATP-binding sites, and nuclear localization signals. Subcellular localization predictions revealed a typical eukaryotic distribution pattern, with 12 localized to the cytosol, two to the endoplasmic reticulum, and one to the mitochondria. Following sequence alignment, nine non-redundant Hsp70 genes were selected for further functional analysis. Thermotolerance assays supported that third-instar nymphs were the most susceptible to heat stress, showing only 53.0 % survival at 40 °C, whereas adults exhibited the highest tolerance, with an LT50 of 43.11 °C. Expression profiling revealed significant upregulation of five Hsp70 genes-R. maidis Hsp70-8, -11, -12, -13 and -14-specifically in third-instar nymphs at 36 °C. RNAi-mediated silencing of these genes resulted in a 56.0-68.0 % increase in mortality among third-instar nymphs. Additionally, the recombinant R. maidis HSP70-7 (55 kDa) was successfully expressed. These findings underscore the existence of developmental trade-offs in thermotolerance in R. maidis and emphasize the functional diversification of Hsp70 genes, supporting their potential as RNAi targets for pest management under increasing climatic temperatures.}, } @article {pmid41143242, year = {2025}, author = {Longo, M and Paolini, E and Meroni, M and Ripolone, M and Napoli, L and Gentile, F and Cespiati, A and Trombetta, E and Lombardi, R and Maggioni, M and Alisi, A and Miele, L and Liguori, A and Soardo, G and Gasbarrini, A and Moggio, M and Fracanzani, AL and Dongiovanni, P}, title = {Artificial intelligence as a ploy to delve into the intricate link between genetics and mitochondria in patients with MASLD.}, journal = {JHEP reports : innovation in hepatology}, volume = {7}, number = {11}, pages = {101539}, pmid = {41143242}, issn = {2589-5559}, abstract = {BACKGROUND & AIMS: Mitochondrial (mt-) D-loop and cell-free circulating (ccf-) mtDNA fragments, respectively reflecting mt-mass and tissue damage, are promising metabolic dysfunction-associated steatotic liver disease (MASLD) biomarkers. We previously found that PNPLA3/MBOAT7/TM6SF2 deficiency in HepG2 cells increased mt-mass, D-loop levels, and ccf-COXIII release. We explored mt-biogenesis and mt-biomarkers in patients with MASLD stratified by the number of risk variants (NRV = 3). We exploited GPT-4 to develop and validate new risk scores, predicting MASLD evolution, in two independent cohorts by integrating anthropometric and genetic data with mt-biomarkers.

METHODS: A cohort of 28 patients with MASLD (Discovery cohort) was consecutively enrolled for hepatic mt-dynamics assessment by transmission electron microscopy and immunohistochemistry. Data were confirmed by quantitative real time-PCR in a retrospective cohort (Hepatic Validation, n = 184). D-loop and ccf-COXIII were retrospectively measured in peripheral blood mononuclear cells and serum samples of biopsied outpatients with MASLD (Serum Validation cohort, n = 824) and individuals with non-invasive MASLD diagnosis (n = 386, Non-invasive cohort). Risk scores were developed using random forest algorithms.

RESULTS: In the Discovery and Hepatic Validation cohorts, the PNPLA3/MBOAT7/TM6SF2 variants altered hepatic mt-dynamics, enhancing mt-content and D-loop levels (p <0.05) through the p38/PGC-1α pathway. Furthermore, NRV = 3 patients showed an increase in mt-fragmentation at transmission electron microscopy (TEM) and ccf-COXIII release (p <0.05). In the Serum Validation cohort, circulating D-loop and ccf-COXIII positively correlated with genetics [β D-loop :0.17 (95% CI: 0.04-0.29), p = 0.01; βccf-COXIII:0.33 (95% CI: 0.19-0.46), p <0.0001] and MASLD severity [OR D-loop :1.31 (95% CI: 1.01-1.71), p = 0.03; ORccf-COXIII:2.41 (95% CI: 1.69-3.44), p <0.0001] at multivariate analysis. Random forest allowed prediction models named Mitochondrial, Anthropometric, and Genetic Integration with Computational intelligence for assessing hepatocellular carcinoma risk (MAGIC-H), considering age, BMI genetics, D-loop, and ccf-COXIII. In both Serum and Non-invasive cohorts, the MAGIC-H score reached AUC >85% in identifying HCC cases regardless of cirrhosis, outperforming existing non-invasive tests.

CONCLUSIONS: Mt-biomarkers have a prognostic significance in genetically-predisposed patients with MASLD.

IMPACT AND IMPLICATIONS: The study highlights that genetic variants in PNPLA3, MBOAT7, and TM6SF2 genes deeply contribute to metabolic dysfunction-associated steatotic liver disease (MASLD) progression by affecting hepatic mitochondrial adaptability. It also identified two novel biomarkers of mitochondrial origin which are strongly linked to disease severity and genetic background of patients with MASLD. The use of generative artificial intelligence tools, such as GPT-4, can enhance the use of biomarkers and polygenic risk scores for clinical risk stratification. We developed a customized version of GPT-4 (rsGPT-4), which identified a machine-learning approach (random forest) as the best method for creating prediction models for metabolic dysfunction-associated steatohepatitis, fibrosis, and hepatocellular carcinoma. The new scores combined the two mitochondrial biomarkers, genetic data, and anthropometric data and outperformed existing non-invasive tests for monitoring patients with MASLD.}, } @article {pmid41143731, year = {2025}, author = {Hill, GE and Hood, WR}, title = {Matching mitochondrial respiration to changing environments through acclimatization and the evolution of fixed genetic differences.}, journal = {Journal of evolutionary biology}, volume = {38}, number = {12}, pages = {1578-1589}, doi = {10.1093/jeb/voaf130}, pmid = {41143731}, issn = {1420-9101}, support = {IOS2223528//National Science Foundation/ ; }, mesh = {Animals ; *Acclimatization/genetics ; *Mitochondria/metabolism ; *Biological Evolution ; Phenotype ; Environment ; }, abstract = {Aerobic respiration in mitochondria is the source for most of the energy that powers complex animals, and maintaining energy flow from mitochondria near the optimum needed for life processes presents challenges for complex animals. Environments of most animals change rapidly. Moreover, individuals pass through developmental stages with different energy demands, and they shift life-history states that require modified production of adenosine triphosphate (ATP). To adjust to changing conditions, all complex animals display some capacity for acclimatization through phenotypic flexibility, whereby key aspects of mitochondrial respiration are reversibly altered. Phenotypic flexibility is a universal feature of the energy-production mechanisms of animals, but all animals face limitations in the range of environments and circumstances to which they can acclimatize. We discuss multiple examples of such phenotypic flexibility in animals, focusing on the different mechanisms employed that acclimatize mitochondrial respiration to exogenous and endogenous challenges. Genotype sets the range of phenotypes related to mitochondrial respiration that is available to an animal. Numerous studies document adaptive evolution of both mitochondrial and nuclear genes that directly affect the range of environments that will support oxidative phosphorylation. Phenotypic flexibility can obscure evolutionary changes in response to changing energy demands, and understanding the interplay of capacity for acclimatization and adaptive evolution of mitochondrial systems presents major challenges for physiological and evolutionary biologists.}, } @article {pmid41144527, year = {2025}, author = {Rabbi, MA and Hossain, MM and Shuvo, MRK and Bhuya, AR and Ghosh, A}, title = {Comprehensive analysis of proline metabolizing genes reveals their functional diversification and abiotic stress response in Solanum lycopersicum.}, journal = {PloS one}, volume = {20}, number = {10}, pages = {e0335608}, pmid = {41144527}, issn = {1932-6203}, mesh = {*Solanum lycopersicum/genetics/metabolism ; *Proline/metabolism ; *Stress, Physiological/genetics ; Gene Expression Regulation, Plant ; Phylogeny ; *Plant Proteins/genetics/metabolism ; *Genes, Plant ; Droughts ; Multigene Family ; }, abstract = {Proline plays a crucial role in plant stress responses. Proline metabolizing genes (PMGs) are a group of enzymes involved in its catabolism in mitochondria and the biosynthesis in the chloroplast and cytoplasm. A total of 21 PMGs were identified in Solanum lycopersicum. Among them, 2 gene pairs were identified as tandemly duplicated, and 6 gene pairs were segmentally duplicated. Phylogenetic analysis revealed distinct gene clusters, suggesting functional diversification. Gene structure analysis provided insights into the arrangement of coding and non-coding regions, while domain analysis highlighted conserved sequences for functional predictions and evolutionary conservation. Microarray expression data of the identified genes revealed that SlOAT8 exhibited maximum expression in different anatomical tissues, particularly in ovules, and SlOAT9 showed maximum response at developmental stages associated with shoot growth. Under stress conditions, SlOAT8 and SlP5CS1 were upregulated in exposure to drought stress but downregulated in response to heat and salt stress. Meanwhile, SlOAT4 was strongly expressed only in roots during salt stress. The qRT-PCR analysis demonstrated significant upregulation of SlOAT8, SlP5CDH2, and SlP5CR alongside a significant downregulation of SlP5CS1 under abiotic stress conditions. Furthermore, biochemical assay indicates the accumulation of proline and H2O2 under stressed conditions. These findings provide an extensive study on the PMGs, which will help in the development of a stress-resilient tomato plant in further.}, } @article {pmid41145224, year = {2026}, author = {Wang, JJ and Ng, PLP and Powers, ME and Rha, CH and Brem, RB}, title = {The role of mitotype variation and positive epistasis in trait differences between Saccharomyces species.}, journal = {Genetics}, volume = {232}, number = {1}, pages = {}, pmid = {41145224}, issn = {1943-2631}, support = {R01 GM120430/GM/NIGMS NIH HHS/United States ; 2R01GM120430/GF/NIH HHS/United States ; }, mesh = {*Saccharomyces/genetics ; *Epistasis, Genetic ; *Saccharomyces cerevisiae/genetics ; DNA, Mitochondrial/genetics ; Thermotolerance/genetics ; *Mitochondria/genetics ; Alleles ; *Genetic Variation ; Genotype ; }, abstract = {Many traits of interest in biology evolved long ago and are fixed in a particular species, distinguishing it from other sister taxa. Elucidating the mechanisms underlying such divergences across reproductive barriers has been a key challenge for evolutionary biologists. The yeast Saccharomyces cerevisiae is unique among its relatives for its ability to thrive at high temperature. The genetic determinants of the trait remain incompletely understood, and we sought to understand the role in its architecture of species variation in mitochondrial DNA. We used mitochondrial transgenesis to show that S. cerevisiae mitotypes were sufficient for a partial boost to thermotolerance and respiration in the Saccharomyces paradoxus background. These mitochondrial alleles worked best when the background also harbored a pro-thermotolerance nuclear genotype, attesting to positive epistasis between the two genomes. The benefits of S. cerevisiae alleles in terms of respiration and growth at high temperature came at the cost of worse performance in cooler conditions. Together, our results establish this system as a case in which mitoalleles drive fitness benefits in a manner compatible with, and fostered by, the nuclear genome.}, } @article {pmid41151232, year = {2026}, author = {Ye, M and Zhou, D and Kong, L and Zhang, Y and Pan, C and Huang, C and Li, G and Chen, H and Tian, C}, title = {Genome-wide characterization of the Hsp40 gene family in Clarias fuscus reveals their roles in thermal stress adaptation and immune modulation.}, journal = {Comparative biochemistry and physiology. Part D, Genomics & proteomics}, volume = {57}, number = {}, pages = {101661}, doi = {10.1016/j.cbd.2025.101661}, pmid = {41151232}, issn = {1878-0407}, mesh = {Animals ; *HSP40 Heat-Shock Proteins/genetics/immunology/chemistry/metabolism ; Phylogeny ; *Catfishes/genetics/immunology/physiology ; *Fish Proteins/genetics/immunology/metabolism/chemistry ; Multigene Family ; Genome ; *Heat-Shock Response ; }, abstract = {Thermal stress poses a significant challenge to fish physiology and aquaculture sustainability, necessitating an in-depth understanding of molecular responses to temperature fluctuations. This study characterizes the Hsp40 gene family in Hong Kong catfish (Clarias fuscus), a species known for its thermal resilience, to elucidate their roles in proteostasis and immune modulation. A total of 55 Hsp40 genes were identified and categorized into three subfamilies: DnaJa (n = 6), DnaJb (n = 16), and DnaJc (n = 33). These genes exhibit conserved J-domains and diverse motifs, indicating adaptations to aquatic stressors. Phylogenetic analysis reveals that the Hsp40 gene family in C. fuscus exhibits the closest evolutionary relationship to Ictalurus punctatus, followed by Danio rerio, with distinct clustering patterns across the subtypes. Collinearity and synteny analyses indicated substantial genomic conservation of Hsp40 genes between C. fuscus, I. punctatus, and D. rerio, with evidence of gene duplication and homologous relationships. The subcellular localization of Hsp40 proteins was observed in the cytoplasm, endoplasmic reticulum, mitochondria, nucleus, and extracellular regions, supporting their roles in chaperone activity and immune response regulation. Protein interaction networks identified two major clusters: one associated with protein folding and another with Hsp90-dependent immune signaling. Molecular docking confirmed stable interactions between Hsp40 and Hsp70, aiding in the mitigation of thermal-induced protein misfolding. Transcriptomic analysis under thermal stress showed significant differential expression of 30 Hsp40 genes, with dnajb11 and dnajc5.1 notably differentially expressed in the liver, gills, and kidneys. Under normal-temperature conditions, 10, 6, and 12 genes were differentially expressed in the liver, gills, and kidneys, respectively. High-temperature acclimation significantly increased the number of differentially expressed genes in the kidneys (20 genes), indicating enhanced thermal tolerance. These genes bolster immunity by stabilizing proteins and modulating inflammatory pathways. These findings suggest that key Hsp40s, such as dnajb11 and dnajc5.1, serve as biomarkers for selective breeding and support the development of strategies like immunomodulatory feed additives to enhance thermal resilience in C. fuscus aquaculture.}, } @article {pmid41154583, year = {2025}, author = {Luo, Y and Hassan, S and Raut, S and Bähler, J}, title = {Mitochondrial Translation Inhibition Triggers an Rst2-Controlled Transcriptional Reprogramming of Carbon Metabolism in Stationary-Phase Cells of Fission Yeast.}, journal = {Biomolecules}, volume = {15}, number = {10}, pages = {}, pmid = {41154583}, issn = {2218-273X}, support = {/WT_/Wellcome Trust/United Kingdom ; 302608/Z/23/Z//Wellcome Discovery Award/ ; 202306860040//China Scholarship Council/ ; }, mesh = {*Schizosaccharomyces/metabolism/genetics/drug effects ; *Mitochondria/metabolism/genetics/drug effects ; *Carbon/metabolism ; *Schizosaccharomyces pombe Proteins/metabolism/genetics ; Gene Expression Regulation, Fungal/drug effects ; *Protein Biosynthesis/drug effects ; *Transcription Factors/metabolism/genetics ; Chloramphenicol/pharmacology ; Transcriptome ; Transcription, Genetic ; }, abstract = {Mitochondria possess their own genome, which encodes subunits of the electron transport chain, rendering mitochondrial protein translation essential for cellular energy metabolism. Mitochondrial dysfunction affects nuclear transcription through the retrograde response. We applied RNA-seq to investigate whether and how the inhibition of mitochondrial translation by chloramphenicol (CAP) affects transcriptome regulation in proliferating or stationary-phase cells of Schizosaccharomyces pombe growing in fermentative or respiratory media. Stationary-phase cells in glucose medium exhibited the strongest transcriptome response to CAP, characterized by expression signatures similar to those observed under other stresses, including the retrograde response. The induced genes were also significantly enriched in cytoplasmic carbon metabolism pathways, reflecting a transcriptional reprogramming from respiration to fermentation. The transcription factors Scr1 and Rst2, regulators of carbon catabolite repression (CCR), controlled a common set of carbon metabolism genes in CAP-treated stationary-phase cells, and they showed opposing effects on the lifespan of these cells. Rst2 was required for the induction of carbon metabolism genes and maintained nuclear localization in CAP-treated stationary-phase cells. A systematic genetic interaction screen revealed functional relationships of Rst2 with processes related to stress and starvation responses. These findings uncover a complex transcriptional program in stationary-phase cells that adapt to inhibited mitochondrial translation, including stress- and retrograde-like responses, contributions of the CCR factors Scr1 and Rst2, and adjustment of carbon metabolism to deal with mitochondrial dysfunction.}, } @article {pmid41166466, year = {2025}, author = {Merondun, J and Fossøy, F and Meshcheryagina, S and Atkinson, P and Bachurin, G and Bulyuk, V and Fenchuk, V and Golovatin, M and Hewson, C and Honza, M and Markovets, M and Moskát, C and Owens, GL and Procházka, P and Red'kin, Y and Rutila, J and Šulc, M and Thorup, K and Stokke, BG and Liang, W and Wolf, JBW}, title = {Genomic architecture of egg mimicry and its consequences for speciation in parasitic cuckoos.}, journal = {Science (New York, N.Y.)}, volume = {390}, number = {6772}, pages = {527-532}, doi = {10.1126/science.adt9355}, pmid = {41166466}, issn = {1095-9203}, mesh = {Animals ; *Genetic Speciation ; *Biological Mimicry/genetics ; *Birds/genetics/classification/physiology ; *Pigmentation/genetics ; Female ; Male ; *Egg Shell ; Genetic Variation ; Ovum/physiology ; Sex Chromosomes/genetics ; Phenotype ; Genome ; Mitochondria/genetics ; }, abstract = {Host-parasite arms races facilitate rapid evolution and can fuel speciation. Cuculus cuckoos are deceptive egg mimics that exhibit a broad diversity of counterfeit egg phenotypes, representing host-adapted subpopulations (gentes). Genome analysis of 298 common (Cuculus canorus) and 50 oriental cuckoos (Cuculus optatus) spanning 15 egg morphs revealed that eggshell background coloration is predominantly influenced by matrilineal genetic variation. Recurrent mitochondrial mutations and an ancient W chromosome-linked translocation of an autosomal assembly factor for respiratory complex I provide a tentative link between mitochondrial function and pigment synthesis through the heme pathway. Biparentally inherited loci contribute to phenotypic variation in both species, mainly for maculation. The evolutionary tug-of-war over a sex-limited, mimetic trait integrates autosomal components with the nonrecombining, matrilineal genome without catalyzing genome-wide divergence between gentes.}, } @article {pmid41172333, year = {2025}, author = {Athreya, GS and Czuppon, P and Gokhale, CS}, title = {The Evolution of Dependence and Cohesion in Incipient Endosymbioses.}, journal = {The American naturalist}, volume = {206}, number = {5}, pages = {435-451}, doi = {10.1086/737588}, pmid = {41172333}, issn = {1537-5323}, mesh = {*Symbiosis ; *Biological Evolution ; Models, Biological ; Animals ; Reproduction ; }, abstract = {AbstractEukaryogenesis is the prototypical example of an egalitarian evolutionary transition in individuality, and endosymbiosis, more generally, is central to the origins of many complex biological systems. Why do only some symbioses undergo such a transition, and how does the host-symbiont relationship change during this process? Here, we characterize endosymbiosis by two emergent collective-level properties: host and symbiont survival as a collective ("mutual dependence") and the level of synchronized reproduction ("reproductive cohesion"). Using adaptive dynamics, we study the evolution of the traits underlying these properties. First, by adding a carrying capacity for the collective population-a realism omitted in previous models-we find novel reasons why complete dependence or cohesion might not evolve, thus providing further theoretical support for the rarity of transitions in individuality. Second, our model suggests that asymmetries in evolutionary outcomes of hosts and symbionts can be explained by a difference in their population growth parameters, coupled with their shared fate when in a collective. Last, we show that during the early stages of an endosymbiosis, even if investments in dependence and cohesion are uncorrelated, mutual dependence arises faster than reproductive cohesion. Our results hence shed light on three aspects of endosymbiosis: coevolution between the host and symbiont, coevolution between dependence and cohesion, and ultimately the opportunity to undergo an evolutionary transition. Connecting to ecological factors, this work uncovers fundamental properties of endosymbioses, providing a clear way forward for theoretical and empirical investigations.}, } @article {pmid41174841, year = {2026}, author = {Yuan, J and Yang, W and Zhao, Z and Cao, J and Yang, W and Deng, W and Zhong, S and Liu, J and Yu, Y}, title = {A new small subunit of the mitochondrial F-ATPase, PhDC, determines flower color by acidifying vacuoles.}, journal = {The New phytologist}, volume = {249}, number = {1}, pages = {232-251}, doi = {10.1111/nph.70676}, pmid = {41174841}, issn = {1469-8137}, support = {32202527//National Natural Science Foundation of China/ ; 32271939//National Natural Science Foundation of China/ ; 32302591//National Natural Science Foundation of China/ ; }, mesh = {*Vacuoles/metabolism ; *Flowers/genetics/enzymology ; Hydrogen-Ion Concentration ; Mitochondria/enzymology/metabolism ; *Petunia/genetics/enzymology/metabolism ; *Plant Proteins/metabolism/genetics/chemistry ; Anthocyanins/metabolism ; Protein Subunits/metabolism/chemistry ; Gene Silencing ; Gene Expression Regulation, Plant ; *Pigmentation/genetics ; *Proton-Translocating ATPases/metabolism/genetics/chemistry ; Phylogeny ; }, abstract = {The pH within the plant vacuole determines the anthocyanin absorption spectrum and affects flower color. V-ATPase, P-ATPase, and pyrophosphatase proton pumps involved in vacuolar acidification have been reported. However, whether other proteins regulate vacuolar pH in Petunia hybrida remains unclear. Here, by using VIGS technology to silence numerous genes annotated as 'unknown protein', we identified a gene whose silencing darkened petal color and named it PhDC (DEEPENING COLOR). PhDC silencing mediated by RNAi also darkened petal color. PhDC has low similarity to yeast mitochondrial F-ATPase subunit and Arabidopsis ATP17 (a predicted mitochondrial F-ATPase subunit). PhATPd and PhATPO, encoding the mitochondrial F-ATPase subunit d and OSCP, respectively, shared similar spatiotemporal expression with PhDC. PhDC localized to mitochondria and interacted with four subunits of mitochondrial F-ATPase. PhDC, PhATPd, and PhATPO silencing led to a similar phenotype in petunia. PhDC silencing reduced mitochondrial F-ATPase activity and impaired mitochondria. The anthocyanin content in PhDC-silenced petals did not significantly change, while the vacuoles of petal cells were alkalized, and the P-ATPase activity and ATP content were reduced. These results suggest that PhDC is a new subunit of the mitochondrial F-ATPase. Furthermore, PhDC silencing affects petal color by altering the vacuole pH and P-ATPase activity.}, } @article {pmid41178341, year = {2026}, author = {Dong, Y and Li, G and Zhang, Y and Wu, S and Liu, K and Yu, D and Wang, Z and Yang, Y and Guo, S and Li, Z and Guo, F and Huang, B and Wang, Y}, title = {Gluconolactonase SMP30 deletion worsens fungal degeneration through ROS accumulation and mitochondrial dysfunction in an insect fungal pathogen.}, journal = {Pest management science}, volume = {82}, number = {2}, pages = {1912-1920}, doi = {10.1002/ps.70337}, pmid = {41178341}, issn = {1526-4998}, support = {32102274//National Science Foundation of China/ ; 202312/WT_/Wellcome Trust/United Kingdom ; 202312/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Reactive Oxygen Species/metabolism ; Animals ; *Carboxylic Ester Hydrolases/genetics/metabolism ; *Mitochondria/metabolism ; *Fungal Proteins/genetics/metabolism ; *Metarhizium/genetics/pathogenicity/enzymology/physiology ; Virulence ; Phylogeny ; Gene Deletion ; }, abstract = {BACKGROUND: Gluconolactonase/Senescence marker protein 30 (SMP30) is a multifunctional enzyme involved in L-ascorbic acid biosynthesis, ROS scavenging, and aging in mammals, but its role in fungi remains partially understood.

RESULTS: Here, we demonstrate that an SMP30 (MrSMP30-1) from the entomopathogenic fungus Metarhizium robertsii is essential for ROS elimination and mitochondrial function. Phylogenetic analysis shows that MrSMP30-1 is more closely related to SMP30 proteins from phytopathogenic fungi than to those from other entomopathogens. Recombinant MrSMP30-1 displays maximum lactonase activity at pH 6.5 and 25 °C. Deletion of MrSMP30-1 results in intracellular ROS buildup, a significant decrease in lipid droplets, and collapse of mitochondrial membrane potential, leading to accelerated, spontaneous fungal degeneration. Virulence tests indicate that the loss of MrSMP30-1 reduces pathogenicity. Immunoprecipitation combined with mass spectrometry identified seven proteins, including polyketide synthase 3, that potentially interact physically with MrSMP30-1.

CONCLUSION: Our results indicate that the gluconolactonase MrSMP30-1 is essential for ROS detoxification and preserving mitochondrial integrity in M. robertsii. This not only enhances our understanding of SMP30's proposed role in fungi but also suggests that it could serve as a biomarker for monitoring fungal culture degeneration. © 2025 Society of Chemical Industry.}, } @article {pmid41182317, year = {2025}, author = {Nishimura, Y and Langan-Evans, C and Taylor, HL and Foo, WL and Morton, JP and Shepherd, S and Strauss, JA and Burniston, JG and Areta, JL}, title = {Endocrine, Metabolic, and Skeletal Muscle Proteomic Responses During Energy Deficit With Concomitant Aerobic Exercise in Humans.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {21}, pages = {e71163}, pmid = {41182317}, issn = {1530-6860}, support = {//Alliance for Potato Research and Education/ ; }, mesh = {Humans ; *Muscle, Skeletal/metabolism ; Male ; *Exercise/physiology ; Adult ; *Energy Metabolism/physiology ; Proteomics/methods ; *Proteome/metabolism ; Young Adult ; *Muscle Proteins/metabolism ; }, abstract = {Energy deficit is a potent physiological stressor that has shaped human evolution and can improve lifespan and healthspan in a wide range of species. Preserving locomotive capacity was likely essential for survival during the human hunter-gatherer period but surprisingly little is known about the molecular effects of energy deficit on human skeletal muscle, which is a key tissue for locomotion and metabolic health. Here we show that after a 5-day 78% reduction in energy availability with concomitant aerobic exercise in healthy men there was a profound modulation of skeletal muscle phenotype alongside increases in fat oxidation at rest and during exercise and a 2.1 ± 0.8 kg loss of fat free mass and 0.8 ± 0.6 kg of fat mass. We used stable isotope (D2O) labelling and peptide mass spectrometry to investigate the abundance and turnover rates of individual proteins. Abundance (1469 proteins) and synthesis rate (736 proteins) data discovered a shift toward a more oxidative phenotype and reorganization of cytoskeleton and extracellular matrix structure during energy deficit. Mitochondrial components: TCA, electron transport chain and beta-oxidation, were prominently represented amongst proteins that increased in abundance and synthesis rate, as well as proteins related to mitochondrial proteostasis, remodeling and quality-control such as BDH1 and LONP1. Changes in muscle metabolic pathways occurred alongside a reduction in extracellular matrix proteins, which may counteract the age-related muscle fibrosis. Our results suggest that muscle metabolic pathways are not only preserved but positively affected during periods of concomitant low energy availability and exercise.}, } @article {pmid41189701, year = {2025}, author = {Zhou, J and Zheng, Y and Zheng, X and Chen, CY and Ding, SC and Wang, R}, title = {Bioinformatics and Experimental Validation of FLVCR1 and SOX4 in Regulating Mitochondria-Macrophage Crosstalk in Disc Degeneration.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {15101-15116}, pmid = {41189701}, issn = {1178-7031}, abstract = {BACKGROUND: Intervertebral disc degeneration (IDD) is a prevalent cause of backache and disability in many people. Mitochondrial homeostasis and macrophage polarization may be pivotal in slowing IDD evolution, but the relationship between mitochondria related genes (MRGs) and macrophage polarization related genes (MPRGs) and IDD is still unclear. This research aims to elucidate the potential mechanism of MRGs and MPRGs during IDD progression through transcriptome data.

METHODS: Publicly available transcriptome datasets were analyzed to identify candidate genes through differential expression analysis, weighted gene co-expression network analysis, and machine learning. Key findings were further validated in an animal model of lumbar disc herniation. Immune infiltration analysis, regulatory network construction, drug prediction, and molecular docking were used to investigate underlying mechanisms and therapeutic potential.

RESULTS: Two genes, FLVCR1 and SOX4, were identified as central players. Immune analysis showed that FLVCR1 was strongly negatively correlated with monocytes (cor = -0.76), while SOX4 was associated with multiple immune cell types. FOXC1 was identified as a shared transcription factor regulating both genes. Drug prediction suggested Remifentanil and MCDF as promising compounds, with molecular docking supporting the potential binding of Remifentanil to FLVCR1.

CONCLUSION: This study highlights the potential roles of FLVCR1 and SOX4 in the development of IDD, providing a reference for the early diagnosis and precise treatment of patients with IDD.}, } @article {pmid41192555, year = {2025}, author = {Bakhtina, AA and Campbell, MD and Sibley, BD and Sanchez-Contreras, M and Keller, A and Sweetwyne, MT and Bruce, JE}, title = {Interactome Quantitation Reveals Non-Energetic Mitochondrial Roles in Cell Type Specialization in Murine Kidney.}, journal = {Molecular & cellular proteomics : MCP}, volume = {24}, number = {12}, pages = {101441}, pmid = {41192555}, issn = {1535-9484}, support = {K01 AG073470/AG/NIA NIH HHS/United States ; R01 AG078279/AG/NIA NIH HHS/United States ; R21 DK128540/DK/NIDDK NIH HHS/United States ; R35 GM136255/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Mitochondria/metabolism ; *Podocytes/metabolism ; Mice ; Proteomics/methods ; Proteome/metabolism ; *Kidney/metabolism/cytology ; Energy Metabolism ; }, abstract = {Evolution of multicellular life forms has involved adaptation of organs that consist of multiple cell types, each with unique functional properties that as a collection, achieve complex organ function. Since each cell type is adapted to deliver specific functionality within the context of an organ, knowledge on functional landscapes occupied by individual cell types could improve comprehension of organ function at the molecular level. In kidney, podocytes and tubules are 2 cell types of the nephron, each with vastly different functional roles. Podocytes envelop the blood vessels in the glomerulus and act as filters while tubules, located downstream of the glomerulus, are responsible for reabsorption of important nutrients. Mitochondria hold a critical and well-studied role in tubules due to the high energetic requirements required to fulfill their function. In podocytes however, questions remain regarding the relevance of mitochondrial function in both normal physiology and pathology. Quantitative cross-linking mass spectrometry and proteomics together with a transgenic mitochondrial tagging strategy were used to investigate kidney cell-type specificity of mitochondria. These efforts revealed that despite similarities of podocyte and tubule mitochondrial proteomes, each contain unique features corresponding to known distinct functional roles. These include increased demand for energy production through the tricarboxylic acid cycle in tubules and increased detoxification demand in podocytes. Moreover, tubule and podocyte mitochondrial interactome differences revealed additional cell-type specific functional insights with alterations in betaine metabolism, lysine degradation, and other pathways not regulated through proteome abundance levels. Most importantly, these efforts illustrate that cell specific mitochondrial interactome differences within an organ can now be visualized. Therefore, this approach can generally be used to map cell-specific mitochondrial changes in disease, aging or even with therapy to better understand the roles and contributions of each cell type in normal physiology and pathology within an organ in ways not previously possible.}, } @article {pmid41198545, year = {2025}, author = {Stefano, GB}, title = {Adaptability Beyond Darwin: Microbial Evolution, Mitochondria, and the Thermodynamic Frontiers of Survival.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {30}, number = {10}, pages = {45962}, doi = {10.31083/FBL45962}, pmid = {41198545}, issn = {2768-6698}, mesh = {*Mitochondria/physiology/metabolism ; *Biological Evolution ; Thermodynamics ; Humans ; *Adaptation, Physiological ; Bacteria/genetics ; Animals ; }, abstract = {Charles Darwin hypothesized that evolution is based on adaptations to a changing environment, and that organisms that developed even slightly favorable variations would ultimately be most likely to survive. This concept is clearly reflected in the life cycles of pathogenic species. While modern antibiotics, antiviral agents, and vaccines can successfully eliminate many pathogens and prevent infections, only susceptible strains are affected. Bacteria and viruses that can adapt and develop resistance mechanisms will survive and thrive in the absence of ongoing competition. We build on this framework by considering the evolutionary impact of microbial-mediated adaptations experienced by the host. For example, intracellular mitochondria, largely believed to be descendants of symbiotic ancestral bacteria, can be specifically targeted by viral pathogens. Taken one step further, we hypothesize that Darwinian theory may also apply to atoms and molecules, which are not "alive" by any conventional definition, but interact with one another and self-assemble according to the principles of thermodynamics that promote stability in defined environments. Building on these foundations, our hypotheses and conceptual framework will facilitate further exploration into the evolution of microbial mechanisms that modulate behavior, shape the development of the immune system, and promote host evolution.}, } @article {pmid41201327, year = {2025}, author = {DuBose, JG and Uhm, T and Bowen, J and Fiedorek, P and Hoogshagen, M and Haselkorn, TS and DiSalvo, S}, title = {The roles of dispersal limitation and pre-adaptation in shaping Paraburkholderia endosymbiont frequencies in social amoeba communities.}, journal = {Applied and environmental microbiology}, volume = {91}, number = {12}, pages = {e0161525}, pmid = {41201327}, issn = {1098-5336}, support = {P20 GM103429/GM/NIGMS NIH HHS/United States ; }, mesh = {*Symbiosis ; *Burkholderiaceae/physiology/genetics ; Phylogeny ; *Dictyostelium/microbiology/physiology ; Adaptation, Physiological ; }, abstract = {UNLABELLED: Endosymbiotic interactions have long played fundamental roles in shaping the evolution and diversification of eukaryotes. However, we still have a limited understanding of how ecological processes govern the distribution of endosymbionts that are still segregating in host populations. To contribute to this understanding, here, we use the interactions between Paraburkholderia endosymbionts and their dictyostelid social amoeba hosts as a model system to investigate the role of dispersal, a fundamental ecological process, in shaping the distribution and evolution of endosymbiotic interactions. We first found that patterns of endosymbiont diversification were highly biogeographic, suggesting a significant degree of dispersal limitation. We then experimentally mediated the dispersal of several endosymbiont species into environments with multiple host species and found that each symbiont was able to sustain a high prevalence in each host population. The benefit/detriment of these mediated interactions did not change with increasing phylogenetic distance from what is suspected to be the focal amoeba host species in nature. Taken together, our findings suggest Paraburkholderia endosymbionts are generally pre-adapted to occupy a variety of dictyostelid host environments, and their distribution among host populations is subject to a high degree of dispersal limitation. Overall, our findings have significant implications for our understanding of how ecological processes facilitate and limit the evolution of endosymbiotic interactions.

IMPORTANCE: Endosymbiotic interactions are ubiquitous in complex eukaryotes, as organelles such as mitochondria and chloroplasts represent the remnants of what were once free-living prokaryotes. However, how ecological processes facilitate the transition from free-living to host-associated is less understood. Selection is the most commonly invoked process to explain this transition: symbionts that are better at infecting hosts and potentially confer some benefit rise in frequency because they are selected for (and otherwise selected against). However, this only describes one fundamental process that can shape the ecology of symbiotic interactions. Here, we present evidence that the importance of dispersal (and its limitations) likely exceeds that of selection in shaping the distribution and frequency of Paraburkholderia endosymbionts in their dictyostelid social amoeba host communities. These findings highlight the need to consider regional ecological processes that operate at a scale beyond the individual when studying ecology and evolution of endosymbiotic interactions.}, } @article {pmid41202814, year = {2025}, author = {Kučerová, J and Zdrha, A and Rozbeský, D and Shinde, AP and Nebesářová, J and Narayanasamy, RK and Smutná, T and Hrdý, I and Tachezy, J}, title = {Characterization of the sTim/MIA pathway in Metamonada reveals different evolutionary adaptations to anaerobiosis.}, journal = {Current biology : CB}, volume = {35}, number = {23}, pages = {5734-5749.e6}, doi = {10.1016/j.cub.2025.10.027}, pmid = {41202814}, issn = {1879-0445}, mesh = {Anaerobiosis ; *Mitochondrial Proteins/metabolism/genetics ; *Adaptation, Physiological ; Mitochondria/metabolism ; Biological Evolution ; }, abstract = {Adaptation of eukaryotic cells to oxygen-poor environments has driven metabolic changes in mitochondria, notably shifting from oxygen-dependent to anaerobic energy metabolism. However, how the mitochondrial protein import machinery adapts in anaerobes remains poorly understood, although oxygen is crucial for this process, particularly for oxidative folding of small Tim (sTim) chaperones. sTim heterohexameric complexes guide imported proteins within the mitochondrial intermembrane space (IMS). Their function depends on conserved twin cysteines, oxidized by the mitochondrial import and assembly (MIA) pathway to stabilize their structure via disulfide bridges. The folding requires molecular oxygen or cytochrome c as electron acceptors, linking sTim folding to respiration. This study elucidates how the sTim/MIA pathway is reshaped in anaerobic types of mitochondria, such as hydrogenosomes. Through structural and homology analyses across anaerobic eukaryotes, three modifications of the sTim/MIA system were identified: (1) a disulfide relay-independent system with sTims lacking twin cysteines (sTim[-cys]), (2) absence of sTim/MIA components, and (3) a conventional sTim/MIA system linked to fumarate reduction. The sTim[-cys] system found in Metamonada was studied in Trichomonas vaginalis hydrogenosomes. Structural modeling, in vitro, and in situ analyses revealed that despite lacking canonical cysteines, sTim[-cys] proteins maintain the helix-loop-helix architecture with the central loop involved in targeting to the IMS and assemble into complexes stabilized by electrostatic interactions. Single-particle analysis confirmed their 6-fold symmetry, similar to conventional sTim heterohexamers. These findings provide insights into the evolutionary shaping of sTim/MIA pathways in anoxic environments, contributing to our understanding of mitochondrial biogenesis across diverse eukaryotes.}, } @article {pmid41205602, year = {2025}, author = {Ly, J and Di Bernardo, M and Tao, YF and Khalizeva, E and Giuliano, CJ and Lourido, S and Fleming, MD and Cheeseman, IM}, title = {Alternative start codon selection shapes mitochondrial function and rare human diseases.}, journal = {Molecular cell}, volume = {85}, number = {22}, pages = {4198-4214.e11}, pmid = {41205602}, issn = {1097-4164}, support = {R01 AI144369/AI/NIAID NIH HHS/United States ; R01 AI158501/AI/NIAID NIH HHS/United States ; R35 GM126930/GM/NIGMS NIH HHS/United States ; R24 DK094746/DK/NIDDK NIH HHS/United States ; R01 DK087992/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Mitochondria/genetics/metabolism/pathology ; *Rare Diseases/genetics/metabolism/pathology ; *Codon, Initiator/genetics ; Protein Isoforms/genetics/metabolism ; *Mitochondrial Proteins/genetics/metabolism ; Evolution, Molecular ; Frameshift Mutation ; Alleles ; Animals ; Codon, Nonsense ; }, abstract = {Rare genetic diseases collectively affect millions of individuals. A common target of many rare diseases is the mitochondria, intracellular organelles that originated through endosymbiosis. Eukaryotic cells require related proteins to function both within the mitochondria and in the host cell. By analyzing N-terminal protein isoforms generated through alternative start codon selection, we identify hundreds of differentially localized isoform pairs, including dual-localized isoforms that are essential for both mitochondrial and host cell function. Subsets of dual mitochondria-localized isoforms emerged during early eukaryotic evolution, coinciding with mitochondrial endosymbiosis. Importantly, we identify dozens of rare disease alleles that affect these alternative protein variants with unique molecular and clinical consequences. Alternative start codon selection can bypass pathogenic nonsense and frameshift mutations, thereby selectively eliminating specific isoforms, which we term isoform-selective alleles (ISAs). Together, our findings illuminate the evolutionary and pathological relevance of alternative translation, offering insights into the molecular basis of rare human diseases.}, } @article {pmid41208259, year = {2025}, author = {DeSalle, R and Tessler, M}, title = {Mitochondrial Gene Phylogenetic Incongruencies Are Linked to Chromosomal Position and Function.}, journal = {Genome biology and evolution}, volume = {17}, number = {12}, pages = {}, pmid = {41208259}, issn = {1759-6653}, mesh = {*Phylogeny ; Animals ; *Genome, Mitochondrial ; *Genes, Mitochondrial ; *Evolution, Molecular ; *Chromosomes/genetics ; DNA, Mitochondrial/genetics ; }, abstract = {Mitochondrial DNA has been one of the key workhorses of evolutionary studies. Hence, understanding the dynamics of DNA sequence change in this tiny genome (15 to 20 kb) is of utmost importance. However, we are unaware of large studies examining how the functionality and chromosomal positioning of mitochondrial genes may impact their phylogenetic patterning. To examine this, we assembled a large database of animal mitochondrial genomes (>10,000 total individuals over 89 taxonomic groups) and compared their phylogenetics, functionality, and location on the mitochondrial genome (heavy and light strand in vertebrates or J and N strand in other animals and distance from the origin of replication). We found that many genes show unique evolutionary patterns, often directly tied to chromosomal location or gene function (eg NADH dehydrogenases or ribosomal RNA genes). We also found rampant phylogenetic incongruence among the linked genes of the mitochondria in most of the taxonomic groups we examined. These results suggest that mitochondrial genomes have accrued complex evolutionary patterns. The accumulated incongruence can influence phylogenetic inference in evolutionary studies, making mitochondrial gene choice for phylogenetics critical. The phenomena we show here should also be examined in other organelle and even nuclear gene studies.}, } @article {pmid41208531, year = {2025}, author = {Sheikh, S and Turpin Knotková, B and Benz, C and Eliáš, M and Bílý, T and Bondar, A and Tesařová, M and Stříbrná, E and Heller, J and Meinecke, M and Hashimi, H}, title = {The Core MICOS Complex Subunit mic60 has Been Substituted by Two Cryptic Mitofilin-containing Proteins in Euglenozoa.}, journal = {Molecular biology and evolution}, volume = {42}, number = {11}, pages = {}, pmid = {41208531}, issn = {1537-1719}, support = {23-07674S//Czech Science Foundation/ ; CZ.10.03.01/00/22_003/0000003//European Union/ ; //Operational Program Just Transition/ ; //Czech BioImaging/ ; //Czech Ministry of Education/ ; //Boehringer Ingelheim Fonds PhD Fellowship/ ; SFB-1638/1-511488495 - P08//Deutsche Forschungsgemeinschaft/ ; FOR-2848-401510699 - P05//Deutsche Forschungsgemeinschaft/ ; 67985823//Institute of Physiology/ ; 68378050//Institute of Molecular Genetics/ ; //Czech Academy of Sciences/ ; //Laboratory of Microscopy and Histology/ ; //Biology Center, Czech Academy of Sciences/ ; //German Research Founda1on/ ; //Federal Ministry of Educa1on and Research/ ; //Ministry of Science Baden-WürOemberg/ ; //Excellence Strategy of the Federal and State Governments of Germany/ ; }, mesh = {*Protozoan Proteins/genetics/metabolism ; *Mitochondrial Proteins/genetics/metabolism ; *Euglenozoa/genetics/metabolism ; Phylogeny ; Mitochondria/metabolism ; Evolution, Molecular ; Amino Acid Sequence ; Mitochondria Associated Membranes ; }, abstract = {Cristae enclose respiratory chain complexes, making them the bioenergetic subcompartments of mitochondria. The Mitochondrial contact site and Cristae Organizing System (MICOS) complex is among the inducers of membrane curvature needed for crista formation. Resembling the respiratory chain complexes, MICOS is organized around a core protein, the mitofilin-domain bearing Mic60, that was inherited from the alphaproteobacterial progenitor of mitochondria. Extant alphaproteobacteria express Mic60 to form their own bioenergetic subcompartments, demonstrating the permeance of Mic60's form and function during prokaryotic and eukaryotic evolution. Yet, unlike virtually all aerobic eukaryotes, Mic60 is not encoded within the genomes of the multifarious protists that comprise the phylum Euglenozoa, including trypanosomes. Here, we show that Mic60 has been replaced in euglenozoans by two cryptic mitofilin domain-containing MICOS subunits, Mic34 and Mic40. Contrasting alphaproteobacterial and mitochondrial Mic60, these are not integral membrane proteins. Mic34 and Mic40 are as diverged from each other as both are to canonical Mic60. Reverse genetics revealed they are intertwined with the oxidative protein folding pathway required for mitochondrial-and crista-biogenesis, veiling a potential membrane remodeling role. Nevertheless, Mic34 binds phospholipid bilayers in vitro. Mic34 and Mic40 heterologous expression remodels gammaproteobacterial cytoplasmic membranes, like Mic60. Unexpectedly, Mic34 overexpression elaborates the simplified tubular mitochondrion of a Trypanosoma brucei life cycle stage with repressed oxidative phosphorylation. Furthermore, this activity was ablated by mutations to Mic34's mitofilin domain that correspond to essential motifs found in yeast Mic60's mitofilin domain. Thus, the mitofilin protein family is more diverse than originally supposed, with two of its structurally most divergent members altering the core of euglenozoan MICOS.}, } @article {pmid41220782, year = {2025}, author = {Yin, H and Dai, X}, title = {Assembly and comparative analysis of the mitochondrial genome of Ceratophyllum demersum L.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1704888}, pmid = {41220782}, issn = {1664-462X}, abstract = {Mitochondria are the powerhouse of eukaryotic cells, whose genomes feature unique structural characteristics and evolutionary significance. Ceratophyllum demersum is a widely distributed aquatic plant that holds special position in the aquatic ecosystem. In this study, we assembled the mitochondrial genome (mitogenome) of C. demersum from the PacBio HiFi sequencing data, yielding three complete circular chromosomes of lengths 285,151 bp, 208,195 bp and 101,944 bp. The three molecules contain 65 unique genes comprising 40 protein coding genes (PCGs), 3 rRNA genes, and 22 tRNA genes. The frequent recombination of mitogenome is driven by the non-tandem repetitive sequences. Genome comparison showed that the content of non-tandem repeats in the mitogenome of the algae-like C. demersum was significantly higher than that in terrestrial angiosperms. In monocotyledonous and dicotyledonous plants, there is a significant loss of large ribosomal and small subunit genes. By contrast, C. demersum possesses all 24 core PCGs and inherits a similar number of PCGs as the ancient angiosperms of Magnoliaceae and Chloranthaceae, with only three variable PCGs (rpl6, rps8, and rps19) lost during evolution, suggesting a special evolutionary position of C. demersum in angiosperms. Phylogenetic analyses support the monophyly of Ceratophyllales and Chloranthales and places this clade as sister to a combined monocot-eudicot group. These findings offer new insights and propose alternative hypotheses for reconstructing the early evolutionary history of angiosperms.}, } @article {pmid41223563, year = {2025}, author = {Mirandola, A and Cartry, J and Bedja, S and Pisareva, E and Prevostel, C and Gongora, C and Ginter, B and Italiano, A and Ducreux, M and Boilève, A and Mathieu, JRR and Jaulin, F and Thierry, AR}, title = {Characterization of the cell-free DNA released by tumor organoids derived from colorectal cancer patients.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {231}, number = {}, pages = {116097}, doi = {10.1016/j.ejca.2025.116097}, pmid = {41223563}, issn = {1879-0852}, mesh = {Humans ; *Colorectal Neoplasms/genetics/pathology/blood ; *Organoids/metabolism/pathology ; Female ; Male ; Middle Aged ; Aged ; Mutation ; *Cell-Free Nucleic Acids/genetics ; *Biomarkers, Tumor/genetics ; DNA, Mitochondrial/genetics ; DNA Mutational Analysis ; *Circulating Tumor DNA/genetics ; Aged, 80 and over ; Prospective Studies ; }, abstract = {INTRODUCTION: Patient-derived tumor organoids (PDTOs) have histological, molecular and clinical (drug sensitivity) characteristics comparable to those of their originating tumors. However, little is known about their ability to replicate the release of tumor-derived DNA.

METHODS: Supernatants from 21 colorectal cancer PDTO cultures, established from 13 patients, were prospectively collected. The presence, structure, and mutational landscape of nuclear (cf-nDNA) and mitochondrial (cf-mtDNA) cell-free DNA as well as extracellular mitochondria (ex-Mito) were analyzed using qPCR, fragmentomics and shallow whole-genome sequencing. Mutation profiling was performed via IntPlex qPCR and whole-exome sequencing (WES).

RESULTS: Cf-nDNA was detected in 95 % of PDTO supernatants with concentrations ranging from 0.009 to 209 ng/mL. Cf-nDNA fragment size analysis revealed patterns consistent with circulating DNA, including mononucleosome-associated profile. Cf-mtDNA was present in all samples (0.27-89.2 pg/mL) and extracellular mitochondria was also detected (0.009-17.4 pg/mL). A strong concordance (>85 %) was observed between oncogenic mutations in cfDNA and the molecular alterations detected in PDTOs and patient tumors.

CONCLUSION: PDTOs release both nuclear and mitochondrial cfDNA into their culture medium displaying high similarity with patient-derived circulating DNA (cirDNA), including fragmentation patterns and oncogenic mutations. This study strengthens the relevance of the PDTOs as patient tumors models and highlights the potential of analyzing PDTO-derived cfDNA as a non-invasive approach to investigate tumor evolution and as a valuable tool to support functional precision oncology.}, } @article {pmid41230226, year = {2025}, author = {Li, W and Wang, L and Zuo, Y and Zhang, H and Zhang, X and Yang, L and Zhang, J and Zheng, F and Deng, H}, title = {Organelle genomes reveal adaptive evolution and phylogenetic position of the endangered Primula mallophylla.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1653128}, pmid = {41230226}, issn = {1664-462X}, abstract = {INTRODUCTION: Species of Primula section Proliferae are predominantly distributed in alpine environments above 2,000 meters and represent an important group for studying environmental adaptation and phylogenetic evolution. Primula mallophylla, holds important ecological, ornamental, and conservation value. However, genomic resources for this species remain unavailable, hindering further research on its genetic evolution and conservation strategies.

METHODS: In this study, we sequenced and assembled the complete mitochondrial and chloroplast genomes of P. mallophylla for the first time. Comprehensive analyses were conducted on their structural characteristics, repetitive sequences, RNA editing site prediction, codon usage bias, intracellular gene transfer, phylogenetic inference, and selective pressure.

RESULTS: The results show that both the mitochondrial and chloroplast genomes exhibit typical master circular structures, with sizes of 340,219 bp and 150,733 bp, respectively. The mitochondrial genome has more abundant repetitive sequences and has undergone genomic rearrangements. There are only 9 MTPTs between mitochondria and chloroplasts, totaling 2,028 bp. In the regulation of mitochondrial genome expression, we predicted 475 RNA editing sites, with ccmB and mttB showing the highest potential editing frequencies. We found that P. mallophylla exhibits similar codon usage bias to most plants, and based on ENC-GC3s analysis, some genes appear to be under natural selection. Chloroplast genes rpl2, rpl22, rbcL, and ndhB exhibit branch-specific positive selection in Primula, reflecting adaptive evolution of photosynthesis and protein synthesis functions in high-altitude environments. Based on phylogenetic trees constructed from PCGs, Primulaceae are most closely related to Ebenaceae. Furthermore, phylogenetic analysis based on chloroplast genomes and PCGs of Primula species showed that sect. Proliferae is not monophyletic, with P. stenodonta being a sister species to P. mallophylla.

DISCUSSION: These findings provide crucial genomic resources and insights into the adaptive evolution of P. mallophylla, while also clarifying phylogenetic relationships within sect. Proliferae and Primulaceae, thereby offering valuable guidance for conservation strategies and further evolutionary studies.}, } @article {pmid41233302, year = {2025}, author = {Chenna, SS and Gajula, SNR and Nalla, LV}, title = {Polyamine metabolism in cancer: drivers of immune evasion, ferroptosis and therapy resistance.}, journal = {Expert reviews in molecular medicine}, volume = {27}, number = {}, pages = {e39}, pmid = {41233302}, issn = {1462-3994}, mesh = {Humans ; *Neoplasms/metabolism/immunology/pathology/drug therapy/etiology ; *Ferroptosis ; *Polyamines/metabolism ; Animals ; *Drug Resistance, Neoplasm ; *Immune Evasion ; }, abstract = {Polyamines putrescine, spermidine and spermine are small, positively charged metabolites indispensable for DNA stabilization, chromatin remodelling, RNA translation and redox balance, with dynamic distribution across the nucleus, mitochondria and endoplasmic reticulum. In cancer, polyamine homeostasis becomes profoundly dysregulated through altered biosynthesis, degradation and transport, driving malignant phenotypes and therapy resistance. Therefore, there is an urgent need to develop precision techniques that combine polyamine metabolism with immunotherapeutic and redox-based therapies, identify biomarkers to predict therapy response and create logical combination regimens to overcome resistance. The existing literature lacks in providing a holistic view of how polyamine dynamics intersect with diverse cancer hallmarks. Thus, this review consolidates emerging evidence on the multifaceted roles of polyamines in cancer hallmarks, with a particular focus on their impact on efferocytosis, ferroptosis and the dynamics of polyploid giant cancer cells (PGCCs). Furthermore, a comprehensive evaluation of contemporary treatment approaches that focus on polyamine metabolism, including transport blockers, biosynthesis inhibitors and various polyamine analogues, was discussed. While addressing context-dependent effects of polyamines that impede therapeutic progress, our discussion also incorporates important findings from pre-clinical and clinical investigations. Going forward, this review aims to enlighten and direct future translational research by situating polyamine biology within the broader context of cancer evolution and treatment adaptation.}, } @article {pmid41234204, year = {2025}, author = {Norizuki, T and Kushida, Y and Sekimoto, T and Sasaki, T and Yamano, K and Matsuda, N and Sasaki, R and Noda, NN and Sato, K and Sato, M}, title = {ALLO-1a is a ubiquitin-binding adaptor for allophagy in Caenorhabditis elegans.}, journal = {Journal of cell science}, volume = {138}, number = {24}, pages = {}, doi = {10.1242/jcs.264252}, pmid = {41234204}, issn = {1477-9137}, support = {22KJ0444//Japan Society for the Promotion of Science/ ; 20J01777, 22K15097, 25K18456//Japan Society for the Promotion of Science/ ; 23K23841//Japan Society for the Promotion of Science/ ; 19H05711, 20H00466, 25H0098//Japan Society for the Promotion of Science/ ; 21H02472, 25K02268//Japan Society for the Promotion of Science/ ; JPMJCR20E3//Core Research for Evolutional Science and Technology/ ; JP24gm1410004//Japan Agency for Medical Research and Development/ ; //Takeda Science Foundation/ ; 23H04923//Ministry of Education, Culture, Sports, Science and Technology/ ; 19H05707, 25H01320, 25H01321//Ministry of Education, Culture, Sports, Science and Technology/ ; 19H05712, 24H02274//Ministry of Education, Culture, Sports, Science and Technology/ ; 24H02274//Ministry of Education, Culture, Sports, Science and Technology/ ; 19H05712//Ministry of Education, Culture, Sports, Science and Technology/ ; 25H01321//Ministry of Education, Culture, Sports, Science and Technology/ ; 25H01320//Ministry of Education, Culture, Sports, Science and Technology/ ; 19H05707//Ministry of Education, Culture, Sports, Science and Technology/ ; 19H05711//Ministry of Education, Culture, Sports, Science and Technology/ ; 25K02268//Japan Society for the Promotion of Science/ ; 21H02472//Japan Society for the Promotion of Science/ ; 25H00987//Japan Society for the Promotion of Science/ ; 20H00466//Japan Society for the Promotion of Science/ ; 25K18456//Japan Society for the Promotion of Science/ ; 22K15097//Japan Society for the Promotion of Science/ ; 20J01777//Japan Society for the Promotion of Science/ ; JPMJCR20E3//Japan Science and Technology Agency/ ; }, mesh = {Animals ; *Caenorhabditis elegans/metabolism/genetics/embryology ; *Caenorhabditis elegans Proteins/metabolism/chemistry/genetics ; *Ubiquitin/metabolism ; Protein Binding ; *Autophagy ; Embryo, Nonmammalian/metabolism ; Mitochondria/metabolism ; }, abstract = {In the nematode Caenorhabditis elegans, sperm-derived mitochondria and membranous organelles (MOs) are selectively degraded by autophagy in embryos in a process termed allophagy. For this process, ALLO-1 functions as an autophagy adaptor. The allo-1 gene encodes two splice isoforms, ALLO-1a and ALLO-1b, which have different C-terminal sequences and are predominantly targeted to MOs and paternal mitochondria, respectively. However, the mechanism by which ALLO-1 targets the paternal organelles remains unknown. In this study, X-ray crystallography analysis reveals that the C-terminal region of ALLO-1a forms a parallel coiled-coil structure. In addition, AlphaFold2-Multimer predicts that this region directly interacts with ubiquitin. We showed that ALLO-1a interacts with K48- and K63-linked polyubiquitin in vitro and found that the D355 residue of ALLO-1a at the predicted interface with ubiquitin is important for its ubiquitin binding in vitro and also for its MO targeting and MO degradation in embryos. These results suggest that ubiquitin is a marker for the recognition of MOs by the autophagy machinery in C. elegans embryos.}, } @article {pmid41235780, year = {2026}, author = {Samani, P}, title = {Digest: Subcellular reallocation and the evolution of anisogamy in nematodes.}, journal = {Evolution; international journal of organic evolution}, volume = {80}, number = {4}, pages = {883-885}, doi = {10.1093/evolut/qpaf231}, pmid = {41235780}, issn = {1558-5646}, mesh = {Animals ; *Biological Evolution ; Male ; *Spermatozoa/physiology/ultrastructure/cytology ; *Caenorhabditis/physiology/genetics ; *Caenorhabditis elegans/physiology/genetics ; }, abstract = {Why has sperm gigantism evolved, and how do subcellular allocations scale with size? Schalkowski & Cutter (2025) addressed these questions with transmission electron microscopy of Caenorhabditis sperm, finding that a species with giant sperm disproportionately invests in mitochondria, consistent with energetic demands of motility and persistence. Here, the results are interpreted through anisogamy theory, highlighting how ecological conditions can favor sperm gigantism, why such costly sperm remain rare, and how new data invite mechanistic models of gamete evolution.}, } @article {pmid41241854, year = {2025}, author = {Gomes, YCP and Bongers, A and Jeannin, P and Vicente, ACP and Gessain, A and Afonso, PV and Espindola, OM}, title = {Cerebrospinal Fluid From Patients With HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) With Rapid Evolution Affects Mitochondrial DNA Transcription and Network Organization in Human Glioblastoma Cells.}, journal = {Journal of medical virology}, volume = {97}, number = {11}, pages = {e70711}, pmid = {41241854}, issn = {1096-9071}, support = {//This research was supported by Programa Jovens Pesquisadores - INI/FIOCRUZ [INI-003-FIO-19-2-14], Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Ministère de la Recherche, ANRS MIE [24150], Institut Pasteur - Programme Transversal de Recherche (PTR) [1786-24], Investissement d'Avenir/Laboratoire d'Excellence(LabEx)/Integrative Biology of Emerging Infectious Diseases [ANR10-LBX-62 IBEID]./ ; }, mesh = {Humans ; *Paraparesis, Tropical Spastic/cerebrospinal fluid/virology ; *Glioblastoma/genetics/pathology ; *Human T-lymphotropic virus 1 ; Cell Line, Tumor ; *DNA, Mitochondrial/genetics ; Female ; Male ; *Transcription, Genetic ; Middle Aged ; Mitochondria/genetics/metabolism ; *Cerebrospinal Fluid/virology ; Disease Progression ; Adult ; }, abstract = {Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurodegenerative disease affecting motor and sensory functions. While alterations in cerebrospinal fluid (CSF) have been used to identify disease biomarkers, the effects of such modified CSF on CNS cells remain unexplored. This study compared the effects of pools of CSF from HTLV-1 asymptomatic carriers (HAC) and HAM/TSP patients-categorized by disease progression as: very slow (HAMvs), typical (HAMt), and rapid (HAMr)-on the glioblastoma cell line U87-MG, a cellular model often used to study neurodegenerative diseases. RNA sequencing of U87-MG cells treated with a pool of CSFs from HAMr patients revealed a significant downregulation of transcription of mitochondrial genes after 24 h of treatment. Confocal microscopy showed phenotypical changes in the mitochondrial network: glioblastoma cells exposed to pooled HAMr CSF exhibited a less complex network compared to other patient groups. Despite these changes, U87-MG cells treated with CSF from HTLV-1-infected donors with distinct neurological outcomes presented similar mitochondrial oxygen consumption. In conclusion, these findings show that pooled HAMr CSF induces mitochondrial stress in glioblastoma cells, suggesting that CSF alterations may participate in rapidly progressing HAM/TSP pathogenesis.}, } @article {pmid41261123, year = {2026}, author = {Valt, M and Pánek, T and Mirzoyan, S and Tice, AK and Jones, RE and Dohnálek, V and Doležal, P and Mikšátko, J and Rotterová, J and Hrubá, P and Brown, MW and Čepička, I}, title = {Rare microbial relict sheds light on an ancient eukaryotic supergroup.}, journal = {Nature}, volume = {649}, number = {8096}, pages = {388-395}, pmid = {41261123}, issn = {1476-4687}, support = {//Czech Science Foundation project/ ; //Ministry of Education, Youth and Sports of the Czech Republic/ ; }, mesh = {*Phylogeny ; *Eukaryotic Cells/classification/cytology/metabolism ; *Eukaryota/classification/cytology/genetics ; Mitochondria/metabolism/genetics ; *Biological Evolution ; }, abstract = {During the past decade, our understanding of eukaryotic evolution has increased immensely. Newly recognized eukaryotic supergroups have been established[1-3], and most enigmatic orphan lineages have had their relationships resolved[4-6]. Studies on unicellular protist eukaryotes have also been key to understanding the evolution of mitochondria, the fundamental organelles of the eukaryotic cell, which originated from an alphaproteobacterial ancestor. The retention of ancestral alphaproteobacterial pathways in some protist lineages reveals that the mitochondrion of the last eukaryotic common ancestor was more metabolically versatile than are the highly derived mitochondria that are found in most modern eukaryotes[7,8]. Here we report the discovery of such a unicellular eukaryote, Solarion arienae gen. et sp. nov., an inconspicuous, free-living heterotrophic protist with two morphologically distinct cell types and a novel type of predatory extrusome. We assign Solarion to the new phylum Caelestes. Together with Provora, hemimastigophoreans and Meteora, they form a new eukaryotic supergroup, Disparia. Moreover, S. arienae has some noteworthy traits associated with the mitochondrial genome; in particular, the mitochondrially encoded secA gene, a remnant of an ancestral alphaproteobacterial protein secretion pathway, which has been lost almost entirely in extant mitochondria[9,10]. The discovery of S. arienae broadens our understanding of early eukaryotic evolution and facilitates the study of proto-mitochondrial metabolic remnants, shedding light on the complexity of ancestral eukaryotic life.}, } @article {pmid41262567, year = {2025}, author = {Kapan, E and Uslu, C and Arab, H and Ahmed, L and Ali, R and Tereshchenkov, AG and Sumbatyan, NV and Lyakhovich, A}, title = {Toward Mitochondrial Targeting of Resistant Triple-Negative Breast Cancer Using Triphenylphosphonium-Conjugated Antimicrobial Peptides.}, journal = {ACS pharmacology & translational science}, volume = {8}, number = {11}, pages = {4159-4171}, pmid = {41262567}, issn = {2575-9108}, abstract = {Metastatic evolution of malignant tumors following standard anticancer therapies and the emergence of resistant cancer cell populations remain major challenges in oncology. One promising strategy is to develop compounds that selectively target mechanisms of therapeutic resistance. Unlike therapy-sensitive malignant cells, which rely primarily on glycolysis for energy, many chemoresistant cells and cancer stem cells (CSCs) preferentially utilize mitochondrial oxidative phosphorylation (OXPHOS). In this study, we employed a triple-negative breast cancer model to demonstrate that short antimicrobial peptides can significantly suppress the metastatic potential of resistant cancer cells and reduce the formation of CSC-like mammospheres by disrupting mitochondrial respiration. This effect was further enhanced by conjugating the peptides to the mitochondrial-targeting cation triphenylphosphonium (TPP). Mechanistic studies revealed that these compounds induce oxidative stress and mitophagy and suppress mitochondrial translation. Collectively, these findings suggest that TPP-conjugated peptides represent a promising therapeutic strategy for targeting OXPHOS-dependent resistance in aggressive solid tumors.}, } @article {pmid41266272, year = {2025}, author = {Xie, B and Zhang, X and Yan, M and Qu, X and Dietrich, CH and Duan, Y}, title = {Mitogenomic analysis and phylogenetic implications for the Deltocephalinae (Hemiptera: Cicadellidae).}, journal = {Invertebrate systematics}, volume = {39}, number = {11}, pages = {}, doi = {10.1071/IS25032}, pmid = {41266272}, issn = {1447-2600}, mesh = {Animals ; *Hemiptera/genetics/classification ; *Phylogeny ; *Genome, Mitochondrial ; }, abstract = {Deltocephalinae (Hemiptera: Cicadellidae) is the largest subfamily within the leafhopper family Cicadellidae and has an almost worldwide distribution. However, the classification and phylogenetic relationships of Deltocephalinae have not yet been fully resolved. In this study, we sequenced the complete mitogenomes of 12 Deltocephalinae species and compared them with the 50 previously reported mitogenomes for this subfamily. Mitogenome size ranged from 14,648 bp in Scaphoideus albovittatus to 16,711 bp in Mukaria splendida. All contained 37 genes and a variable number of non-coding A + T-rich regions. Nucleotide composition analysis showed that the AT content was higher than GC. And while most protein-coding genes use ATN as the start codon and TAA or TAG as the stop codons, some genes use T as a stop codon. The Ka/Ks ratio showed that the cox1 gene has the slowest evolutionary rate, while atp8 is the gene with the fastest evolutionary rate. These new analyses confirm that Deltocephalinae mitochondrial genomes are highly conservative in overall structure, with only a few rare rearrangements of tRNAs, primarily concentrated in the trnW-trnC-trnY and trnA-trnR-trnN-trnS1-trnE-trnF gene clusters. Deltocephalinae mitochondrial genomes exhibit gene overlaps with three stable regions: trnW and trnC, atp6 and atp8, nad4 and nad4l. The overlapping sequences are typically AAGTCTTA, ATGATAA and TTATCAT. Phylogenetic analyses by maximum likelihood and Bayesian inference were conducted based on five datasets including either amino acid sequences alone or nucleotide sequences from different combinations of protein coding and ribosomal RNA genes, with or without third codon positions (AA, PCG12, PCG12R, PCG123 and PCG123R). Phylogenies obtained from different analyses consistently supported the monophyly of Deltocephalinae and showed high congruence within the subfamily, with few short, deep internal branches unstable among analyses. Included members of the following tribes were consistently monophyletic: Athysanini, Chiasmini, Deltocephalini, Drabescini, Macrostelini, Paralimnini, Penthimiini, Scaphoideini and Stenometopiini. Consistent with other recent analyses, Fieberiellini, Goniagnathini and Penthimiini are early diverging lineages within Deltocephalinae. Overall, our results indicate that complete mitogenome sequences provide robust data for phylogenetic reconstruction.}, } @article {pmid41273393, year = {2026}, author = {Bilinski, SM and Sekula, M and Sochaczewska, M and Tworzydlo, W}, title = {Analysis of Bush Cricket Oogenesis Provides an Insight into the Function and Anagenesis of an Enigmatic Organelle Assemblage: The Balbiani Body.}, journal = {Results and problems in cell differentiation}, volume = {76}, number = {}, pages = {167-182}, pmid = {41273393}, issn = {0080-1844}, mesh = {Animals ; Female ; *Gryllidae/cytology/physiology ; Mitochondria/metabolism ; *Oocytes/ultrastructure/cytology ; *Oogenesis/physiology ; *Organelles/physiology/ultrastructure ; }, abstract = {Balbiani body (Bb) is an intricate, oocyte-specific organelle complex described in the ooplasm of nearly all examined vertebrates and invertebrates. The Bb is devoid of a limiting membrane and consists of such organelles as elements of endoplasmic reticulum (ER), Golgi complexes (GCs), mitochondria, and characteristic accumulations of fibrillo-granular material, termed the "nuage." Despite numerous studies, the functioning of the Bb remains not completely understood. Until now at least four disparate functions have been attributed to the Bb: (1) delivery of germinal granules and localized mRNAs to the oocyte vegetal cortex; (2) transfer of mitochondria to the polar (germ) plasm; (3) selective elimination of dysfunctional (damaged, containing mutated mitochondrial DNA (mtDNA)) mitochondrial units in female germline cells; and (4) formation of oocyte reserve materials, e.g., lipid droplets. Such functional variability obviously raises several intriguing questions for students of developmental and cellular biology. Here we present the results of our studies on oogenesis of bush crickets that advance our understanding of the Bb function and anagenesis of this organelle complex during the evolution of bilateral animals.}, } @article {pmid41278143, year = {2025}, author = {Shan, S and Qing, Y and Chen, S and Liao, Y and Zhao, D and Jiang, L}, title = {Characterization of the complete mitochondrial genome data of Asiatic Toad, Bufo gargarizans (Cantor, 1842) (Neobatrachia: Bufonidae) from Mianyang, China.}, journal = {Data in brief}, volume = {63}, number = {}, pages = {112213}, pmid = {41278143}, issn = {2352-3409}, abstract = {A common amphibian in East Asia, the Bufo gargarizans is significant for research on ecology, conservation biology, and evolution. Thus, the B. gargarizans mitochondrial genome was sequenced and subjected to a methodical analysis. The sequence was 17,431 base pairs long, with 13 protein-coding genes (PCG), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and a D-loop control region. The nucleotide base composition of the mitochondrial genome was skewed toward AT content (57.17%), including adenine (28.80%), thymine (28.37%), cytosine (27.40%), and guanine (15.43%). For phylogenetic analysis, Bayesian inference (BI) techniques were used to build a phylogenetic tree from the mitochondrial genomes of 27 other species and the B. gargarizans. The findings demonstrated that species of the Bufonidae family formed a monophyletic group with the B. gargarizans. The mitochondrial genome of B. gargarizans will serve as an invaluable asset for future investigations into the evolution, taxonomy, and genetic preservation strategies of this species. Mitochondria genomic data can be found in GenBank under accession number PV083742.}, } @article {pmid41280737, year = {2025}, author = {Wang, X and Guo, Z and Tao, J and Guo, Y and Wang, G and Xu, G and Li, Q and Liu, H}, title = {Phylogeny and comparative analysis of mitochondrial genomes of Gomphus spp. Pers. (Basidiomycota, Agaricomycetes), with descriptions of G. matijun J.W. Liu & F.Q. Yu and G. bijiensis sp. nov.}, journal = {MycoKeys}, volume = {124}, number = {}, pages = {357-381}, pmid = {41280737}, issn = {1314-4049}, abstract = {The genus Gomphus Pers. presents persistent taxonomic challenges due to its morphological similarities with related genera. In this study, we collected two specimens of Gomphus from Guizhou, China; one specimen is described as a new species, Gomphus bijiensis sp. nov. and the other is identified as G. matijun J.W. Liu & F.Q. Yu based on morphological traits and phylogenetic analyses of the nuclear rDNA internal transcribed spacer (ITS) and nuclear rDNA large subunit (LSU). To resolve their evolutionary relationships we assembled and annotated the mitochondrial genomes of both species using next-generation sequencing. Comparative analyses revealed codon usage strongly biased toward A- or U-ending codons, consistent with the low GC content typical of fungal mitochondria. Variation in protein-coding gene lengths and base composition suggests that diverse evolutionary pressures have shaped these genomes. Divergence time estimation indicates that morphological diversity within Gomphus and related macrofungi has largely resulted from convergent evolution. Phylogenetic reconstruction places G. bijiensis and G. matijun within a distinct clade, supporting their close evolutionary affinity and the coexistence of ancestral and derived traits. This study provides the first comprehensive mitochondrial genomic data for Gomphus, offering new insights into its taxonomy, phylogeny, and evolutionary dynamics, and establishing a framework for future studies within the Gomphaceae.}, } @article {pmid41287464, year = {2025}, author = {Mingoti, GZ and Nunes, GB and Souza-Cáceres, MB and da Silva, CR and Nociti, RP and de Athayde, FF and Mogollón-García, HD and Bastos, NM and Rosa, PMS and de Oliveira Alves, L and Pereira-Júnior, SAG and Franchi, FF and Ferreira, JCP and da Silveira, JC and Chiaratti, MR}, title = {Extracellular Vesicles Derived From Antral Follicles Significantly Change the Transcriptional Profile of Cumulus Cells and Oocytes During Pre-In Vitro Maturation in Cattle.}, journal = {Molecular reproduction and development}, volume = {92}, number = {11}, pages = {e70068}, pmid = {41287464}, issn = {1098-2795}, support = {//This work was supported by CAPES (Finance Code 001), CNPq (313505/2021-7 and 305544/2025-0) and FAPESP (12/18297-7, 19/11174-6, 20/15412-6, 21/09886-8, 21/06645-0, 21/14019-1 and 23/04558-8)./ ; }, mesh = {Animals ; Cattle ; *Cumulus Cells/metabolism/cytology ; Female ; *Extracellular Vesicles/metabolism ; *Oocytes/metabolism/cytology ; *In Vitro Oocyte Maturation Techniques/methods ; *Ovarian Follicle/metabolism/cytology ; *Transcriptome ; }, abstract = {Cumulus-oocyte complexes (COCs) used for in vitro production (IVP) of bovine embryos originate from antral follicles of different sizes, leading to variations in developmental competence. To address this, pre-in vitro maturation (pre-IVM) allows oocytes with additional time to acquire developmental competence. Given the role of follicular fluid-derived extracellular vesicles (EVs) in ovarian follicle communication, which has been shown to vary in content and function across folliculogenesis, we investigated whether EVs from early versus late antral follicles influence COCs during pre-IVM. EV supplementation significantly altered gene expression in cumulus cells and oocytes. In cumulus cells, affected pathways included MAPK signaling, Gap junctions, Cytokine-cytokine receptor interaction, Axon guidance, cAMP, and Cushing syndrome. In oocytes, fewer genes were altered, with effects on Inositol phosphate metabolism, p53 signaling and Cholesterol metabolism. Despite these changes, no significant effects of the EV treatment were noted on oocyte chromatin configuration and developmental competence, except for a significant increase of mitochondrial membrane potential (Δψm) in blastocysts. In conclusion, EV supplementation during pre-IVM significantly altered the transcriptional profile of COCs, with EVs from early follicles modulating the expression of genes regulating cumulus cell proliferation and gap junctions, while EVs from late follicles impacted pathways associated with meiotic resumption, cumulus cell expansion, and apoptosis. Along with improved Δψm in blastocysts, these results support a positive effect of EVs on bovine COCs, but further research is needed to better characterize the functional consequences, mainly in terms of the effects of early versus late follicle-derived EVs on oocyte developmental potential.}, } @article {pmid41290218, year = {2026}, author = {Montalvo, RN}, title = {Postmodern Mitochondria and the Architecture of Function.}, journal = {Physiology (Bethesda, Md.)}, volume = {41}, number = {5}, pages = {0}, doi = {10.1152/physiol.00053.2025}, pmid = {41290218}, issn = {1548-9221}, support = {5364//American College of Sports Medicine (ACSM)/ ; }, } @article {pmid41290871, year = {2025}, author = {Kim, G and Choi, EH and Hwang, UW}, title = {Three distinct genetic lineages of Trichonephila clavata based on mitochondrial COI and genome-wide SNPs on the Korean Peninsula.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {41911}, pmid = {41290871}, issn = {2045-2322}, support = {NIBR202104202//National Institute of Biological Resources/ ; RS-2025-00561309//National Research Foundation of Korea/ ; }, mesh = {*Spiders/genetics ; Republic of Korea ; *Genetics, Population ; Polymorphism, Single Nucleotide ; Mitochondria/enzymology/genetics ; *Introduced Species ; United States ; Animals ; *Electron Transport Complex IV/genetics ; }, abstract = {Trichonephila clavata L. Koch, 1878, an East Asian species renowned for its long-distance ballooning dispersal, has recently drawn attention as an invasive species following its introduction into the southeastern United States. However, few population genetic studies have been undertaken to investigate population genetic diversity and structure which will be helpful for its management. Here, we examined ten populations of T. clavata on the Korean Peninsula using mitochondrial COI and genome-wide SNP data to broadens the understanding of genetic and demographic processes of the species. Our results revealed: (1) high genetic diversity in COI but relatively low diversity in SNPs; (2) the presence of three genetic lineages detected by both markers; (4) population expansion in each COI genetic lineage and constant population size in each SNP genetic lineage; and (5) stepwise lineage divergence estimated based on COI and lineage divergence with admixture event based on SNPs. These findings suggest that multiple factors, which are ballooning dispersal, demographic dynamics and geological event, may play a pivotal role in shaping population genetic patterns with geographic co-occurrence among the lineages. Consequently, this study provides insights into the genetic architecture of natural populations and offers a valuable baseline for understanding the population genetic pools of invasive populations of this species.}, } @article {pmid41299448, year = {2025}, author = {Iannello, M and Piccinini, G and Salatiello, F and Forni, G and Nicolini, F and Valdrè, U and Martini, M and Martelossi, J and Ghiselli, F and D'Aniello, E and Milani, L}, title = {New insights into mitochondrial segregation from the Doubly Uniparental Inheritance system in bivalves.}, journal = {BMC biology}, volume = {23}, number = {1}, pages = {371}, pmid = {41299448}, issn = {1741-7007}, support = {IIG22Q401//Zymo Impact Initiative Grant/ ; CUPJ53D23006200006//PRIN 2022 - European Union - Next Generation EU/ ; }, mesh = {Animals ; *Mitochondria/genetics ; Female ; Male ; *Mytilus/genetics ; *Inheritance Patterns ; }, abstract = {BACKGROUND: While nuclear genome segregation is well characterized, mechanisms underlying mitochondrial partitioning remain partially obscure, even though its failure can cause developmental arrest or harmful mutations. This knowledge gap invokes the need for new, more suitable model systems to study such mechanisms. Doubly Uniparental Inheritance (DUI) of mitochondria in bivalves is a useful system for such studies. In DUI, sperm mitochondria in male embryos are actively transported across cell divisions to precursors of the germline, and this male-specific pattern depends on maternal factors stored in eggs. The presence of distinct mitochondrial segregation patterns in male and female embryos offers a unique opportunity to investigate the molecular bases of this process.

RESULTS: Here, we leveraged this system by (1) performing RNA-Seq on eggs producing male-biased versus female-biased progenies in the Mediterranean mussel Mytilus galloprovincialis to identify factors involved in differential mitochondrial segregation; and (2) inferring signatures of convergent evolutionary rate across DUI bivalve genomes to separate segregation-specific factors from those involved in sex determination. We show that differentially transcribed genes across eggs that give rise to either male- or female-biased progeny are predominantly associated with mitochondrial dynamics, cytoskeletal organization, and vesicular trafficking. We also identified multiple long noncoding RNAs-many derived from transposable elements-that might have roles in the regulation of other maternally supplied factors that shepherd paternal mitochondria.

CONCLUSIONS: By overlaying clues from expression and sequence evolution, we delineate a conserved protein-protein interaction network of factors that mediate mitochondrial segregation. This study reveals general principles of organelle selection in animals and unveils the contribution of new factors.}, } @article {pmid41300639, year = {2025}, author = {Jeon, M and Yang, SS and Lee, S and Choi, JY}, title = {From Congenital Torticollis to Leigh Syndrome: A Case Report of Diagnostic Evolution in an Infant.}, journal = {Children (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {41300639}, issn = {2227-9067}, support = {(#2020R1C1C1010794//National Research Foundation of Korea/ ; }, abstract = {Leigh syndrome is a rare, progressive mitochondrial disorder of childhood. Early diagnosis is often challenging due to nonspecific clinical manifestations. We report a 1-month-old male infant initially referred for suspected congenital muscular torticollis who ultimately received a diagnosis of Leigh syndrome. Despite unremarkable perinatal history, he subsequently developed persistent feeding difficulties, recurrent vomiting, failure to thrive, and global developmental delay. Early neurological assessment revealed poor repertoire patterns on General Movement Assessment. The Neonatal Oral-Motor Assessment Scale (NOMAS) demonstrated dysfunctional oral-motor control, whereas the video fluoroscopic swallowing study (VFSS) revealed aspiration during swallowing. Brain MRI revealed symmetric basal ganglia lesions. Expanded whole-exome sequencing identified a pathogenic MT-ATP6 m.8993T>G variant with high heteroplasmy level (>90% in blood), confirming the diagnosis of Leigh syndrome. The variant was maternally inherited, although neither the mother nor the older sibling exhibited clinical features of mitochondrial disease. Leigh syndrome can initially manifest with subtle systemic features rather than overt neurological features. Persistent feeding difficulties and growth delay in infancy warrant thorough evaluation, including neuroimaging and comprehensive genomic testing, to enable timely diagnosis and optimize clinical management.}, } @article {pmid41318756, year = {2025}, author = {Talarico, L and Petrosino, G and Rossi, AR and Franchini, P and Gratton, P and Tancioni, L}, title = {Efficient eDNA-based assessment of mitochondrial lineage diversity in wild brown trout populations.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {317}, pmid = {41318756}, issn = {2045-2322}, support = {PRIN 2022 - 2022JJ7STN//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, mesh = {Animals ; *Trout/genetics ; *Genetic Variation ; *DNA, Mitochondrial/genetics ; *DNA, Environmental/genetics/analysis ; Phylogeography ; Phylogeny ; Genotype ; *Mitochondria/genetics ; }, abstract = {Among the numerous applications of environmental DNA (eDNA), the assessment of genetic diversity in wild populations of target taxa remains moderately investigated. Focusing on 10 selected sites inhabited by brown trout (Salmo trutta complex) in central Italian watercourses, we: (1) developed a non-invasive genetic monitoring protocol combining environmental DNA sampling, amplicon sequencing with custom-designed primers targeting a 192 bp fragment of the mitochondrial Control Region (CR) - whose evolutionary lineages are informative for brown trout phylogeography and genetic conservation status-and a curated reference database; (2) validate it comparing CR lineages assemblages revealed by eDNA with those obtained through traditional CR genotyping of trouts collected by electrofishing in recent surveys, while accounting for uncertainty associated with sample size of genotyped individuals. The two methods returned strongly correlated per-site raw frequencies of CR lineages (Pearson r = 0.93, p < 0.0001), and remarkably similar lineage assemblages (Mantel r = 0.832, p = 0.0001). Concordances between (semi-quantitative) lineage assemblages retrieved by the two methods increased at increasing trout densities and decreased at warmer water temperatures. Discordances mostly involved low-frequency lineages that were not detected by traditional CR genotyping. This study supports the effectiveness of eDNA for reliably characterising mitochondrial intra-population diversity in brown trout, a widely distributed and actively managed taxon of important conservation and economic value, offering a valuable tool to assist the genetic monitoring of wild populations, including the identification and quantification of exotic lineages.}, } @article {pmid41334600, year = {2026}, author = {Ramanathan, S and Hanraths, A and Xie, J and Schallenberg-Rüdinger, M and Knoop, V}, title = {Plant organelle C-to-U RNA editing factors can operate successfully in yeast (Saccharomyces cerevisiae) as an easily amenable eukaryotic system for their functional analysis.}, journal = {The FEBS journal}, volume = {293}, number = {11}, pages = {3166-3186}, doi = {10.1111/febs.70352}, pmid = {41334600}, issn = {1742-4658}, mesh = {*Saccharomyces cerevisiae/genetics/metabolism ; *RNA Editing/genetics ; *Plant Proteins/genetics/metabolism ; *RNA-Binding Proteins/genetics/metabolism ; *Bryopsida/genetics/metabolism ; Mitochondria/genetics/metabolism ; Uridine/genetics/metabolism ; *RNA, Plant/genetics/metabolism ; }, abstract = {Site-specific cytidine-to-uridine (C-to-U) RNA editing is essential for gene expression in plant mitochondria and chloroplasts. Specific RNA-binding pentatricopeptide repeat (PPR) proteins equipped with a DYW-type cytidine deaminase have been identified as the core RNA editing factors. Multiple circumstances impede their analysis in planta and call for experimental approaches in easily amenable heterologous setups for functional analyses of these intriguing proteins. Here, we report the establishment of the yeast Saccharomyces cerevisiae as such a system. Three plant RNA editing factors from the model moss Physcomitrium patens, namely PPR56 (PpPPR_56), PPR65 (PpPPR_65), and PPR78 (PpPPR_78), were successfully expressed in the yeast cytosol and faithfully edit not only their respective co-delivered targets but also variable ranges of off-targets with similar recognition sequences in the yeast background transcriptome. Convincingly, we found that the different editing factors behaved in the new system very much like previously found in bacteria or human cells, not only with respect to off-target conservation profiles but also with surprising differences in off-target numbers, championed by more than 125 off-targets for PPR56 with editing efficiencies of up to 41% in the S. cerevisiae transcriptome. We conclude that S. cerevisiae will be a helpful heterologous system for studying the intricacies of plant RNA editing.}, } @article {pmid41335200, year = {2026}, author = {Zhao, Z and Ma, J and Yang, Q and Wörheide, G and Erpenbeck, D}, title = {First Report on Presence of Mitochondrial Introns in Freshwater Sponges, and Pseudogenic Evidence of Their Loss.}, journal = {Journal of molecular evolution}, volume = {94}, number = {1}, pages = {19-23}, pmid = {41335200}, issn = {1432-1432}, mesh = {*Porifera/genetics ; *Introns/genetics ; Animals ; Phylogeny ; Genome, Mitochondrial/genetics ; Evolution, Molecular ; Open Reading Frames/genetics ; Fresh Water ; *Mitochondria/genetics ; Pseudogenes/genetics ; }, abstract = {Mitochondrial introns have a patchy distribution in sponge lineages. Here, we report on the finding of a group-II-intron in Eunapius rarus (Demospongiae, Spongillidae), which constitutes the first report of a mitochondrial intron in freshwater sponges. Group-II-introns are self-splicing ribozymes, and are particularly rare among sponge mitochondrial genomes. The intron contains complete open reading frames (ORFs), including typical intron-encoded proteins (IEPs). Phylogenetic analysis reveals that the intron is more closely related to those found in brown algae, and distant from other sponge group-II-introns, indicating an acquisition of this intron independent from other sponges. Remarkably, the congeneric E. fragilis does not possess this intron in their mitochondrial genome. However, we found pseudogenic copies of the E. rarus group-II-intron in the nuclear genome of E. fragilis, which indicates patterns of group-II-intron presence and their pseudogene transposition into the nuclear genomes in sponges for the first time. Our results show that a group-II-intron must have been present in the last common ancestor of both Eunapius mt genomes, and subsequently lost in E. fragilis, rather than independent acquisition. Consequently, our findings provide an explanation for the patchy distribution of introns in sponges as a result of frequent losses, besides multiple acquisitions.}, } @article {pmid41339551, year = {2026}, author = {Kay, CJ and Spang, A and Szöllősi, GJ and Pisani, D and Williams, TA and Donoghue, PCJ}, title = {Dated gene duplications elucidate the evolutionary assembly of eukaryotes.}, journal = {Nature}, volume = {650}, number = {8100}, pages = {129-140}, pmid = {41339551}, issn = {1476-4687}, support = {//Gordon and Betty Moore Foundation/ ; //Leverhulme Trust/ ; }, mesh = {Archaea/genetics/cytology ; *Eukaryota/genetics/cytology/classification ; Eukaryotic Cells/cytology/metabolism ; *Evolution, Molecular ; *Gene Duplication ; Mitochondria/genetics ; Phylogeny ; Symbiosis ; Time Factors ; }, abstract = {The origin of eukaryotes was a formative but poorly understood event in the history of life. Current hypotheses of eukaryogenesis differ principally in the timing of mitochondrial endosymbiosis relative to the acquisition of other eukaryote novelties[1]. Discriminating among these hypotheses has been challenging, because there are no living lineages representative of intermediate steps within eukaryogenesis. However, many eukaryotic cell functions are contingent on genes that emerged from duplication events during eukaryogenesis[2,3]. Consequently, the timescale of these duplications can provide insights into the sequence of steps in the evolutionary assembly of the eukaryotic cell. Here we show, using a relaxed molecular clock[4], that the process of eukaryogenesis spanned the Mesoarchaean to late Palaeoproterozoic eras. Within these constraints, we dated the timing of these gene duplications, revealing that the eukaryotic host cell already had complex cellular features before mitochondrial endosymbiosis, including an elaborated cytoskeleton, membrane trafficking, endomembrane, phagocytotic machinery and a nucleus, all between 3.0 and 2.25 billion years ago, after which mitochondrial endosymbiosis occurred. Our results enable us to reject mitochondrion-early scenarios of eukaryogenesis[5], instead supporting a complexified-archaean, late-mitochondrion sequence for the assembly of eukaryote characteristics. Our inference of a complex archaeal host cell is compatible with hypotheses on the adaptive benefits of syntrophy[6,7] in oceans that would have remained largely anoxic for more than a billion years[8,9].}, } @article {pmid41345699, year = {2025}, author = {Yilmaz, A and Kasap, OE}, title = {Prevalence of Wolbachia in natural sand fly (diptera: psychodidae) populations from Türkiye and its potential role in mitochondrial divergence.}, journal = {Parasites & vectors}, volume = {19}, number = {1}, pages = {16}, pmid = {41345699}, issn = {1756-3305}, support = {2211-A National PhD Scholarship Program//TÜBİTAK/ ; 101057690//European Commission/ ; 10038150 and 10038150//UK Research and Innovation/ ; TBAG 105T205 and SBAG 114S999//Türkiye Bilimsel ve Teknolojik Araştırma Kurumu/ ; 09D01601002 and 01001601001//Hacettepe University Scientific Research Unit/ ; W911QY-16-C-0160//AFHSB-GEIS/ ; }, mesh = {Animals ; *Wolbachia/genetics/isolation & purification ; *Psychodidae/microbiology/classification/genetics ; *Genetic Variation ; Multilocus Sequence Typing ; Phylogeny ; Female ; Male ; Prevalence ; *Mitochondria/genetics ; Insect Vectors/microbiology ; Phlebotomus/microbiology ; }, abstract = {BACKGROUND: Phlebotomine sand flies are vectors of various pathogens, most notably Leishmania spp. Symbiotic bacteria have recently gained considerable attention owing to their effects on hosts and on other organisms co-infecting the same host. In this study, we investigated the natural Wolbachia infection status of sand fly taxa distributed in Türkiye and examined its potential role in driving the deep mitochondrial divergence observed within certain taxa.

METHODS: We analysed 858 sand fly specimens, mostly collected between 2005 and 2016, with additional samples obtained in 2023. Specimens were morphologically identified, and the mitochondrial cox1 gene was sequenced for DNA barcoding. For selected taxa showing marked mitochondrial divergence, species delimitation methods were applied, and genetic diversity indices and neutrality tests were calculated. Wolbachia infection was detected via PCR amplification of the wsp gene, and strain diversity was characterised using multilocus sequence typing (MLST) of five housekeeping genes. Logistic regression was used to evaluate associations between infection status and mitochondrial lineage, sex or collection period.

RESULTS: Wolbachia infection was detected in 16.67% of specimens, occurring exclusively in Phlebotomus papatasi, Ph. major s.l., Ph. tobbi, Ph. economidesi and Sergentomyia minuta. Analyses of wsp and MLST data identified all sequences as belonging to Supergroup A, with multiple strains present within and across host taxa. Infection among the five Ph. major s.l. lineages delineated by species delimitation was significantly associated with lineage, with lineages 3-5 showing a higher probability of infection. The reduced haplotype and nucleotide diversity, along with a significant negative deviation from neutrality observed in lineage 5, suggest a selective sweep likely driven by Wolbachia infection.

CONCLUSIONS: This study represents the first comprehensive screening of Wolbachia infection in sand fly taxa distributed across Türkiye, during which several novel Wolbachia strains were identified. Our findings suggest a potential role of Wolbachia infection in driving lineage differentiation within certain sand fly taxa. However, further detailed investigations are required to elucidate the mechanisms by which Wolbachia influences sand fly diversification and to assess the broader epidemiological implications related to sand fly-borne diseases (SFBDs).}, } @article {pmid41349255, year = {2025}, author = {Yu, X and Li, M and Li, H}, title = {The role of gut dysbiosis and mitochondrial dysfunction in type 2 diabetes: Insights on pathogenesis, intervention and future perspective.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {193}, number = {}, pages = {118846}, doi = {10.1016/j.biopha.2025.118846}, pmid = {41349255}, issn = {1950-6007}, mesh = {Humans ; *Diabetes Mellitus, Type 2/metabolism/microbiology ; *Dysbiosis/metabolism/complications ; *Gastrointestinal Microbiome/physiology ; Animals ; *Mitochondria/metabolism/pathology ; Oxidative Stress ; Energy Metabolism ; }, abstract = {Type 2 diabetes (T2D) is a typical metabolic disease which is attributed to genetic and environmental factors. Emerging evidence has highlighted that either gut dysbiosis or mitochondrial dysfunction plays critical roles in the development of T2D through various ways. After searching preclinical and clinical studies, our review concludes that gut dysbiosis contribute to T2D through gut metabolites-induced inflammation, dysregulation of glucose homeostasis and the change of β-cell evolution. Moreover, we found out that the overproduction of oxidative stress, disruption of energy metabolism, mitochondrial dynamic network and mitochondrial permeability transition are major mechanisms which contribute to the development of T2D by mitochondrial dysfunction. We particularly focused on summarizing the advances of how gut dysbiosis and mitochondrial dysfunction contributed to T2D development, respectively, and elaborating their interplay in central and peripheral organs. Moreover, the latest strategies on T2D management were also discussed, in which modulation on gut microbiota and mitochondrial function were primarily included, as well as perspectives on future investigations.}, } @article {pmid41350619, year = {2025}, author = {Pham, NT and Duplouy, A and See, J and Knowles, LS and Marquina, E and Gallice, G and Molleman, F and Oostra, V}, title = {A high-quality draft genome assembly of the Neotropical butterfly, Batesia hypochlora (Nymphalidae: Biblidinae).}, journal = {BMC genomics}, volume = {27}, number = {1}, pages = {31}, pmid = {41350619}, issn = {1471-2164}, support = {2021/43/B/NZ8/00966//Narodowym Centrum Nauki/ ; 321543//Research Council of Finland/ ; NEOF1388//Natural Environment Research Council/ ; MR/V024744/2//UKRI Future Leaders Fellowship/ ; SR20-1273//British Ecological Society/ ; }, mesh = {Animals ; *Butterflies/genetics ; *Genome, Insect ; Molecular Sequence Annotation ; *Genomics/methods ; }, abstract = {We report a long-read high-coverage reference genome assembly of the Neotropical butterfly, Batesia hypochlora (Nymphalidae: Biblidinae). This represents the first reference genome in the Biblidinae subfamily, a clade subject to ongoing studies on seasonal and climate adaptation in the Amazon. We assembled the genome from PacBio HiFi long reads (66X coverage), polished it with Illumina short reads (15X coverage), and annotated it using PacBio IsoSeq RNA data. We observed 15 chromosome-sized scaffolds, varying in length from 13.2 Mbp to 37.6 Mbp (median, 24.3 Mbp), which combined to form a total genome size of 395.788 Mbp. This assembly is highly contiguous (contig N50 of 25.14 Mbp) and complete (BUSCO completeness score of 98.6% and 0.2% duplication rate). Repeat annotation revealed that the genome comprises approximately one-third transposable elements. Gene prediction using RNA-seq evidence identified 19,395 genes, of which 17,400 were assigned to 2,883 orthogroups, including genomes of the fruit fly, silk moth, and three other Nymphalid butterfly species. The high sequencing depth also allowed us to assemble the genomes of the mitochondria and the common endosymbiotic bacterium Wolbachia. The mitochondrial genome was fully assembled (15,540 bp in size) with all expected genes annotated. The Wolbachia genome was fragmented, and we determined that it belongs to the B-supergroup. The high-quality assembly of B. hypochlora can represent the subfamily in further comparative analysis of evolution and provide a key resource for ongoing work to explore reproductive biology and adaptations to seasonality in Neotropical butterflies.}, } @article {pmid41351664, year = {2026}, author = {Yang, C and Luo, C and Wang, Q and Xu, X and Zhang, J and Zhao, C and Mu, Y and Lang, D and Hu, W}, title = {Insight into the Evolution of Mitochondrial Genetic Basis of Amphibious Adaptation in the Goby (Teleostei: Gobiidae).}, journal = {Journal of molecular evolution}, volume = {94}, number = {1}, pages = {3-13}, pmid = {41351664}, issn = {1432-1432}, support = {32360119//National Natural Science Foundation of China/ ; DXDGCZX03//Erhai Watershed Ecological Environment Quality Testing Engineering Research Center of Yunnan Provincial Universities/ ; KY1916101940//the start-up projects on high-level talent introduction of Dali University/ ; }, mesh = {Animals ; *Perciformes/genetics ; *Evolution, Molecular ; *Adaptation, Physiological/genetics ; Phylogeny ; Genome, Mitochondrial ; Selection, Genetic ; *Mitochondria/genetics ; Oxidative Phosphorylation ; *Adaptation, Biological/genetics ; Genes, Mitochondrial ; }, abstract = {The adaptation to terrestrial environments from aquatic environments has always been regarded as a major evolutionary transition in fishes, during which it has been accompanied with diverse phenotypic innovations. Mitochondrial energy metabolism fundamentally enables this shift, but the evolutionary trajectory and molecular mechanisms of mitogenomic adaptations to energy demands are poorly characterized. Mudskippers, a group of gobies with amphibious adaptive traits, serve as ideal models for studying energy metabolism during the water-to-land transition. To test whether amphibious adaptation in gobies corresponds to adaptive evolution in mitochondrial OXPHOS genes, we performed an in silico analysis of the 13 OXPHOS genes from the mitochondrial genomes of 33 goby species and two outgroups. The results showed that: (1) No matter ML or BI methods, four subfamilies Amblyopinae, Gobiinae, Gobionellinae, Oxudercinae are paraphyletic origin, except for subfamily Sicydiinae; besides, genus Scartelaos was first confirmed that it is paraphyletic origin. (2) 13 OXPHOS genes have been under the strong selective constraints, yet, the episodic positive selection was also detected, and ND4 and ATP8 evolution has been found to be under the accelerated evolution. Interestingly, (3) Significant divergent selection was detected between amphibious and fully aquatic lineages in 11 of the 13 OXPHOS genes (84%). And (4) the much stronger selective constraints were uncovered in amphibious lineages. To sum up, OXPHOS genes have undergone adaptive evolution with notable divergent patterns associated with the water-to-land transition during transition from water to land. These results provided some new insights into the genetic basis of amphibious adaptation in goby.}, } @article {pmid41353705, year = {2025}, author = {Okamoto, T and Okamoto, K and Yamamoto, T and Tao, SD and Kurita, K and Toda, M}, title = {A mitogenomic phylogenetic analysis of the Japanese Plestiodon species (Scincidae, Squamata) clarifies a mito-nuclear discordance caused by a past long distance dispersal.}, journal = {Genetica}, volume = {154}, number = {1}, pages = {3}, pmid = {41353705}, issn = {1573-6857}, support = {24770080//JSPS KAKENHI/ ; JPMEERF20204002//Environment Research and Technology Development Fund/ ; }, mesh = {Animals ; *Phylogeny ; *Lizards/genetics/classification ; *Genome, Mitochondrial ; Japan ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; }, abstract = {The whole mitochondrial genomes (mitogenomes) excluding the control region were sequenced for 42 samples of the ten species of scincid lizards of the genus Plestiodon occurring in Japan, and the mitochondrial genealogy of the East Asian Plestiodon was reconstructed on the basis of the mitogenomic dataset. A comparison with a species phylogeny based on five nuclear DNA fragments revealed that P. latiscutatus, a species distributed on the Izu Peninsula of the Japanese Main Islands, was a sister to the clade consisting of P. japonicus and P. finitimus, species occurring in the remaining parts of the Main Island in the species phylogeny, whereas the former species was a sister to the P. capito group occurring in continental China in the mitogenomic phylogeny. A tree reconciliation analysis of the species and the mitochondrial phylogenies revealed horizontal transfer of mitochondria, suggesting that the position of P. latiscutatus was caused by past introgression of mtDNA from the ancestral P. capito group to the ancestral P. latiscutatus. This further suggests a past long-distance dispersal of the skink from the Eurasian continent to the Izu Peninsula and Izu Islands beyond the western part of the Japanese Main Islands in the Miocene.}, } @article {pmid41359517, year = {2026}, author = {Luangtrakul, W and Söderhäll, K and Söderhäll, I}, title = {The role of mitophagy during hematopoiesis in an invertebrate, Pacifastacus leniusculus.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {215}, number = {3}, pages = {}, doi = {10.1093/jimmun/vkaf325}, pmid = {41359517}, issn = {1550-6606}, support = {2022-03236//The Swedish Research Council (Vetenskapsrådet)/ ; }, mesh = {Animals ; *Hematopoiesis/immunology ; *Mitophagy/immunology ; *Hemocytes/physiology/immunology/cytology ; *Hematopoietic Stem Cells/physiology/cytology ; *Astacoidea/immunology/physiology ; Cell Differentiation ; Immunity, Innate ; Mitochondria/metabolism ; Humans ; Signal Transduction ; }, abstract = {Freshwater crayfish as most aquatic crustaceans live for up to 20-30 years on the bottom of lakes and rivers, constantly exposed to millions of microorganisms. Consequently, they must have an effective immune system to combat and eliminate pathogens. The main immune cells are the hemocytes, and they are regularly consumed during the animal's whole life and are continuously produced through hematopoiesis. We used DMSO as a tool to induce differentiation of hematopoietic stem cells and we can show that differentiation of hematopoietic stem cells to mature hemocytes in a freshwater crayfish is preceded by degradation of mitochondria by mitophagy and this process could be inhibited by a mitophagy inhibitor. The differentiation process was regulated by β-catenin signaling in similarity to differentiation of human neutrophils. A better understanding of the molecular mechanisms that regulate hemocyte development in these animals will provide new insights into the evolution of the innate immune system and hematopoiesis in general.}, } @article {pmid41367310, year = {2025}, author = {Nguyen, THM and Klein, DA and Weklar, OS and Wengrow, ER and Rockman, MV}, title = {Abundant Recurrent Mitochondrial Mutations and Widespread Mitonuclear Epistasis in Caenorhabditis elegans.}, journal = {Molecular biology and evolution}, volume = {42}, number = {12}, pages = {}, pmid = {41367310}, issn = {1537-1719}, support = {R01 ES029930/ES/NIEHS NIH HHS/United States ; R35 GM141906/GM/NIGMS NIH HHS/United States ; ES029930/NH/NIH HHS/United States ; GM141906/NH/NIH HHS/United States ; }, mesh = {Animals ; *Caenorhabditis elegans/genetics ; *Epistasis, Genetic ; Genome, Mitochondrial ; *Mitochondria/genetics ; Mutation ; Cell Nucleus/genetics ; Phylogeny ; Caenorhabditis elegans Proteins/genetics ; }, abstract = {Coordinated genetic and physical interactions between mitochondrial and nuclear gene products regulate ATP production in the mitochondria. Linking mitochondrial genotypes and mitonuclear genetic interactions to phenotypes remains a complex challenge. Here, we have developed Caenorhabditis elegans as a model for mitonuclear epistasis studies. In a sample of 540 genetically distinct wild isolates, 10% of sites in the mitochondrial genome vary, with hundreds of missense mutations segregating in the species. Recurrent mutations and triallelic sites are common. Phylogenetic analyses of mitogenome sequences identified 8 distinct lineages, each with diagnostic variants. Principal component analysis of the nuclear genomes showed considerable concordance between mitochondrial and nuclear genomes in C. elegans populations, suggesting that disrupting coevolved mitonuclear genetic combinations could reveal substantial epistasis. We used GPR-1 overexpression, which disrupts the first mitotic division, to efficiently exchange nuclear and mitochondrial genomes between all pairs of 18 naturally isolated C. elegans strains, generating the largest-to-date animal mitonuclear exchange panel, with 323 unique viable mitonuclear genotypes. We phenotyped development of a subset of strains, with 30 unique genotypes, under 6 different environmental conditions, including high temperature and exposure to heavy metals. Mitonuclear epistasis contributed significantly to phenotypic variance across all tested conditions. We also tested for mitonuclear coadaptation by comparing the stress resistance of matched and mismatched cybrids. Interestingly, some mismatched strains exhibited greater resistance, highlighting the complexity and context dependence of mitonuclear interactions.}, } @article {pmid41379967, year = {2025}, author = {Valencia-Montoya, WA and Liénard, MA and Rosser, N and Calonje, M and Salzman, S and Tsai, CC and Yu, N and Carlson, JR and Cogni, R and Pierce, NE and Bellono, NW}, title = {Infrared radiation is an ancient pollination signal.}, journal = {Science (New York, N.Y.)}, volume = {390}, number = {6778}, pages = {1164-1170}, doi = {10.1126/science.adz1728}, pmid = {41379967}, issn = {1095-9203}, mesh = {Animals ; Biological Evolution ; Circadian Rhythm ; *Coleoptera/physiology ; Flowers/physiology ; Hot Temperature ; *Infrared Rays ; Mitochondria/physiology ; Neurons/physiology ; *Pollination ; Thermogenesis ; Thermosensing ; *Cycadopsida/physiology ; }, abstract = {Color and scent are well-known pollinator cues. Some plants also produce heat, but its role remains unclear. Here, we report that plant-generated thermal infrared radiation serves as a pollination signal and describe the underlying mechanisms of heat production and infrared detection. Mitochondrial adaptations heat plant reproductive structures in a circadian pattern, radiating infrared that is sufficient to attract beetle pollinators. Beetle antennae contain infrared-activated neurons with thermosensitive ion channels that are structurally tuned to match host plant thermogenesis. Comparative analyses revealed that infrared is among the earliest pollination signals, and indicate a deep-time transition from infrared-based to color-dominated signaling in flowering plants. Our findings uncover an ancient sensory modality shaping the early evolution of pollination, one of the world's most vital processes linking plants and animals.}, } @article {pmid41383010, year = {2026}, author = {Li, G and Zhang, Y and Yu, H and Xie, Y and Luo, H and Wang, Y and Tang, J and Zhang, J and Xie, X and Zong, W and Liu, K and Wang, X and Long, Y and Song, Q and Wu, Z and Liu, YG and Chen, L}, title = {A tripartite pollen killer-protector system confers temperature-sensitive inter-subspecific reproductive isolation in rice.}, journal = {Molecular plant}, volume = {19}, number = {2}, pages = {295-312}, doi = {10.1016/j.molp.2025.12.008}, pmid = {41383010}, issn = {1752-9867}, mesh = {*Oryza/genetics/physiology ; *Pollen/genetics/physiology ; *Reproductive Isolation ; *Plant Proteins/metabolism/genetics ; Temperature ; Plant Infertility/genetics ; }, abstract = {Hybrid-sterility-mediated reproductive isolation is pivotal for speciation, yet the underlying molecular mechanisms and environmental responses remain unclear. Here, we report a temperature-sensitive pollen killer-protector system at a three-gene Sa locus for indica-japonica rice hybrid sterility. Genetic analyses identified SaFL[+], a strong pollen protector from Sa-i (indica allele), and SaFL[-], a weak japonica allele from Sa-j, which is exclusively functional under high temperatures. Protein interaction, ubiquitination, and degradation assays showed that SaF[+] and SaM[+] from Sa-i form a pollen-killer complex to bind and ubiquitinate the reactive oxygen species scavenger COX11 for degradation in mitochondria, causing male sterility of the Sa-j pollen. Protein affinity and competitive binding assays indicated that in the Sa-i pollen, SaFL[+] binds SaM[+] to disrupt the killer complex and restore fertility. However, the weak protector SaFL[-] can bind SaM[+] under high temperatures, sparing the Sa-j pollen from sterility. Synteny comparisons and haplotype analyses showed that the Sa locus originated in ancient wild rice and underwent divergence within the Oryza genus during expansion from tropical to temperate environments, which might have driven latitudinal adaptation and reproductive isolation in rice populations. Thus, Sa represents a temperature-sensitive reproductive-isolation system associated with domestication and environmental adaptation in rice.}, } @article {pmid41405130, year = {2025}, author = {Kuznetsov, P and Temereva, E}, title = {Toward the Origin and Evolution of Unique Echiurid Excretory Organs: New Data From Females of Bonellia viridis.}, journal = {Journal of morphology}, volume = {286}, number = {12}, pages = {e70105}, doi = {10.1002/jmor.70105}, pmid = {41405130}, issn = {1097-4687}, mesh = {Animals ; Female ; *Biological Evolution ; Microscopy, Electron, Transmission ; Microscopy, Electron, Scanning ; *Polychaeta/anatomy & histology/ultrastructure ; Anal Canal/ultrastructure/anatomy & histology ; }, abstract = {Echiurids, as nonsegmented annelids, have an excretory system of a special organization. The excretory system of the echiuran worms is known to consist of ultrafiltration zones on blood vessels and anal sacs. Prior to this study, the fine structure of the anal sacs had been described in detail only for Thalassema thalassemum (Thalassematinae). In contrast, the more complex anal sacs of Bonelliinae, which contain additional structural elements such as tubules, remained unexplored. This study describes the anatomy, histology, and ultrastructure of the anal sacs of Bonellia viridis Rolando, 1822 (Bonelliinae) using a set of modern morphological methods: computer microtomography, araldite histology, scanning and transmission electron microscopy. New data suggest functional implications for structural elements of the anal sacs: the conical part and the neck of the funnel, the tubules, and the end sac. The ciliary funnels are responsible for collecting filtrate to their conical parts and can close at their base, thus preventing reverse flow. According to the ultrastructural data, the inner epithelium of the tubules and the end sac modifies the incoming filtrate in two ways. The inner epithelium of the tubules carries out pinocytosis and accumulates electron-dense granules. The inner epithelium of the end sac has a basal labyrinth consisting of basal processes with numerous mitochondria extending deep into the extracellular matrix and indicates active ion transport. Additional zones responsible for ultrafiltration were identified in the outer epithelium of the anal sac-specifically within the tubule and at the base of the funnel. The origin of the echiurid anal sacs as a result of fusion and multiplication of the metanephridia at the posterior growth zone of metameric annelid-like ancestor is suggested.}, } @article {pmid41412833, year = {2026}, author = {Feng, C and Ren, X and Xing, T and Zheng, X and Cheng, T and Huang, S and Gao, C and Yin, J}, title = {Bimodal Visualization of Mitochondrial Viscosity Remodeling, Morphological Dynamics and Interorganelle Networks in Acute Kidney Injury.}, journal = {Analytical chemistry}, volume = {98}, number = {1}, pages = {354-363}, doi = {10.1021/acs.analchem.5c04744}, pmid = {41412833}, issn = {1520-6882}, mesh = {*Acute Kidney Injury/chemically induced/metabolism/pathology/diagnostic imaging ; *Mitochondria/metabolism/pathology/chemistry ; Humans ; Viscosity ; Cisplatin ; Cell Line ; }, abstract = {The spatiotemporal dynamics of mitochondrial viscosity and its regulatory relationship with organelle interaction networks in cisplatin-induced acute kidney injury (AKI) remain poorly understood, primarily due to the absence of high-precision, multiscale, cross-modal imaging technologies. To overcome this limitation, we pioneered a "trinity" molecular probe design strategy that synergistically integrates electrostatic-driven organelle targeting, microenvironment viscosity-responsive activation, and fluorescence-photoacoustic signal coamplification. Based on this paradigm, we developed ACP, an intelligent dual-modal probe that enables functional spatiotemporal mapping of mitochondrial viscosity dynamics in cisplatin-injured HK-2 cells. Furthermore, we established a sophisticated multiparameter quantitative analysis framework, combining dihedral angle spatial conformation analysis, nanometer-scale organelle membrane distance measurement, and mitochondrial morphometry to systematically decode the dynamic evolution of mitochondrial-lysosomal interaction networks during AKI progression. Therefore, the molecular probe technology and multimodal analytical framework developed in this study may open new avenues for AKI research and pave the way for deeper understanding of organelle-level pathophysiology.}, } @article {pmid41419014, year = {2026}, author = {Lynch, M}, title = {Energetics and evolution: Response to Martin.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1867}, number = {2}, pages = {149576}, pmid = {41419014}, issn = {1879-2650}, support = {R35 GM122566/GM/NIGMS NIH HHS/United States ; }, mesh = {*Energy Metabolism ; *Biological Evolution ; *Mitochondria/metabolism ; Humans ; }, abstract = {A recent paper in this journal claims that prior estimates of the bioenergetic costs of producing cells are off by more than 100-fold. Here, it is shown that this conclusion is based on an erroneous interpretation of the methods previously employed by a diversity of authors and that the downstream arguments are conceptually flawed. Likewise, the author's claim that the establishment of the mitochondrion caused a quantum leap in bioenergetic capacity that spurred a revolution in eukaryotic innovation is inconsistent with empirical data and evolutionary theory.}, } @article {pmid41422226, year = {2025}, author = {Si, R and Shen, Z and Sui, Y and Shi, Y and Zhang, Y and Hu, B and Chen, X and Feng, B and Zhu, ML and Sha, X and Ding, N and Zhou, G and Jiang, F and Xu, C and Shen, B}, title = {Suppressing the OTUD7A/KDM5B/GABPA axis enhances the sensitivity of cisplatin through inducing ferroptosis in KRAS-mutant LUAD.}, journal = {Cell death & disease}, volume = {17}, number = {1}, pages = {112}, pmid = {41422226}, issn = {2041-4889}, support = {82272863//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2024KF0228//Nanjing Medical University (NMU)/ ; }, mesh = {*Cisplatin/pharmacology/therapeutic use ; Humans ; *Ferroptosis/drug effects/genetics ; Animals ; *Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; Mice ; *Lung Neoplasms/genetics/drug therapy/pathology/metabolism ; *Adenocarcinoma of Lung/genetics/drug therapy/pathology/metabolism ; Cell Line, Tumor ; *GA-Binding Protein Transcription Factor/metabolism/genetics ; Mutation/genetics ; Reactive Oxygen Species/metabolism ; Antineoplastic Agents/pharmacology ; Mitochondria/metabolism/drug effects ; Mice, Nude ; }, abstract = {KRAS-mutant lung adenocarcinoma (LUAD), due to its evolution of more complex antioxidant metabolic mechanisms, exhibits poorer sensitivity to conventional platinum-based drugs compared to other types of LUAD. Ferroptosis, as a means of inducing cell death in cancer therapy, shows unique features and potential therapeutic effects compared to the conventional form of apoptosis, which is frequently obstructed by drug resistance. In human KRAS-mutant LUAD cell lines and mouse models, we found that the deubiquitinase OTU deubiquitinase 7A (OTUD7A) precisely regulates the lysine demethylase 5B (KDM5B). Inhibition of KDM5B expression increases the H4K20me3 level, which in turn downregulates the expression of transcription factor GABPA associated with mitochondrial function, ultimately promoting the production of more Reactive Oxygen Species (ROS) by mitochondria and inducing ferroptosis. Additionally, in in vivo organoid models, cisplatin (CDDP) induced ferroptosis combined with GABPA inhibition demonstrated superior anticancer effects compared to conventional platinum-based drugs. This research identifies new targets and regulatory networks that hold promise for developing ferroptosis-based therapies for KRAS-mutant LUAD.}, } @article {pmid41432143, year = {2026}, author = {Yuan, F and Li, W and Li, A and Tang, T and Zhang, Y and Xie, S and Li, F and Liu, F}, title = {Mitochondrial remodeling and metabolic reprogramming drive long-term salinity adaptation in Tetrahymena thermophila.}, journal = {mSystems}, volume = {11}, number = {2}, pages = {e0154925}, pmid = {41432143}, issn = {2379-5077}, mesh = {*Tetrahymena thermophila/metabolism/genetics/physiology ; *Mitochondria/metabolism ; *Adaptation, Physiological ; *Salinity ; Transcriptome ; Salt Tolerance ; Salt Stress ; Proteomics ; Metabolic Reprogramming ; }, abstract = {Salinization of inland waters, driven by climate change and human activities, poses a major threat to aquatic ecosystems. While species can swiftly adapt to environmental stress, the molecular mechanisms underpinning this adaptation remain to be fully elucidated. This study seeks to clarify the complex adaptive strategies employed by the freshwater ciliate Tetrahymena thermophila in response to chronic salt stress through the methodologies of experimental evolution and multi-omics integration. The findings indicate that three lineages adapted to salt (ST-4, ST-8, and ST-12), which evolved under a regime of increasing NaCl concentration, demonstrated a trade-off between delayed growth and osmotic resilience. Transcriptomic and proteomic analyses revealed key evolutionary priorities, including (i) the co-upregulation of pathways related to DNA replication, glutathione metabolism, and endoplasmic reticulum (ER) protein processing, (ii) the suppression of lipid catabolism alongside the accumulation of lipid droplets mediated by START2, and (iii) mitochondrial remodeling through the expansion of ER contacts to sustain ATP production. Interestingly, the adaptation to salt appears to tolerate genome instability induced by replication stress through the dysregulation of replisome components, specifically the upregulation of Prim1 and downregulation of LIG, while also evading antioxidant defenses via the compartmentalization of oxidative damage. These results contribute to a framework in which protists effectively balance lipid-mediated osmoregulation, controlled mutagenesis, and organelle metabolism to navigate salinity challenges, thereby offering predictive insights into microbial adaptation thresholds within evolving ecosystems.IMPORTANCESalinization of inland waters is a growing concern due to climate change and human activities. Understanding how organisms adapt to saline environments is vital. Tetrahymena thermophila, a model organism, was studied to explore its adaptation mechanisms. The findings show that through gene regulation, it can acclimate to high salt conditions. The role of mitochondria in metabolic reprogramming during this process is significant. This research contributes to a more profound understanding of how organisms adapt to saline stress and the molecular mechanisms underlying such adaptations, which may aid in predicting and managing the impacts of salinization on aquatic ecosystems.}, } @article {pmid41436641, year = {2026}, author = {Nuryadi, H and Anoop, VK and Kakioka, R and Gojobori, J and Raghavan, R and Yamahira, K}, title = {Routine mitochondrial recombination drives rapid concerted evolution of duplicated control regions in a wild fish.}, journal = {Heredity}, volume = {135}, number = {1}, pages = {46-54}, pmid = {41436641}, issn = {1365-2540}, support = {KAKENHI 17H01675//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; KAKENHI 21H04782//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JPMJCR20S2//MEXT | JST | Core Research for Evolutional Science and Technology (CREST)/ ; }, mesh = {Animals ; *Evolution, Molecular ; *Genome, Mitochondrial ; *Recombination, Genetic ; Gene Conversion ; Homologous Recombination ; *Gene Duplication ; *Mitochondria/genetics ; Phylogeny ; *Locus Control Region ; DNA, Mitochondrial/genetics ; }, abstract = {Duplications and concerted evolution of control regions (CRs) in animal mitogenomes have been reported across diverse taxa, yet the tempo and mechanism of gene conversion remain poorly understood. Here, we assembled the complete mitochondrial genome of the western Indian ricefish Oryzias setnai and found that the CR is duplicated. Comparative analysis of CR1 and CR2 sequences across individuals sampled throughout the species' range revealed that they are identical in most individuals, and differ by only one or two mutations in the rest-indicating recent and ongoing concerted evolution. We estimated that gene conversion events occur at a rapid pace, on the order of once every 1000 years or less. Using both short- and long-read amplicon sequencing, we directly detected a substantial number of recombinant mitogenome molecules resulting from homologous recombination between CR paralogues. This provides the first clear evidence that homologous recombination is the mechanism driving mitochondrial gene conversion. Our findings challenge the prevailing view that recombination in animal mitochondria is exceedingly rare, and demonstrate that mitogenome recombination can occur routinely in natural populations.}, } @article {pmid41446184, year = {2025}, author = {Lee, S and Chakraborty, S and Kim, S and Ali, A and Mitra, K and Zajac, M and Brown, A and Pincus, D and Krishnan, Y}, title = {Organelles harbour pH gradients.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41446184}, issn = {2692-8205}, support = {RM1 GM153533/GM/NIGMS NIH HHS/United States ; R01 GM147197/GM/NIGMS NIH HHS/United States ; R01 NS112139/NS/NINDS NIH HHS/United States ; DP1 GM149751/GM/NIGMS NIH HHS/United States ; R01 GM138689/GM/NIGMS NIH HHS/United States ; }, abstract = {Organelle pH is critical to organelle identity and function. Resident proteins that define each organelle modify transiting cargo proteins, with both retention and trafficking between organelles governed by pH-dependent mechanisms. For example, lysosomal enzymes bind mannose-6-phosphate receptors at the higher pH (~6.5) of the Golgi and dissociate at the lower pH (~5.5) of late endosomes[1]. Proteins that stray from the endoplasmic reticulum (ER) are captured by KDEL receptors in the acidic Golgi and returned into the neutral ER[2,3]. This pH-tuned trafficking system compartmentalizes organelle function and prevents mis-localization of critical enzymes[4]. Dysregulated organelle pH disrupts their function and leads to various diseases. Because protons move rapidly in water, the pH within a single organelle is currently assumed to be spatially uniform[5]. Here, using a reporter sensitive from pH 5.5 - 10.5 to map a spectrum of organelles at high resolution, we discovered that pH gradients exist within single, large or long organelles such as the ER and mitochondria, and in membrane-less organelles without ion-transporting proteins such as the nucleolus. These new findings upend our understanding of organellar pH, prompting new questions about proton diffusion within the cell, and its potential consequences on organelle function.}, } @article {pmid41453915, year = {2025}, author = {Belosludtsev, KN and Dubinin, MV and Belosludtseva, NV}, title = {Ca[2+]-Dependent Mitochondrial Permeability Transition Pore: Structure, Properties, and Role in Cellular Pathophysiology.}, journal = {Biochemistry. Biokhimiia}, volume = {90}, number = {12}, pages = {1789-1810}, doi = {10.1134/S0006297925602369}, pmid = {41453915}, issn = {1608-3040}, mesh = {Humans ; Mitochondrial Permeability Transition Pore ; *Calcium/metabolism ; *Mitochondrial Membrane Transport Proteins/metabolism/chemistry/genetics ; Animals ; *Mitochondria/metabolism ; Mitochondrial Membranes/metabolism ; }, abstract = {The Mitochondrial Permeability Transition pore (MPT pore) activated by Ca[2+] ions is a phenomenon that has long been the subject of intense study. Cyclophilin D-dependent opening of the MPT pore in mitochondria in response to calcium overload and oxidative stress leads to swelling of the mitochondrial matrix, depolarization of the inner membrane and dysregulation of ion homeostasis. These processes are accompanied by damage to mitochondrial membranes and, ultimately, to cell death. Despite decades of research, the molecular identity of the MPT pore remains unclear. Currently, the inner membrane proteins - ATP synthase and adenine nucleotide translocator (ANT) - are considered to be its key structural components, along with the regulatory protein cyclophilin D. The involvement of the MPT pore in the progression of various pathological conditions and diseases, as well as in a number of physiological processes, such as the regulation of cellular bioenergetics and rapid release of Ca[2+], is widely discussed. This review summarizes modern molecular genetic data on the putative structure of the MPT pore, traces the evolution of views on its functioning - from interpreting it as a simple experimental artifact to its recognition as a putative key regulator of energy metabolism - and also considers the mechanisms of its regulation and its multifaceted pathophysiological role.}, } @article {pmid41453922, year = {2025}, author = {Muravyov, G and Knorre, DA}, title = {Mechanisms of Intracellular Selection of Mitochondrial DNA.}, journal = {Biochemistry. Biokhimiia}, volume = {90}, number = {12}, pages = {1919-1928}, doi = {10.1134/S0006297925603296}, pmid = {41453922}, issn = {1608-3040}, mesh = {*DNA, Mitochondrial/genetics/metabolism ; Humans ; Animals ; *Mitochondria/genetics/metabolism ; Heteroplasmy ; Saccharomyces cerevisiae/genetics ; }, abstract = {Eukaryotic cells contain multiple mitochondrial DNA (mtDNA) molecules. Heteroplasmy is coexistence in the same cell of different mtDNA variants competing for cellular resources required for their replication. Here, we review documented cases of emergence and spread of selfish mtDNA (i.e., mtDNA that has a selective advantage in a cell but decreases cell fitness) in eukaryotic species, from humans to baker's yeast. The review discusses hypothetical mechanisms enabling preferential proliferation of certain mtDNA variants in heteroplasmy. We propose that selfish mtDNAs have significantly influenced the evolution of eukaryotes and may be responsible for the emergence of uniparental inheritance and constraints on the mtDNA copy number in germline cells.}, } @article {pmid41463293, year = {2025}, author = {Xie, V and Franco, MC and Martin, LJ}, title = {Human Mutant Dynactin Subunit 1 Causes Profound Motor Neuron Disease Consistent with Possible Mechanisms Involving Axonopathy, Mitochondriopathy, Protein Nitration, and T-Cell-Mediated Cytolysis.}, journal = {Biomolecules}, volume = {15}, number = {12}, pages = {}, pmid = {41463293}, issn = {2218-273X}, support = {R01 NS102479/NS/NINDS NIH HHS/United States ; 1R01NS107417-04A1/NH/NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Anterior Horn Cells/metabolism/pathology ; *Axons/pathology ; *Dynactin Complex/genetics ; Mice, Transgenic ; *Mitochondrial Diseases/genetics ; *Motor Neuron Disease/genetics ; *Motor Neurons/metabolism/pathology ; Mutation ; *Protein Processing, Post-Translational/genetics ; Quinazolinones/pharmacology ; Spinal Cord Diseases ; T-Lymphocytes/immunology ; *Tyrosine/metabolism/analogs & derivatives ; Mitochondrial Dynamics/drug effects ; Male ; Female ; }, abstract = {Mutations in the gene encoding the p150 subunit of the dynactin complex (DCTN1) are linked to amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, and Perry syndrome. These neurodegenerative diseases can cause muscle weakness and atrophy, parkinsonian-like symptoms, and paralysis. To examine the evolution of neuropathology caused by a mutation in DCTN1 and cellular mechanisms of disease for therapeutic discovery, we characterized mice expressing either human wildtype or mutant (G59S) DCTN1. Neuron-specific expression of mutant, but not wildtype, DCTN1 caused fatal age-related paralytic disease and motor neuron (MN) degeneration in the spinal cord with axonopathy and chromatolysis without apoptotic morphology. MNs became positive for cleaved caspase-3, cleaved caspase-8, and nitrated Hsp90. Mitochondria accumulated and appeared fragmented and dysmorphic and then were lost. This pathology was accompanied by invasion of CD95- and CD8-positive mononuclear T cells into the ventral horn and accumulation of TNFα and IL9. Administration of the mitochondrial division inhibitor-1 (Mdivi-1) protected MNs and extended the lifespan of G59S-DCTN1 mice. A mitochondrial permeability transition pore inhibitor also extended lifespan. Thus, mutant DCTN1 causes degeneration of MNs associated with axonopathy, mitochondriopathy, nitrative stress, and caspase activation. It appears as retrograde neurodegeneration and inflammatory T-cell-like cytolysis. Mitochondria are possible therapeutic targets in DCTN1-linked neurodegenerative disorders.}, } @article {pmid41463501, year = {2025}, author = {Sun, YT and Yang, WX}, title = {Gatekeepers of the Germ Line: How Mitochondria Shape Reproductive Evolution in Metazoans.}, journal = {Biology}, volume = {14}, number = {12}, pages = {}, pmid = {41463501}, issn = {2079-7737}, support = {32270555//National Natural Science Foundation of China/ ; 32072954//National Natural Science Foundation of China/ ; }, abstract = {Mitochondria play essential roles for animal reproduction, influencing not only cellular energetics but also gamete quality, inheritance and evolutionary patterns. Currently, most research still focuses on chordates or mitochondrial diseases and their impact on the health of germ cells. However, few studies focus on integrative synthesis that connect comparative morphology, inheritance mechanisms and evolutionary theory. In this review, we integrate cross-phyla evidence to explore two interconnected dimensions: the fate of mitochondria during gametogenesis and the strategy shaping their evolution. We compare mitochondrial morphology, distribution, and metabolic strategies in gametogenesis, revealing how these traits align with reproductive modes and ecological adaptations. Then we further discuss how mitochondrial genome evolution, bottleneck effects and mito-nuclear coevolution contribute to germline stability and maternal inheritance. Special attention is given to exceptional systems such as Doubly Uniparental Inheritance (DUI) in bivalves, which challenges conventional mode of strictly maternal transmission and illuminates the flexibility of mito-nuclear evolution. Altogether, these perspectives highlight mitochondria as gatekeepers and evolutionary recorders in the reproductive systems across metazoans, providing a unifying framework for future research across ecology, evolution and molecular biology.}, } @article {pmid41463520, year = {2025}, author = {Wu, Y and Xu, J and Hong, T and He, J and Chen, Y and Zhang, Y and Hu, X and Sun, H and He, L and Liu, D}, title = {The Complete Mitochondrial Genome of Callicarpa americana L. Reveals the Structural Evolution and Size Differences in Lamiaceae.}, journal = {Biology}, volume = {14}, number = {12}, pages = {}, pmid = {41463520}, issn = {2079-7737}, support = {20252BAC200368//Natural Science Foundation Joint Fund Key Project of Jiangxi Province/ ; JZB2412//Doctoral Scientific Research Start-up Project of Jinggangshan University/ ; 20255-011349//Guiding Science and Technology Project of Ji'an City/ ; 20244BAB28058//Natural Science Foundation Joint Fund Key Project of Jiangxi Province/ ; 2023SSY02111//Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity/ ; }, abstract = {Callicarpa americana L. is a member of the Lamiaceae family with important ornamental and medicinal value. Although the chloroplast genome of Lamiaceae has been extensively studied, its mitochondrial genome remains unreported, limiting a comprehensive understanding of the phylogeny and genome evolution of Lamiaceae. In this study, the complete mitochondrial genome of C. americana was successfully assembled for the first time. The genome is 499,565 bp in length, showing a complex multi-branched closed-loop structure that contains 37 protein-coding genes, 23 tRNA genes, and 4 rRNA genes. The difference in mitochondrial genome size is relatively large compared to Orobanchaceae species, but the difference in GC content is not obvious. The expansion of genome size was mainly due to the accumulation of non-coding regions and repetitive sequences. Meanwhile, two pairs of long repetitive sequences (LR3 and LR5) mediated homologous recombination. The mitogenome was also identified; there were a total of 494 C-to-U RNA editing sites in protein-coding genes. In addition, 42 mitochondrial plastid DNA fragments (MTPTs) were detected, with a total length of 21,464 bp, accounting for 4.30% of the genome. Repeat sequence analysis showed that tetranucleotide SSR was the most abundant repeat type in the mitochondria of Lamiaceae. Phylogenetic analysis based on the alignment of 32 protein-coding gene sequences showed that Callicarpa is sister to the other eight species of Lamiaceae. This work fills an important gap by presenting the first complete mitochondrial genome of C. americana, providing an important data resource for further understanding the structural evolution, dynamic recombination mechanism, and phylogeny of the mitochondrial genome of Lamiaceae.}, } @article {pmid41480148, year = {2025}, author = {Lu, Z and Xia, R and Xu, A and Gu, J and Cai, H and Liu, Y and Koonin, EV and Li, M}, title = {Oxygen-adaptive plasticity of Asgard archaea dependent on terminal oxidase and globin.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.11.07.685452}, pmid = {41480148}, issn = {2692-8205}, abstract = {The oxygenation of ancient Earth is thought to have driven eukaryogenesis, beginning with the endosymbiosis of an aerobic alphaproteobacterium (proto-mitochondria) with an archaeal host. Given that the archaeal host likely evolved from within Asgard archaea (phylum Promethearchaeota), the metabolic traits of Asgard archaea could provide key insights into eukaryotic origins. Although Asgard archaea cultured to date are obligate anaerobes, their genomes encode oxygen-adaptive proteins, suggesting they might be oxygen-tolerant. Here, we demonstrate that some Asgard archaea, in particular, Hodarchaeales , the closest known relatives of eukaryotes, and Kariarchaeaceae , exhibit oxygen adaptation mediated by terminal oxidase and globin. Phylogenetic analysis reveals long-term vertical evolution of terminal oxidases in Asgard archaea, suggesting ancient adaptation to molecular oxygen. By contrast, globin was likely acquired by Asgard archaea via horizontal gene transfer from facultative aerobic Chloroflexales bacteria. Heterologous expression of the Asgard globin enhances aerobic growth of Haloarchaea and Escherichia coli in the presence of terminal oxidase-dependent electron transfer chain, suggesting that Asgard growth benefits from ambient oxygen. The Asgard globin gene is embedded in an oxygen-sensitive bidirectional promoter region, with one promoter driving oxygen-induced globin expression, and the other anaerobically activating expression of two enzymes, PdxS and PdxT, involved in a pyridoxal 5'-phosphate biosynthesis. The Asgard globin and promoter region exhibit high functional robustness across archaea and bacteria, and could contribute to the symbiosis between the Asgard and aerobic bacterial partners. These findings highlight the oxygen-adaptive plasticity of Asgard archaea and its potential contribution to eukaryogenesis.}, } @article {pmid41499318, year = {2026}, author = {Melrose, J}, title = {Roles for Electrochemical Proton Gradients in Mitochondrial Energy Production and Neurosensory Processes in Health and Disease.}, journal = {Developmental neurobiology}, volume = {86}, number = {1}, pages = {e70006}, doi = {10.1002/dneu.70006}, pmid = {41499318}, issn = {1932-846X}, support = {//Melrose Personal Research Fund/ ; }, mesh = {Humans ; Animals ; *Mitochondria/metabolism ; *Energy Metabolism/physiology ; *Protons ; *Proton-Motive Force/physiology ; Oxidative Stress/physiology ; *Nervous System Diseases/metabolism ; Brain/metabolism ; }, abstract = {This study reviews the roles of proton electrochemical gradients in ubiquitous mitochondrial energy production systems in cellular activation and functions in neurosensory signaling. Proton electrochemical gradients crucially shaped the evolution of life. The emergence of the proton-motive force in mitochondria was fundamental in energy production and central to the function of eukaryotic cells. Dysfunctional mitochondria, however, result in impaired formation of proton gradients and a wide spectrum of diseases. This is particularly prominent in tissues with high energetic demands, such as muscle and nervous tissues. Oxidant stress generated by dysfunctional proton conductance in the brain results in Alzheimer's and Parkinson's disease, muscular sclerosis, amyotrophic sclerosis, and Huntington's disease. In these disorders, oxidative stress, protein misfolding, and neuroinflammation lead to dysfunctional neuronal activity, neuronal damage, and death. Advancements in nanozyme-engineered synthetic enzymes offer a promising innovative approach to the treatment of these disorders. Nanozymes target proton conductance and the oxidant species they generate, scavenging oxygen free radicals and restoring redox balance, and offer neuronal protection and functional recovery of brain tissues. Neural injury and associated neurological diseases affect almost 1 billion people globally, so there is a clear need to develop effective methods that stimulate neural repair and regeneration. Glycosaminoglycans with proton capture and transport properties regulate intercellular signaling processes, synaptic functions, and cellular communication. Electroconductive hydrogels are showing impressive results in neural repair and regeneration. Glycosaminoglycans, particularly keratan sulfate, show useful electroconductive proton capture and transport properties, suggesting they may be worth evaluation in such procedures.}, } @article {pmid41499932, year = {2026}, author = {Gabas, ML and Otvos, LP and Almeida, NBO and Farias, SO and Val, GS and Machado, LESF}, title = {Design-driven optimization of mitochondrial protein phosphatases for in vitro studies.}, journal = {Biochemical and biophysical research communications}, volume = {799}, number = {}, pages = {153200}, doi = {10.1016/j.bbrc.2025.153200}, pmid = {41499932}, issn = {1090-2104}, mesh = {*Phosphoprotein Phosphatases/genetics/chemistry/metabolism/isolation & purification ; *Mitochondrial Proteins/genetics/chemistry/metabolism ; *Mitochondria/enzymology ; Cloning, Molecular/methods ; Humans ; Solubility ; Recombinant Fusion Proteins/genetics/chemistry/metabolism ; }, abstract = {Molecular cloning and heterologous protein expression are essential for investigating protein function and interactions with ligands such as small molecules, drugs, and other proteins. Studies on the redox regulation, intermolecular interactions, structural determination, and structural dynamics of mitochondrial protein phosphatases require high-yield expression of soluble, catalytically active enzymes. Accordingly, the aim of this study was to optimize the cloning, expression, and soluble purification of mitochondrial protein phosphatases in their monomeric and active forms. We designed 22 expression constructs encoding the mitochondrial protein phosphatases PTPMT1, PP2Cm, PPTc7, and PGAM5, incorporating variations with or without the mitochondrial targeting sequence (MTS) and solubility-enhancing fusion tags. Our results demonstrate that, for matrix localized phosphatases, MTS removal combined with a soluble fusion tag is essential for obtaining soluble, structurally stable, properly folded, and catalytically active proteins. In contrast, intermembrane space phosphatase PGAM5 was well structured and active across constructs, thoug MTS presence reduced expression yields and increased protein instability. Overall, this work underscores the critical role of rational construct design for the successful production of mitochondrial protein phosphatases suitable for in vitro biochemical and structural studies.}, } @article {pmid41508847, year = {2026}, author = {Łabędzka-Dmoch, K and Bui, THD and Piątkowski, J and Dilling, M and Jagiełło, P and Kabza, W and Golik, P}, title = {Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts.}, journal = {Molecular biology and evolution}, volume = {43}, number = {2}, pages = {}, pmid = {41508847}, issn = {1537-1719}, support = {IDUB 501-D114-20-1004310//Excellence Initiative-Research University/ ; OPUS 2015/19/B/NZ2/00201//National Science Center/ ; }, mesh = {*Candida albicans/genetics/pathogenicity/metabolism ; *Mitochondria/metabolism/genetics ; Transcription Factors/genetics/metabolism ; Virulence/genetics ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal ; Fungal Proteins/genetics/metabolism ; Oxidative Stress ; Saccharomyces cerevisiae/genetics ; Adaptation, Physiological/genetics ; Evolution, Molecular ; Stress, Physiological ; Transcription, Genetic ; Mitochondrial Proteins/genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; }, abstract = {The pathway involving the paralogous transcription factors Rtg1 and Rtg3 was first described in Saccharomyces cerevisiae as the retrograde regulation that adapts cellular metabolism in response to the state of mitochondrial respiration. We investigated the evolution of this pathway by studying its target genes in respiratory-deficient mutants of Candida albicans-a phylogenetically distant and metabolically distinct yeast species. We show that in C. albicans the Rtg pathway is also responsible for adaptation to cellular stresses related to respiratory dysfunction, but the repertoire of its target genes is different than in S. cerevisiae, and includes genes encoding proteins involved in alternative respiration, oxidative stress, mitophagy, and other aspects of metabolism. We also traced the evolution of the main components of the Rtg pathway and its target genes in the budding yeast (Saccharomycotina) subphylum. We show that the system originated within this clade following a single duplication of the gene encoding the ancestor of Rtg1 and Rtg3, but employs other factors, like the regulatory proteins Rtg2 and Mks1 that were likely present in the last common ancestor of budding yeasts. The regulation of the Rtg transcription factors in C. albicans is different than in S. cerevisiae, as both Rtg2 and Mks1 were lost in the majority of Serinales. Among the target genes, of particular interest is the evolution of the alternative oxidase (Aox), which was either lost or duplicated in multiple independent events. The presence of Aox strongly correlates with the mitochondrially encoded Complex I-a major source of oxidative stress.}, } @article {pmid41514857, year = {2025}, author = {Zhan, Q and Tang, Y and Zhao, Y and Hou, S and Huang, Y and Zhao, X and Chen, Y and Xue, X}, title = {Complete Mitochondrial Genome Sequencing of Brachypelma albiceps and Comparative Codon Usage Bias Analysis Across Seven Mygalomorphae Species.}, journal = {Biology}, volume = {15}, number = {1}, pages = {}, pmid = {41514857}, issn = {2079-7737}, support = {LGZD202507//Fundamental Research Funds for the Central Universities/ ; 2025//Qinglan Project" of Jiangsu Province in 2025/ ; 32100366//National Natural Science Foundation of China/ ; 2022YFC2601200//National Key R&D Program of China/ ; "Public Security Technology" project (2022)//the Jiangsu Province "14th Five-Year Plan" Key Construction Discipline/ ; }, abstract = {Tarantulas (family Theraphosidae) are ecologically significant invertebrate predators in terrestrial ecosystems, but many species face threats from habitat fragmentation and unsustainable collection for the international pet trade. Brachypelma albiceps, a CITES Appendix II-listed species, lacks comprehensive mitochondrial genome characterization, limiting phylogenetic and evolutionary studies. Here, we report a complete mitochondrial genome sequence for B. albiceps (13,856 bp; GC content 32.84%) and provide detailed annotation. The genome exhibits typical metazoan mitochondrial organization, containing 13 protein-coding genes (PCGs), 22 tRNAs, and 2 rRNAs, with an AT-rich nucleotide composition (67.16%) characteristic of arthropod mitochondria. Comparative analyses of B. albiceps and six other Mygalomorphae species revealed strong biases toward A/T-ending codons and avoidance of G/C-ending codons. ENC-GC3s, neutrality, and PR2 analyses consistently indicate that natural selection plays a dominant role in shaping synonymous codon usage, with mutation pressure also contributing. Phylogenetic reconstruction based on 10 high-quality mitochondrial protein-coding genes from 23 spider species confirmed the placement of B. albiceps within the family Theraphosidae and its close phylogenetic relationship to Cyriopagopus species. These results provide valuable genomic resources for the Theraphosidae systematics, enhance our understanding of codon bias evolution, and provide critical DNA barcode data for forensic identification of CITES-regulated specimens in the illegal wildlife trade.}, } @article {pmid41520850, year = {2026}, author = {Gudiksen, A and Hansen, CC and van der Stede, T and Daugaard, AH and Schmidt, JH and Ringholm, S and Merimi, M and Al-Obaidi, FR and Kristoffersen, AT and Zole, E and Regenberg, B and Kjøbsted, R and Wojtaszewski, J and Hellsten, Y and Pilegaard, H}, title = {MOTS-c improves intrinsic muscle mitochondrial bioenergetic health and efficiency in a PGC-1α/AMPK-dependent manner.}, journal = {Free radical biology & medicine}, volume = {246}, number = {}, pages = {682-696}, doi = {10.1016/j.freeradbiomed.2026.01.002}, pmid = {41520850}, issn = {1873-4596}, mesh = {Animals ; *AMP-Activated Protein Kinases/metabolism/genetics ; *Energy Metabolism/drug effects ; Mice ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; *Mitochondria, Muscle/metabolism/drug effects ; *Muscle, Skeletal/metabolism/drug effects ; Humans ; Mice, Transgenic ; Mitochondrial Proteins/metabolism ; *Transcription Factors/metabolism ; Reactive Oxygen Species/metabolism ; Oxidative Stress ; }, abstract = {Mitochondrial-derived peptides are a small class of regulatory peptides encoded by short open reading frames in mitochondrial DNA. One such peptide, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), has been shown to exert numerous beneficial effects on whole-cell and systemic metabolic parameters when administered exogenously. However, potential MOTS-c-mediated effects on mitochondrial bioenergetics have been largely overlooked. Therefore, the primary aim of the present study was to elucidate whether and, if so, how MOTS-c regulates skeletal muscle (SkM) mitochondrial function. We demonstrate, using two distinct transgenic mouse strains, that administration of MOTS-c augments muscle mitochondrial bioenergetic performance through reliance on both the transcriptional coactivator, Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), and cellular energy-sensing kinase, 5' adenosine monophosphate-activated protein kinase (AMPK). These effects seem to be exerted without apparent impact on mitochondrial respiratory protein content, alluding to intrinsic mitochondrial changes rather than changes in volume. Furthermore, MOTS-c treatment lowers mitochondrial reactive oxygen species (ROS) emission and ROS-related protein damage indicating substantial alleviation of cellular oxidative stress. RNA-sequence data reveal the effects of MOTS-c treatment to potentially be exerted subtly across a number of mitochondrial parameters such as redox handling, mitochondrial integrity and OXPHOS efficiency, jointly indicating a mechanistic basis for the observed functional improvements in mitochondrial bioenergetics. Despite increased interstitial MOTS-c levels no change was observed in the arterio-venous difference during one-legged knee extensor exercise in humans. This suggests that SkM may not be the source of circulating MOTS-c in response to exercise.}, } @article {pmid41528575, year = {2026}, author = {Punia, V and Das, G and Kumar, S and Verma, R and Nath, S and Choudhary, R and Chourasia, R and Nayak, A and Singh, AP}, title = {Comparative diagnostic performance of microscopy and PCR assays with preliminary mitochondrial sequence analysis of Babesia species infecting dogs in Jabalpur, central India.}, journal = {Molecular biology reports}, volume = {53}, number = {1}, pages = {286}, pmid = {41528575}, issn = {1573-4978}, mesh = {Animals ; Dogs ; *Babesia/genetics/isolation & purification ; India ; *Babesiosis/diagnosis/parasitology/genetics ; *Polymerase Chain Reaction/methods/veterinary ; *Dog Diseases/parasitology/diagnosis/genetics ; *Microscopy/methods ; Phylogeny ; Mitochondria/genetics ; Sequence Analysis, DNA/methods ; Sensitivity and Specificity ; Electron Transport Complex IV/genetics ; DNA, Mitochondrial/genetics ; }, abstract = {BACKGROUND: The present study evaluated the diagnostic performance of conventional microscopy and polymerase chain reaction (PCR) based assays for the detection of Babesia infections in dogs, including semi-nested PCR (SN-PCR) targeting the 18 S rRNA gene and single-round PCR (SR-PCR) assays targeting the mitochondrial cytochrome b (cytb) and cytochrome c oxidase subunit 1 (cox1) genes for B. gibsoni and B. vogeli, respectively. Mitochondrial sequence variation was further assessed by integrating newly generated sequences from Jabalpur, Madhya Pradesh (central India), with global reference datasets.

METHODS AND RESULTS: A total of 100 blood samples from dogs suspected of having haemoprotozoan infections were analysed between June 2022 and May 2023. Microscopic examination of Giemsa-stained smears detected Babesia parasites in 13% of the samples, whereas the 18 S rRNA SN-PCR assay identified infections in 29%, comprising B. gibsoni (25%) and B. vogeli (4%). Representative sequences showed 98-99% identity with corresponding GenBank reference sequences. Representative sequences showed 98-99% identity with corresponding GenBank reference sequences. Compared with SN-PCR, microscopy demonstrated moderate sensitivity but perfect specificity, resulting in an overall diagnostic accuracy of 84.0% (p < 0.01). Mitochondrial SR-PCR assays detected B. gibsoni and B. vogeli in 5% and 4% of the samples, respectively. The cytb-based assay showed higher sensitivity and a significant diagnostic association (p < 0.01) than the cox1 assay, whereas the cox1 assay demonstrated lower sensitivity with a non-significant association (p > 0.05). All PCR assays showed 100% specificity and positive predictive value. Bayesian phylogenetic and haplotype analyses indicated that B. gibsoni cytb sequences formed a monophyletic lineage with limited regional structuring, with Indian isolates clustering within a distinct sub-lineage. In contrast, B. vogeli cox1 sequences exhibited low global diversity with a dominant shared haplotype across geographic regions.

CONCLUSIONS: The 18S rRNA SN-PCR assay showed the highest sensitive method for detecting Babesia infections in dogs. Mitochondrial markers (cytb and cox1) supported species confirmation and comparative phylogenetic assessment, highlighting the complementary value of nuclear and mitochondrial gene targets for molecular surveillance and control of canine babesiosis in India.}, } @article {pmid41533582, year = {2026}, author = {Ahrendt, SR and Haridas, S and Stong, S and Salamov, A and Steindorff, A and LaButti, K and Riley, R and Shabalov, I and Lukashin, I and Dusheyko, S and Schulz, F and Romero, MF and Villada, JC and Grigoriev, IV and Mondo, SJ}, title = {Comparative mitogenomics of kingdom Fungi - evolutionary insights and metagenomic applications.}, journal = {Nucleic acids research}, volume = {54}, number = {2}, pages = {}, pmid = {41533582}, issn = {1362-4962}, support = {//U.S. Department of Energy Joint Genome Institute/ ; DE-AC02-05CH11231//U.S. Department of Energy/ ; }, mesh = {*Genome, Mitochondrial ; *Evolution, Molecular ; *Metagenomics/methods ; *Fungi/genetics/classification ; Phylogeny ; Ascomycota/genetics ; Genome, Fungal ; RNA, Transfer/genetics ; Oxidative Phosphorylation ; Molecular Sequence Annotation ; Mitochondria/genetics ; Cell Nucleus/genetics ; }, abstract = {Mitochondria are essential components of eukaryotic cells, responsible for ATP production through oxidative phosphorylation. Despite their biological importance, unique challenges have hindered the adoption of automated mitochondrial genome (mitogenome) annotation methods, obstructing mitochondrial comparative genomics in a broad evolutionary context. Using Fungi as a study system and a Joint Genome Institute (JGI) annotated high-quality reference set, we observed broad patterns of mitochondrial evolution across the kingdom. We found that the median fungal mitogenome size is 58 kb and identified exceptionally large examples over 1 Mb in Pezizomycetes. All 14 expected oxidative phosphorylation protein-coding genes, plus rps3, were generally conserved. We found evidence of major evolutionary transitions within the Ascomycota, including the transfer of mitochondrially encoded atp8 and atp9 to the nuclear genomes across the Pezizomycotina and shifts in mitogenome tRNA patterns across the kingdom. We found substantial concordance between mitochondrial and nuclear evolution, enabling us to document 3131 total fungal mitogenomes from JGI-derived metagenomic datasets. We also identified 6467 total undeclared mitogenomes embedded in Genbank fungal nuclear assemblies. We provide interactive tools for mitogenome analysis through the JGI MycoCosm platform. Collectively, this work generated nearly 10 000 new fungal mitogenome annotations, providing a foundation and resources for future exploration of comparative fungal mitogenomics.}, } @article {pmid41535464, year = {2026}, author = {Tobiasson, V and Luo, J and Wolf, YI and Koonin, EV}, title = {Dominant contribution of Asgard archaea to eukaryogenesis.}, journal = {Nature}, volume = {650}, number = {8100}, pages = {141-149}, pmid = {41535464}, issn = {1476-4687}, mesh = {Alphaproteobacteria/genetics ; Archaea/genetics/classification/metabolism/cytology ; *Biological Evolution ; *Eukaryota/genetics/cytology/classification ; Eukaryotic Cells/cytology/metabolism ; Mitochondria/genetics/metabolism ; Phylogeny ; Symbiosis/genetics ; }, abstract = {The origin of eukaryotes is one of the key problems in evolutionary biology[1,2]. The demonstration that the last eukaryotic common ancestor (LECA) already contained the mitochondrion-an endosymbiotic organelle derived from an alphaproteobacterium-and the discovery of Asgard archaea-the closest archaeal relatives of eukaryotes[3-7]-inform and constrain evolutionary scenarios of eukaryogenesis[8]. We conducted a comprehensive analysis of the origins of core eukaryotic genes tracing to the LECA within a rigorous statistical framework centred around evolutionary hypothesis testing using constrained phylogenetic trees. The results show dominant contributions of Asgard archaea to the origin of most of the conserved eukaryotic functional systems and pathways. A limited contribution from Alphaproteobacteria was identified, relating primarily to energy transformation systems and Fe-S cluster biogenesis, whereas ancestry from other bacterial phyla was scattered across the eukaryotic functional landscape, without clear, consistent trends. These findings imply a model of eukaryogenesis in which key features of eukaryotic cell organization evolved in the Asgard lineage leading to the LECA, followed by the capture of the alphaproteobacterial endosymbiont and augmented by numerous but sporadic horizontal acquisitions of genes from other bacteria both before and after endosymbiosis.}, } @article {pmid41545150, year = {2026}, author = {Liang, L and Feng, Y and Han, Z and Zhang, F and Fu, A and Gao, X and Liu, W and Yang, Q and Yang, J and Tang, W}, title = {Comparative analysis of mitochondrial genomes and evolutionary characteristics of five Alternaria species causing potato leaf spot diseases.}, journal = {Fungal biology}, volume = {130}, number = {1}, pages = {101715}, doi = {10.1016/j.funbio.2025.101715}, pmid = {41545150}, issn = {1878-6146}, mesh = {*Alternaria/genetics/classification/isolation & purification ; Phylogeny ; *Evolution, Molecular ; *Genome, Mitochondrial ; *Plant Diseases/microbiology ; Genetic Variation ; Genome, Fungal ; }, abstract = {Mitochondria play a central role in fungal metabolism, adaptation, and pathogenesis, yet the evolutionary dynamics of mitochondrial genomes in plant-pathogenic Alternaria species remain poorly understood. In this study, we conducted a comprehensive comparative mitochondrial genomes analysis of five economically important Alternaria species-Alternaria burnsii, A. tenuissima, A. arborescens, A. alternata, and A. gossypina-to investigate structural architecture, genomic variation, selection pressures, repeat element dynamics, and phylogenetic relationships. The mitochondrial genomes exhibited a conserved gene content of 13-14 core genes, 30-33 tRNA and 2 rRNA, but varied in size due to differences in intron insertions, intergenic spacers, and repetitive sequences. Strong A/U-biased codon usage was observed across species, consistent with high AT-richness and translational optimization. Purifying selection dominated across essential respiratory complexes (cox1-3, atp6-9 and cob), indicating functional constraint, while signals of positive selection and pseudogenization (disrupted rps3 in A. burnsii YUN-Z1107) suggest lineage-specific adaptations. We identified evolutionary hotspots in both coding and non-coding regions enriched with InDeLs and repeat expansions. A total of 920 simple sequence repeats (SSRs) were annotated, with A. burnsii YUN-Z1107 showing the highest SSR density, particularly pentanucleotide motifs, implicating replication slippage in genome plasticity. Long repetitive elements were associated with intron mobility and possible recombination events, especially in A. arborescens YUN-Z0872. Phylogenomic analysis of 29 Ascomycota species confirmed a monophyletic Alternaria clade within Pleosporales, although limited resolution within the genus suggests complex evolutionary histories. Our findings support a "conserved core with flexible periphery" model of mitochondrial genomes evolution, where mitochondrial innovation contributes to host adaptation and pathogenicity. This study highlights the mitochondrial genomes as an active driver of fungal evolution and provides a foundation for exploring mitochondria-host coevolution in plant-pathogen interactions.}, } @article {pmid41548483, year = {2026}, author = {Meguro-Horike, M and Iwata, K and Matsuzaki, H and Horike, SI}, title = {Haploinsufficiency of MBD5 and MBD6 impairs mitochondrial respiration through chromatin-mediated gene regulation.}, journal = {Biochemical and biophysical research communications}, volume = {800}, number = {}, pages = {153288}, doi = {10.1016/j.bbrc.2026.153288}, pmid = {41548483}, issn = {1090-2104}, mesh = {Humans ; *Mitochondria/metabolism/genetics ; *Haploinsufficiency ; *Chromatin/metabolism/genetics ; *DNA-Binding Proteins/genetics/metabolism ; Cell Line, Tumor ; *Gene Expression Regulation ; Cell Respiration/genetics ; }, abstract = {Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, yet the molecular mechanisms linking ASD-associated genes to cellular dysfunction remain incompletely understood. Among methyl-CpG binding domain (MBD) proteins, MBD5 and MBD6 are recurrently disrupted in individuals with ASD, but their roles in neuronal cells remain poorly defined. Here, we investigated the cellular and transcriptional consequences of MBD5 and MBD6 haploinsufficiency using human neuroblastoma SH-SY5Y cells. We established MBD5-and MBD6-heterozygous SH-SY5Y cell lines by genome editing and performed genome-wide transcriptome analysis. Microarray profiling revealed widespread transcriptional dysregulation characterized by predominant gene upregulation, consistent with repressive roles for both proteins. Notably, a shared subset of downregulated genes was enriched for mitochondrial-related functions, including COX17, COX4I2, DHRS2, MCUB, and PDK1. These expression changes were validated by quantitative real-time PCR. Analysis of publicly available ChIP-seq datasets further demonstrated co-localization of MBD5, MBD6, and components of the BAP1 complex at the COX17 promoter, suggesting direct chromatin-mediated regulation. Functionally, MBD5 and MBD6 haploinsufficiency impaired mitochondrial respiration, as evidenced by reduced basal and ATP-linked oxygen consumption rates without changes in mitochondrial content. Consistent with this defect, heterozygous cells exhibited severe growth impairment under galactose conditions and a compensatory shift toward glycolytic metabolism. Together, these findings uncover a previously unrecognized chromatin-mitochondria regulatory axis linking MBD5 and MBD6 haploinsufficiency to mitochondrial dysfunction, providing mechanistic insight into how epigenetic dysregulation may contribute to ASD pathogenesis.}, } @article {pmid41554357, year = {2026}, author = {Zhong, Y and Zhang, J and Jia, A and Wen, K and Sun, Y and Guo, L and Deng, H and Feng, X and Feng, L}, title = {Three-ringed mitochondrial architecture and inter-compartmental gene exchange reveal dynamic genome evolution in Durio zibethinus (Malvaceae).}, journal = {International journal of biological macromolecules}, volume = {342}, number = {Pt 1}, pages = {150359}, doi = {10.1016/j.ijbiomac.2026.150359}, pmid = {41554357}, issn = {1879-0003}, mesh = {*Genome, Mitochondrial/genetics ; *Evolution, Molecular ; Phylogeny ; *Malvaceae/genetics ; *Mitochondria/genetics ; *Genome, Plant ; Cell Nucleus/genetics ; }, abstract = {Durian (Durio zibethinus), often hailed as the "king of fruits", is a tropical tree of high economic and nutritional value whose mitochondrial genome has remained virtually unexplored. Here, we report the first complete mitochondrial genome sequences of durian, assembled from two cultivars 'Monthong' and 'Kanyao'. Both assemblies revealed a striking three-ringed multipartite structure totaling 2.27 Mb, representing the largest and most structurally complex mitogenomes reported to date in Malvaceae. These circular subgenomes are interconnected by numerous repeat sequences that mediate frequent recombination and dynamic structural interconversion. Comparative and evolutionary analyses uncovered extensive bidirectional DNA transfer among the mitochondrial, chloroplast, and nuclear genomes, positioning durian mitochondria as a hub of inter-compartmental gene exchange. Evolutionary rate analyses revealed that most shared organellar genes are under strong purifying selection, whereas a subset-including rps4 and atp1 exhibits signatures of adaptive evolution, suggesting fine-tuned coadaptation between the nucleus and mitochondria. Moreover, durian's mitochondrial genome is exceptionally repeat-rich: comparative mitogenomics across 25 Malvaceae species identified short repeats (30-500 bp) as major drivers of genome expansion in this lineage. Together, these findings not only fill a major gap in durian genomics but also advance our understanding of how repeat-driven structural variation and nuclear-cytoplasmic gene flux shape mitochondrial genome evolution.}, } @article {pmid41563622, year = {2026}, author = {Wu, S and Bakky, MAH and Zhang, M and Tran, NT and Li, S}, title = {Harnessing mitochondrial quality control in oxidative stress and environmental resilience in aquaculture.}, journal = {Veterinary research communications}, volume = {50}, number = {2}, pages = {121}, pmid = {41563622}, issn = {1573-7446}, support = {42476099//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Oxidative Stress/physiology ; *Aquaculture ; *Mitochondria/physiology/metabolism ; Stress, Physiological ; }, abstract = {Mitochondria, as central hubs of cellular metabolism and signaling, play a pivotal role in mediating the physiological response of aquatic animals to environmental stressors, largely through their involvement in oxidative stress pathway and quality control mechanism. Understanding these molecular pathways is crucial for addressing key challenges in both aquaculture and environmental toxicology. Rather than focusing on the established fact of stress induced mitochondrial damage, this review synthesizes current knowledge to highlighting the emerging role of the mitochondrial quality control (MQC) system as a decisive determinant of stress resilience. A key research evolution is documented, showing a shift from describing oxidative stress towards exploiting MQC for adaptation and performance optimization. Furthermore, a novel theoretical framework is proposed, explaining how aquatic animals perceive and respond to environmental stress through a multi-stage process: 'stress perception-metabolic reprogramming-quality control'. This framework not only integrates a wide range of existing research but also pinpoints key intervention points for enhancing stress resilience. Collectively, these findings provide a significant theoretical foundation and practical guidance for stress tolerance breeding in aquaculture, precise environmental management, and sustainable development.}, } @article {pmid41563631, year = {2026}, author = {Nehela, Y and Killiny, N}, title = {Not just a cycle: mitochondrial CsgabD is involved in GABA metabolism during citrus defense against biotic stress.}, journal = {Plant molecular biology}, volume = {116}, number = {1}, pages = {11}, pmid = {41563631}, issn = {1573-5028}, mesh = {*gamma-Aminobutyric Acid/metabolism ; *Succinate-Semialdehyde Dehydrogenase/metabolism/genetics/chemistry ; Phylogeny ; *Plant Proteins/metabolism/genetics/chemistry ; *Mitochondria/metabolism ; Amino Acid Sequence ; *Stress, Physiological ; *Citrus sinensis/genetics/microbiology/metabolism ; Gene Expression Regulation, Plant ; *Citrus/genetics/metabolism/microbiology ; Plant Diseases/microbiology/immunology ; Rhizobiaceae/physiology ; Liberibacter/physiology ; Succinic Acid/metabolism ; Sequence Alignment ; Molecular Docking Simulation ; }, abstract = {While the role of succinic semialdehyde (SSA) dehydrogenase (SSADH; also known as gabD) is well-reported from model plants, the lack of functionality and structure of SSADH from citrus represents a significant knowledge gap. Herein, genome-wide analyses identified 17 high-confidence SSADH-like proteins from Citrus sinensis, among which three putative SSADHs have potential GABA dehydrogenase function. Sequence alignment, phylogenetic analyses, and domain architecture demonstrated high conservation among CsSSADHs (aka CsgabD) and their homologs across diverse plant taxa. Notably, CsSSADH-2 lacked a conserved QGIVC motif found in CsSSADH-1/-3. Secondary structure analyses indicated conserved aldehyde dehydrogenase domains. Homology-based 3D modeling predicted CsSSADH-1 and 2 as homo-tetramers; however, AlphaFold2-based modeling suggested their full-length monomer structures. PPI networks revealed CsSSADH-1 interacts with 10 proteins, primarily involved in GABA/succinate metabolism and the TCA cycle. Docking studies indicated that CsSSADH-1 displayed acceptable affinity and binding modes with GABA, SSA, and succinate. GABA supplementation enhances CsSSADH expression, GABA, and succinate content in a dose-dependent manner in both healthy and infected citrus plants under greenhouse conditions. CsSSADH was involved in citrus responses to 'Candidatus Liberibacter asiaticus' and/or its vector, Diaphorina citri. Nevertheless, GABA accumulation under biotic stress leads to condition-specific rerouting of GABA metabolism. Chemical inhibition of CsSSADH resulted in increased GABA accumulation but reduced succinate levels in both healthy and infected plants. This study offers the first comprehensive characterization of C. sinensis SSADH isoforms, providing insights into their evolutionary divergence, structural features, and potential functions, and enhancing our understanding of their possible roles in GABA metabolism and citrus defense responses.}, } @article {pmid41564688, year = {2026}, author = {Bhalodi, JA and Surm, JM and Reitzel, AM}, title = {Transcription dynamics and regulation of heat shock protein genes during stress and development in the estuarine cnidarian Nematostella vectensis.}, journal = {Comparative biochemistry and physiology. Part D, Genomics & proteomics}, volume = {58}, number = {}, pages = {101754}, doi = {10.1016/j.cbd.2026.101754}, pmid = {41564688}, issn = {1878-0407}, mesh = {Animals ; *HSP90 Heat-Shock Proteins/genetics ; *HSP70 Heat-Shock Proteins/genetics ; *Stress, Physiological/genetics ; Phylogeny ; *Transcription, Genetic ; *Gene Expression Regulation, Developmental ; *Sea Anemones/genetics/growth & development ; *Cnidaria/genetics/growth & development ; }, abstract = {Heat shock proteins (HSPs) are molecular chaperones that function in protecting cells from proteotoxicity. Eukaryotes have multiple HSPs that localize in the cytoplasm, endoplasmic reticulum (ER), and mitochondria. In cnidarian species, where HSPs are often used as biomarkers of environmental stress, little is known about how particular HSPs vary in copy number, expression, inducibility, and regulation within a species. Here, we characterized the full repertoire of HSP70 and HSP90 genes in an emerging model cnidarian, Nematostella vectensis. We identified five HSP70 and three HSP90 genes, with at least one homolog from each family belonging to the three primary clades based on subcellular localization. Although transcriptional induction remained insignificant by a 10 °C temperature change, two cytosolic HSP70s and one cytosolic HSP90 were significantly upregulated with a 20 °C temperature increase. Most HSPs exhibited similar developmental expression patterns, with elevated expression during the early larval stage followed by reduced expression in the juvenile stage. HSPs showed evidence for differential expression across cell types, with multiple cytosolic and ER HSPs being highly expressed in neuronal and cnidocyte populations. Moreover, the putative promoters of N. vectensis HSPs differed in both the abundance and sequences of regulatory heat shock element motifs, providing a potential mechanism of functional diversification in response to temperature and development. By characterizing expression of all HSP70 and HSP90 genes in this cnidarian, we reveal distinct roles of these core chaperones in the proteostasis response, providing a foundation for future functional studies on contributions of HSPs to cnidarian life cycle and stress resilience.}, } @article {pmid41566057, year = {2026}, author = {Huang, X and Zhao, L and Liu, Z and Long, N and Zou, W and Gong, F and Cheng, T and Shi, C and Zhang, X and Wang, W and Chen, H and Cheung, AY and Sun, MX}, title = {ATG5-HSP90.2-mediated micromitophagy as a cytological basis for maternal inheritance of plant mitochondria.}, journal = {Nature plants}, volume = {12}, number = {2}, pages = {417-431}, pmid = {41566057}, issn = {2055-0278}, support = {32130031//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2025J01025//Natural Science Foundation of Fujian Province (Fujian Provincial Natural Science Foundation)/ ; }, mesh = {*Mitochondria/genetics/metabolism ; *Maternal Inheritance ; *HSP90 Heat-Shock Proteins/metabolism/genetics ; *Plant Proteins/metabolism/genetics ; Germ Cells, Plant ; }, abstract = {Mitochondria are inherited maternally in most plants as a classical paradigm of non-Mendelian inheritance, but the mechanism underlying paternal mitochondrial elimination (PME) remains almost unknown. We report here that angiosperms have evolved micromitophagy-mediated PME, in which vacuoles directly engulf paternal mitochondria via tonoplast invagination. We show that micromitophagy occurs specifically in male germline (MG) cells. To gain mechanistic insights, we used a vegetative-to-germline cell fate transition system to establish that micromitophagy is triggered by MG cell fate determination. We found evidence that ATG5 is translocated to vacuoles upon MG-cell-fate determination and interacts with mitochondrion-located HSP90.2 during mitochondrial engulfment by vacuoles, elucidating a cell-type-specific ATG neofunctionalization to mediate micromitophagy. This mechanism not only contributes to maternal inheritance of plant mitochondria but also supports the zygote-to-embryo transition. We further determined that micromitophagy is conserved in angiosperms but was continually optimized during evolution to support the best functioning of PME in MG cells with different properties. These findings bridge a long-standing gap in understanding plant PME with emerging mechanistic knowledge.}, } @article {pmid41570014, year = {2026}, author = {Hu, H and He, L and Chen, R and Jing, Z and Wan, H and Xiao, Z and Cheng, H and Wu, C and Liu, X}, title = {Genome-wide identification and multi-dimensional functional characterization of the SIR2 family in Brassica napus L.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0340688}, pmid = {41570014}, issn = {1932-6203}, mesh = {*Brassica napus/genetics/metabolism ; Phylogeny ; Gene Expression Regulation, Plant ; *Plant Proteins/genetics/metabolism/chemistry ; Genome, Plant ; *Histone Deacetylases/genetics/metabolism/chemistry ; Stress, Physiological/genetics ; Promoter Regions, Genetic ; Multigene Family ; Synteny ; Amino Acid Sequence ; Epigenesis, Genetic ; }, abstract = {Silent Information Regulator 2 (SIR2) family proteins are NAD+-dependent histone deacetylases that play key roles in epigenetic regulation, plant development, and stress responses; however, systematic characterization of this family (hereafter SRTs) in the important oilseed crop Brassica napus (rapeseed) remains limited. In this study, we identified 4 SRT genes in the rapeseed genome, designated BnaASRT1/2 and BnaCSRT1/2, based on their homology to Arabidopsis SRTs and chromosomal localization. These genes encode proteins with conserved SIR2 domains, sharing >80% sequence identity and >95% coverage with Arabidopsis SRTs, and exhibit similar subcellular localizations (SRT1s in the nucleus, SRT2s in mitochondria). Phylogenetic and synteny analyses confirmed the evolutionary conservation of rapeseed SRTs, which originated from whole-genome duplication events and were stably inherited from its diploid ancestors (Brassica rapa and Brassica oleracea). Structural analysis indicates that gene structure, motifs, and promoter elements related to stress and hormone responses are conserved, although subtle differences in the promoters suggest functional specialization. Notably, GO enrichment and molecular docking assays demonstrated that BnaSRTs possess histone deacetylase activity, with strong binding affinity to key acetylation sites (e.g., H3K9ac). Treatment with the SIRT-specific inhibitor nicotinamide (NAM) significantly elevated histone acetylation levels and altered the expression of genes involved in photosynthesis, metabolism, and stress responses-further supporting BnaSRTs' ole in epigenetic regulation. Furthermore, expression profiling via the BnIR database showed tissue-specific expression of BnaSRTs (e.g., high BnaASRT2 expression in buds, flowers, and siliques) and dynamic responses to abiotic stresses (salt, drought, cold) and hormones (ABA, JA, IAA), with BnaSRT2s showing the most prominent expression changes. Collectively, these findings clarify the evolutionary conservation, structural features, and functional roles of the SIR2 family in rapeseed, laying a foundation for epigenetic improvement of its agronomic traits.}, } @article {pmid41576162, year = {2026}, author = {Yuan, K and Dai, T and Gao, X and Shen, J and Yang, J and Lu, X and Li, G and He, Y and Fu, Y and Wang, Y and Miao, J and Liu, X}, title = {Mitochondrial heterogeneity drives the evolution of fungicide resistance in Phytophthora sojae, with associated fitness trade-offs.}, journal = {Science advances}, volume = {12}, number = {4}, pages = {eadz4601}, pmid = {41576162}, issn = {2375-2548}, mesh = {*Phytophthora/genetics/drug effects ; *Mitochondria/genetics/drug effects/metabolism ; *Fungicides, Industrial/pharmacology ; Mutation ; *Drug Resistance, Fungal/genetics ; Evolution, Molecular ; Plant Diseases/parasitology ; *Genetic Fitness ; }, abstract = {Mitochondrial complex III inhibitors, such as ametoctradin, are crucial for controlling oomycete diseases. However, the increasing severity of fungicide resistance necessitates urgent clarification of its evolutionary mechanisms to optimize disease management and delay resistance development. The DddA-derived cytosine base editors (DdCBEs)-mediated base editing in oomycetes confirmed that the PsCytb[S33L] mutation is sufficient to confer ametoctradin resistance in Phytophthora sojae. We clarified that low-resistant and medium-resistant mutants serve as transitional populations during the resistance evolution process, with high-resistant mutants eventually becoming the dominant population. We revealed the dynamic changes in mitochondrial heterogeneity under fungicide selection, proving that the gradual increase of mutated mitochondria drives resistance evolution. There is a trade-off between ametoctradin resistance and fitness. While the PsCytb[S33L] mutation confers this resistance, it impairs mitochondrial function and thereby reduces fitness. Up-regulation of TFAM1, however, can partially offset this fitness cost. Resistance evolution in plant pathogens involves not only standing variation but also de novo mutations, providing unique insights into the "chicken-and-egg" dilemma.}, } @article {pmid41588947, year = {2026}, author = {Pandey, SK and Kulshreshtha, A and Mishra, A}, title = {The Role of Mitochondrial Ion Channels in the Evolution of Anticancer Drug Resistance.}, journal = {Current protein & peptide science}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113892037410334251021155546}, pmid = {41588947}, issn = {1875-5550}, abstract = {Apoptosis, drug resistance, and cellular metabolism are all crucially regulated by mitochondria, especially through ion channels and translocases embedded in their membranes. The outer mitochondrial membrane (OMM) contains the voltage dependent anion channel (VDAC), which acts with proteins such as hexokinase II and BAX to regulate apoptosis and metabolic reprogramming in cancer while facilitating the flow of important metabolites and ions. Anti apoptotic proteins like Bcl2 and Mcl1 closely regulate the mitochondrial apoptosis induced channel (MAC), which is created by pro-apoptotic Bcl2 family members BAX and BAK and controls cytochrome c release when overexpressed, leading to drug resistance. Furthermore, the translocase of the outer membrane (TOM) complex, which regulates mitochondrial protein import, is frequently dysregulated in cancers. Numerous ion channels, such as potassium channels, the mitochondrial calcium uniporter (MCU), and the mitochondrial permeability transition pore (m-PTP), are found within the inner mitochondrial membrane (IMM) and regulate important functions like ATP synthesis, the control of reactive oxygen species (ROS), and apoptotic signaling. Cancer cells can avoid apoptosis, adapt to environmental stress, and become resistant to treatments like doxorubicin and cisplatin when these channels are dysregulated. Metabolic flexibility and antioxidant defense are improved by overexpressing or functionally modifying IMM potassium channels and calcium transporters. Additionally, drug resistance is facilitated by increased mitophagy and anti-apoptotic proteins that inhibit m-PTP opening. This review discusses the functions of mitochondrial ion channels.}, } @article {pmid41599654, year = {2025}, author = {Bartusik-Aebisher, D and Rogóż, K and Henrykowska, G and Aebisher, D}, title = {Advances in Near-Infrared BODIPY Photosensitizers: Design Strategies and Applications in Photodynamic and Photothermal Therapy.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {1}, pages = {}, pmid = {41599654}, issn = {1424-8247}, abstract = {Background/Objectives: Boron-dipyrromethene (BODIPY) derivatives are a superior class of fluorophores prized for their exceptional photostability and tunable photophysical properties. While ideal for imaging, their translation to photodynamic therapy (PDT) has been hampered by excitation in the visible range, leading to poor tissue penetration. To overcome this, intense research has focused on developing near-infrared (NIR)-absorbing BODIPY photosensitizers (PS). This review aims to systematically summarize the hierarchical design strategies, from molecular engineering to advanced nanoplatform construction, that underpin the recent progress of NIR-BODIPY PS in therapeutic applications. Methods: We conducted a comprehensive literature review using PubMed, Scopus, and Web of Science databases. The search focused on keywords such as "BODIPY", "aza-BODIPY", "near-infrared", "photodynamic therapy", "photothermal therapy", "nanocarriers", "hypoxia", "immuno-phototherapy", and "antibacterial." This review analyzes key studies describing molecular design, chemical modification strategies (e.g., heavy-atom effect, π-extension), nanoplatform formulation, and therapeutic applications in vitro and in vivo. Results: Our analysis reveals a clear progression in design complexity. At the molecular level, we summarize strategies to enhance selectivity, including active targeting, designing "smart" PS responsive to the tumor microenvironment (TME) (e.g., hypoxia or low pH), and precise subcellular localization (e.g., mitochondria, lysosomes). We then detail the core chemical strategies for achieving NIR absorption and high singlet oxygen yield, including π-extension, the internal heavy-atom effect, and heavy-atom-free mechanisms (e.g., dimerization). The main body of the review categorizes the evolution of advanced theranostic nanoplatforms, including targeted systems, stimuli-responsive 'smart' systems, photo-immunotherapy (PIT) platforms inducing immunogenic cell death (ICD), hypoxia-overcoming systems, and synergistic chemo-phototherapy carriers. Finally, we highlight emerging applications beyond oncology, focusing on the use of NIR-BODIPY PS for antibacterial therapy and biofilm eradication. Conclusions: NIR-BODIPY photosensitizers are a highly versatile and powerful class of theranostic agents. The field is rapidly moving from simple molecules to sophisticated, multifunctional nanoplatforms designed to overcome key clinical hurdles like hypoxia, poor selectivity, and drug resistance. While challenges in scalability and clinical translation remain, the rational design strategies and expanding applications, including in infectious diseases, confirm that NIR-BODIPY derivatives will be foundational to the next generation of precision photomedicine.}, } @article {pmid41601402, year = {2026}, author = {Cai, L and Havird, JC and Jansen, RK}, title = {Recombination and Retroprocessing in Broomrapes Reveal RNA-Mediated Gene Transfer Mechanism and a Generalizable Model for Mitochondrial Evolution in Heterotrophic Plants.}, journal = {Genome biology and evolution}, volume = {18}, number = {2}, pages = {}, pmid = {41601402}, issn = {1759-6653}, support = {//Stengl Wyer Postdoctoral/ ; R35 GM142836/GM/NIGMS NIH HHS/United States ; //University of Florida/ ; R35GM142836/GF/NIH HHS/United States ; //Oak Spring Garden Foundation/ ; }, mesh = {*Gene Transfer, Horizontal ; *Evolution, Molecular ; *Genome, Mitochondrial ; RNA Editing ; *Recombination, Genetic ; *Orobanchaceae/genetics ; Heterotrophic Processes ; Mitochondria/genetics ; Phylogeny ; RNA, Plant/genetics ; }, abstract = {The altered life history strategies of heterotrophic organisms often leave a profound genetic footprint on energy metabolism related functions. In parasitic plants, the reliance on host-derived nutrients and loss of photosynthesis in holoparasites have led to highly degraded to absent plastid genomes, but its impact on mitochondrial genome (mitogenome) evolution has remained controversial. By examining mitogenomes from 45 Orobanchaceae species including three independent transitions to holoparasitism and key evolutionary intermediates, we identified measurable and predictable genetic alterations in genomic shuffling, RNA editing, and intracellular (IGT) and horizontal gene transfer (HGT) en route to a nonphotosynthetic lifestyle. In-depth comparative analyses revealed DNA recombination and repair processes, especially conversion of RNA-mediated retroprocessing, as significant drivers for genome structure evolution. In particular, we identified a novel RNA-mediated IGT and HGT mechanism, which has not been demonstrated previously in cross-species and inter-organelle transfers. We propose a dosage effect mechanism to explain the biased transferability of plastid DNA to mitochondria across green plants, especially in heterotrophic lineages like parasites and mycoheterotrophs. Evolutionary rates scaled with these genomic changes, but the direction and strength of selection varied substantially among genes and clades, resulting in high contingency in mitochondrial genome evolution. Finally, we summarize mitochondrial evolutionary trends in Orobanchaceae that are potentially generalizable to other heterotrophic plants: increased recombination and repair activities, rather than relaxed selection alone, lead to differentiated genome structure compared to free-living species.}, } @article {pmid41604424, year = {2026}, author = {Chevret, CJL and Echegaray, JF and Walton, A and Lo, M and Rueppell, O and Lemieux, H}, title = {Tissue-specific mitochondrial pathway remodeling linked to longevity in honeybee queens.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0341233}, pmid = {41604424}, issn = {1932-6203}, mesh = {Animals ; Bees/physiology/metabolism ; *Longevity/physiology ; *Mitochondria/metabolism ; Female ; NAD/metabolism ; Organ Specificity ; Oxidative Phosphorylation ; }, abstract = {Mitochondrial metabolism plays a critical role in determining lifespan across animal taxa. In our study, we used the Western honeybee (Apis mellifera) as a model, capitalizing on the stark lifespan difference between queens, which often live more than two years, and summer workers, which survive only about 30 days, despite sharing the same genetic background. We investigated mitochondrial function in head tissue, thoracic muscle, and abdominal fat tissue of queens and workers, comparing early (7 days) and late adult stages (28-30 days in workers; 2 years in queens). No significant differences in mitochondrial flux control ratio for the NADH- Succinate- and glycerophosphate (Gp) pathways were found in thoracic muscles across castes or age groups. In head and abdominal fat tissues, early-life queens showed reduced reliance on NADH-linked pathways for maximal respiratory flux compared to workers. The decrease in the NADH-pathway was compensated by an increase in the Gp-pathway contribution. Queens exhibited reduced phosphorylation-pathway control over OXPHOS compared to workers, both in head tissue during early life and in abdominal fat tissue later in life. These findings reveal caste- and tissue-specific patterns of mitochondrial regulation that may contribute to dramatic lifespan divergence observed in eusocial insects. They suggest that early-life metabolic flexibility could play an important role in shaping life history evolution in Apis mellifera.}, } @article {pmid41610858, year = {2026}, author = {Chen, G and Dong, H and Tian, Y}, title = {Mito-nuclear communication: From cellular responses to organismal health.}, journal = {Molecular cell}, volume = {86}, number = {3}, pages = {522-532}, doi = {10.1016/j.molcel.2026.01.001}, pmid = {41610858}, issn = {1097-4164}, mesh = {Animals ; *Mitochondria/metabolism/genetics ; *Cell Nucleus/metabolism/genetics ; Humans ; Unfolded Protein Response ; Signal Transduction ; *Aging/metabolism/genetics ; Integrated Stress Response ; Homeostasis ; }, abstract = {The co-evolution of mitochondria and the nucleus established constant mito-nuclear communication that is essential for both cellular and organismal homeostasis. At the cell-autonomous level, mitochondrial perturbations activate retrograde pathways such as the mitochondrial unfolded protein response (UPR[mt]) and the mitochondrial integrated stress response (ISR[mt]), which couple organelle dysfunction to nuclear transcriptional programs, thereby promoting mitochondrial function and preserving cellular integrity. Importantly, this communication is not confined to individual cells but extends across tissues to coordinate systemic adaptations. Stress signals can be sensed, broadcasted through secreted mitokines and neural circuits, and then interpreted by distal organs to coordinate systemic adaptations. These systemic responses integrate metabolism, immunity, and behavior, conferring resilience to stress and shaping the trajectory of aging. Understanding this multi-layered communication, from the organelle to the organism and its microbial ecosystem, promises new therapeutic strategies to enhance mitochondrial function, promote resilience, and extend healthspan.}, } @article {pmid41612313, year = {2026}, author = {Corre, P and Pilátová, J and Bílý, T and Zadrobílková, E and Čepička, I and Vancová, M and Lohr, M and Caspari, OD and Eliáš, M and Pánek, T}, title = {Energy metabolism and adaptation to hypoxia in the non-photosynthetic green alga Leontynka.}, journal = {BMC biology}, volume = {24}, number = {1}, pages = {}, pmid = {41612313}, issn = {1741-7007}, support = {118222//Grantová Agentura, Univerzita Karlova, Czechia/ ; 23-06203S//Grantová Agentura České Republiky, Czechia/ ; }, mesh = {*Energy Metabolism ; Anaerobiosis ; *Chlorophyta/physiology/metabolism/genetics ; *Adaptation, Physiological ; Mitochondria/metabolism ; *Oxygen/metabolism ; }, abstract = {BACKGROUND: Leontynka is a non-photosynthetic lineage of the order Chlamydomonadales (Chlorophyta). Although many Chlamydomonadales members encode components of the anaerobic energy metabolism, studies focused on Chlamydomonadales algae thriving in hypoxia and not prospering in oxic conditions are missing. Using a combination of experimental approaches, comparative genomics, and advanced in silico protein localization analyses, we employed Leontynka as a model to investigate the evolution of anaerobiosis in Chlamydomonadales.

RESULTS: Leontynka spp. accumulate a wide range of storage forms, enabling them to cope with nutritional stresses. Their mitochondria contain well-developed cristae mediating a conventional aerobic energy metabolism. Moreover, colocalization of a Raman signal for cytochromes with the position of mitochondria in the cell indicates that oxidative phosphorylation is an important route of energy metabolism in the alga. Interestingly, Leontynka spp. concentrate enzymes potentially involved in oxygen-independent ATP synthesis within the plastid, which lost the ability to produce ATP using proton gradient generated by membrane complexes that exploit redox reactions. We analyzed the composition of prokaryotic communities co-isolated with Leontynka spp. and hypothesize that their preference for hypoxic/microoxic conditions is facilitated by metabolic interactions with certain microaerophilic and anaerobic bacteria.

CONCLUSIONS: This study represents the first comprehensive analysis of microaerophilic Chlamydomonadales algae. Having retained several ancestral enzymes of the anaerobic energy metabolism, Leontynka represents a unique vantage point for understanding the evolution of the hydrogen production machinery and adaptations to low oxygen in Chlamydomonadales (and core chlorophytes in general). Our findings suggest that the plastid of non-photosynthetic Leontynka follows a similar evolutionary path as mitochondria when adapting to anaerobiosis and parallels the transition of a mitochondrion into a hydrogenosome.}, } @article {pmid41617585, year = {2026}, author = {Acharya, S and Hanssen, E and Bouwer, JC and Schjenken, JE and Pringle, KG and Smith, R and Fisher, JJ}, title = {Exploring placental ultrastructure: A review of electron microscopy techniques and emerging methods for resolving 3D organelle architecture.}, journal = {Placenta}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.placenta.2026.01.009}, pmid = {41617585}, issn = {1532-3102}, abstract = {Trophoblast cells line the surface of placental villi, facilitating the exchange of nutrients, gases, and wastes between the maternal and fetal circulations. The fusion of cytotrophoblast (CTB) cells into the surrounding multinucleated syncytiotrophoblast (STB), is accompanied by a shift in cellular ultrastructure (subcellular architecture). Mitochondria undergo a remarkable decrease in size and alteration in morphology following trophoblast differentiation, and have thus been the subject of investigations due to their crucial role in producing energy for placental development. Observing this shift in structure has relied on the use of electron microscopy, which has offered insights into underlying mitochondrial functions. Since the initial use of electron microscopy to study villous trophoblasts in the 1950s, novel techniques have emerged that have the capacity to interrogate placental ultrastructure with unprecedented resolution. This review discusses the evolution of electron microscopy techniques to study the placenta over the last 70 years. Moreover, we discuss emerging methods for resolving 3D organelle structure within the placenta, which offer more physiologically pertinent information and context for complex topologies. Further, we discuss advanced methods of cryo-electron tomography (cryo-ET) that present the placental field with an exciting opportunity to determine the complex relationship between mitochondrial architecture and protein structure in the human placenta. By specifically focusing on mitochondrial imaging, we showcase the capacity for volume electron microscopy and cryo-ET to reveal the role of organelle structure in placental development.}, } @article {pmid41617915, year = {2026}, author = {Bertschmann, J and Liu, G and Djamshidi, M and Heshmatazad, K and Romanov, Y and Dhaliwahl, J and Hojjat, H and Yang, Y and de Koning, APJ and Riabowol, K and Hill, A}, title = {A recently evolved domain of the human ING1 epigenetic regulator targets mitochondria and induces senescence.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {83}, number = {1}, pages = {91}, pmid = {41617915}, issn = {1420-9071}, support = {PJT-178099/CAPMC/CIHR/Canada ; PJT-178099/CAPMC/CIHR/Canada ; }, abstract = {ING proteins are epigenetic readers, targeting histone acetyl transferase (HAT; ING3-5) or histone deacetylase (HDAC; ING1-2) complexes to modify gene expression. Expression of the ING1a alternatively expressed isoform of ING1 increases markedly with cell age and in response to other exogenous stresses that induce senescence. Overexpression of ING1a rapidly induces cell senescence in human cells by affecting transcription to inhibit endocytosis and activate the retinoblastoma (Rb) cell cycle checkpoint pathway. In this study we detected ING1a expression in several primary and immortalized human cell types, but we were unable to detect ING1a expression in fibroblasts derived from other species. To identify ING1a homologs or orthologs in other species we searched available databases and found that sequences corresponding to the unique region of the ING1a isoform were only found in humans and gorillas, with truncated versions found in orangutans, chimpanzees, mandrills and macaques. In contrast, the ING1b isoform and other ING genes such as ING3-5 are well conserved evolutionarily, including in vascular plants and fungi. ING1a inhibited metabolic activity in numerous primary and established human cells and in Macaca mulatta fibroblasts, but not in murine fibroblasts. The unique amino-terminal region of ING1a we have designated the senescence-associated domain (SAD) targeted ING1a to mitochondria while ING1a missing this sequence was localized exclusively to nucleoli and nuclei and was less effective in inhibing cell cycle progression or inducing senescence-associated beta-galactosidase activity. Considering the natural induction of this isoform as human cells age in culture, expression of ING1a may contribute to limiting the replicative lifespan of cells through altering nuclear transcription, and in a subset of primates, by a distinct mitochondrial mechanism.}, } @article {pmid41618562, year = {2026}, author = {Shelake, RM and Waghunde, RR and Kim, JY}, title = {Coevolution of plant-microbe interactions, friend-foe continuum, and microbiome engineering for a sustainable future.}, journal = {Molecular plant}, volume = {19}, number = {4}, pages = {719-754}, doi = {10.1016/j.molp.2026.01.010}, pmid = {41618562}, issn = {1752-9867}, mesh = {*Microbiota/genetics/physiology ; *Plants/microbiology ; Symbiosis ; *Biological Evolution ; }, abstract = {The coevolution of plant-microbe (PM) associations over approximately 450 million years has been a fundamental driver of terrestrial life, giving rise to mutualistic, commensal, and pathogenic relationships along a dynamic friend-foe continuum. The need to adapt to the host environment has driven the convergent evolution of common strategies among mutualists and pathogens, enabling them to evade or modulate the plant immune system. This review synthesizes PM coevolution within a deep-time, three-pillar framework: organellogenesis, root evolution, and immune gatekeeping, linking ancient endosymbiotic events (mitochondria, chloroplasts, and nitroplasts) to contemporary holobiont-level phenotypes and biotechnological applications. We organize the friend-foe continuum around a coevolution-guided cost-benefit and tipping-point framework, using identified molecular switches and evolutionary constraints to derive actionable design rules for engineering PM associations. Moving beyond a descriptive toolbox of technologies, we integrate recent breakthroughs to analyze how four principal axes (host and microbial genetics, evolutionary dynamics, environmental and ecological conditions, and metabolic switches) define the thresholds that govern microbial lifestyle transitions. Finally, we propose specific, testable strategies for PM coevolution-informed crop improvement, distinguishing near-term feasible targets from long-term speculative goals in nitrogen utilization, synthetic microbial communities, immune receptor engineering, modulation of plant memory, and microbiome-integrated breeding through genome editing, synthetic biology, AI, and microbiome engineering. Together, these approaches extend existing syntheses into a predictive, evolution-informed framework that translates coevolutionary principles into a functional blueprint for sustainable, resilient agriculture.}, } @article {pmid41619003, year = {2026}, author = {Shao, BY and Liu, SJ and Zhang, TQ and Xue, JY}, title = {Mitochondrial genomes of Mentha reveal structural complexity and evolutionary diversity.}, journal = {Molecular genetics and genomics : MGG}, volume = {301}, number = {1}, pages = {25}, pmid = {41619003}, issn = {1617-4623}, support = {Grant No. zyyzdxk-2023293//National Administration of Traditional Chinese Medicine High-level Key Discipline Construction Project/ ; 32570265//National Natural Science Foundation of China/ ; RENCAI2025034//Fundamental Research Funds for the Central Universities/ ; KYCXJC2025002//Fundamental Research Funds for the Central Universities/ ; }, mesh = {*Genome, Mitochondrial/genetics ; Phylogeny ; *Evolution, Molecular ; *Mentha/genetics/classification ; RNA Editing/genetics ; Genome, Plant/genetics ; Genome, Chloroplast/genetics ; Codon Usage ; Mitochondria/genetics ; }, abstract = {Mitochondrial genomes play essential roles in plant energy metabolism and evolution, yet their structural complexity and diversity in plants remain poorly understood. This study aims to address the question by analyzing four newly assembled Mentha mitochondrial genomes (M. longifolia, M. suaveolens, M. pulegium, and M. requienii), which serve as valuable genomic resources for phylogenetic and evolutionary studies. Comparative analyses revealed structural diversity, codon usage bias, extensive RNA editing, and abundant repetitive sequences driving genomic rearrangements in the four mitochondrial genomes. Chloroplast-derived DNA fragments were dynamically integrated into the four Mentha mitochondrial genomes, highlighting ongoing interorganellar DNA transfer between plastids and mitochondria. Phylogenetic reconstructions based on mitochondrial, nuclear, and chloroplast genomes exhibit considerable discordance, reflecting complex evolutionary processes such as hybridization, introgression, and allopolyploidization within the genus. In conclusion, the structural diversity, codon usage bias, and ongoing interorganellar DNA transfer observed in Mentha mitochondrial genomes underscore their dynamic evolutionary nature. The discordance among mitochondrial, plastid, and nuclear phylogenies reflects complex evolutionary processes (possibly hybridization and allo-polyplodization) of Mentha species. These findings enhance the understanding of the mechanisms underlying the complexity and diversity of Mentha species and provide broader insights into the evolution of plant mitochondrial genomes.}, } @article {pmid41621609, year = {2026}, author = {Gusmão, IV and Figueredo, RTA and Corrêa, LL and Maia, AAM and Adriano, EA}, title = {Integrative taxonomy reveals a novel Ceratomyxa (Cnidaria: Myxozoa) parasitizing the gallbladder of the Amazonian fish Pellona castelnaeana.}, journal = {Acta tropica}, volume = {275}, number = {}, pages = {108005}, doi = {10.1016/j.actatropica.2026.108005}, pmid = {41621609}, issn = {1873-6254}, mesh = {Animals ; *Myxozoa/classification/isolation & purification/genetics/ultrastructure ; *Gallbladder/parasitology ; Phylogeny ; *Fish Diseases/parasitology/epidemiology ; DNA, Ribosomal/chemistry/genetics ; *Parasitic Diseases, Animal/parasitology/epidemiology ; Sequence Analysis, DNA ; Molecular Sequence Data ; Fishes ; Cluster Analysis ; Microscopy, Electron, Transmission ; Prevalence ; }, abstract = {Freshwater species of the myxozoan genus Ceratomyxa have recently emerged as a diverse group of parasites infecting fish in South America, many of which exhibit vermiform plasmodia with dynamic motility. In this integrative taxonomic study, we describe Ceratomyxa souzapintorum n. sp., a novel species infecting the gallbladder of the Amazonian clupeiform fish Pellona castelnaeana. The prevalence of infection was 73%, and the parasite displayed worm-like plasmodia exhibiting nematode-like motility. Arcuate myxospores measured 14.8 ± 1.7 µm in thickness and 6.1 ± 0.7 µm in length, with a posterior angle of 59° (42-78°). The two spherical nematocysts measured 2.0 µm and contained filaments with 3-4 coils. Ultrastructural analyses revealed plasmodia consisting of an outer cytoplasmic region containing sporogonic stages and numerous tubular mitochondria, and internally a large central vacuole. Mature plasmodia exhibited a thin cytoplasmic layer, with mature myxospores apparently free within the central vacuole. Phylogenetic analyses positioned C. souzapintorum n. sp. within the clade of Amazonian Ceratomyxa species.}, } @article {pmid41627905, year = {2026}, author = {Saldamando, CI and Candamil-Cortés, MS and Rodríguez-Cabal, HA and Montoya-Ruiz, C and Cano-Calle, D}, title = {Genomic and phylogenetic insights for three species of thrips (Thysanoptera: Terebrantia) associated with Colombian avocado.}, journal = {Journal of insect science (Online)}, volume = {26}, number = {1}, pages = {}, pmid = {41627905}, issn = {1536-2442}, support = {45565//Universidad Nacional de Colombia to Clara Inés Saldamando-Benjumea/ ; }, mesh = {Animals ; *Thysanoptera/genetics ; *Persea ; Phylogeny ; Colombia ; *Genome, Insect ; Genome, Mitochondrial ; }, abstract = {Thrips are small, cosmopolitan pests that attack a wide variety of crops, including avocado (Persea americana Mill.), where they feed on the fruit surface, hindering export quality. In Colombia, 7 thrips species have been identified in avocado where Frankliniella gardeniae (Fg) (Moulton, 1948), F. panamensis (Fp) (Hood, 1925), and Scirtothrips hansoni (Sh) (Mound and Hoddle, 2016) are the most abundant. Despite their economic importance, limited genomic and transcriptomic data are available for these pests. Here, we present the first draft genomes of these species and compare them to the reference genome of Frankliniella occidentalis. The mitochondrial genomes (mitogenomes) of the 3 species differ in size and gene order, with F. gardeniae exhibiting the largest mitochondria. Phylogenetic analysis clustered F. gardeniae and F. panamensis together and S. hansoni with S. dorsalis. Genome assembly revealed differences in genome sizes: 397 Mbp (Fp), 454 Mbp (Sh), and 601 Mbp (Fg), with F. gardeniae having the largest genome. Coverage was 118× for S. hansoni and 35× for the other 2 species. S. hansoni showed the highest sequence count and N50 values. BUSCO analysis estimated genome completeness between 96% and 97.95%. Annotated genes shared among these species included insecticide resistance and metabolism, particularly P450 and CYP family genes, as well as chemosensory genes (Ir). They are promising targets for RNA interference-based studies to enhance pest management strategies thus further studies are required in this issue.}, } @article {pmid41628193, year = {2026}, author = {Owaresat, JK and Dey, D and Siam, MAH and Anam, MA and Siddiki, AZ}, title = {Genetic diversity, phylogeography, population structure, and demographic history of wild Catla catla at a transboundary scale across South Asia revealed by Mitochondrial COI sequences.}, journal = {PloS one}, volume = {21}, number = {2}, pages = {e0341820}, pmid = {41628193}, issn = {1932-6203}, mesh = {Animals ; *Genetic Variation ; Phylogeography ; *Electron Transport Complex IV/genetics ; Haplotypes ; Phylogeny ; *DNA, Mitochondrial/genetics ; Genetics, Population ; Asia, Southern ; Asia ; *Mitochondria/genetics/enzymology ; }, abstract = {This study presents the first assessment of mitochondrial cytochrome c oxidase I (COI) sequences from multiple countries to evaluate the genetic diversity, phylogeographic relationships, population structure, and demographic history of wild Catla catla in South Asia. A total of 18 haplotypes, with moderate haplotype diversity (Hd = 0.599), low nucleotide diversity (π = 0.017), and limited mutational steps among most haplotypes, were identified after analyzing 133 COI sequences collected from Bangladesh, India, and Pakistan. The results revealed low genetic differentiation among all wild Catla samples, influenced by introgression from hatchery-reared fry and population bottlenecks. Phylogenetic analyses identified two distinct haplogroups for Pakistani populations, supporting the existence of divergent mitochondrial lineages. AMOVA test showed that most genetic variation occurred within populations (74.46.%) rather than among the seven river basin populations (25.54%). The high pairwise genetic distance (FST= 0.255), together with the presence of numerous population-specific haplotypes and low gene flow (Nm = 0.729), indicated significant population structure among these river populations. A positive Mantel test (r = 0.12) confirmed a significant increase in genetic divergence with increasing geographic distance. The neutrality test and mismatch distribution presented a contrasting demographic history. A significantly negative Fu's Fs (Fu's Fs = -24.431) pointed to recent population expansion, whereas a significant Harpending's raggedness index (r = 0.009) and a multimodal mismatch distribution suggested long-term demographic substructure. These findings provide essential COI-based baseline genetic information for conserving the genetic integrity of the wild Catla catla and guiding sustainable transboundary fisheries management in South Asia.}, } @article {pmid41630175, year = {2026}, author = {Lim, SJ and Breitbart, M}, title = {Genetic Features of the Scuticociliate Pathogen Philaster sp. Isolate FWC2 That Causes Sea Urchin Mass Mortality.}, journal = {The Journal of eukaryotic microbiology}, volume = {73}, number = {2}, pages = {e70065}, pmid = {41630175}, issn = {1550-7408}, support = {//University of South Florida/ ; OCE- 2527605//National Science Foundation/ ; }, mesh = {Animals ; *Sea Urchins/parasitology ; *Ciliophora/genetics/isolation & purification/pathogenicity/classification ; Phylogeny ; Genome, Mitochondrial ; Base Composition ; Sequence Analysis, DNA ; }, abstract = {A scuticociliate most closely related to Philaster apodigitiformis caused mass mortalities of diadematoid sea urchins and was cultured as Philaster sp. isolate FWC2. We sequenced the metagenomic content of this isolate, which was predicted to represent ≤ 56% of the complete genome. Based on k-mer counts, the haploid genome size was predicted to be 122-136 Mbp. We assembled and annotated a 4,088 bp nuclear ribosomal operon, a 41,396 bp mitochondrial genome with 19.22% G + C content, 24 protein-coding genes, 6 tRNA genes, and 2 rRNA genes, and a protein sequence homologous to β-PKA in Philaster apodigitiformis potentially involved in host infection.}, } @article {pmid41633006, year = {2026}, author = {Tan, HX and Gao, QH and Tong, X}, title = {The morphology of male accessory glands in the Glenea cantor (Fabricius, 1787) (Coleoptera: Cerambycidae: Lamiinae).}, journal = {Micron (Oxford, England : 1993)}, volume = {203}, number = {}, pages = {103999}, doi = {10.1016/j.micron.2026.103999}, pmid = {41633006}, issn = {1878-4291}, mesh = {Animals ; Male ; *Coleoptera/anatomy & histology/ultrastructure ; Microscopy, Electron, Transmission ; China ; *Genitalia, Male/ultrastructure/anatomy & histology ; Microscopy ; }, abstract = {Male accessory glands of insects serve as secretory organs, exhibiting the ability to produce secretions that regulate reproductive processes. Their histology and ultrastructure are generally regarded as being diverse within insect groups, however, as one of the largest groups of insects, the ultrastructure of male accessory glands in Cerambycidae has never received sufficient attention. The longhorn beetle Glenea cantor (Fabricius, 1787) (Coleoptera: Cerambycidae: Lamiinae) is a wood-boring pest infesting urban landscape trees in southern China, significantly compromising urban greening. In this study, light and transmission electron microscopes were used to reveal the histological and ultrastructural characteristics of the male accessory glands of G. cantor. Results show that the males of G. cantor possess two pairs of morphologically distinct mesodermal glands (mesadenia). One pair exhibits an overall elongated tubular shape, while the other displays a tightly coiled, clew-like structure proximally and free-ending tubular regions distally. Ultrastructurally, both pairs of mesadenia exhibit identical cell types, with abundant secretory granules observed within the cytoplasm and lumen. Each gland possesses a muscular layer, an epithelium, and a lumen. The epithelial cell layer contains cellular structures and organelles indicative of active protein synthesis, including rough endoplasmic reticulum (RER), mitochondria, Golgi appartus, and secretory vesicles. This epithelium is also characterized by the presence of microvilli. The lumen is filled with electron-dense secretion. Notably, distinct morphological and ultrastructural differences exist both between the two mesadenial pairs and within each pair between their proximal and distal regions. This study provides the first comparative morphological and ultrastructural analysis of regional differentiation in two pairs of male accessory glands of G. cantor, revealing adaptive changes acquired during their evolution.}, } @article {pmid41637520, year = {2026}, author = {Zhu, Q and Zhang, J and Zhou, W and Liang, SA and Wang, S and Cai, X and Li, F and Li, J and Zhang, G and Feng, H and Fu, Q and Akey, JM and Zhang, F and Jin, L and Xu, S and Zheng, HX and Chen, L}, title = {Introgressed mitochondrial fragments from archaic hominins alter nuclear genome function in modern humans.}, journal = {Science advances}, volume = {12}, number = {6}, pages = {eaea0706}, pmid = {41637520}, issn = {2375-2548}, mesh = {Humans ; Animals ; *DNA, Mitochondrial/genetics ; *Hominidae/genetics ; *Cell Nucleus/genetics ; Phylogeny ; Evolution, Molecular ; Haplotypes ; *Genome, Human ; *Genetic Introgression ; *Mitochondria/genetics ; Neanderthals/genetics ; }, abstract = {Archaic introgression introduced functionally relevant variants into modern humans, yet small-scale insertions remain understudied. Here, we leverage 2519 modern human genomes and four high-coverage archaic hominin genomes to systematically characterize nuclear mitochondrial DNA segments (NUMTs). We uncover 483 polymorphic NUMTs across globally diverse human populations and 10 in archaic genomes. By combining overlap with Neanderthal-derived and Denisovan-derived haplotypes, phylogenetic analyses, insertion time estimates, and haplotype colocalization, we identify five NUMTs introduced into modern humans via archaic hominin introgression. Functional analyses reveal that introgressed NUMTs can modulate gene expression, including allele-specific up-regulation of the immune-related gene RASGRP3, and reshape three-dimensional chromatin structure at loci such as SCD5 and HNRNPD. These findings highlight an underappreciated mechanism by which archaic mitochondrial fragments shape nuclear genome function and evolution. Our study reframes NUMTs not as passive genomic fossils but as dynamic elements influencing modern human diversity and adaptation.}, } @article {pmid41637653, year = {2026}, author = {Varikasuvu, SR}, title = {Mitochondria and moon: footprints shaping life's evolution and cosmic exploration.}, journal = {Advances in physiology education}, volume = {50}, number = {2}, pages = {370-373}, doi = {10.1152/advan.00268.2025}, pmid = {41637653}, issn = {1522-1229}, mesh = {Humans ; *Biological Evolution ; *Mitochondria/physiology ; *Moon ; Animals ; *Physiology/education ; Academia ; }, abstract = {NEW & NOTEWORTHY This Personal View offers a fresh conceptual perspective for physiology education by framing cellular structures in the context of broader patterns and milestones. It encourages readers to consider the symbolic and historical significance of biological and exploratory imprints, fostering reflective thinking about how scientific concepts can be interpreted and communicated beyond the classroom.}, } @article {pmid41646419, year = {2026}, author = {Lee, S and Chakraborty, S and Kim, S and Ali, A and Mitra, K and Zajac, M and Brown, A and Pincus, D and Krishnan, Y}, title = {Organelles harbour pH gradients.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {41646419}, issn = {2693-5015}, support = {RM1 GM153533/GM/NIGMS NIH HHS/United States ; R01 GM147197/GM/NIGMS NIH HHS/United States ; R01 NS112139/NS/NINDS NIH HHS/United States ; DP1 GM149751/GM/NIGMS NIH HHS/United States ; R01 GM138689/GM/NIGMS NIH HHS/United States ; }, abstract = {Organelle pH is critical to organelle identity and function. Resident proteins that define each organelle modify transiting cargo proteins, with both retention and trafficking between organelles governed by pH-dependent mechanisms. For example, lysosomal enzymes bind mannose-6-phosphate receptors at the higher pH (~6.5) of the Golgi and dissociate at the lower pH (~5.5) of late endosomes[1]. Proteins that stray from the endoplasmic reticulum (ER) are captured by KDEL receptors in the acidic Golgi and returned into the neutral ER[2,3]. This pH-tuned trafficking system compartmentalizes organelle function and prevents mis-localization of critical enzymes[4]. Dysregulated organelle pH disrupts their function and leads to various diseases. Because protons move rapidly in water, the pH within a single organelle is currently assumed to be spatially uniform[5]. Here, using a reporter sensitive from pH 5.5 - 10.5 to map a spectrum of organelles at high resolution, we discovered that pH gradients exist within single, large or long organelles such as the ER and mitochondria, and in membrane-less organelles without ion-transporting proteins such as the nucleolus. These new findings upend our understanding of organellar pH, prompting new questions about proton diffusion within the cell, and its potential consequences on organelle function.}, } @article {pmid41664414, year = {2026}, author = {Intarasit, S and Inwongwan, S}, title = {Coordinating photosynthesis and respiration: evolution and functional integration of mitochondria and chloroplasts in algae.}, journal = {Plant physiology}, volume = {200}, number = {2}, pages = {}, doi = {10.1093/plphys/kiag054}, pmid = {41664414}, issn = {1532-2548}, support = {//Chiang Mai University/ ; }, mesh = {*Photosynthesis/physiology ; *Chloroplasts/metabolism ; *Mitochondria/metabolism ; *Biological Evolution ; *Chlorophyta/metabolism/physiology ; Cell Respiration ; Oxidation-Reduction ; Diatoms/metabolism ; }, abstract = {The coordination of photosynthesis and respiration is central to cellular energy balance, yet in algae, this relationship exhibits exceptional diversity. Shaped by successive endosymbioses, algal lineages represent natural experiments in merging two energy systems of distinct bacterial ancestry: the chloroplast and the mitochondrion. Their structural proximity, shared redox pathways, and dual-targeted proteins enable dynamic communication between photosynthetic and respiratory metabolism. Recent imaging and multi-omics studies reveal that this interaction is highly responsive to environmental variables such as light intensity, nutrient availability, and oxidative stress. In diatoms, mitochondria envelop the plastid to exchange ATP and reducing power, whereas in green algae and euglenoids, malate/oxaloacetate shuttles, alternative oxidases, and cyclic electron flow collectively stabilize chloroplast redox states. This functional coupling optimizes CO2 fixation and photoprotection under stress and underlies the metabolic flexibility of mixotrophic species such as Euglena gracilis. This review synthesizes the current understanding of mitochondria-chloroplast integration in algae from evolutionary, structural, and mechanistic perspectives, highlighting photosynthesis-respiration coordination as a unifying physiological principle. By elucidating how inter-organelle networks sustain carbon assimilation and redox homeostasis, these insights advance our understanding of algal productivity and resilience and inform strategies for improving energy efficiency in photosynthetic systems.}, } @article {pmid41676893, year = {2026}, author = {Shahbazi, M and Sharbrough, J and Knerova, J and Wendel, JF and Kopecky, D}, title = {Causes and Consequences of Cytonuclear Incompatibility in Hybrids of Flowering Plants.}, journal = {Journal of experimental botany}, volume = {}, number = {}, pages = {}, doi = {10.1093/jxb/erag075}, pmid = {41676893}, issn = {1460-2431}, abstract = {Hybridization and polyploidization combine divergent nuclear genomes with maternally inherited organelles, often disrupting cytonuclear coadaptation critical for respiration and photosynthesis. This review examines the mechanisms, outcomes, and evolutionary significance of cytonuclear incompatibility in plants. We focus on how divergence in nuclear-encoded, organelle-targeted proteins and organelle genomes leads to mismatched interactions in protein import, folding, and assembly of multi-subunit enzyme complexes. The evidence highlights taxon- and complex-specific responses that mitigate incompatibilities, including the biased retention and expression of maternal alleles, gene conversions, and regulatory adjustments. We highlight how cytonuclear compatibility in hybrid lineages entails responses at multiple levels of regulation, including methylation/chromatin accessibility, gene expression, alternative splicing, translation rates, organelle import, protein-folding and assembly, and protein degradation pathways. Manifestations such as chlorosis, seed sterility, or hybrid breakdown underscore their role in shaping reproductive barriers. Conversely, maternal bias and compensatory mechanisms often act to restore functional integration of parental genomes, allowing hybrid and polyploid persistence. Beyond their evolutionary role in speciation and adaptation, cytonuclear incompatibilities underpin key practical applications, notably cytoplasmic male sterility, a cornerstone of hybrid crop breeding. We conclude that cytonuclear dynamics reveal both constraints and opportunities, illuminating plant diversification, hybrid resilience, and agricultural innovation.}, } @article {pmid41683746, year = {2026}, author = {Shemarova, IV and Nikitina, ER}, title = {Mechanisms of Protection Against Oxidative Stress During Hibernation.}, journal = {International journal of molecular sciences}, volume = {27}, number = {3}, pages = {}, pmid = {41683746}, issn = {1422-0067}, mesh = {*Hibernation/physiology ; *Oxidative Stress ; Animals ; Mitochondria/metabolism ; Antioxidants/metabolism ; Humans ; Adaptation, Physiological ; Hypoxia/metabolism ; }, abstract = {Hibernation-the ability of some animals to enter prolonged winter sleep-is a natural hypometabolic state that allows them to withstand adverse environmental factors (low temperatures, food and water shortages). The ability to hibernate is a consequence of adaptations accumulated over evolution at various physiological levels, among which molecular adaptation to hypoxia plays a key role, which eliminates not only the negative effect of oxygen deficiency on cells, but also the danger of oxidative stress (OS) after awakening. This aspect of hibernation is medically important because understanding the mechanisms underlying the adaptation of hibernating animals to hypoxia and OS can help address a number of important issues related to preventing post-hypoxic complications in people with chronic neurodegenerative and heart disease. The molecular basis of adaptation to hypoxia in hibernating animals is the presence of an effective antioxidant system (AOC) and regulatory mechanisms that provide extraordinary mitochondrial plasticity, which is especially pronounced when animals emerge from hibernation. This review summarizes and systematizes the latest advances in the study of mitochondria and antioxidant defenses during mammalian hibernation, primarily gophers-a common experimental model of hibernation.}, } @article {pmid41692172, year = {2026}, author = {Ruan, H and Chen, Y and Qian, J and Ma, X and Xu, Y and Deng, Y and Pan, Y and Kushwaha, A and Kumar, A and Zheng, B and Liu, J}, title = {Advances in metal-organic framework-based drug delivery system in cuproptosis-mediated cancer therapy.}, journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V}, volume = {222}, number = {}, pages = {115021}, doi = {10.1016/j.ejpb.2026.115021}, pmid = {41692172}, issn = {1873-3441}, mesh = {Humans ; *Cuproptosis ; *Neoplasms/drug therapy ; *Drug Delivery Systems/methods ; Animals ; *Metal-Organic Frameworks/chemistry ; *Antineoplastic Agents/administration & dosage/chemistry ; Copper/chemistry ; }, abstract = {Cancer continues to pose an immense burden on global health, ranking among the foremost causes of disease-associated mortality. Conventional diagnostic platforms for tumor biomarkers, while widely adopted, remain constrained by limited sensitivity, protracted workflows, and substantial economic costs, thereby restricting their clinical applicability. Therapeutic modalities such as chemotherapy and radiotherapy further compound the challenge, offering only modest selectivity and being accompanied by significant systemic toxicity and a high likelihood of relapse. Metal-organic frameworks (MOFs) represent a class of structurally tailorable nanomaterials composed of modular building units, featuring tunable porosity and favourable biocompatibility, which together provide an efficient platform for drug encapsulation and controlled release. Their tumour accumulation behaviour is strongly governed by key physicochemical parameters, including particle size, morphology, and surface chemistry. Pristine MOFs primarily rely on passive tumour targeting through the enhanced permeability and retention effect, whereas surface functionalization with targeting ligands can markedly improve tumor selective enrichment and cellular uptake. Consequently, the therapeutic delivery performance of MOFs must be critically assessed in relation to their specific structural design and surface engineering strategies. In parallel, the identification of cuproptosis, a mitochondria-centered copper-dependent mode of regulated cell death, has opened a distinct mechanistic avenue for oncological intervention. This process arises from the aberrant interaction of copper ions with lipoylated tricarboxylic acid cycle proteins, culminating in excessive protein acylation, destabilization of Fe-S cluster enzymes, proteotoxic stress, and mitochondrial collapse. The rapid evolution of pharmacological agents exploiting this pathway underscores its transformative therapeutic potential. This review critically consolidates recent progress at the interface of MOFs and cuproptosis, emphasizing design strategies, mechanistic insights, and therapeutic deployment, while also addressing unresolved issues in pharmacokinetics, biosafety, and translational feasibility that must be overcome for clinical realization.}, } @article {pmid41695269, year = {2026}, author = {Zhang, J and Zhao, Z and Xiang, T and Teng, D and Wan, H and Zhang, Q and Liu, X}, title = {From knowledge landscapes to network mechanisms: charting regulated cell death pathways in ALS.}, journal = {Frontiers in aging neuroscience}, volume = {18}, number = {}, pages = {1742805}, pmid = {41695269}, issn = {1663-4365}, abstract = {OBJECTIVE: To map the research landscape linking amyotrophic lateral sclerosis (ALS) with regulated cell death (RCD) and to integrate bibliometric trends with bioinformatics evidence to identify convergent mechanisms and actionable targets.

METHODS: Web of Science Core Collection, PubMed, and Scopus were searched for 2005-2024 (English; Article/Review). After merging and de-duplication, 6,272 records were analyzed using CiteSpace, VOSviewer, and bibliometrix to evaluate publication trends, collaboration, co-citation structure, and keyword evolution. In parallel, ALS-related genes were intersected with apoptosis-, ferroptosis-, and pyroptosis-associated gene sets. Shared targets were used to construct PPI networks, identify core modules and hub genes, and perform GO/KEGG enrichment analyses.

RESULTS: Publications and citations increased steadily with a clear rise after 2015. The field is anchored by the USA and shows rapidly growing contributions from Asia and Europe. Keyword evolution indicates a shift from "oxidative stress/apoptosis" toward multi-pathway RCD, with prominent recent bursts in ferroptosis, pyroptosis, necroptosis, and autophagy/mitophagy, alongside persistent themes in motor-neuron degeneration, mitochondria, and neuro-inflammation. Bio-informatics results showed substantial genetic overlap between ALS and RCD modalities. Hub-gene analysis highlighted TP53, AKT1, STAT3, MYC, RELA, EP300, CREBBP, JUN, HSP90AA1, and MAPK3 as central nodes. Enrichment analyses implicated FoxO, HIF-1, and lipid-related pathways, and GO terms related to chemical/oxidative stress responses and autophagy regulation.

CONCLUSION: ALS-cell death research is consolidating around interconnected RCD programs. Integrated bibliometric and bioinformatics evidence supports an immunometabolic convergence involving ferroptosis-inflammation-autophagy signaling, providing a focused set of candidate pathways and hub targets for mechanistic validation and translation.}, } @article {pmid41695472, year = {2026}, author = {Chen, P and Liu, G and Yin, J and Sun, L and Wang, X and Wang, B and Gong, Q and Luo, K}, title = {Therapeutic Promise of Mitophagy in Cancer: Advancing from Small-Molecule Regulation to Nanotechnology-Enhanced Targeting Therapy.}, journal = {Theranostics}, volume = {16}, number = {8}, pages = {4308-4335}, pmid = {41695472}, issn = {1838-7640}, mesh = {*Mitophagy/drug effects ; Humans ; *Neoplasms/drug therapy/pathology/therapy ; Animals ; *Antineoplastic Agents/pharmacology ; Mitochondria/metabolism/drug effects ; Drug Delivery Systems/methods ; Tumor Microenvironment ; Nanotechnology/methods ; }, abstract = {Mitophagy, a selective autophagic pathway that clears damaged or dysfunctional mitochondria, has emerged as a promising therapeutic approach. Mitophagy maintains a delicate balance between cell survival and death, while mounting evidence suggests that it predominantly promotes tumor cell survival under stress, particularly in responses to cancer therapy. Moreover, aberrant regulation of mitophagy results in cancer pathology with characteristic hallmarks, including remodeling of metabolic plasticity, maintenance of cancer stem cell characteristics, and immune regulation of the tumor microenvironment. This review synthesizes multifaceted roles of mitophagy in cancer biology, from tumor initiation and progression to therapy responses. It also summarizes molecular mechanisms underlying mitophagy. How cancer cells exploit mitophagy to survive therapy has been harnessed to develop therapeutic strategies. We elaborate the evolution of mitophagic therapy from small-molecule modulators to nanotechnology-based targeted delivery systems. Finally, we highlight the promise of targeting mitophagy in overcoming treatment resistance and improving clinical outcomes for patients.}, } @article {pmid41701624, year = {2026}, author = {Grover-Thomas, F and van Dorp, L and Balloux, F and Andrés, AM and Camus, MF}, title = {Climate-associated natural selection in the human mitochondrial genome.}, journal = {Molecular biology and evolution}, volume = {43}, number = {5}, pages = {}, pmid = {41701624}, issn = {1537-1719}, support = {NE/S007229/1//Natural Environment Research Council/ ; NE/V014307/1//UKRI/ ; MR/X034828/1//UKRI/ ; RPG-2023-198//Leverhulme Trust/ ; }, mesh = {Humans ; *Genome, Mitochondrial ; *Selection, Genetic ; *Climate ; DNA, Mitochondrial/genetics ; Genome, Human ; Evolution, Molecular ; }, abstract = {Mitochondria are essential for cellular energy production and biosynthesis, thermogenesis, and cell signaling, and thus help coordinate physiological responses to changing environments. Humans (Homo sapiens) have adapted to cope with a wide range of climatic conditions, however the role of the mitochondrial genome (mtDNA) in mediating this process remains poorly understood. Here, we curated a dataset of 19,570 publicly available full human mitochondrial genomes, an approximate 40-fold increase on earlier studies, paired with modern climate and reconstructed paleoclimate variables. Using a Generalized Linear Model approach, we identify 18 independent candidate variants significantly associated with climatic conditions, suggesting local adaptation in human mitochondrial genomes. Candidate variants are distributed across multiple loci in regulatory, tRNA, rRNA and protein-coding regions-including prominently in ND2 and ND4 complex I subunits. Specific variants are predicted to impact mtDNA transcription, ribosome or protein structure, and multiple have been associated with disease pathologies. We further show that candidate variant genotype distributions are each best modeled by different paleo-bioclimatic variables, consistent with environmental stressors linked to our measured variables exerting subtly distinct selective effects. These stressors may reflect dietary changes or different thermogenic demands at lower temperatures. Our results provide genetic evidence to support the accumulating body of work from functional studies that mitochondria can modulate adaptation to diverse environments. This work underscores the importance of mtDNA in evolutionary biology and its relevance for understanding both disease and physiological variation in global populations.}, } @article {pmid41707207, year = {2026}, author = {Zhou, J and Wu, Q and Wu, L and Li, L and Xue, S and Yan, J and Hu, Z and Niu, XM}, title = {Nematode-trapping devices of Arthrobotrys oligospora is an iron storage system mediated by elevated temperatures.}, journal = {FEMS microbiology ecology}, volume = {102}, number = {3}, pages = {}, pmid = {41707207}, issn = {1574-6941}, support = {202407AB110021//Hubei Provincial Central Guidance Local Science and Technology Development Project/ ; 202201BF070001-012//Yunnan University/ ; }, mesh = {*Ascomycota/genetics/metabolism/physiology ; *Iron/metabolism ; Animals ; *Nematoda/microbiology/physiology ; Temperature ; Fungal Proteins/genetics/metabolism ; Hot Temperature ; Vacuoles/metabolism ; }, abstract = {Under low-nutrient conditions, nematode-trapping fungi (NTFs) can differentiate their mycelia into specialized trapping devices for capturing prey. Using energy-dispersive X-ray spectroscopy in conjunction with transmission electron microscopy, together with a series of bioassay, we identified that the characteristic electron-dense bodies in trapping devices contained more iron than vacuoles and mitochondria, functioning as an unrecognized iron storage organelle. Genomic analysis revealed that all NTFs lack the Ccc1-mediated vacuolar iron detoxification mechanism conserved in most fungi. Heterogenous expression of yeast-derived Ccc1 gene in Arthrobotrys oligospora significantly reduced trapping device formation and nematicidal activity. Mapping key factor fluctuations onto Bayesian relaxed molecular clock analysis indicated that the loss of Ccc1-mediated vacuolar iron storage occurred during Late Paleozoic Ice Age, whereas the emergence of trapping devices and the acquisition of desferriferrichrome were closely associated with elevated temperatures. Temperature bioassays showed that trap formation is highly temperature-dependent, with free iron levels inversely correlated with temperature, consistent with the temperature sensitivity of A. oligospora, which cannot grow above 30°C. Our findings demonstrated that global temperature fluctuations serve as a critical driver of the evolution of NTFs and act as a catalyst for the emergence of trapping devices, novel phenotypic indicator of eukaryotic iron overload.}, } @article {pmid41707917, year = {2026}, author = {Meneses-Plascencia, J and Moreno-Méndez, E and Ascencio, D and Pérez-Aguilar, C and Munguía-Figueroa, M and Abreu-Goodger, C and Funes, S and DeLuna, A}, title = {Metformin-induced longevity is associated with retrotransposon dynamics in yeast chronological aging.}, journal = {Mechanisms of ageing and development}, volume = {231}, number = {}, pages = {112162}, doi = {10.1016/j.mad.2026.112162}, pmid = {41707917}, issn = {1872-6216}, mesh = {*Metformin/pharmacology ; *Retroelements/drug effects ; *Saccharomyces cerevisiae/genetics/metabolism ; *Longevity/drug effects ; *Gene Expression Regulation, Fungal/drug effects ; Saccharomyces cerevisiae Proteins/metabolism/genetics ; Chromatin/metabolism ; }, abstract = {The widely used antidiabetic drug metformin promotes longevity across diverse model organisms, from yeast to primates, yet the cellular mechanisms by which it acts are not fully resolved. Here, we use high-resolution genetic profiling to define metformin's impact on the chronological lifespan of Saccharomyces cerevisiae. Unexpectedly, our analyses uncover pronounced gene-drug interactions between metformin and chromatin modification. In particular, impairment of the histone deacetylase Set3C phenocopies the effects of metformin, suggesting convergence on a shared pathway. Consistent with this genetic interaction, transcriptome sequencing shows that metformin reprograms stationary-phase gene expression, with Ty1-copia retrotransposons emerging as a dominant signature. Notably, targeted analysis of Ty1 expression reveals that Set3C perturbation reproduces the metformin-induced Ty1 response, directly linking chromatin regulation to the observed lifespan phenotypes. Despite this transcriptional activation, metformin reduces TYA Gag-like protein levels without increasing insertion frequency, revealing an uncoupling between retrotransposon expression and mobility. In parallel, proteome analysis identifies increased mitochondrial and stress-response proteins as early outcomes of metformin exposure, both known modulators of Ty1 dynamics and potential mediators of this response. Together, our findings position chromatin regulation and retrotransposon expression as integral components of metformin's effects on longevity, expanding its influence beyond signaling, metabolism, and stress response.}, } @article {pmid41718137, year = {2026}, author = {Meduri, GU and Torres, A}, title = {Evolutionary Integration and Glucocorticoid Regulation of the Respiratory System: Structure, Function, and Homeostatic Adaptation.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {41718137}, issn = {2076-3271}, mesh = {Animals ; *Glucocorticoids/metabolism ; Humans ; *Homeostasis ; *Receptors, Glucocorticoid/metabolism ; *Biological Evolution ; *Adaptation, Physiological ; *Respiratory System/metabolism/anatomy & histology ; Signal Transduction ; }, abstract = {The vertebrate respiratory system arose under evolutionary pressures that linked increasing atmospheric oxygen levels to the metabolic demands of mitochondria. This transition-from ancestral gill-based exchange to the highly alveolated mammalian lung-was accompanied by the emergence of a hormonal regulatory axis centered on the glucocorticoid receptor alpha (GRα). Over time, GRα became deeply integrated into the architecture and function of the respiratory system, aligning pulmonary performance with organismal homeostasis across different developmental stages, environmental challenges, and disease states. This review combines evolutionary, embryological, and molecular evidence to explain how GRα shapes respiratory structure and function. We trace the evolution from ancient oxygen-sensing systems to mammalian alveoli and endothelial adaptations, demonstrating how conserved developmental pathways (including WNT, FGF, BMP, and SHH) are repurposed during both organogenesis and repair. Genetic models show that GRα is essential for preparing the lung for postnatal life, coordinating the reciprocal signaling between mesenchyme and epithelium that drives branching, septation, extracellular matrix organization, and the development of functional alveolar units. In the mature lung, GRα maintains the stability of the alveolar-capillary interface and coordinates immune, vascular, and metabolic functions to support efficient gas exchange. Its actions also extend to red blood cell biology and the regulation of stress erythropoiesis, linking pulmonary oxygen management with systemic oxygen delivery. Mechanistically, GRα interacts with circadian and hypoxia pathways and activates mitochondrial programs that enhance energy production and redox homeostasis during stress. By integrating these regulatory layers across developmental and physiological contexts, this review reframes GRα not simply as a stress-response receptor but as a non-redundant system-level integrator of respiratory homeostasis. Understanding this layered control not only explains the benefits of antenatal corticosteroids but also highlights the therapeutic value of phase-specific, precision modulation of the GC-GRα axis-along with strategies that support GC-GR signaling-to reestablishing and maintaining homeostasis in acute and chronic pulmonary disorders.}, } @article {pmid41719251, year = {2026}, author = {Unten, Y and Takafuji, K and Masukagami, Y and Shiiba, I and Horiuchi, K and Husnik, F and Yanagi, S and Tateishi, N and Suzuki, T}, title = {Characterizing mitochondrial phenotypes and MERCS in aged human skeletal muscle myoblasts.}, journal = {PloS one}, volume = {21}, number = {2}, pages = {e0343604}, pmid = {41719251}, issn = {1932-6203}, mesh = {Humans ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Phenotype ; *Myoblasts, Skeletal/metabolism/cytology ; Cellular Senescence ; Aged ; *Mitochondria/metabolism ; *Endoplasmic Reticulum/metabolism ; Adult ; *Aging ; *Muscle, Skeletal/cytology/metabolism ; Oxygen Consumption ; Middle Aged ; DNA, Mitochondrial/metabolism ; Membrane Potential, Mitochondrial ; Cells, Cultured ; *Mitochondria, Muscle/metabolism ; Female ; Male ; }, abstract = {Age-associated declines in skeletal muscle function are linked to cellular senescence and mitochondrial alterations, yet mitochondrial phenotypes in aged human myoblasts remain insufficiently characterized. Here, we examined primary skeletal muscle myoblasts from young and elderly donors to assess mitochondrial function, morphology, and mitochondria-endoplasmic reticulum (ER) contact sites (MERCS). Myoblasts from older donors exhibited senescence features, including elevated SA-β-gal activity and reduced Lamin B1 expression, accompanied by increased mitochondrial oxidative stress. Despite marked mitochondrial hyperfusion and increased mitochondrial DNA content, mitochondrial oxygen consumption rate and membrane potential per mitochondrial area were comparable between young and old cells. MERCS were significantly elevated in aged myoblasts and were reduced by scavenging mitochondrial reactive oxygen species (mtROS), indicating an association between oxidative stress and MERCS formation. These findings suggest that mitochondrial hyperfusion and enhanced MERCS accompany cellular aging in human myoblasts and may contribute to maintaining mitochondrial function under elevated oxidative stress.}, } @article {pmid41729694, year = {2026}, author = {Pang, J and Zhang, Y and Tian, Y and Cao, X and Tao, X and Sun, C and Cao, Z}, title = {Mapping the scientific landscape of mitochondria-associated membranes: a bibliometric insight into emerging frontiers in aging and diseases.}, journal = {International journal of surgery (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1097/JS9.0000000000004989}, pmid = {41729694}, issn = {1743-9159}, abstract = {BACKGROUND: Mitochondria-associated membranes (MAMs) are critical hubs coordinating energy metabolism, lipid homeostasis, and Ca2[+] signaling, thereby regulating cell survival, stress responses, and apoptosis. Increasing evidence links MAMs dysfunction to aging, neurodegenerative diseases, metabolic disorders, and cancer. Although numerous mechanistic studies and narrative reviews have been published, a systematic, mechanism-oriented bibliometric evaluation of the global MAMs research landscape is still lacking.

METHODS: We performed a comprehensive bibliometric analysis of MAMs-related literature indexed in the Web of Science Core Collection from 2009 to 2024, using Bibliometrix, VOSviewer, and CiteSpace to integrate publication trends, collaboration networks, keyword co-occurrence, thematic evolution, and citation impact.

RESULTS: A total of 1199 publications were identified, showing a rapid annual growth rate of 21.57%. Beyond general trend analysis, our study reveals that research hotspots converge on Ca2⁺ homeostasis, ER stress, apoptosis, and mitochondrial dynamics, and progressively shift toward aging-related biological processes. By mapping high-frequency keywords to known MAMs-associated pathways, we identify aging, ER stress, and apoptosis as interconnected emerging themes. Importantly, this analysis highlights specific MAMs-related proteins, including HSP90α, as potential regulatory hubs linking stress responses and aging.

CONCLUSIONS: This study provides the first integrative, mechanism-oriented bibliometric framework of MAMs research, bridging quantitative publication patterns with underlying biological pathways. Our findings not only delineate the intellectual structure and evolving themes of the field but also generate testable hypotheses implicating MAMs and key regulatory proteins in aging-related processes, thereby offering guidance for future mechanistic and translational studies.}, } @article {pmid41740769, year = {2026}, author = {Wang, L and Li, H and Shi, Y and Li, W and Gao, W and Wu, D and Wang, S and Qin, Q}, title = {Functional characterization of the Rab11 and its response to SGIV infection in the orange-spotted grouper (Epinephelus coioides).}, journal = {Fish & shellfish immunology}, volume = {172}, number = {}, pages = {111230}, doi = {10.1016/j.fsi.2026.111230}, pmid = {41740769}, issn = {1095-9947}, mesh = {Animals ; *rab GTP-Binding Proteins/genetics/chemistry/immunology/metabolism ; Amino Acid Sequence ; *Fish Diseases/immunology/virology/genetics ; Sequence Alignment/veterinary ; *Fish Proteins/genetics/chemistry/metabolism/immunology ; *DNA Virus Infections/immunology/veterinary/genetics/virology ; *Immunity, Innate/genetics ; *Bass/genetics/immunology ; Ranavirus/physiology ; Phylogeny ; rab11 GTP-Binding Proteins ; *Gene Expression Regulation/immunology ; Gene Expression Profiling/veterinary ; }, abstract = {Rab11, a member of the Rab GTPase family, serves as a key regulator of vesicular trafficking and modulates viral infection in mammals, yet its functional role in aquatic viral infection remains largely uncharacterized. Singapore grouper iridovirus (SGIV), a member of the genus Ranavirus in the family Iridoviridae, is one of the most important viral pathogens afflicting grouper aquaculture. In this study, we investigated the influence of a novel Rab11 homolog (EcRab11) from the orange-spotted grouper (Epinephelus coioides) on SGIV infection and the role in host innate immune responses. EcRab11 shares high amino acid sequence identity with Rab11 orthologs spanning from mammals to teleost fishes, indicating evolutionary conservation of this GTPase. In healthy groupers, EcRab11 was predominantly expressed in major immune organs including the liver and spleen, and its transcript levels were significantly upregulated following immune challenges. Confocal imaging revealed that EcRab11 localizes to the cytoplasm as distinct punctate and vesicle-like structures. In contrast, overexpression of a constitutively active EcRab11 mutant (CA-EcRab11, with a GTP-locked mutation at the conserved Q70L site that renders the protein persistently activated and unable to hydrolyze GTP to GDP) induced the formation of enlarged vesicular structures, whereas overexpression of a dominant-negative EcRab11 mutant (DN-EcRab11, with a GDP-locked mutation at the conserved S25N site that abrogates GTP binding and locks the protein in an inactive state) resulted in a marked reduction in vesicle formation. Co-localization analyses further demonstrated that EcRab11 extensively colocalizes with the Golgi apparatus, early endosomes and late endosomes, and partially with the endoplasmic reticulum or lysosomes, but did not colocalize with mitochondria. Functional assays revealed that EcRab11 overexpression significantly suppressed SGIV infection, whereas overexpression of either CA-EcRab11 or DN-EcRab11 enhanced viral replication. Moreover, EcRab11 was found to positively regulate both autophagy and IFN immune responses in grouper cells. Taken together, our findings demonstrate that EcRab11 modulates SGIV infection by orchestrating host innate immune responses, thereby uncovering a novel antiviral mechanism of Rab11 against SGIV and providing new insights for the development of antiviral strategies for grouper aquaculture.}, } @article {pmid41741417, year = {2026}, author = {Huang, Y and He, T and Zheng, J and Chen, J and Yang, Z}, title = {Circular RNAs in metabolic health: bridging the gap between molecular biology and therapy.}, journal = {Cell death & disease}, volume = {17}, number = {1}, pages = {}, pmid = {41741417}, issn = {2041-4889}, support = {31902167//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *RNA, Circular/genetics/metabolism ; Animals ; *Obesity/genetics/metabolism/therapy ; Lipid Metabolism/genetics ; Mitochondria/metabolism ; Energy Metabolism/genetics ; Endoplasmic Reticulum/metabolism ; }, abstract = {Recent advances in obesity research have shifted focus toward biological mechanisms, paralleling progress in pharmacotherapy. Fat browning-the conversion of white to brown adipocytes-emerges as a promising therapeutic strategy. Circular RNAs (circRNAs), stable non-coding RNAs with regulatory functions, are now recognized as key modulators of this process through organelle-mediated mechanisms. This review synthesizes current understanding of circRNA biogenesis and their roles in fat browning, particularly their interactions with mitochondria and endoplasmic reticulum in lipid metabolism. We highlight their capacity to encode peptides and regulate metabolic pathways, positioning circRNAs as potential precision therapeutics. While preclinical studies demonstrate mechanistic efficacy, clinical translation requires addressing delivery challenges and tissue-specific effects. This biological perspective advances obesity treatment paradigms beyond simplistic energy-balance models, mirroring the evolution seen in pharmacotherapeutic development.}, } @article {pmid41751627, year = {2026}, author = {Xu, B and Jia, M and Kong, J and Nie, L and Wang, J and Tembrock, LR and Wu, Z and Li, S and Liao, X}, title = {The Mitochondrial Genome of Curcuma longa: A Large and Structurally Complex Genome with Extensive Intracellular DNA Transfer.}, journal = {Genes}, volume = {17}, number = {2}, pages = {}, pmid = {41751627}, issn = {2073-4425}, support = {110243160001007//Chinese Academy of Agricultural Sciences/ ; 2026BQ69//Introduction of Talent Research Initiation Project/ ; }, mesh = {*Curcuma/genetics ; *Genome, Mitochondrial/genetics ; *Genome, Plant ; Evolution, Molecular ; Phylogeny ; Genome, Plastid ; Mitochondria/genetics ; }, abstract = {Background: Plant mitochondrial genomes exhibit extreme variation in size and structure while maintaining a conserved set of core protein-coding genes. This combination of structural diversity and functional conservation provides valuable insights into evolutionary processes such as genome expansion, rearrangement, and intracellular DNA transfer. Curcuma longa, an economically and medicinally important species in the genus Curcuma (Zingiberaceae), has not yet been studied in terms of the organization and evolution of its mitochondrial genome. Methods: In this study, we assembled and annotated the mitochondrial and plastid genomes of C. longa using third-generation HiFi sequencing data, systematically analyzing their genomic structure, repetitive sequence content, and features of sequence transfer between nuclear and organellar genomes. Results: The mitochondrial genome of C. longa was assembled as a complex, network-like structure consisting of 12 contigs with a total length of approximately 7.7 Mb, making it one of the largest mitochondrial genomes reported in monocots to date. Comparative analysis revealed significant differences in repeat types, abundance, and length distribution between the two organellar genomes. Additionally, extensive intracellular DNA transfer events were identified among the nuclear, mitochondrial, and plastid genomes. Conclusions: Overall, this study provides the first comprehensive report on the giant mitochondrial genome of C. longa, detailing its structural organization, repeat content, and intergenomic transfers. These findings lay a foundation for understanding mitochondrial genome evolution in Curcuma and offer broader insights into the mechanisms driving extreme mitochondrial genome expansion in angiosperms and monocots specifically.}, } @article {pmid41751903, year = {2026}, author = {Marton, J and Ciocan, RA and Bâldea, I and Gherman, ML and Gheban, D and Filip, A and Pașcalău, IR and Mihăileanu, FV and Pop, RM and Gherman, CD}, title = {Molecular Mechanisms, Dynamic Lesions, and Therapeutic Targets in Intestinal Ischemia-Reperfusion Injury: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {27}, number = {4}, pages = {}, pmid = {41751903}, issn = {1422-0067}, mesh = {Humans ; *Reperfusion Injury/metabolism/therapy/pathology ; Animals ; *Intestines/pathology/blood supply ; Oxidative Stress ; Intestinal Barrier Function ; Signal Transduction ; *Intestinal Diseases/therapy/metabolism ; }, abstract = {Intestinal ischemia-reperfusion injury (IRI) represents a major cause of morbidity and mortality in abdominal surgery, trauma, and intestinal transplantation. The pathophysiological process involves a biphasic cascade that begins with ischemic hypoxia and progresses to amplified cellular and molecular injury upon reperfusion. This review synthesizes recent mechanistic insights regarding endothelial and microvascular dysfunction, epithelial barrier breakdown, microbiota-driven systemic propagation, and the involvement of oxidative/nitrosative stress and inflammatory signaling. The novelty of our review's approach is the focus on experimental and translational studies and correlation of the data with future directions for mechanistic research and clinical implementation. Despite promising preclinical results, heterogeneity in study protocols or/and model limitations make clinical translation challenging. Recent studies have demonstrated that mitochondria, tight junction proteins, adhesion molecules and innate immune receptors are critical determinants of lesion evolution. Based on these, the current therapeutic strategies include antioxidants, adenosine pathway modulators, dexmedetomidine, ischemic conditioning, hyperbaric oxygen therapy, and microbiota-targeted interventions. Since each mechanism is acting on distinct molecular pathways, a multimodal therapy that integrates redox modulation, endothelial protection, microbiome regulation, and the identification and employment of precision biomarkers is likely to improve outcomes. Beyond summarizing established molecular mechanisms, this review critically reassesses why decades of promising experimental strategies for intestinal ischemia-reperfusion injury has largely failed to translate into effective clinical therapies. By distinguishing context-dependent mechanisms from pathways with consistent translational relevance, we highlight key methodological and biological barriers limiting clinical applicability. Furthermore, we propose a temporally structured, multimodal therapeutic framework that integrates phase-specific pathophysiology with targeted interventions, aiming to inform future experimental design and improve translational success.}, } @article {pmid41752171, year = {2026}, author = {Khan, A and Ziyi, Y and Rahman, FU and Luo, H and Hu, Z}, title = {The Impact of Mitochondrial DNA Depletion on Mitochondrial Ultrastructure, Photosynthesis, and the mTERF Gene Family in Chlamydomonas reinhardtii.}, journal = {International journal of molecular sciences}, volume = {27}, number = {4}, pages = {}, pmid = {41752171}, issn = {1422-0067}, support = {32273118//National Natural Science Foundation of China/ ; GuikeAA24263042//Guangxi Major Program for Science and Technology/ ; 2018YFA0902500//Chinese National Key 576 R&D Project for Synthetic Biology/ ; KCXFZ20211020164013021//Shenzhen Special Fund for Sustainable Development/ ; 2022B1111070005//Guangdong Key R&D Project/ ; 2022B010//Shenzhen University 2035 Program for Excellent Research/ ; }, mesh = {*Chlamydomonas reinhardtii/genetics/metabolism/ultrastructure ; *DNA, Mitochondrial/genetics/metabolism ; *Photosynthesis/genetics ; *Mitochondria/ultrastructure/genetics/metabolism ; Phylogeny ; Multigene Family ; *Mitochondrial Proteins/genetics/metabolism ; Chloroplasts/metabolism/genetics ; }, abstract = {Mitochondrial biogenesis requires coordinated expression from both nuclear and mitochondrial genomes. To understand the consequences of mitochondrial genome loss, we generated a mitochondrial DNA-depleted line (crm[-]) in Chlamydomonas reinhardtii via long-term ethidium bromide treatment. We then examined how mtDNA disruption affects mitochondrial ultrastructure, chloroplast function, and the mitochondrial transcription termination factor (mTERF) gene family. Our results reveal that mitochondrial dysfunction is associated with severe organelle remodeling, including mitochondrial elongation, matrix condensation, and cristae collapse. Consequently, mitochondria reduce the electron sink capacity which appears to over-reduce the chloroplast electron transport chain, correlating with causing damage to photosystem II (PSII), as indicated by higher plastoquinone PQ redox state and PSII excitation pressure and lower non-photochemical quantum yield [Y(NPQ)]. Furthermore, we identified and characterized eight nuclear-encoded mTERF genes in C. reinhardtii (CrmTERFs). Phylogenetic analysis grouped them into three clades with potential functional conservation. Collinearity analysis suggested potential evolutionary relationships between mTERF genes in Chlamydomonas and Marchantia polymorpha. Gene ontology annotation linked CrmTERFs to transcription termination and RNA biosynthesis regulation. Additionally, in silico prediction identified twelve putative miRNAs targeting seven of the eight CrmTERFs, with CrmTERF3 as the only exception, providing candidates for future experimental validation. This study provides the first comprehensive analysis of the nuclear encoded mTERF gene family in Chlamydomonas and demonstrates that mtDNA loss is correlated with mTERF genes expression, as well as mitochondrial structure and chloroplast photoprotective impairments. These findings suggest a potential role for CrmTERFs in mitochondrial retrograde signaling and organellar crosstalk, though functional validation is required to establish causality.}, } @article {pmid41764643, year = {2026}, author = {Zeller, LM and Schorn, S and Nicolas-Asselineau, L and Zopfi, J and Ahmerkamp, S and Schubert, CJ and Lepori, F and Kuypers, MMM and Graf, JS and Milucka, J}, title = {Redox gradients define the ecological niche of ciliates with denitrifying endosymbionts in anoxic lake waters.}, journal = {The ISME journal}, volume = {20}, number = {1}, pages = {}, pmid = {41764643}, issn = {1751-7370}, support = {//internal funds of Eawag/ ; //Max Planck Society/ ; }, mesh = {*Symbiosis ; *Lakes/microbiology/chemistry ; *Ciliophora/microbiology/physiology ; Nitrates/metabolism ; Oxidation-Reduction ; Switzerland ; Phylogeny ; Oxygen/metabolism ; Anaerobiosis ; Denitrification ; Sequence Analysis, DNA ; Sulfides/metabolism ; Ecosystem ; Molecular Sequence Data ; }, abstract = {Bacterial endosymbionts of the family Candidatus Azoamicaceae obligately associate with anaerobic ciliates belonging to the class Plagiopylea. The symbionts' unique role for their host involves anaerobic respiration of nitrate and generation of adenosine triphosphate (ATP), analogous to the role of mitochondria in aerobic eukaryotes. As this symbiosis remains so far uncultured, insights into its functioning have been mainly inferred from environmental metagenomes. Here, we investigated the distribution and environmental role of this symbiosis in the anoxic basins of two freshwater lakes, Zug and Lugano (Switzerland), over a course of several years. We found that the environmental niche of the ciliate host is defined by the combined effects of sulfide, oxygen, and nitrate, the latter of which is essential for the symbiont's respiratory function. Moreover, the distribution and abundance of ciliates with denitrifying endosymbionts in the water column suggest that they may substantially contribute to nitrate consumption in Lake Zug. Our microscopic analyses further demonstrated a coordinated division of the Ca. Azoamicus ciliaticola symbionts and their ciliate hosts, implying a vertical inheritance of denitrifying symbionts. These observations offer new insights into the evolution of ciliates with denitrifying endosymbionts and their ecological role in oxygen-depleted lake waters.}, } @article {pmid41772230, year = {2026}, author = {Lai, KL and Smith, TB and Maroofian, R and Zaki, MS and Ramadesikan, S and Reynolds, T and Koboldt, DC and Hunter, JM and Vidaurre, J and Atanasova, M and Marsden, BD and Yue, WW and Houlden, H and Taylor, RW and Newman, WG and O'Keefe, RT}, title = {Expanding the genotypic spectrum of combined oxidative phosphorylation deficiency 54.}, journal = {Neurogenetics}, volume = {27}, number = {1}, pages = {}, pmid = {41772230}, issn = {1364-6753}, support = {203105/Z/16/Z//Wellcome Centre for Mitochondrial Research/ ; MR/W019027/1/MRC_/Medical Research Council/United Kingdom ; MR/W019027/1/MRC_/Medical Research Council/United Kingdom ; MR/W019027/1/MRC_/Medical Research Council/United Kingdom ; S60_Newman//Royal National Institute for the Deaf/Masonic Charitable Foundation/ ; S60_Newman//Royal National Institute for the Deaf/Masonic Charitable Foundation/ ; NIHR 203308//NIHR Manchester Biomedical Research Centre/ ; }, abstract = {UNLABELLED: Biallelic hypomorphic variants in PRORP cause the rare autosomal recessive disorder combined oxidative phosphorylation deficiency type 54 (COXPD54). COXPD54 encompasses a clinical spectrum of sensorineural hearing loss and ovarian insufficiency (Perrault syndrome) to leukodystrophy with developmental delay and epilepsy. Here, we report two new affected individuals with biallelic PRORP variants with clinical features consistent with COXPD54. One individual was homozygous for c.1505G > A p.Arg502Gln, whereas the other was compound heterozygous for c.1510C > T, p.His504Tyr and c.893C > A, p.Ser298Ter (NM_014672.4). In vitro tRNA processing assays revealed decreased mitochondrial 5′ tRNA leader cleavage by human RNase P complex with the two novel missense PRORP metallonuclease domain variants. These data provide further evidence that biallelic PRORP variants disrupt 5’ tRNA leader cleavage and are associated with a pleiotropic phenotype of COXPD54.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10048-026-00892-5.}, } @article {pmid41776601, year = {2026}, author = {Hong, W and Long, S and Ashrafizadeh, M and Sethi, G and Duan, C}, title = {From symbiosis to immunity: the evolutionary revival of mitochondrial defense programs in inflammatory diseases.}, journal = {Cell communication and signaling : CCS}, volume = {24}, number = {1}, pages = {}, pmid = {41776601}, issn = {1478-811X}, support = {Nos. 82472182 and 82272252//National Natural Science Foundation of China/ ; CSTB2023NSCQ-MSX0192//General Project of the Chongqing Natural Science Foundation/ ; HBRC202419//Chongqing National Talent Reserve Project/ ; }, abstract = {Mitochondria, descendants of ancestral α-proteobacteria, embody a dual identity that unites metabolic symbiosis with immune regulation. While evolution has transformed their form and function, mitochondria still preserve a tripartite heritage, an outer membrane resembling the host, an inner membrane of bacterial origin, and a matrix enriched with prokaryotic remnants such as unmethylated mitochondrial DNA (mtDNA), N-formyl peptides, and cardiolipin. Under physiological conditions, this architecture supports efficient energy generation while maintaining immunological silence. However, during infection, hypoxia, or systemic inflammation, this endosymbiotic equilibrium collapses, reawakening innate immune programs encoded in their bacterial ancestry. This review introduces the framework of Mitochondrial Endosymbiotic Dysregulation (MED) to describe the progressive transition of mitochondria from metabolic collaborators to immune activators under inflammatory stress. The MED model delineates three sequential stages: MED-I (Adaptive Remodeling), where mitochondria dynamically reorganize to preserve homeostasis, exhibiting characteristic structures such as mitochondrial flagella-like acquisition and retrieval extension (mitoFLARE) and mito-donut; MED-II (Functional Collapse), characterized by the failure of mitochondrial communication and the emergence of defensive structures such as mito-matryoshka; and MED-III (Structural Disintegration), marked by membrane rupture, release of mitochondrial damage-associated molecular patterns (DAMPs), and amplification of innate immune cascades. Rather than viewing mitochondrial dysfunction as a passive byproduct of injury, the MED paradigm reframes it as a reactivation of ancient bacterial defense programs, coupling bioenergetic failure to immune amplification. Thus, by integrating evolutionary, structural, and immunometabolic perspectives, this review discusses how mitochondrial remodeling under inflammatory stress contributes to diseases such as sepsis, autoimmune disorders, and neuroinflammation, and explores emerging therapeutic strategies aimed at restoring mitochondrial–host symbiosis.}, } @article {pmid41779208, year = {2026}, author = {Dahal, U and Shakya, R and Kour, B and Khanal, B and Singh, B}, title = {Evolution and Functional Implications of Codon Usage Bias in Eukaryotes.}, journal = {Journal of molecular evolution}, volume = {94}, number = {2}, pages = {286-303}, pmid = {41779208}, issn = {1432-1432}, abstract = {This review explores codon usage bias, the non-random preference for synonymous codons, as a fundamental aspect of gene regulation, translation efficiency, and genome evolution in eukaryotes. Unlike prokaryotes, eukaryotic codon usage is influenced by GC content, gene expression levels, tRNA availability, and selection pressures. Evolutionarily, mutation, genetic drift, and natural selection shape codon preferences, leading to distinct biases across unicellular and multicellular organisms. Fungi, plants, and animals exhibit lineage-specific codon usage, often linked to translational efficiency and environmental adaptation via optimized protein production. Additionally, organelle genomes such as mitochondria and chloroplasts retain unique codon patterns due to their endosymbiotic origins. Beyond evolutionary roles, codon bias impacts human health, contributing to genetic diseases, cancer progression, and neurodegenerative disorders, distinct from its applications in gene therapy and vaccine design. Advances in computational approaches, including indices like Effective number of codons (ENC), Codon adaptation index (CAI), and Relative synonymous codon usage (RSCU), along with machine learning models and specialized databases, have enhanced codon usage analysis, providing insights into gene expression and functional genomics. Despite significant progress, many aspects of eukaryotic codon usage remain unexplored, presenting new opportunities in biotechnology, synthetic biology, and genomic research. A deeper understanding of codon bias can improve translational control strategies and optimize gene expression for therapeutic and industrial applications.}, } @article {pmid41781394, year = {2026}, author = {Huang, C and Wang, B and Yu, J and Rossiter, SJ and Zhao, H}, title = {Convergent evolutionary shifts in AGT targeting between mitochondria and peroxisomes across mammal transitions to herbivory.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {}, pmid = {41781394}, issn = {2041-1723}, support = {32270436//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2023AFA015//Natural Science Foundation of Hubei Province (Hubei Provincial Natural Science Foundation)/ ; //Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; *Peroxisomes/metabolism/enzymology ; *Herbivory/physiology ; *Mitochondria/metabolism/enzymology ; *Transaminases/metabolism/genetics ; *Evolution, Molecular ; *Mammals/genetics/metabolism ; Phylogeny ; Protein Transport ; Glyoxylates/metabolism ; }, abstract = {Herbivory has evolved multiple times during mammalian diversification, playing a key role in the success of this globally distributed clade. A central metabolic challenge for herbivores is the detoxification of glyoxylate. The enzyme alanine:glyoxylate aminotransferase (AGT) converts glyoxylate to glycine, preventing the formation of harmful calcium oxalate crystals. AGT localizes to mitochondria and peroxisomes based on the mitochondrial targeting sequence (MTS) and the peroxisomal targeting signal (PTS1), respectively. While most studies focused on MTS, MTS variation alone does not fully explain AGT localization patterns. To assess the relative importance of the PTS1 motif, we combined comparative sequence analyses with functional assays. We find that multiple herbivorous lineages underwent independent mutations resulting in disrupted or truncated MTS regions, whereas the PTS1 motif remains functional. Immunofluorescence assays revealed more efficient peroxisomal localization of AGT in herbivores, with PTS1 often overriding mitochondrial signals even when the MTS is intact. Additionally, transcriptomic analyses show that several herbivorous lineages preferentially use downstream transcriptional start sites, producing AGT isoforms lacking the MTS. Together, our findings reveal a central role of AGT peroxisomal targeting in evolution of plant-based diets, and demonstrate how increased targeting efficiency has evolved convergently via the interplay of transcriptional regulation and targeting signals.}, } @article {pmid41782893, year = {2026}, author = {Lisa, AK and Reeve, WG and Laird, DW and Chopra, A and Moheimani, NR}, title = {The complete mitochondrial genome of Dunaliella salina CS-265: insights into gene content and phylogenetic placement.}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {11}, number = {4}, pages = {468-472}, pmid = {41782893}, issn = {2380-2359}, abstract = {We report the complete mitochondrial genome of the halotolerant green alga Dunaliella salina CS-265, isolated from a hypersaline lake in central Australia. The genome is a circular DNA molecule of 30,073 bp, encoding seven protein-coding genes, nine rRNAs, and three tRNAs. Four core genes (cox1, cob, nad1, and nad5) are fragmented by multiple introns, whereas others remain intact. The absence of ATP synthase subunits and ribosomal protein genes reflects ongoing reductive evolution in Dunaliella mitochondria. This genome adds a new organellar resource from an Australian isolate, complementing previous studies and providing further insight into mitochondrial genome dynamics in halotolerant green algae.}, } @article {pmid41793841, year = {2026}, author = {Martin, WF}, title = {Demand-only energetics at 120 ATP per glucose: A reply to Lynch.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1867}, number = {2}, pages = {149587}, pmid = {41793841}, issn = {1879-2650}, mesh = {*Adenosine Triphosphate/metabolism/biosynthesis ; *Glucose/metabolism ; *Energy Metabolism ; *Escherichia coli/metabolism ; Mitochondria/metabolism ; Thermodynamics ; }, abstract = {Recently in these pages, a paper by Lynch appeared in response to a report showing that his numbers for biosynthetic costs (ATP demand) in cells are inflated, so much so that they would require E. coli to obtain >100 ATP per glucose and mitochondria to obtain >240 ATP per glucose. The inflated estimates trace to one factor: Lynch exclusively considers ATP demand and systematically neglects ATP supply-the essence of bioenergetics. Thermodynamics stipulate that a cell cannot grow if its ATP demands exceed its ATP supply. Here I compare Lynch's calculated ATP demands to laboratory measurements of the ATP supply that E. coli synthesizes during cell division. The results bear out my case, and leave no doubt: Lynch's calculations require E. coli to synthesize ∼120 ATP per glucose, which is thermodynamically impossible. As a consequence, his demand-only 'energetic' attacks on mitochondria and endosymbiosis in evolution are baseless.}, } @article {pmid41802974, year = {2026}, author = {Žihala, D and Salamonová, J and Eliáš, M}, title = {Corrigendum to "Evolution of the genetic code in the mitochondria of Labyrinthulea (Stramenopiles)" [Mol. Phylogenet. Evol. 152 (2020) 106908].}, journal = {Molecular phylogenetics and evolution}, volume = {220}, number = {}, pages = {108593}, doi = {10.1016/j.ympev.2026.108593}, pmid = {41802974}, issn = {1095-9513}, } @article {pmid41807573, year = {2026}, author = {Ghosh, D and Thakur, S and Bali, S and Sharma, S and Dogra, V}, title = {Comparative genome-wide analysis in Setaria italica and Arabidopsis thaliana revealed functional conservation of specific FtsH proteases under high light and heat stress.}, journal = {Plant cell reports}, volume = {45}, number = {4}, pages = {}, pmid = {41807573}, issn = {1432-203X}, support = {6/1/FIRST/2020-RPPBDD-TMD-SeMI//Council of Scientific and Industrial Research, India/ ; BT/RLF/Re-entry/02/2019//Department of Biotechnology, Ministry of Science and Technology, India/ ; }, mesh = {*Arabidopsis/genetics/radiation effects/physiology/enzymology ; Gene Expression Regulation, Plant/radiation effects ; *Light ; *Heat-Shock Response/genetics ; *Arabidopsis Proteins/genetics/metabolism ; *ATP-Dependent Proteases/genetics/metabolism ; Hot Temperature ; Promoter Regions, Genetic/genetics ; Phylogeny ; Photosystem II Protein Complex/metabolism/genetics ; Metalloproteases/genetics/metabolism ; Plant Proteins/genetics/metabolism ; Genome, Plant ; Stress, Physiological ; }, abstract = {The study identified and characterized FtsH gene family in Setaria italica, where a comparative analysis with Arabidopsis thaliana revealed a conservation of expression patterns and functioning of specific FtsH proteases under heat and high light stress. The filamentation temperature-sensitive H (FtsH) metalloproteases maintain proteostasis in chloroplasts and mitochondria under both normal and stress conditions. Here, we compared the specificity of FtsH proteases to heat (HS) and high light (HL) stress (HLS) in C3 model plant Arabidopsis thaliana and an important C4 model crop with high nutritional value, Setaria italica. We identified 9 FtsH genes representing all homologs of functional AtFtsH genes, except for the homologs of AtFtsH12 in S. italica. Gene ontology (GO) analysis revealed a significant enrichment towards the photosynthetic process. Promoter analysis revealed the presence of cis-elements responsive to HL and HS. Interestingly, only selective genes encoding photosystem (PS) II-repairing FtsHs (AtFtsH1, AtFtsH2, AtFtsH5, and AtFtsH8), and FtsHs involved in PSII biogenesis and protein import regulation (AtFtsH4 and AtFtsH11, respectively), and their homologs in S. italica, showed transcriptional upregulation in response to HL, revealing their conserved function under photoinhibitory stresses, which is further reinforced by a rapid induction of FtsH2 and concurrent degradation of PSII reaction center proteins (D1 and D2). On the contrary, almost all FtsH genes were upregulated in response to elevated temperature, establishing their critical and conserved function in maintaining chloroplast proteostasis under HS. AtFtsH6 and its homolog, SiFtsH4, showed a marked induction in both transcript and protein levels with concurrent degradation of PSII-LHC proteins upon elevated temperatures, indicating their possible role in PSII-LHC proteostasis under HS. In summary, this study highlights the specificity of FtsHs in maintaining proteostasis under HS and HLS conditions in C3 and C4 plants.}, } @article {pmid41812958, year = {2026}, author = {Zhang, J and Liu, B and Meng, L and You, L and Liu, Z and Wu, Y and Zhang, C and Zhou, Y and Chen, R and Cao, Z and Sun, Y}, title = {Identification and functional analysis of Bcl2-associated agonist of cell death (Bad) reveals its pro-apoptotic and antibacterial roles in Cromileptes altivelis.}, journal = {Fish & shellfish immunology}, volume = {173}, number = {}, pages = {111264}, doi = {10.1016/j.fsi.2026.111264}, pmid = {41812958}, issn = {1095-9947}, mesh = {Animals ; Vibrio/physiology ; Fish Proteins/genetics/immunology/chemistry ; *Apoptosis/genetics ; *Fish Diseases/immunology ; Vibrio Infections/immunology/veterinary ; *Gene Expression Regulation/immunology ; Amino Acid Sequence ; Sequence Alignment/veterinary ; *bcl-Associated Death Protein/genetics/immunology/chemistry ; Gene Expression Profiling/veterinary ; *Immunity, Innate/genetics ; *Perciformes/immunology/genetics ; Phylogeny ; Base Sequence ; }, abstract = {Bcl-2-associated agonist of cell death (Bad) is a pro-apoptotic member of the Bcl-2 family that contains only the BH3 domain and plays a critical role in mitochondrial apoptosis in mammals. However, its functional role in teleosts remains to be fully elucidated. In this study, we identified and characterized the Bad homolog from Cromileptes altivelis (designated CaBad). The complete coding sequence of CaBad comprises 504 bp, encoding a protein of 167 amino acids with only one conserved BH3 domain. CaBad was ubiquitously expressed in healthy C. altivelis, with highest transcript levels detected in immune-related tissues including liver, spleen, and head kidney. Following challenge with Vibrio harveyi, CaBad expression was significantly upregulated in the liver, spleen, and head kidney. Subcellular localization analysis revealed that CaBad was distributed in the cytoplasm and nucleus, and showed enhanced mitochondrial translocation during apoptosis. Flow cytometry assays demonstrated that CaBad promoted apoptosis of C. altivelis brain (CAB) cells upon V. harveyi flagellin B (Fla B) stimulation. This pro-apoptotic effect was mediated through the mitochondrial pathway, as demonstrated by loss of mitochondrial membrane potential, increased DNA fragmentation, activation of Caspase 9 and Caspase 3, and upregulation of key pro-apoptotic proteins including cytochrome c and p53. Furthermore, CaBad was found to inhibit the NF-κB signaling pathway, as evidenced by suppressed IKKα phosphorylation and downregulated transcription of NF-κB subunits and pro-inflammatory cytokines both in vitro and in vivo. Importantly, in vivo infection experiments showed that CaBad overexpression significantly reduced bacterial loads in immune tissues, whereas CaBad knockdown led to increased bacterial colonization. Collectively, our results indicate that CaBad exerts a conserved pro-apoptotic function via the mitochondrial pathway and contributes to antibacterial immunity in C. altivelis, providing new insights into the role of BH3-only proteins in teleosts host defense.}, } @article {pmid41818954, year = {2026}, author = {Alghamdi, M and Alahmad, A and Alaboudi, M and Alsheikh, S and Alanazy, MH and Albash, B and Alaqeel, A and Almontashiri, NA and Jamjoom, D and Bashiri, FA and Hamad, MH and Ali, HH and Alwatidi, M and Alharbi, E and Omar, S and Marafi, D and Alabdulrazzaq, F and Arold, ST and McFarland, R and W Taylor, R}, title = {TTC19-related mitochondrial complex III deficiency: Clinical and genetic characterization of 10 patients from 5 unrelated Arab families.}, journal = {Molecular genetics and metabolism}, volume = {148}, number = {2}, pages = {109867}, doi = {10.1016/j.ymgme.2026.109867}, pmid = {41818954}, issn = {1096-7206}, mesh = {Humans ; Female ; Male ; *Mitochondrial Diseases/genetics/pathology ; Arabs/genetics ; Child ; *Electron Transport Complex III/deficiency/genetics ; *Mitochondrial Proteins/genetics ; Child, Preschool ; Adolescent ; Pedigree ; Phenotype ; Adult ; Exome Sequencing ; Mutation ; Mitochondria/genetics/pathology ; Membrane Proteins ; }, abstract = {Isolated mitochondrial complex III deficiency can result from pathogenic variants in several nuclear or mitochondrial genes, encoding structural subunits or assembly factors of the enzyme. It is a rare cause of mitochondrial phenotypes with clinically heterogeneous presentations. Pathogenic variants in the Tetratricopeptide Repeat Domain 19 (TTC19) gene have been identified as a cause of mitochondrial complex III deficiency, nuclear type 2 (MIM #615157). We report 10 patients from five unrelated Arab families, all presenting with variable severity of a progressive neurodegenerative disorder characterized by loss of ambulation, speech impairment, and cognitive regression. Long-term clinical follow-up, supported by serial neuroradiological imaging, demonstrated progressive disease evolution, further highlighting the degenerative nature of the condition. In this cohort, exome sequencing (ES) identified three distinct pathogenic variants in the TTC19 gene across the five unrelated families, highlighting both genetic heterogeneity and regional clustering. In a Saudi family, A novel in-frame TTC19 variant NM_017775.4:c.680_709del; p.(Glu227_Leu236del) was identified, resulting in the loss of 10 amino acids in the protein. The second variant, NM_017775.4:c.779_780del; p.(Tyr260*), is a frameshift deletion leading to truncation of the TTC19 protein. This recurrent variant was identified in three independent Syrian families (Families 2, 3, and 4). The third variant, NM_017775.4:c.153_156del; p.(Arg52Alafs*48), also a frameshift variant, was detected in a fifth family of Kuwaiti origin. These loss of function TTC19 variants are proposed to underlie the observed phenotypes, as supported by mitochondrial functional studies, and contribute to the expanding spectrum of TTC19-related disorders, with specific variants recurring in particular regional or ethnic populations.}, } @article {pmid41821201, year = {2026}, author = {Aoudache, Y and Inturri, S and Das Neves, B and de Bont, L and Remacle, C and Rouhier, N}, title = {Updated Inventory and Refined Classification of the Ferredoxin Family in Archaeplastida.}, journal = {Physiologia plantarum}, volume = {178}, number = {2}, pages = {e70836}, doi = {10.1111/ppl.70836}, pmid = {41821201}, issn = {1399-3054}, support = {CDR J.0149.23//Fonds De La Recherche Scientifique - FNRS/ ; ANR-11-LABX-0002-01//Agence Nationale de la Recherche/ ; }, mesh = {*Ferredoxins/metabolism/genetics/classification ; Phylogeny ; Chlamydomonas reinhardtii/genetics/metabolism ; Arabidopsis/genetics/metabolism ; Plastids/metabolism/genetics ; Mitochondria/metabolism ; Iron-Sulfur Proteins/metabolism ; }, abstract = {Ferredoxins (FDXs) are ubiquitous proteins that bind iron-sulfur (Fe-S) clusters and usually catalyse electron transfer reactions. In eukaryotic photosynthetic organisms, a relatively high number of [2Fe-2S] cluster-containing FDXs is present in plastids and mitochondria. These are mostly redox-active FDXs, except one mitochondrial FDX that no longer binds an Fe-S cluster and is a component of the respiratory complex I. We have performed a phylogenomic study to describe the content and distribution of FDXs in different phylogenetic groups of the Archaeplastida clade, including the two models Arabidopsis thaliana and Chlamydomonas reinhardtii. Important differences exist since the number of FDXs ranges from four to 19. From the sequence characteristics and phylogenetic analyses, they cluster in 10 clades: eight containing plastidial FDXs and two mitochondrial FDXs. Six clades are present in most organisms, while four clades comprising plastidial FDXs (FDX5, FDX7, FDX8, and FDX9) are present in a small subset of organisms, mostly algae and lower Embryophytes; the FDX5 and FDX9 clades are even only present in Chlorophyceae. The expression patterns of these two FDXs in Chlamydomonas combined with the physiological and biochemical studies performed with FDX5 suggest specific roles of FDX5 in anoxia and of FDX9 in the dark. Structural analyses provide additional support to the functional divergence among plastidial FDXs. Overall, these analyses revealed the existence of an important diversity within the FDX family and allowed refining the FDX classification in Archaeplastida. It also provides clues for future physiological analyses to decipher the functions of the uncharacterised FDXs.}, } @article {pmid41824493, year = {2026}, author = {De Anda, V and Appler, KE and Aguilar-Pine, E and Aitolo, GL and Halverson, GP and Baker, BJ}, title = {The archaeal roots of eukaryotic life.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {13}, pages = {e2516062123}, pmid = {41824493}, issn = {1091-6490}, support = {73592LPI//Simons Foundation (SF)/ ; LI-SIAME-00002001//Simons Foundation (SF)/ ; }, mesh = {*Archaea/genetics/classification/metabolism ; Biological Evolution ; Phylogeny ; *Eukaryota/genetics ; *Eukaryotic Cells ; }, abstract = {Resolving the biological and geological events that led to the origin of eukaryotes is an ongoing challenge in biology. A major step in the evolution of complex cellular life was the merger between an ancestral host cell and a bacterium (that became the mitochondrion) some two billion years ago. Recently, metagenomics has enabled the reconstruction of a broad diversity of genomes, referred to as the Asgard Archaea. The Asgards are monophyletic with eukaryotes on the tree of life. Asgards have an array of genes, previously thought exclusive to eukaryotes, involved in cellular trafficking, the ubiquitin system, endosomal sorting, and cytoskeleton formation, with growing evidence demonstrating the functions of these proteins mirror those in eukaryotes. This gene repertoire suggests that these Archaea are descendants of the archaeal host from which eukaryotes evolved. Increased sampling has revealed that Asgard lineages are metabolically versatile and play key roles in various ecosystems and uncovered evolutionary transitions between Archaea and eukaryotes, such as innovations in eukaryotic defense systems. The positioning of eukaryotes in the Asgards is debated, but eukaryotes appear to branch within the Heimdallarchaeia. Lineages within this group, particularly Hodarchaeales and Kariarchaeaceae, contain a broad repertoire of eukaryote-like traits, including high-energy yielding metabolisms. Observing and studying Asgard interactions with bacterial descendants of mitochondria in a modern setting will transform our understanding of the origin of complex cellular life.}, } @article {pmid41825141, year = {2026}, author = {Carneiro da Cunha Martorelli, V and Akabuogu, E and Tank, R and Krašovec, R and Roberts, IS and Waigh, TA}, title = {AC electro-osmosis in bacterial communities with fluorescence-based electrophysiology measurements using exogeneous fluorophores.}, journal = {Physical biology}, volume = {23}, number = {2}, pages = {}, doi = {10.1088/1478-3975/ae51fd}, pmid = {41825141}, issn = {1478-3975}, mesh = {*Fluorescent Dyes/chemistry ; *Electroosmosis ; Fluorescence ; }, abstract = {Synthetic cationic fluorophores are widely used as probes to measure the membrane potentials of bacterial cells, eukaryotic cells, and organelles (such as mitochondria) in electrophysiology experiments and live/dead assays. We applied an external oscillating electric field toEscherichia coliusing microelectrodes and observed that AC electro-osmosis caused fluorescence transients independent of bacterial electrophysiology, which could be mistaken for membrane depolarisation events. The fluorophores migrated within the microfluidic device in vortices, leading to concentration fluctuations manifested as dips in fluorescence. These fluorescent dips were universally present when using cationic fluorophores such as thioflavin-T, propidium iodide, Syto9, and Sytox Green, with or withoutE. colipresent, whenever AC voltages were applied. Furthermore, we also demonstrate that fluorescence dips in dense bacterial communities can arise from AC electro-osmosis rather than ion-channel activity. This cautionary tale highlights how electrical stimulation experiments in microbial communities can yield misleading results if electrokinetic effects are not accounted for. We quantified the relaxation times of fluorophores under AC electro-osmosis, which depended on the community, the cells, and the dye used: PI showed the shortest relaxation time and Syto9 the longest. Removing cells resulted in longer relaxation times, and introducing dense communities did not significantly alter the relaxation times compared with single-cell experiments. Furthermore, fluorescently labelled DNA and fluorescent colloidal beads (30-130 nm) also exhibited fluorescence dips due to AC electro-osmosis, demonstrating that charged molecules and particles readily penetrate and accumulate within these assemblies. To our knowledge, this is the first study to characterise AC electro-osmosis in dense bacterial communities, revealing the high mobility of charged molecules in such systems and suggesting possible applications for enhancing antibiotic delivery.}, } @article {pmid41830411, year = {2026}, author = {Matos, LCP and Milburn, A and MacDonald, C}, title = {Uptake Mechanisms and Physiological Effects of Furanic Compounds From the Maillard Reaction in Budding Yeast.}, journal = {Yeast (Chichester, England)}, volume = {43}, number = {1-2}, pages = {55-70}, pmid = {41830411}, issn = {1097-0061}, support = {204636/Z/16/Z//Wellcome Trust and the Royal Society/ ; 405816/2021-9//National Council for Scientific and Technological Development/ ; }, mesh = {*Maillard Reaction ; *Furaldehyde/analogs & derivatives/metabolism/toxicity ; *Furans/metabolism/toxicity ; Saccharomyces cerevisiae Proteins/metabolism/genetics ; *Saccharomyces cerevisiae/metabolism/drug effects ; ATP-Binding Cassette Transporters/metabolism/genetics ; Biological Transport ; Mitochondria/drug effects/metabolism ; *Saccharomycetales/metabolism/drug effects ; }, abstract = {Maillard reaction products (MRPs) are formed during the thermal processing of foods and exhibit important sensory attributes. Furanic compounds are a subset of MRPs commonly found in food products that are toxic to eukarytoic cells, although the mechanisms of toxicity are poorly understood. We used budding yeast to explore uptake mechanisms of common furanic compounds: 5-hydroxymethylfurfural (HMF), furfural (FUR), and 2-Furyl methyl ketone (FMK). Titrations of each furanic compound were used to identify concentrations that have an inhibitory effect on growth. We identified HMF as a potential substrate of the Pdr5 multidrug resistance pump and linked HMF and FUR toxicity to surface nutrient transporter levels. Live cell imaging shows that HMF disrupts mitochondria whilst FUR affects the endolysosomal system. Results indicate these furanic compounds may have distinct uptake, efflux, and toxicity mechanisms. As many of these cellular components are conserved throughout evolution, this work could shed light on the metabolism of toxic compounds commonly found within animal food sources.}, } @article {pmid41831440, year = {2026}, author = {Cho, A and Burns, JA and Woyke, T and Stepanauskas, R and Poulton, N and Wideman, JG}, title = {Aerobic sister lineage of breviates has gene-rich mitochondrial genomes.}, journal = {Current biology : CB}, volume = {36}, number = {6}, pages = {1481-1493.e6}, doi = {10.1016/j.cub.2026.02.024}, pmid = {41831440}, issn = {1879-0445}, mesh = {*Genome, Mitochondrial/genetics ; Phylogeny ; Aerobiosis ; *Eukaryota/genetics ; Mitochondria/genetics ; }, abstract = {The tree of eukaryotes has gone through numerous overhauls in recent decades, leading to a growing consensus on major supergroups. This stabilization has revealed that anaerobic eukaryotic lineages evolved convergently and that the variety of non-canonical mitochondria in these anaerobes evolved in parallel. These non-canonical mitochondria, known as mitochondrion-related organelles (MROs), are found in organisms that thrive in oxygen-limited environments and have highly reduced or no mitochondrial genomes (mtDNA). Breviates are anaerobic/microaerophilic flagellates that harbor hydrogen-producing MROs and lack mtDNA. Breviates, alongside apusomonads and opisthokonts, form a lineage called Obazoa. To identify novel microaerophiles within Obazoa, we sampled an intertidal mudflat and used flow cytometry-based single-cell sorting to generate single-cell amplified genomes (SAGs). We identified a new lineage closely related to known breviates using phylogenomics. Surprisingly, we recovered several mtDNAs in the breviate-related (BR) SAGs, with genes encoding most of the electron-transport chain complexes. These BR mtDNAs harbor rare mitochondrial genes such as rpl21 and rnpB that are lost or usually encoded in nuclear genomes in most eukaryotes. In several nuclear genomes of the BR SAGs, we detected genes encoding enzymes for anaerobic respiration and hydrogen production (e.g., [FeFe]-hydrogenase and pyruvate:ferredoxin oxidoreductase), suggesting that these organisms could be facultative anaerobes. We additionally recovered mtDNAs from apusomonad SAGs that are gene-rich compared with other known apusomonad mtDNAs. The identification and initial characterization of a new clade within Obazoa provide avenues to better understand the process of mitochondrial reductive evolution and highlight the important role of microscope-independent approaches in discovering new lineages.}, } @article {pmid41833805, year = {2026}, author = {Huang, R and Yan, C and Lv, Y and Jin, Y and Zhang, D}, title = {Immunological functional studies of a putative lipocalin member LcApoM_AGPRP in large yellow croaker (Larimichthys crocea).}, journal = {Fish & shellfish immunology}, volume = {173}, number = {}, pages = {111274}, doi = {10.1016/j.fsi.2026.111274}, pmid = {41833805}, issn = {1095-9947}, mesh = {Animals ; *Perciformes/immunology/genetics ; *Immunity, Innate/genetics ; Fish Proteins/genetics/immunology/chemistry ; Poly I-C/pharmacology ; Sequence Alignment/veterinary ; *Fish Diseases/immunology ; Amino Acid Sequence ; *Gene Expression Regulation/immunology ; *Lipocalins/genetics/immunology/chemistry ; Phylogeny ; Lipopolysaccharides/pharmacology ; Gene Expression Profiling/veterinary ; }, abstract = {Lipocalins play crucial roles in immune defense in vertebrates; however, their functional mechanisms in teleost fish remain poorly understood. In this study, the economically important marine fish large yellow croaker (Larimichthys crocea) was used as a model to investigate a novel lipocalin-like protein, LcApoM_AGPRP, and to elucidate its role in immune responses. A putative antibacterial protein, LcApoM_AGPRP, which lacks functional annotation in the genome, was identified in large yellow croaker. LcApoM_AGPRP was highly constitutively expressed in the liver, head kidney, ovary, gill and spermary of healthy large yellow croaker. It expression was significantly upregulated following LPS and Poly(I:C) stimulation, indicating a potential role in innate immune responses. Subcellular localization analysis demonstrated that LcApoM_AGPRP is predominantly localized in lysosomes, mainly distributed in the Golgi apparatus and mitochondria and partially distributed in the endoplasmic reticulum, implying its involvement in organelle-mediated immune defense. Functional assays showed that LcApoM_AGPRP possesses broad-spectrum antimicrobial activity. The recombinant protein exerts its antibacterial effects through multiple mechanisms, including disruption of bacterial membrane integrity, inhibition of bacterial motility, and interference with biofilm formation. Stability assays further confirmed that its antibacterial activity is maintained over a wide range of temperatures (25-100 °C) and salinities (0-40 ‰), highlighting its strong environmental adaptability. These properties suggest that LcApoM_AGPRP has considerable potential for application as an antibacterial agent, aquaculture feed additive, or food preservative. This study provides the first systematic identification and functional characterization of LcApoM_AGPRP, offering new insights into the innate immune system of teleost fish.}, } @article {pmid41837793, year = {2026}, author = {Sterling, JE and Zwonitzer, KD and Havird, JC}, title = {Lifespan Predicts Mitochondrial Substitution Rates across Vertebrates, but Methodology Matters.}, journal = {Genome biology and evolution}, volume = {18}, number = {3}, pages = {}, pmid = {41837793}, issn = {1759-6653}, support = {R35GM142836//National Health Institute/ ; }, mesh = {Animals ; *DNA, Mitochondrial/genetics ; *Longevity/genetics ; *Evolution, Molecular ; *Mutation Rate ; Phylogeny ; *Vertebrates/genetics ; *Mitochondria/genetics ; Mutation ; }, abstract = {Why do some species live for mere months, while others persist for centuries? A leading explanation implicates mitochondria. The mitochondrial theory of aging predicts that mitochondrial efficiency diminishes with age due to the accumulation of mutations within mitochondrial DNA (mtDNA). While experimental evidence for this theory is mixed, evolutionary analyses offer an ideal opportunity to determine if mitochondrial substitution rates are linked to longevity. Here, we explored the relationship between mtDNA evolution and species' lifespans across four clades-Aves, Actinopterygii, Bivalvia, and Sebastidae-using five normalization strategies. Across most methods, long-lived vertebrates showed reduced synonymous and nonsynonymous substitution rates, suggesting lower mtDNA mutation. However, we found that the strength and direction of these relationships varied drastically depending on the normalization approach used (ie correcting for divergence, generation time, and phylogeny). We also analyzed mtDNA mutation spectra and found similar patterns in long- and short-lived species, suggesting decreased rates of mtDNA mutations in long-lived species are not due to suppression of specific mutation processes, as predicted from the free radical theory of aging. We also find little evidence for a relationship between selection on mitochondrial protein-coding genes and lifespan. Our results align with the idea that decreased mutation rates may help preserve mitochondrial integrity in long-lived vertebrate species, but that these species have not been selected to have particularly efficient OXPHOS or protection against a specific mitochondrial mutation process. Together, these findings underscore the critical link between mitochondrial stability and lifespan, and highlight the power of natural systems in this field.}, } @article {pmid41862009, year = {2026}, author = {Lin, L and Ke, H and Chen, M and Zhang, Y and Fu, S and Yu, F and Su, J and Yang, X and Guo, Y and Ding, Q and Zhang, Y and Zhao, L}, title = {Downregulation of TDP43 by atovaquone inhibits oxidative phosphorylation and enhances sensitivity of triple-negative breast cancer to EGFR-TKIs.}, journal = {Free radical biology & medicine}, volume = {250}, number = {}, pages = {64-79}, doi = {10.1016/j.freeradbiomed.2026.03.047}, pmid = {41862009}, issn = {1873-4596}, mesh = {Humans ; *Triple Negative Breast Neoplasms/drug therapy/pathology/genetics/metabolism ; *Oxidative Phosphorylation/drug effects ; ErbB Receptors/antagonists & inhibitors/genetics/metabolism ; Female ; *DNA-Binding Proteins/genetics/metabolism/antagonists & inhibitors ; *Protein Kinase Inhibitors/pharmacology ; *Drug Resistance, Neoplasm/drug effects/genetics ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic/drug effects ; Neoplastic Stem Cells/drug effects/metabolism/pathology ; Animals ; Down-Regulation ; Mitochondria/metabolism/drug effects ; }, abstract = {Epidermal growth factor receptor (EGFR) is overexpressed in most triple-negative breast cancer (TNBC) patients with poor prognosis; however, the therapeutic benefit of EGFR inhibitors (EGFRi) in breast cancer remains limited. In this study, we found poor response to EGFRi in TNBC was related to oxidative phosphorylation (OXPHOS) and breast cancer stem cells (BCSCs), and demonstrated that TDP43 (TAR DNA-binding protein 43) expression is positively correlated with non-response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). TDP43 knockdown significantly enhances EGFR-TKI sensitivity and decreases EGFR-TKI resistance. Mechanistically, TDP43, a DNA/RNA-binding protein predominantly localized to the nucleus, translocates to mitochondria upon EGFR-TKI stimulation. The increased mitochondrial localization promotes OXPHOS, thereby enriching BCSCs and contributing to EGFR-TKI resistance. Inhibiting TDP43 expression or using our newly identified TDP43 inhibitor, atovaquone, suppresses OXPHOS and reduces EGFR-TKI resistance. Overall, our research identified TDP43 as a key regulator of EGFR-TKI sensitivity and resistance, and offers new therapeutic targets and promising application perspectives in TNBC.}, } @article {pmid41864362, year = {2026}, author = {Shahzaib, M and Aprile, D and Alessio, N and Laporta, G and Peluso, G and Di Bernardo, G and Galderisi, U}, title = {Humanin as an evolutionarily tuned mitochondrial peptide: Insights from mammalian oxidative stress diversity.}, journal = {Free radical biology & medicine}, volume = {250}, number = {}, pages = {49-63}, doi = {10.1016/j.freeradbiomed.2026.03.033}, pmid = {41864362}, issn = {1873-4596}, mesh = {Animals ; *Oxidative Stress ; Humans ; *Evolution, Molecular ; *Mitochondria/metabolism ; Reactive Oxygen Species/metabolism ; Amino Acid Sequence ; Mammals ; Molecular Docking Simulation ; *Mitochondrial Proteins/metabolism/genetics ; Peptides ; Intracellular Signaling Peptides and Proteins ; }, abstract = {Humanin is a mitochondrial-derived peptide with cytoprotective properties, but how it has evolved in response to different oxidative stress levels in mammals is not fully understood. This study examines how Humanin sequences have adapted to species-specific metabolic and environmental pressures. We compared the peptide in several mammalian species categorized by their distinct oxidative stress profiles: small mammals such as shrews with high metabolic rates and elevated endogenous ROS production, cetaceans exposed to hypoxia-reoxygenation cycles during deep diving, and long-lived primates facing cumulative oxidative stress over extended lifespans. Using bioinformatic tools, we analyzed physicochemical traits such as structural stability, the aliphatic index, and oxidation susceptibility. We also used protein-protein docking to estimate binding affinities between Humanin variants and key ligands like BAX and FPRL1. Our results show that Humanin is not a static molecule. Species facing high oxidative stress, such as cetaceans and bats, possess variants that are more stable and chemically robust. In contrast, species with high ROS production but lower antioxidant capacity, like the shrew, have less robust versions of the peptide. Simulation data indicate that variants from mammals living in extreme conditions maintain or improve interactions with proteins involved in cell survival. These findings suggest that evolution has tuned Humanin to optimize mitochondrial protection across different physiological contexts. These natural isoforms provide a structural basis for designing new therapeutic analogs to treat oxidative stress-related diseases in humans.}, } @article {pmid41877583, year = {2026}, author = {Carlström, A and Vazquez-Calvo, C and Ott, M}, title = {The complexities of respiratory chain biogenesis and maintenance in yeast mitochondria.}, journal = {Protein science : a publication of the Protein Society}, volume = {35}, number = {4}, pages = {e70545}, pmid = {41877583}, issn = {1469-896X}, support = {//Vetenskapsrådet/ ; //Knut och Alice Wallenbergs Stiftelse/ ; //Cancerfonden/ ; }, mesh = {*Saccharomyces cerevisiae/metabolism/genetics ; *Mitochondria/metabolism/genetics ; Oxidative Phosphorylation ; *Saccharomyces cerevisiae Proteins/metabolism/genetics ; Electron Transport ; Mitochondrial Membranes/metabolism ; *Electron Transport Complex III/metabolism/genetics ; }, abstract = {Mitochondrial oxidative phosphorylation is the most efficient way of energy conversion for eukaryotic cells. It is executed by a series of high-molecular weight enzyme complexes in the inner mitochondrial membrane that were acquired during endosymbiosis at the root of eukaryotic evolution. Biogenesis of this machinery depends not only on nuclear gene expression and protein import, but also on an organelle-specific system to express a handful of proteins encoded in mitochondrial DNA. These two genetic systems cooperate for the biogenesis and maintenance of oxidative phosphorylation complexes. Here, we use the respiratory chain complex III as an example to highlight the complexities of this process. Specifically, we will describe the intricate mechanisms by which respiratory chain complexes are assembled, how the two genetic systems are coordinated and how biogenesis and function are physically separated within the inner mitochondrial membrane. To do so, we will primarily discuss findings from baker's yeast, where a wealth of recent data revealed exciting insights into these processes.}, } @article {pmid41884264, year = {2026}, author = {Yu, F and Li, Y and Qu, R and Wang, Z and An, W and Chen, Y and Yue, Z and Wang, W}, title = {Mitochondrial complex I in focus: mechanisms and therapeutic strategies of urinary system diseases.}, journal = {Frontiers in physiology}, volume = {17}, number = {}, pages = {1753159}, pmid = {41884264}, issn = {1664-042X}, abstract = {Recent research findings on the role of mitochondrial complex I (CI) in promoting renal cell carcinoma metastasis have been published in Nature. Mitochondria, as essential intracellular organelles in mammalian cells, play a pivotal role in orchestrating biological oxidation processes and are crucial for maintaining cellular metabolic homeostasis. Severe mitochondrial dysfunction, particularly involving CI, can lead to the development of urinary system diseases by initiating a cascade of events such as inflammation, impaired mitochondrial autophagy, and related processes. This article explores the involvement of CI in the pathogenesis and progression of urinary system diseases. It begins by introducing fundamental theories related to CI research in urinary system diseases, including its evolution, structure, function, and role in cellular metabolism. The epidemiology of CI-associated urinary system diseases, encompassing both neoplastic and non-neoplastic conditions and their associated risk factors, is subsequently discussed. The article further elaborates on the pathological mechanisms, diagnostic techniques, and therapeutic strategies targeting CI in these diseases. In conclusion, this review addresses the controversies and future directions within this research domain, aiming to provide a comprehensive understanding of the CI in urinary system diseases. It also emphasizes potential avenues for future research and translational applications.}, } @article {pmid41895656, year = {2026}, author = {Peng, L and Dai, Y}, title = {Prevalence of anti-mitochondrial antibodies and clinical features in autoimmune hepatitis (AIH) patients.}, journal = {Clinics and research in hepatology and gastroenterology}, volume = {50}, number = {5}, pages = {102810}, doi = {10.1016/j.clinre.2026.102810}, pmid = {41895656}, issn = {2210-741X}, mesh = {Humans ; *Hepatitis, Autoimmune/immunology/blood/diagnosis ; Female ; Male ; *Autoantibodies/blood ; Retrospective Studies ; Middle Aged ; *Mitochondria/immunology ; Liver Cirrhosis, Biliary/immunology/blood ; Adult ; Prevalence ; Aged ; }, abstract = {OBJECTIVE: To assess the prevalence of anti-mitochondrial antibodies (AMA) in autoimmune hepatitis (AIH) patients and to compare the clinical, biochemical, immunological, and histopathological profiles among AMA-positive AIH, AMA-negative AIH, and AIH/primary biliary cholangitis (PBC) overlap syndrome cohorts.

METHODS: A retrospective cohort study was conducted to analyze clinical data from 228 AIH patients and 227 AIH/PBC overlap syndrome patients diagnosed at Wuxi Fifth People's Hospital between 2017 and 2025.

RESULTS: The AMA prevalence among the diagnosed and probable AIH patients was 19.05% and 18.63%, respectively. AMA-positive AIH patients exhibited significantly lower AMA-M2 titers compared to AIH/PBC patients. Biochemically and immunologically, the prevalence of anti-gp210 antibodies in confirmed and probable AMA-positive AIH patients was higher than that in AMA-negative AIH patients. Confirmed AMA-positive AIH patients showed lower levels of γ-GT, ALP, and IgM compared to AIH/PBC overlap patients. Probable AMA-positive AIH patients also demonstrated reduced γ-GT and ALP levels relative to AIH/PBC overlap syndrome.Regarding clinical symptoms, definite AMA-positive AIH patients had a higher prevalence of pruritus than AMA-negative AIH patients and AIH/PBC overlap syndrome patients, and a lower prevalence of anorexia than AMA-negative AIH patients. In probable AIH patients, no statistically significant differences in clinical symptoms were observed among different AMA statuses or when compared to AIH/PBC overlap syndrome patients. Clinical symptoms across different patient groups showed varying degrees of positive or negative correlation with serological markers. Pathologically, the prevalence of bile duct injury positivity in confirmed and probable AIH patients were lower than in AIH/PBC overlap syndrome patients. The inflammatory activity levels in confirmed and probable AMA-positive AIH patients were lower than in AMA-negative patients.Serial liver biopsy results indicated that bile duct injury in AIH patients often regressed, whereas in AIH/PBC overlap syndrome patients, it predominantly persisted.

CONCLUSION: AMA positivity is not uncommon among AIH patients, and positivity for anti-gp210 antibodies may be associated with AMA status. The AIH/PBC overlap syndrome exhibits features of both conditions, characterized by more pronounced bile duct injury and cholestasis than isolated AIH.The dynamic evolution characteristics of bile duct injury can provide important pathological evidence for differentiating between the two diseases. The correlation between clinical symptoms and serological markers may offer valuable reference for assessing disease activity in AIH patients.}, } @article {pmid41898477, year = {2026}, author = {Liu, F and Jin, S and Song, H}, title = {Structural Remodeling and Enzymatic Replacement Shape the Evolution of Organellar Group II Introns in Ulva.}, journal = {International journal of molecular sciences}, volume = {27}, number = {6}, pages = {}, pmid = {41898477}, issn = {1422-0067}, support = {42276133//National Natural Science Foundation of China/ ; 2025TSGCCZZB0313//Shandong Provincial Key Research and Development Program Project/ ; }, mesh = {*Introns/genetics ; *Ulva/genetics/enzymology ; *Evolution, Molecular ; Phylogeny ; Nucleic Acid Conformation ; RNA, Catalytic/genetics ; Chloroplasts/genetics ; Mitochondria/genetics ; }, abstract = {Group II introns are catalytic RNAs that combine self-splicing ribozyme activity with mobility and have played major roles in shaping organellar genome evolution. In green macroalgae of the genus Ulva, organellar genomes are highly compact, yet they harbor unusually diverse and dynamic repertoires of group II introns. To understand how organellar group II introns diversify and persist within compact organellar genomes, we performed a comparative analysis of mitochondrial and chloroplast group II introns across Ulva, integrating secondary structure reconstruction, intron occurrence patterns, and phylogenetic inference based on both conserved intron RNA regions and intron-encoded proteins (IEPs), including reverse transcriptase/maturase (RT/M) and LAGLIDADG homing endonuclease (LHE). A total of 168 mitochondrial and 123 chloroplast introns were identified and classified into 32 families belonging to seven major subgroups (IIA1-RT/M, IIA2-RT/M, IIB1-RT/M, IIB1-LHE, IIB2-RT/M, IIB2-LHE, and IIB-like). Most intron families retain the canonical six-domain architecture (DI-DVI), but four mitochondrial IIA families display a seven-domain configuration generated by the lineage-specific insertion of an additional stem-loop structure (DIIIa). Phylogenetic analyses revealed a high degree of congruence, supporting persistent coevolution between RNA scaffolds and their IEPs. Notably, the LHE-encoding families were scattered across distinct IIB lineages instead of forming a single clade, suggesting that at least two independent invasion events occurred within the IIB1 and IIB2 lineages. Analysis of intron occurrence frequency revealed an evolutionary continuum ranging from structurally intact and broadly distributed families to lineage-specific families exhibiting progressive scaffold degeneration, with the chloroplast infA-62 family representing a stably inherited lineage maintained through vertical transmission. These results suggest that organellar group II introns in Ulva evolve through coordinated scaffold remodeling, enzymatic replacement, and differential distribution patterns across genomic compartments, highlighting Ulva organellar genomes as a valuable comparative model for investigating the long-term evolution of mobile ribozymes within compact genomic environments.}, } @article {pmid41898747, year = {2026}, author = {Mohsin, MM and Azher, M and Asghar, F and Rahiman, HH and Dube, R and Kar, SS and Bahutair, SNM and Goud, BKM and Kar, SS}, title = {Mitochondrial DNA Modification in Assisted Reproduction: Concept to Practice-A Narrative Review.}, journal = {International journal of molecular sciences}, volume = {27}, number = {6}, pages = {}, pmid = {41898747}, issn = {1422-0067}, mesh = {Humans ; *DNA, Mitochondrial/genetics ; *Reproductive Techniques, Assisted ; *Mitochondrial Replacement Therapy/methods ; *Mitochondria/genetics ; Animals ; *Mitochondrial Diseases/genetics/therapy ; }, abstract = {Mitochondria play a fundamental role in human reproduction by supplying the energy required for key early reproductive processes. As mitochondrial Deoxyribonucleic acid (mtDNA) is maternally inherited, pathogenic mutations can lead to multisystem disorders that are transmitted to offspring. Mitochondrial replacement therapy (MRT) has emerged as a promising assisted reproductive approach to prevent the transmission of pathogenic mtDNA by replacing defective mitochondria with healthy donor mitochondria. There have been recent reports of successful MRT in humans. However, MRT remains a relatively new procedure and needs further experiments to establish its long-term safety and effectiveness. Overall, mitochondrial replacement therapy holds significant promise in helping families build healthier futures. This review explores the evolution of mitochondrial DNA modification in reproductive cells and addresses the associated ethical considerations, including acceptable clinical indications, reproductive choices, and long-term considerations for affected children.}, } @article {pmid41911061, year = {2026}, author = {Guna, A and Nguyen, VN and Stevens, TA and Voorhees, RM}, title = {Membrane Protein Insertion in Mammalian Cells.}, journal = {Annual review of biochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-biochem-080125-020218}, pmid = {41911061}, issn = {1545-4509}, abstract = {Integral membrane proteins play critical roles in mammalian cells, ranging from mediating cell-cell interactions to regulating apoptosis. These increasingly diverse functions necessitated the evolution of membrane proteins with more complex biophysical properties and architectures. In turn, specialized complexes called insertases have coevolved to integrate these proteins into the appropriate lipid bilayer. Notably, key sites of membrane protein biogenesis such as the endoplasmic reticulum and the outer and inner membranes of the mitochondria rely on distinct sets of insertases that work in concert, each specializing in membrane protein segments with particular features or properties. Here, we describe recent discoveries that shed light both on the molecular mechanisms of these insertases and on the many distinct pathways required for the insertion and folding of the mammalian membrane proteome.}, } @article {pmid41911639, year = {2026}, author = {Deng, Y and Guo, N and Li, D and Wang, Z}, title = {Mitochondrial translational control in cardiovascular diseases: from mechanisms to therapies.}, journal = {Redox biology}, volume = {92}, number = {}, pages = {104143}, pmid = {41911639}, issn = {2213-2317}, mesh = {Humans ; *Cardiovascular Diseases/metabolism/genetics/therapy/pathology ; *Protein Biosynthesis ; Animals ; Oxidative Phosphorylation ; *Mitochondria/metabolism/genetics ; MicroRNAs/genetics ; Gene Expression Regulation ; *Mitochondria, Heart/metabolism/genetics ; RNA, Mitochondrial/genetics ; RNA, Transfer/genetics ; }, abstract = {Mitochondria orchestrate cardiac metabolic homeostasis, and their dysfunction constitutes a fundamental mechanism driving cardiovascular diseases (CVDs). During eukaryotic evolution, most of the mitochondrial genes required for oxidative phosphorylation (OXPHOS) function have been transferred to the nuclear genome, except for 13 genes coding for core subunits of the OXPHOS machinery. The translational regulation of these 13 genes inside mitochondria is precisely and dynamically regulated according to the external environment under diverse metabolic conditions. However, our understanding of these biological processes in CVDs remains limited. This review summarizes recent advances in the regulatory processes of mitochondrial translation, highlighting mitoribosome biogenesis, dynamic tRNA epitranscriptomic modifications, and coupling between translation and inner-membrane assembly. We additionally integrate emerging upstream regulatory mechanisms, including redox and metabolite-sensitive signaling, mitoepigenetic remodeling, and mitochondria-localized microRNA (mitomiR)-mediated control of mitochondrial RNA fate, which collectively tune translational output under stress. Moreover, this review delineates how these processes are dysregulated in major cardiovascular pathologies, including ischemia-reperfusion (I/R) injury, cardiac hypertrophy, heart failure (HF), and inherited cardiomyopathies. Emerging therapeutic strategies designed to restore translational fidelity and throughput, ranging from pharmacological interventions and metabolic tuning to precise mitochondrial gene editing, are also discussed. By repositioning mitochondrial translation from a passive marker of injury to a druggable control node, this review offers a new paradigm for targeting mitochondrial translation to preserve myocardial resilience and treat CVDs.}, } @article {pmid41914285, year = {2026}, author = {Stefano, GB}, title = {NAD[+] Homeostasis and Mitochondrial Modifiability: Resilience in Alzheimer's Disease.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {31}, number = {3}, pages = {49714}, doi = {10.31083/FBL49714}, pmid = {41914285}, issn = {2768-6698}, mesh = {*Alzheimer Disease/metabolism/pathology ; Humans ; *Homeostasis ; *NAD/metabolism ; *Mitochondria/metabolism/pathology ; Animals ; Energy Metabolism ; Oxidation-Reduction ; }, abstract = {Alzheimer's disease (AD) is increasingly associated with mitochondrial dysfunction and disrupted metabolism. Thus, the maintenance of nicotinamide adenine dinucleotide (NAD[+]) homeostasis is proposed as a potential therapeutic strategy. Toward this end, we suggest that AD-related mitochondrial dysfunction might be viewed as a regulatable, redox-dependent vulnerability rather than an inherently degenerative and irreversible process. This perspective advances an evolutionary model in which NAD[+]-mediated redox systems represent a conserved regulatory axis, and that destabilization of this axis during aging may increase susceptibility to degeneration. Here, we assess the potential of a therapeutic approach that combines this understanding of mitochondrial energy metabolism with results from preclinical studies demonstrating the impact of pharmacologic correction of NAD[+] homeostasis (e.g., P7C3-A20) as contextual motivation. We explicitly elevate redox balance, rather than absolute NAD[+] abundance, as the mechanistically dominant variable that shapes mitochondrial resilience, inflammatory tone, and neurovascular stability. Accordingly, the key unresolved issue is whether specific physiologic benefits might accrue from increased NAD[+] availability per se or rather, the restoration of the NAD[+]/NADH redox ratio, with important implications for the interpretation of the results of directed metabolic interventions. Within this framework, metabolic failure in AD can be understood as an upstream permissive condition that explains, rather than replaces, canonical amyloid-β and tau-associated pathologies. While extended human lifespan may expose late-life vulnerabilities in otherwise conserved metabolic systems, claims of causal primacy, disease reversibility, and cross-neurodegenerative generalization remain premature, underscoring the need for redox-resolved, genetic, and clinical validation.}, } @article {pmid41916594, year = {2026}, author = {Pouliot-Drouin, A and Bettinazzi, S and Paque, O and Breton, S}, title = {Metabolic consequences of naturally occurring mitochondrial heteroplasmy in bivalves.}, journal = {Proceedings. Biological sciences}, volume = {293}, number = {2068}, pages = {}, doi = {10.1098/rspb.2025.2965}, pmid = {41916594}, issn = {1471-2954}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; //EU Horizon 2020 Marie Skłodowska-Curie IF/ ; }, mesh = {Animals ; Male ; Female ; *Bivalvia/genetics/metabolism ; *Heteroplasmy ; *Energy Metabolism ; *DNA, Mitochondrial/genetics ; *Mitochondria/genetics/metabolism ; *Mytilus edulis/genetics/metabolism ; }, abstract = {Oxidative phosphorylation, the cornerstone of mitochondrial energy production, is a tightly regulated process that relies on the strict interaction between mitochondrial and nuclear genomes. This intricate relationship requires the two genomes to coevolve to maintain mitochondrial function. However, when multiple mitochondrial variants coexist within an individual, a phenomenon known as heteroplasmy, this delicate balance can be disrupted, leading to bioenergetic inefficiencies and diseases. Interestingly, heteroplasmy naturally occurs in over a hundred species of bivalve molluscs, where paternal mitochondrial DNA is, in theory, exclusively inherited by male offspring and segregates in male gametes. Here, we leveraged this unique natural system to investigate the sex-specific distribution and translation pattern of somatic heteroplasmy, along with its impact on cellular bioenergetics in the bivalve species Mytilus edulis and Ruditapes philippinarum. By examining the relationship between heteroplasmy levels, haplotype expression and key enzymes involved in energy production, we uncovered unexpected findings. Contrary to predictions, somatic heteroplasmy was prevalent in both sexes and across both species. While heteroplasmy did not significantly affect overall bioenergetics, females of M. edulis showed notable exceptions in their gills. Possible compensatory mechanisms and species- or sex-specific adaptation to heteroplasmy are discussed.}, } @article {pmid41923598, year = {2026}, author = {Johnston, IG}, title = {Segregation of mtDNA mutations protects mitochondria across kingdoms, with impacts from longevity to agriculture and evolvability.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {381}, number = {1947}, pages = {}, doi = {10.1098/rstb.2025.0075}, pmid = {41923598}, issn = {1471-2970}, support = {805046//H2020 European Research Council/ ; }, mesh = {*DNA, Mitochondrial/genetics ; *Mutation ; *Mitochondria/genetics ; *Longevity/genetics ; Animals ; *Biological Evolution ; *Evolution, Molecular ; *Eukaryota/genetics ; Humans ; }, abstract = {Mitochondrial DNA (mtDNA) encodes essential bioenergetic and metabolic machinery across eukaryotes, but it is susceptible to mutational damage. The high copy number, physical location and inheritance patterns of mtDNA mean that specialist approaches to mitigate such damage are needed. A common theme across many species is segregation or 'sorting out' of different mtDNA types-generating variance in mutant frequencies within and between generations, so that multiscale selection can act to remove deleterious mutations. Eukaryotes with different physiologies and ecologies use different strategies for this segregation. This article attempts to review and-with the aid of some bioinformatics and new modelling results-synthesize the ways that this segregation is achieved across different eukaryotic organisms. In parallel, the importance of segregation in human disease, longevity, agriculture and for biology on a rapidly changing planet is discussed. This article is part of the theme issue 'Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya'.}, } @article {pmid41923599, year = {2026}, author = {Lane, N and Pomiankowski, A}, title = {Why selection for mitochondrial quality drives the evolution of sexes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {381}, number = {1947}, pages = {}, doi = {10.1098/rstb.2025.0076}, pmid = {41923599}, issn = {1471-2970}, support = {NE/X009734/1//UKRI Natural Environment Research Council/ ; INV-064683//Bill and Melinda Gates Foundation/ ; BB/V003542/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; EP/X041921/1//Engineering and Physical Sciences Research Council/ ; }, mesh = {Animals ; *DNA, Mitochondrial/genetics ; *Biological Evolution ; *Selection, Genetic ; *Mitochondria/genetics ; Female ; Germ Cells ; }, abstract = {The evolution of sexes is closely tied to uniparental inheritance (UPI) of mitochondrial DNA (mtDNA), where only females transmit mtDNA. Unlike nuclear DNA, mtDNA is highly polyploid and never evolved to be part of meiotic sex. Modelling shows that UPI increases mtDNA mutational variance, enhancing selection for high-quality mtDNA and promoting the emergence of sexes from mating types in unicellular eukaryotes. Paternal control of mitochondrial transfer favours some degree of mtDNA leakage, whereas maternal control favours strict UPI, leading to sexual conflict driving turnover in transmission mechanisms. In multicellular organisms, mitotic segregation of mtDNA increases variance in gametes, again facilitating selection. Surprisingly, germline evolution seems to reflect mtDNA mutation rates: plants and sessile metazoans have low rates and produce gametes from somatic cells, while bilaterians and ctenophores with higher rates sequester germlines with restricted cell division. High mtDNA ploidy in oocytes allows early embryonic cell division without replication, reducing mutational variance across tissues and enhancing somatic fitness. Germline mtDNA quality is maintained by mitotic over-proliferation of germ cells and the selective transfer of mtDNA into primordial oocytes linked with massive apoptotic germ-cell atresia. Overall, selection for mtDNA quality elucidates the evolution of sexes and the architecture of the female germline. This article is part of the theme issue 'Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya'.}, } @article {pmid41923600, year = {2026}, author = {Shtolz, N and Horovitz, L and Caruchero, Y and Mishmar, D}, title = {The functional importance of mitochondrial sequences with dual functions: overlapping protein-protein and protein-RNA gene sequences as test cases.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {381}, number = {1947}, pages = {}, doi = {10.1098/rstb.2025.0074}, pmid = {41923600}, issn = {1471-2970}, support = {//US Army Life Sciences division/ ; //Israel Science Foundation/ ; }, mesh = {Humans ; *DNA, Mitochondrial/genetics ; *Mitochondrial Proteins/genetics ; Mutation ; *Selection, Genetic ; *Mitochondria/genetics ; Evolution, Molecular ; }, abstract = {Human mitochondrial DNA (mtDNA) contains 13 protein-coding subunits of the oxidative phosphorylation pathway, 22 tRNA and two rRNA genes. However, accumulating evidence suggests that mtDNA encodes additional overlapping genetic elements, including mitochondrial-derived peptides (MDPs) and alternative reading frames. Here, we assessed signatures of selection across 66 328 human mtDNAs and studied the potential impact of disease-causing mutation within these mtDNA overlapping sequences. By employing frame-specific dN/dS analysis for the overlapping reading frames, and codon position-specific diversity calculations we found that SHLP6 and SHLP3 (within 16S rRNA) display significant signatures of purifying selection. Mutational asymmetry analysis revealed purifying selection in both frames and strands of GAU/COX1, while other alternative reading frames show asymmetric patterns, supporting negative selection primarily on the encompassing canonical gene. Analysis of mito-ribosome profiling (HEK293 cells) revealed translation initiation signatures only for SHLP6 and ALTND4, providing functional support for their translation in HEK293 cells. Analysis of disease-causing mutations revealed that several such mutations have predicted deleterious effects on both canonical and alternative sequences, though canonical genes tend to be more frequently affected. Taken together, we provide evolutionary and functional evidence supporting biological relevance of certain MDPs and underline the need to re-evaluate the functionality of mutations in such sequences. This article is part of the theme issue 'Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya'.}, } @article {pmid41923601, year = {2026}, author = {Kannangara, JR and Ma, H and Dowling, DK}, title = {Rethinking mitochondrial heteroplasmy: selection, conflict and adaptation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {381}, number = {1947}, pages = {}, doi = {10.1098/rstb.2025.0079}, pmid = {41923601}, issn = {1471-2970}, support = {BB/Z516910/1//BBSRC Biotechnology and Biological Sciences Research Counci/ ; }, mesh = {*Selection, Genetic ; Animals ; *DNA, Mitochondrial/genetics ; *Heteroplasmy ; *Biological Evolution ; *Adaptation, Physiological/genetics ; *Adaptation, Biological ; *Genetic Variation ; Evolution, Molecular ; }, abstract = {Mitochondrial DNA (mtDNA) variation is increasingly recognized for its role in shaping evolutionary changes at the species and population levels. Yet, its evolutionary relevance within individuals remains less explored. Eukaryotic cells typically carry multiple copies of mtDNA. When these copies differ in sequence, heteroplasmy arises-a form of intra-organismal genetic diversity with potentially profound biological implications. To elucidate the evolutionary significance of heteroplasmy in animals, we first review how natural selection shapes adaptive mtDNA dynamics at broader biological levels, via cases of mito-nuclear coadaptation, environmental-mediated and sex-specific selection and balancing selection. We then explore whether analogous selective pressures may operate at the intra-individual level. Heteroplasmy introduces the potential for multi-level selection-from the genome to the organism-potentially yielding synergistic or antagonistic evolutionary outcomes. This framework encompasses both the selfish transmission of certain mtDNA variants and emerging evidence for adaptive shifts in heteroplasmy levels under environmental stress. These findings are supported by theoretical models suggesting that paternal mtDNA transmission-historically viewed as a stochastic anomaly-may confer adaptive benefits under specific ecological and evolutionary contexts by introducing intra-individual mtDNA diversity. Collectively, these insights suggest that heteroplasmy may act as an underappreciated reservoir of adaptive potential, enhancing the evolutionary capacity of organisms in a changing world. This article is part of the theme issue 'Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya'.}, } @article {pmid41923602, year = {2026}, author = {Havird, J and Wang, E and Zwonitzer, K and Aitolo, G and Xu, X and Zhang, B}, title = {Positive and relaxed selection on mitochondrial DNA in parasitic versus predatory mites.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {381}, number = {1947}, pages = {}, pmid = {41923602}, issn = {1471-2970}, support = {//National Key Research and Development Program of China/ ; /GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Selection, Genetic ; *Mites/genetics/physiology ; *DNA, Mitochondrial/genetics ; *Evolution, Molecular ; *Genome, Mitochondrial ; }, abstract = {Mitochondrial genomes (mtDNA) have distinct evolutionary trajectories owing to their inheritance, ploidy and underlying mutation rates, making them prone to accumulate slightly deleterious mutations. Positive selection on mtDNA has been suggested to be important during adaptation to 'high-energy' lifestyles and environments. Disentangling positive versus relaxed selection in molecular mtDNA evolution studies is therefore important, although common metrics such as elevated dN/dS ratios (the ratio of non-synonymous to synonymous substitution rates) can be interpreted as signs of both relaxed purifying selection and positive selection. Here, we examined mtDNA evolution in mites (superorder Parasitiformes) to characterize selection during transitions from a parasitic to a free-living, predatory lifestyle. We predicted energetic demands on predatory mites would be associated with positive selection on mtDNA and that reduced effective population sizes in parasitic lineages would lead to relaxed selection. Using newly sequenced mite mitogenomes, we found a signature of accelerated mtDNA evolution in predatory lineages. Unexpectedly, this is likely due to relaxed, not positive selection on the mtDNA of predatory mites, which is supported by massive, ongoing gene rearrangements in the mtDNA of some predatory lineages (family Phytoseiidae). We discuss why 'high-energy' lifestyles are not always associated with adaptive mtDNA evolution. This article is part of the theme issue 'Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya'.}, } @article {pmid41923603, year = {2026}, author = {Le Cam, S and Mortz, M and Gagnier-Michel, A and Dufresne, F and Blier, PU}, title = {The influence of size, longevity and environmental temperature on mitochondrial DNA evolution in fishes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {381}, number = {1947}, pages = {}, doi = {10.1098/rstb.2025.0085}, pmid = {41923603}, issn = {1471-2970}, support = {//Natural Sciences and Engineering Council of Canada/ ; }, mesh = {Animals ; *Longevity/genetics ; *DNA, Mitochondrial/genetics ; Temperature ; *Fishes/genetics/physiology ; *Evolution, Molecular ; *Body Size ; Electron Transport Complex IV/genetics ; }, abstract = {The link between longevity and mitochondrial function has been documented; therefore, we suspect that the evolution of mitochondrial DNA (mtDNA) is linked to the evolution of longevity. We selected 128 fish species with a wide range of longevity and inhabiting habitats with differing temperatures and examined their association with dN/dS ratios of mtDNA genes. Our findings (i) rule out environmental temperature as a primary driver of longevity, (ii) confirm the negative relationship between synonymous substitution rate and longevity for four of the mitochondrial protein coding genes, (iii) reveal a correlation of the fish body length at maturity with the dN/dS ratio for ATP6, ND1 and ND4, and (iv) highlight for the first time to our knowledge, a link between high conservation of the three cytochrome c oxidase (COX) genes and adaptation to temperatures in fishes. By extending conclusions drawn from mtDNA to individual genes, our study opens new avenues for exploring the ageing process. Moreover, the specific link between the evolution of COX genes and habitat temperature confirms the importance of complex IV in temperature adaptation. Our findings also suggest a link between dN/dS in complex I genes and longevity, highlighting the need to examine the functional association between their encoded peptides and lifespan. This article is part of the theme issue 'Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya'.}, } @article {pmid41923605, year = {2026}, author = {Kuster, SA and Schumer, M and Havird, J and Sloan, DB}, title = {Sensitivity of genome-wide tests for mitonuclear genetic incompatibilities.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {381}, number = {1947}, pages = {}, pmid = {41923605}, issn = {1471-2970}, support = {R35-GM142836//Division of Integrative Organismal Systems/ ; T32/GM/NIGMS NIH HHS/United States ; R35-GM148134//National Science Foundation Graduate Research Fellowship Program/ ; }, mesh = {Animals ; *Hybridization, Genetic ; *Cell Nucleus/genetics ; *Genetic Speciation ; }, abstract = {Mismatches between interacting mitochondrial and nuclear gene products in hybrids have been proposed to disproportionately contribute to early species boundaries. Under this model, genetic incompatibilities emerge when mitochondrial haplotypes are in a cellular context without their coevolved nuclear-encoded mitochondrial (n-mt) proteins. Some case studies have shown that such disruptions in mitonuclear coevolution can contribute to reproductive isolation, but whether mitonuclear incompatibilities generate selection that impacts multiple n-mt loci and/or causes broad, genome-wide contributions to speciation is unclear. Here, we leverage a system with several hybridizing species pairs (Xiphophorus fishes) that have known mitonuclear incompatibilities of large effect. We divided nuclear-encoded genes into three classes based on level of interaction with mitochondrial gene products. We found only inconsistent statistical support for a difference between these classes in the degree of positive covariation in mitonuclear ancestry. We discuss evidence that these analyses are sensitive to the amount of non-synonymous divergence between parent species in interacting n-mt genes or the age of the hybridization event. Overall, our results imply that genome-wide scans focused on enrichment of broad functional gene classes may often be insufficient for detecting a history of mitonuclear coevolution, even when strong selection is acting on mitonuclear incompatibilities at multiple loci. This article is part of the theme issue 'Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya'.}, } @article {pmid41923606, year = {2026}, author = {Zachar, I and Máté, J and Oszoli, I}, title = {The cell nucleus as a barrier against horizontal gene transfer in microbial endosymbioses.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {381}, number = {1947}, pages = {}, doi = {10.1098/rstb.2025.0096}, pmid = {41923606}, issn = {1471-2970}, support = {//MTA Bolyai János Research Scholarship/ ; //John Templeton Foundation/ ; 152615//NKFI Hivatal/ ; }, mesh = {*Gene Transfer, Horizontal ; *Symbiosis ; *Cell Nucleus/genetics ; *Archaea/genetics/physiology ; Bacteria/genetics ; }, abstract = {The origin of eukaryotic cells remains a highly contested problem. While eukaryotes arose from the merger of a bacterial and an archaeal partner giving rise to mitochondria and the cell proper, the order of steps is not known, nor is it understood why it was a singular event. Prokaryotes engage in various cooperative interactions everywhere, yet there is no evidence that they could establish stable endosymbiotic relationships on their own. Many assume that mitochondria came first, and their critical presence and features enabled the complex cellular architecture, including the nucleus. Here we find support for the alternative, claiming that a nuclear compartment was a prerequisite for successful stable endosymbiosis. We review independent lines of evidence suggesting that the pre-existence of a nuclear membrane or equivalent mechanism to separate translation from transcription may have been essential to limit genetic inference owing to extensive horizontal gene transfer in the wake of pre-mitochondrial (endo)symbionts and to stabilize the host genome against foreign DNA, especially from (endo)symbiotic partners. We claim that an asymmetry in control potential between partners is required for successful integration of an endosymbiont. This would explain why there are no further prokaryotic endosymbioses known to us (extant or extinct). We propose predictions that can be tested to support the hypothesis. This article is part of the theme issue 'Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya'.}, } @article {pmid41923607, year = {2026}, author = {Klabacka, RL and Hill, GE and Dowling, DK and Sharbrough, J and Denton, RD and Hall, JM and Havird, JC}, title = {Mitonuclear dynamics in unisexual vertebrates.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {381}, number = {1947}, pages = {}, doi = {10.1098/rstb.2025.0081}, pmid = {41923607}, issn = {1471-2970}, mesh = {Animals ; *Vertebrates/genetics/physiology ; *Mitochondria/genetics ; *Biological Evolution ; *Cell Nucleus/genetics ; Reproduction ; Evolution, Molecular ; }, abstract = {Sex and mitochondria are inextricably linked in the eukaryotic tree of life, a confounding situation given the uniparental inheritance of mitochondria and the biparental inheritance that sexual reproduction entails. Unisexual vertebrate lineages, which arise via hybridization and asexually pass on their genetic material to clonal descendants, provide a unique opportunity to study mitochondrial evolution without potentially confounding effects of sex. Hybridity and clonality set unisexual vertebrates apart from other vertebrates and establish a distinct genetic environment that shapes their evolution, especially dynamics between mitochondrial and nuclear genomes. Here, we provide a perspective on the mitonuclear genomic interactions experienced by unisexual vertebrates and the implications of these interactions on mitochondrial function and integration into organismal performance and fitness. Building upon the hypothesis that sexual reproduction arose to maintain coadaptation between co-functioning nuclear and mitochondrial genes, we propose that unisexual vertebrates may be confined to predominantly 'young' lineages because mitonuclear incompatibilities-arising from either hybridity or clonality-increase the probability of extinction over time (the Mitonuclear Erosion Hypothesis). We provide a multidisciplinary collection of strategies to disentangle the effects of clonality and hybridity and quantify the relative degree to which these characteristics contribute to differences in mitochondrial function, organismal performance and fitness. This article is part of the theme issue 'Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya'.}, } @article {pmid41923608, year = {2026}, author = {Lavrov, DV and Gettle, N}, title = {Extreme mitochondrial genome complexity in the calcaronean sponge Sycon ciliatum (Fabricius, 1780): fragmentation, gene duplication and mRNA editing.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {381}, number = {1947}, pages = {}, doi = {10.1098/rstb.2025.0082}, pmid = {41923608}, issn = {1471-2970}, support = {206194-/WT_/Wellcome Trust/United Kingdom ; GBMF8897//Gordon and Betty Moore Foundation/ ; }, mesh = {Animals ; *Genome, Mitochondrial ; *RNA Editing ; *Gene Duplication ; *Porifera/genetics ; RNA, Messenger/genetics ; }, abstract = {Mitochondrial genomes (mt-genomes) of calcaronean sponges are among the most unusual in Metazoa. They are fragmented into multiple linear chromosomes (mt-chromosomes) and often rely on insertional mRNA editing to generate functional transcripts. These unusual features have precluded complete characterization of calcaronean mt-genomes using short-read sequencing technologies. Here, we assembled and analyzed the mt-genome of Sycon ciliatum (Fabricius, 1780) using HiFi PacBio data generated by the Aquatic Symbiosis Genomics Project. The mt-genome comprised several megabases of sequence distributed across thousands of chromosomes. While most protein-coding genes were preset in multiple copies, three typical animal mitochondrial protein-coding genes (atp8, nad4L and nad6) and multiple tRNA isotypes were not detected, and only short fragments of mt-rRNA genes were identified. We confirmed that mitochondrial mRNA editing in S. ciliatum occurred through single or double uridine insertions at 200+ sites, and that editing patterns were largely predictable from primary sequence motifs. Unexpectedly, editing sites varied among gene copies and were frequently disrupted by point mutations, leading to substantial changes in encoded amino acid sequences. Most mt-chromosomes were associated with repetitive elements that may function in genome maintenance and recombination. Together, our results reveal a distinctive mode of mt-genome evolution and function, shaped by extreme genome fragmentation, extensive gene duplication and pervasive RNA editing. This article is part of the theme issue 'Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya'.}, } @article {pmid41923609, year = {2026}, author = {Zania, A and Hogeweg, P and von der Dunk, S}, title = {The risk of sexual reproduction promotes the evolution of regulation between host and symbionts.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {381}, number = {1947}, pages = {}, doi = {10.1098/rstb.2025.0077}, pmid = {41923609}, issn = {1471-2970}, support = {//Issachar Fund/ ; }, mesh = {*Symbiosis ; Reproduction ; *Biological Evolution ; *Eukaryota/physiology/genetics ; Animals ; }, abstract = {Sexual reproduction is a widely spread feature of eukaryotes and was already present in the last eukaryotic common ancestor. While most extant eukaryotes inherit mitochondria from a single parent, the mechanisms enforcing uniparental inheritance vary widely. The first eukaryotes likely would not have evolved such mechanisms yet, so cellular fusion would have led to mitochondrial mixing (biparental inheritance). Here, we explore the evolutionary consequences of biparental inheritance of endosymbionts during host-symbiont coevolution using a multi-level, individual-based model of endosymbiosis. Our results show that biparental inheritance introduces evolutionary conflict, as it facilitates the spread of fast-replicating symbionts, which can drive host populations to extinction. However, in a diverse environment, proto-eukaryotes diversify and adapt to distinct niches, protecting the population from total collapse caused by selfish symbionts. Moreover, this conflict can be resolved through the evolution of signalling mechanisms that allow hosts to regulate symbiont cell cycles. In many cases, sexually reproducing populations not only survive but also outperform their asexual counterparts. We conclude that sexual reproduction could have appeared early during eukaryogenesis and may have facilitated the evolution of host control over the endosymbiont cell cycle. This article is part of the theme issue 'Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya'.}, } @article {pmid41930450, year = {2026}, author = {Wang, X and Qin, Q and Xu, S and Wu, J and Li, K and Lu, C and Peng, P and Qin, Y}, title = {[The evolution and impacts of post-tramatic cell death modalities].}, journal = {Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology}, volume = {42}, number = {3}, pages = {274-281}, pmid = {41930450}, issn = {1007-8738}, mesh = {Humans ; Animals ; *Cell Death ; Mitochondria/metabolism ; Apoptosis ; Signal Transduction ; Inflammasomes/metabolism ; Necroptosis ; *Wounds and Injuries/metabolism/pathology ; Pyroptosis ; Ferroptosis ; Lipid Peroxidation ; Inflammation ; }, abstract = {Trauma-induced cell death modalities, which serve as the initiating events of systemic inflammation and multi-organ dysfunction, have emerged as a pivotal focus in trauma pathology research. After trauma, the activation of distinct programmed cell death pathways exhibits a phased progression and intricate crosstalk, involving multi-tiered regulatory mechanisms such as mitochondrial pathway activation, inflammasome assembly, lipid peroxidation cascades, and dysregulated metal ion homeostasis. Notably, apoptosis, pyroptosis, necroptosis, and ferroptosis successively dominate inflammatory and metabolic dysregulation over time, while PANoptosis, as an integrated cell death program, demonstrates cross-pathway signal convergence. Emerging cell death paradigms further elucidate the complex interplay among mitochondrial stress, metal homeostasis, metabolic reprogramming, and trauma pathology. This review synthesizes the dual roles and therapeutic potential of these cell death modalities in tissue repair, aiming to provide a theoretical framework and intervention targets for the precise modulation of post-traumatic pathological responses.}, } @article {pmid41935920, year = {2026}, author = {Cao, YL and Yang, CP and Shen, B and Hu, J and Gao, S}, title = {Targeting mitochondrial dynamics against cancer.}, journal = {Trends in cell biology}, volume = {36}, number = {6}, pages = {507-520}, doi = {10.1016/j.tcb.2026.03.006}, pmid = {41935920}, issn = {1879-3088}, mesh = {Humans ; *Mitochondrial Dynamics/drug effects ; *Neoplasms/pathology/immunology/therapy/metabolism/drug therapy ; Animals ; Tumor Microenvironment ; *Mitochondria/metabolism ; }, abstract = {Although cancer treatment has improved, many patients exhibit limited responses due to the intrinsic heterogeneity and adaptability of tumors, coupled with immunosuppressive conditions in the tumor microenvironment (TME). Mitochondrial dynamics, characterized by continuous fusion and fission, influences cellular processes such as metabolism, cell cycle, cell death, and stemness, thereby profoundly shaping tumor cell evolution and TME plasticity. In this review, we summarize recent advances regarding the roles of mitochondrial dynamics in cancer biology and discuss how it regulates the behavior of both tumor cells and tumor-associated immune cells in the TME. We propose that targeting mitochondrial dynamics represents a dual therapeutic strategy that disrupts core oncogenic programs while potentiating antitumor immunity, offering a promising direction for future cancer treatment.}, } @article {pmid41944199, year = {2026}, author = {Konishi, Y and Sakaue, H and Takeda, H and Endo, T}, title = {Identifying targeting signals and distinct localization-based roles of yeast aldehyde dehydrogenase Hfd1.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.70536}, pmid = {41944199}, issn = {1742-4658}, support = {//Takeda Medical Research Foundation/ ; 21gm1410002//Core Research for Evolutional Science and Technology/ ; 15H05705//Japan Society for the Promotion of Science/ ; 20H00458//Japan Society for the Promotion of Science/ ; 20H04912//Japan Society for the Promotion of Science/ ; 20H05689//Japan Society for the Promotion of Science/ ; 20H05929//Japan Society for the Promotion of Science/ ; 25H00978//Japan Society for the Promotion of Science/ ; 25H21752//Japan Society for the Promotion of Science/ ; SPRING JPMJSP2157//Japan Science and Technology agency/ ; }, abstract = {Hfd1 is a yeast fatty aldehyde dehydrogenase that catalyzes the oxidation of long-chain aliphatic aldehydes and localizes to membranes in multiple organelles, including mitochondria, the endoplasmic reticulum (ER), and lipid droplets. Here, we identified the segments of Hfd1 responsible for this multiple-organelle targeting and generated variants that localize exclusively to mitochondria, the ER, or the cytosol. These Hfd1 variants allowed us to reveal the relationship between the subcellular localization and the function of Hfd1 in coenzyme Q biosynthesis and sphingolipid metabolism. The catalytic N-terminal domain of Hfd1, when exposed to the cytosol, is sufficient to support coenzyme Q biosynthesis regardless of whether Hfd1 has an anchor or is anchored to either the mitochondrial or ER membranes. Furthermore, Hfd1 contributes to the mitigation of reactive oxygen species and to the oxidation of hexadecanal and hexadecenal, which may be important for efficient mitochondrial protein transport and/or quality control in cooperation with Ubx2 and the TOM complex.}, } @article {pmid41956069, year = {2026}, author = {Tucci, S}, title = {A unified ACSF3-mtFAS model linking mitochondrial energy metabolism to human anthropometric evolution.}, journal = {Cell genomics}, volume = {6}, number = {4}, pages = {101195}, pmid = {41956069}, issn = {2666-979X}, mesh = {Humans ; *Energy Metabolism ; *Mitochondria/metabolism ; *Fatty Acids/metabolism/biosynthesis ; Animals ; Models, Biological ; Biological Evolution ; }, abstract = {We here propose a mitochondria-centered reinterpretation of the ACSF3 regulatory variant reported by Zhang et al., integrating advances in mitochondrial fatty acid synthesis and ACSF3-deficient models to link subcellular control of oxidative efficiency with organismal traits such as basal metabolic rate, height, and systemic growth regulation in humans.}, } @article {pmid41967383, year = {2026}, author = {Isogai, R and Wei, M and Harada, R and Yazaki, E and Nakayama, T and Gawryluk, RMR and Inagaki, Y}, title = {Diversity and evolution of DNA polymerase θ in eukaryotes and the origin of mitochondrion-localized DNA polymerase PolIA in euglenozoa.}, journal = {Protist}, volume = {181}, number = {}, pages = {126160}, doi = {10.1016/j.protis.2026.126160}, pmid = {41967383}, issn = {1618-0941}, mesh = {*DNA-Directed DNA Polymerase/genetics/metabolism ; Phylogeny ; *Evolution, Molecular ; DNA Polymerase theta ; *Euglenozoa/enzymology/genetics/classification ; *Mitochondria/enzymology/genetics ; *Genetic Variation ; Molecular Sequence Data ; }, abstract = {Pioneering phylogenetic studies recovered the sister relationship between two distinct types of DNA polymerase (DNAP)-one is nucleus-localized Polθ with a pan-eukaryotic distribution, and the other is mitochondrion-localized PolIA found exclusively in Euglenozoa. Nevertheless, previous phylogenetic analyses considered Polθ sequences from a highly restricted set of eukaryotes, leaving the precise evolutionary trajectory of PolIA unsettled. In this study, we conducted phylogenetic analyses using a large collection of Polθ sequences from diverse eukaryotes to examine the evolutionary relationship between Polθ and PolIA more rigorously than previously reported. We recovered the maximum likelihood tree in which the clade of PolIA was nested within the clade of Polθ. In the radiation of Polθ sequences, the PolIA clade branched specifically with one of the two types of Polθ identified in euglenozoans. These results suggest that a gene duplication of one of the two Polθ types in Euglenozoa produced PolIA specific to the members of this phylum. We also propose, based on the putative distributions of the two Polθ types and PolIA, the vertical inheritance of the three DNAPs from the ancestral euglenozoan to its descendants with multiple losses of one of the two Polθ types.}, } @article {pmid41968281, year = {2026}, author = {Wang, P and Que, Y and Zhang, R}, title = {Mitochondrial-Nuclear Interactions, Co-Transcription, and Adaptive Evolution in Cytoplasmic Male Sterility.}, journal = {Plant, cell & environment}, volume = {}, number = {}, pages = {}, doi = {10.1111/pce.70526}, pmid = {41968281}, issn = {1365-3040}, support = {52161145104//The National Natural Science Foundation of China/ ; CATASCXTD202402//Chinese Academy of Tropical Agricultural Sciences for Science and Technology Innovation Team of National Tropical Agricultural Science Center/ ; NKLTCBCXTD24//Project of State Key Laboratory of Tropical Crop Breeding/ ; NKLTCBCXTD38//Project of State Key Laboratory of Tropical Crop Breeding/ ; NKLTCBCXTD38//Project of State Key Laboratory of Tropical Crop Breeding/ ; CARS-17//China Agriculture Research System of MOF and MARA/ ; 2024-NPY-00-044//Invigoration of the Seed Industry of Guangdong Province/ ; }, abstract = {Prokaryotic genomes are compact and are commonly organised into operons that generate polycistronic transcripts. Plant mitochondrial genomes preserve several prokaryote-like expression features, including frequent polycistronic transcription and extensive post-transcriptional processing. At the same time, frequent rearrangement and recombination in plant mitochondria can create novel open reading frames, some of which cause cytoplasmic male sterility by perturbing mitochondrial function during pollen development. A recurring observation across species is that many sterility-associated open reading frames are co-transcribed in tandem with neighbouring mitochondrial genes, generating characteristic chimeric or extended transcripts that become key targets of nuclear fertility restorer genes. In this review, we synthesise co-transcription patterns of sterility-associated genes in two monocots (rice and maize) and two dicots (oilseed rape and sunflower), and outline how representative restorer genes recognise, cleave, destabilise, or translationally block the corresponding co-transcripts. Building on operon concepts, we discuss how co-transcription may shape transcript abundance, processing, and coupling to retrograde signalling. Finally, we summarise evidence linking sterility gene activity to reactive oxygen species homoeostasis and propose testable hypotheses for how these mitochondrial-nuclear interactions may influence plant adaptation and evolution.}, } @article {pmid41975732, year = {2026}, author = {Fanò-Illic, G and Coscia, F and Gigliotti, PV and Checcaglini, F and Carraro, U and Fulle, S and Mancinelli, R}, title = {Pathophysiological, Translational, and Diagnostic Aspects of ME/CFS: A Focus on Skeletal Muscle Involvement.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {7}, pages = {}, pmid = {41975732}, issn = {2075-4418}, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, multisystemic disorder characterized by severe, persistent fatigue not alleviated by rest and worsened by minimal exertion, often accompanied by post-exertional malaise (PEM), unrefreshing sleep, cognitive dysfunction, and autonomic disturbances. Despite decades of research, its pathophysiology remains incompletely understood, and skeletal muscle involvement has only recently gained attention. This review aims to provide a historical and pathophysiological synthesis of ME/CFS, emphasizing the pivotal role of skeletal muscle in the onset and persistence of symptoms, and to integrate molecular, cellular, and pathophysiological evidence into a coherent explanatory framework. This is a narrative review of published literature (1990-2025) with critical integration of clinical, biochemical, and experimental data on oxidative stress, mitochondrial dysfunction, Excitation-Contraction (E-C coupling) dysregulation, and muscle secretome alterations in ME/CFS also in relation to post-viral syndromes (e.g., Long COVID). Evidence consistently points to mitochondrial oxidative stress, redox imbalance, impaired Ca[2+] handling, and altered signaling pathways in skeletal muscle of patients with ME/CFS. Historical milestones show an evolution from psychogenic interpretations toward recognition of ME/CFS as a biological disorder with neuromuscular and metabolic underpinnings. ME/CFS can be interpreted as a skeletal muscle-metabolic disorder characterized by oxidative distress, mitochondrial dysfunction, and impaired energy regulation, leading to the clinical picture of exercise intolerance and post-exertional malaise. Integrating basic and clinical research through a translational approach provides the foundation for new diagnostic tools, targeted therapies, and biomarkers.}, } @article {pmid41977316, year = {2026}, author = {Ma, R and Li, W and Miao, Y and Yang, R and Shao, Y and Shang, J and Li, Y and Gao, Y and Bao, D and Wu, Y}, title = {Mitochondrial Graph-Based Pan-Genome Analysis of Hypsizygus marmoreus: Structural Variation, Adaptive Evolution, and Its Implications for Germplasm Resource Improvement.}, journal = {International journal of molecular sciences}, volume = {27}, number = {7}, pages = {}, pmid = {41977316}, issn = {1422-0067}, support = {32372789//the National Natural Science Foundation of China/ ; (2022)014//the Excellent Team Plan of Shanghai Academy of Agricultural Sciences/ ; }, mesh = {*Genome, Mitochondrial ; *Evolution, Molecular ; *Agaricales/genetics ; Polymorphism, Single Nucleotide ; Phylogeny ; RNA, Transfer/genetics/chemistry ; *Genome, Fungal ; }, abstract = {Mitochondria regulate nuclear genomes and their own genetic material, primarily to provide energy in eukaryotes. Currently, high-throughput sequencing technologies are being used to resolve the mitochondrial genomes of various edible fungi. However, the application of pan-genomes for the analysis of edible mushroom mitochondrial genomes remains unexplored. In this study, we conducted a comparative mitochondrial genome analysis of 31 Hypsizygus marmoreus strains (four newly sequenced monotypes and 27 public datasets), ranging from 98,284 to 111,087 bp. This variation was determined to be primarily driven by dynamic changes in non-coding regions, particularly intronic polymorphisms in the cox1 gene. Further, transfer RNA (tRNA) secondary structures exhibited atypical globular and elongated conformations alongside copy number variations. Additionally, codon usage showed a pronounced A/T bias, whereas core respiratory chain genes demonstrated an evolutionary pattern of strong purifying selection. Furthermore, the 31 mitochondrial genomes of H. marmoreus were found to harbor eight gene rearrangement patterns and five genetic clusters, and the pan-genome analysis (220,364 bp, 217 nodes) captured abundant single-nucleotide polymorphisms (SNPs), insertions/deletions (InDels), and structural variations. This study provides breeding-relevant genetic markers and a genomic framework for H. marmoreus germplasm classification, genetic improvements, and the molecular breeding of stress-resilient varieties.}, } @article {pmid41977770, year = {2026}, author = {Long, W and Wang, J and Luo, L and Zhou, L and Chen, W and Luo, L and Xu, W and Li, Y and Yan, L and Cai, Y and Xie, H}, title = {Comprehensive Analysis of Wild Rice Mitochondrial Genomes Reveals Structural Variation, Repeat Dynamics, and the Evolution of orf182.}, journal = {Plants (Basel, Switzerland)}, volume = {15}, number = {7}, pages = {}, pmid = {41977770}, issn = {2223-7747}, support = {JXSNKYJCRC202501//Major Talent Development Program of the Jiangxi Academy of Agricultural Sciences/ ; 20224BAB215008//Jiangxi Province Science Foundation for Youths/ ; 20213BCJL22044//Major Discipline Academic and Technical Leaders Training Program of Jiangxi Province/ ; CARS-01-08//China Agriculture Research System/ ; }, abstract = {The widespread adoption of hybrid rice has played a pivotal role in ensuring food security in China. However, the heavy reliance on wild-abortive (WA) cytoplasmic male sterility (CMS) systems raises potential biosafety concerns. In this study, we screened a global collection of wild rice (Oryza rufipogon) accessions using orf182-specific molecular markers to characterize the geographic distribution patterns of this gene. Mitochondrial sequencing and assembly of 11 representative wild rice species harboring orf182 revealed 16 novel genes. A total of 469 mitochondrial genes were classified into 23 gene families, with nine families containing single-copy homologous genes, indicating significant gene duplication in mitochondria. We observed a strong positive correlation between mitochondrial genome size and the quantity and size of repetitive sequences. Collinearity analysis revealed extensive mitochondrial variation and large-scale inversions in Guangdong wild rice. Comparative genome analysis uncovered inversions, translocations, and several variations surrounding orf182, with a 71 bp repeat sequence mediating the formation of the orf182-nad6 chimeric gene. Gene copy number analysis (GCNV) revealed variable orf182 gene copy counts (1, 2, and 3) in wild rice species. Additionally, successful transformation of orf182 from various sources into sterile lines was achieved. These findings provide valuable resources for advancing hybrid rice development in China, thus contributing to enhanced food security.}, } @article {pmid41981464, year = {2026}, author = {Wang, FC and He, Z and Yan, RG and Wang, YJ and Wu, JL and Yang, QE}, title = {The transcription factor E4F1 is crucial for spermatogonial differentiation and meiosis progression in mice.}, journal = {BMC genomics}, volume = {27}, number = {1}, pages = {}, pmid = {41981464}, issn = {1471-2164}, support = {2021YFD1200405//National Key Research and Development Program of China/ ; 31771656//National Natural Science Foundation of China/ ; 2025-ZJ-970T//Natural Science Foundation of Qinghai Province/ ; }, mesh = {Animals ; Male ; *Meiosis/genetics ; Mice ; *Spermatogonia/cytology/metabolism ; *Cell Differentiation/genetics ; Spermatogenesis/genetics ; Mice, Knockout ; *Transcription Factors/genetics/metabolism ; Spermatocytes/metabolism/cytology ; Gene Expression Profiling ; }, abstract = {BACKGROUND: Spermatogonial differentiation is a key step in spermatogenesis, yet the transcriptional programs that control this process are not fully defined. E4f1 has been reported to be essential for embryonic development, mitochondrial function and spermatogonial stem cell (SSC) maintenance in mice. However, its function in spermatogonial differentiation and meiosis progression is unknown.

RESULTS: The Cre-loxP system was used to delete E4f1 in differentiated spermatogonia and early meiotic spermatocytes. E4f1 knockout significantly affected the development of spermatogonia and spermatocytes. The mitochondria in the spermatogonia of the E4f1-cKO mice were morphologically abnormal, and apoptosis was elevated. The most advanced germ cells in the seminiferous tubules of E4f1-cKO mice were spermatocytes at the early pachytene stage. Single-cell transcriptome analysis revealed that loss of E4f1 suppressed the expression of transcriptional regulators related to SSC maintenance (e.g., Uchl1, Zbtb16, Lin28a), spermatogonial differentiation and meiotic entry (e.g., Dmrt1, Sohlh1, Stra8). Furthermore, CUT&Tag analysis of a HIS-Tag knock-in mouse line revealed that 237 genes were associated with E4F1, including Cks2 and Hmgb2, two previously identified genes related to meiosis progression.

CONCLUSIONS: Our results suggest that E4f1 helps ensure normal spermatogonial differentiation by regulating the expression of key differentiation-associated genes. It may also influence the meiotic procession of spermatocytes, potentially through modulating the expression of downstream candidate target genes such as Cks2 and Hmgb2. These results establish a crucial role for the E4f1-dependent transcriptional program in spermatogonial differentiation and meiosis, although further validation is required to fully elucidate the underlying mechanisms involved.}, } @article {pmid41984830, year = {2026}, author = {Brillante, S and Volpe, M and Diana, A and Negueruela, S and Molinari, M and Saurino, R and Cipollaro, E and Polishchuk, E and Tenderini, E and Damiano, C and Tornabene, P and Polishchuk, R and Parenti, G and Tarallo, A and Banfi, S and Trapani, I and Carrella, S and Indrieri, A}, title = {Uncovering mitochondrial defects in photoreceptors opens therapeutic opportunities for Stargardt disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {16}, pages = {e2504764123}, pmid = {41984830}, issn = {1091-6490}, support = {M2020184//BrightFocus Foundation (BFF)/ ; PRIN2020 grant 2020XBCMHJ//Ministero dell'Università e della Ricerca (MUR)/ ; TGM22MT01//Fondazione Telethon (FT)/ ; }, mesh = {Animals ; *Mitochondria/metabolism/pathology/genetics ; *Stargardt Disease/genetics/pathology ; Mice ; ATP-Binding Cassette Transporters/genetics/metabolism ; Humans ; MicroRNAs/genetics/metabolism ; Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/congenital/genetics/pathology/metabolism/therapy ; GTP Phosphohydrolases/genetics/metabolism ; Mice, Knockout ; *Photoreceptor Cells, Vertebrate/metabolism/pathology ; }, abstract = {Stargardt disease type 1 (STGD1) is the most common hereditary macular degeneration. It is caused by mutations in ABCA4, which result in the progressive degeneration of the retinal pigment epithelium (RPE), ultimately leading to photoreceptor loss. Despite extensive efforts, STGD1 currently lacks effective treatments. Here, we first identified mitochondrial defects in the photoreceptors of Abca4[-/-] mice and STGD1 patient-derived retinal organoids. Specifically, we found reduced mitochondrial content, defective cristae morphology, and downregulation of OPA1, a critical regulator of mitochondrial integrity, demonstrating that photoreceptor defects in STGD1 also have a cell-autonomous origin, besides the RPE dysfunction. Importantly, we also demonstrated that correcting this pathological phenotype through the modulation of microRNAs 181a and b (miR-181a/b), key regulators of mitochondrial function, ameliorates the STGD1 phenotype. Indeed, genetic inactivation and adeno-associated viral vector-mediated silencing of miR-181a/b in STGD1 models restored OPA1 levels, improved mitochondrial phenotype, and reduced lipofuscin accumulation in the RPE. Our study demonstrates that mitochondrial dysfunction in photoreceptors is an important contributor to STGD1 pathology, opening promising therapeutic avenues for this disorder.}, } @article {pmid42000320, year = {2026}, author = {Xu, Z and Wu, J and Yang, Z and Huang, X and Bao, L and Liu, P and Li, X and Liu, Y}, title = {Responses of transcriptomic profile to cryopreservation in dwarf surfclam (Mulinia lateralis) sperm.}, journal = {Cryobiology}, volume = {123}, number = {}, pages = {105631}, doi = {10.1016/j.cryobiol.2026.105631}, pmid = {42000320}, issn = {1090-2392}, mesh = {Animals ; Male ; *Cryopreservation/methods/veterinary ; *Spermatozoa/metabolism/cytology ; *Transcriptome ; *Semen Preservation/methods/veterinary ; *Bivalvia/genetics ; Gene Expression Profiling ; Sperm Proteins ; }, abstract = {Non-programmable sperm cryopreservation technique has been established for many farmed bivalve species, however, the quality of post-thaw sperm remains substantially variable in practical applications. Although cryodamage to sperm has been investigated cellularly and physiologically, the underpinning molecular mechanism is still not fully elucidated. The dwarf surfclams (Mulinia lateralis) have been used as a model species for bivalves across multiple biological studies. In this study, this species was utilized to investigate the changes in transcriptomic profiles of post-thaw sperm through RNA sequencing (RNA-seq). The results identified 805 differentially expressed transcripts (DETs) between fresh and cryopreserved sperm. The enrichment network analysis of the significantly altered Gene Ontology terms indicated that theses DETs were mainly involved in the structure or functions of cellular membrane, motility, cytoskeleton, mitochondria, immunity and proteasome. Further pathway enrichment analysis revealed that the genes transferred from these DETs were predominantly involved in mitogen-activated protein kinase (MAPK) signaling, insulin signaling, proteasome and oxidative phosphorylation pathways. The findings in this study could offer valuable insights in sperm cryodamage at molecular level, which can therefore be applied to further improve sperm cryopreservation technique for both dwarf surfclam and commercially important bivalve species.}, } @article {pmid42012302, year = {2026}, author = {Ghosh, A and Singh, J}, title = {Interplay between proteostasis pathways and innate immune responses in Caenorhabditis elegans.}, journal = {Infection and immunity}, volume = {94}, number = {5}, pages = {e0003726}, pmid = {42012302}, issn = {1098-5522}, support = {HRD-17011/2/2023-HRD-DBT//Department of Biotechnology, Ministry of Science and Technology, India/ ; BT/RLF/Re-entry/50/2020//Department of Biotechnology, Ministry of Science and Technology, India/ ; MoE-STARS/STARS-2/2023-0116//Ministry of Education, India/ ; CRG/2023/001136//Science and Engineering Research Board/ ; 37/1741/23/EMR-II//Council of Scientific and Industrial Research, India/ ; }, mesh = {Animals ; *Caenorhabditis elegans/immunology ; *Immunity, Innate ; *Proteostasis/immunology ; Signal Transduction ; Unfolded Protein Response ; Host-Pathogen Interactions/immunology ; }, abstract = {Microbial pathogens frequently manipulate host protein homeostasis to undermine immunity by targeting protein synthesis, folding, trafficking, and degradation. Conversely, effective immune responses themselves impose substantial proteostatic demands, as the rapid production of antimicrobial effectors increases the burden on cellular quality-control systems. This bidirectional pressure has likely driven the evolution of surveillance mechanisms that sense disruptions in protein homeostasis as indicators of infection. Using Caenorhabditis elegans as a genetically tractable model, recent studies have revealed that perturbations in proteostasis across multiple cellular compartments, including the cytosol, endoplasmic reticulum (ER), mitochondria, proteasome, and extracellular space, are actively integrated with innate immune signaling. Stress-response pathways such as the heat shock response, translational regulation, and the unfolded protein responses of the ER and mitochondria function not only to restore proteome integrity but also to directly shape immune gene expression and pathogen resistance in a context-dependent manner. This review highlights proteostasis as an evolutionarily conserved immune surveillance system, linking cellular stress sensing to host defense and offering broader insights into the coupling of stress adaptation, immunity, and organismal health.}, } @article {pmid42012907, year = {2026}, author = {Roulet, ME and Garcia, LE and Yu, R and Wang, C and Zhou, R and Sanchez-Puerta, MV}, title = {Circle-mediated HGT shapes the multichromosomal mitochondrial genome of the endoparasitic plant Mitrastemon yamamotoi.}, journal = {The Plant journal : for cell and molecular biology}, volume = {126}, number = {2}, pages = {e70889}, doi = {10.1111/tpj.70889}, pmid = {42012907}, issn = {1365-313X}, support = {PICT2020x2010;01018//Fondo para la Investigación Científica y Tecnológica/ ; 31811530297//National Natural Science Foundation of China/ ; }, mesh = {*Genome, Mitochondrial/genetics ; *Gene Transfer, Horizontal/genetics ; Phylogeny ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Genome, Plant/genetics ; DNA, Circular/genetics ; }, abstract = {Horizontal gene transfer (HGT), a well-established driver of genome evolution in prokaryotes, was historically considered rare in plants. However, accumulating genomic evidence supports its occurrence in angiosperms, impacting both nuclear and mitochondrial genomes, particularly in parasitic species that establish vascular connections with their hosts. Despite the increasing recognition of HGT in a few clades of parasitic plants (e.g., Cuscuta, Balanophoraceae, Rafflesiaceae, and Orobanchaceae), the underlying mechanisms and evolutionary consequences of these transfers are still not fully understood, and a few parasitic lineages have not been thoroughly examined yet (i.e., Apodanthaceae, Cytinaceae, Lennoaceae, Mitrastemonaceae). In this study, we assembled the first mtDNA of Mitrastemonaceae. Mitrastemon yamamotoi, a holoparasitic endoparasite in the order Ericales, invades the roots of host trees in the Fagaceae family, creating favorable conditions for HGT. The M. yamamotoi mtDNA exhibits a multipartite structure consisting of 54 circular-mapping chromosomes. Phylogenetic and comparative genomic analyses uncovered extensive HGT from Fagaceae hosts, affecting both coding and non-coding regions. Notably, almost 60% of the M. yamamotoi mtDNA is of foreign origin, and seven chromosomes are entirely foreign, with structural signatures in the donor mtDNA consistent with the recently proposed circle-mediated HGT model. Additionally, we detected six protein-coding genes of foreign origin and one chimeric gene. Remarkably, a foreign atp1 gene has replaced the missing native copy and represents a rare event of functional HGT in plant mitochondria. These results position M. yamamotoi as a valuable model for studying mtDNA evolution and deepening our understanding of the HGT process. Our findings expand the range of lineages in which circle-mediated HGT has been documented, suggesting it is a more widespread and fundamental mode of mitochondrial HGT in plants.}, } @article {pmid42018132, year = {2026}, author = {Fu, Y and Zhang, W and Zhang, Y and He, Y and Du, Y and Zhao, Y and Yao, C and Sun, S and Sheng, X and Gao, Q and Tong, C and Shuai, L}, title = {Metabolic Imbalance Triggers Adaptive Remodeling to Accelerate Diploidization in Murine Haploid Embryonic Stem Cells.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e22570}, doi = {10.1002/advs.202522570}, pmid = {42018132}, issn = {2198-3844}, support = {2024YFA0917400//National Key R&D Program of China, Synthetic Biology Research/ ; D250401001//Shenzhen Medical Research Fund/ ; 63261183//Fundamental Research Funds for the Central Universities/ ; U25A2026//National Natural Science Foundation of China/ ; 82371671//National Natural Science Foundation of China/ ; 82301879//National Natural Science Foundation of China/ ; U23A20406//National Natural Science Foundation of China/ ; 25JCQNJC01200//Natural Science Foundation of Tianjin City/ ; NKTM2023003//Institute of Transplantation Medicine/ ; 24ZXZSSS00150//Key Project of Tianjin Science and Technology/ ; Redlab202401//Shanghai Key Laboratory of Reproduction and Development/ ; BYSYSZKF2025006//Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education/ ; }, abstract = {Murine haploid embryonic stem cells (haESCs) are ideal tools for functional genetics analyses because of their single-genome stem cell features. However, self-diploidization severely restricts their broader application. Although numerous attempts have been made to prevent diploidization, an effective and reliable strategy is lacking. In this study, we performed multiomics comparative analyses between haESCs and their diploidized counterparts (Di-haESCs), which revealed that metabolic remodeling induced the adaptive evolution of haESCs toward a diploid state. Notably, an overload of intramitochondrial ROS in haESCs impaired mitochondrial bioenergetics, increasing their susceptibility to cell death and driving the progressive accumulation of diploidized cells in culture. We further found that a disrupted pyruvate-lactate balance in haESCs led to altered tricarboxylic acid (TCA) cycle activity, which was closely linked to mitochondrial dysfunction and haploid instability. Leveraging the recovery of mitochondrial function and a doubled mitochondrial number after diploidization, we performed a genome-wide screening to identify key mitochondrial quality control (MQC) genes involved in this process. On the basis of these mechanistic insights, we developed a metabolically optimized medium for haploidy maintenance. These findings benefit haploid stem cell-based genetic screening analyses and deepen the understanding of MQC in mammalian cells.}, } @article {pmid42024652, year = {2026}, author = {Chiavacci, E and Steffensen, KF and Delaroche, P and Astoricchio, E and Poulsen, AB and Brayson, D and Garibaldi, F and Lanteri, L and Pinali, C and Valente, GR and Vignati, F and Steffensen, JF and Shiels, H and Tozzini, ET and Cellerino, A}, title = {Resilience to Cardiac Aging in Greenland Shark Somniosus microcephalus.}, journal = {Aging cell}, volume = {25}, number = {5}, pages = {e70505}, pmid = {42024652}, issn = {1474-9726}, mesh = {Animals ; *Aging/physiology ; *Sharks/physiology ; Male ; *Myocardium/pathology/metabolism/ultrastructure ; Female ; Oxidative Stress ; *Heart/physiology ; Lipofuscin/metabolism ; Myocytes, Cardiac/metabolism ; }, abstract = {The Greenland shark (Somniosus microcephalus), with a lifespan estimated around 300 years, represents a unique model for studying vertebrate longevity. Here, we characterize its cardiac aging profile and compare it with two other species: the deep-sea shark Etmopterus spinax and the short-lived teleost Nothobranchius furzeri. Histological analysis revealed extensive interstitial and perivascular fibrosis throughout the ventricular myocardium of S. microcephalus, affecting both compact and spongy layers of both sexes. This fibrotic pattern was absent in E. spinax and N. furzeri, suggesting it is a specific feature of S. microcephalus. We also observed extreme lipofuscin accumulation within cardiomyocytes of S. microcephalus, which correlates at the ultrastructural level with the abundance of damaged mitochondria and the presence of strikingly enlarged lysosomes filled with electrondense material of likely mitochondrial origin. Additionally, in the myocardium of S. microcephalus we found abundant deposition of the oxidative stress marker 3-nitrotyrosine. Remarkably, despite showing multiple canonical markers of aging such as fibrosis, lipofuscin accumulation, and oxidative stress, S. microcephalus individuals appeared healthy and physiologically uncompromised at the time of capture. These findings suggest that S. microcephalus has evolved resilience to molecular and tissue-level aging signs and hallmarks, supporting sustained cardiac function over centuries and offering new insights into the mechanisms of extreme vertebrate longevity.}, } @article {pmid42025458, year = {2026}, author = {Behnke, A and Shaulson, E and Pontzer, H and Kempes, CP and Picard, M}, title = {Energy constraint on human health.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {}, number = {}, pages = {}, pmid = {42025458}, issn = {1879-3061}, support = {R01 AG076821/AG/NIA NIH HHS/United States ; R01 MH122706/MH/NIMH NIH HHS/United States ; }, abstract = {Evolved constraints to human energy transformation force the body-brain system to operate an economy of energy. To survive and thrive, an organism's finite internal energy resources must be dynamically reallocated, forcing trade-offs from organelle to organism. Building on an energy trade-off framework integrating life history theory and cellular biology, we propose that energy trade-offs occur between three main classes of processes relevant to health: (i) vital, (ii) stress, and (iii) growth, maintenance, and repair (GMR). Competing demands for these processes exist within a hierarchy of energy needs where more 'urgent' vital- and stress-related functions are prioritized by suppressing longevity-promoting growth, maintenance, and repair processes. The energy constraint model of human health provides an energy-based framework to address health/disease dynamics across the lifespan.}, } @article {pmid42030936, year = {2026}, author = {Xiao, FH and Wang, HT and Zhao, L and Li, GH and Ma, SY and Yang, LQ and Wang, H and Zhang, YX and Li, J and Kong, QP}, title = {Preserved mitochondrial ribosomal protein gene expression marks a youthful transcriptional state in Chinese nonagenarians and centenarians.}, journal = {Cell reports. Medicine}, volume = {7}, number = {5}, pages = {102767}, pmid = {42030936}, issn = {2666-3791}, mesh = {Humans ; *Ribosomal Proteins/genetics/metabolism ; Aged, 80 and over ; Male ; Female ; *Longevity/genetics ; *Aging/genetics ; Mitochondria/genetics/metabolism ; *Mitochondrial Proteins/genetics/metabolism ; Transcriptome/genetics ; Asian People/genetics ; Aged ; *Transcription, Genetic ; China ; East Asian People ; }, abstract = {A youthful molecular profile reflects attenuated aging and preserved health in advanced age. Long-lived individuals (LLIs) show youthful patterns in DNA methylation and gut microbiota, yet their transcriptional trajectories remain undercharacterized. We analyze transcriptomes from 811 LLIs and 940 younger controls (YCs) to map transcriptional aging trajectories. Clocks trained on YCs reveal that LLIs possess markedly younger transcriptional ages than expected. We identify gene clusters deviating from YC-derived aging trajectories in LLIs, notably eight mitochondrial ribosomal protein genes (mRPGs) resisting typical age-related expression decline. An elevated 8-mRPG expression score correlates with lower aging levels inferred from established aging- and senescence-related gene gets. Samples with higher 8-mRPG scores exhibit increased expression of mitochondrial-function-related genes, including those in aerobic respiration and respiratory electron transport. Together, these findings indicate that the sustained expression of specific mRPGs in LLIs is a signature of attenuated transcriptomic aging that may reflect preserved mitochondrial function.}, } @article {pmid42033747, year = {2026}, author = {Alachkar, A and Civelli, O}, title = {From Skin to Brain: Antagonism and Parallelism in the MCH and MSH Systems.}, journal = {Annals of the New York Academy of Sciences}, volume = {1558}, number = {1}, pages = {e70267}, doi = {10.1111/nyas.70267}, pmid = {42033747}, issn = {1749-6632}, mesh = {Humans ; *Melanins/metabolism ; *Brain/metabolism/physiology ; Animals ; *Hypothalamic Hormones/metabolism ; *Pituitary Hormones/metabolism ; Circadian Rhythm/physiology ; *Skin/metabolism ; *Melanocyte-Stimulating Hormones/metabolism ; Skin Pigmentation/physiology ; }, abstract = {The melanin-concentrating hormone (MCH) and melanocyte-stimulating hormone (MSH, α-MSH) systems are examples of functional antagonism built upon mechanistic parallelism. Evolved from light-responsive pigment mechanisms, these peptides were repurposed into hypothalamic circuits regulating energy balance, circadian rhythms, and complex behaviors. Their antagonism manifests across multiple biological scales. In the skin, MCH induces melanosome aggregation in low light, whereas MSH promotes their dispersion for ultraviolet protection. In the brain, this pigmentary logic was repurposed into circadian and metabolic regulation: MCH promotes feeding, energy conservation, and sleep, while MSH drives satiety, thermogenesis, and wakefulness. Strikingly, their antagonism extends to subcellular organelles. MCH shortens neuronal primary cilia, whereas MSH elongates them, paralleling their opposite actions on melanosomes. Both processes depend on cAMP-PKA-regulated microtubule transport, reflecting a conserved cellular architecture probably rooted in the shared neural crest origins of melanocytes and neurons. Importantly, these pathways remain tightly entrained to the circadian clock, translating external light-dark cycles into rhythmic control of skin pigmentation and the body's internal metabolic state. Disruptions of these systems contribute to diverse metabolic and neuropsychiatric disorders, often through opposite imbalances of signaling, and understanding this deep evolutionary continuity reveals new therapeutic targets, from receptor ligands to circadian interventions and cilia-targeted therapies.}, } @article {pmid42045377, year = {2026}, author = {Callier, V}, title = {Mitochondria can spawn new 'organelles' - hinting at how modern cells evolved.}, journal = {Nature}, volume = {653}, number = {8113}, pages = {11-12}, pmid = {42045377}, issn = {1476-4687}, } @article {pmid42048289, year = {2026}, author = {Fachi, JL and Trsan, T and Sécca, C and de Oliveira, S and Rodovalho, VR and Rodrigues, PF and Beatty, WL and Sudan, R and Wu, S and Bhattarai, B and Panda, SK and Cella, M and Gilfillan, S and Colonna, M}, title = {LINGO4 coordinates ILC3-intrinsic IL-22 production and microbiota-mediated ILC3 homeostasis.}, journal = {The Journal of experimental medicine}, volume = {223}, number = {6}, pages = {}, pmid = {42048289}, issn = {1540-9538}, support = {#P30 CA91842/CA/NCI NIH HHS/United States ; S10 OD032131/NH/NIH HHS/United States ; 00035299//Pew Charitable Trusts/ ; R01DK132327/NH/NIH HHS/United States ; /RR/NCRR NIH HHS/United States ; WLC6313040077/NH/NIH HHS/United States ; R01DK126969/NH/NIH HHS/United States ; UL1TR000448//Clinical and Translational Science Award/ ; R01 DK132327/DK/NIDDK NIH HHS/United States ; //Institute of Clinical and Translational Sciences/ ; 2023/00393-4//São Paulo Research Foundation/ ; FAPESP 2017/06577-9//São Paulo Research Foundation/ ; No. DBI-1827534//National Science Foundation/ ; R01 DK126969/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Interleukin-22 ; *Interleukins/metabolism/biosynthesis ; *Homeostasis/immunology ; *Lymphocytes/immunology/metabolism ; *Gastrointestinal Microbiome/immunology ; Mice ; *Membrane Proteins/metabolism/genetics ; Immunity, Innate ; Mice, Knockout ; Mice, Inbred C57BL ; Mitochondria/metabolism ; STAT3 Transcription Factor/metabolism ; Citrobacter rodentium ; Apoptosis ; }, abstract = {LINGO4 is a leucine-rich repeat and immunoglobulin-like domain-containing transmembrane protein encoded immediately adjacent to Rorc, the gene for RORγt, raising the possibility that it contributes to the biology of RORγt+ lymphocytes. However, its impact on these cells and resistance to enteric infections has remained unknown. Here, we identify LINGO4 as a critical regulator of group 3 innate lymphoid cells (ILC3s). Lingo4-/- ILC3s exhibit a profound, cell-intrinsic defect in IL-22 production linked to impaired STAT3 activation, mitochondrial dysfunction, elevated ROS, and increased apoptosis. In vivo, Lingo4 deficiency also drives a dysbiotic gut microbiota, resulting in an additional, microbiota-dependent loss of ILC3s. These combined defects increase susceptibility to Clostridioides difficile and Citrobacter rodentium, whereas IL-22 reduction in Lingo4-/- mice confers protection against Salmonellatyphimurium. Immunoprecipitation of tagged LINGO4 reveals interaction networks enriched in mitochondrial pathways, providing mechanistic insight into its role in ILC3 metabolic fitness and intestinal immunity.}, } @article {pmid42062477, year = {2026}, author = {Cheng, X and Li, L and Fang, S and Yu, L and Liu, C and Jiao, Y and Fang, Y and Lin, L and Zhao, L and Su, Y}, title = {Mitochondrial protein Mrpl13 regulates zebrafish liver development through the mTORC1-mitochondrial homeostasis pathway.}, journal = {Communications biology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s42003-026-10137-8}, pmid = {42062477}, issn = {2399-3642}, support = {32170832//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32170541//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {The liver is the largest metabolic organ in the human body, performing functions as metabolism, secretion, immunity, and detoxification. Due to the high energy demand, liver cells are rich in mitochondria. Mitochondrial homeostasis is crucial for liver development and function, yet the molecular pathways linking mitochondrial dysfunction to liver defects remain incompletely understood. In this study, using the zebrafish model, we show that loss of Mrpl13, a component of the mitochondrial ribosomal subunit, results in pronounced abnormalities in liver development. The deficiency of Mrpl13 disrupts mitochondrial homeostasis, as evidenced by fragmentated mitochondria, impaired energy metabolism, excessive reactive oxygen species, and lipid accumulation in liver cells. Notably, loss of Mrpl13 triggers mTORC1 signaling, and treatment with the mTORC1 inhibitor rapamycin significantly alleviates liver developmental defects, suggesting that mTORC1 signaling mediates the role of Mrpl13 in regulating mitochondrial homeostasis and liver development. Overall, our findings reveal a regulatory axis involving Mrpl13, mTORC1, and mitochondrial homeostasis during liver development, providing a theoretical basis for exploring therapeutic strategies for liver defects associated with mitochondrial dysfunction.}, } @article {pmid42067602, year = {2026}, author = {Thompson, B and Bundell, S}, title = {Briefing Chat: Stressed mitochondria spawn new 'organelles' in cells.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-026-01439-2}, pmid = {42067602}, issn = {1476-4687}, } @article {pmid42073468, year = {2026}, author = {Felczak, P}, title = {Atypical Phenotypes of Mitochondrial Cristae Architecture in Selected Human Aging Striated Muscles-Transmission Electron Microscope Studies.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {4}, pages = {}, pmid = {42073468}, issn = {2075-1729}, support = {503-42-071-24002 HORIZON-HLTH-2024-DISEASE-03//This work is co-financed from the OPK project VaMPIRE/ ; }, abstract = {The diversity of mitochondria ultrastructure in human aging striated muscles is presented in relation to the complexity and variability of the cristae architecture and in relation to the environment of mitochondrial occurrence in the muscle fiber on the example of the orbicularis oculi. Ultrastructure analysis of mitochondria in muscles was performed using a transmission electron microscope. The studies revealed the presence of mitochondria of various sizes and unexpected shapes, and also modifications of the cristae architecture which included the occurrence of different configurations of membranes. In some mitochondria, instead of cristae, crystalline inclusion bodies and granules resembling calcium deposits were found. The range of diversity of the studied morphotypes of mitochondria exceeds the algorithms for the morphology of these organelles presented in the literature to date. This diversity of mitochondria should probably be viewed as a manifestation of evolution from the classical cristae architecture to a wide range of forms of mitochondria corresponding to the current environmental conditions of the muscle fiber.}, } @article {pmid42074121, year = {2026}, author = {Daskalova, E and Lee, JS and Zahmanova, G and Minkov, I}, title = {Integrated Symbiotic Pleiotropy: Long Non-Coding RNAs and Disordered Proteins Interweaving the Functional Layers of the Eukaryotic Cell.}, journal = {International journal of molecular sciences}, volume = {27}, number = {8}, pages = {}, pmid = {42074121}, issn = {1422-0067}, support = {BG16RFPR002-1.014-0003-C01//the European Regional Development Fund through Programme Research Innovation and Digitalisation for Smart Transformation/ ; MUPD25-BF-004//Plovdiv University/ ; }, mesh = {*Symbiosis/genetics ; *Intrinsically Disordered Proteins/genetics/metabolism ; *RNA, Long Noncoding/genetics/metabolism ; *Eukaryotic Cells/metabolism ; Humans ; Animals ; *Genetic Pleiotropy ; Evolution, Molecular ; }, abstract = {Long non-coding RNAs (lncRNAs) and RNA-protein complexes (RNPs) are increasingly recognized as central to the regulatory complexity of modern eukaryotes. This review proposes that the remarkable diversity of eukaryotic systems arises from the long-term integration of ancient RNA/RNP mechanisms, layered with innovations introduced by successive symbioses. We outline four interconnected levels of symbiosis contributing to this process: (1) molecular symbiosis, involving dynamic assemblies of RNAs, proteins, and membraneless organelles (MLOs); (2) genome symbiosis, driven by the expansion of non-coding and repetitive DNA; (3) intracellular symbiosis, initiated by mitochondria acquisition; and (4) intercellular symbiosis, rooted in the cellular cooperation that enables multicellularity. We highlight lncRNAs and intrinsically disordered proteins (IDPs) as versatile mediators that interweave interactions across scales, predominantly within phase-separated condensates. Building upon these multi-level processes, we propose the framework of integrated symbiotic pleiotropy-a concept where molecular components acquire layered functional roles as a direct consequence of successive symbiotic acquisitions. This paradigm unites information layering, functional moonlighting, molecular tinkering, and exaptation into a coherent trajectory for eukaryotic evolution.}, } @article {pmid42074573, year = {2026}, author = {Jurado-Angulo, P and Recuero, E and Ruiz, JL and García-París, M}, title = {Morphological and Cyto-Nuclear Conflicting Signals Across Non-Sister Lineages in Darkling Beetles (Tenebrionidae: Akis).}, journal = {Genes}, volume = {17}, number = {4}, pages = {}, pmid = {42074573}, issn = {2073-4425}, support = {(Convocatoria Ayudas a la Investigación 2008)//Instituto de Estudios Ceutíes/ ; PID2019-110243GB-100//Ministerio de Ciencia, Innovación y Universidades/ ; PID2024-159987NB-I00//Ministerio de Ciencia, Innovación y Universidades/ ; }, mesh = {Animals ; *Coleoptera/genetics/classification/anatomy & histology ; Phylogeny ; *Cell Nucleus/genetics ; Electron Transport Complex IV/genetics ; Evolution, Molecular ; Histones/genetics ; Mitochondria/genetics ; DNA, Mitochondrial/genetics ; }, abstract = {Background/Objectives: Cyto-nuclear discordances, resulting from the independent evolutionary histories of cytoplasmic and nuclear genomes, often obscure phylogenetic inference and species delimitation, particularly at shallow taxonomic levels. In this study, we examine the extent and causes of cyto-nuclear discordances within the darkling beetle tribe Akidini (Coleoptera: Tenebrionidae), focusing on the genera Akis Herbst, 1799 and Morica Dejean, 1834. Methods: Using two molecular markers-nuclear histone 3 (H3) and mitochondrial cytochrome c oxidase subunit I (COI)-and a comprehensive sampling from western Europe and northern Africa, we assess reciprocal monophyly, internal relationships, and phylogenetic incongruence across datasets. Results: Discordances between morphological species assignment and mitochondrial topologies may result from retained ancient polymorphisms or historical introgression among closely related species (e.g., Akis genei vs. Akis lusitanica). However, these causes seem less plausible for explaining discordances between nuclear and mitochondrial markers involving non-closely related species (e.g., A. discoidea and A. granulifera). The geographic location of the problematic specimens, limited to a narrow marginal contact zone between the two non-sister species, suggests that local hybridisation may occur. Conclusions: Our results indicate that cyto-nuclear discordances between mitochondrial and nuclear markers, even across morphologically well-differentiated non-sister lineages, may be more frequent than previously assumed in darkling beetles, highlighting both their evolutionary relevance and the need for caution when relying solely on mitochondrial data for species identification.}, } @article {pmid42075358, year = {2026}, author = {Jardim-Messeder, D and de Souza-Vieira, Y and Felix-Cordeiro, T and Corrêa, RL and Sachetto-Martins, G}, title = {Nucleoside Diphosphate Kinase Family: Evolutionary Analysis and Protective Role in Mitochondrial ROS Production.}, journal = {Plants (Basel, Switzerland)}, volume = {15}, number = {8}, pages = {}, pmid = {42075358}, issn = {2223-7747}, support = {423279/2021-1; 420385/2023-1; 307492/2025-7; 402572/2025-4//National Council for Scientific and Technological Development/ ; E-26/210.298/2024; E-26/010.003022/2014; E-26/210.335/2024//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; }, abstract = {Nucleoside diphosphate kinase (NDPK) is a ubiquitous enzyme that maintains cellular nucleotide balance by catalyzing the transfer of phosphate groups between nucleoside diphosphates and triphosphates. Although the evolutionary conservation of NDPK is well established, several aspects of its diversification and functional adaptation remain unclear. The central question of this work is how NDPK evolved across plant species, focusing on the Solanaceae family and how its evolutionary history relates to the diversification of its cellular functions. Phylogenetic and molecular dating analyses showed that the division between NDPK groups 1 and 2 predates the divergence of plants and animals, whereas plant-specific NDPK types (I-IV) originated early in streptophyte evolution. Solanaceae species retain a conserved set of NDPK genes, including a type III isoform with features consistent with mitochondrial targeting. Functional assays in isolated potato tuber mitochondria revealed high NDPK activity in the intermembrane space, sustaining ADP supply to oxidative phosphorylation. Activation of mitochondrial NDPK induced a phosphorylative respiratory state, which partially dissipated the mitochondrial membrane potential and significantly reduced reactive oxygen species (ROS) production. GDP and UDP were preferentially phosphorylated, conferring a stronger antioxidant effect than other nucleotides. Consistently, the mitochondrial isoform StNDPK3 was upregulated during tuber development. Together, our results demonstrate that NDPKs are evolutionarily conserved yet functionally diversified enzymes in plants and identify mitochondrial NDPK as a key modulator of mitochondrial redox homeostasis. By linking nucleotide metabolism to Δψm control and ROS suppression, this study highlights a previously underappreciated antioxidant mechanism that integrates mitochondrial energy metabolism with developmental and stress-related processes in plants.}, } @article {pmid42079717, year = {2026}, author = {Alther, E and Abdelmula, AA and Elsanosi, HA and Mostafa, S and Zhou, G}, title = {Comprehensive genome characterization and expression analysis of the DUF4228 gene family in Sorghum (Sorghum bicolor L.) under salt stress conditions.}, journal = {PeerJ}, volume = {14}, number = {}, pages = {e21175}, pmid = {42079717}, issn = {2167-8359}, mesh = {*Sorghum/genetics ; *Salt Stress/genetics ; *Gene Expression Regulation, Plant ; Phylogeny ; *Plant Proteins/genetics/metabolism ; *Genome, Plant ; *Multigene Family ; Gene Expression Profiling ; *Genes, Plant ; Stress, Physiological/genetics ; }, abstract = {Sorghum (Sorghum bicolor L.) is recognized for its resilience to environmental adversities; the DUF4228 gene family plays vital roles in development, growth, and response to stress in number of plant species such as Arabidopsis thaliana, and Glycine max, however, the systematic analysis of these gene families lacks reports in Sorghum. In this study, we identified and characterized members of the DUF4228 gene family in the Sorghum genome through comprehensive bioinformatics analyses. A total of 25 SbDUF4228 genes were discovered and mapped across eight chromosomes. Phylogenetic analysis divided these genes into six different groupings. Subcellular localization indicated that SbDUF4228 proteins are distributed across the nucleus, mitochondria, cytoplasm, and plasma membrane, indicating potential functional diversity. Expression analysis based on Fragments Per Kilobase of transcript per Million mapped reads (FPKM) values revealed that SbDUF4228 genes are differentially expressed across distinct tissues. Furthermore, the promoter regions of the DUF4228 gene were enriched with cis-regulatory elements associated with stress responses (MYB, MYC) and hormone signaling (ABA, MeJA). To further examine their role in abiotic stress response, we preformed quantitative real-time polymerase chain reaction (qRT-PCR) on seven SbDUF4228 genes under salt stress conditions. The results indicated SbDUF4228-4, SbDUF4228-14, SbDUF4228-1, and SbDUF4228-15 genes were significantly up-regulated following salt treatment, indicating their crucial role in salt stress tolerance. Overall, this study identifies key stress-responsive members of the SbDUF4228 family and provides a foundation for future functional research and Sorghum improvement strategies.}, } @article {pmid42086885, year = {2026}, author = {Lan, YS and Tu, JH and Wang, YC and Hsiao, C}, title = {Architectural principles of the ribosomal large subunit revealed by A-helix spatial organization.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-52028-2}, pmid = {42086885}, issn = {2045-2322}, support = {NSTC-114-2311-B-002-013-//National Science and Technology Council/ ; NSTC-114-2311-B-002-013-//National Science and Technology Council/ ; NSTC-114-2311-B-002-013-//National Science and Technology Council/ ; NSTC-114-2311-B-002-013-//National Science and Technology Council/ ; }, abstract = {The ribosome, biology's universal translation apparatus, is one of the deepest molecular imprints of life's early evolution. Among its structural motifs, the RNA A-helix is the most abundant and fundamental architectural element. Here, we investigate how A-helices collectively shape the three-dimensional organization of the large ribosomal subunit (LSU) across bacteria, archaea, eukaryotes, and mitochondria. By mapping each A-helix onto a centroid-based geometric framework, we identify a conserved peak-centered radial distribution of A-helices that characterizes the spatial organization of LSUs. Applying this approach across diverse ribosomes reveals reproducible architectural states while accommodating lineage-specific structural variation. Notably, mitochondrial LSUs exhibit remodeled radial distributions while retaining the core architectural pattern, consistent with extensive structural adaptation accompanying mitochondrial ribosome evolution. Together, these findings establish the A-helix as a fundamental architectural element of the LSU and provide a generalizable framework for describing ribosomal structure across evolutionary diversity.}, } @article {pmid42116196, year = {2026}, author = {Abreu, FVS and Mosmann, LB and Martins, CB and da Silva Xavier, A and da Rocha Corpas Maciel, IM and Nascimento-Pereira, AC and Ribeiro, PS and Alencar, J and Tubaki, RM and Motta, MA and Lourenço-de-Oliveira, R and Pavan, MG}, title = {Mitochondrial introgression hampers the DNA barcoding of cryptic yellow fever vectors Haemagogus capricornii Lutz and Hg. janthinomys in the Atlantic Forest, Brazil.}, journal = {Parasites & vectors}, volume = {19}, number = {1}, pages = {}, pmid = {42116196}, issn = {1756-3305}, support = {309577/2013-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Animals ; Brazil/epidemiology ; Phylogeny ; *Mosquito Vectors/genetics/classification/anatomy & histology ; *Yellow Fever/transmission ; Female ; Male ; *DNA Barcoding, Taxonomic ; Forests ; *Culicidae/genetics/classification/anatomy & histology ; DNA, Mitochondrial/genetics ; *Genetic Introgression ; *Mitochondria/genetics ; Bayes Theorem ; }, abstract = {BACKGROUND: Yellow fever is a major public health concern in Brazil, transmitted in sylvatic cycles by Haemagogus and Sabethes mosquitoes. Among them, Haemagogus janthinomys and Hg. capricornii occur in sympatry in the Atlantic Forest and females are morphologically indistinguishable, complicating vector identification during outbreaks. Here, we aimed to investigate their taxonomic status and evolutionary history using an integrative approach including morphological and phylogenetic analyses.

METHODS: Mosquitoes were collected in 17 municipalities across nine Brazilian states, including simultaneous captures of both species in sympatric areas. Males were identified by genitalia morphology and molecular analyses were performed using three mitochondrial and two nuclear genes. Diversity analyses and neutrality tests were performed, and phylogenies were reconstructed with Maximum Likelihood and Bayesian inferences. Divergence times were estimated using strict molecular clock, and population history was assessed through mismatch distribution analysis and Bayesian Skyline Plots.

RESULTS: A total of 79 specimens were morphologically identified, with Hg. janthinomys showing a broader geographic and altitudinal distribution than Hg. capricornii, which was usually restricted to higher elevations. Phylogenetic analyses based on mitochondrial markers revealed two clades, but did not recover clear reciprocal monophyly, thus evidencing that these markers alone cannot separate the two species. The inclusion of nuclear markers evidenced introgression events of Hg. janthinomys mitochondria in Hg. capricornii specimens in the Paraíba River Valley and Espírito Santo State, and successive breeding of Hg. capricornii on few samples morphologically identified as Hg. janthinomys in São Paulo State. Molecular clock and population history analyses evidenced that these species have probably speciated in peripatry or parapatry during the Pleistocene era at approximately 1.2 million years ago, and a recent sudden expansion of Hg. capricornii in the last 10 thousand years ago has tripled its population and likely led to a secondary contact between the two species.

CONCLUSIONS: Haemagogus janthinomys and Hg. capricornii are valid and closely related species with evolutionary histories shaped by divergence during the Pleistocene era and subsequent introgression events. The use of cytochrome c oxidase subunit I gene (COI) DNA barcoding alone could not reliably distinguish them, and integrating morphology with multiple molecular markers is essential for accurate identification. Future work is needed for a finer resolution of hybridization patterns to help clarify if the observed mito-nuclear discordance reflects historical introgression or active genetic exchange between species.}, } @article {pmid42127551, year = {2026}, author = {Liu, H and Zhu, Y and Geng, X and Zhao, H and Zhao, Y}, title = {Zinc dyshomeostasis, mitochondrial dysfunction, and their pathological cycle in ischemic stroke pathophysiology: Mechanisms and potential therapeutic targets.}, journal = {Redox biology}, volume = {94}, number = {}, pages = {104208}, pmid = {42127551}, issn = {2213-2317}, mesh = {Humans ; *Zinc/metabolism ; *Mitochondria/metabolism/pathology/drug effects ; *Ischemic Stroke/metabolism/pathology/etiology/drug therapy/physiopathology ; Animals ; Homeostasis ; Oxidative Stress ; *Brain Ischemia/metabolism ; Neurons/metabolism/pathology ; }, abstract = {Ischemic stroke is a leading cause of global mortality and long-term neurological disability. Zinc, an essential trace element critical for neuronal survival within the central nervous system, becomes a key pathological mediator when its homeostasis is disrupted following ischemia. Mitochondria, which are essential for neuronal energy production and survival, are primary targets of zinc-induced toxicity. Excess zinc disrupts mitochondria through multiple mechanisms, causing significant structural damage (swelling and cristae remodeling), impairing dynamic balance (fission/fusion and mitophagy), disrupting oxidative respiratory chain function, reducing ATP production, inducing loss of membrane potential, and triggering oxidative stress responses. Notably, mitochondrial impairment during cerebral ischemia-reperfusion further promotes intracellular zinc accumulation by disrupting cytosolic zinc pools and calcium homeostasis, as well as impairing the interactions between mitochondria and other organelles including the endoplasmic reticulum and lysosomes, creating a vicious cycle that exacerbate ischemic damage. Due to the critical role of zinc ions, emerging zinc-related technologies such as the AggHX sensor, antioxidant zinc oxide nanoparticles and modern zinc chelation strategies offer promising diagnosing and therapeutic avenues for neurological disorders like cerebral ischemia. Meanwhile, the emergence of mitochondrial DNA editing tools marks a new era of precise mitochondrial therapy. Firstly, this review systematically traces the historical evolution of the understanding of zinc's dual roles in neural physiology and pathology, and subsequently summarizes the pathogenic interplay between zinc dyshomeostasis and mitochondrial dysfunction in ischemic stroke, highlighting the "zinc-mitochondria axis" as a potential therapeutic target. It also provides a comprehensive overview of recent advances in zinc-based technologies for neurological diseases, evaluating their opportunities and challenges in neuroprotection and clinical applications, aiming to provide novel insights for developing advanced therapeutic strategies.}, } @article {pmid42144522, year = {2026}, author = {Fadavi, P and Taghizadeh-Hesary, F}, title = {Mitochondrial Metabolism and Dynamics in Cancer Cells.}, journal = {Cancer treatment and research}, volume = {195}, number = {}, pages = {109-120}, pmid = {42144522}, issn = {0927-3042}, mesh = {Humans ; *Neoplasms/metabolism/pathology ; *Mitochondria/metabolism ; *Mitochondrial Dynamics ; Tumor Microenvironment ; Animals ; Oxidative Phosphorylation ; Energy Metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Cancer metabolism has long been interpreted through Otto Warburg's original observation that malignant cells favor aerobic glycolysis due to defective mitochondria. Although foundational, this view is now recognized as incomplete. Contemporary evidence demonstrates that mitochondria in cancer cells remain highly functional and play indispensable roles far beyond adenosine triphosphate (ATP) production. Many tumors actively engage mitochondrial oxidative phosphorylation (OXPHOS) alongside glycolysis, enabling metabolic flexibility across the heterogeneous tumor microenvironment (TME). Mitochondria also generate reactive oxygen species (ROS) that stabilize hypoxia-inducible factor-1 (HIF-1), reinforcing pathways that promote angiogenesis, invasion, and survival under hypoxic stress. Beyond bioenergetics and redox regulation, mitochondria critically shape cancer progression through calcium homeostasis and dynamic remodeling. Meanwhile, mitochondrial fusion and fission govern organelle quality control and functional redistribution. Fusion sustains OXPHOS and cancer stem cell quiescence, whereas fission promotes proliferation, migration, immune evasion, and therapy resistance. Collectively, these findings establish mitochondria as central regulators of tumor evolution, influencing survival in the TME, immune escape, malignant upgrading, and resistance to chemotherapy, radiotherapy, and immunotherapy. Understanding mitochondrial biology, therefore, provides essential insight into cancer progression and reveals promising therapeutic opportunities.}, } @article {pmid42156689, year = {2026}, author = {Nguyen, L and Herwig, S and Gerlach, L and Gholami, S and Schürmann, N and Kleinschmidt, JH}, title = {Sited-Directed Fluorescence Spectroscopy for Studies on the Folding and Insertion of Proteins in Lipid Bilayers and Model Membranes.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {3001}, number = {}, pages = {491-518}, pmid = {42156689}, issn = {1940-6029}, mesh = {*Lipid Bilayers/chemistry/metabolism ; *Protein Folding ; Spectrometry, Fluorescence/methods ; *Membrane Proteins/chemistry/metabolism/genetics ; Mutagenesis, Site-Directed/methods ; Kinetics ; }, abstract = {Protein-lipid interactions are important for folding and membrane insertion of integral membrane proteins that are composed either of α-helical or of β-barrel structure in their transmembrane domains. While α-helical transmembrane proteins fold cotranslationally that they are synthesized by a ribosome, β-barrel transmembrane proteins (β-TMPs) fold and insert post-translationally; in bacteria after translocation across the cytoplasmic membrane, in cell organelles of eukaryotes after import across the outer membrane of the organelle. β-TMPs unfold in aqueous solutions of high concentrations of chaotropic denaturants like urea and spontaneously refold upon denaturant dilution in the presence of preformed lipid bilayers. This facilitates studies on lipid interactions during folding into lipid bilayers. For several β-TMPs, the kinetics of folding has been reported as strongly dependent on protein-lipid interactions. The kinetics of adsorption/insertion and folding of β-TMPs can be monitored by fluorescence spectroscopy. These fluorescence methods are even more powerful when combined with site-directed mutagenesis for the preparation of mutants of a β-TMP that are site-specifically labeled with a fluorophore or a fluorophore and either a fluorescence quencher or fluorescence resonance energy acceptor. Single tryptophan or single cysteine mutants of the β-TMP allow the investigation of local protein-lipid interactions, at specific regions within the protein. To examine the structure formation of β-TMPs in a lipid environment, fluorescence spectroscopy has been used for double mutants of β-TMPs that contain a fluorescent tryptophan and a spin-label, covalently attached to a cysteine as a fluorescence quencher. The sites of mutation are selected in close proximity to another in the folded state of the β-TMP. In a folding experiment, the evolution of fluorescence or fluorescence quenching as a function of time at specific sites within the protein can provide important information on the folding mechanism of the β-TMP. Here, we report protocols to examine membrane protein folding for two β-TMPs in a lipid environment, the outer membrane protein A from Escherichia coli (OmpA) and the voltage-dependent anion-selective channel, human isoform 1 (hVDAC1) from mitochondria.}, } @article {pmid42161732, year = {2026}, author = {Brand, JA and Bertram, MG and Bolstad, GH and Brodin, T and Florencia Camus, M and Hagen, IJ and Havird, JC and Hill, GE and Hindar, K and Iverson, ENK and Kannangara, J and Karlsson, S and Wacker, S and Dowling, DK}, title = {The importance of mitochondrial DNA introgression for conservation.}, journal = {Trends in ecology & evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tree.2026.04.017}, pmid = {42161732}, issn = {1872-8383}, abstract = {Human-mediated gene flow is increasingly altering the genetic composition of populations, yet conservation assessments typically focus on nuclear introgression alone. We synthesise evidence showing that mitochondrial DNA (mtDNA) introgression can have distinct consequences for performance, adaptation, and the viability of animal populations. Unlike most nuclear loci, mtDNA is uniparentally inherited, nonrecombining, and encodes core components of cellular energy metabolism that must function in tight coordination with nuclear genes. As a result, introgression of nonnative mtDNA can disrupt co-adapted mito-nuclear interactions, sometimes generating sex-specific or environment-dependent costs. Conversely, mtDNA introgression can also be neutral or beneficial in certain circumstances. We argue that ignoring mtDNA risks unintended maladaptation and that mitochondrial and nuclear genetics should be considered jointly in conservation planning.}, } @article {pmid42162429, year = {2026}, author = {Lechte, MA and Riedman, LA and Porter, SM and Halverson, GP and Whelan, M}, title = {Early fossil eukaryotes were benthic aerobes.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {42162429}, issn = {1476-4687}, abstract = {The evolution of the eukaryotic cell paved the way for the emergence of all complex life on Earth. Despite its significance, the environmental context of early eukaryote evolution is largely unknown[1,2]. Here we use the geological record to reconstruct the habitats of the oldest known fossil eukaryotes, approximately 1.75-1.4 billion years old. Our integrated palaeontological, sedimentological and geochemical analyses show that although fossil eukaryotes are found in samples deposited in a range of environments from coastal to offshore, they are almost entirely restricted to those from settings with oxygenated bottom waters. This distribution suggests these organisms were aerobes (obligate, facultative and/or microaerophilic) and, given their size and morphological complexity, probably possessed mitochondria. Furthermore, their near absence from otherwise fossiliferous anoxic samples suggests a benthic habit, as planktonic eukaryotes would be expected to be present in both oxic and anoxic samples. We propose that eukaryotes were largely restricted to oxic benthic habitats for much of the Proterozoic eon, only expanding into planktonic habitats during the Neoproterozoic era (1-0.54 billion years ago). This late ecological expansion could account for the mismatch between the appearance of eukaryotic body fossils and molecular biomarkers[3] and explain the stepwise increase in eukaryote diversity during the Neoproterozoic era[4].}, } @article {pmid42164326, year = {2026}, author = {Brüser, T and Sanders, C}, title = {The mechanism of Tat-dependent protein translocation.}, journal = {Microbial cell (Graz, Austria)}, volume = {13}, number = {}, pages = {169-185}, pmid = {42164326}, issn = {2311-2638}, abstract = {The twin-arginine translocation (Tat) system is the only general pathway for the transport of folded proteins across energized biological membranes. It is found in the bacterial or archaeal cytoplasmic membrane, the plant thylakoid membrane or the inner membrane of plant mitochondria. The biological importance of this translocation system can be exemplified by the fact that all bacterial or plant photosynthesis and photosynthetic oxygen evolution on earth requires this system. Despite many biochemical and biophysical studies, the Tat mechanism has been puzzling since the system was discovered in the 1990ies. Important characteristics of the Tat system could not be explained, and also recent high-resolution structures of the Tat system's core with bound substrate has not led to a general transport mechanism yet. In this integrative review, we attempted to answer the key open questions relevant to the Tat mechanism and thereby developed an in its molecular detail new comprehensive explanation of how folded proteins are translocated across membranes by the Tat system.}, } @article {pmid42165416, year = {2026}, author = {Zajac, N and Feijen, F and Jokela, J}, title = {A Whole-Genome Investigation of Mitonuclear Discordance in the Trematode Parasite Atriophallophorus winterbourni.}, journal = {Molecular ecology}, volume = {35}, number = {10}, pages = {e70391}, doi = {10.1111/mec.70391}, pmid = {42165416}, issn = {1365-294X}, support = {ETH-36 15-2//Eidgenössische Technische Hochschule Zürich/ ; 31003A_166667/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {Animals ; *Genome, Mitochondrial/genetics ; *Trematoda/genetics ; Gene Flow ; *Cell Nucleus/genetics ; Haplotypes ; New Zealand ; Lakes ; Genetics, Population ; DNA, Mitochondrial/genetics ; Phylogeny ; Evolution, Molecular ; }, abstract = {Faster evolution of mitochondrial genomes relative to nuclear genomes creates selective pressure on nuclear genes involved in mitochondrial function to preserve mitonuclear compatibility required for energy production. In isolated populations, such coevolution occurs independently. Upon secondary contact, selection against mismatched mitonuclear combinations or for advantageous mitochondrial variants together with their co-adapted nuclear backgrounds can generate asymmetric gene flow between genomes, resulting in mitonuclear discordance. Under these scenarios, nuclear-encoded mitochondrial genes are expected to exhibit divergence concordant with the mitochondrial genome. Mitonuclear discordance has been reported in the trematode parasite Atriophallophorus winterbourni, endemic to New Zealand, and attributed to vicariant isolation followed by postglacial recolonization. Here, we used high-coverage whole-genome pooled resequencing of parasites from five lakes across three geographic regions to characterize genome-wide patterns of divergence and test whether selection on mitonuclear interactions underlies this discordance. We identified three geographically structured mitochondrial haplotypes alongside low nuclear differentiation maintained by extensive but asymmetric gene flow. The central Canterbury population showed discordant mitochondrial and nuclear genome affinities. Most mutations distinguishing the two mitotype groups were synonymous (85%). Of nuclear-encoded mitochondrial genes, only 48% were polymorphic; among these, 95% followed genome-wide nuclear divergence patterns, while 5% showed mildly reduced divergence between closely related mitotypes. Instead, loci with divergence patterns concordant with mtDNA (0.09% of the genome) were enriched for functions unrelated to mitochondria and potentially related to host-parasite interactions, suggesting host-driven adaptive nuclear introgression with mitochondrial co-segregation. These results highlight the utility of genome-wide data in disentangling the mechanisms underlying mitonuclear discordance.}, } @article {pmid42167054, year = {2026}, author = {Mège, M and Berquier, F and Bonsergent, C and Malandrin, L}, title = {Theileria equi sensu lato genetic diversity and phylogeny: new insights from mitochondrion, apicoplast and nucleus multilocus gene analysis.}, journal = {Ticks and tick-borne diseases}, volume = {17}, number = {3}, pages = {102656}, doi = {10.1016/j.ttbdis.2026.102656}, pmid = {42167054}, issn = {1877-9603}, mesh = {*Phylogeny ; *Theileria/genetics/classification ; *Genetic Variation ; Animals ; Horses ; *Theileriasis/parasitology ; Cell Nucleus/genetics ; Multilocus Sequence Typing ; *Horse Diseases/parasitology ; Mitochondria/genetics ; DNA, Protozoan/genetics ; Molecular Sequence Data ; }, abstract = {Equine piroplasmosis is a significant tick-borne disease with a global distribution. Among the two causative agents, Theileria equi has undergone numerous taxonomic reclassifications over time, reflecting advances in our understanding of its biology, molecular characteristics, and phylogenetic relationships. Formerly named Babesia equi, now classified in the Equus group apart from Babesia and Theileria species, its genus name will again certainly change. The genetic diversity also within T. equi lead to the renaming of one lineage as Theileria haneyi. Theileria equi should better now be considered as T. equi sensu lato (including T. haneyi) with a set of different cryptic species awaiting for formal taxonomical changes to be taken. A better knowledge within this group is therefore essential as this diversity has an impact on the diagnostic of this disease which is submitted to strict regulations governing the international movement of horses. In the present study, we designed primers to study the same five genes from the nucleus (hsp70, clamp and ama-1), the mitochondria (cox1) and the apicoplast (tufA), on a set of 36 mono-infected samples of the lineages A, C (T. haneyi) and E of T. equi sensu lato. The phylogenetic separation in lineages A, C and E based on 18S rRNA sequencing was confirmed by this multi-locus analysis. Genetic diversity and phylogenetic separation within lineage A into two sub-lineages A1 and A2 were demonstrated on the basis of all five genes, with an additional A3 sub-lineage on the basis of nuclear (hsp70) and mitochondrial (cox1) markers. All these sub-lineages would deserve the rank of species based on cox1 divergence confirmed by other markers. Phylogenetic and haplotype networks analyses were also conducted on genes used in molecular or serological diagnostic, ema-1 and ema-11, to evaluate the impact of this diversity on currently used tests. We confirmed the absence of molecular detection of the lineage E DNA with any of these two gene targets. We linked the sub-lineages A1 and A3 to the ema-1 clades A and B, with a worldwide distribution. We confirmed the link of the rare A2 sub-lineage from France to a new ema-1 clade D, with additional Eurasian sequences from Croatia, Mongolia and China. A fifth ema-1 clade E was also confirmed. Separation of lineage C (T. haneyi) into at least two sub-lineages was also confirmed with the few ema-11 sequences available, based on their genetic diversity, and their phylogenetic and haplotype network analyses. From this study, it becomes clear that the division of T. equi sensu lato into species corresponding either to the lineage (5 species) or to the sub-lineage (at least 10) should await a more comprehensive knowledge of its genetic diversity worldwide, as it may impact the diagnostic tools to be developed.}, } @article {pmid42213193, year = {2026}, author = {Skossyrskiy, V and Prozorenko, E and Gadaev, I and Skossyrskiy, A and Orlova, E and Sekacheva, M}, title = {Cholesterol as a metabolic integrator of oncogenic signaling, immune evasion, and therapy resistance.}, journal = {Apoptosis : an international journal on programmed cell death}, volume = {31}, number = {6}, pages = {}, pmid = {42213193}, issn = {1573-675X}, mesh = {Humans ; *Cholesterol/metabolism ; *Signal Transduction ; Animals ; *Neoplasms/immunology/metabolism/drug therapy/pathology/genetics ; *Drug Resistance, Neoplasm ; Tumor Microenvironment/immunology ; *Immune Evasion ; Membrane Microdomains/metabolism ; Apoptosis ; }, abstract = {Cholesterol is increasingly recognized as a central coordinator of tumor signaling, metabolism, and immune evasion. In addition to their structural role in membranes, cholesterol-enriched lipid rafts stabilize oncogenic pathways such as those involving EGFR, Src, and ERRα, promoting cancer stemness and therapeutic resistance. Excess cholesterol within mitochondria reduces membrane permeability, prevents cytochrome c release, and contributes to resistance to apoptosis. Moreover, cholesterol-derived oxysterols reshape the tumor microenvironment by inducing Th17 polarization, XBP1-dependent CD8[+] T-cell exhaustion, and macrophage M2 reprogramming. These interconnected mechanisms reveal that cholesterol is a metabolic hub linking intracellular survival pathways with immune dysfunction. Pharmacologic and dietary modulators: Statin, ezetimibe, and ω-3 fatty acids can remodel cholesterol pools, reverse raft stabilization, and partially restore sensitivity to targeted or immune therapies in preclinical models. Recognizing cholesterol metabolism as a contributing factor to oncogenic signaling and immune suppression highlights potential theoretical avenues for biomarker-guided treatment combinations. This integrative framework positions cholesterol not only as a structural lipid but also as a dynamic regulator of tumor evolution and therapy response.}, } @article {pmid42231172, year = {2026}, author = {Xiang, C and Zhu, Z and Xie, S and Chen, C and Huang, X and Zhang, Y and Tao, A}, title = {Characterization and comparative analysis of the complete mitochondrial genome sequence of Aucklandia lappa Decne.}, journal = {BMC plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12870-026-08921-z}, pmid = {42231172}, issn = {1471-2229}, abstract = {BACKGROUND: Aucklandia lappa Decne, a precious medicinal herb in China, utilises the dried rhizome as its medicinal part, which riches in volatile oils, sesquiterpene compounds and other active constituents. Although the mitogenome of A. lappa has been assembled, related research remains in its preliminary stages, far from achieving comprehensive and in-depth understanding.

RESULTS: In this paper, the complete mitogenome of A. lappa was assembled by employing a hybrid strategy that combined Illumina short-read and Nanopore long-read sequencing. The assembled mitogenome is 436,648 bp in size with a GC content of 45.06%. The mitogenome has only one chromosomal structure, It contains 54 genes, including 31 protein-coding genes(PCG), 19 tRNA genes, and 4 rRNA genes. A total of 32 high-frequency codons exhibiting significant AT-bias, 431 RNA editing sites, and 24 homologous fragments were were transferred from the chloroplast to mitochondria genes (7,337 bp, 1.68%). Furthermore, we conducted a phylogenetic analysis involving in A. lappa and 27 other taxa to clarify its evolutionary and taxonomic status. These findings provide a foundation for further understanding the evolutionary relationships within Asteraceae plant.

CONCLUSION: Through the assembly and comprehensive analysis of A. lappa mitogenome, This study has for the first time fully elucidated its mitogenomic structural characteristics.These results not only provide high-quality genetic resources for research on the Asteraceae mitogenome but also lay a solid foundation for in-depth exploration of the evolution and functional genomics of medicinal plants in the Asteraceae family.}, } @article {pmid42243693, year = {2026}, author = {Lu, S}, title = {Comparative analysis of the complete multi-chromosomal mitogenome of Anoectochilus emeiensis (Orchidaceae).}, journal = {BMC plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12870-026-09180-8}, pmid = {42243693}, issn = {1471-2229}, support = {2023NSFSC0015//Sichuan Natural Science Foundation/ ; }, abstract = {BACKGROUND: Anoectochilus emeiensis K. Y. Lang, an orchid with high ornamental and medicinal value, serves as a core raw material in numerous herbal medicines owing to its pharmacological effects. In 2015, its wild populations comprised six local groups with approximately 5,000 individuals. By 2023, only two populations with fewer than 500 individuals remained, largely resulting from habitat destruction and overexploitation. Deciphering the mitochondrial genome of A. emeiensis will help elucidate the structural diversity and functional conservation of Anoectochilus mitogenomes, and offer insights into genome evolution and adaptive strategies. To date, the A. emeiensis mitogenome has not been documented.

RESULTS: The mitogenome of A. emeiensis exhibits a multi-chromosomal structure consisting of 20 circular isoforms. Individual chromosome lengths vary from 13,437 bp to 43,704 bp, with a total length of 490,926 bp and an average GC content of 45.07%. The mitogenome harbors 29 protein-coding genes, 21 tRNA genes, and 3 rRNA genes. Codon usage analysis revealed neutral characteristics with A/U bias at the third codon position. Repetitive sequences, intracellular gene migration, genome size and structure, as well as RNA editing sites were all analyzed. These findings offer key clues for exploring the evolutionary process of multi-chromosomal mitochondria in Orchidaceae.

CONCLUSION: Hybrid sequencing integrating second- and third-generation technologies enabled successful assembly of the A emeiensis mitogenome. This study deepens the understanding of multi-chromosomal mitogenomes in Orchidaceae, illuminates their evolutionary history, and provides valuable resources for germplasm conservation and breeding of this endangered herb.}, } @article {pmid42247036, year = {2026}, author = {Sahraoui, N and Belkahia, H and Ben Said, M and Boukert, R and Ben Ali, S and Denis, F}, title = {Global cytochrome c oxidase subunit I analysis reveals mitochondrial conservation in Camelus dromedarius with clear interspecific separation from other camelids.}, journal = {Molecular biology reports}, volume = {53}, number = {1}, pages = {}, pmid = {42247036}, issn = {1573-4978}, mesh = {Animals ; *Camelus/genetics/classification ; Phylogeny ; *Electron Transport Complex IV/genetics ; *Mitochondria/genetics ; Genetic Variation ; Species Specificity ; DNA Barcoding, Taxonomic/methods ; Sequence Analysis, DNA ; DNA, Mitochondrial/genetics ; Algeria ; Genotype ; }, abstract = {BACKGROUND: The mitochondrial cytochrome c oxidase subunit I (COI) gene is widely used as a DNA barcoding marker; however, its ability to discriminate closely related camelid species and capture intraspecific variation in Camelus dromedarius remains insufficiently assessed at a global scale.

METHODS AND RESULTS: In this study, we sequenced COI from 20 Algerian dromedaries and combined these data with publicly available sequences covering the same fragment, along with representative sequences from the six other extant camelid species and Bos taurus as an outgroup. Sequence alignment, diversity indices, and neutrality tests were performed using DnaSP, while genetic distances and phylogenetic relationships were inferred using Maximum Likelihood under the Tamura-Nei model. Analysis of 136 C. dromedarius COI sequences (625 bp) revealed only five polymorphic sites and four genotypes worldwide, with very low genotype diversity (Gd = 0.277), nucleotide diversity (π = 0.00145), and mean nucleotide differences (k = 0.905). The Algerian genotypes (G1 and G2) fell within this limited variation, showing ≥ 99.2% identity and minimal genetic distances (≤ 0.008) relative to reference sequences. In contrast, interspecific distances between dromedaries and other camelids were substantially higher (≈ 0.014-0.188). Phylogenetic analysis recovered well-supported clades corresponding to C. dromedarius, Bactrian camels, and New World camelids, with no overlap between intra- and interspecific variation.

CONCLUSIONS: These findings indicate that the COI region is highly conserved within C. dromedarius but remains effective for species discrimination. The inclusion of Algerian sequences supports the low mitochondrial diversity of dromedaries and suggests a recent shared maternal ancestry across their global range.}, } @article {pmid42256794, year = {2026}, author = {Olivas-Rasmussen, CA and Gao, P and Rasmussen, ES and Green, CB}, title = {Evolutionary divergence of nocturnin led to redox regulation in mammalian orthologs.}, journal = {Biochemistry and biophysics reports}, volume = {46}, number = {}, pages = {102643}, pmid = {42256794}, issn = {2405-5808}, abstract = {NADP(H) and NAD(H) are essential cofactors involved in nearly 500 metabolic reactions, making them fundamental to cellular function and redox homeostasis. Loss of redox homeostasis through alterations in NADP(H) regulation has been implicated in various diseases, including neurodegenerative disorders and cardiovascular diseases. The levels of these metabolites are tightly regulated and highly compartmentalized. Nocturnin (NOCT), a circadian clock-controlled phosphatase, hydrolyzes both oxidized and reduced forms of NADP(H) and exists in cytosolic and mitochondrial forms. Here, we compare the activity of Xenopus and mammalian NOCT, which reveals a novel redox-dependent regulatory mechanism in mammals. Mammalian NOCT undergoes cysteine-mediated disulfide bond formation, leading to enzyme oligomerization and inactivation, while reduction of these cysteines restores NOCT to its monomeric, active form. In contrast, Xenopus laevis NOCT lacks these regulatory cysteines, does not oligomerize, and remains constitutively active. We show that oligomerization of mammalian NOCT occurs physiologically in the mitochondria while the comparatively highly reduced environment of the cytosol keeps NOCT in its monomeric conformation. Furthermore, sequence analysis reveals that mitochondrial NOCT emerges predominantly in mammals and coincides with the acquisition of redox-sensitive cysteines, highlighting a possible adaptation to oxidative metabolic environments. These findings suggest that mammalian NOCT functions as a redox sensor, dynamically modulating NADP(H) availability in response to oxidative stress. Understanding NOCT's evolution and regulation offers new insights into NADP(H) metabolism and its broader implications for oxidative stress.}, } @article {pmid42268898, year = {2026}, author = {Warren, JM and Prasad, KVSK and Mendez, AM and Temnyk, S and McCutcheon, JP}, title = {Expression of four mitochondrial tRNAs from only two loci.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {24}, pages = {e2534946123}, pmid = {42268898}, issn = {1091-6490}, support = {Investigator Program//HHMI (HHMI)/ ; MCB-2322154//NSF | BIO | Division of Molecular and Cellular Biosciences (MCB)/ ; }, mesh = {*RNA, Transfer/genetics/metabolism/chemistry ; Animals ; RNA, Mitochondrial ; *Mitochondria/genetics/metabolism ; RNA Editing ; *RNA/genetics ; Base Sequence ; Nucleic Acid Conformation ; *Genetic Loci ; }, abstract = {Transfer RNAs (tRNAs) are among the few genes retained in animal mitochondrial genomes after more than a billion years of gene loss. These ancient bacterial vestiges are often structurally aberrant and less stable than their bacterial or cytosolic tRNA counterparts. In some lineages, mitochondrial tRNAs (mt-tRNAs) have become so truncated that the loss of one or both arms has expanded our understanding of what constitutes a functional tRNA. Here, we report another radical departure from canonical tRNA gene architecture: two overlapping tRNAs produced from opposite strands of the same locus. These "mirror" tRNA pairs eliminate the need to retain separate loci for all tRNA genes, as a single locus can produce tRNAs to decode two different amino acids. We show that these mirror tRNAs are aminoacylated and demonstrate their presence in mitoribosomes. Furthermore, mirror tRNAs display strand-specific patterns of nucleotide modification and RNA editing, reflecting specific posttranscriptional maturation that depends on transcriptional orientation. This demonstration of functional, bidirectional tRNA expression reveals an unexpected strategy by which mitochondrial genomes maintain a complete set of tRNAs in the face of unrelenting gene loss. The presence of mirror tRNAs has broad implications for the evolution of tRNA-interacting enzymes, mitochondrial biology, and even the origins of the protein synthesis machinery itself.}, } @article {pmid42270510, year = {2026}, author = {Okwan-Duodu, D and Li, B and Engleman, E}, title = {Mitochondrial transfer reveals an organellar layer of cancer ecology.}, journal = {Trends in cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.trecan.2026.05.006}, pmid = {42270510}, issn = {2405-8025}, abstract = {Tumors are ecological systems shaped by continuous exchange with surrounding cells. The transfer of functional mitochondria, which reprograms malignant behavior, introduces a distinct layer to this ecology. Cancer evolution may proceed not solely through mutation and selection but also through the horizontal assimilation of organellar traits acquired from neighboring cells.}, } @article {pmid42276202, year = {2026}, author = {Cruz, ALD and Heinrichs-Caldas, W and Vilela, B and Val, AL}, title = {White muscle and mitochondrial traits under different locomotor demands in Amazonian fishes.}, journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology}, volume = {319}, number = {}, pages = {112036}, doi = {10.1016/j.cbpa.2026.112036}, pmid = {42276202}, issn = {1531-4332}, abstract = {This study characterized mitochondrial and muscle fiber organization in the white muscle of six Amazonian fish species from the Negro and Solimões rivers, representing distinct locomotor strategies and ecological contexts. Mitochondrial traits (number, area, and volume) and muscle fiber characteristics (nuclei number, fiber size, and sarcomere length) were quantified using light and transmission electron microscopy. Significant interspecific differences were observed, particularly in the nuclear number, with Semaprochilodus taeniurus and Triportheus albus exhibiting the highest values, Pygocentrus nattereri intermediate values, and Oxydoras niger, Pterygoplichthys pardalis, and Serrasalmus gouldingi the lowest. Differences in mitochondrial traits were also detected among species. Multivariate analyses revealed that morphological variation was better explained at the species level than by dietary grouping, with higher classification accuracy when species were analyzed individually. CAP analysis further indicated that trait variation is structured along coordinated multivariate gradients integrating nuclear density, mitochondrial characteristics, and muscle fiber architecture, providing a clear separation of species according to locomotor profiles. These results indicate that muscle and mitochondrial organization are more closely associated with functional demands related to locomotor behavior than with trophic category alone. Species characterized by sustained swimming exhibited greater structural and metabolic investment, whereas benthic and burst-swimming species showed reduced or alternative organizational strategies. Diet appears to play an indirect role by influencing behavioral and locomotor patterns. Overall, our findings highlight the importance of integrating morphological and ecological approaches to understand functional adaptation in fish muscle and identify locomotor demand as the primary axis structuring white muscle and mitochondrial traits in Amazonian fishes.}, } @article {pmid42278388, year = {2026}, author = {Fan, H and Yu, J and Wang, W and Lv, Z and Zhu, S and Li, C}, title = {Perilipin 2 Stabilizes Lipid Droplets and Coordinates Mitochondrial Fatty Acid Flux and ER Stress Adaptation in Apostichopus japonicus.}, journal = {International journal of molecular sciences}, volume = {27}, number = {11}, pages = {}, pmid = {42278388}, issn = {1422-0067}, support = {32303042//National Natural Science Foundation of China/ ; 32325050//National Science Fund for Distinguished Young Scholars of China/ ; LQ24C190001//Zhejiang Provincial Natural Science Foundation/ ; LZ25C190002//Zhejiang Provincial Natural Science Foundation/ ; 2024JCYJ070//Yantai Science and Technology Innovation Development Plan-Basic Research Project/ ; }, mesh = {Animals ; *Mitochondria/metabolism ; *Stichopus/metabolism/genetics/microbiology ; *Lipid Droplets/metabolism ; *Fatty Acids/metabolism ; *Perilipin-2/metabolism/genetics/chemistry ; Phylogeny ; *Endoplasmic Reticulum Stress ; Endoplasmic Reticulum/metabolism ; Vibrio ; Lipolysis ; Adaptation, Physiological ; }, abstract = {Perilipins (PLINs) are lipid droplet-associated proteins that regulate lipid storage, mobilization, and metabolism, yet their roles in invertebrates remain poorly characterized. This study aimed to investigate the evolutionary conservation and functional adaptation of PLIN2 in the sea cucumber Apostichopus japonicus. Phylogenetic analysis placed A. japonicus PLIN2 within the PLIN2 clade, forming an echinoderm-specific branch distinct from vertebrate PLIN2s. Structural prediction revealed an N-terminal PAT domain containing an amphipathic helix that was required for lipid droplet targeting, as deletion of this region abolished its localization to lipid droplet. Functionally, PLIN2 abundance positively correlated with lipid droplet formation, and its knockdown reduced triacylglycerol accumulation while upregulating lipolysis-related genes. Pull-down and co-immunoprecipitation assays identified interactions between PLIN2 and the endoplasmic reticulum protein ERP44, as well as the mitochondrial protein TRXR2, suggesting a role in lipid droplet-organelle coupling. Consistently, disruption of the PLIN2-TRXR2 module impaired fatty acid transfer from lipid droplets to mitochondria, leading to suppressed β-oxidation and decreased ATP production. In addition, PLIN2 mediates the protective role of lipid droplets against Vibrio splendidus-induced ER stress. Together, these findings establish A. japonicus PLIN2 as a multifunctional lipid droplet-associated protein that coordinates lipid droplet stability with organelle communication, energy metabolism, and ER homeostasis.}, } @article {pmid42282756, year = {2026}, author = {Raval, PK and Thaler, NK and Mitchell, C and Lozano-Quiles, M and Kajander, T and Djamriani, DW and Reiners, J and Smits, SH and Butcher, SJ and Battersby, BJ and Gould, SB}, title = {Structure determination and dual targeting of a plant TACO1 identifies its ancient role as an organelle translation regulator.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.05.28.728419}, pmid = {42282756}, issn = {2692-8205}, abstract = {UNLABELLED: Ribosome stalling caused by polyproline (PPs) motifs is common. Their translation is enhanced by accessory proteins such as YebC in bacteria, whose homolog, TRANSLATIONAL ACTIVATOR OF CYTOCHROME C OXIDASE 1 (TACO1), aids the translation of mitochondria-encoded proteins. The prevalence of PP motifs across plastid-encoded genes and their impact on the translation of photosynthesis-relevant proteins remains unexplored. Equally, a translation-enhancer of PP motifs equivalent to TACO1 for plastid ribosomes has not been reported. Here, we show that plastid genomes encode 24 proteins with a minimum of one PP motif on average, half of which are conserved in their cyanobacterial homologs, and that the vast majority of eukaryotes, including plants, encode a single TACO1 that we demonstrate to be dually targeted to mitochondria and plastids of Marchantia polymorpha . We resolved the MpTACO1 structure at 2.34 Å by X-ray crystallography and the flexibility by small-angle X-ray scattering. Through modelling, we demonstrate that MpTACO1 can fit into the peptidyl transfer centre of plant chlororibosomes in a similar manner as human TACO1 in the mitoribosome. The identification and structure determination of the first plastid-targeted YebC/TACO1 allows us to sketch a unified model for the function and evolution of this ancient family of ribosomal accessory proteins, underscoring their indispensable role in the translation of bioenergetic membrane proteins reaching back almost 4 billion years.

HIGHLIGHTS: Dozens of GC-rich polyproline (PP) encoding regions are retained by AT-rich genomesPP motif conservation hints at regulatory mechanisms and required translation pausesChloroplast targeting of a (mitochondrial) translation enhancer of PP motifsMpTACO1 structure at 2.34 Å resolution demonstrates its high level of conservation.}, } @article {pmid42289377, year = {2026}, author = {Vecchi, M and Surmacz, B and Jönsson, IK and Stec, D}, title = {Fragmentation of Long Reads Enables Reliable Mitogenome Assembly From Whole-Genome Amplification Data With Pervasive Palindromic Reads.}, journal = {Molecular ecology resources}, volume = {26}, number = {5}, pages = {e70165}, pmid = {42289377}, issn = {1755-0998}, support = {2022/45/P/NZ8/01512//Narodowe Centrum Nauki/ ; }, mesh = {*Genome, Mitochondrial ; Animals ; *Tardigrada/genetics/classification ; Sequence Analysis, DNA/methods ; *Nucleic Acid Amplification Techniques/methods ; *Computational Biology/methods ; *Inverted Repeat Sequences ; }, abstract = {Whole genome amplification (WGA), and in particular multiple displacement amplification (MDA), has become a key technique for genomic sequencing of microscopic organisms, yet it introduces artefacts such as palindromic (inverted chimeric) reads that may compromise downstream analyses. We assessed how pervasive palindromic reads generated by MDA impact the assembly of tardigrade (Acutuncus giovanniniae and A. mecnuffi) mitogenomes sequenced with Oxford Nanopore technology. We show that the MDA produces a high proportion of palindromic reads, often exceeding one-third of mitochondrial reads and frequently exhibiting complex multi-inversion structures. These artefacts severely impair long-read assembly, leading to low success rates and inconsistent genome reconstruction. To solve this issue, a strategy based on in silico fragmentation of long reads into short, high-quality fragments, followed by short-read assembly, consistently produced complete and accurate circularised mitochondrial genomes. Our results demonstrate that palindromic read formation can be, in some cases, a limitation of MDA coupled with long-read sequencing, but this issue can be mitigated through read fragmentation. This approach provides a simple, robust and scalable solution for mitogenome assembly from data heavily affected by amplification artefacts, particularly in microscopic taxa where whole genome amplification is often unavoidable.}, } @article {pmid42301420, year = {2026}, author = {Hill, GE and Powers, MJ and Weaver, RJ}, title = {Shared Pathways, Physiological Constraint, and the Evolutionary Origins of an Honest Signal. A commentary on Számadó et al. (2025).}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jeb/voag048}, pmid = {42301420}, issn = {1420-9101}, abstract = {A recent review of honest signaling theory criticized constraint-based (index) explanations for traits that serve as honest signals of individual quality, contending that such explanations offer only proximate mechanisms and fail to explain evolutionary stability or the origin of reliability. A key point in this critique is the contention that ultimate explanations require the possibility of cheating. The authors advocate for the Signaling Trade-off Theory-where trade-offs make cheating evolutionarily unfavorable-as essentially a complete explanation for the evolution of signal honesty. Here we argue that this critique rests on a false dichotomy between proximate and ultimate explanation. When signal production is mechanistically embedded within vital cellular processes, this shared pathway inherently restricts the evolution of cheating. Using avian ketocarotenoid coloration as a model, we show that condition-dependent signal production is not explained by trade-offs because pigment transformation is coupled to mitochondrial energy metabolism and core cellular performance, making high-signal expression unattainable for low-condition individuals. Deception may therefore be physiologically inaccessible rather than merely costly. Moreover, the enzymatic machinery underlying ketocarotenoid production likely evolved for visual function before being co-opted for social assessment, such that condition-dependent color expression preceded assessment of coloration in social interactions. Uncheatable honest signals can thus arise as an exaptation of biochemical processes needed to sustain complex life rather than as outcomes of unfavorable trade-offs.}, } @article {pmid42303018, year = {2026}, author = {Samad, A and Ptáčková, J and Motlová, L and Kučera, T and Novák, P and Bařinka, C and Černý, J and Kutejová, E and Cianci, M and Janata, J and Tachezy, J}, title = {Changes in the structure of mitochondrial processing peptidase driven by adaptation to anaerobiosis.}, journal = {International journal of biological macromolecules}, volume = {372}, number = {}, pages = {153058}, doi = {10.1016/j.ijbiomac.2026.153058}, pmid = {42303018}, issn = {1879-0003}, abstract = {Transition of eukaryotes from oxygen-rich to oligoxic or anoxic environments drove profound physiological changes, particularly in mitochondria. Low oxygen led to the loss of respiratory complexes that generate the inner mitochondrial membrane (IM) electrochemical gradient, as seen in anaerobic types of mitochondria, like the hydrogenosomes in Trichomonas vaginalis. Besides energy metabolism, IM potential is critical for organelle biogenesis, particularly the import of matrix preproteins. These preproteins contain positively charged N-terminal targeting sequences (NTSs) that facilitate import via the TIM23 translocase. Upon translocation, NTS is cleaved by mitochondrial processing peptidase (MPP), a zinc metallopeptidase composed of α and β subunits. The α-MPP glycine-rich loop (GRL) recognizes and delivers the presequence to the β-MPP active site. Hydrogenosomal NTSs are shorter and less positively charged, reflecting reduced IM potential. Using X-ray crystallography, modeling, and mutagenesis, we reveal distinctive structural adaptations of the hydrogenosomal processing peptidase (HPP). Compared to MPP, HPP has a central chamber about half the size, with predominantly electropositive and neutral surface charges. The α-HPP GRL features a reduced conserved glycine motif and is positioned closer to the β-HPP active site. Enzymatic assays of β-HPP mutants revealed a novel substrate interaction site involved in Zn[2+] dependent catalysis. These structural adaptations match the unique properties of hydrogenosomal NTSs, optimizing their processing under anaerobic conditions. They illustrate how adaptation to anaerobiosis drives protein structural evolution to sustain life in oxygen-poor environments.}, } @article {pmid42308315, year = {2026}, author = {Stevens, TA and Luo, Z and Lee, C and Hazu, M and Galatis, EG and Inglis, AJ and Guna, A and Voorhees, RM}, title = {Structural evolution of the MTCH family of mitochondrial insertases.}, journal = {Science advances}, volume = {12}, number = {25}, pages = {eaeh2957}, pmid = {42308315}, issn = {2375-2548}, mesh = {*Evolution, Molecular ; Humans ; Cryoelectron Microscopy ; *Mitochondrial Membrane Transport Proteins/chemistry/genetics/metabolism ; Models, Molecular ; *Mitochondria/metabolism ; Hydrophobic and Hydrophilic Interactions ; Mitochondrial Membranes/metabolism ; }, abstract = {We demonstrate that MTCH2 is the defining member of a large family of mitochondrial outer membrane (OM) insertases. MTCH insertases are conserved across holozoa and have diverged from the solute carrier 25 transporters. The cryoelectron microscopy structure of the 33-kilodalton human MTCH2 revealed that evolution of its insertase activity required loss of a transmembrane helix, which created a lipid-accessible hydrophilic groove stabilized by its unique, structured C terminus. Mutational analyses showed that MTCH insertase activity is attenuated, while experimental structures and reconstitution of hyperactive mutants demonstrated that the hydrophobicity, charge, and size of the residues that line its groove regulated MTCH function. Leveraging the MTCH2 structure, we identified the plant OM insertase and proposed a universal mechanism for OM insertion across all kingdoms of life.}, } @article {pmid42319595, year = {2026}, author = {Sengupta, A and Samanta, P and Basu, J and Biswas, S and Pakhira, S and Mondal, M and Saha, P and Hajra, S}, title = {From Ferroptotic Stress to Stemness: TNT-Mediated EMT Plasticity in Cancer Progression.}, journal = {Stem cell reviews and reports}, volume = {}, number = {}, pages = {}, pmid = {42319595}, issn = {2629-3277}, support = {IIRP-2023-3962//Indian Council of Medical Research/ ; }, abstract = {Tumor evolution is shaped by adaptive responses to metabolic and oxidative stress, rather than solely by genetic mutations. Ferroptosis is an iron-dependent mechanism of cell death driven by lipid peroxidation. This process acts both as a tumor suppressive barrier and as a selective pressure for tumor adaptation. Cancer cells that escape ferroptosis undergo metabolic and transcriptional reprogramming, resulting in enhanced antioxidant capacity and increased resistance to oxidative stress. These adaptative changes closely intersect with epithelial-mesenchymal transition (EMT), generating hybrid phenotypes enriched in cancer stem cell (CSC)-like properties. Concurrently, tunneling nanotubes (TNTs) emerge as stress-responsive intercellular communication networks that facilitate the transfer of mitochondria, metabolites and redox regulators, thereby enabling cooperative survival. Through this review, we outline an integrative framework connecting ferroptosis, EMT plasticity, TNT-mediated communication and CSC dynamics, offering insights into novel strategies to overcome therapeutic resistance, prevent metastatic dissemination and limit tumor relapse. It further highlights the current landscape of emerging biomarkers and therapeutic agents that may enable the translation of this integrated network as a target in cancer treatment.}, } @article {pmid32719405, year = {2020}, author = {Flament-Simon, SC and de Toro, M and Chuprikova, L and Blanco, M and Moreno-González, J and Salas, M and Blanco, J and Redrejo-Rodríguez, M}, title = {High diversity and variability of pipolins among a wide range of pathogenic Escherichia coli strains.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {12452}, pmid = {32719405}, issn = {2045-2322}, mesh = {Animals ; *DNA Transposable Elements ; Escherichia coli/classification/*genetics/isolation & purification/metabolism ; Escherichia coli Infections/*microbiology/*veterinary ; Genetic Variation ; Genome, Bacterial ; Humans ; Phylogeny ; }, abstract = {Self-synthesizing transposons are integrative mobile genetic elements (MGEs) that encode their own B-family DNA polymerase (PolB). Discovered a few years ago, they are proposed as key players in the evolution of several groups of DNA viruses and virus-host interaction machinery. Pipolins are the most recent addition to the group, are integrated in the genomes of bacteria from diverse phyla and also present as circular plasmids in mitochondria. Remarkably, pipolins-encoded PolBs are proficient DNA polymerases endowed with DNA priming capacity, hence the name, primer-independent PolB (piPolB). We have now surveyed the presence of pipolins in a collection of 2,238 human and animal pathogenic Escherichia coli strains and found that, although detected in only 25 positive isolates (1.1%), they are present in E. coli strains from a wide variety of pathotypes, serotypes, phylogenetic groups and sequence types. Overall, the pangenome of strains carrying pipolins is highly diverse, despite the fact that a considerable number of strains belong to only three clonal complexes (CC10, CC23 and CC32). Comparative analysis with a set of 67 additional pipolin-harboring genomes from GenBank database spanning strains from diverse origin, further confirmed these results. The genetic structure of pipolins shows great flexibility and variability, with the piPolB gene and the attachment sites being the only common features. Most pipolins contain one or more recombinases that would be involved in excision/integration of the element in the same conserved tRNA gene. This mobilization mechanism might explain the apparent incompatibility of pipolins with other integrative MGEs such as integrons. In addition, analysis of cophylogeny between pipolins and pipolin-harboring strains showed a lack of congruence between several pipolins and their host strains, in agreement with horizontal transfer between hosts. Overall, these results indicate that pipolins can serve as a vehicle for genetic transfer among circulating E. coli and possibly also among other pathogenic bacteria.}, } @article {pmid32722672, year = {2020}, author = {Fernando, HSD and Hapugoda, M and Perera, R and Black Iv, WC and De Silva, BGDNK}, title = {Mitochondrial metabolic genes provide phylogeographic relationships of global collections of Aedes aegypti (Diptera: Culicidae).}, journal = {PloS one}, volume = {15}, number = {7}, pages = {e0235430}, pmid = {32722672}, issn = {1932-6203}, mesh = {Aedes/classification/*genetics ; Africa ; Africa, Eastern ; Animals ; DNA, Mitochondrial/*genetics ; Electron Transport Complex IV/genetics ; Gene Flow ; Genes, Mitochondrial/genetics ; Haplotypes ; India ; Mitochondria/*genetics/metabolism ; Pakistan ; Phylogeny ; *Phylogeography ; Sri Lanka ; }, abstract = {Phylogeographic relationships among global collections of the mosquito Aedes aegypti were evaluated using the mitochondrial Cytochrome C Oxidase 1 (CO1) and NADH dehydrogenase subunit 4 (ND4) genes including new sequences from Sri Lanka. Phylogeographic analysis estimated that Ae. aegypti arose as a species ~614 thousand years ago (kya) in the late Pleistocene. At 545 kya an "early" East African clade arose that continued to differentiate in East Africa, and eventually gave rise to three lineages one of which is distributed throughout all tropical and subtropical regions, a second that contains Southeast Asian/Sri Lankan mosquitoes and a third that contains mostly New World mosquitoes. West African collections were not represented in this early clade. The late clade continued to differentiate throughout Africa and gave rise to a lineage that spread globally. The most recent branches of the late clade are represented by South-East Asia and India/Pakistan collections. Analysis of migration rates suggests abundant gene flow between India/Pakistan and the rest of the world with the exception of Africa.}, } @article {pmid32727571, year = {2020}, author = {Wang, X and Wang, J and Liu, J and Liu, A and He, X and Xiang, Q and Li, Y and Yin, H and Luo, J and Guan, G}, title = {Insights into the phylogenetic relationships and drug targets of Babesia isolates infective to small ruminants from the mitochondrial genomes.}, journal = {Parasites & vectors}, volume = {13}, number = {1}, pages = {378}, pmid = {32727571}, issn = {1756-3305}, support = {2017YFD0501200//the National Key Research and Development Programme of China/ ; 2015CB150300//the 973 Programme/ ; }, mesh = {Animals ; *Babesia/classification/genetics/isolation & purification ; Babesiosis/drug therapy/genetics ; *Classification ; Cytochromes b/genetics ; Drug Delivery Systems ; *Genome, Mitochondrial ; Genome, Protozoan ; Phylogeny ; Sheep ; Sheep Diseases/parasitology ; Tick-Borne Diseases/parasitology ; }, abstract = {BACKGROUND: Babesiosis, a tick-borne disease caused by protozoans of the genus Babesia, is widespread in subtropical and tropical countries. Mitochondria are essential organelles that are responsible for energy transduction and metabolism, calcium homeostasis and cell signaling. Mitochondrial genomes could provide new insights to help elucidate and investigate the biological features, genetic evolution and classification of the protozoans. Nevertheless, there are limited data on the mitochondrial genomes of ovine Babesia spp. in China.

METHODS: Herein, we sequenced, assembled and annotated the mitochondrial genomes of six ovine Babesia isolates; analyzed the genome size, gene content, genome structure and cytochrome b (cytb) amino acid sequences and performed comparative mitochondrial genomics and phylogenomic analyses among apicomplexan parasites.

RESULTS: The mitochondrial genomes range from 5767 to 5946 bp in length with a linear form and contain three protein-encoding genes, cytochrome c oxidase subunit 1 (cox1), cytochrome c oxidase subunit 3 (cox3) and cytb, six large subunit rRNA genes (LSU) and two terminal inverted repeats (TIR) on both ends. The cytb gene sequence analysis indicated the binding site of anti-Babesia drugs that targeted the cytochrome bc1 complex. Babesia microti and Babesia rodhaini have a dual flip-flop inversion of 184-1082 bp, whereas other Babesia spp. and Theileria spp. have one pair of TIRs, 25-1563 bp. Phylogenetic analysis indicated that the six ovine Babesia isolates were divided into two clades, Babesia sp. and Babesia motasi. Babesia motasi isolates were further separated into two small clades (B. motasi Hebei/Ningxian and B. motasi Tianzhu/Lintan).

CONCLUSIONS: The data provided new insights into the taxonomic relationships and drug targets of apicomplexan parasites.}, } @article {pmid32730281, year = {2020}, author = {Pelster, B and Wood, CM and Campos, DF and Val, AL}, title = {Cellular oxygen consumption, ROS production and ROS defense in two different size-classes of an Amazonian obligate air-breathing fish (Arapaima gigas).}, journal = {PloS one}, volume = {15}, number = {7}, pages = {e0236507}, pmid = {32730281}, issn = {1932-6203}, support = {I 2984/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; Brazil ; Catalase/metabolism ; Fishes/*physiology ; Gills/enzymology/metabolism ; Glutathione/metabolism ; Glutathione Peroxidase/metabolism ; Kidney/metabolism ; Mitochondria/metabolism ; Oxygen Consumption/*physiology ; Reactive Oxygen Species/*metabolism ; Superoxide Dismutase/metabolism ; }, abstract = {In air-breathing fish a reduction of gill surface area reduces the danger of losing oxygen taken up in the air-breathing organ (ABO) to hypoxic water, but it also reduces the surface area available for ion exchange, so that ion regulation may at least in part be transferred to other organs, like the kidney or the gut. In the air-breathing Arapaima gigas, gill lamellae regress as development proceeds, and starting as a water-breathing embryo Arapaima turns into an obligate air-breathing fish with proceeding development, suggesting that ion regulation is shifted away from the gills as the fish grows. In Arapaima the kidney projects medially into the ABO and thus, probably a unique situation among fishes, is in close contact to the gas of the ABO. We therefore hypothesized that the kidney would be predestined to adopt an increased importance for ion homeostasis, because the elevated ATP turnover connected to ion transport can easily be met by aerobic metabolism based on the excellent oxygen supply directly from the ABO. We also hypothesized that in gill tissue the reduced ion regulatory activity should result in a reduced metabolic activity. High metabolic activity and exposure to high oxygen tensions are connected to the production of reactive oxygen species (ROS), therefore the tissues exposed to these conditions should have a high ROS defense capacity. Using in vitro studies, we assessed metabolic activity and ROS production of gill, kidney and ABO tissue, and determined the activity of ROS degrading enzymes in small (~ 5g, 2-3 weeks old) and larger (~ 670 g, 3-4 months old) A. gigas. Comparing the three tissues revealed that kidney tissue oxygen uptake by far exceeded the uptake measured in gill tissue or ABO. ROS production was particularly high in gill tissue, and all three tissues had a high capacity to degrade ROS. Gill tissue was characterized by high activities of enzymes involved in the glutathione pathway to degrade ROS. By contrast, the tissues of the ABO and in particular the kidney were characterized by high catalase activities, revealing different, tissue-specific strategies in ROS defense in this species. Overall the differences in the activity of cells taken from small and larger fish were not as pronounced as expected, while at the tissue level the metabolic activity of kidney cells by far exceeded the activity of ABO and gill cells.}, } @article {pmid32735771, year = {2020}, author = {Williams, R and Laskovs, M and Williams, RI and Mahadevan, A and Labbadia, J}, title = {A Mitochondrial Stress-Specific Form of HSF1 Protects against Age-Related Proteostasis Collapse.}, journal = {Developmental cell}, volume = {54}, number = {6}, pages = {758-772.e5}, doi = {10.1016/j.devcel.2020.06.038}, pmid = {32735771}, issn = {1878-1551}, support = {BB/P005535/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; /BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Aging/*physiology ; Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/*metabolism ; Heat-Shock Response/physiology ; Mitochondria/*metabolism ; Molecular Chaperones/metabolism ; Proteome/metabolism ; Proteostasis/*physiology ; Stress, Physiological/physiology ; Transcription Factors/*metabolism ; }, abstract = {The loss of protein homeostasis (proteostasis) is a primary driver of age-related tissue dysfunction. Recent studies have revealed that the failure of proteostasis with age is triggered by developmental and reproductive cues that repress the activity of proteostasis-related pathways in early adulthood. In Caenorhabditis elegans, reduced mitochondrial electron transport chain (ETC) function during development can override signals that promote proteostasis collapse in aged tissues. However, it is unclear precisely how these beneficial effects are mediated. Here, we reveal that in response to ETC impairment, the PP2A complex generates a dephosphorylated, mitochondrial stress-specific variant of the transcription factor HSF-1. This results in the selective induction of small heat shock proteins in adulthood, thereby protecting against age-related proteostasis collapse. We propose that mitochondrial signals early in life can protect the aging cytosolic proteome by tailoring HSF-1 activity to preferentially drive the expression of non-ATP-dependent chaperones.}, } @article {pmid32735957, year = {2020}, author = {Harasgama, JC and Kasthuriarachchi, TDW and Kwon, H and Wan, Q and Lee, J}, title = {Molecular and functional characterization of a mitochondrial glutathione reductase homolog from redlip mullet (Liza haematocheila): Disclosing its antioxidant properties in the fish immune response mechanism.}, journal = {Developmental and comparative immunology}, volume = {113}, number = {}, pages = {103785}, doi = {10.1016/j.dci.2020.103785}, pmid = {32735957}, issn = {1879-0089}, mesh = {Animals ; Antioxidants/*metabolism ; Cloning, Molecular ; Fish Proteins/*genetics/metabolism ; Gills/*metabolism ; Glutathione Reductase/*genetics/metabolism ; Homeostasis ; Immunity, Innate ; Mitochondria/*metabolism ; Oxidation-Reduction ; Oxidative Stress ; Phylogeny ; Sequence Alignment ; Smegmamorpha/*immunology ; Transcriptome ; }, abstract = {Glutathione reductase (GSHR) is a biologically important enzyme involved in the conversion of oxidized glutathione (GSSG) into its reduced form, reduced glutathione (GSH), with the catalytic activity of NADPH. Most animals and aquatic organisms, including fish, possess high levels of this enzyme system to neutralize oxidative stress in cells. The current study was conducted to broaden our knowledge of GSHR in fish by identifying a mitochondrial isoform of this enzyme (LhGSHRm) in redlip mullet, Liza haematocheila, and clarifying its structure and function. The complete open reading frame of LhGSHRm consists of 1527 base pairs, encoding 508 amino acids, with a predicted molecular weight of 55.43 kDa. Multiple sequence alignment revealed the conservation of important amino acids in this fish. Phylogenetic analysis demonstrated the closest evolutionary relationship between LhGSHRm and other fish GSHRm counterparts. In tissue distribution analysis, the highest mRNA expression of LhGSHRm was observed in the gill tissue under normal physiological conditions. Following pathogenic challenges, the LhGSHRm transcription level was upregulated in a time-dependent manner in the gill and liver tissues, which may modulate the immune reaction against pathogens. rLhGSHRm showed considerable glutathione reductase activity in an enzyme assay. Further, the biological activity of rLhGSHRm in balancing cellular oxidative stress was observed in both disk diffusion and DPPH assays. Collectively, these results support that LhGSHRm has profound effects on modulating the immune reaction in fish to sustain precise redox homeostasis.}, } @article {pmid32739012, year = {2020}, author = {Smith, SK and Musiek, ES}, title = {Impact of circadian and diurnal rhythms on cellular metabolic function and neurodegenerative diseases.}, journal = {International review of neurobiology}, volume = {154}, number = {}, pages = {393-412}, pmid = {32739012}, issn = {2162-5514}, support = {P30 DK056341/DK/NIDDK NIH HHS/United States ; T32 GM108539/GM/NIGMS NIH HHS/United States ; }, mesh = {Chronobiology Disorders/complications/*metabolism ; Humans ; Mitochondria/*metabolism ; NAD/*metabolism ; Neurodegenerative Diseases/etiology/*metabolism ; Sirtuins/*metabolism ; Sleep Wake Disorders/etiology/*metabolism ; }, abstract = {The 24-h rotational period of the earth has driven evolution of biological systems that serve to synchronize organismal physiology and behavior to this predictable environmental event. In mammals, the circadian (circa, "about" and dia, "a day") clock keeps 24-h time at the organismal and cellular level, optimizing biological function for a given time of day. The most obvious circadian output is the sleep-wake cycle, though countless bodily functions, ranging from hormone levels to cognitive function, are influenced by the circadian clock. Here we discuss the regulation of metabolic pathways by the circadian clock, discuss the evidence implicating circadian and sleep disruption in neurodegenerative diseases, and suggest some possible connections between the clock, metabolism, and neurodegenerative disease.}, } @article {pmid32745723, year = {2020}, author = {Nechushtai, R and Karmi, O and Zuo, K and Marjault, HB and Darash-Yahana, M and Sohn, YS and King, SD and Zandalinas, SI and Carloni, P and Mittler, R}, title = {The balancing act of NEET proteins: Iron, ROS, calcium and metabolism.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {1867}, number = {11}, pages = {118805}, doi = {10.1016/j.bbamcr.2020.118805}, pmid = {32745723}, issn = {1879-2596}, mesh = {Calcium/*metabolism ; Cell Proliferation/genetics ; Endoplasmic Reticulum/metabolism ; Humans ; Iron/chemistry/*metabolism ; Iron-Sulfur Proteins/chemistry/genetics/*metabolism ; Mitochondria/metabolism ; Protein Binding/genetics ; Reactive Oxygen Species/*metabolism ; }, abstract = {NEET proteins belong to a highly conserved group of [2Fe-2S] proteins found across all kingdoms of life. Due to their unique [2Fe2S] cluster structure, they play a key role in the regulation of many different redox and oxidation processes. In eukaryotes, NEET proteins are localized to the mitochondria, endoplasmic reticulum (ER) and the mitochondrial-associated membranes connecting these organelles (MAM), and are involved in the control of multiple processes, ranging from autophagy and apoptosis to ferroptosis, oxidative stress, cell proliferation, redox control and iron and iron‑sulfur homeostasis. Through their different functions and interactions with key proteins such as VDAC and Bcl-2, NEET proteins coordinate different mitochondrial, MAM, ER and cytosolic processes and functions and regulate major signaling molecules such as calcium and reactive oxygen species. Owing to their central role in cells, NEET proteins are associated with numerous human maladies including cancer, metabolic diseases, diabetes, obesity, and neurodegenerative diseases. In recent years, a new and exciting role for NEET proteins was uncovered, i.e., the regulation of mitochondrial dynamics and morphology. This new role places NEET proteins at the forefront of studies into cancer and different metabolic diseases, both associated with the regulation of mitochondrial dynamics. Here we review recent studies focused on the evolution, biological role, and structure of NEET proteins, as well as discuss different studies conducted on NEET proteins function using transgenic organisms. We further discuss the different strategies used in the development of drugs that target NEET proteins, and link these with the different roles of NEET proteins in cells.}, } @article {pmid32758535, year = {2020}, author = {Dupuis, JR and Sperling, FAH}, title = {Phylogenomic test of mitochondrial clues to archaic ancestors in a group of hybridizing swallowtail butterflies.}, journal = {Molecular phylogenetics and evolution}, volume = {152}, number = {}, pages = {106921}, doi = {10.1016/j.ympev.2020.106921}, pmid = {32758535}, issn = {1095-9513}, mesh = {Animals ; Biological Evolution ; Butterflies/*classification/*genetics ; DNA, Mitochondrial/genetics ; Genome, Insect/genetics ; Hybridization, Genetic ; Mitochondria/*genetics ; North America ; Nucleic Acid Hybridization ; *Phylogeny ; }, abstract = {Genomics has revolutionized our understanding of hybridization and introgression, but most of the early evidence for these processes came from studies of mitochondrial introgression. To expand these evolutionary insights from mitochondrial patterns, we evaluate phylogenetic discordance across the nuclear genomes of a hybridizing system, the Papilio machaon group of swallowtail butterflies. This species group contains three hybrid lineages (P. brevicauda, P. joanae, and P. m. kahli) that are geographically disjunct across North America and have complete fixation of a mitochondrial lineage that is otherwise primarily found in P. m. hudsonianus, a boreal subspecies of the Holarctic P. machaon. Genome-wide nuclear markers place the three hybrid lineages as a monophyletic group that is sister to P. polyxenes/P. zelicaon rather than P. machaon, although ancient hybridization between a subspecies of P. machaon and the ancestor of these three lineages is also shown by their greater nuclear affinity to P. m. hudsonianus than to other subspecies of P. machaon. Individuals from contemporary hybrid swarms in Alberta, where mitochondrial DNA fixation has not occurred, were more intermediate between their respective parent species, demonstrating diversity in mito-nuclear discordance following hybrid interactions. Our new phylogenetic findings for the P. machaon species group also include: subspecific paraphyly within P. machaon itself across its Holarctic distribution; paraphyly of P. zelicaon relative to P. polyxenes; and more divergent placement of a Mediterranean species, P. hospiton. These results provide the first comprehensive genomic evaluation of relationships within this species group and provide insight into the evolutionary dynamics of hybridization and mitochondrial introgression.}, } @article {pmid32768405, year = {2020}, author = {Bennewitz, B and Sharma, M and Tannert, F and Klösgen, RB}, title = {Dual targeting of TatA points to a chloroplast-like Tat pathway in plant mitochondria.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {1867}, number = {11}, pages = {118816}, doi = {10.1016/j.bbamcr.2020.118816}, pmid = {32768405}, issn = {1879-2596}, mesh = {Arabidopsis/genetics ; Arabidopsis Proteins/genetics/metabolism ; Cell Membrane/genetics/metabolism ; Chloroplasts/*genetics/metabolism ; Electron Transport Complex III/genetics ; Escherichia coli/genetics ; Escherichia coli Proteins/genetics/metabolism ; Membrane Proteins/*genetics ; Membrane Transport Proteins/*genetics/metabolism ; Mitochondria/*genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; Pisum sativum/genetics ; Plant Proteins/*genetics ; Protein Folding ; Protein Sorting Signals ; Signal Transduction/genetics ; Twin-Arginine-Translocation System/*genetics ; }, abstract = {The biogenesis of membrane-bound electron transport chains requires membrane translocation pathways for folded proteins carrying complex cofactors, like the Rieske Fe/S proteins. Two independent systems were developed during evolution, namely the Twin-arginine translocation (Tat) pathway, which is present in bacteria and chloroplasts, and the Bcs1 pathway found in mitochondria of yeast and mammals. Mitochondria of plants carry a Tat-like pathway which was hypothesized to operate with only two subunits, a TatB-like protein and a TatC homolog (OrfX), but lacking TatA. Here we show that the nuclearly encoded TatA from pea has dual targeting properties, i.e., it can be imported into both, chloroplasts and mitochondria. Dual targeting of TatA was observed with in organello experiments employing chloroplasts and mitochondria isolated from pea as well as after transient expression of suitable reporter constructs in leaf tissue from pea and Nicotiana benthamiana. The extent of transport of these constructs into mitochondria of transiently transformed leaf cells was relatively low, causing a demand for highly sensitive methods to be detected, like the sasplitGFP approach. Yet, the dual import of TatA into mitochondria and chloroplasts observed here points to a common mechanism of Tat transport for folded proteins within both endosymbiotic organelles in plants.}, } @article {pmid32769116, year = {2020}, author = {MacEwen, MJ and Markhard, AL and Bozbeyoglu, M and Bradford, F and Goldberger, O and Mootha, VK and Sancak, Y}, title = {Evolutionary divergence reveals the molecular basis of EMRE dependence of the human MCU.}, journal = {Life science alliance}, volume = {3}, number = {10}, pages = {}, pmid = {32769116}, issn = {2575-1077}, support = {R01 AR071942/AR/NIAMS NIH HHS/United States ; R01 HL130143/HL/NHLBI NIH HHS/United States ; T32 GM007750/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Calcium/metabolism ; Calcium Channels/*metabolism/physiology ; Dictyostelium/genetics/metabolism ; Evolution, Molecular ; HEK293 Cells ; Humans ; Ion Transport/genetics/physiology ; Mitochondria/metabolism ; Protein Domains ; }, abstract = {The mitochondrial calcium uniporter (MCU) is a calcium-activated calcium channel critical for signaling and bioenergetics. MCU, the pore-forming subunit of the uniporter, contains two transmembrane domains and is found in all major eukaryotic taxa. In amoeba and fungi, MCU homologs are sufficient to form a functional calcium channel, whereas human MCU exhibits a strict requirement for the metazoan protein essential MCU regulator (EMRE) for conductance. Here, we exploit this evolutionary divergence to decipher the molecular basis of human MCU's dependence on EMRE. By systematically generating chimeric proteins that consist of EMRE-independent Dictyostelium discoideum MCU and Homo sapiens MCU (HsMCU), we converged on a stretch of 10 amino acids in D. discoideum MCU that can be transplanted to HsMCU to render it EMRE independent. We call this region in human MCU the EMRE dependence domain (EDD). Crosslinking experiments show that EMRE directly interacts with HsMCU at its transmembrane domains as well as the EDD. Our results suggest that EMRE stabilizes the EDD of MCU, permitting both channel opening and calcium conductance, consistent with recently published structures of MCU-EMRE.}, } @article {pmid32771550, year = {2020}, author = {Kornilios, P and Jablonski, D and Sadek, RA and Kumlutaş, Y and Olgun, K and Avci, A and Ilgaz, C}, title = {Multilocus species-delimitation in the Xerotyphlops vermicularis (Reptilia: Typhlopidae) species complex.}, journal = {Molecular phylogenetics and evolution}, volume = {152}, number = {}, pages = {106922}, doi = {10.1016/j.ympev.2020.106922}, pmid = {32771550}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial/genetics ; Genetic Variation ; Haplotypes ; Mitochondria/genetics ; *Molecular Typing ; *Phylogeny ; Snakes/*classification/*genetics ; Species Specificity ; }, abstract = {Scolecophidia (worm snakes) are a vertebrate group with high ecomorphological conservatism due to their burrowing lifestyle. The Eurasian or Greek blindsnake Xerotyphlops vermicularis is their only European representative, a species-complex with an old diversification history. However, its systematics and taxonomy has remained untouched. Here, we extend previous work that relied heavily on mitochondrial markers, following a multi-locus approach and applying several species-delimitation methods, including a Bayesian coalescence-based approach (STACEY). Four "species" delimitation analyses based on the mtDNA (ABGD, bGMYC, mPTP, parsimony networks) returned 14, 11, 9 and 10 clusters, respectively. By mitotyping twice as many specimens as before, we have a complete picture of each cluster's distribution. With the exception of the highly-divergent Levantine lineage, the three independent nuclear markers did not help with phylogenetic resolution, as demonstrated in haplotype networks, concatenated and species-trees, a result of incomplete lineage sorting. The prevailing model from the coalescence-based species-delimitation identified two species: the lineage from the Levant and all others. We formally recognize them as distinct species and resurrect Xerotyphlops syriacus (Jan, 1864) to include the Levantine blindsnakes. Finally, X. vermicularis and X. syriacus may represent species-complexes themselves, since they include high levels of cryptic diversity.}, } @article {pmid32788582, year = {2020}, author = {Pittis, AA and Goh, V and Cebrian-Serrano, A and Wettmarshausen, J and Perocchi, F and Gabaldón, T}, title = {Discovery of EMRE in fungi resolves the true evolutionary history of the mitochondrial calcium uniporter.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4031}, pmid = {32788582}, issn = {2041-1723}, mesh = {Amino Acid Sequence ; Calcium/metabolism ; Calcium Channels/chemistry/*genetics ; Chytridiomycota/genetics ; *Evolution, Molecular ; Fungal Proteins/chemistry/*genetics ; HeLa Cells ; Humans ; Likelihood Functions ; Phylogeny ; Species Specificity ; }, abstract = {Calcium (Ca[2+]) influx into mitochondria occurs through a Ca[2+]-selective uniporter channel, which regulates essential cellular processes in eukaryotic organisms. Previous evolutionary analyses of its pore-forming subunits MCU and EMRE, and gatekeeper MICU1, pinpointed an evolutionary paradox: the presence of MCU homologs in fungal species devoid of any other uniporter components and of mt-Ca[2+] uptake. Here, we trace the mt-Ca[2+] uniporter evolution across 1,156 fully-sequenced eukaryotes and show that animal and fungal MCUs represent two distinct paralogous subfamilies originating from an ancestral duplication. Accordingly, we find EMRE orthologs outside Holoza and uncover the existence of an animal-like uniporter within chytrid fungi, which enables mt-Ca[2+] uptake when reconstituted in vivo in the yeast Saccharomyces cerevisiae. Our study represents the most comprehensive phylogenomic analysis of the mt-Ca[2+] uptake system and demonstrates that MCU, EMRE, and MICU formed the core of the ancestral opisthokont uniporter, with major implications for comparative structural and functional studies.}, } @article {pmid32788668, year = {2021}, author = {Lareau, CA and Ludwig, LS and Muus, C and Gohil, SH and Zhao, T and Chiang, Z and Pelka, K and Verboon, JM and Luo, W and Christian, E and Rosebrock, D and Getz, G and Boland, GM and Chen, F and Buenrostro, JD and Hacohen, N and Wu, CJ and Aryee, MJ and Regev, A and Sankaran, VG}, title = {Massively parallel single-cell mitochondrial DNA genotyping and chromatin profiling.}, journal = {Nature biotechnology}, volume = {39}, number = {4}, pages = {451-461}, pmid = {32788668}, issn = {1546-1696}, support = {U10 CA180861/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; T32 HG002295/HG/NHGRI NIH HHS/United States ; F31 CA232670/CA/NCI NIH HHS/United States ; UG1 CA233338/CA/NCI NIH HHS/United States ; T32 CA207021/CA/NCI NIH HHS/United States ; P01 CA206978/CA/NCI NIH HHS/United States ; R33 HL120791/HL/NHLBI NIH HHS/United States ; R01 CA208756/CA/NCI NIH HHS/United States ; R01 DK103794/DK/NIDDK NIH HHS/United States ; }, mesh = {Aged, 80 and over ; Cell Differentiation ; Cells, Cultured ; Clonal Evolution ; Clone Cells ; DNA, Mitochondrial/*genetics ; Epigenesis, Genetic ; Female ; Genotyping Techniques ; Hematopoiesis ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Mitochondria/*genetics ; Mutation ; Neoplasms/*genetics ; Sequence Analysis, DNA ; Single-Cell Analysis/*methods ; }, abstract = {Natural mitochondrial DNA (mtDNA) mutations enable the inference of clonal relationships among cells. mtDNA can be profiled along with measures of cell state, but has not yet been combined with the massively parallel approaches needed to tackle the complexity of human tissue. Here, we introduce a high-throughput, droplet-based mitochondrial single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq), a method that combines high-confidence mtDNA mutation calling in thousands of single cells with their concomitant high-quality accessible chromatin profile. This enables the inference of mtDNA heteroplasmy, clonal relationships, cell state and accessible chromatin variation in individual cells. We reveal single-cell variation in heteroplasmy of a pathologic mtDNA variant, which we associate with intra-individual chromatin variability and clonal evolution. We clonally trace thousands of cells from cancers, linking epigenomic variability to subclonal evolution, and infer cellular dynamics of differentiating hematopoietic cells in vitro and in vivo. Taken together, our approach enables the study of cellular population dynamics and clonal properties in vivo.}, } @article {pmid32788982, year = {2020}, author = {N Miyata, M and Nomura, M and Kageyama, D}, title = {Wolbachia have made it twice: Hybrid introgression between two sister species of Eurema butterflies.}, journal = {Ecology and evolution}, volume = {10}, number = {15}, pages = {8323-8330}, pmid = {32788982}, issn = {2045-7758}, abstract = {Wolbachia, cytoplasmically inherited endosymbionts of arthropods, are known to hijack their host reproduction in various ways to increase their own vertical transmission. This may lead to the selective sweep of associated mitochondria, which can have a large impact on the evolution of mitochondrial lineages. In Japan, two different Wolbacahia strains (wCI and wFem) are found in two sister species of pierid butterflies, Eurema mandarina and Eurema hecabe. In both species, females infected with wCI (C females) produce offspring with a nearly 1:1 sex ratio, while females infected with both wCI and wFem (CF females) produce all-female offspring. Previous studies have suggested the historical occurrence of hybrid introgression in C individuals between the two species. Furthermore, hybrid introgression in CF individuals is suggested by the distinct mitochondrial lineages between C females and CF females of E. mandarina. In this study, we performed phylogenetic analyses based on nuclear DNA and mitochondrial DNA markers of E. hecabe with previously published data on E. mandarina. We found that the nuclear DNA of this species significantly diverged from that of E. mandarina. By contrast, mitochondrial DNA haplotypes comprised two clades, mostly reflecting Wolbachia infection status rather than the individual species. Collectively, our results support the previously suggested occurrence of two independent historical events wherein the cytoplasms of CF females and C females moved between E. hecabe and E. mandarina through hybrid introgression.}, } @article {pmid32806678, year = {2020}, author = {Santos, HJ and Chiba, Y and Makiuchi, T and Arakawa, S and Murakami, Y and Tomii, K and Imai, K and Nozaki, T}, title = {Import of Entamoeba histolytica Mitosomal ATP Sulfurylase Relies on Internal Targeting Sequences.}, journal = {Microorganisms}, volume = {8}, number = {8}, pages = {}, pmid = {32806678}, issn = {2076-2607}, support = {23117001, 23117005//Ministry of Education, Culture, Sports, Science and Technology/ ; 17K19416; JP18H02650; JP20K16233//Japan Society for the Promotion of Science/ ; }, abstract = {Mitochondrial matrix proteins synthesized in the cytosol often contain amino (N)-terminal targeting sequences (NTSs), or alternately internal targeting sequences (ITSs), which enable them to be properly translocated to the organelle. Such sequences are also required for proteins targeted to mitochondrion-related organelles (MROs) that are present in a few species of anaerobic eukaryotes. Similar to other MROs, the mitosomes of the human intestinal parasite Entamoeba histolytica are highly degenerate, because a majority of the components involved in various processes occurring in the canonical mitochondria are either missing or modified. As of yet, sulfate activation continues to be the only identified role of the relic mitochondria of Entamoeba. Mitosomes influence the parasitic nature of E. histolytica, as the downstream cytosolic products of sulfate activation have been reported to be essential in proliferation and encystation. Here, we investigated the position of the targeting sequence of one of the mitosomal matrix enzymes involved in the sulfate activation pathway, ATP sulfurylase (AS). We confirmed by immunofluorescence assay and subcellular fractionation that hemagluttinin (HA)-tagged EhAS was targeted to mitosomes. However, its ortholog in the δ-proteobacterium Desulfovibrio vulgaris, expressed as DvAS-HA in amoebic trophozoites, indicated cytosolic localization, suggesting a lack of recognizable mitosome targeting sequence in this protein. By expressing chimeric proteins containing swapped sequences between EhAS and DvAS in amoebic cells, we identified the ITSs responsible for mitosome targeting of EhAS. This observation is similar to other parasitic protozoans that harbor MROs, suggesting a convergent feature among various MROs in favoring ITS for the recognition and translocation of targeted proteins.}, } @article {pmid32808073, year = {2020}, author = {Bernacki, LE and Kilpatrick, CW}, title = {Structural Variation of the Turtle Mitochondrial Control Region.}, journal = {Journal of molecular evolution}, volume = {88}, number = {7}, pages = {618-640}, doi = {10.1007/s00239-020-09962-0}, pmid = {32808073}, issn = {1432-1432}, mesh = {Animals ; Base Sequence ; Conserved Sequence ; DNA, Mitochondrial/genetics/*metabolism ; *Evolution, Molecular ; Genetic Variation ; Genome, Mitochondrial ; Mitochondria/genetics ; *Nucleic Acid Conformation ; Phylogeny ; Sequence Alignment ; Sequence Analysis, DNA ; Turtles/*genetics ; }, abstract = {The present study describes the most comprehensive comparison of turtle mtD-loop regions to date. The primary structure was compared from DNA sequences accessed from GenBank from 48 species in 13 families of extant turtles, and secondary structures of the mtD-loop region were inferred from thermal stabilities, using the program Mfold, for each superfamiliy of turtles. Both primary and secondary structures were found to be highly variable across the order. The Cryptodira showed conservation in the primary structure at conserved sequence blocks (CSBs), but the Pleurodira displayed limited conservation of primary structural characters, other than the coreTAS, a binding site for the helicase TWINKLE, which was highly conserved in the Central and Right Domains across the order. No secondary structure was associated with a TAS, but an AT-rich fold (secondary structure) near the 3' terminus of the mtD-loop region was detected in all turtle superfamilies. Mapping of character states of structural features of the mtD-loop region revealed that most character states were autapomorphies and inferred a number of homoplasies. The Left Domain of turtles, containing no highly conserved structural elements, likely does not serve a functional role; therefore, the Central Domain in turtles is likely equivalent to the Left Domain of mammals. The AT-rich secondary structural element near the 3' terminus of the mtD-loop region may be conserved across turtles because of a functional role, perhaps containing the Light Strand Promotor, or perhaps interacting with the TWINKLE-coreTAS complex in the Central and Right Domains to regulate mtDNA replication and transcription.}, } @article {pmid32812630, year = {2020}, author = {Shen, H and Zheng, X and Zhou, Z and He, W and Li, M and Su, P and Song, J and Yang, Y}, title = {Oriented immobilization of enzyme-DNA conjugates on magnetic Janus particles for constructing a multicompartment multienzyme system with high activity and stability.}, journal = {Journal of materials chemistry. B}, volume = {8}, number = {36}, pages = {8467-8475}, doi = {10.1039/d0tb01439g}, pmid = {32812630}, issn = {2050-7518}, mesh = {Armoracia/enzymology ; Aspergillus niger/enzymology ; Biocatalysis ; Biomimetics/methods ; DNA/*chemistry ; Enzymes, Immobilized/*chemistry ; Fluoresceins/chemistry ; Fluorescent Dyes/chemistry ; Fungal Proteins/chemistry ; Glucose/analysis/chemistry ; Glucose Oxidase/*chemistry ; Horseradish Peroxidase/*chemistry ; Magnetite Nanoparticles/*chemistry ; Oxidation-Reduction ; Plant Proteins/chemistry ; }, abstract = {Various organelles (e.g., mitochondria and chloroplasts) have a multicompartment structure, providing superior function of material transformation, selective segregation and energy conversion. Enlightened by the elegant evolution of nature, intended isolation of the biochemical process by cooperative multicompartments in cells has become an appealing blueprint to construct bioreactors. In this study, we develop a "soft separation" way to establish a delicate multicompartment multienzyme system (MMS) with polyphenol-encapsulated enzyme-DNA conjugates, which are anchored on magnetic Janus particles, providing a biomimetic catalysis network with the model cascade reactions in confinement. The well-designed MMS exhibits preferable bioactivity benefitting from the dependable DNA bridges and the oriented immobilization of enzymes, while the polyphenol shell further protects the anchored enzymes from exterior attacks, such as heat and enzymatic degradation. Moreover, by applying the MMS as nanomotors, the asymmetrical distribution of enzymes on Janus particles is found to improve mutual elevation between the self-driven locomotion and enzyme-mediated reactions, delivering enhanced dispersal ability and bioactivity. Owing to the excellent enzymatic activity, promoted stability and satisfying biocompatibility, the assembled MMS is proved to be promising for the in vitro and intracellular sensing of glucose, showing significant potential for biochemical analysis applications.}, } @article {pmid32817169, year = {2020}, author = {Srivastava, SR and Mahalakshmi, R}, title = {Evolutionary selection of a 19-stranded mitochondrial β-barrel scaffold bears structural and functional significance.}, journal = {The Journal of biological chemistry}, volume = {295}, number = {43}, pages = {14653-14665}, pmid = {32817169}, issn = {1083-351X}, support = {/WT_/Wellcome Trust/United Kingdom ; IA/I/14/1/501305/WTDBT_/DBT-Wellcome Trust India Alliance/India ; }, mesh = {Animals ; Evolution, Molecular ; Humans ; Lipid Bilayers/chemistry/*metabolism ; Mitochondria/chemistry/genetics/metabolism ; Models, Molecular ; Mutation ; Porins/chemistry/genetics/metabolism ; Protein Conformation, beta-Strand ; Protein Engineering ; Protein Stability ; Saccharomyces cerevisiae/chemistry/genetics/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism ; Thermodynamics ; Voltage-Dependent Anion Channel 2/chemistry/genetics/metabolism ; Voltage-Dependent Anion Channels/*chemistry/genetics/*metabolism ; }, abstract = {Transmembrane β-barrels of eukaryotic outer mitochondrial membranes (OMMs) are major channels of communication between the cytosol and mitochondria and are indispensable for cellular homeostasis. A structurally intriguing exception to all known transmembrane β-barrels is the unique odd-stranded, i.e. 19-stranded, structures found solely in the OMM. The molecular origins of this 19-stranded structure and its associated functional significance are unclear. In humans, the most abundant OMM transporter is the voltage-dependent anion channel. Here, using the human voltage-dependent anion channel as our template scaffold, we designed and engineered odd- and even-stranded structures of smaller (V2[16], V2[17], V2[18]) and larger (V2[20], V2[21]) barrel diameters. Determination of the structure, dynamics, and energetics of these engineered structures in bilayer membranes reveals that the 19-stranded barrel surprisingly holds modest to low stability in a lipid-dependent manner. However, we demonstrate that this structurally metastable protein possesses superior voltage-gated channel regulation, efficient mitochondrial targeting, and in vivo cell survival, with lipid-modulated stability, all of which supersede the occurrence of a metastable 19-stranded scaffold. We propose that the unique structural adaptation of these transmembrane transporters exclusively in mitochondria bears strong evolutionary basis and is functionally significant for homeostasis.}, } @article {pmid32822607, year = {2020}, author = {Deng, J and Xie, XL and Wang, DF and Zhao, C and Lv, FH and Li, X and Yang, J and Yu, JL and Shen, M and Gao, L and Yang, JQ and Liu, MJ and Li, WR and Wang, YT and Wang, F and Li, JQ and Hehua, E and Liu, YG and Shen, ZQ and Ren, YL and Liu, GJ and Chen, ZH and Gorkhali, NA and Rushdi, HE and Salehian-Dehkordi, H and Esmailizadeh, A and Nosrati, M and Paiva, SR and Caetano, AR and Štěpánek, O and Olsaker, I and Weimann, C and Erhardt, G and Curik, I and Kantanen, J and Mwacharo, JM and Hanotte, O and Bruford, MW and Ciani, E and Periasamy, K and Amills, M and Lenstra, JA and Han, JL and Zhang, HP and Li, L and Li, MH}, title = {Paternal Origins and Migratory Episodes of Domestic Sheep.}, journal = {Current biology : CB}, volume = {30}, number = {20}, pages = {4085-4095.e6}, doi = {10.1016/j.cub.2020.07.077}, pmid = {32822607}, issn = {1879-0445}, mesh = {Animals ; Breeding ; Cell Lineage/genetics ; Chromosome Mapping ; DNA, Mitochondrial/*genetics ; Genetic Variation/genetics ; Genome/*genetics ; Male ; Mitochondria/genetics ; Phenotype ; Phylogeny ; Polymorphism, Single Nucleotide/*genetics ; Sheep ; Sheep, Domestic/classification/*genetics ; Whole Genome Sequencing ; Y Chromosome/*genetics ; }, abstract = {The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution.}, } @article {pmid32824295, year = {2020}, author = {Yamada, M and Akashi, K and Ooka, R and Miyado, K and Akutsu, H}, title = {Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes.}, journal = {International journal of molecular sciences}, volume = {21}, number = {16}, pages = {}, pmid = {32824295}, issn = {1422-0067}, mesh = {Gene Editing/methods ; *Genes, Mitochondrial ; *Genetic Drift ; Humans ; Mitochondrial Replacement Therapy/adverse effects/*methods ; Nuclear Transfer Techniques/*adverse effects ; Oocytes/*metabolism ; }, abstract = {Mitochondria are energy-producing intracellular organelles containing their own genetic material in the form of mitochondrial DNA (mtDNA), which codes for proteins and RNAs essential for mitochondrial function. Some mtDNA mutations can cause mitochondria-related diseases. Mitochondrial diseases are a heterogeneous group of inherited disorders with no cure, in which mutated mtDNA is passed from mothers to offspring via maternal egg cytoplasm. Mitochondrial replacement (MR) is a genome transfer technology in which mtDNA carrying disease-related mutations is replaced by presumably disease-free mtDNA. This therapy aims at preventing the transmission of known disease-causing mitochondria to the next generation. Here, a proof of concept for the specific removal or editing of mtDNA disease-related mutations by genome editing is introduced. Although the amount of mtDNA carryover introduced into human oocytes during nuclear transfer is low, the safety of mtDNA heteroplasmy remains a concern. This is particularly true regarding donor-recipient mtDNA mismatch (mtDNA-mtDNA), mtDNA-nuclear DNA (nDNA) mismatch caused by mixing recipient nDNA with donor mtDNA, and mtDNA replicative segregation. These conditions can lead to mtDNA genetic drift and reversion to the original genotype. In this review, we address the current state of knowledge regarding nuclear transplantation for preventing the inheritance of mitochondrial diseases.}, } @article {pmid32827633, year = {2020}, author = {Esch, T and Kream, RM and Stefano, GB}, title = {Emerging regulatory roles of opioid peptides, endogenous morphine, and opioid receptor subtypes in immunomodulatory processes: Metabolic, behavioral, and evolutionary perspectives.}, journal = {Immunology letters}, volume = {227}, number = {}, pages = {28-33}, doi = {10.1016/j.imlet.2020.08.007}, pmid = {32827633}, issn = {1879-0542}, mesh = {Animals ; Behavior ; Biological Evolution ; Humans ; Immunity ; Immunomodulation ; Inflammation/*metabolism ; Morphine/*metabolism ; Nitric Oxide/metabolism ; Opioid Peptides/*metabolism ; Pain/*metabolism ; Receptors, Opioid/genetics/*metabolism ; }, abstract = {Integrated behavioral paradigms such as nociceptive processing coupled to anti-nociceptive responsiveness include systemically-mediated states of alertness, vigilance, motivation, and avoidance. Within a historical and cultural context, opium and its biologically active compounds, codeine and morphine, have been widely used as frontline anti-nociceptive agents. In eukaryotic cells, opiate alkaloids and opioid peptides were evolutionarily fashioned as regulatory factors in neuroimmune, vascular immune, and systemic immune communication and auto-immunoregulation. The significance of opioidergic regulation of immune function was validated by the identification of novel μ and δ opioid receptors on circulating leukocytes. The novel μ3 opioid receptor subtype has been characterized as an opioid peptide-insensitive and opiate alkaloid-selective G protein-coupled receptor (GPCR) that is functionally linked to the activation of constitutive nitric oxide synthase (cNOS). Opioid peptides stimulate granulocyte and immunocyte activation and chemotaxis via activation of a novel leukocyte δ2 receptor subtype. However, opiate alkaloid μ3 receptor agonists inhibit these same cellular activities. Opiate coupling to cNOS and subsequent production and release of mitochondrial nitric oxide (NO) suggests an evolutionary linkage to similar physiological events in prokaryotic cells. A subpopulation of immunocytes from Mytilus edulis and Leucophaea maderae and human granulocytes respond to low opioid concentrations, mediated by the adherence-promoting role of (D-Ala2-D-Met5)-enkephalinamide (DAMA), which is blocked by naloxone in a dose-dependent manner. Neutral endopeptidase 24.11 (NEP), or enkephalinase (CD10), is present on both human and invertebrate immunocytes. Alkaloids, including morphine, are found in both prokaryotic and eukaryotic cells and may have evolved much later in evolution through horizontal gene transfer. It is possible that opioid-mediated regulatory activities were conserved and elaborated during evolution as the central nervous system (CNS) became immunologically isolated by the blood-brain barrier. Thus, opioid receptor coupling became significant for cognitive and behavioural processes. Although opioid peptides and alkaloids work synergistically to suppress nociception, they mediate different actions in immune surveillance. Increased understanding of the evolutionary development of opioid receptors, nociceptive and anti-nociceptive pathways, and immunomodulation may help in the understanding of the development of tolerance to the clinical use of opiates for pain management. The significance of endogenous morphine's importance to evolution can be ascertained by the number of physiological tissues and systems that can be affected by this chemical messenger mechanism, which transcends pain. An integrated review is presented of opioid and opiate receptors, immunomodulation, and pain associated with inflammation, from an evolutionary perspective.}, } @article {pmid32841735, year = {2021}, author = {Pallardó, FV and Pagano, G and Rodríguez, LR and Gonzalez-Cabo, P and Lyakhovich, A and Trifuoggi, M}, title = {Friedreich Ataxia: current state-of-the-art, and future prospects for mitochondrial-focused therapies.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {229}, number = {}, pages = {135-141}, doi = {10.1016/j.trsl.2020.08.009}, pmid = {32841735}, issn = {1878-1810}, mesh = {Animals ; Antioxidants/pharmacology/therapeutic use ; Carnitine/pharmacology ; Deferiprone/therapeutic use ; Friedreich Ataxia/*drug therapy/pathology ; Humans ; Iron Chelating Agents/therapeutic use ; Linoleic Acids/pharmacology ; Mitochondria/*drug effects/metabolism/pathology ; Ubiquinone/analogs & derivatives/pharmacology ; }, abstract = {Friedreich's Ataxia is an autosomal recessive genetic disease causing the defective gene product, frataxin. A body of literature has been focused on the attempts to counteract frataxin deficiency and the consequent iron imbalance, in order to mitigate the disease-associated pro-oxidant state and clinical course. The present mini review is aimed at evaluating the basic and clinical reports on the roles and the use of a set of iron chelators, antioxidants and some cofactors involved in the key mitochondrial functions. Extensive literature has focused on the protective roles of iron chelators, coenzyme Q10 and analogs, and vitamin E, altogether with varying outcomes in clinical studies. Other studies have suggested mitoprotective roles for other mitochondrial cofactors, involved in Krebs cycle, such as alpha-lipoic acid and carnitine, involved in acyl transport across the mitochondrial membrane. A body of evidence points to the strong antioxidant properties of these cofactors, and to their potential contribution in mitoprotective strategies in Friedreich's Ataxia clinical evolution. Thus, we suggest the rationale for planning combination strategies based on the 3 mitochondrial cofactors and of some antioxidants and iron binders as mitoprotective cocktails in Friedreich Ataxia patients, calling attention to clinical practitioners of the importance to implement clinical trials.}, } @article {pmid32846873, year = {2020}, author = {Nunes-Nesi, A and Cavalcanti, JHF and Fernie, AR}, title = {Characterization of In Vivo Function(s) of Members of the Plant Mitochondrial Carrier Family.}, journal = {Biomolecules}, volume = {10}, number = {9}, pages = {}, pmid = {32846873}, issn = {2218-273X}, support = {TRR 175/1//Collaborative Research Centers, SFB (Sonderforschungsbereich)/International ; 306818/2016-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/International ; }, mesh = {Amino Acid Transport Systems/genetics/metabolism ; Arabidopsis/genetics/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Coenzyme A/metabolism ; Gene Expression Regulation, Plant ; Iron/metabolism ; Mitochondria/metabolism ; Mitochondrial Membrane Transport Proteins/genetics/*metabolism ; Mitochondrial Uncoupling Proteins/genetics/metabolism ; Models, Biological ; NAD/metabolism ; Organic Anion Transporters/genetics/metabolism ; Phosphate Transport Proteins/genetics/metabolism ; Plant Proteins/genetics/*metabolism ; }, abstract = {Although structurally related, mitochondrial carrier family (MCF) proteins catalyze the specific transport of a range of diverse substrates including nucleotides, amino acids, dicarboxylates, tricarboxylates, cofactors, vitamins, phosphate and H[+]. Despite their name, they do not, however, always localize to the mitochondria, with plasma membrane, peroxisomal, chloroplast and thylakoid and endoplasmic reticulum localizations also being reported. The existence of plastid-specific MCF proteins is suggestive that the evolution of these proteins occurred after the separation of the green lineage. That said, plant-specific MCF proteins are not all plastid-localized, with members also situated at the endoplasmic reticulum and plasma membrane. While by no means yet comprehensive, the in vivo function of a wide range of these transporters is carried out here, and we discuss the employment of genetic variants of the MCF as a means to provide insight into their in vivo function complementary to that obtained from studies following their reconstitution into liposomes.}, } @article {pmid32849413, year = {2020}, author = {Chen, M and Chen, N and Wu, T and Bian, Y and Deng, Y and Xu, Z}, title = {Characterization of Two Mitochondrial Genomes and Gene Expression Analysis Reveal Clues for Variations, Evolution, and Large-Sclerotium Formation in Medical Fungus Wolfiporia cocos.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1804}, pmid = {32849413}, issn = {1664-302X}, abstract = {Wolfiporia cocos, a precious mushroom with a long history as an edible food and Asian traditional medicine, remains unclear in the genetic mechanism underlying the formation of large sclerotia. Here, two complete circular mitogenomes (BL16, 135,686 bp and MD-104 SS10, 124,842 bp, respectively) were presented in detail first. The salient features in the mitogenomes of W. cocos include an intron in the tRNA (trnQ-UUG[2]), and an obvious gene rearrangement identified between the two mitogenomes from the widely geographically separated W. cocos strains. Genome comparison and phylogenetic analyses reveal some variations and evolutional characteristics in W. cocos. Whether the mitochondrion is functional in W. cocos sclerotium development was investigated by analyzing the mitogenome synteny of 10 sclerotium-forming fungi and mitochondrial gene expression patterns in different W. cocos sclerotium-developmental stages. Three common homologous genes identified across ten sclerotium-forming fungi were also found to exhibit significant differential expression levels during W. cocos sclerotium development. Most of the mitogenomic genes are not expressed in the mycelial stage but highly expressed in the sclerotium initial or developmental stage. These results indicate that some of mitochondrial genes may play a role in the development of sclerotium in W. cocos, which needs to be further elucidated in future studies. This study will stimulate new ideas on cytoplasmic inheritance of W. cocos and facilitate the research on the role of mitochondria in large sclerotium formation.}, } @article {pmid32849440, year = {2020}, author = {Aguirre-López, B and Escalera-Fanjul, X and Hersch-González, J and Rojas-Ortega, E and El-Hafidi, M and Lezama, M and González, J and Bianchi, MM and López, G and Márquez, D and Scazzocchio, C and Riego-Ruiz, L and González, A}, title = {In Kluyveromyces lactis a Pair of Paralogous Isozymes Catalyze the First Committed Step of Leucine Biosynthesis in Either the Mitochondria or the Cytosol.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1843}, pmid = {32849440}, issn = {1664-302X}, abstract = {Divergence of paralogous pairs, resulting from gene duplication, plays an important role in the evolution of specialized or novel gene functions. Analysis of selected duplicated pairs has elucidated some of the mechanisms underlying the functional diversification of Saccharomyces cerevisiae (S. cerevisiae) paralogous genes. Similar studies of the orthologous pairs extant in pre-whole genome duplication yeast species, such as Kluyveromyces lactis (K. lactis) remain to be addressed. The genome of K. lactis, an aerobic yeast, includes gene pairs generated by sporadic duplications. The genome of this organism comprises the KlLEU4 and KlLEU4BIS paralogous pair, annotated as putative α-isopropylmalate synthases (α-IPMSs), considered to be the orthologs of the S. cerevisiae ScLEU4/ScLEU9 paralogous genes. The enzymes encoded by the latter two genes are mitochondrially located, differing in their sensitivity to leucine allosteric inhibition resulting in ScLeu4-ScLeu4 and ScLeu4-ScLeu9 sensitive dimers and ScLeu9-ScLeu9 relatively resistant homodimers. Previous work has shown that, in a Scleu4Δ mutant, ScLEU9 expression is increased and assembly of ScLeu9-ScLeu9 leucine resistant homodimers results in loss of feedback regulation of leucine biosynthesis, leading to leucine accumulation and decreased growth rate. Here we report that: (i) K. lactis harbors a sporadic gene duplication, comprising the KlLEU4, syntenic with S. cerevisiae ScLEU4 and ScLEU9, and the non-syntenic KlLEU4BIS, arising from a pre-WGD event. (ii) That both, KlLEU4 and KlLEU4BIS encode leucine sensitive α-IPMSs isozymes, located in the mitochondria (KlLeu4) and the cytosol (KlLeu4BIS), respectively. (iii) That both, KlLEU4 or KlLEU4BIS complement the Scleu4Δ Scleu9Δ leucine auxotrophic phenotype and revert the enhanced ScLEU9 transcription observed in a Scleu4Δ ScLEU9 mutant. The Scleu4Δ ScLEU9 growth mutant phenotype is only fully complemented when transformed with the syntenic KlLEU4 mitochondrial isoform. KlLEU4 and KlLEU4BIS underwent a different diversification pathways than that leading to ScLEU4/ScLEU9. KlLEU4 could be considered as the functional ortholog of ScLEU4, since its encoded isozyme can complement both the Scleu4Δ Scleu9Δ leucine auxotrophy and the Scleu4Δ ScLEU9 complex phenotype.}, } @article {pmid32849605, year = {2020}, author = {Pérez-Hernández, CA and Kern, CC and Butkeviciute, E and McCarthy, E and Dockrell, HM and Moreno-Altamirano, MMB and Aguilar-López, BA and Bhosale, G and Wang, H and Gems, D and Duchen, MR and Smith, SG and Sánchez-García, FJ}, title = {Mitochondrial Signature in Human Monocytes and Resistance to Infection in C. elegans During Fumarate-Induced Innate Immune Training.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1715}, pmid = {32849605}, issn = {1664-3224}, support = {215574/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; 215574/WT_/Wellcome Trust/United Kingdom ; MR/R005850/1/MRC_/Medical Research Council/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 098565/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Caenorhabditis elegans/*drug effects/immunology/metabolism/microbiology ; Calcium Signaling/drug effects ; Cells, Cultured ; Cytokines/metabolism ; Escherichia coli/immunology/*pathogenicity ; Escherichia coli Infections/immunology/metabolism/microbiology/*prevention & control ; Fumarates/*pharmacology ; Host-Pathogen Interactions ; Humans ; Immunity, Innate/*drug effects ; Immunologic Memory/*drug effects ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/*drug effects/immunology/metabolism ; Mitochondrial Dynamics/drug effects ; Monocytes/*drug effects/immunology/metabolism ; }, abstract = {Monocytes can develop immunological memory, a functional characteristic widely recognized as innate immune training, to distinguish it from memory in adaptive immune cells. Upon a secondary immune challenge, either homologous or heterologous, trained monocytes/macrophages exhibit a more robust production of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, than untrained monocytes. Candida albicans, β-glucan, and BCG are all inducers of monocyte training and recent metabolic profiling analyses have revealed that training induction is dependent on glycolysis, glutaminolysis, and the cholesterol synthesis pathway, along with fumarate accumulation; interestingly, fumarate itself can induce training. Since fumarate is produced by the tricarboxylic acid (TCA) cycle within mitochondria, we asked whether extra-mitochondrial fumarate has an effect on mitochondrial function. Results showed that the addition of fumarate to monocytes induces mitochondrial Ca[2+] uptake, fusion, and increased membrane potential (Δψm), while mitochondrial cristae became closer to each other, suggesting that immediate (from minutes to hours) mitochondrial activation plays a role in the induction phase of innate immune training of monocytes. To establish whether fumarate induces similar mitochondrial changes in vivo in a multicellular organism, effects of fumarate supplementation were tested in the nematode worm Caenorhabditis elegans. This induced mitochondrial fusion in both muscle and intestinal cells and also increased resistance to infection of the pharynx with E. coli. Together, these findings contribute to defining a mitochondrial signature associated with the induction of innate immune training by fumarate treatment, and to the understanding of whole organism infection resistance.}, } @article {pmid32853350, year = {2020}, author = {Arakawa, T and Kagami, H and Katsuyama, T and Kitazaki, K and Kubo, T}, title = {A Lineage-Specific Paralog of Oma1 Evolved into a Gene Family from Which a Suppressor of Male Sterility-Inducing Mitochondria Emerged in Plants.}, journal = {Genome biology and evolution}, volume = {12}, number = {12}, pages = {2314-2327}, pmid = {32853350}, issn = {1759-6653}, mesh = {Beta vulgaris/*genetics ; *Evolution, Molecular ; Genes, Mitochondrial ; Multigene Family ; Phylogeny ; Plant Infertility/*genetics ; Selection, Genetic ; }, abstract = {Cytoplasmic male sterility (MS) in plants is caused by MS-inducing mitochondria, which have emerged frequently during plant evolution. Nuclear restorer-of-fertility (Rf)genes can suppress their cognate MS-inducing mitochondria. Whereas many Rfs encode a class of RNA-binding protein, the sugar beet (Caryophyllales) Rf encodes a protein resembling Oma1, which is involved in the quality control of mitochondria. In this study, we investigated the molecular evolution of Oma1 homologs in plants. We analyzed 37 plant genomes and concluded that a single copy is the ancestral state in Caryophyllales. Among the sugar beet Oma1 homologs, the orthologous copy is located in a syntenic region that is preserved in Arabidopsis thaliana. The sugar beet Rf is a complex locus consisting of a small Oma1 homolog family (RF-Oma1 family) unique to sugar beet. The gene arrangement in the vicinity of the locus is seen in some but not all Caryophyllalean plants and is absent from Ar. thaliana. This suggests a segmental duplication rather than a whole-genome duplication as the mechanism of RF-Oma1 evolution. Of thirty-seven positively selected codons in RF-Oma1, twenty-six of these sites are located in predicted transmembrane helices. Phylogenetic network analysis indicated that homologous recombination among the RF-Oma1 members played an important role to generate protein activity related to suppression. Together, our data illustrate how an evolutionarily young Rf has emerged from a lineage-specific paralog. Interestingly, several evolutionary features are shared with the RNA-binding protein type Rfs. Hence, the evolution of the sugar beet Rf is representative of Rf evolution in general.}, } @article {pmid32853372, year = {2020}, author = {Li, SJ and Zhang, X and Lukeš, J and Li, BQ and Wang, JF and Qu, LH and Hide, G and Lai, DH and Lun, ZR}, title = {Novel organization of mitochondrial minicircles and guide RNAs in the zoonotic pathogen Trypanosoma lewisi.}, journal = {Nucleic acids research}, volume = {48}, number = {17}, pages = {9747-9761}, pmid = {32853372}, issn = {1362-4962}, mesh = {Adenosine Triphosphatases/genetics ; DNA, Protozoan/genetics ; Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics ; Phylogeny ; Protein Subunits/genetics ; RNA Editing ; RNA, Guide, Kinetoplastida/*genetics ; RNA, Protozoan/*genetics ; Trypanosoma lewisi/*genetics ; }, abstract = {Kinetoplastid flagellates are known for several unusual features, one of which is their complex mitochondrial genome, known as kinetoplast (k) DNA, composed of mutually catenated maxi- and minicircles. Trypanosoma lewisi is a member of the Stercorarian group of trypanosomes which is, based on human infections and experimental data, now considered a zoonotic pathogen. By assembling a total of 58 minicircle classes, which fall into two distinct categories, we describe a novel type of kDNA organization in T. lewisi. RNA-seq approaches allowed us to map the details of uridine insertion and deletion editing events upon the kDNA transcriptome. Moreover, sequencing of small RNA molecules enabled the identification of 169 unique guide (g) RNA genes, with two differently organized minicircle categories both encoding essential gRNAs. The unprecedented organization of minicircles and gRNAs in T. lewisi broadens our knowledge of the structure and expression of the mitochondrial genomes of these human and animal pathogens. Finally, a scenario describing the evolution of minicircles is presented.}, } @article {pmid32857636, year = {2020}, author = {Medini, H and Cohen, T and Mishmar, D}, title = {Mitochondria Are Fundamental for the Emergence of Metazoans: On Metabolism, Genomic Regulation, and the Birth of Complex Organisms.}, journal = {Annual review of genetics}, volume = {54}, number = {}, pages = {151-166}, doi = {10.1146/annurev-genet-021920-105545}, pmid = {32857636}, issn = {1545-2948}, mesh = {Animals ; Chromatin/genetics ; Embryonic Development/genetics ; Epigenesis, Genetic/genetics ; Genome/*genetics ; Humans ; Mitochondria/*genetics ; }, abstract = {Out of many intracellular bacteria, only the mitochondria and chloroplasts abandoned their independence billions of years ago and became endosymbionts within the host eukaryotic cell. Consequently, one cannot grow eukaryotic cells without their mitochondria, and the mitochondria cannot divide outside of the cell, thus reflecting interdependence. Here, we argue that such interdependence underlies the fundamental role of mitochondrial activities in the emergence of metazoans. Several lines of evidence support our hypothesis: (a) Differentiation and embryogenesis rely on mitochondrial function; (b) mitochondrial metabolites are primary precursors for epigenetic modifications (such as methyl and acetyl), which are critical for chromatin remodeling and gene expression, particularly during differentiation and embryogenesis; and (c) mitonuclear coregulation adapted to accommodate both housekeeping and tissue-dependent metabolic needs. We discuss the evolution of the unique mitochondrial genetic system, mitochondrial metabolites, mitonuclear coregulation, and their critical roles in the emergence of metazoans and in human disorders.}, } @article {pmid32861874, year = {2020}, author = {Marotta, R and Chin, J and Chiotis, M and Shuey, N and Collins, SJ}, title = {Long-term screening for primary mitochondrial DNA variants associated with Leber hereditary optic neuropathy: incidence, penetrance and clinical features.}, journal = {Mitochondrion}, volume = {54}, number = {}, pages = {128-132}, doi = {10.1016/j.mito.2020.08.007}, pmid = {32861874}, issn = {1872-8278}, mesh = {Adolescent ; Adult ; Case-Control Studies ; DNA, Mitochondrial/genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Incidence ; Male ; Middle Aged ; Mutation Rate ; NADH Dehydrogenase/*genetics ; Optic Atrophy, Hereditary, Leber/*genetics ; Pedigree ; Penetrance ; *Polymorphism, Single Nucleotide ; }, abstract = {Leber hereditary optic neuropathy (LHON) is a neurodegenerative disorder characterised by bilateral, painless, subacute, central vision loss caused by pathogenic sequence variants in mitochondrial DNA (mtDNA). Over the course of 20 years, 734 people were systematically screened by our diagnostic laboratory for suspected LHON or for being at risk of LHON, with 98 found to harbour one of the three primary pathogenic mtDNA variants. Detection incidences were: 0.95% for NC_012920.1(MT-ND1):m.3460G>A; 9.4% for (MT-ND4):m.11778G>A; and 2.9% for (MT-ND6):m.14484T>C. The median age for symptomatic males was 27.3 years and for females 29.5 years, with a male to female ratio of 4.4:1 (62 males; 14 females). Most pathogenic variant carriers were propositi with the other individuals belonging to one of 14 pedigrees with noteworthy intra-family variability of clinical severity of the disease.}, } @article {pmid32865900, year = {2020}, author = {Veena, RK and Carmel, EJ and Ramya, H and Ajith, TA and Wasser, SP and Janardhanan, KK}, title = {Caterpillar Medicinal Mushroom, Cordyceps militaris (Ascomycetes), Mycelia Attenuates Doxorubicin-Induced Oxidative Stress and Upregulates Krebs Cycle Dehydrogenases Activity and ATP Level in Rat Brain.}, journal = {International journal of medicinal mushrooms}, volume = {22}, number = {6}, pages = {593-604}, doi = {10.1615/IntJMedMushrooms.2020035093}, pmid = {32865900}, issn = {1940-4344}, mesh = {Acetylcholinesterase/metabolism ; Adenosine Triphosphate/*metabolism ; Animals ; Antioxidants/metabolism ; Biological Products/*pharmacology ; Body Weight ; Brain/drug effects/*metabolism ; Citric Acid Cycle/*drug effects ; Cordyceps/*chemistry ; Doxorubicin/*pharmacology ; Electron Transport/drug effects ; Glutathione/metabolism ; Lipid Peroxidation/drug effects ; Male ; Mitochondria/enzymology ; Mycelium/chemistry ; Oxidation-Reduction ; Oxidative Stress/*drug effects ; Oxidoreductases/metabolism ; Proteins/metabolism ; Rats ; Rats, Wistar ; Up-Regulation ; }, abstract = {Post-chemotherapy-induced cognitive dysfunction remains one of the challenges in cancer survivors. Cytokine-induced neurotoxicity manifests in subjects at any time after doxorubicin (DOX) chemotherapy. We examined the effect of bioactive Cordyceps militaris mycelia extract (CM) on the energy status, oxidative stress, and acetylcholinesterase activity in the brain of DOX treated rats. The CM (150 and 300 mg/kg b.w.) and DL-α lipoic acid (LA, 100 mg/kg b.w) were administered orally once daily for 5 days to male Wistar rats prior to the DOX administration (18 mg/kg as 3 doses of 6 mg/kg, i.p. b.w.) and continued for 6 more days. Cellular antioxidant status, Krebs cycle dehydrogenases, electron transport chain complexes (ETC) (I, III, and IV), adenosine triphosphate (ATP) level, advanced oxidation of protein products (AOPP), and acetylcholinesterase (AchE) activities were determined in the brain homogenate. The DOX alone treated group of animals showed significant decrease (p < 0.05) of brain antioxidant levels, Krebs cycle dehydrogenases activities, ETC complex activities, and decreased ATP level, while lipid peroxidation and AOPP levels were elevated. CM at 300 mg/kg b.w. or LA at 100 mg/kg b.w. elevated antioxidant status, Krebs cycle dehydrogenases, and complex activities and thus alleviated the toxicity. CM also inhibited the AchE activity in brain. The experimental results thus reveal that CM possessed excellent capacity to attenuate oxidative stress, upregulate respiratory chain complex activity and ATP levels, as well as inhibition of AchE activity.}, } @article {pmid32868785, year = {2020}, author = {Dawson, ER and Patananan, AN and Sercel, AJ and Teitell, MA}, title = {Stable retention of chloramphenicol-resistant mtDNA to rescue metabolically impaired cells.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {14328}, pmid = {32868785}, issn = {2045-2322}, support = {R01GM127985/NH/NIH HHS/United States ; T32CA009120/NH/NIH HHS/United States ; R01 GM073981/GM/NIGMS NIH HHS/United States ; R01 CA185189/CA/NCI NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; R01 GM114188/GM/NIGMS NIH HHS/United States ; R01 GM127985/GM/NIGMS NIH HHS/United States ; R21 MH119020/MH/NIMH NIH HHS/United States ; T32 CA009120/CA/NCI NIH HHS/United States ; T32 GM007185/GM/NIGMS NIH HHS/United States ; R21 CA227480/CA/NCI NIH HHS/United States ; T34 GM008563/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; Chloramphenicol ; *DNA, Mitochondrial ; *Gene Transfer Techniques ; HEK293 Cells ; Humans ; *Hybrid Cells ; Mice ; *Mitochondria ; }, abstract = {The permanent transfer of specific mtDNA sequences into mammalian cells could generate improved models of mtDNA disease and support future cell-based therapies. Previous studies documented multiple biochemical changes in recipient cells shortly after mtDNA transfer, but the long-term retention and function of transferred mtDNA remains unknown. Here, we evaluate mtDNA retention in new host cells using 'MitoPunch', a device that transfers isolated mitochondria into mouse and human cells. We show that newly introduced mtDNA is stably retained in mtDNA-deficient (ρ0) recipient cells following uridine-free selection, although exogenous mtDNA is lost from metabolically impaired, mtDNA-intact (ρ+) cells. We then introduced a second selective pressure by transferring chloramphenicol-resistant mitochondria into chloramphenicol-sensitive, metabolically impaired ρ+ mouse cybrid cells. Following double selection, recipient cells with mismatched nuclear (nDNA) and mitochondrial (mtDNA) genomes retained transferred mtDNA, which replaced the endogenous mutant mtDNA and improved cell respiration. However, recipient cells with matched mtDNA-nDNA failed to retain transferred mtDNA and sustained impaired respiration. Our results suggest that exogenous mtDNA retention in metabolically impaired ρ+ recipients depends on the degree of recipient mtDNA-nDNA co-evolution. Uncovering factors that stabilize exogenous mtDNA integration will improve our understanding of in vivo mitochondrial transfer and the interplay between mitochondrial and nuclear genomes.}, } @article {pmid32869868, year = {2020}, author = {Seeliger, B and Alesina, PF and Walz, MK and Pop, R and Charles, AL and Geny, B and Messaddeq, N and Kontogeorgos, G and Mascagni, P and Seyller, E and Marescaux, J and Agnus, V and Diana, M}, title = {Intraoperative imaging for remnant viability assessment in bilateral posterior retroperitoneoscopic partial adrenalectomy in an experimental model.}, journal = {The British journal of surgery}, volume = {107}, number = {13}, pages = {1780-1790}, doi = {10.1002/bjs.11839}, pmid = {32869868}, issn = {1365-2168}, support = {10-IAHU-0002//Agence Nationale de la Recherche/ ; //Fondation ARC pour la Recherche sur le Cancer/ ; }, mesh = {Adrenal Glands/*blood supply/*diagnostic imaging/physiology/surgery ; Adrenalectomy/*methods ; Animals ; Biomarkers/metabolism ; Female ; Intraoperative Care/*methods ; Lactic Acid/metabolism ; Male ; Microscopy, Confocal ; Microscopy, Electron ; Mitochondria/metabolism ; Models, Animal ; Optical Imaging ; Postoperative Period ; Sus scrofa ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: A surgical approach preserving functional adrenal tissue allows biochemical cure while avoiding the need for lifelong steroid replacement. The aim of this experimental study was to evaluate the impact of intraoperative imaging during bilateral partial adrenalectomy on remnant perfusion and function.

METHODS: Five pigs underwent bilateral posterior retroperitoneoscopic central adrenal gland division (9 divided glands, 1 undivided). Intraoperative perfusion assessment included computer-assisted quantitative fluorescence imaging, contrast-enhanced CT, confocal laser endomicroscopy (CLE) and local lactate sampling. Specimen analysis after completion adrenalectomy (10 adrenal glands) comprised mitochondrial activity and electron microscopy.

RESULTS: Fluorescence signal intensity evolution over time was significantly lower in the cranial segment of each adrenal gland (mean(s.d.) 0·052(0·057) versus 0·133(0·057) change in intensity per s for cranial versus caudal parts respectively; P = 0·020). Concordantly, intraoperative CT in the portal phase demonstrated significantly lower contrast uptake in cranial segments (P = 0·031). In CLE, fluorescein contrast was observed in all caudal segments, but in only four of nine cranial segments (P = 0·035). Imaging findings favouring caudal perfusion were congruent, with significantly lower local capillary lactate levels caudally (mean(s.d.) 5·66(5·79) versus 11·58(6·53) mmol/l for caudal versus cranial parts respectively; P = 0·008). Electron microscopy showed more necrotic cells cranially (P = 0·031). There was no disparity in mitochondrial activity (respiratory rates, reactive oxygen species and hydrogen peroxide production) between the different segments.

CONCLUSION: In a model of bilateral partial adrenalectomy, three intraoperative imaging modalities consistently discriminated between regular and reduced adrenal remnant perfusion. By avoiding circumferential dissection, mitochondrial function was preserved in each segment of the adrenal glands. Surgical relevance Preservation of adrenal tissue to maintain postoperative function is essential in bilateral and hereditary adrenal pathologies. There is interindividual variation in residual adrenocortical stress capacity, and the minimal functional remnant size is unknown. New intraoperative imaging technologies allow improved remnant size and perfusion assessment. Fluorescence imaging and contrast-enhanced intraoperative CT showed congruent results in evaluation of perfusion. Intraoperative imaging can help to visualize the remnant vascular supply in partial adrenalectomy. Intraoperative assessment of perfusion may foster maximal functional tissue preservation in bilateral adrenal pathologies and procedures.}, } @article {pmid32873198, year = {2020}, author = {Yazaki, E and Kume, K and Shiratori, T and Eglit, Y and Tanifuji, G and Harada, R and Simpson, AGB and Ishida, KI and Hashimoto, T and Inagaki, Y}, title = {Barthelonids represent a deep-branching metamonad clade with mitochondrion-related organelles predicted to generate no ATP.}, journal = {Proceedings. Biological sciences}, volume = {287}, number = {1934}, pages = {20201538}, pmid = {32873198}, issn = {1471-2954}, mesh = {Anaerobiosis ; *Biological Evolution ; Eukaryota/metabolism/*physiology ; Mitochondria/metabolism ; Organelles/metabolism ; *Phylogeny ; }, abstract = {We here report the phylogenetic position of barthelonids, small anaerobic flagellates previously examined using light microscopy alone. Barthelona spp. were isolated from geographically distinct regions and we established five laboratory strains. Transcriptomic data generated from one Barthelona strain (PAP020) were used for large-scale, multi-gene phylogenetic (phylogenomic) analyses. Our analyses robustly placed strain PAP020 at the base of the Fornicata clade, indicating that barthelonids represent a deep-branching metamonad clade. Considering the anaerobic/microaerophilic nature of barthelonids and preliminary electron microscopy observations on strain PAP020, we suspected that barthelonids possess functionally and structurally reduced mitochondria (i.e. mitochondrion-related organelles or MROs). The metabolic pathways localized in the MRO of strain PAP020 were predicted based on its transcriptomic data and compared with those in the MROs of fornicates. We here propose that strain PAP020 is incapable of generating ATP in the MRO, as no mitochondrial/MRO enzymes involved in substrate-level phosphorylation were detected. Instead, we detected a putative cytosolic ATP-generating enzyme (acetyl-CoA synthetase), suggesting that strain PAP020 depends on ATP generated in the cytosol. We propose two separate losses of substrate-level phosphorylation from the MRO in the clade containing barthelonids and (other) fornicates.}, } @article {pmid32878185, year = {2020}, author = {Karakaidos, P and Rampias, T}, title = {Mitonuclear Interactions in the Maintenance of Mitochondrial Integrity.}, journal = {Life (Basel, Switzerland)}, volume = {10}, number = {9}, pages = {}, pmid = {32878185}, issn = {2075-1729}, abstract = {In eukaryotic cells, mitochondria originated in an α-proteobacterial endosymbiont. Although these organelles harbor their own genome, the large majority of genes, originally encoded in the endosymbiont, were either lost or transferred to the nucleus. As a consequence, mitochondria have become semi-autonomous and most of their processes require the import of nuclear-encoded components to be functional. Therefore, the mitochondrial-specific translation has evolved to be coordinated by mitonuclear interactions to respond to the energetic demands of the cell, acquiring unique and mosaic features. However, mitochondrial-DNA-encoded genes are essential for the assembly of the respiratory chain complexes. Impaired mitochondrial function due to oxidative damage and mutations has been associated with numerous human pathologies, the aging process, and cancer. In this review, we highlight the unique features of mitochondrial protein synthesis and provide a comprehensive insight into the mitonuclear crosstalk and its co-evolution, as well as the vulnerabilities of the animal mitochondrial genome.}, } @article {pmid32886780, year = {2020}, author = {Mandel, JR and Ramsey, AJ and Holley, JM and Scott, VA and Mody, D and Abbot, P}, title = {Disentangling Complex Inheritance Patterns of Plant Organellar Genomes: An Example From Carrot.}, journal = {The Journal of heredity}, volume = {111}, number = {6}, pages = {531-538}, doi = {10.1093/jhered/esaa037}, pmid = {32886780}, issn = {1465-7333}, mesh = {Crosses, Genetic ; Daucus carota/*genetics ; Evolution, Molecular ; Genome, Mitochondrial/*genetics ; Genome, Plant/*genetics ; Genome, Plastid/*genetics ; Heteroplasmy/*genetics ; Inheritance Patterns/genetics ; Maternal Inheritance ; Mitochondria/genetics ; Multifactorial Inheritance/*genetics ; Organelles/genetics ; Phylogeny ; Plastids/genetics ; }, abstract = {Plant mitochondria and plastids display an array of inheritance patterns and varying levels of heteroplasmy, where individuals harbor more than 1 version of a mitochondrial or plastid genome. Organelle inheritance in plants has the potential to be quite complex and can vary with plant growth, development, and reproduction. Few studies have sought to investigate these complicated patterns of within-individual variation and inheritance using experimental crosses in plants. We carried out crosses in carrot, Daucus carota L. (Apiaceae), which has previously been shown to exhibit organellar heteroplasmy. We used mitochondrial and plastid markers to begin to disentangle the patterns of organellar inheritance and the fate of heteroplasmic variation, with special focus on cases where the mother displayed heteroplasmy. We also investigated heteroplasmy across the plant, assaying leaf samples at different development stages and ages. Mitochondrial and plastid paternal leakage was rare and offspring received remarkably similar heteroplasmic mixtures to their heteroplasmic mothers, indicating that heteroplasmy is maintained over the course of maternal inheritance. When offspring did differ from their mother, they were likely to exhibit a loss of the genetic variation that was present in their mother. Finally, we found that mitochondrial variation did not vary significantly over plant development, indicating that substantial vegetative sorting did not occur. Our study is one of the first to quantitatively investigate inheritance patterns and heteroplasmy in plants using controlled crosses, and we look forward to future studies making use of whole genome information to study the complex evolutionary dynamics of plant organellar genomes.}, } @article {pmid32887610, year = {2020}, author = {Royes, J and Biou, V and Dautin, N and Tribet, C and Miroux, B}, title = {Inducible intracellular membranes: molecular aspects and emerging applications.}, journal = {Microbial cell factories}, volume = {19}, number = {1}, pages = {176}, pmid = {32887610}, issn = {1475-2859}, support = {ANR-11-LABEX-0011-01//Agence Nationale de la Recherche/ ; ANR-17-CE09-0007//Agence Nationale de la Recherche/ ; }, mesh = {Cell Membrane/*physiology/ultrastructure ; Cell Surface Extensions/*metabolism/ultrastructure ; Membrane Proteins/*physiology ; Organelles/*physiology/ultrastructure ; Phospholipids/*physiology ; Protein Conformation ; }, abstract = {Membrane remodeling and phospholipid biosynthesis are normally tightly regulated to maintain the shape and function of cells. Indeed, different physiological mechanisms ensure a precise coordination between de novo phospholipid biosynthesis and modulation of membrane morphology. Interestingly, the overproduction of certain membrane proteins hijack these regulation networks, leading to the formation of impressive intracellular membrane structures in both prokaryotic and eukaryotic cells. The proteins triggering an abnormal accumulation of membrane structures inside the cells (or membrane proliferation) share two major common features: (1) they promote the formation of highly curved membrane domains and (2) they lead to an enrichment in anionic, cone-shaped phospholipids (cardiolipin or phosphatidic acid) in the newly formed membranes. Taking into account the available examples of membrane proliferation upon protein overproduction, together with the latest biochemical, biophysical and structural data, we explore the relationship between protein synthesis and membrane biogenesis. We propose a mechanism for the formation of these non-physiological intracellular membranes that shares similarities with natural inner membrane structures found in α-proteobacteria, mitochondria and some viruses-infected cells, pointing towards a conserved feature through evolution. We hope that the information discussed in this review will give a better grasp of the biophysical mechanisms behind physiological and induced intracellular membrane proliferation, and inspire new applications, either for academia (high-yield membrane protein production and nanovesicle production) or industry (biofuel production and vaccine preparation).}, } @article {pmid32891682, year = {2020}, author = {Darriba, S and Lee, RS and López, C}, title = {Mikrocytos mytilicoli n.sp. (Cercozoa, Mikrocytida, Mikrocytiidae) infecting the copepod Mytilicola intestinalis (Arthropoda, Cyclopoida, Mytilicolidae), a symbiont of Mytilus galloprovincialis in Galicia (NW Spain).}, journal = {Journal of invertebrate pathology}, volume = {176}, number = {}, pages = {107460}, doi = {10.1016/j.jip.2020.107460}, pmid = {32891682}, issn = {1096-0805}, mesh = {Animals ; Cercozoa/*classification/cytology/genetics/ultrastructure ; Copepoda/*parasitology/physiology ; DNA, Protozoan/analysis ; DNA, Ribosomal Spacer/analysis ; *Host-Parasite Interactions ; Microscopy ; Microscopy, Electron, Transmission ; Mytilus/physiology ; Phylogeny ; RNA, Ribosomal, 18S/analysis ; RNA, Ribosomal, 28S/analysis ; Spain ; Symbiosis ; }, abstract = {During a histopathological survey of Mytilus galloprovincialis in Galicia (NW Spain), microcells were observed infecting several organs of the symbiont copepod Mytilicola intestinalis. Positive results of PCR assay with specific primers for genus Mikrocytos and a clear signal of in situ hybridization with MACKINI-1 digoxigenin- labelled DNA probe (DIG-ISH) indicated a protozoan parasite of Mikrocytos genus. The ultrastructural study revealed intra and extracellular locations, polymorphic nuclei, intracellular round vesicles in the cytoplasm and absence of mitochondria. The present paper reports the characterization of the Mikrocytos sp. infecting M. intestinalis and proposes a novel species in the genus: Mikrocytos mytilicoli n. sp. A sequence of 18S-28S rDNA was obtained with 95.6% maximum identity (query cover 100%) with Mikrocytos mackini. Phylogenetic analysis showed that M. mytilicoli n. sp. and M. mackini share a common ancestor. However, comparison of the ITS1 rDNA region showed low similarity (75.8%) with M. mackini, which, combined with differences in ultrastructural details, host and geographic location, support the designation of a new species. This is the first description of a microcytid parasite of the genus Mikrocytos from a non-bivalve host.}, } @article {pmid32893838, year = {2020}, author = {Chung, HH and Anak Kamar, CK and Kit Lim, LW and Roja, JS and Liao, Y and Tsan-Yuk Lam, T and Chong, YL}, title = {Sequencing and characterization of complete mitogenome DNA of Rasbora tornieri (Cypriniformes: Cyprinidae: Rasbora) and its evolutionary significance.}, journal = {Journal of genetics}, volume = {99}, number = {}, pages = {}, pmid = {32893838}, issn = {0973-7731}, mesh = {Animals ; *Biological Evolution ; Cypriniformes/*genetics ; Fish Proteins/*genetics ; Genome, Mitochondrial/*genetics ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA/*methods ; }, abstract = {The yellowtail rasbora (Rasbora tornieri) is a miniature ray-finned fish categorized under the genus Rasbora in the family of Cyprinidae. In this study, a complete mitogenome sequence of R. tornieri was sequenced using four primers targeting two halves of the mitogenome with overlapping flanking regions. The size of mitogenome was 16,573 bp, housing 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes and a putative control region. Identical gene organization was detected between this species and other members of Rasbora genus. The heavy strand encompassed 28 genes while the light strand accommodated the other nine genes. Most protein-coding genes execute ATG as start codon, excluding COI and ND3 genes, which utilized GTG instead. The central conserved sequence blocks (CSB-E, CSB-F and CSB-D), variable sequence blocks (CSB-1, CSB-3 and CSB-2) as well as the terminal associated sequence (TAS) were conserved within the control region. The maximum likelihood phylogenetic family tree revealed the divergence of R. tornieri from the basal region of the Rasbora clade, where its evolutionary relationships with other Rasbora members are poorly resolved as indicated by the low bootstrap values. This work acts as window for further population genetics and molecular evolution studies of Rasbora genus in future.}, } @article {pmid32896490, year = {2021}, author = {Zhao, D and Wang, H and Chen, S and Yu, D and Reiter, RJ}, title = {Phytomelatonin: An Emerging Regulator of Plant Biotic Stress Resistance.}, journal = {Trends in plant science}, volume = {26}, number = {1}, pages = {70-82}, doi = {10.1016/j.tplants.2020.08.009}, pmid = {32896490}, issn = {1878-4372}, mesh = {Disease Resistance ; Humans ; *Melatonin ; Plant Growth Regulators ; Reactive Oxygen Species ; *Stress, Physiological ; }, abstract = {Melatonin has diverse functions in plant development and stress tolerance, with recent evidence showing a beneficial role in plant biotic stress tolerance. It has been hypothesized that pathogenic invasion causes the immediate generation of melatonin, reactive oxygen species (ROS), and reactive nitrogen species (RNS), with these being mutually dependent, forming the integrative melatonin-ROS-RNS feedforward loop. Here we discuss how the loop, possibly located in the mitochondria and chloroplasts, maximizes disease resistance in the early pathogen ingress stage, providing on-site protection. We also review how melatonin interacts with phytohormone signaling pathways to mediate defense responses and discuss the evolutionary context from the beginnings of the melatonin receptor-mitogen-activated protein kinase (MAPK) cascade in unicellular green algae, followed by the occurrence of phytohormone pathways in land plants.}, } @article {pmid32896572, year = {2021}, author = {Gupta, A and Shrivastava, D and Shakya, AK and Gupta, K and Pratap, JV and Habib, S}, title = {PfKsgA1 functions as a transcription initiation factor and interacts with the N-terminal region of the mitochondrial RNA polymerase of Plasmodium falciparum.}, journal = {International journal for parasitology}, volume = {51}, number = {1}, pages = {23-37}, doi = {10.1016/j.ijpara.2020.07.010}, pmid = {32896572}, issn = {1879-0135}, mesh = {DNA-Directed RNA Polymerases/genetics ; Mitochondria/genetics ; *Mitochondrial Proteins/genetics ; Peptide Initiation Factors ; Phylogeny ; *Plasmodium falciparum/genetics ; RNA, Mitochondrial ; Transcription Factors/genetics ; }, abstract = {The small mitochondrial genome (mtDNA) of the malaria parasite is known to transcribe its genes polycistonically, although promoter element(s) have not yet been identified. An unusually large Plasmodium falciparum candidate mitochondrial phage-like RNA polymerase (PfmtRNAP) with an extended N-terminal region is encoded by the parasite nuclear genome. Using specific antibodies against the enzyme, we established that PfmtRNAP was targeted exclusively to the mitochondrion and interacted with mtDNA. Phylogenetic analysis showed that it is part of a separate apicomplexan clade. A search for PfmtRNAP-associated transcription initiation factors using sequence homology and in silico protein-protein interaction network analysis identified PfKsgA1. PfKsgA1 is a dual cytosol- and mitochondrion-targeted protein that functions as a small subunit rRNA dimethyltransferase in ribosome biogenesis. Chromatin immunoprecipitation showed that PfKsgA1 interacts with mtDNA, and in vivo crosslinking and pull-down experiments confirmed PfmtRNAP-PfKsgA1 interaction. The ability of PfKsgA1 to serve as a transcription initiation factor was demonstrated by complementation of yeast mitochondrial transcription factor Mtf1 function in Rpo41-driven in vitro transcription. Pull-down experiments using PfKsgA1 and PfmtRNAP domains indicated that the N-terminal region of PfmtRNAP interacts primarily with the PfKsgA1 C-terminal domain with some contacts being made with the linker and N-terminal domain of PfKsgA1. In the absence of full-length recombinant PfmtRNAP, solution structures of yeast mitochondrial RNA polymerase Rpo41 complexes with Mtf1 or PfKsgA1 were determined by small-angle X-ray scattering. Protein interaction interfaces thus identified matched with those reported earlier for Rpo41-Mtf1 interaction and overlaid with the PfmtRNAP-interfacing region identified experimentally for PfKsgA1. Our results indicate that in addition to a role in mitochondrial ribosome biogenesis, PfKsgA1 has an independent function as a transcription initiation factor for PfmtRNAP.}, } @article {pmid32903594, year = {2020}, author = {Mallard, J and Hucteau, E and Schott, R and Petit, T and Demarchi, M and Belletier, C and Ben Abdelghani, M and Carinato, H and Chiappa, P and Fischbach, C and Kalish-Weindling, M and Bousinière, A and Dufour, S and Favret, F and Pivot, X and Hureau, TJ and Pagano, AF}, title = {Evolution of Physical Status From Diagnosis to the End of First-Line Treatment in Breast, Lung, and Colorectal Cancer Patients: The PROTECT-01 Cohort Study Protocol.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {1304}, pmid = {32903594}, issn = {2234-943X}, abstract = {Background: Cancer cachexia and exacerbated fatigue represent two hallmarks in cancer patients, negatively impacting their exercise tolerance and ultimately their quality of life. However, the characterization of patients' physical status and exercise tolerance and, most importantly, their evolution throughout cancer treatment may represent the first step in efficiently counteracting their development with prescribed and tailored exercise training. In this context, the aim of the PROTECT-01 study will be to investigate the evolution of physical status, from diagnosis to the end of first-line treatment, of patients with one of the three most common cancers (i.e., lung, breast, and colorectal). Methods: The PROTECT-01 cohort study will include 300 patients equally divided between lung, breast and colorectal cancer. Patients will perform a series of assessments at three visits throughout the treatment: (1) between the date of diagnosis and the start of treatment, (2) 8 weeks after the start of treatment, and (3) after the completion of first-line treatment or at the 6-months mark, whichever occurs first. For each of the three visits, subjective and objective fatigue, maximal voluntary force, body composition, cachexia, physical activity level, quality of life, respiratory function, overall physical performance, and exercise tolerance will be assessed. Discussion: The present study is aimed at identifying the nature and severity of maladaptation related to exercise intolerance in the three most common cancers. Therefore, our results should contribute to the delineation of the needs of each group of patients and to the determination of the most valuable exercise interventions in order to counteract these maladaptations. This descriptive and comprehensive approach is a prerequisite in order to elaborate, through future interventional research projects, tailored exercise strategies to counteract specific symptoms that are potentially cancer type-dependent and, in fine, to improve the health and quality of life of cancer patients. Moreover, our concomitant focus on fatigue and cachexia will provide insightful information about two factors that may have substantial interaction but require further investigation. Trial registration: This prospective study has been registered at ClinicalTrials.gov (NCT03956641), May, 2019.}, } @article {pmid32916006, year = {2020}, author = {Gueuning, M and Frey, JE and Praz, C}, title = {Ultraconserved yet informative for species delimitation: Ultraconserved elements resolve long-standing systematic enigma in Central European bees.}, journal = {Molecular ecology}, volume = {29}, number = {21}, pages = {4203-4220}, doi = {10.1111/mec.15629}, pmid = {32916006}, issn = {1365-294X}, mesh = {Animals ; Bees/genetics ; Biodiversity ; Cell Nucleus ; DNA Barcoding, Taxonomic ; *DNA, Mitochondrial/genetics ; Genomics ; *Mitochondria/genetics ; Phylogeny ; }, abstract = {Accurate and testable species hypotheses are essential for measuring, surveying and managing biodiversity. Taxonomists often rely on mitochondrial DNA barcoding to complement morphological species delimitations. Although COI-barcoding has largely proven successful in assisting identifications for most animal taxa, there are nevertheless numerous cases where mitochondrial barcodes do not reflect species hypotheses. For instance, what is regarded as a single species can be associated with two distinct DNA barcodes, which can point either to cryptic diversity or to within-species mitochondrial divergences without reproductive isolation. In contrast, two or more species can share barcodes, for instance due to mitochondrial introgression. These intrinsic limitations of DNA barcoding are commonly addressed with nuclear genomic markers, which are expensive, may have low repeatability and often require high-quality DNA. To overcome these limitations, we examined the use of ultraconserved elements (UCEs) as a quick and robust genomic approach to address such problematic cases of species delimitation in bees. This genomic method was assessed using six different species complexes suspected to harbour cryptic diversity, mitochondrial introgression or mitochondrial paraphyly. The sequencing of UCEs recovered between 686 and 1,860 homologous nuclear loci and provided explicit species delimitation in all investigated species complexes. These results provide strong evidence for the suitability of UCEs as a fast method for species delimitation even in recently diverged lineages. Furthermore, we provide the first evidence for both mitochondrial introgression among distinct bee species, and mitochondrial paraphyly within a single bee species.}, } @article {pmid32916227, year = {2020}, author = {Yamada, Y and Sato, Y and Nakamura, T and Harashima, H}, title = {Evolution of drug delivery system from viewpoint of controlled intracellular trafficking and selective tissue targeting toward future nanomedicine.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {327}, number = {}, pages = {533-545}, pmid = {32916227}, issn = {1873-4995}, mesh = {Drug Delivery Systems ; Gene Transfer Techniques ; Lipids ; *Nanomedicine ; *Nucleic Acids ; }, abstract = {Due to the rapid changes that have occurred in the field of drug discovery and the recent developments in the early 21st century, the role of drug delivery systems (DDS) has become increasingly more important. For the past 20 years, our laboratory has been developing gene delivery systems based on lipid-based delivery systems. One of our efforts has been directed toward developing a multifunctional envelope-type nano device (MEND) by modifying the particle surface with octaarginine, which resulted in a remarkably enhanced cellular uptake and improved intracellular trafficking of plasmid DNA (pDNA). When we moved to in vivo applications, however, we were faced with the PEG-dilemma and we shifted our strategy to the incorporation of ionizable cationic lipids into our system. This resulted in some dramatic improvements over our original design and this can be attributed to the development of a new lipid library. We have also developed a mitochondrial targeting system based on a membrane fusion mechanism using a MITO-Porter, which can deliver nucleic acids/pDNA into the matrix of mitochondria. After the appearance of antibody medicines, Opdivo, an immune checkpoint inhibitor, has established cancer immunology as the 4th strategy in cancer therapy. Our DDS technologies can also be applied to this new field of cancer therapy to cure cancer by controlling our immune mechanisms. The latest studies are summarized in this review article.}, } @article {pmid32917087, year = {2020}, author = {Teske, D and Peters, A and Möllers, A and Fischer, M}, title = {Genomic Profiling: The Strengths and Limitations of Chloroplast Genome-Based Plant Variety Authentication.}, journal = {Journal of agricultural and food chemistry}, volume = {68}, number = {49}, pages = {14323-14333}, doi = {10.1021/acs.jafc.0c03001}, pmid = {32917087}, issn = {1520-5118}, mesh = {Chloroplasts/*genetics ; *Genome, Chloroplast ; *Genome, Plant ; Genomics ; Phylogeny ; Plants/classification/*genetics ; }, abstract = {Genomic profiling is a suitable tool for variety authentication and has applications in both operational quality and regulatory raw material control. It can be used to differentiate species or varieties and to identify admixtures as well as field contaminants. To establish a molecular profile, reliable and very accurate sequence data are required. As a result of the influence of the pollinator plant, nuclear genome-based authentication is in most cases not suitable for a direct application on the fruit. Sequences must be used that come exclusively from the localized mother plant. Parts of the fruit of maternal origin, e.g., components derived from the blossom, are suitable as a basis for this. Alternatively, DNA from cell organelles that are maternally inherited, such as mitochondria or chloroplasts, can be used. The latter will be discussed in this review in closer detail. Although individual gene segments on the chloroplast genome are already used for species differentiation in barcoding studies on plants, little is known about the usefulness of the entire chloroplast genome for intraspecies differentiation in general and for differentiation between modern varieties in particular. Results from the literature as well as from our own work suggest that chloroplast genome sequences are indeed very well-suited for the differentiation of old varieties. On the other hand, they are less or not suitable for the genetic differentiation of modern cultivars, because they are often too closely related.}, } @article {pmid32920905, year = {2020}, author = {Ghifari, AS and Teixeira, PF and Kmiec, B and Pružinská, A and Glaser, E and Murcha, MW}, title = {A mitochondrial prolyl aminopeptidase PAP2 releases N-terminal proline and regulates proline homeostasis during stress response.}, journal = {The Plant journal : for cell and molecular biology}, volume = {104}, number = {5}, pages = {1182-1194}, doi = {10.1111/tpj.14987}, pmid = {32920905}, issn = {1365-313X}, mesh = {Amino Acid Motifs ; Aminopeptidases/genetics/*metabolism ; Arabidopsis/cytology/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Cellular Senescence/physiology ; Darkness ; Green Fluorescent Proteins/genetics ; Loss of Function Mutation ; Mitochondria/metabolism ; Phylogeny ; Plants, Genetically Modified ; Pollen/physiology ; Proline/*metabolism ; Stress, Physiological/*physiology ; Transcription Factors/genetics/*metabolism ; }, abstract = {Most mitochondrial proteins are synthesised in the cytosol and targeted into the organelle via N-terminal targeting peptides that are cleaved upon import. The free targeting peptide is subsequently processed in a stepwise manner, with single amino acids released as final products. Here, we have characterised a proline-cleaving aminopeptidase in Arabidopsis thaliana, prolyl aminopeptidase-2 (PAP2, At3g61540). Activity assays show that PAP2 has a preferred activity to hydrolyse N-terminal proline. Protein localisation studies revealed that PAP2 is exclusively targeted to mitochondria. Characterisation of pap2 mutants show defective pollen, enhanced dark-induced senescence and increased susceptibility to abiotic stresses, which are likely attributed to a reduced level of accumulated free proline. Taken together, these results demonstrate the role of PAP2 in proline cleavage from mitochondrial peptides and proline homeostasis, which is required for the development of male gametophyte, tolerance to abiotic stresses, and leaf senescence.}, } @article {pmid32933406, year = {2020}, author = {Weaver, RJ and Carrion, G and Nix, R and Maeda, GP and Rabinowitz, S and Iverson, ENK and Thueson, K and Havird, JC}, title = {High mitochondrial mutation rates in Silene are associated with nuclear-mediated changes in mitochondrial physiology.}, journal = {Biology letters}, volume = {16}, number = {9}, pages = {20200450}, pmid = {32933406}, issn = {1744-957X}, mesh = {DNA, Mitochondrial ; Evolution, Molecular ; Genome, Plant ; Mitochondria/genetics ; Mitochondrial Proteins/genetics ; Mutation ; Mutation Rate ; *Silene/genetics ; }, abstract = {Mitochondrial (mt) respiration depends on proteins encoded both by the mitochondrial and nuclear genomes. Variation in mt-DNA mutation rates exists across eukaryotes, although the functional consequences of elevated mt mutation rates in some lineages remain underexplored. In the angiosperm genus Silene, closely related, ecologically similar species have either 'fast' or 'slow' mt-DNA mutation rates. Here, we investigated the functional consequences of elevated mt-DNA mutation rates on mt respiration profiles of Silene mitochondria. Overall levels of respiration were similar among Species. Fast species had lower respiration efficiency than slow species and relied up to 48% more on nuclear-encoded respiratory enzymes alternative oxidase (AOX) and accessory dehydrogenases (DHex), which participate in stress responses in plants. However, not all fast species showed these trends. Respiratory profiles of some enzymes were correlated, most notably AOX and DHex. We conclude that subtle differences in mt physiology among Silene lineages with dramatically different mt mutation rates may underly similar phenotypes at higher levels of biological organization, betraying the consequences of mt mutations.}, } @article {pmid32934270, year = {2020}, author = {Simaika, JP and Ware, JL and Garrison, RW and Samways, MJ}, title = {Phylogeny of the Synlestidae (Odonata: Zygoptera), with an emphasis on Chlorolestes Selys and Ecchlorolestes Barnard.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {15088}, pmid = {32934270}, issn = {2045-2322}, mesh = {Animals ; Cell Nucleus/genetics ; Mitochondria/genetics ; Odonata/*genetics ; Phylogeny ; South Africa ; }, abstract = {The Synlestidae (Odonata: Zygoptera) of southern Africa comprise some highly localized species. All but one species are endemic to South Africa, and many to the Cape Floristic Region. Here we present the first phylogenetic reconstruction of the southern African Synlestidae using nuclear and mitochondrial molecular data. The genera Ecchlorolestes and Chlorolestes are monophyletic, and we propose that the Neotropical family Perilestidae consisting of two genera, Perilestes and Perissolestes, be sunk within Synlestidae. We discuss the intra-familial relationships for the southern African Synlestidae.}, } @article {pmid32935660, year = {2021}, author = {Li, H and Qiao, H and Liu, Y and Li, S and Tan, J and Hao, D}, title = {Characterization, expression profiling, and thermal tolerance analysis of heat shock protein 70 in pine sawyer beetle, Monochamus alternatus hope (Coleoptera: Cerambycidae).}, journal = {Bulletin of entomological research}, volume = {111}, number = {2}, pages = {217-228}, doi = {10.1017/S0007485320000541}, pmid = {32935660}, issn = {1475-2670}, mesh = {Animals ; *Coleoptera/genetics/metabolism ; Genes, Insect ; *HSP70 Heat-Shock Proteins/genetics/metabolism ; Larva/genetics/metabolism ; Phylogeny ; Thermotolerance/*genetics ; }, abstract = {Monochamus alternatus Hope (Coleoptera: Cerambycidae) warrants attention as a dominant transmission vector of the pinewood nematode, and it exhibits tolerance to high temperature. Heat shock protein 70 (HSP70) family members, including inducible HSP70 and heat shock cognate protein 70 (HSC70), are major contributors to the molecular chaperone networks of insects under heat stress. In this regard, we specifically cloned and characterized three MaltHSP70s and three MaltHSC70s. Bioinformatics analysis on the deduced amino acid sequences showed these genes, having close genetic relationships with HSP70s of Coleopteran species, collectively shared conserved signature structures and ATPase domains. Subcellular localization prediction revealed the HSP70s of M. alternatus were located not only in the cytoplasm and endoplasmic reticulum but also in the nucleus and mitochondria. The transcript levels of MaltHSP70s and MaltHSC70s in each state were significantly upregulated by exposure to 35-50°C for early 3 h, while MaltHSP70s reached a peak after exposure to 45°C for 2-3 h in contrast to less-upregulated MaltHSC70s. In terms of MaltHSP70s, the expression threshold in females was lower than that in males. Also, both fat bodies and Malpighian tubules were the tissues most sensitive to heat stress in M. alternatus larvae. Lastly, the ATPase activity of recombinant MaltHSP70-2 in vitro remained stable at 25-40°C, and this recombinant availably enhanced the thermotolerance of Escherichia coli. Overall, our findings unraveled HSP70s might be the intrinsic mediators of the strong heat tolerance of M. alternatus due to their stabilized structure and bioactivity.}, } @article {pmid32937139, year = {2020}, author = {Schneider, K and Nelson, GM and Watson, JL and Morf, J and Dalglish, M and Luh, LM and Weber, A and Bertolotti, A}, title = {Protein Stability Buffers the Cost of Translation Attenuation following eIF2α Phosphorylation.}, journal = {Cell reports}, volume = {32}, number = {11}, pages = {108154}, pmid = {32937139}, issn = {2211-1247}, support = {/WT_/Wellcome Trust/United Kingdom ; MC_U105185860/MRC_/Medical Research Council/United Kingdom ; 206367/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {5' Untranslated Regions/genetics ; Animals ; Down-Regulation/genetics ; Endoplasmic Reticulum Stress/genetics ; Eukaryotic Initiation Factor-2/*metabolism ; HEK293 Cells ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism ; Models, Biological ; NIH 3T3 Cells ; Phosphorylation ; Polyribosomes/metabolism ; *Protein Biosynthesis ; Protein Stability ; RNA, Messenger/genetics/metabolism ; Ribosomal Proteins/metabolism ; Transcription, Genetic ; Unfolded Protein Response/genetics ; }, abstract = {Phosphorylation of the translation initiation factor eIF2α is a rapid and vital response to many forms of stress, including protein-misfolding stress in the endoplasmic reticulum (ER stress). It is believed to cause a general reduction in protein synthesis while enabling translation of few transcripts. Such a reduction of protein synthesis comes with the threat of depleting essential proteins, a risk thought to be mitigated by its transient nature. Here, we find that translation attenuation is not uniform, with cytosolic and mitochondrial ribosomal subunits being prominently downregulated. Translation attenuation of these targets persists after translation recovery. Surprisingly, this occurs without a measurable decrease in ribosomal proteins. Explaining this conundrum, translation attenuation preferentially targets long-lived proteins, a finding not only demonstrated by ribosomal proteins but also observed at a global level. This shows that protein stability buffers the cost of translational attenuation, establishing an evolutionary principle of cellular robustness.}, } @article {pmid32938978, year = {2020}, author = {Ben Chehida, Y and Thumloup, J and Schumacher, C and Harkins, T and Aguilar, A and Borrell, A and Ferreira, M and Rojas-Bracho, L and Robertson, KM and Taylor, BL and Víkingsson, GA and Weyna, A and Romiguier, J and Morin, PA and Fontaine, MC}, title = {Mitochondrial genomics reveals the evolutionary history of the porpoises (Phocoenidae) across the speciation continuum.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {15190}, pmid = {32938978}, issn = {2045-2322}, mesh = {Animals ; Biodiversity ; *Biological Evolution ; Ecosystem ; Evolution, Molecular ; Genetic Speciation ; Genome, Mitochondrial/*genetics ; Genomics/*methods ; Mitochondria/*genetics ; Phylogeny ; Porpoises/*physiology ; Species Specificity ; }, abstract = {Historical variation in food resources is expected to be a major driver of cetacean evolution, especially for the smallest species like porpoises. Despite major conservation issues among porpoise species (e.g., vaquita and finless), their evolutionary history remains understudied. Here, we reconstructed their evolutionary history across the speciation continuum. Phylogenetic analyses of 63 mitochondrial genomes suggest that porpoises radiated during the deep environmental changes of the Pliocene. However, all intra-specific subdivisions were shaped during the Quaternary glaciations. We observed analogous evolutionary patterns in both hemispheres associated with convergent evolution to coastal versus oceanic environments. This suggests that similar mechanisms are driving species diversification in northern (harbor and Dall's) and southern species (spectacled and Burmeister's). In contrast to previous studies, spectacled and Burmeister's porpoises shared a more recent common ancestor than with the vaquita that diverged from southern species during the Pliocene. The low genetic diversity observed in the vaquita carried signatures of a very low population size since the last 5,000 years. Cryptic lineages within Dall's, spectacled and Pacific harbor porpoises suggest a richer evolutionary history than previously suspected. These results provide a new perspective on the mechanisms driving diversification in porpoises and an evolutionary framework for their conservation.}, } @article {pmid32949792, year = {2020}, author = {Cihlar, JC and Strobl, C and Lagacé, R and Muenzler, M and Parson, W and Budowle, B}, title = {Distinguishing mitochondrial DNA and NUMT sequences amplified with the precision ID mtDNA whole genome panel.}, journal = {Mitochondrion}, volume = {55}, number = {}, pages = {122-133}, doi = {10.1016/j.mito.2020.09.001}, pmid = {32949792}, issn = {1872-8278}, mesh = {Cell Nucleus/*genetics ; Computational Biology/methods ; DNA, Mitochondrial/*classification/isolation & purification ; Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Mitochondria/*genetics ; Phylogeny ; Whole Genome Sequencing/*methods ; }, abstract = {Nuclear mitochondrial DNA segments (NUMTs) are generated via transfer of portions of the mitochondrial genome into the nuclear genome. Given their common origin, there is the possibility that both the mitochondrial and NUMT segments may co-amplify using the same set of primers. Thus, analysis of the variation of the mitochondrial genome must take into account this co-amplification of mitochondrial and NUMT sequences. The study herein builds on data from the study by Strobl et al. (Strobl et al., 2019), in which multiple point heteroplasmies were called with an "N" to prevent labeling NUMT sequences mimicking mitochondrial heteroplasmy and being interpreted as true mitochondrial in origin sequence variants. Each of these point heteroplasmies was studied in greater detail, both molecularly and bioinformatically, to determine whether NUMT or true mitochondrial DNA variation was present. The bioinformatic and molecular tools available to help distinguish between NUMT and mitochondrial DNA and the effect of NUMT sequences on interpretation were discussed.}, } @article {pmid32959778, year = {2020}, author = {Gitschlag, BL and Tate, AT and Patel, MR}, title = {Nutrient status shapes selfish mitochondrial genome dynamics across different levels of selection.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32959778}, issn = {2050-084X}, support = {R01 GM123260/GM/NIGMS NIH HHS/United States ; GM123260/GM/NIGMS NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; F31 GM125344/GM/NIGMS NIH HHS/United States ; P30 EY008126/EY/NEI NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; 1 F31 GM125344/GM/NIGMS NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Caenorhabditis elegans/genetics/physiology ; Cell Proliferation/genetics ; Genetic Fitness/genetics ; Genome, Mitochondrial/*genetics ; Mitochondrial Dynamics/*genetics ; Nutrients/*metabolism ; Repetitive Sequences, Nucleic Acid/*genetics ; }, abstract = {Cooperation and cheating are widespread evolutionary strategies. While cheating confers an advantage to individual entities within a group, competition between groups favors cooperation. Selfish or cheater mitochondrial DNA (mtDNA) proliferates within hosts while being selected against at the level of host fitness. How does environment shape cheater dynamics across different selection levels? Focusing on food availability, we address this question using heteroplasmic Caenorhabditis elegans. We find that the proliferation of selfish mtDNA within hosts depends on nutrient status stimulating mtDNA biogenesis in the developing germline. Interestingly, mtDNA biogenesis is not sufficient for this proliferation, which also requires the stress-response transcription factor FoxO/DAF-16. At the level of host fitness, FoxO/DAF-16 also prevents food scarcity from accelerating the selection against selfish mtDNA. This suggests that the ability to cope with nutrient stress can promote host tolerance of cheaters. Our study delineates environmental effects on selfish mtDNA dynamics at different levels of selection.}, } @article {pmid32959780, year = {2020}, author = {Camus, MF}, title = {The perils of cheating.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32959780}, issn = {2050-084X}, mesh = {DNA, Mitochondrial ; *Genome, Mitochondrial ; Mitochondria/genetics ; Mitochondrial Dynamics ; Nutrients ; }, abstract = {Experiments on mitochondrial DNA in worms highlight that cheating does not always pay off.}, } @article {pmid32960450, year = {2021}, author = {Barbhuiya, PA and Uddin, A and Chakraborty, S}, title = {Codon usage pattern and evolutionary forces of mitochondrial ND genes among orders of class Amphibia.}, journal = {Journal of cellular physiology}, volume = {236}, number = {4}, pages = {2850-2868}, doi = {10.1002/jcp.30050}, pmid = {32960450}, issn = {1097-4652}, mesh = {Amphibian Proteins/genetics/metabolism ; Amphibians/*genetics/metabolism ; Animals ; Anura/genetics/metabolism ; *Codon Usage ; *Evolution, Molecular ; Mitochondria/enzymology/*genetics ; Mitochondrial Proteins/*genetics/metabolism ; NADH Dehydrogenase/*genetics/metabolism ; Species Specificity ; Caudata/genetics/metabolism ; }, abstract = {In this study, we used a bioinformatics approach to analyze the nucleotide composition and pattern of synonymous codon usage in mitochondrial ND genes in three amphibian groups, that is, orders Anura, Caudata, and Gymnophiona to identify the commonality and the differences of codon usage as no research work was reported yet. The high value of the effective number of codons revealed that the codon usage bias (CUB) was low in mitochondrial ND genes among the orders. Nucleotide composition analysis suggested that for each gene, the compositional features differed among Anura, Caudata, and Gymnophiona and the GC content was lower than AT content. Furthermore, a highly significant difference (p < .05) for GC content was found in each gene among the orders. The heat map showed contrasting patterns of codon usage among different ND genes. The regression of GC12 on GC3 suggested a narrow range of GC3 distribution and some points were located in the diagonal, indicating both mutation pressure and natural selection might influence the CUB. Moreover, the slope of the regression line was less than 0.5 in all ND genes among orders, indicating natural selection might have played the dominant role whereas mutation pressure had played a minor role in shaping CUB of ND genes across orders.}, } @article {pmid32966934, year = {2020}, author = {Silva de Souza, S and Machado, RN and Custódio da Costa, J and Campos, DF and Sebrenski da Silva, G and Fonseca de Almeida-Val, VM}, title = {Severe damages caused by Malathion exposure in Colossoma macropomum.}, journal = {Ecotoxicology and environmental safety}, volume = {205}, number = {}, pages = {111340}, doi = {10.1016/j.ecoenv.2020.111340}, pmid = {32966934}, issn = {1090-2414}, mesh = {Animals ; Antioxidants/*metabolism ; Characiformes/genetics/*metabolism ; *DNA Damage ; Gills/drug effects/pathology ; Insecticides/*toxicity ; Lethal Dose 50 ; Malathion/*toxicity ; Mitochondria/drug effects/metabolism ; Proto-Oncogene Mas ; Reactive Oxygen Species/metabolism ; Toxicity Tests, Acute ; Water Pollutants, Chemical/*toxicity ; }, abstract = {The increase in pesticide use in response to agricultural demands poses a risk to non-target organisms, including fish. Integrated analysis of biochemical, histopathological and genetic parameters in fish exposed to Malathion insecticide provide information on the toxicity mechanisms of this pesticide, which is classified as a probable carcinogen for humans. The present study assessed the biological responses of Colossoma macropomum after exposure to Malathion. We started determining the lethal concentration, which is the concentration capable of killing 50% of the subjects in an acute toxicity test (LC50-96 h), which was 15.77 ± 3.30 mgL[-1]. The fish were, then, exposed to Malathion during 96 h at a sublethal concentration, 7.30 mgL[-1]. Overall, we observed an increased activity of biotransformation and antioxidant enzymes, which reduced production of mitochondrial reactive oxygen species after 96 h exposure, as well as kept constant the mitochondrial respiration, Acetylcholinesterase activity and DNA damage. However, fish exposed to insecticide presented severe gill histopathological damage and increased expression of proto-oncogene ras. Taken together, the results suggest that, after four days of exposure to the Malathion, C. macropomum efficiently activates its defense mechanisms, suggesting that the basal response mechanisms are responsive. On the other hand, histopathologic damages evidenced the adverse effects of Malathion on fish, since it promoted gill necrosis and increased the expression of ras oncogene that is directly related to tumorigenesis events.}, } @article {pmid32987154, year = {2020}, author = {Cheong, A and Lingutla, R and Mager, J}, title = {Expression analysis of mammalian mitochondrial ribosomal protein genes.}, journal = {Gene expression patterns : GEP}, volume = {38}, number = {}, pages = {119147}, pmid = {32987154}, issn = {1872-7298}, support = {R01 HD083311/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Blastocyst/metabolism ; Cells, Cultured ; *Gene Expression Regulation, Developmental ; Mice ; Mice, Inbred C57BL ; Mitochondrial Proteins/*genetics/metabolism ; Ribosomal Proteins/*genetics/metabolism ; }, abstract = {Mitochondrial ribosomal proteins (MRPs) are essential components for the structural and functional integrity of the mitoribosome complex. Throughout evolution, the mammalian mitoribosome has acquired new Mrp genes to compensate for loss of ribosomal RNA. More than 80 MRPs have been identified in mammals. Here we document expression pattern of 79 Mrp genes during mouse development and adult tissues and find that these genes are consistently expressed throughout early embryogenesis with little stage or tissue specificity. Further investigation of the amino acid sequence reveals that this group of proteins has little to no protein similarity. Recent work has shown that the majority of Mrp genes are essential resulting in early embryonic lethality, suggesting no functional redundancy among the group. Taken together, these results indicate that the Mrp genes are not a gene family descended from a single ancestral gene, and that each MRP has unique and essential role in the mitoribosome complex. The lack of functional redundancy is surprising given the importance of the mitoribosome for cellular and organismal viability. Further, these data suggest that genomic variants in Mrp genes may be causative for early pregnancy loss and should be evaluated as clinically.}, } @article {pmid32992603, year = {2020}, author = {Laptev, I and Dontsova, O and Sergiev, P}, title = {Epitranscriptomics of Mammalian Mitochondrial Ribosomal RNA.}, journal = {Cells}, volume = {9}, number = {10}, pages = {}, pmid = {32992603}, issn = {2073-4409}, mesh = {Animals ; Evolution, Molecular ; Humans ; Mammals ; Mitochondria/*genetics ; Peptidyl Transferases/genetics ; Pseudouridine/genetics ; RNA, Mitochondrial/*genetics ; RNA, Ribosomal/*genetics ; Ribosomes/*genetics ; }, abstract = {Modified nucleotides are present in all ribosomal RNA molecules. Mitochondrial ribosomes are unique to have a set of methylated residues that includes universally conserved ones, those that could be found either in bacterial or in archaeal/eukaryotic cytosolic ribosomes and those that are present exclusively in mitochondria. A single pseudouridine within the mt-rRNA is located in the peptidyltransferase center at a position similar to that in bacteria. After recent completion of the list of enzymes responsible for the modification of mammalian mitochondrial rRNA it became possible to summarize an evolutionary history, functional role of mt-rRNA modification enzymes and an interplay of the mt-rRNA modification and mitoribosome assembly process, which is a goal of this review.}, } @article {pmid32992875, year = {2020}, author = {Tan, DX and Hardeland, R}, title = {Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19.}, journal = {Molecules (Basel, Switzerland)}, volume = {25}, number = {19}, pages = {}, pmid = {32992875}, issn = {1420-3049}, mesh = {COVID-19 ; Coronavirus Infections/*drug therapy/metabolism ; Drug Delivery Systems ; Humans ; Melatonin/metabolism/*therapeutic use ; Mitochondria/*drug effects/metabolism ; Pandemics ; Pneumonia, Viral/*drug therapy/metabolism ; Virus Diseases/*drug therapy/*immunology/metabolism ; }, abstract = {Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen's spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution. Practically, it has a broader protective spectrum than that of only targeting the specific pathogens, which differ in terms of susceptibility. Methods for host targeting applied in one pandemic can even be effective for upcoming pandemics with different pathogens. This is even more urgent if we consider the possible concomitance of two respiratory diseases with potential multi-organ afflictions such as Coronavirus disease 2019 (COVID-19) and seasonal flu. Melatonin is a molecule that can enhance the host's tolerance against pathogen invasions. Due to its antioxidant, anti-inflammatory, and immunoregulatory activities, melatonin has the capacity to reduce the severity and mortality of deadly virus infections including COVID-19. Melatonin is synthesized and functions in mitochondria, which play a critical role in viral infections. Not surprisingly, melatonin synthesis can become a target of viral strategies that manipulate the mitochondrial status. For example, a viral infection can switch energy metabolism from respiration to widely anaerobic glycolysis even if plenty of oxygen is available (the Warburg effect) when the host cell cannot generate acetyl-coenzyme A, a metabolite required for melatonin biosynthesis. Under some conditions, including aging, gender, predisposed health conditions, already compromised mitochondria, when exposed to further viral challenges, lose their capacity for producing sufficient amounts of melatonin. This leads to a reduced support of mitochondrial functions and makes these individuals more vulnerable to infectious diseases. Thus, the maintenance of mitochondrial function by melatonin supplementation can be expected to generate beneficial effects on the outcome of viral infectious diseases, particularly COVID-19.}, } @article {pmid32997570, year = {2020}, author = {Friedl, J and Knopp, MR and Groh, C and Paz, E and Gould, SB and Herrmann, JM and Boos, F}, title = {More than just a ticket canceller: the mitochondrial processing peptidase tailors complex precursor proteins at internal cleavage sites.}, journal = {Molecular biology of the cell}, volume = {31}, number = {24}, pages = {2657-2668}, pmid = {32997570}, issn = {1939-4586}, mesh = {Aldehyde Oxidoreductases/metabolism ; Amino Acid Sequence/genetics ; Binding Sites/genetics ; Metalloendopeptidases/*metabolism/physiology ; Mitochondria/*metabolism ; Mitochondrial Proteins/*metabolism ; Multienzyme Complexes/metabolism ; Phosphotransferases (Carboxyl Group Acceptor)/metabolism ; Protein Precursors/metabolism ; Protein Processing, Post-Translational/physiology ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Substrate Specificity/genetics ; Mitochondrial Processing Peptidase ; }, abstract = {Most mitochondrial proteins are synthesized as precursors that carry N-terminal presequences. After they are imported into mitochondria, these targeting signals are cleaved off by the mitochondrial processing peptidase (MPP). Using the mitochondrial tandem protein Arg5,6 as a model substrate, we demonstrate that MPP has an additional role in preprotein maturation, beyond the removal of presequences. Arg5,6 is synthesized as a polyprotein precursor that is imported into mitochondria and subsequently separated into two distinct enzymes. This internal processing is performed by MPP, which cleaves the Arg5,6 precursor at its N-terminus and at an internal site. The peculiar organization of Arg5,6 is conserved across fungi and reflects the polycistronic arginine operon in prokaryotes. MPP cleavage sites are also present in other mitochondrial fusion proteins from fungi, plants, and animals. Hence, besides its role as a "ticket canceller" for removal of presequences, MPP exhibits a second conserved activity as an internal processing peptidase for complex mitochondrial precursor proteins.}, } @article {pmid32998193, year = {2020}, author = {Marshall, C and Sturk-Andreaggi, K and Ring, JD and Dür, A and Parson, W}, title = {Pathogenic Variant Filtering for Mitochondrial Genome Haplotype Reporting.}, journal = {Genes}, volume = {11}, number = {10}, pages = {}, pmid = {32998193}, issn = {2073-4425}, mesh = {*Algorithms ; DNA, Mitochondrial/analysis/*genetics ; *Genetic Variation ; *Genetics, Population ; *Genome, Mitochondrial ; *Haplotypes ; Humans ; Mitochondria/*genetics/metabolism/pathology ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Given the enhanced discriminatory power of the mitochondrial DNA (mtDNA) genome (mitogenome) over the commonly sequenced control region (CR) portion, the scientific merit of mitogenome sequencing is generally accepted. However, many laboratories remain beholden to CR sequencing due to privacy policies and legal requirements restricting the use of disease information or coding region (codR) information. In this report, we present an approach to obviate the reporting of sensitive codR data in forensic haplotypes. We consulted the MitoMap database to identify 92 mtDNA codR variants with confirmed pathogenicity. We determined the frequencies of these pathogenic variants in literature-quality and forensic-quality databases to be very low, at 1.2% and 0.36%, respectively. The observed effect of pathogenic variant filtering on random match statistics in 2488 forensic-quality mitogenome haplotypes from four populations was nil. We propose that pathogenic variant filtering should be incorporated into variant calling algorithms for mitogenome haplotype reporting to maximize the discriminatory power of the locus while minimizing the reveal of sensitive genetic information.}, } @article {pmid32998881, year = {2020}, author = {Popgeorgiev, N and Sa, JD and Jabbour, L and Banjara, S and Nguyen, TTM and Akhavan-E-Sabet, A and Gadet, R and Ralchev, N and Manon, S and Hinds, MG and Osigus, HJ and Schierwater, B and Humbert, PO and Rimokh, R and Gillet, G and Kvansakul, M}, title = {Ancient and conserved functional interplay between Bcl-2 family proteins in the mitochondrial pathway of apoptosis.}, journal = {Science advances}, volume = {6}, number = {40}, pages = {}, pmid = {32998881}, issn = {2375-2548}, mesh = {Animals ; *Apoptosis ; Humans ; Mammals/metabolism ; Mitochondria/metabolism ; Mitochondrial Membranes/metabolism ; *bcl-2 Homologous Antagonist-Killer Protein/chemistry/genetics/metabolism ; }, abstract = {In metazoans, Bcl-2 family proteins are major regulators of mitochondrially mediated apoptosis; however, their evolution remains poorly understood. Here, we describe the molecular characterization of the four members of the Bcl-2 family in the most primitive metazoan, Trichoplax adhaerens All four trBcl-2 homologs are multimotif Bcl-2 group, with trBcl-2L1 and trBcl-2L2 being highly divergent antiapoptotic Bcl-2 members, whereas trBcl-2L3 and trBcl-2L4 are homologs of proapoptotic Bax and Bak, respectively. trBax expression permeabilizes the mitochondrial outer membrane, while trBak operates as a BH3-only sensitizer repressing antiapoptotic activities of trBcl-2L1 and trBcl-2L2. The crystal structure of a trBcl-2L2:trBak BH3 complex reveals that trBcl-2L2 uses the canonical Bcl-2 ligand binding groove to sequester trBak BH3, indicating that the structural basis for apoptosis control is conserved from T. adhaerens to mammals. Finally, we demonstrate that both trBax and trBak BH3 peptides bind selectively to human Bcl-2 homologs to sensitize cancer cells to chemotherapy treatment.}, } @article {pmid33002605, year = {2020}, author = {Pacheco, MA and Ceríaco, LMP and Matta, NE and Vargas-Ramírez, M and Bauer, AM and Escalante, AA}, title = {A phylogenetic study of Haemocystidium parasites and other Haemosporida using complete mitochondrial genome sequences.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {85}, number = {}, pages = {104576}, doi = {10.1016/j.meegid.2020.104576}, pmid = {33002605}, issn = {1567-7257}, mesh = {Africa ; Biodiversity ; DNA, Protozoan ; *Genome, Mitochondrial ; *Genomics/methods ; Haemosporida/*classification/*genetics ; High-Throughput Nucleotide Sequencing ; *Phylogeny ; South America ; }, abstract = {Haemosporida are diverse vector-borne parasites associated with terrestrial vertebrates. Driven by the interest in species causing malaria (genus Plasmodium), the diversity of avian and mammalian haemosporidian species has been extensively studied, relying mostly on mitochondrial genes, particularly cytochrome b. However, parasites from reptiles have been neglected in biodiversity surveys. Reptilian haemosporidian parasites include Haemocystidium, a genus that shares morphological features with Plasmodium and Haemoproteus. Here, the first complete Haemocystidium mitochondrial DNA (mtDNA) genomes are studied. In particular, three mtDNA genomes from Haemocystidium spp. sampled in Africa, Oceania, and South America, are described. The Haemocystidium mtDNA genomes showed a high A + T content and a gene organization, including an extreme fragmentation of the rRNAs, found in other Haemosporida. These Haemocystidium mtDNA genomes were incorporated in phylogenetic and molecular clock analyses together with a representative sample of haemosporidian parasites from birds, mammals, and reptiles. The recovered phylogeny supported Haemocystidium as a monophyletic group apart from Plasmodium and other Haemosporida. Both the phylogenetic and molecular clock analyses yielded results consistent with a scenario in which haemosporidian parasites radiated with modern birds. Haemocystidium, like mammalian parasite clades, seems to originate from host switches by avian Haemosporida that allowed for the colonization of new vertebrate hosts. This hypothesis can be tested by investigating additional parasite species from all vertebrate hosts, particularly from reptiles. The mtDNA genomes reported here provide baseline data that can be used to scale up studies in haemosporidian parasites of reptiles using barcode approaches.}, } @article {pmid33004955, year = {2020}, author = {Park, S and Park, S}, title = {Large-scale phylogenomics reveals ancient introgression in Asian Hepatica and new insights into the origin of the insular endemic Hepatica maxima.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {16288}, pmid = {33004955}, issn = {2045-2322}, mesh = {Biological Evolution ; Asia, Eastern ; Genes, Plant/genetics ; Genetic Introgression/genetics ; Genome, Plant/genetics ; Mitochondria/genetics ; Phylogeny ; Plastids/genetics ; Ranunculaceae/*genetics ; }, abstract = {Hepatica maxima is native to Ulleungdo, which is one of the oceanic islands in Korea, and it likely originated via anagenetic speciation from the Korean mainland species H. asiatica. However, the relationships among the Asian lineages remain unresolved. Phylogenomics based on plant genomes can provide new insights into the evolutionary history of plants. We first generated plastid, mitochondrial and transcriptome sequences of the insular endemic species H. maxima. Using the genomic data for H. maxima, we obtained a phylogenomic dataset consisting of 76 plastid, 37 mitochondrial and 413 nuclear genes from Asian Hepatica and two outgroups. Coalescent- and concatenation-based methods revealed cytonuclear and organellar discordance in the lineage. The presence of gynodioecy with cytoplasmic male sterility in Asian Hepatica suggests that the discordance is correlated with potential disruption of linkage disequilibrium between the organellar genomes. Species network analyses revealed a deep history of hybridization and introgression in Asian Hepatica. We discovered that ancient and recent introgression events occurred throughout the evolutionary history of the insular endemic species H. maxima. The introgression may serve as an important source of genetic variation to facilitate adaptation to the Ulleungdo environment.}, } @article {pmid33007329, year = {2021}, author = {Braymer, JJ and Freibert, SA and Rakwalska-Bange, M and Lill, R}, title = {Mechanistic concepts of iron-sulfur protein biogenesis in Biology.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {1868}, number = {1}, pages = {118863}, doi = {10.1016/j.bbamcr.2020.118863}, pmid = {33007329}, issn = {1879-2596}, mesh = {Bacteria/genetics ; Cytosol/metabolism ; Humans ; Iron/metabolism ; Iron-Sulfur Proteins/*genetics/metabolism ; Mitochondria/*genetics/metabolism ; Photosynthesis/*genetics ; Respiration/genetics ; Saccharomyces cerevisiae/genetics ; Sulfur/metabolism ; Symbiosis/*genetics ; }, abstract = {Iron-sulfur (Fe/S) proteins are present in virtually all living organisms and are involved in numerous cellular processes such as respiration, photosynthesis, metabolic reactions, nitrogen fixation, radical biochemistry, protein synthesis, antiviral defense, and genome maintenance. Their versatile functions may go back to the proposed role of their Fe/S cofactors in the origin of life as efficient catalysts and electron carriers. More than two decades ago, it was discovered that the in vivo synthesis of cellular Fe/S clusters and their integration into polypeptide chains requires assistance by complex proteinaceous machineries, despite the fact that Fe/S proteins can be assembled chemically in vitro. In prokaryotes, three Fe/S protein biogenesis systems are known; ISC, SUF, and the more specialized NIF. The former two systems have been transferred by endosymbiosis from bacteria to mitochondria and plastids, respectively, of eukaryotes. In their cytosol, eukaryotes use the CIA machinery for the biogenesis of cytosolic and nuclear Fe/S proteins. Despite the structural diversity of the protein constituents of these four machineries, general mechanistic concepts underlie the complex process of Fe/S protein biogenesis. This review provides a comprehensive and comparative overview of the various known biogenesis systems in Biology, and summarizes their common or diverging molecular mechanisms, thereby illustrating both the conservation and diverse adaptions of these four machineries during evolution and under different lifestyles. Knowledge of these fundamental biochemical pathways is not only of basic scientific interest, but is important for the understanding of human 'Fe/S diseases' and can be used in biotechnology.}, } @article {pmid33017596, year = {2021}, author = {Mayr, SJ and Mendel, RR and Schwarz, G}, title = {Molybdenum cofactor biology, evolution and deficiency.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {1868}, number = {1}, pages = {118883}, doi = {10.1016/j.bbamcr.2020.118883}, pmid = {33017596}, issn = {1879-2596}, mesh = {Coenzymes/biosynthesis/classification/*genetics ; Eukaryota/*genetics ; Gene Fusion/genetics ; Humans ; Metalloproteins/biosynthesis/classification/*genetics ; Molybdenum/*metabolism ; Molybdenum Cofactors ; Pteridines/classification ; Substrate Specificity ; }, abstract = {The molybdenum cofactor (Moco) represents an ancient metal‑sulfur cofactor, which participates as catalyst in carbon, nitrogen and sulfur cycles, both on individual and global scale. Given the diversity of biological processes dependent on Moco and their evolutionary age, Moco is traced back to the last universal common ancestor (LUCA), while Moco biosynthetic genes underwent significant changes through evolution and acquired additional functions. In this review, focused on eukaryotic Moco biology, we elucidate the benefits of gene fusions on Moco biosynthesis and beyond. While originally the gene fusions were driven by biosynthetic advantages such as coordinated expression of functionally related proteins and product/substrate channeling, they also served as origin for the development of novel functions. Today, Moco biosynthetic genes are involved in a multitude of cellular processes and loss of the according gene products result in severe disorders, both related to Moco biosynthesis and secondary enzyme functions.}, } @article {pmid33026033, year = {2020}, author = {Bolmatov, D and Carrillo, JY and Sumpter, BG and Katsaras, J and Lavrentovich, MO}, title = {Double membrane formation in heterogeneous vesicles.}, journal = {Soft matter}, volume = {16}, number = {38}, pages = {8806-8817}, doi = {10.1039/d0sm01167c}, pmid = {33026033}, issn = {1744-6848}, mesh = {*Lipid Bilayers ; *Molecular Dynamics Simulation ; }, abstract = {Lipids are capable of forming a variety of structures, including multi-lamellar vesicles. Layered lipid membranes are found in cell organelles, such as autophagosomes and mitochondria. Here, we present a mechanism for the formation of a double-walled vesicle (i.e., two lipid bilayers) from a unilamellar vesicle through the partitioning and phase separation of a small molecule. Using molecular dynamics simulations, we show that double membrane formation proceeds via a nucleation and growth process - i.e., after a critical concentration of the small molecules, a patch of double membrane nucleates and grows to cover the entire vesicle. We discuss the implications of this mechanism and theoretical approaches for understanding the evolution and formation of double membranes.}, } @article {pmid33030068, year = {2020}, author = {Kumar, KS and Chandrika, SK and George, S}, title = {Genetic structure and demographic history of Indirana semipalmata, an endemic frog species of the Western Ghats, India.}, journal = {Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis}, volume = {31}, number = {8}, pages = {365-378}, doi = {10.1080/24701394.2020.1830077}, pmid = {33030068}, issn = {2470-1408}, mesh = {Animals ; Anura/*classification/genetics ; Cell Nucleus/*genetics ; Conservation of Natural Resources ; DNA/*genetics ; Evolution, Molecular ; Gene Flow ; Genetics, Population ; India ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {The evolutionary potential of a species mainly depends on the level of genetic variation in their populations. Maintenance of gene variation enables populations to adapt more quickly to environmental changes. The geographical gaps also influence the distribution and evolutionary history of many mountain frogs in the world. Hence, a sound knowledge in population genetic structure of a species will help understand its population dynamics and develop conservation strategies. In the context of facing threats to the amphibian fauna of Western Ghats due to habitat loss, we used both mitochondrial and nuclear DNA markers to investigate the genetic structure of an endemic frog species of the Western Ghats (Indirana semipalmata) with restricted distribution. The present study showed the importance of mountain gaps in shaping the species' structuring in the Western Ghats. Though a high genetic diversity was observed for the species when considering a single unit in the southern Western Ghats, the restricted gene flow on/between either side of the Shencottah gap with genetic clustering of the sampled populations may warrant a unique management plan for the species. The habitat fragmentation of the Western Ghats through anthropogenic activities may result in severe setbacks to the survival of the species in the future.}, } @article {pmid33030077, year = {2020}, author = {Han, L and Zhang, JT and Wang, MM and Zhu, KX and Wang, XY}, title = {Mitochondrial DNA diversity and population structure of Laodelphax striatellus across a broad geographic area in China.}, journal = {Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis}, volume = {31}, number = {8}, pages = {346-354}, doi = {10.1080/24701394.2020.1830075}, pmid = {33030077}, issn = {2470-1408}, mesh = {Animals ; China ; DNA, Mitochondrial/*genetics ; Genetic Variation ; Genetics, Population ; Haplotypes ; Hemiptera/*classification/genetics ; Mitochondria/*genetics ; Pest Control ; Phylogeny ; Sequence Analysis, DNA/*methods ; }, abstract = {The small brown planthopper (SBPH), Laodelphax striatellus Fallén (Hemiptera: Delphacidae), is a crucial devastating rice pest in East Asia. To effectively control this pest, we investigate the genetic diversity, genetic differentiation and genetic structure of 49 populations in China based on a 596 bp fragment of the mitochondrial DNA cytochrome c oxidase subunit I (mtDNA COI) gene. Overall, 83 haplotypes were detected in 1253 mtDNA COI sequences. High levels of genetic variability (Hd = 0.756 ± 0.009, π = 0.00416 ± 0.00011) and genetic differentiation (FST = 0.262, p < .001) were observed. Bayesian inference phylogenetic and median-joining haplotype network analyses indicated no obvious geographical distribution pattern among haplotypes. Hierarchical AMOVA and SAMOVA revealed no genetically distinct groups and lack of obvious phylogeographic structure. Isolation by distance (IBD) analysis results demonstrated no correlation between genetic differentiation and geographic distance. Finally, the demographic history of SBPH examined by neutrality tests and mismatch distribution analyses illustrated a sudden population expansion at the large spatial scale in China.}, } @article {pmid33031489, year = {2021}, author = {Miyazawa, H and Osigus, HJ and Rolfes, S and Kamm, K and Schierwater, B and Nakano, H}, title = {Mitochondrial Genome Evolution of Placozoans: Gene Rearrangements and Repeat Expansions.}, journal = {Genome biology and evolution}, volume = {13}, number = {1}, pages = {}, pmid = {33031489}, issn = {1759-6653}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *Evolution, Molecular ; Exons ; Gene Order ; *Gene Rearrangement ; *Genome, Mitochondrial ; Haplotypes ; Introns ; Mitochondria/*genetics ; Phylogeny ; Placozoa/*genetics ; RNA, Ribosomal ; RNA, Ribosomal, 16S ; RNA, Transfer ; }, abstract = {Placozoans, nonbilaterian animals with the simplest known metazoan bauplan, are currently classified into 20 haplotypes belonging to three genera, Polyplacotoma, Trichoplax, and Hoilungia. The latter two comprise two and five clades, respectively. In Trichoplax and Hoilungia, previous studies on six haplotypes belonging to four different clades have shown that their mtDNAs are circular chromosomes of 32-43 kb in size, which encode 12 protein-coding genes, 24 tRNAs, and two rRNAs. These mitochondrial genomes (mitogenomes) also show unique features rarely seen in other metazoans, including open reading frames (ORFs) of unknown function, and group I and II introns. Here, we report seven new mitogenomes, covering the five previously described haplotypes H2, H17, H19, H9, and H11, as well as two new haplotypes, H23 (clade III) and H24 (clade VII). The overall gene content is shared between all placozoan mitochondrial genomes, but genome sizes, gene orders, and several exon-intron boundaries vary among clades. Phylogenomic analyses strongly support a tree topology different from previous 16S rRNA analyses, with clade VI as the sister group to all other Hoilungia clades. We found small inverted repeats in all 13 mitochondrial genomes of the Trichoplax and Hoilungia genera and evaluated their distribution patterns among haplotypes. Because Polyplacotoma mediterranea (H0), the sister to the remaining haplotypes, has a small mitochondrial genome with few small inverted repeats and ORFs, we hypothesized that the proliferation of inverted repeats and ORFs substantially contributed to the observed increase in the size and GC content of the Trichoplax and Hoilungia mitochondrial genomes.}, } @article {pmid33031928, year = {2021}, author = {Rancilhac, L and Irisarri, I and Angelini, C and Arntzen, JW and Babik, W and Bossuyt, F and Künzel, S and Lüddecke, T and Pasmans, F and Sanchez, E and Weisrock, D and Veith, M and Wielstra, B and Steinfartz, S and Hofreiter, M and Philippe, H and Vences, M}, title = {Phylotranscriptomic evidence for pervasive ancient hybridization among Old World salamanders.}, journal = {Molecular phylogenetics and evolution}, volume = {155}, number = {}, pages = {106967}, doi = {10.1016/j.ympev.2020.106967}, pmid = {33031928}, issn = {1095-9513}, mesh = {Animals ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Genome, Mitochondrial ; *Hybridization, Genetic ; Mitochondria/genetics ; *Phylogeny ; Transcriptome/genetics ; Caudata/*classification/*genetics ; }, abstract = {Hybridization can leave genealogical signatures in an organism's genome, originating from the parental lineages and persisting over time. This potentially confounds phylogenetic inference methods that aim to represent evolution as a strictly bifurcating tree. We apply a phylotranscriptomic approach to study the evolutionary history of, and test for inter-lineage introgression in the Salamandridae, a Holarctic salamanders group of interest in studies of toxicity and aposematism, courtship behavior, and molecular evolution. Although the relationships between the 21 currently recognized salamandrid genera have been the subject of numerous molecular phylogenetic studies, some branches have remained controversial and sometimes affected by discordances between mitochondrial vs. nuclear trees. To resolve the phylogeny of this family, and understand the source of mito-nuclear discordance, we generated new transcriptomic (RNAseq) data for 20 salamandrids and used these along with published data, including 28 mitochondrial genomes, to obtain a comprehensive nuclear and mitochondrial perspective on salamandrid evolution. Our final phylotranscriptomic data set included 5455 gene alignments for 40 species representing 17 of the 21 salamandrid genera. Using concatenation and species-tree phylogenetic methods, we find (1) Salamandrina sister to the clade of the "True Salamanders" (consisting of Chioglossa, Mertensiella, Lyciasalamandra, and Salamandra), (2) Ichthyosaura sister to the Near Eastern genera Neurergus and Ommatotriton, (3) Triturus sister to Lissotriton, and (4) Cynops paraphyletic with respect to Paramesotriton and Pachytriton. Combining introgression tests and phylogenetic networks, we find evidence for introgression among taxa within the clades of "Modern Asian Newts" and "Modern European Newts". However, we could not unambiguously identify the number, position, and direction of introgressive events. Combining evidence from nuclear gene analysis with the observed mito-nuclear phylogenetic discordances, we hypothesize a scenario with hybridization and mitochondrial capture among ancestral lineages of (1) Lissotriton into Ichthyosaura and (2) Triturus into Calotriton, plus introgression of nuclear genes from Triturus into Lissotriton. Furthermore, both mitochondrial capture and nuclear introgression may have occurred among lineages assigned to Cynops. More comprehensive genomic data will, in the future, allow testing this against alternative scenarios involving hybridization with other, extinct lineages of newts.}, } @article {pmid33032063, year = {2020}, author = {Chen, C and Meng, Y and Shopan, J and Whelan, J and Hu, Z and Yang, J and Zhang, M}, title = {Identification and characterization of Arabidopsis thaliana mitochondrial F1F0-ATPase inhibitor factor 1.}, journal = {Journal of plant physiology}, volume = {254}, number = {}, pages = {153264}, doi = {10.1016/j.jplph.2020.153264}, pmid = {33032063}, issn = {1618-1328}, mesh = {Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Green Fluorescent Proteins ; Mitochondria/enzymology/metabolism ; Phylogeny ; Proteins/genetics/*metabolism ; Proton-Translocating ATPases/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Alignment ; ATPase Inhibitory Protein ; }, abstract = {Mitochondrial F1F0-ATP synthase (F1F0-ATPase) inhibitor factor 1 (IF1) has been extensively characterized as an endogenous inhibitor that prevents the hydrolysis of adenosine-5'-triphosphate (ATP) by mitochondrial ATPases in mammals and yeasts; however, IF1's functions in plants remain unclear. Here, a comprehensive bioinformatic analysis was performed to identify plant mitochondrial F1F0-ATPase IF1 orthologs. Plant IF1s contain a conserved F1F0-ATPase inhibitory domain, but lack the antiparallel α-helical coiled-coil structure compared with mammalian IF1s. A subcellular localization analysis in Arabidopsis thaliana revealed that AtIF1-green fluorescent protein was present only in mitochondria. Additionally, AtIF1 was widely expressed in diverse organs and intense β-glucuronidase staining was observed in reproductive tissues and germinating seeds. Compared with the wild-type and p35S:AtIF1-if1 etiolated seedlings, the ATP/ADP ratio was significantly lower in the AtIF1 T-DNA knockout seedlings (if1 mutant) growing under dark conditions, suggesting that AtIF1 can influence the energy state of cells. A significant reduction in seed yield and strong growth retardation under dark conditions were observed in the if1 mutant line. Furthermore, if1 plants exhibited a substantially decreased sensitivity to abscisic acid. Thus, the A. thaliana mitochondrial IF1, which is a conserved F1F0-ATPase inhibitor, is crucial for plant growth and responses to abscisic acid.}, } @article {pmid33035389, year = {2021}, author = {Novo, N and Ferreira, P and Medina, M}, title = {The apoptosis-inducing factor family: Moonlighting proteins in the crosstalk between mitochondria and nuclei.}, journal = {IUBMB life}, volume = {73}, number = {3}, pages = {568-581}, doi = {10.1002/iub.2390}, pmid = {33035389}, issn = {1521-6551}, mesh = {Animals ; Apoptosis ; Apoptosis Inducing Factor/*chemistry/genetics/*metabolism ; Apoptosis Regulatory Proteins/genetics/metabolism ; Cell Death ; Cell Nucleus/*metabolism ; Humans ; Mitochondria/*metabolism ; Mitochondrial Diseases/genetics/*metabolism/pathology ; Mitochondrial Proteins/genetics/metabolism ; Multigene Family ; Neoplasms/metabolism/pathology ; Phylogeny ; }, abstract = {In Homo sapiens, the apoptosis-inducing factor (AIF) family is represented by three different proteins, known as AIF, AMID and AIFL, that have in common the mitochondrial localisation in healthy cells, the presence of FAD- and NADH-dependent domains involved in an -albeit yet not well understood- oxidoreductase function and their capability to induce programmed cell death. AIF is the best characterised family member, while the information about AMID and AIFL is much scarcer. Nonetheless, available data support different roles as well as mechanisms of action of their particular apoptogenic and redox domains regarding both pro-apoptotic and anti-apoptotic activities. Moreover, diverse cellular functions, to date far from fully clarified, are envisaged for the transcripts corresponding to these three proteins. Here, we review the so far available knowledge on the moonlighting human AIF family from their molecular properties to their relevance in health and disease, through the evaluation of their potential cell death and redox functions in their different subcellular locations. This picture emerging from the current knowledge of the AIF family envisages its contribution to regulate signalling and transcription machineries in the crosstalk among mitochondria, the cytoplasm and the nucleus.}, } @article {pmid33036486, year = {2020}, author = {Zhu, Y and Berkowitz, O and Selinski, J and Hartmann, A and Narsai, R and Wang, Y and Mao, P and Whelan, J}, title = {Conserved and Opposite Transcriptome Patterns during Germination in Hordeum vulgare and Arabidopsis thaliana.}, journal = {International journal of molecular sciences}, volume = {21}, number = {19}, pages = {}, pmid = {33036486}, issn = {1422-0067}, support = {CE140100008//Centre of Excellence in Plant Energy Biology, Australian Research Council/ ; DE160101536//Australian Research Council/ ; }, mesh = {Arabidopsis/*genetics ; Computational Biology/methods ; Evolution, Molecular ; *Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Germination/*genetics ; Hordeum/*genetics ; Molecular Sequence Annotation ; Seeds/*genetics/metabolism ; *Transcriptome ; }, abstract = {Seed germination is a critical process for completion of the plant life cycle and for global food production. Comparing the germination transcriptomes of barley (Hordeum vulgare) to Arabidopsis thaliana revealed the overall pattern was conserved in terms of functional gene ontology; however, many oppositely responsive orthologous genes were identified. Conserved processes included a set of approximately 6000 genes that peaked early in germination and were enriched in processes associated with RNA metabolism, e.g., pentatricopeptide repeat (PPR)-containing proteins. Comparison of orthologous genes revealed more than 3000 orthogroups containing almost 4000 genes that displayed similar expression patterns including functions associated with mitochondrial tricarboxylic acid (TCA) cycle, carbohydrate and RNA/DNA metabolism, autophagy, protein modifications, and organellar function. Biochemical and proteomic analyses indicated mitochondrial biogenesis occurred early in germination, but detailed analyses revealed the timing involved in mitochondrial biogenesis may vary between species. More than 1800 orthogroups representing 2000 genes displayed opposite patterns in transcript abundance, representing functions of energy (carbohydrate) metabolism, photosynthesis, protein synthesis and degradation, and gene regulation. Differences in expression of basic-leucine zippers (bZIPs) and Apetala 2 (AP2)/ethylene-responsive element binding proteins (EREBPs) point to differences in regulatory processes at a high level, which provide opportunities to modify processes in order to enhance grain quality, germination, and storage as needed for different uses.}, } @article {pmid33042846, year = {2020}, author = {da Veiga Moreira, J and Schwartz, L and Jolicoeur, M}, title = {Targeting Mitochondrial Singlet Oxygen Dynamics Offers New Perspectives for Effective Metabolic Therapies of Cancer.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {573399}, pmid = {33042846}, issn = {2234-943X}, abstract = {The occurrence of mitochondrial respiration has allowed evolution toward more complex and advanced life forms. However, its dysfunction is now also seen as the most probable cause of one of the biggest scourges in human health, cancer. Conventional cancer treatments such as chemotherapy, which mainly focus on disrupting the cell division process, have shown being effective in the attenuation of various cancers but also showing significant limits as well as serious sides effects. Indeed, the idea that cancer is a metabolic disease with mitochondria as the central site of the pathology is now emerging, and we provide here a review supporting this "novel" hypothesis re-actualizing past century Otto Warburg's thoughts. Our conclusion, while integrating literature, is that mitochondrial activity and, in particular, the activity of cytochrome c oxidase, complex IV of the ETC, plays a fundamental role in the effectiveness or non-effectiveness of chemotherapy, immunotherapy and probably radiotherapy treatments. We therefore propose that cancer cells mitochondrial singlet oxygen ([1]O2) dynamics may be an efficient target for metabolic therapy development.}, } @article {pmid33056243, year = {2020}, author = {GÓmez-Zurita, J and Platania, L and Cardoso, A}, title = {A new species of the genus Tricholapita nom. nov. and stat. nov. (Coleoptera: Chrysomelidae, Eumolpinae) from New Caledonia.}, journal = {Zootaxa}, volume = {4858}, number = {1}, pages = {zootaxa.4858.1.5}, doi = {10.11646/zootaxa.4858.1.5}, pmid = {33056243}, issn = {1175-5334}, mesh = {Animals ; *Coleoptera ; Mitochondria ; New Caledonia ; Phylogeny ; }, abstract = {Tricholapita Gómez-Zurita and Cardoso nom. nov. is proposed as the replacement name for the leaf beetle taxon Lapita Gómez-Zurita and Cardoso, 2014, nec Bickel, 2002. Moreover, the rank of Tricholapita stat. nov. is elevated from subgenus of Taophila Heller, 1916 to generic status. Phylogenetic evidence based on mtDNA rrnS sequences and diagnostic morphological characters reveals a new species from the south of Grande Terre in New Caledonia, which is described: Tricholapita reidi sp. nov.}, } @article {pmid33056981, year = {2020}, author = {Brady, SW and Liu, Y and Ma, X and Gout, AM and Hagiwara, K and Zhou, X and Wang, J and Macias, M and Chen, X and Easton, J and Mulder, HL and Rusch, M and Wang, L and Nakitandwe, J and Lei, S and Davis, EM and Naranjo, A and Cheng, C and Maris, JM and Downing, JR and Cheung, NV and Hogarty, MD and Dyer, MA and Zhang, J}, title = {Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {5183}, pmid = {33056981}, issn = {2041-1723}, support = {R01 CA216391/CA/NCI NIH HHS/United States ; R35 CA220500/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA021765/CA/NCI NIH HHS/United States ; U10 CA180899/CA/NCI NIH HHS/United States ; U10 CA180886/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Age Factors ; Anaplastic Lymphoma Kinase/genetics ; Biomarkers, Tumor/*genetics ; Child ; Child, Preschool ; Cohort Studies ; DNA Copy Number Variations ; DNA Mutational Analysis ; Datasets as Topic ; Electron Transport/genetics ; Exome/genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Infant ; Infant, Newborn ; Male ; Mitochondrial Ribosomes ; Mutation ; Neuroblastoma/*genetics/pathology ; Receptor, Fibroblast Growth Factor, Type 1/genetics ; Ribosomal Proteins/genetics ; Transcriptome/genetics ; Whole Genome Sequencing ; Young Adult ; }, abstract = {Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. To better understand neuroblastoma pathogenesis, here we analyze whole-genome, whole-exome and/or transcriptome data from 702 neuroblastoma samples. Forty percent of samples harbor at least one recurrent driver gene alteration and most aberrations, including MYCN, ATRX, and TERT alterations, differ in frequency by age. MYCN alterations occur at median 2.3 years of age, TERT at 3.8 years, and ATRX at 5.6 years. COSMIC mutational signature 18, previously associated with reactive oxygen species, is the most common cause of driver point mutations in neuroblastoma, including most ALK and Ras-activating variants. Signature 18 appears early and is continuous throughout disease evolution. Signature 18 is enriched in neuroblastomas with MYCN amplification, 17q gain, and increased expression of mitochondrial ribosome and electron transport-associated genes. Recurrent FGFR1 variants in six patients, and ALK N-terminal structural alterations in five samples, identify additional patients potentially amenable to precision therapy.}, } @article {pmid33058388, year = {2021}, author = {Lima-Posada, I and Bobadilla, NA}, title = {Understanding the opposite effects of sex hormones in mediating renal injury.}, journal = {Nephrology (Carlton, Vic.)}, volume = {26}, number = {3}, pages = {217-226}, doi = {10.1111/nep.13806}, pmid = {33058388}, issn = {1440-1797}, support = {235855//Consejo Nacional de Ciencia y Tecnología/ ; 235964//Consejo Nacional de Ciencia y Tecnología/ ; 272390//Consejo Nacional de Ciencia y Tecnología/ ; A1-S-8715//Consejo Nacional de Ciencia y Tecnología/ ; IN223915//Universidad Nacional Autónoma de México/ ; IN201619//Universidad Nacional Autónoma de México/ ; }, mesh = {Age Factors ; *Disease Progression ; Estrogens/*physiology ; Humans ; Incidence ; *Renal Insufficiency, Chronic/epidemiology/metabolism/physiopathology ; *Sex Factors ; Testosterone/*physiology ; }, abstract = {According to epidemiological studies, chronic kidney disease (CKD) affects more women than men, but the incidence of end-stage renal disease is higher in men than in women. However, most of these studies have not considered the incidence of CKD in women of reproductive or post-menopausal age, and even fewer with hormone replacement therapy. Some meta-analyses have reported an exacerbated progression of CKD in men compared with women. Consequently, in most of the experimental models of renal injury, men of reproductive age exhibit more abnormalities in renal function and structure that lead to greater progression to CKD than women, which suggests that these differences are mediated by sex hormones rather than by other factors. This review intends to show the mechanisms regulated by oestrogen or testosterone that may explain the different risks and evolution of renal diseases between men and women. Regardless of the initial cause of kidney disease, sex hormones have been implicated in modulating vascular tone, oxidative stress, inflammation and apoptosis. Finally, our previous study highlights the mechanisms by which the transition from acute kidney injury to CKD does not occur in female rats as commonly as it does in male rats. This review not only identifies sex differences in several kidney diseases but also supports potential therapeutic opportunities to reduce or prevent the progression of CKD and highlights the importance of considering sex differences in the design of any clinical study.}, } @article {pmid33058877, year = {2020}, author = {Patel, BV and Yao, F and Howenstine, A and Takenaka, R and Hyatt, JA and Sears, KE and Shewchuk, BM}, title = {Emergent Coordination of the CHKB and CPT1B Genes in Eutherian Mammals: Implications for the Origin of Brown Adipose Tissue.}, journal = {Journal of molecular biology}, volume = {432}, number = {23}, pages = {6127-6145}, pmid = {33058877}, issn = {1089-8638}, support = {R21 OD022988/OD/NIH HHS/United States ; }, mesh = {3-Hydroxyacyl CoA Dehydrogenases/genetics ; Acetyl-CoA C-Acyltransferase/genetics ; Adipose Tissue, Brown/*metabolism ; Animals ; *Biological Evolution ; Carbon-Carbon Double Bond Isomerases/genetics ; Carnitine O-Palmitoyltransferase/*genetics ; Choline Kinase/*genetics ; Enoyl-CoA Hydratase/genetics ; Eutheria/genetics/metabolism ; Female ; Mammals/genetics/metabolism ; Mitochondria/genetics/metabolism ; Phylogeny ; Pregnancy ; Racemases and Epimerases/genetics ; }, abstract = {Mitochondrial fatty acid oxidation (FAO) contributes to the proton motive force that drives ATP synthesis in many mammalian tissues. In eutherian (placental) mammals, brown adipose tissue (BAT) can also dissipate this proton gradient through uncoupling protein 1 (UCP1) to generate heat, but the evolutionary events underlying the emergence of BAT are unknown. An essential step in FAO is the transport of cytoplasmic long chain acyl-coenzyme A (acyl-CoA) into the mitochondrial matrix, which requires the action of carnitine palmitoyltransferase 1B (CPT1B) in striated muscle and BAT. In eutherians, the CPT1B gene is closely linked to the choline kinase beta (CHKB) gene, which is transcribed from the same DNA strand and terminates just upstream of CPT1B. CHKB is a rate-limiting enzyme in the synthesis of phosphatidylcholine (PC), a predominant mitochondrial membrane phospholipid, suggesting that the coordinated expression of CHKB and CPT1B may cooperatively enhance mitochondrial FAO. The present findings show that transcription of the eutherian CHKB and CPT1B genes is linked within a unitary epigenetic domain targeted to the CHKB gene, and that that this regulatory linkage appears to have resulted from an intergenic deletion in eutherians that significantly altered the distribution of CHKB and CPT1B expression. Informed by the timing of this event relative to the emergence of BAT, the phylogeny of CHKB-CPT1B synteny, and the insufficiency of UCP1 to account for eutherian BAT, these data support a mechanism for the emergence of BAT based on the acquisition of a novel capacity for adipocyte FAO in a background of extant UCP1.}, } @article {pmid33059067, year = {2021}, author = {Bocalini, F and Bolívar-Leguizamón, SD and Silveira, LF and Bravo, GA}, title = {Comparative phylogeographic and demographic analyses reveal a congruent pattern of sister relationships between bird populations of the northern and south-central Atlantic Forest.}, journal = {Molecular phylogenetics and evolution}, volume = {154}, number = {}, pages = {106973}, doi = {10.1016/j.ympev.2020.106973}, pmid = {33059067}, issn = {1095-9513}, mesh = {Animals ; Brazil ; Demography ; *Forests ; Gene Flow ; Genetic Variation ; Genetics, Population ; Haplotypes/genetics ; Mitochondria/genetics ; Passeriformes/*classification/genetics ; Phylogeny ; *Phylogeography ; Polymorphism, Single Nucleotide/genetics ; Species Specificity ; }, abstract = {The Pernambuco Center of Endemism (PCE) is the northernmost strip of the Atlantic Forest (AF). Biogeographic affinities among avifaunas in the PCE, the southern-central Atlantic Forest (SCAF), and Amazonia (AM) have not been studied comprehensively, and current patterns of genetic diversity in the PCE remain unclear. The interplay between species' ecological attributes and historical processes, such as Pleistocene climate fluctuations or the appearance of rivers, may have affected population genetic structures in the PCE. Moreover, the role of past connections between the PCE and AM and the elevational distribution of species in assembling the PCE avifauna remain untested. Here, we investigated the biogeographic history of seven taxa endemic to the PCE within a comparative phylogeographic framework based on a mean of 3,618 independent single nucleotide polymorphisms (SNPs) extracted from flanking regions of ultraconserved elements (UCEs) and one mitochondrial gene. We found that PCE populations were more closely related to SCAF populations than they were to those in AM, regardless of their elevational range, with divergence times placed during the Mid-Pleistocene. These splits were consistent with a pattern of allopatric divergence with gene flow until the upper Pleistocene and no signal of rapid changes in population sizes. Our results support the existence of a Pleistocene refugium driving current genetic diversity in the PCE, thereby rejecting the role of the São Francisco River as a primary barrier for population divergence. Additionally, we found that connections with Amazonia also played a significant role in assembling the PCE avifauna through subsequent migration events.}, } @article {pmid33059071, year = {2021}, author = {van der Merwe, PW and Cotterill, FPD and Kandziora, M and Watters, BR and Nagy, B and Genade, T and Flügel, TJ and Svendsen, DS and Bellstedt, DU}, title = {Genomic fingerprints of palaeogeographic history: The tempo and mode of rift tectonics across tropical Africa has shaped the diversification of the killifish genus Nothobranchius (Teleostei: Cyprinodontiformes).}, journal = {Molecular phylogenetics and evolution}, volume = {158}, number = {}, pages = {106988}, doi = {10.1016/j.ympev.2020.106988}, pmid = {33059071}, issn = {1095-9513}, mesh = {Africa ; Animals ; Cell Nucleus/genetics ; DNA/chemistry/isolation & purification/metabolism ; Electron Transport Complex IV/classification/genetics ; *Genome ; Glycosyltransferases/classification/genetics ; Killifishes/*classification/genetics ; Mitochondria/genetics ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; }, abstract = {This paper reports a phylogeny of the African killifishes (Genus Nothobranchius, Order Cyprinodontiformes) informed by five genetic markers (three nuclear, two mitochondrial) of 80 taxa (seven undescribed and 73 of the 92 recognized species). These short-lived annual fishes occupy seasonally wet habitats in central and eastern Africa, and their distribution coincides largely with the East African Rift System (EARS). The fossil dates of sister clades used to constrain a chronometric tree of all sampled Nothobranchius recovered the origin of the genus at ~13.27 Mya. It was followed by the radiations of six principal clades through the Neogene. An ancestral area estimation tested competing biogeographical hypotheses to constrain the ancestral origin of the genus to the Nilo-Sudan Ecoregion, which seeded a mid-Miocene dispersal event into the Coastal ecoregion, followed closely (~10 Mya) by dispersals southward across the Mozambique coastal plain into the Limpopo Ecoregion. Extending westwards across the Tanzanian plateau, a pulse of radiations through the Pliocene were associated with dispersals and fragmentation of wetlands across the Kalahari and Uganda Ecoregions. We interpret this congruence of drainage rearrangements with dispersals and cladogenic events of Nothobranchius to reflect congruent responses to recurrent uplift and rifting. The coevolution of these freshwater fishes and wetlands is attributed to ultimate control by tectonics, as the EARS extended southwards during the Neogene. Geobiological consilience of the combined evidence supports a tectonic hypothesis for the evolution of Nothobranchius.}, } @article {pmid33070735, year = {2020}, author = {Friesen, CR and Noble, DWA and Olsson, M}, title = {The role of oxidative stress in postcopulatory selection.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {375}, number = {1813}, pages = {20200065}, pmid = {33070735}, issn = {1471-2970}, mesh = {Adenosine Triphosphate/metabolism ; Animals ; *Biological Evolution ; Humans ; Male ; *Oxidative Stress ; Reactive Oxygen Species/metabolism ; Reproduction/*physiology ; Spermatozoa/*physiology ; }, abstract = {Two decades ago, von Schantz et al. (von Schantz T, Bensch S, Grahn M, Hasselquist D, Wittzell H. 1999 Good genes, oxidative stress and condition-dependent sexual signals. Proc. R. Soc. B 266, 1-12. (doi:10.1098/rspb.1999.0597)) united oxidative stress (OS) biology with sexual selection and life-history theory. This set the scene for analysis of how evolutionary trade-offs may be mediated by the increase in reactive molecules resulting from metabolic processes at reproduction. Despite 30 years of research on OS effects on infertility in humans, one research area that has been left behind in this integration of evolution and OS biology is postcopulatory sexual selection-this integration is long overdue. We review the basic mechanisms in OS biology, why mitochondria are the primary source of ROS and ATP production during oxidative metabolism, and why sperm, and its performance, is uniquely susceptible to OS. We also review how postcopulatory processes select for antioxidation in seminal fluids to counter OS and the implications of the net outcome of these processes on sperm damage, sperm storage, and female and oocyte manipulation of sperm metabolism and repair of DNA to enhance offspring fitness. This article is part of the theme issue 'Fifty years of sperm competition'.}, } @article {pmid33072737, year = {2020}, author = {Teulière, J and Bernard, G and Bapteste, E}, title = {The Distribution of Genes Associated With Regulated Cell Death Is Decoupled From the Mitochondrial Phenotypes Within Unicellular Eukaryotic Hosts.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {536389}, pmid = {33072737}, issn = {2296-634X}, abstract = {Genetically regulated cell death (RCD) occurs in all domains of life. In eukaryotes, the evolutionary origin of the mitochondrion and of certain forms of RCD, in particular apoptosis, are thought to coincide, suggesting a central general role for mitochondria in cellular suicide. We tested this mitochondrial centrality hypothesis across a dataset of 67 species of protists, presenting 5 classes of mitochondrial phenotypes, including functional mitochondria, metabolically diversified mitochondria, functionally reduced mitochondria (Mitochondrion Related Organelle or MRO) and even complete absence of mitochondria. We investigated the distribution of genes associated with various forms of RCD. No homologs for described mammalian regulators of regulated necrosis could be identified in our set of 67 unicellular taxa. Protists with MRO and the secondarily a mitochondriate Monocercomonoides exilis display heterogeneous reductions of apoptosis gene sets with respect to typical mitochondriate protists. Remarkably, despite the total lack of mitochondria in M. exilis, apoptosis-associated genes could still be identified. These same species of protists with MRO and M. exilis harbored non-reduced autophagic cell death gene sets. Moreover, transiently multicellular protist taxa appeared enriched in apoptotic and autophagy associated genes compared to free-living protists. This analysis suggests that genes associated with apoptosis in animals and the presence of the mitochondria are significant yet non-essential biological components for RCD in protists. More generally, our results support the hypothesis of a selection for RCD, including both apoptosis and autophagy, as a developmental mechanism linked to multicellularity.}, } @article {pmid33073395, year = {2020}, author = {Kang, JS and Zhang, HR and Wang, YR and Liang, SQ and Mao, ZY and Zhang, XC and Xiang, QP}, title = {Distinctive evolutionary pattern of organelle genomes linked to the nuclear genome in Selaginellaceae.}, journal = {The Plant journal : for cell and molecular biology}, volume = {104}, number = {6}, pages = {1657-1672}, doi = {10.1111/tpj.15028}, pmid = {33073395}, issn = {1365-313X}, mesh = {Evolution, Molecular ; Gene Rearrangement/genetics ; Genes, Plant/genetics ; Genome, Mitochondrial/genetics ; Genome, Plant/*genetics ; Genome, Plastid/*genetics ; Huperzia/genetics ; Organelles/genetics ; Recombination, Genetic/genetics ; Selaginellaceae/*genetics ; }, abstract = {Plastids and mitochondria are endosymbiotic organelles that store genetic information. The genomes of these organelles generally exhibit contrasting patterns regarding genome architecture and genetic content. However, they have similar genetic features in Selaginellaceae, and little is known about what causes parallel evolution. Here, we document the multipartite plastid genomes (plastomes) and the highly divergent mitochondrial genomes (mitogenomes) from spikemoss obtained by combining short- and long-reads. The 188-kb multipartite plastome has three ribosomal operon copies in the master genomic conformation, creating the alternative subgenomic conformation composed of 110- and 78-kb subgenomes. The long-read data indicated that the two different genomic conformations were present in almost equal proportions in the plastomes of Selaginella nipponica. The mitogenome of S. nipponica was assembled into 27 contigs with a total size of 110 kb. All contigs contained directly arranged repeats at both ends, which introduced multiple conformations. Our results showed that plastomes and mitogenomes share high tRNA losses, GC-biased nucleotides, elevated substitution rates and complicated organization. The exploration of nuclear-encoded organelle DNA replication, recombination and repair proteins indicated that, several single-targeted proteins, particularly plastid-targeted recombinase A1, have been lost in Selaginellaceae; conversely, the dual-targeted proteins remain intact. According to the reported function of recombinase A1, we propose that the plastomes of spikemoss often fail to pair homologous sequences during recombination, and the dual-targeted proteins play a key role in the convergent genetic features of plastomes and mitogenomes. Our results provide a distinctive evolutionary pattern of the organelle genomes in Selaginellaceae and evidence of their convergent evolution.}, } @article {pmid33076444, year = {2020}, author = {Qu, C and Wang, L and Zhao, Y and Liu, C}, title = {Molecular Evolution of Maize Ascorbate Peroxidase Genes and Their Functional Divergence.}, journal = {Genes}, volume = {11}, number = {10}, pages = {}, pmid = {33076444}, issn = {2073-4425}, mesh = {Ascorbate Peroxidases/*genetics/metabolism ; *Evolution, Molecular ; *Gene Expression Regulation, Plant ; Multigene Family ; Phylogeny ; Plant Proteins/*genetics/*metabolism ; Zea mays/*enzymology/*genetics/growth & development ; }, abstract = {Ascorbate peroxidase (APX) is an important antioxidant enzyme. APXs in maize are encoded by multiple genes and exist as isoenzymes. The evolutionary history and functional divergence of the maize APX gene family were analyzed through comparative genomic and experimental data on the Internet in this paper. APX genes in higher plants were divided into classes A, B, and C. Each type of APX gene in angiosperms only had one ancestral gene that was duplicated along with the genome duplication or local (or tandem) duplication of the angiosperm. A total of eight genes were retained in maize and named APXa1, APXa2, APXa3, APXb1, APXb2, APXc1.1, APXc1.2, and APXc2. The APX genes of class A were located in the chloroplasts or mitochondria, and the class B and C genes were localized in the peroxisomes and cytoplasm, respectively. The expression patterns of eight APXs were different in vegetative and reproductive organs at different growth and development stages. APXa1 and APXb1 of maize may participate in the antioxidant metabolism of vegetative organs under normal conditions. APXa2, APXb2, APXc1.1, and APXc1.2 may be involved in the stress response, and APXb2 and APXc2 may participate in the senescence response. These results provide a basis for cultivating high-yield and resistant maize varieties.}, } @article {pmid33086570, year = {2020}, author = {Piłsyk, S and Mieczkowski, A and Golan, MP and Wawrzyniak, A and Kruszewska, JS}, title = {Internalization of the Aspergillus nidulans AstA Transporter into Mitochondria Depends on Growth Conditions, and Affects ATP Levels and Sulfite Oxidase Activity.}, journal = {International journal of molecular sciences}, volume = {21}, number = {20}, pages = {}, pmid = {33086570}, issn = {1422-0067}, mesh = {Adenosine Triphosphate/*metabolism ; Aspergillus nidulans/*growth & development/*metabolism ; Endocytosis ; Endophytes/metabolism ; Fungal Proteins/*metabolism ; Green Fluorescent Proteins/metabolism ; Mitochondria/*metabolism ; Models, Biological ; Oxidation-Reduction ; Phenotype ; Phylogeny ; Sulfite Oxidase/*metabolism ; Sulfur/metabolism ; }, abstract = {The astA gene encoding an alternative sulfate transporter was originally cloned from the genome of the Japanese Aspergillus nidulans isolate as a suppressor of sulfate permease-deficient strains. Expression of the astA gene is under the control of the sulfur metabolite repression system. The encoded protein transports sulfate across the cell membrane. In this study we show that AstA, having orthologs in numerous pathogenic or endophytic fungi, has a second function and, depending on growth conditions, can be translocated into mitochondria. This effect is especially pronounced when an astA-overexpressing strain grows on solid medium at 37 °C. AstA is also recruited to the mitochondria in the presence of mitochondria-affecting compounds such as menadione or antimycin A, which are also detrimental to the growth of the astA-overexpressing strain. Disruption of the Hsp70-Porin1 mitochondrial import system either by methylene blue, an Hsp70 inhibitor, or by deletion of the porin1-encoding gene abolishes AstA translocation into the mitochondria. Furthermore, we observed altered ATP levels and sulfite oxidase activity in the astA-overexpressing strain in a manner dependent on sulfur sources. The presented data indicate that AstA is also involved in the mitochondrial sulfur metabolism in some fungi, and thereby indirectly manages redox potential and energy state.}, } @article {pmid33093463, year = {2020}, author = {Baltazar-Soares, M and Klein, JD and Correia, SM and Reischig, T and Taxonera, A and Roque, SM and Dos Passos, L and Durão, J and Lomba, JP and Dinis, H and Cameron, SJK and Stiebens, VA and Eizaguirre, C}, title = {Distribution of genetic diversity reveals colonization patterns and philopatry of the loggerhead sea turtles across geographic scales.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {18001}, pmid = {33093463}, issn = {2045-2322}, mesh = {Animals ; *Biological Evolution ; Brazil ; Cabo Verde ; DNA, Mitochondrial/analysis/*genetics ; *Gene Flow ; *Genetic Variation ; *Genetics, Population ; Mediterranean Sea ; Mexico ; Mitochondria/*genetics ; Panama ; Turtles/*genetics ; United States ; }, abstract = {Understanding the processes that underlie the current distribution of genetic diversity in endangered species is a goal of modern conservation biology. Specifically, the role of colonization and dispersal events throughout a species' evolutionary history often remains elusive. The loggerhead sea turtle (Caretta caretta) faces multiple conservation challenges due to its migratory nature and philopatric behaviour. Here, using 4207 mtDNA sequences, we analysed the colonisation patterns and distribution of genetic diversity within a major ocean basin (the Atlantic), a regional rookery (Cabo Verde Archipelago) and a local island (Island of Boa Vista, Cabo Verde). Data analysis using hypothesis-driven population genetic models suggests the colonization of the Atlantic has occurred in two distinct waves, each corresponding to a major mtDNA lineage. We propose the oldest lineage entered the basin via the isthmus of Panama and sequentially established aggregations in Brazil, Cabo Verde and in the area of USA and Mexico. The second lineage entered the Atlantic via the Cape of Good Hope, establishing colonies in the Mediterranean Sea, and from then on, re-colonized the already existing rookeries of the Atlantic. At the Cabo Verde level, we reveal an asymmetric gene flow maintaining links across island-specific nesting groups, despite significant genetic structure. This structure stems from female philopatric behaviours, which could further be detected by weak but significant differentiation amongst beaches separated by only a few kilometres on the island of Boa Vista. Exploring biogeographic processes at diverse geographic scales improves our understanding of the complex evolutionary history of highly migratory philopatric species. Unveiling the past facilitates the design of conservation programmes targeting the right management scale to maintain a species' evolutionary potential.}, } @article {pmid33096232, year = {2021}, author = {van der Mescht, L and Matthee, S and Matthee, CA}, title = {New taxonomic and evolutionary insights relevant to the cat flea, Ctenocephalides felis: A geographic perspective.}, journal = {Molecular phylogenetics and evolution}, volume = {155}, number = {}, pages = {106990}, doi = {10.1016/j.ympev.2020.106990}, pmid = {33096232}, issn = {1095-9513}, mesh = {Africa, Southern ; Animals ; Bayes Theorem ; *Biological Evolution ; Body Size ; Cats/*parasitology ; Ctenocephalides/*classification/genetics ; Electron Transport Complex IV/genetics ; Female ; *Geography ; Haplotypes/genetics ; Head/anatomy & histology ; Male ; Mitochondria/genetics ; Phylogeny ; Principal Component Analysis ; Species Specificity ; }, abstract = {The cat flea, Ctenocephalides felis, is an obligate haematophagous ectoparasite of wildlife and domestic cats and dogs worldwide. Since cat fleas can affect the health of humans and their pets, an uncertain taxonomy of this taxon can greatly inhibit pest and disease management. To address the evolution and taxonomy of the cat flea, we set out to determine 1) how many genetically distinct taxa exist, 2) whether there is morphological support for the genetically distinct taxa, and 3) the role of host range and paleoclimatic events in speciation. We collected a total of 3352 fleas sampled from 576 domestic cats and dogs as well as 10 wildlife species across 30 localities in South Africa. A total of three flea genera, five species, and three of the currently recognized cat flea subspecies, C. f. damarensis, C. f. strongylus and C. f. felis were obtained. Geometric morphometric analyses on head shape were performed on 68 female and 107 male cat flea individuals. Principal component analysis demonstrated large overlap in head shape variation between C. f. strongylus and C. f. felis, rendering this character not useful for phylogenetic inferences. DNA was extracted from 188 Ctenocephalides spp. and mitochondrial COII and nuclear EF1-α sequences were generated. Bayesian and Maximum Likelihood analyses as well as a TCS parsimony haplotype network of the mitochondrial DNA confirmed the presence of three well supported monophyletic clades. These assemblages did not fully corroborate the existence of the three C. felis subspecies. A single well-supported molecular clade included only C. f. damarensis morphotypes that were mostly collected from wildlife. The recognition of this subspecies as a distinct taxon was further corroborated by sequence distances and also the number of plantar spiniform bristles on fore-tarsi V in males. Despite the overall lack of support for the recognition of C. f. damarensis and C. f. strongylus, a geographic trend was visible whereby one genetic lineage corresponded to the western dryer hot subregion, whereas the other was found throughout the region. Bayesian dating suggested that these two clades diverged during the early Pliocene (4.18 mya), a date that corresponds well with the establishment of a dry hot climate in the west of southern Africa. If so, the off-host environment, particularly temperature and humidity, are important factors to consider in the evolution of the cat flea. The present study rejects recent assertions that the three cat flea subspecies are valid entities and rather point to a situation where more sampling is required before the taxonomic status of C. f. damarensis can be resolved.}, } @article {pmid33106602, year = {2021}, author = {Vosseberg, J and van Hooff, JJE and Marcet-Houben, M and van Vlimmeren, A and van Wijk, LM and Gabaldón, T and Snel, B}, title = {Timing the origin of eukaryotic cellular complexity with ancient duplications.}, journal = {Nature ecology & evolution}, volume = {5}, number = {1}, pages = {92-100}, pmid = {33106602}, issn = {2397-334X}, support = {724173/ERC_/European Research Council/International ; }, mesh = {Archaea/genetics ; *Biological Evolution ; Eukaryota/genetics ; *Eukaryotic Cells ; Humans ; Phylogeny ; }, abstract = {Eukaryogenesis is one of the most enigmatic evolutionary transitions, during which simple prokaryotic cells gave rise to complex eukaryotic cells. While evolutionary intermediates are lacking, gene duplications provide information on the order of events by which eukaryotes originated. Here we use a phylogenomics approach to reconstruct successive steps during eukaryogenesis. We find that gene duplications roughly doubled the proto-eukaryotic gene repertoire, with families inherited from the Asgard archaea-related host being duplicated most. By relatively timing events using phylogenetic distances, we inferred that duplications in cytoskeletal and membrane-trafficking families were among the earliest events, whereas most other families expanded predominantly after mitochondrial endosymbiosis. Altogether, we infer that the host that engulfed the proto-mitochondrion had some eukaryote-like complexity, which drastically increased upon mitochondrial acquisition. This scenario bridges the signs of complexity observed in Asgard archaeal genomes to the proposed role of mitochondria in triggering eukaryogenesis.}, } @article {pmid33108945, year = {2022}, author = {Fadhil, IA and Al-Shuhaib, MBS}, title = {Phylogenetic differentiation between Awassi and Hamdani sheep using the mitochondrial 12S rRNA.}, journal = {Animal biotechnology}, volume = {33}, number = {5}, pages = {801-809}, doi = {10.1080/10495398.2020.1837146}, pmid = {33108945}, issn = {1532-2378}, mesh = {Animals ; DNA, Mitochondrial/genetics ; Genetic Markers ; *Genetic Variation/genetics ; Haplotypes/genetics ; Phylogeny ; *RNA, Ribosomal/genetics ; Sheep/genetics ; }, abstract = {This study was conducted to assess the role of the mitochondrial 12S rRNA variations in the phylogenetic discrimination between two Iraqi breeds of sheep that differ in geographical distribution. A total of 122 animals (68 Awassi and 54 Hamdani) were included in the study. Direct sequencing of amplicons followed by the construction of a median-joining network and several trees were performed to identify the possible phylogenetic differences between both involved breeds. Genetic diversity, relative frequencies, and analysis of molecular variance (AMOVA) were performed to assess the genetic correlation between both populations. The median-joining network and minimized tree values showed that all observed haplotypes were separated into two groups according to their breed. Comprehensive phylogenetic data revealed only one Asian ancestor for all observed haplotypes. As indicated by AMOVA, the observed diversity was mostly due to between-population variation (1.24836%), while within-population variation (0.91221%) accounted for much less. The currently investigated rRNA amplicons exhibited different mitochondrial manifestations between Awassi and Hamdani breeds. Due to the ability of these 12S rRNA amplicons to mimic the geographical diversity for the currently investigated breeds, it is highly recommended to be used as potent mitochondrial genetic markers among broader ovine sequences.}, } @article {pmid33113229, year = {2021}, author = {Hartmann, FE and Duhamel, M and Carpentier, F and Hood, ME and Foulongne-Oriol, M and Silar, P and Malagnac, F and Grognet, P and Giraud, T}, title = {Recombination suppression and evolutionary strata around mating-type loci in fungi: documenting patterns and understanding evolutionary and mechanistic causes.}, journal = {The New phytologist}, volume = {229}, number = {5}, pages = {2470-2491}, pmid = {33113229}, issn = {1469-8137}, support = {R15 GM119092/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; Fungi/genetics ; *Genes, Mating Type, Fungal/genetics ; Recombination, Genetic/genetics ; Sex Chromosomes ; }, abstract = {Genomic regions determining sexual compatibility often display recombination suppression, as occurs in sex chromosomes, plant self-incompatibility loci and fungal mating-type loci. Regions lacking recombination can extend beyond the genes determining sexes or mating types, by several successive steps of recombination suppression. Here we review the evidence for recombination suppression around mating-type loci in fungi, sometimes encompassing vast regions of the mating-type chromosomes. The suppression of recombination at mating-type loci in fungi has long been recognized and maintains the multiallelic combinations required for correct compatibility determination. We review more recent evidence for expansions of recombination suppression beyond mating-type genes in fungi ('evolutionary strata'), which have been little studied and may be more pervasive than commonly thought. We discuss testable hypotheses for the ultimate (evolutionary) and proximate (mechanistic) causes for such expansions of recombination suppression, including (1) antagonistic selection, (2) association of additional functions to mating-type, such as uniparental mitochondria inheritance, (3) accumulation in the margin of nonrecombining regions of various factors, including deleterious mutations or transposable elements resulting from relaxed selection, or neutral rearrangements resulting from genetic drift. The study of recombination suppression in fungi could thus contribute to our understanding of recombination suppression expansion across a broader range of organisms.}, } @article {pmid33124163, year = {2021}, author = {Kelley, JL and Desvignes, T and McGowan, KL and Perez, M and Rodriguez, LA and Brown, AP and Culumber, Z and Tobler, M}, title = {microRNA expression variation as a potential molecular mechanism contributing to adaptation to hydrogen sulphide.}, journal = {Journal of evolutionary biology}, volume = {34}, number = {6}, pages = {977-988}, doi = {10.1111/jeb.13727}, pmid = {33124163}, issn = {1420-9101}, mesh = {*Adaptation, Biological ; Animals ; Biological Evolution ; Female ; Gene Expression Regulation ; Gills/*metabolism ; *Hydrogen Sulfide ; Male ; MicroRNAs/genetics/*metabolism ; Poecilia/genetics/*metabolism ; }, abstract = {microRNAs (miRNAs) are post-transcriptional regulators of gene expression and can play an important role in modulating organismal development and physiology in response to environmental stress. However, the role of miRNAs in mediating adaptation to diverse environments in natural study systems remains largely unexplored. Here, we characterized miRNAs and their expression in Poecilia mexicana, a species of small fish that inhabits both normal streams and extreme environments in the form of springs rich in toxic hydrogen sulphide (H2 S). We found that P. mexicana has a similar number of miRNA genes as other teleosts. In addition, we identified a large population of mature miRNAs that were differentially expressed between locally adapted populations in contrasting habitats, indicating that miRNAs may contribute to P. mexicana adaptation to sulphidic environments. In silico identification of differentially expressed miRNA-mRNA pairs revealed, in the sulphidic environment, the downregulation of miRNAs predicted to target mRNAs involved in sulphide detoxification and cellular homeostasis, which are pathways essential for life in H2 S-rich springs. In addition, we found that predicted targets of upregulated miRNAs act in the mitochondria (16.6% of predicted annotated targets), which is the main site of H2 S toxicity and detoxification, possibly modulating mitochondrial function. Together, the differential regulation of miRNAs between these natural populations suggests that miRNAs may be involved in H2 S adaptation by promoting functions needed for survival and reducing functions affected by H2 S. This study lays the groundwork for further research to directly demonstrate the role of miRNAs in adaptation to H2 S. Overall, this study provides a critical stepping-stone towards a comprehensive understanding of the regulatory mechanisms underlying the adaptive variation in gene expression in a natural system.}, } @article {pmid33124220, year = {2021}, author = {Wang, ZJ and Chen, GJ and Zhang, GJ and Zhou, Q}, title = {Dynamic evolution of transposable elements, demographic history, and gene content of paleognathous birds.}, journal = {Zoological research}, volume = {42}, number = {1}, pages = {51-61}, pmid = {33124220}, issn = {2095-8137}, mesh = {Animals ; *Biological Evolution ; Birds/*genetics ; DNA Transposable Elements/*genetics ; DNA, Mitochondrial/genetics ; Female ; Male ; Multigene Family ; Sex Chromosomes/genetics ; Time Factors ; }, abstract = {Palaeognathae includes ratite and tinamou species that are important for understanding early avian evolution. Here, we analyzed the whole-genome sequences of 15 paleognathous species to infer their demographic histories, which are presently unknown. We found that most species showed a reduction of population size since the beginning of the last glacial period, except for those species distributed in Australasia and in the far south of South America. Different degrees of contraction and expansion of transposable elements (TE) have shaped the paleognathous genome architecture, with a higher transposon removal rate in tinamous than in ratites. One repeat family, AviRTE, likely underwent horizontal transfer from tropical parasites to the ancestor of little and undulated tinamous about 30 million years ago. Our analysis of gene families identified rapid turnover of immune and reproduction-related genes but found no evidence of gene family changes underlying the convergent evolution of flightlessness among ratites. We also found that mitochondrial genes have experienced a faster evolutionary rate in tinamous than in ratites, with the former also showing more degenerated W chromosomes. This result can be explained by the Hill-Robertson interference affecting genetically linked W chromosomes and mitochondria. Overall, we reconstructed the evolutionary history of the Palaeognathae populations, genes, and TEs. Our findings of co-evolution between mitochondria and W chromosomes highlight the key difference in genome evolution between species with ZW sex chromosomes and those with XY sex chromosomes.}, } @article {pmid33124702, year = {2020}, author = {Glare, T and Campbell, M and Biggs, P and Winter, D and Durrant, A and McKinnon, A and Cox, M}, title = {Mitochondrial evolution in the entomopathogenic fungal genus Beauveria.}, journal = {Archives of insect biochemistry and physiology}, volume = {105}, number = {4}, pages = {e21754}, doi = {10.1002/arch.21754}, pmid = {33124702}, issn = {1520-6327}, mesh = {Beauveria/*classification/*genetics ; Evolution, Molecular ; Genome, Fungal ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Species in the fungal genus Beauveria are pathogens of invertebrates and have been commonly used as the active agent in biopesticides. After many decades with few species described, recent molecular approaches to classification have led to over 25 species now delimited. Little attention has been given to the mitochondrial genomes of Beauveria but better understanding may led to insights into the nature of species and evolution in this important genus. In this study, we sequenced the mitochondrial genomes of four new strains belonging to Beauveria bassiana, Beauveria caledonica and Beauveria malawiensis, and compared them to existing mitochondrial sequences of related fungi. The mitochondrial genomes of Beauveria ranged widely from 28,806 to 44,135 base pairs, with intron insertions accounting for most size variation and up to 39% (B. malawiensis) of the mitochondrial length due to introns in genes. Gene order of the common mitochondrial genes did not vary among the Beauveria sequences, but variation was observed in the number of transfer ribonucleic acid genes. Although phylogenetic analysis using whole mitochondrial genomes showed, unsurprisingly, that B. bassiana isolates were the most closely related to each other, mitochondrial codon usage suggested that some B. bassiana isolates were more similar to B. malawiensis and B. caledonica than the other B. bassiana isolates analyzed.}, } @article {pmid33127981, year = {2020}, author = {Zhang, N and Jiang, H and Meng, X and Qian, K and Liu, Y and Song, Q and Stanley, D and Wu, J and Park, Y and Wang, J}, title = {Broad-complex transcription factor mediates opposing hormonal regulation of two phylogenetically distant arginine kinase genes in Tribolium castaneum.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {631}, pmid = {33127981}, issn = {2399-3642}, mesh = {Animals ; Arginine Kinase/*genetics/metabolism ; Cloning, Molecular ; Ecdysterone/metabolism ; Female ; Fertility/genetics ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Enzymologic ; Insect Proteins/*genetics/metabolism ; Juvenile Hormones/metabolism ; Male ; Metamorphosis, Biological/genetics ; Phylogeny ; Pupa/genetics ; Stress, Physiological ; Transcription Factors/*genetics/metabolism ; Tribolium/*genetics/*metabolism ; }, abstract = {The phosphoarginine-arginine kinase shuttle system plays a critical role in maintaining insect cellular energy homeostasis. Insect molting and metamorphosis are coordinated by fluctuations of the ecdysteroid and juvenile hormone. However, the hormonal regulation of insect arginine kinases remain largely elusive. In this report, we comparatively characterized two arginine kinase genes, TcAK1 and TcAK2, in Tribolium castaneum. Functional analysis using RNAi showed that TcAK1 and TcAK2 play similar roles in adult fertility and stress response. TcAK1 was detected in cytoplasm including mitochondria, whereas TcAK2 was detected in cytoplasm excluding mitochondria. Interestingly, TcAK1 expression was negatively regulated by 20-hydroxyecdysone and positively by juvenile hormone, whereas TcAK2 was regulated by the opposite pattern. RNAi, dual-luciferase reporter assays and electrophoretic mobility shift assay further revealed that the opposite hormonal regulation of TcAK1 and TcAK2 was mediated by transcription factor Broad-Complex. Finally, relatively stable AK activities were observed during larval-pupal metamorphosis, which was generally consistent with the constant ATP levels. These results provide new insights into the mechanisms underlying the ATP homeostasis in insects by revealing opposite hormonal regulation of two phylogenetically distant arginine kinase genes.}, } @article {pmid33130297, year = {2021}, author = {Raphalo, EM and Cole, ML and Daniels, SR}, title = {Climatic oscillations during the Mio/Pliocene epochs induced cladogenesis in the terrestrial snail genus Gittenedouardia (Mollusca: Gastropoda: Cerastidae) from South Africa.}, journal = {Molecular phylogenetics and evolution}, volume = {155}, number = {}, pages = {107000}, doi = {10.1016/j.ympev.2020.107000}, pmid = {33130297}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; *Climate ; DNA, Mitochondrial/genetics ; Databases, Genetic ; Electron Transport Complex IV/genetics ; Genetic Speciation ; Genetics, Population ; Geography ; Mitochondria/genetics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Snails/*classification/genetics ; South Africa ; Time Factors ; }, abstract = {In South Africa, the terrestrial snail genus Gittenedouardia is the most species-rich member of the Cerastidae, where it is primarily distributed in the highly fragmented Afrotemperate and Indian Ocean coastal belt (IOCB) forest biomes. Phylogenetic relationships and cladogenetic events within the genus remain unstudied. In this respect, we reconstructed a dated phylogeny for eight Gittenedouardia species, and two populations identified to genus level using a combined mitochondrial (16S rRNA and COI) DNA sequencing dataset analysed using Bayesian inference and Maximum Likelihood framework. Furthermore, we investigated the population genetic substructure of the three widely distributed species (Gittenedouardia spadicea, G. natalensis and G. arenicola) for the COI locus, while also subsampling these species using the nuclear DNA ITS-2 locus. Phylogenetic results based on the combined mtDNA dataset supported the monophyly of Gittenedouardia and revealed three major clades and deep genetic structure among the three widely distributed species. Divergence-time estimates suggest that diversification within Gittenedouardia occurred during the middle Miocene/late Pliocene, a period characterised by a decrease in precipitation and the contraction of the Afrotemperate and IOCB forest biomes. We used two species delimitation methods, (PTP and STACEY) to infer putative species in G. spadicea, G. natalensis and G. arenicola. The two methods recovered a large number of evolutionary distinct units, with minimal consensus in the exact number of lineages. Our findings suggest the presence of undescribed diversity, necessitating the need for taxonomic revisionary work on Gittenedouardia. We discuss the climatic factors which may have contributed to the observed cladogenesis and compare our results with other studies of forest dwelling faunal taxa.}, } @article {pmid33135056, year = {2020}, author = {Ji, J and Day, A}, title = {Construction of a highly error-prone DNA polymerase for developing organelle mutation systems.}, journal = {Nucleic acids research}, volume = {48}, number = {21}, pages = {11868-11879}, pmid = {33135056}, issn = {1362-4962}, mesh = {Amino Acid Sequence ; Bacterial Outer Membrane Proteins/chemistry/*genetics/metabolism ; Binding Sites ; Chloroplasts/*genetics/*metabolism ; Cloning, Molecular ; DNA Polymerase gamma/chemistry/*genetics/metabolism ; DNA Replication ; Escherichia coli/genetics/metabolism ; Gene Expression ; Genetic Vectors/chemistry/metabolism ; Mitochondria/*genetics/metabolism ; Models, Molecular ; Mutation ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; Polymorphism, Single Nucleotide ; Porins/chemistry/*genetics/metabolism ; Protein Binding ; Protein Conformation, alpha-Helical ; Protein Conformation, beta-Strand ; Protein Interaction Domains and Motifs ; Receptors, Virus/chemistry/*genetics/metabolism ; Recombinant Proteins/chemistry/genetics/metabolism ; Selection, Genetic ; Sequence Alignment ; Sequence Homology, Amino Acid ; Nicotiana/classification/*genetics/metabolism ; }, abstract = {A novel family of DNA polymerases replicates organelle genomes in a wide distribution of taxa encompassing plants and protozoans. Making error-prone mutator versions of gamma DNA polymerases revolutionised our understanding of animal mitochondrial genomes but similar advances have not been made for the organelle DNA polymerases present in plant mitochondria and chloroplasts. We tested the fidelities of error prone tobacco organelle DNA polymerases using a novel positive selection method involving replication of the phage lambda cI repressor gene. Unlike gamma DNA polymerases, ablation of 3'-5' exonuclease function resulted in a modest 5-8-fold error rate increase. Combining exonuclease deficiency with a polymerisation domain substitution raised the organelle DNA polymerase error rate by 140-fold relative to the wild type enzyme. This high error rate compares favourably with error-rates of mutator versions of animal gamma DNA polymerases. The error prone organelle DNA polymerase introduced mutations at multiple locations ranging from two to seven sites in half of the mutant cI genes studied. Single base substitutions predominated including frequent A:A (template: dNMP) mispairings. High error rate and semi-dominance to the wild type enzyme in vitro make the error prone organelle DNA polymerase suitable for elevating mutation rates in chloroplasts and mitochondria.}, } @article {pmid33137653, year = {2021}, author = {Ryan, DG and Frezza, C and O'Neill, LA}, title = {TCA cycle signalling and the evolution of eukaryotes.}, journal = {Current opinion in biotechnology}, volume = {68}, number = {}, pages = {72-88}, pmid = {33137653}, issn = {1879-0429}, support = {109443/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; MC_UU_12022/6/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Archaea/genetics ; *Biological Evolution ; *Eukaryota/genetics ; Eukaryotic Cells ; Phylogeny ; Prokaryotic Cells ; Symbiosis ; }, abstract = {A major question remaining in the field of evolutionary biology is how prokaryotic organisms made the leap to complex eukaryotic life. The prevailing theory depicts the origin of eukaryotic cell complexity as emerging from the symbiosis between an α-proteobacterium, the ancestor of present-day mitochondria, and an archaeal host (endosymbiont theory). A primary contribution of mitochondria to eukaryogenesis has been attributed to the mitochondrial genome, which enabled the successful internalisation of bioenergetic membranes and facilitated remarkable genome expansion. It has also been postulated that a key contribution of the archaeal host during eukaryogenesis was in providing 'archaeal histones' that would enable compaction and regulation of an expanded genome. Yet, how the communication between the host and the symbiont evolved is unclear. Here, we propose an evolutionary concept in which mitochondrial TCA cycle signalling was also a crucial player during eukaryogenesis enabling the dynamic control of an expanded genome via regulation of DNA and histone modifications. Furthermore, we discuss how TCA cycle remodelling is a common evolutionary strategy invoked by eukaryotic organisms to coordinate stress responses and gene expression programmes, with a particular focus on the TCA cycle-derived metabolite itaconate.}, } @article {pmid33138913, year = {2020}, author = {Fukuda, T and Ebi, Y and Saigusa, T and Furukawa, K and Yamashita, SI and Inoue, K and Kobayashi, D and Yoshida, Y and Kanki, T}, title = {Atg43 tethers isolation membranes to mitochondria to promote starvation-induced mitophagy in fission yeast.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {33138913}, issn = {2050-084X}, support = {17K07330//Japan Society for the Promotion of Science/International ; 20K06552//Japan Society for the Promotion of Science/International ; 18H04858//Japan Society for the Promotion of Science/International ; 19H05712//Japan Society for the Promotion of Science/International ; 19K22419//Japan Society for the Promotion of Science/International ; 20gm6110013h0003//Japan Agency for Medical Research and Development/International ; }, mesh = {Autophagy ; Autophagy-Related Protein 8 Family/*metabolism ; Autophagy-Related Proteins/*metabolism ; Cytosol/metabolism ; Evolution, Molecular ; Mitochondria/*metabolism ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/*metabolism ; *Mitophagy ; Protein Domains ; Schizosaccharomyces/*metabolism ; Schizosaccharomyces pombe Proteins/*metabolism ; Species Specificity ; Two-Hybrid System Techniques ; }, abstract = {Degradation of mitochondria through mitophagy contributes to the maintenance of mitochondrial function. In this study, we identified that Atg43, a mitochondrial outer membrane protein, serves as a mitophagy receptor in the model organism Schizosaccharomyces pombe to promote the selective degradation of mitochondria. Atg43 contains an Atg8-family-interacting motif essential for mitophagy. Forced recruitment of Atg8 to mitochondria restores mitophagy in Atg43-deficient cells, suggesting that Atg43 tethers expanding isolation membranes to mitochondria. We found that the mitochondrial import factors, including the Mim1-Mim2 complex and Tom70, are crucial for mitophagy. Artificial mitochondrial loading of Atg43 bypasses the requirement of the import factors, suggesting that they contribute to mitophagy through Atg43. Atg43 not only maintains growth ability during starvation but also facilitates vegetative growth through its mitophagy-independent function. Thus, Atg43 is a useful model to study the mechanism and physiological roles, as well as the origin and evolution, of mitophagy in eukaryotes.}, } @article {pmid33139764, year = {2020}, author = {da Silva, AF and Machado, LC and de Paula, MB and da Silva Pessoa Vieira, CJ and de Morais Bronzoni, RV and de Melo Santos, MAV and Wallau, GL}, title = {Culicidae evolutionary history focusing on the Culicinae subfamily based on mitochondrial phylogenomics.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {18823}, pmid = {33139764}, issn = {2045-2322}, mesh = {Animals ; Culicidae/classification/*genetics/pathogenicity ; *Evolution, Molecular ; Genome, Mitochondrial/*genetics ; Mitochondria/*genetics ; Mosquito Vectors ; *Phylogeny ; Species Specificity ; Whole Genome Sequencing ; }, abstract = {Mosquitoes are insects of medical importance due their role as vectors of different pathogens to humans. There is a lack of information about the evolutionary history and phylogenetic positioning of the majority of mosquito species. Here we characterized the mitogenomes of mosquito species through low-coverage whole genome sequencing and data mining. A total of 37 draft mitogenomes of different species were assembled from which 16 are newly-sequenced species. We datamined additional 49 mosquito mitogenomes, and together with our 37 mitogenomes, we reconstructed the evolutionary history of 86 species including representatives from 15 genera and 7 tribes. Our results showed that most of the species clustered in clades with other members of their own genus with exception of Aedes genus which was paraphyletic. We confirmed the monophyletic status of the Mansoniini tribe including both Coquillettidia and Mansonia genus. The Aedeomyiini and Uranotaeniini were consistently recovered as basal to other tribes in the subfamily Culicinae, although the exact relationships among these tribes differed between analyses. These results demonstrate that low-coverage sequencing is effective to recover mitogenomes, establish phylogenetic knowledge and hence generate basic fundamental information that will help in the understanding of the role of these species as pathogen vectors.}, } @article {pmid33142007, year = {2021}, author = {Russell, S and Jackson, C and Reyes-Prieto, A}, title = {High Sequence Divergence but Limited Architectural Rearrangements in Organelle Genomes of Cyanophora (Glaucophyta) Species.}, journal = {The Journal of eukaryotic microbiology}, volume = {68}, number = {1}, pages = {e12831}, doi = {10.1111/jeu.12831}, pmid = {33142007}, issn = {1550-7408}, mesh = {Biological Evolution ; Cyanophora/*genetics ; DNA, Mitochondrial/analysis ; *Evolution, Molecular ; *Genetic Variation ; *Genome, Mitochondrial ; *Genome, Plastid ; }, abstract = {Cyanophora is the glaucophyte model taxon. Following the sequencing of the nuclear genome of C. paradoxa, studies based on single organelle and nuclear molecular markers revealed previously unrecognized species diversity within this glaucophyte genus. Here, we present the complete plastid (ptDNA) and mitochondrial (mtDNA) genomes of C. kugrensii, C. sudae, and C. biloba. The respective sizes and coding capacities of both ptDNAs and mtDNAs are conserved among Cyanophora species with only minor differences due to specific gene duplications. Organelle phylogenomic analyses consistently recover the species C. kugrensii and C. paradoxa as a clade and C. sudae and C. biloba as a separate group. The phylogenetic affiliations of the four Cyanophora species are consistent with architectural similarities shared at the organelle genomic level. Genetic distance estimations from both organelle sequences are also consistent with phylogenetic and architecture evidence. Comparative analyses confirm that the Cyanophora mitochondrial genes accumulate substitutions at 3-fold higher rates than plastid counterparts, suggesting that mtDNA markers are more appropriate to investigate glaucophyte diversity and evolutionary events that occur at a population level. The study of complete organelle genomes is becoming the standard for species delimitation and is particularly relevant to study cryptic diversity in microbial groups.}, } @article {pmid33142719, year = {2020}, author = {Penna, E and Pizzella, A and Cimmino, F and Trinchese, G and Cavaliere, G and Catapano, A and Allocca, I and Chun, JT and Campanozzi, A and Messina, G and Precenzano, F and Lanzara, V and Messina, A and Monda, V and Monda, M and Perrone-Capano, C and Mollica, MP and Crispino, M}, title = {Neurodevelopmental Disorders: Effect of High-Fat Diet on Synaptic Plasticity and Mitochondrial Functions.}, journal = {Brain sciences}, volume = {10}, number = {11}, pages = {}, pmid = {33142719}, issn = {2076-3425}, support = {B61G18000470007//Regione Campania/ ; }, abstract = {Neurodevelopmental disorders (NDDs) include diverse neuropathologies characterized by abnormal brain development leading to impaired cognition, communication and social skills. A common feature of NDDs is defective synaptic plasticity, but the underlying molecular mechanisms are only partially known. Several studies have indicated that people's lifestyles such as diet pattern and physical exercise have significant influence on synaptic plasticity of the brain. Indeed, it has been reported that a high-fat diet (HFD, with 30-50% fat content), which leads to systemic low-grade inflammation, has also a detrimental effect on synaptic efficiency. Interestingly, metabolic alterations associated with obesity in pregnant woman may represent a risk factor for NDDs in the offspring. In this review, we have discussed the potential molecular mechanisms linking the HFD-induced metabolic dysfunctions to altered synaptic plasticity underlying NDDs, with a special emphasis on the roles played by synaptic protein synthesis and mitochondrial functions.}, } @article {pmid33153867, year = {2020}, author = {Tort, F and Barredo, E and Parthasarathy, R and Ugarteburu, O and Ferrer-Cortès, X and García-Villoria, J and Gort, L and González-Quintana, A and Martín, MA and Fernández-Vizarra, E and Zeviani, M and Ribes, A}, title = {Biallelic mutations in NDUFA8 cause complex I deficiency in two siblings with favorable clinical evolution.}, journal = {Molecular genetics and metabolism}, volume = {131}, number = {3}, pages = {349-357}, doi = {10.1016/j.ymgme.2020.10.005}, pmid = {33153867}, issn = {1096-7206}, mesh = {Child ; Female ; Fibroblasts/metabolism ; *Genetic Predisposition to Disease ; Humans ; Male ; Metabolism, Inborn Errors/genetics/pathology ; Mitochondria/genetics/pathology ; Mitochondrial Diseases/*genetics/pathology ; NADH Dehydrogenase/*genetics ; *Oxidative Phosphorylation ; Siblings ; Exome Sequencing ; }, abstract = {Isolated complex I (CI) deficiency is the most common cause of oxidative phosphorylation (OXPHOS) dysfunction. Whole-exome sequencing identified biallelic mutations in NDUFA8 (c.[293G > T]; [293G > T], encoding for an accessory subunit of CI, in two siblings with a favorable clinical evolution. The individuals reported here are practically asymptomatic, with the exception of slight failure to thrive and some language difficulties at the age of 6 and 9 years, respectively. These observations are remarkable since the vast majority of patients with CI deficiency, including the only NDUFA8 patient reported so far, showed an extremely poor clinical outcome. Western blot studies demonstrated that NDUFA8 protein was strongly reduced in the patients' fibroblasts and muscle extracts. In addition, there was a marked and specific decrease in the steady-state levels of CI subunits. BN-PAGE demonstrated an isolated defect in the assembly and the activity of CI with impaired supercomplexes formation and abnormal accumulation of CI subassemblies. Confocal microscopy analysis in fibroblasts showed rounder mitochondria and diminished branching degree of the mitochondrial network. Functional complementation studies demonstrated disease-causality for the identified mutation as lentiviral transduction with wild-type NDUFA8 cDNA restored the steady-state levels of CI subunits and completely recovered the deficient enzymatic activity in immortalized mutant fibroblasts. In summary, we provide additional evidence of the involvement of NDUFA8 as a mitochondrial disease-causing gene associated with altered mitochondrial morphology, CI deficiency, impaired supercomplexes formation, and very mild progression of the disease.}, } @article {pmid33157103, year = {2021}, author = {Pearson, SA and Cowan, JA}, title = {Evolution of the human mitochondrial ABCB7 [2Fe-2S](GS)4 cluster exporter and the molecular mechanism of an E433K disease-causing mutation.}, journal = {Archives of biochemistry and biophysics}, volume = {697}, number = {}, pages = {108661}, pmid = {33157103}, issn = {1096-0384}, support = {R21 AI072443/AI/NIAID NIH HHS/United States ; }, mesh = {ATP-Binding Cassette Transporters/chemistry/*genetics/*metabolism ; Adenosine Triphosphatases/metabolism ; *Evolution, Molecular ; Humans ; Kinetics ; Models, Molecular ; *Mutation ; Protein Conformation ; }, abstract = {Iron-sulfur cluster proteins play key roles in a multitude of cellular processes. Iron-sulfur cofactors are assembled primarily in mitochondria and are then exported to the cytosol by use of an ABCB7 transporter. It has been shown that the yeast mitochondrial transporter Atm1 can export glutathione-coordinated iron-sulfur clusters, [2Fe-2S](SG)4, providing a source of cluster units for cytosolic iron-sulfur cluster assembly systems. This pathway is consistent with the endosymbiotic model of mitochondrial evolution where homologous bacterial heavy metal transporters, utilizing metal glutathione adducts, were adapted for use in eukaryotic mitochondria. Herein, the basis for endosymbiotic evolution of the human cluster export protein (ABCB7) is developed through a BLAST analysis of transporters from ancient proteobacteria. In addition, a functional comparison of native human protein, versus a disease-causing mutant, demonstrates a key role for residue E433 in promoting cluster transport. Dysfunction in mitochondrial export of Fe-S clusters is a likely cause of the disease condition X-linked sideroblastic anemia.}, } @article {pmid33159171, year = {2020}, author = {Strack, PR and Brodie, EJ and Zhan, H and Schuenemann, VJ and Valente, LJ and Saiyed, T and Lowth, BR and Angley, LM and Perugini, MA and Zeth, K and Truscott, KN and Dougan, DA}, title = {Polymerase delta-interacting protein 38 (PDIP38) modulates the stability and activity of the mitochondrial AAA+ protease CLPXP.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {646}, pmid = {33159171}, issn = {2399-3642}, mesh = {Endopeptidase Clp/genetics/*metabolism ; Gene Expression Regulation ; HeLa Cells ; Humans ; Mitochondria/*metabolism ; Nuclear Proteins/genetics/*metabolism ; Recombinant Proteins ; }, abstract = {Over a decade ago Polymerase δ interacting protein of 38 kDa (PDIP38) was proposed to play a role in DNA repair. Since this time, both the physiological function and subcellular location of PDIP38 has remained ambiguous and our present understanding of PDIP38 function has been hampered by a lack of detailed biochemical and structural studies. Here we show, that human PDIP38 is directed to the mitochondrion in a membrane potential dependent manner, where it resides in the matrix compartment, together with its partner protein CLPX. Our structural analysis revealed that PDIP38 is composed of two conserved domains separated by an α/β linker region. The N-terminal (YccV-like) domain of PDIP38 forms an SH3-like β-barrel, which interacts specifically with CLPX, via the adaptor docking loop within the N-terminal Zinc binding domain of CLPX. In contrast, the C-terminal (DUF525) domain forms an immunoglobin-like β-sandwich fold, which contains a highly conserved putative substrate binding pocket. Importantly, PDIP38 modulates the substrate specificity of CLPX and protects CLPX from LONM-mediated degradation, which stabilises the cellular levels of CLPX. Collectively, our findings shed new light on the mechanism and function of mitochondrial PDIP38, demonstrating that PDIP38 is a bona fide adaptor protein for the mitochondrial protease, CLPXP.}, } @article {pmid33159940, year = {2021}, author = {Lin, ZJ and Wang, X and Wang, J and Tan, Y and Tang, X and Werren, JH and Zhang, D and Wang, X}, title = {Comparative analysis reveals the expansion of mitochondrial DNA control region containing unusually high G-C tandem repeat arrays in Nasonia vitripennis.}, journal = {International journal of biological macromolecules}, volume = {166}, number = {}, pages = {1246-1257}, doi = {10.1016/j.ijbiomac.2020.11.007}, pmid = {33159940}, issn = {1879-0003}, mesh = {Animals ; Base Composition/*genetics ; Base Sequence ; CpG Islands/genetics ; DNA Methylation/genetics ; DNA, Mitochondrial/*genetics ; Gene Rearrangement/genetics ; *Genome, Insect ; Genome, Mitochondrial ; Molecular Sequence Annotation ; Phylogeny ; Tandem Repeat Sequences/*genetics ; Wasps/*genetics ; }, abstract = {Insect mitochondrial DNA (mtDNA) ranges from 14 to 19 kbp, and the size difference is attributed to the AT-rich control region. Jewel wasps have a parasitoid lifestyle, which may affect mitochondria function and evolution. We sequenced, assembled, and annotated mitochondrial genomes in Nasonia and outgroup species. Gene composition and order are conserved within Nasonia, but they differ from other parasitoids by two large inversion events that were not reported before. We observed a much higher substitution rate relative to the nuclear genome and mitochondrial introgression between N. giraulti and N. oneida, which is consistent with previous studies. Most strikingly, N. vitripennis mtDNA has an extremely long control region (7665 bp), containing twenty-nine 217 bp tandem repeats and can fold into a super-cruciform structure. In contrast to tandem repeats commonly found in other mitochondria, these high-copy repeats are highly conserved (98.7% sequence identity), much longer in length (approximately 8 Kb), extremely GC-rich (50.7%), and CpG-rich (percent CpG 19.4% vs. 1.1% in coding region), resulting in a 23 kbp mtDNA beyond the typical size range in insects. These N. vitripennis-specific mitochondrial repeats are not related to any known sequences in insect mitochondria. Their evolutionary origin and functional consequences warrant further investigations.}, } @article {pmid33160039, year = {2021}, author = {Hánová, A and Konečný, A and Nicolas, V and Denys, C and Granjon, L and Lavrenchenko, LA and Šumbera, R and Mikula, O and Bryja, J}, title = {Multilocus phylogeny of African striped grass mice (Lemniscomys): Stripe pattern only partly reflects evolutionary relationships.}, journal = {Molecular phylogenetics and evolution}, volume = {155}, number = {}, pages = {107007}, doi = {10.1016/j.ympev.2020.107007}, pmid = {33160039}, issn = {1095-9513}, mesh = {Africa South of the Sahara ; Animals ; Bayes Theorem ; Calibration ; Climate ; DNA, Mitochondrial/genetics ; *Genetic Loci ; Genetic Variation ; Geography ; Haplotypes/genetics ; Mitochondria/genetics ; *Phylogeny ; Sigmodontinae/*anatomy & histology/*classification ; Species Specificity ; Time Factors ; }, abstract = {Murine rodents are one of the most evolutionary successful groups of extant mammals. They are also important for human as vectors and reservoirs of zoonoses and agricultural pests. Unfortunately, their fast and relatively recent diversification impedes our understanding of phylogenetic relationships and species limits of many murine taxa, including those with very conspicuous phenotype that has been frequently used for taxonomic purposes. One of such groups are the striped grass mice (genus Lemniscomys), distributed across sub-Saharan Africa in 11 currently recognized species. These are traditionally classified into three morphological groups according to different pelage colouration on the back: (a) L. barbarus group (three species) with several continuous pale longitudinal stripes; (b) L. striatus group (four species) with pale stripes diffused into short lines or dots; and (c) L. griselda group (four species) with a single mid-dorsal black stripe. Here we reconstructed the most comprehensive molecular phylogeny of the genus Lemniscomys to date, using the largest currently available multi-locus genetic dataset of all but two species. The results show four main lineages (=species complexes) with the distribution corresponding to the major biogeographical regions of Africa. Surprisingly, the four phylogenetic lineages are only in partial agreement with the morphological classification, suggesting that the single-stripe and/or multi-striped phenotypes evolved independently in multiple lineages. Divergence dating showed the split of Lemniscomys and Arvicanthis genera at the beginning of Pleistocene; most of subsequent speciation processes within Lemniscomys were affected by Pleistocene climate oscillations, with predominantly allopatric diversification in fragmented savanna biome. We propose taxonomic suggestions and directions for future research of this striking group of African rodents.}, } @article {pmid33164622, year = {2021}, author = {Iketani, G and Pimentel, L and Torres, EDS and Rêgo, PSD and Sampaio, I}, title = {Mitochondrial heteroplasmy and pseudogenes in the freshwater prawn, Macrobrachium amazonicum (Heller, 1862): DNA barcoding and phylogeographic implications.}, journal = {Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis}, volume = {32}, number = {1}, pages = {1-11}, doi = {10.1080/24701394.2020.1844677}, pmid = {33164622}, issn = {2470-1408}, mesh = {Animals ; Arthropod Proteins/genetics ; Brazil ; Cell Nucleus/*genetics ; Cloning, Molecular ; DNA Barcoding, Taxonomic/*methods ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/*genetics ; Genetics, Population ; Heteroplasmy ; Mitochondria/*genetics ; Palaemonidae/*classification/genetics ; Paraguay ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; }, abstract = {The mitochondrial cytochrome oxidase c subunit 1 (COI) gene has been widely used in phylogenetic studies of crustaceans and analyses in population genetics. As COI studies have become more popular, there has been an increase in the number of reports of the presence of nuclear insertions of mitochondrial DNA (Numts) and mitochondrial heteroplasmy. Here, we provide evidence of both types of event in the COI sequences of Macrobrachium amazonicum, an economically important freshwater prawn, which is widespread in South America. Heteroplasmy and Numts were confirmed by different methods of DNA extraction (genomic, mitochondrial, and nuclear-enriched DNA), cloning, and sequencing, and were observed in 11 of the 14 populations sampled, primarily in the Amazon region. We discuss how the occurrence of these events affects the interpretation of the genetic relationships among the M. amazonicum populations, and we recommend caution when using COI for genetic inferences in prawns of the genus Macrobrachium, and in particular that any analysis should include nuclear markers.}, } @article {pmid33164854, year = {2021}, author = {Ortiz, D and Pekár, S and Bilat, J and Alvarez, N}, title = {Poor performance of DNA barcoding and the impact of RAD loci filtering on the species delimitation of an Iberian ant-eating spider.}, journal = {Molecular phylogenetics and evolution}, volume = {154}, number = {}, pages = {106997}, doi = {10.1016/j.ympev.2020.106997}, pmid = {33164854}, issn = {1095-9513}, mesh = {Animals ; Cell Nucleus/genetics ; Cluster Analysis ; *DNA Barcoding, Taxonomic ; Electron Transport Complex IV/genetics ; *Genetic Loci ; Genetics, Population ; Genomics ; Geography ; Likelihood Functions ; Mitochondria/genetics ; *Phylogeny ; *Restriction Mapping ; *Sequence Analysis, DNA ; Species Specificity ; Spiders/classification/*genetics ; }, abstract = {Genomic data provide unprecedented power for species delimitation. However, current implementations are still time and resource consuming. In addition, bioinformatic processing is contentious and its impact on downstream analyses is insufficiently understood. Here we employ ddRAD sequencing and a thorough sampling for species delimitation in Zodarion styliferum, a widespread Iberian ant-eating spider. We explore the influence of the loci filtering strategy on the downstream phylogenetic analyses, genomic clustering and coalescent species delimitation. We also assess the accuracy of one mitochondrial (COI) and one nuclear (ITS) barcode for fast and inexpensive species delineation in the group. Our genomic data strongly support two morphologically cryptic but ecologically divergent lineages, mainly restricted to the central-eastern and western parts of the Iberian Peninsula, respectively. Larger matrices with more missing data showed increased genomic diversity, supporting that bioinformatic strategies to maximize matrix completion disproportionately exclude loci with the highest mutation rates. Moderate loci filtering gave the best results across analyses: although larger matrices returned concatenated phylogenies with higher support, middle-sized matrices performed better in genetic structure analyses. COI displayed high diversity and a conspicuous barcode gap, revealing 13 mitochondrial lineages. Mitonuclear discordance is consistent with ancestral isolation in multiple groups, probably in glacial refugia, followed by range expansion and secondary contact that produced genomic homogenization. Several apparently (unidirectionally) introgressed specimens further challenge the accuracy of species identification through mitochondrial barcodes in the group. Conversely, ITS failed to separate both lineages of Z. styliferum. This study shows an extreme case of mitonuclear discordance that highlights the limitations of single molecular barcodes for species delimitation, even in presence of distinct barcode gaps, and brings new light on the effects of parameterization on shallow-divergence studies using RAD data.}, } @article {pmid33165944, year = {2021}, author = {Hirase, S and Tezuka, A and Nagano, AJ and Sato, M and Hosoya, S and Kikuchi, K and Iwasaki, W}, title = {Integrative genomic phylogeography reveals signs of mitonuclear incompatibility in a natural hybrid goby population.}, journal = {Evolution; international journal of organic evolution}, volume = {75}, number = {1}, pages = {176-194}, pmid = {33165944}, issn = {1558-5646}, mesh = {Animals ; *Biological Evolution ; *Genome, Mitochondrial ; *Hybridization, Genetic ; Japan ; Perciformes/*genetics ; Phylogeography ; Sequence Analysis, RNA ; }, abstract = {Hybridization between divergent lineages generates new allelic combinations. One mechanism that can hinder the formation of hybrid populations is mitonuclear incompatibility, that is, dysfunctional interactions between proteins encoded in the nuclear and mitochondrial genomes (mitogenomes) of diverged lineages. Theoretically, selective pressure due to mitonuclear incompatibility can affect genotypes in a hybrid population in which nuclear genomes and mitogenomes from divergent lineages admix. To directly and thoroughly observe this key process, we de novo sequenced the 747-Mb genome of the coastal goby, Chaenogobius annularis, and investigated its integrative genomic phylogeographics using RNA-sequencing, RAD-sequencing, genome resequencing, whole mitogenome sequencing, amplicon sequencing, and small RNA-sequencing. Chaenogobius annularis populations have been geographically separated into Pacific Ocean (PO) and Sea of Japan (SJ) lineages by past isolation events around the Japanese archipelago. Despite the divergence history and potential mitonuclear incompatibility between these lineages, the mitogenomes of the PO and SJ lineages have coexisted for generations in a hybrid population on the Sanriku Coast. Our analyses revealed accumulation of nonsynonymous substitutions in the PO-lineage mitogenomes, including two convergent substitutions, as well as signals of mitochondrial lineage-specific selection on mitochondria-related nuclear genes. Finally, our data implied that a microRNA gene was involved in resolving mitonuclear incompatibility. Our integrative genomic phylogeographic approach revealed that mitonuclear incompatibility can affect genome evolution in a natural hybrid population.}, } @article {pmid33176683, year = {2020}, author = {Dhorne-Pollet, S and Barrey, E and Pollet, N}, title = {A new method for long-read sequencing of animal mitochondrial genomes: application to the identification of equine mitochondrial DNA variants.}, journal = {BMC genomics}, volume = {21}, number = {1}, pages = {785}, pmid = {33176683}, issn = {1471-2164}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial/genetics ; High-Throughput Nucleotide Sequencing ; Horses/genetics ; *Nanopores ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Mitochondrial DNA is remarkably polymorphic. This is why animal geneticists survey mitochondrial genomes variations for fundamental and applied purposes. We present here an approach to sequence whole mitochondrial genomes using nanopore long-read sequencing. Our method relies on the selective elimination of nuclear DNA using an exonuclease treatment and on the amplification of circular mitochondrial DNA using a multiple displacement amplification step.

RESULTS: We optimized each preparative step to obtain a 100 million-fold enrichment of horse mitochondrial DNA relative to nuclear DNA. We sequenced these amplified mitochondrial DNA using nanopore sequencing technology and obtained mitochondrial DNA reads that represented up to half of the sequencing output. The sequence reads were 2.3 kb of mean length and provided an even coverage of the mitochondrial genome. Long-reads spanning half or more of the whole mtDNA provided a coverage that varied between 118X and 488X. We evaluated SNPs identified using these long-reads by Sanger sequencing as ground truth and found a precision of 100.0%; a recall of 93.1% and a F1-score of 0.964 using the Twilight horse mtDNA reference. The choice of the mtDNA reference impacted variant calling efficiency with F1-scores varying between 0.947 and 0.964.

CONCLUSIONS: Our method to amplify mtDNA and to sequence it using the nanopore technology is usable for mitochondrial DNA variant analysis. With minor modifications, this approach could easily be applied to other large circular DNA molecules.}, } @article {pmid33179562, year = {2021}, author = {Khan, S and Nisar, A and Ahmad, H and Mehmood, SA and Hameed, M and Zhao, X and Yang, X and Feng, X}, title = {Analyses of mitogenomic markers shed light on the divergence, population dynamics, and demographic history of Pakistani chickens.}, journal = {Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis}, volume = {32}, number = {1}, pages = {34-42}, doi = {10.1080/24701394.2020.1845323}, pmid = {33179562}, issn = {2470-1408}, mesh = {Animals ; Chickens/*classification/genetics ; DNA, Mitochondrial/*genetics ; Feathers/chemistry ; Gene Pool ; Genetic Markers/*genetics ; Genetic Variation ; Haplotypes ; Mitochondria/*genetics ; Pakistan ; Phylogeny ; Population Dynamics ; Sequence Analysis, DNA/*methods ; }, abstract = {Pakistan is one of a few sites, associated with the earliest known independent domestication event in the evolutionary history of chicken, which is socio-economically and historically the most important poultry bird in the country. However, the divergence, past population dynamics, and demographic history of Pakistani chickens have not been addressed so far. Therefore, we herein investigated the indigenous Pakistani chickens using mitogenomic markers. We first prepared individual DNA samples from the chicken feathers, and generated nucleotide sequence data, which was then subjected to various population genetics analyses. In molecular phylogenetic analysis, the Pakistani chickens were clustered under nine different clades. Among the wild fowls, the Indian red jungle fowl (IRJF) shared very close affinities to Pakistani chickens. The Bayesian skyline plot showed an increase in the effective population size of Pakistani chickens during the last 50 years. Finally, a time-calibrated phylogeny inferred molecular divergence of the Pakistani chickens. A molecular rate of 3.6 × 10[-6] mutations/site/year (95% HPD interval: 2.28 × 10[-8] to 9.32 × 10[-6]) was estimated for the data set. In a rooted tree with root-age of 12058 years (95% HPD interval: 1161-38411), the Pakistani chicken haplotypes showed divergence from IRJF haplotypes around 6987 years (95% HPD interval: 1132-20746) ago, and they shared their most recent common ancestor with Gallus gallus spadiceus, and G. g. jabouillei at the root of the tree. Overall, these results suggest that Pakistani chicken haplotypes share their ancestral gene pool with the IRJF as compared to other red jungle fowl subspecies.}, } @article {pmid33180850, year = {2020}, author = {Vorobieva, NV and Makunin, AI and Druzhkova, AS and Kusliy, MA and Trifonov, VA and Popova, KO and Polosmak, NV and Molodin, VI and Vasiliev, SK and Shunkov, MV and Graphodatsky, AS}, title = {High genetic diversity of ancient horses from the Ukok Plateau.}, journal = {PloS one}, volume = {15}, number = {11}, pages = {e0241997}, pmid = {33180850}, issn = {1932-6203}, mesh = {Animals ; Animals, Domestic/*genetics ; Animals, Wild/*genetics ; DNA, Ancient/analysis ; Evolution, Molecular ; Extinction, Biological ; Fossils/history ; Genome, Mitochondrial ; Haplotypes ; High-Throughput Nucleotide Sequencing/veterinary ; History, Ancient ; Horses ; Mitochondria/*genetics ; Phylogeny ; Russia ; Whole Genome Sequencing/*veterinary ; }, abstract = {A growing number of researchers studying horse domestication come to a conclusion that this process happened in multiple locations and involved multiple wild maternal lines. The most promising approach to address this problem involves mitochondrial haplotype comparison of wild and domestic horses from various locations coupled with studies of possible migration routes of the ancient shepherds. Here, we sequenced complete mitochondrial genomes of six horses from burials of the Ukok plateau (Russia, Altai Mountains) dated from 2.7 to 1.4 thousand years before present and a single late Pleistocene wild horse from the neighboring region (Denisova cave). Sequencing data indicates that the wild horse belongs to an extinct pre-domestication lineage. Integration of the domestic horse data with known Eurasian haplotypes of a similar age revealed two distinct groups: the first one widely distributed in Europe and presumably imported to Altai, and the second one specific for Altai Mountains and surrounding area.}, } @article {pmid33185659, year = {2021}, author = {Ettahi, K and Lhee, D and Sung, JY and Simpson, AGB and Park, JS and Yoon, HS}, title = {Evolutionary History of Mitochondrial Genomes in Discoba, Including the Extreme Halophile Pleurostomum flabellatum (Heterolobosea).}, journal = {Genome biology and evolution}, volume = {13}, number = {2}, pages = {}, pmid = {33185659}, issn = {1759-6653}, mesh = {Electron Transport/genetics ; Eukaryota/classification/*genetics ; *Evolution, Molecular ; Genes ; *Genome, Mitochondrial ; Mitochondria/ultrastructure ; Mitochondrial Proteins/genetics ; Phylogeny ; }, abstract = {Data from Discoba (Heterolobosea, Euglenozoa, Tsukubamonadida, and Jakobida) are essential to understand the evolution of mitochondrial genomes (mitogenomes), because this clade includes the most primitive-looking mitogenomes known, as well some extremely divergent genome information systems. Heterolobosea encompasses more than 150 described species, many of them from extreme habitats, but only six heterolobosean mitogenomes have been fully sequenced to date. Here we complete the mitogenome of the heterolobosean Pleurostomum flabellatum, which is extremely halophilic and reportedly also lacks classical mitochondrial cristae, hinting at reduction or loss of respiratory function. The mitogenome of P. flabellatum maps as a 57,829-bp-long circular molecule, including 40 coding sequences (19 tRNA, two rRNA, and 19 orfs). The gene content and gene arrangement are similar to Naegleria gruberi and Naegleria fowleri, the closest relatives with sequenced mitogenomes. The P. flabellatum mitogenome contains genes that encode components of the electron transport chain similar to those of Naegleria mitogenomes. Homology searches against a draft nuclear genome showed that P. flabellatum has two homologs of the highly conserved Mic60 subunit of the MICOS complex, and likely lost Mic19 and Mic10. However, electron microscopy showed no cristae structures. We infer that P. flabellatum, which originates from high salinity (313‰) water where the dissolved oxygen concentration is low, possesses a mitochondrion capable of aerobic respiration, but with reduced development of cristae structure reflecting limited use of this aerobic capacity (e.g., microaerophily).}, } @article {pmid33197746, year = {2020}, author = {Azim, MF and Burch-Smith, TM}, title = {Organelles-nucleus-plasmodesmata signaling (ONPS): an update on its roles in plant physiology, metabolism and stress responses.}, journal = {Current opinion in plant biology}, volume = {58}, number = {}, pages = {48-59}, doi = {10.1016/j.pbi.2020.09.005}, pmid = {33197746}, issn = {1879-0356}, mesh = {Chloroplasts ; Plant Development ; *Plant Physiological Phenomena ; *Plasmodesmata ; Signal Transduction ; }, abstract = {Plasmodesmata allow movement of metabolites and signaling molecules between plant cells and are, therefore, critical players in plant development and physiology, and in responding to environmental signals and stresses. There is emerging evidence that plasmodesmata are controlled by signaling originating from other organelles, primarily the chloroplasts and mitochondria. These signals act in the nucleus to alter expression of genetic pathways that control both trafficking via plasmodesmata and the plasmodesmatal pores themselves. This control circuit was dubbed organelle-nucleus-plasmodesmata signaling (ONPS). Here we discuss how ONPS arose during plant evolution and highlight the discovery of an ONPS-like module for regulating stomata. We also consider recent findings that illuminate details of the ONPS circuit and its roles in plant physiology, metabolism, and defense.}, } @article {pmid33203574, year = {2021}, author = {Lukeš, J and Kaur, B and Speijer, D}, title = {RNA Editing in Mitochondria and Plastids: Weird and Widespread.}, journal = {Trends in genetics : TIG}, volume = {37}, number = {2}, pages = {99-102}, doi = {10.1016/j.tig.2020.10.004}, pmid = {33203574}, issn = {0168-9525}, mesh = {Mitochondria/*genetics ; Mutation/genetics ; Mutation Rate ; Phylogeny ; Plastids/*genetics ; RNA Editing/*genetics ; Symbiosis/genetics ; }, abstract = {Though widespread, RNA editing is rare, except in endosymbiotic organelles. A combination of higher mutation rates, relaxation of energetic constraints, and high genetic drift is found within plastids and mitochondria and is conducive for evolution and expansion of editing processes, possibly starting as repair mechanisms. To illustrate this, we present an exhaustive phylogenetic overview of editing types.}, } @article {pmid33217579, year = {2021}, author = {Plese, B and Kenny, NJ and Rossi, ME and Cárdenas, P and Schuster, A and Taboada, S and Koutsouveli, V and Riesgo, A}, title = {Mitochondrial evolution in the Demospongiae (Porifera): Phylogeny, divergence time, and genome biology.}, journal = {Molecular phylogenetics and evolution}, volume = {155}, number = {}, pages = {107011}, doi = {10.1016/j.ympev.2020.107011}, pmid = {33217579}, issn = {1095-9513}, mesh = {Animals ; Calibration ; Cell Nucleus/genetics ; Codon, Initiator/genetics ; Codon, Terminator/genetics ; *Evolution, Molecular ; Gene Expression Regulation ; Gene Order ; Gene Rearrangement ; Genes, Mitochondrial ; *Genome, Mitochondrial ; Mitochondria/*genetics ; Mitochondrial Proteins/genetics ; *Phylogeny ; Porifera/*genetics ; Time Factors ; }, abstract = {The sponge class Demospongiae is the most speciose and morphologically diverse in the phylum Porifera, and the species within it are vital components of a range of ecosystems worldwide. Despite their ubiquity, a number of recalcitrant problems still remain to be solved regarding their phylogenetic inter-relationships, the timing of their appearance, and their mitochondrial biology, the latter of which is only beginning to be investigated. Here we generated 14 new demosponge mitochondrial genomes which, alongside previously published mitochondrial resources, were used to address these issues. In addition to phylogenomic analysis, we have used syntenic data and analysis of coding regions to forge a framework for understanding the inter-relationships between Demospongiae sub-classes and orders. We have also leveraged our new resources to study the mitochondrial biology of these clades in terms of codon usage, optimisation and gene expression, to understand how these vital cellular components may have contributed to the success of the Porifera. Our results strongly support a sister relationship between Keratosa and (Verongimorpha + Heteroscleromorpha), contradicting previous studies using nuclear markers. Our study includes one species of Clionaida, and show for the first time support for a grouping of Suberitida+(Clionaida+(Tethyida + Poecilosclerida). The findings of our phylogenetic analyses are supported by in-depth examination of structural and coding-level evidence from our mitochondrial data. A time-calibrated phylogeny estimated the origin of Demospongiae in the Cambrian (~529 Mya), and suggests that most demosponge order crown-groups emerged in the Mesozoic. This work therefore provides a robust basis for considering demosponge phylogenetic relationships, as well as essential mitochondrial data for understanding the biological basis for their success and diversity.}, } @article {pmid33220346, year = {2021}, author = {Sweet, AD and Johnson, KP and Cao, Y and de Moya, RS and Skinner, RK and Tan, M and Virrueta Herrera, S and Cameron, SL}, title = {Structure, gene order, and nucleotide composition of mitochondrial genomes in parasitic lice from Amblycera.}, journal = {Gene}, volume = {768}, number = {}, pages = {145312}, doi = {10.1016/j.gene.2020.145312}, pmid = {33220346}, issn = {1879-0038}, mesh = {Amblycera/classification/*genetics ; Animals ; Base Composition ; Base Sequence ; Evolution, Molecular ; Gene Order ; *Genetic Variation ; Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA/*methods ; }, abstract = {Parasitic lice have unique mitochondrial (mt) genomes characterized by rearranged gene orders, variable genome structures, and less AT content compared to most other insects. However, relatively little is known about the mt genomes of Amblycera, the suborder sister to all other parasitic lice. Comparing among nine different genera (including representative of all seven families), we show that Amblycera have variable and highly rearranged mt genomes. Some genera have fragmented genomes that vary considerably in length, whereas others have a single mt chromosome. Notably, these genomes are more AT-biased than most other lice. We also recover genus-level phylogenetic relationships among Amblycera that are consistent with those reported from large nuclear datasets, indicating that mt sequences are reliable for reconstructing evolutionary relationships in Amblycera. However, gene order data cannot reliably recover these same relationships. Overall, our results suggest that the mt genomes of lice, already know to be distinctive, are even more variable than previously thought.}, } @article {pmid33221746, year = {2020}, author = {Xu, H and Zhou, W and Zhan, L and Sui, H and Zhang, L and Zhao, C and Lu, X}, title = {The ZiBuPiYin recipe regulates proteomic alterations in brain mitochondria-associated ER membranes caused by chronic psychological stress exposure: Implications for cognitive decline in Zucker diabetic fatty rats.}, journal = {Aging}, volume = {12}, number = {23}, pages = {23698-23726}, pmid = {33221746}, issn = {1945-4589}, mesh = {Animals ; Behavior, Animal/*drug effects ; Brain/*drug effects/metabolism ; Chronic Disease ; Cognition/*drug effects ; Cognitive Dysfunction/etiology/metabolism/*prevention & control/psychology ; Diabetes Mellitus/*drug therapy/metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal/*pharmacology ; Endoplasmic Reticulum/*drug effects/metabolism ; Exploratory Behavior/drug effects ; Male ; Memory/drug effects ; Mitochondria/*drug effects/metabolism ; Mitochondrial Membranes/*drug effects/metabolism ; Neuroprotective Agents/*pharmacology ; Protein Interaction Maps ; Proteome/*drug effects ; Proteomics ; Rats, Zucker ; Signal Transduction ; Spatial Learning/drug effects ; Stress, Psychological/complications/*drug therapy/metabolism/psychology ; }, abstract = {Chronic psychological stress (PS) cumulatively affects memory performance through the deleterious effects on hypothalamic-pituitary-adrenal axis regulation. Several functions damaged in cognitive impairment-related diseases are regulated by mitochondria-associated ER membranes (MAMs). To elucidate the role of ZiBuPiYin recipe (ZBPYR) in regulating the MAM proteome to improve PS-induced diabetes-associated cognitive decline (PSD), differentially expressed MAM proteins were identified among Zucker diabetic fatty rats, PSD rats, and PS combined with ZBPYR administration rats via iTRAQ with LC-MS/MS. Proteomic analysis revealed that the expressions of 85 and 33 proteins were altered by PS and ZBPYR treatment, respectively. Among these, 21 proteins were differentially expressed under both PS and ZBPYR treatments, whose functional categories included energy metabolism, lipid and protein metabolism, and synaptic dysfunction. Furthermore, calcium signaling and autophagy-related proteins may play roles in the pathogenesis of PSD and the mechanism of ZBPYR, respectively. Notably, KEGG pathway analysis suggested that 'Alzheimer's disease' and 'oxidative phosphorylation' pathways may be impaired in PSD pathogenesis, while ZBPYR could play a neuroprotective role through regulating the above pathways. Overall, exposure to chronic PS contributes to the evolution of diabetes-associated cognitive decline and ZBPYR might prevent and treat PSD by regulating the MAM proteome.}, } @article {pmid33222011, year = {2021}, author = {Liu, H and Liu, M and Zhu, H and Zhong, J and Liao, X and Zhou, Q}, title = {Molecular characterization of a novel mitovirus from the plant‑pathogenic fungus Botryosphaeria dothidea.}, journal = {Archives of virology}, volume = {166}, number = {2}, pages = {633-637}, pmid = {33222011}, issn = {1432-8798}, support = {2018JJ3220//Hunan Provincial Natural Science Fund/ ; CX20190522//Hunan Provincial Innovation Foundation for Postgraduate/ ; }, mesh = {Amino Acids/genetics ; Ascomycota/*virology ; Genome, Viral/*genetics ; Mitochondria/genetics ; Open Reading Frames/genetics ; Phylogeny ; Plants/*microbiology ; RNA Viruses/*genetics ; RNA, Viral/genetics ; RNA-Dependent RNA Polymerase ; Viral Proteins/genetics ; }, abstract = {Here, a novel mycovirus, Botryosphaeria dothidea mitovirus 1 (BdMV1), was isolated from a phytopathogenic fungus, Botryosphaeria dothidea, and its molecular characteristics were determined. BdMV1 has a genome of 2,667 nt that contains a single large open reading frame (ORF) using the fungal mitochondrial genetic code. The ORF encodes an RNA-dependent RNA polymerase (RdRp) of 727 amino acids with a molecular mass of 81.64 kDa. BLASTp analysis revealed that the RdRp domain of BdMV1 has 39.59% and 39.18% sequence identity to Plasmopara viticola associated mitovirus 43 and Setosphaeria turcica mitovirus 1, respectively. Phylogenetic analysis further suggested that BdMV1 is a new member of the genus Mitovirus within the family Mitoviridae. To the best of our knowledge, this is the first report of a mitovirus in B. dothidea.}, } @article {pmid33224166, year = {2020}, author = {Khoshravesh, R and Stata, M and Adachi, S and Sage, TL and Sage, RF}, title = {Evolutionary Convergence of C4 Photosynthesis: A Case Study in the Nyctaginaceae.}, journal = {Frontiers in plant science}, volume = {11}, number = {}, pages = {578739}, pmid = {33224166}, issn = {1664-462X}, abstract = {C4 photosynthesis evolved over 65 times, with around 24 origins in the eudicot order Caryophyllales. In the Caryophyllales family Nyctaginaceae, the C4 pathway is known in three genera of the tribe Nyctagineae: Allionia, Okenia and Boerhavia. Phylogenetically, Allionia and Boerhavia/Okenia are separated by three genera whose photosynthetic pathway is uncertain. To clarify the distribution of photosynthetic pathways in the Nyctaginaceae, we surveyed carbon isotope ratios of 159 species of the Nyctaginaceae, along with bundle sheath (BS) cell ultrastructure, leaf gas exchange, and C4 pathway biochemistry in five species from the two C4 clades and closely related C3 genera. All species in Allionia, Okenia and Boerhavia are C4, while no C4 species occur in any other genera of the family, including three that branch between Allionia and Boerhavia. This demonstrates that C4 photosynthesis evolved twice in Nyctaginaceae. Boerhavia species use the NADP-malic enzyme (NADP-ME) subtype of C4 photosynthesis, while Allionia species use the NAD-malic enzyme (NAD-ME) subtype. The BS cells of Allionia have many more mitochondria than the BS of Boerhavia. Bundle sheath mitochondria are closely associated with chloroplasts in Allionia which facilitates CO2 refixation following decarboxylation by mitochondrial NAD-ME. The close relationship between Allionia and Boerhavia could provide insights into why NADP-ME versus NAD-ME subtypes evolve, particularly when coupled to analysis of their respective genomes. As such, the group is an excellent system to dissect the organizational hierarchy of convergent versus divergent traits produced by C4 evolution, enabling us to understand when convergence is favored versus when divergent modifications can result in a common phenotype.}, } @article {pmid33227379, year = {2021}, author = {Agafonov, VA and Negrobov, VV and Igamberdiev, AU}, title = {Symbiogenesis as a driving force of evolution: The legacy of Boris Kozo-Polyansky.}, journal = {Bio Systems}, volume = {199}, number = {}, pages = {104302}, doi = {10.1016/j.biosystems.2020.104302}, pmid = {33227379}, issn = {1872-8324}, mesh = {Animals ; *Biological Evolution ; Chloroplasts/metabolism ; Eukaryota/cytology/*metabolism ; Eukaryotic Cells/cytology/*metabolism ; Humans ; Mitochondria/metabolism ; Organelles/metabolism ; Plants/metabolism ; *Symbiosis ; }, abstract = {We analyze evolutionary views of Boris Kozo-Polyansky (1890-1957) who was the first who formulated the symbiotic theory of evolution as a concept in his book, Symbiogenesis: A New Principle of Evolution (1924). Later, starting from 1967, Lynn Margulis independently formulated and further developed the concept of symbiogenesis. Although the ideas on the symbiotic origin of chloroplasts and mitochondria appeared earlier, the book of Kozo-Polyansky presented symbiogenesis as the main factor of complexification in the course of evolution, not only in relation to the origin of eukaryotic cell. Kozo-Polyansky incorporated the ideas of symbiogenesis into a broader paradigm that anticipated the important concepts of the modern Extended Evolutionary Synthesis such as the idea of net of life, the evolutionary role of apoptosis, the ideas of punctuated equilibrium, and the concept of metasystem transition.}, } @article {pmid33228188, year = {2020}, author = {Peralta-Castro, A and García-Medel, PL and Baruch-Torres, N and Trasviña-Arenas, CH and Juarez-Quintero, V and Morales-Vazquez, CM and Brieba, LG}, title = {Plant Organellar DNA Polymerases Evolved Multifunctionality through the Acquisition of Novel Amino Acid Insertions.}, journal = {Genes}, volume = {11}, number = {11}, pages = {}, pmid = {33228188}, issn = {2073-4425}, mesh = {Amino Acids/genetics/metabolism ; Arabidopsis/genetics ; Arabidopsis Proteins/genetics/metabolism ; DNA End-Joining Repair/physiology ; DNA Repair/*physiology ; DNA-Directed DNA Polymerase/*genetics/metabolism ; Evolution, Molecular ; Organelles/*enzymology ; Plant Proteins/*genetics/metabolism ; }, abstract = {The majority of DNA polymerases (DNAPs) are specialized enzymes with specific roles in DNA replication, translesion DNA synthesis (TLS), or DNA repair. The enzymatic characteristics to perform accurate DNA replication are in apparent contradiction with TLS or DNA repair abilities. For instance, replicative DNAPs incorporate nucleotides with high fidelity and processivity, whereas TLS DNAPs are low-fidelity polymerases with distributive nucleotide incorporation. Plant organelles (mitochondria and chloroplast) are replicated by family-A DNA polymerases that are both replicative and TLS DNAPs. Furthermore, plant organellar DNA polymerases from the plant model Arabidopsis thaliana (AtPOLIs) execute repair of double-stranded breaks by microhomology-mediated end-joining and perform Base Excision Repair (BER) using lyase and strand-displacement activities. AtPOLIs harbor three unique insertions in their polymerization domain that are associated with TLS, microhomology-mediated end-joining (MMEJ), strand-displacement, and lyase activities. We postulate that AtPOLIs are able to execute those different functions through the acquisition of these novel amino acid insertions, making them multifunctional enzymes able to participate in DNA replication and DNA repair.}, } @article {pmid33229320, year = {2020}, author = {Gao, ZW and Wang, L}, title = {[Progress in elucidating the origin of eukaryotes].}, journal = {Yi chuan = Hereditas}, volume = {42}, number = {10}, pages = {929-948}, doi = {10.16288/j.yczz.20-107}, pmid = {33229320}, issn = {0253-9772}, mesh = {Archaea/classification/genetics ; *Biological Evolution ; *Eukaryota/classification/genetics ; Research/trends ; }, abstract = {Knowledge of the origin of eukaryotes is key to broadening our understanding of the eukaryotic genome and the relationship among internal structures within a eukaryotic cell. Since the discovery of archaea in 1977 and the proposal of three-domain tree of life by the American microbiologist Carl Woese, the intimate relationship in evolution between eukaryotes and archaea has been demonstrated by considerable experiments and analyses. From the beginning of the 21st century, with the development of phylogenetic methods and the discovery of new archaeal phyla more related to eukaryotes, increasing evidence has shown that Eukarya and Archaea should be merged into one domain, leading to a two-domain tree of life. Nowadays, the Asgard superphylum discovered via metagenomic analysis is regarded as the closest prokaryotes to eukaryotes. Nevertheless, several key questions are still under debate, such as what the ancestors of the eukaryotes were and when mitochondria emerged. Here, we review the current research progress regarding the changes of the tree of life and the detailed eukaryotic evolutionary mechanism. We show that the recent findings have greatly improved our knowledge on the origin of eukaryotes, which will pave the way for future studies.}, } @article {pmid33230146, year = {2020}, author = {Yu, H and Haja, DK and Schut, GJ and Wu, CH and Meng, X and Zhao, G and Li, H and Adams, MWW}, title = {Structure of the respiratory MBS complex reveals iron-sulfur cluster catalyzed sulfane sulfur reduction in ancient life.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {5953}, pmid = {33230146}, issn = {2041-1723}, mesh = {Catalysis ; Catalytic Domain ; Cryoelectron Microscopy ; Electron Transport Complex I/chemistry/metabolism ; Hydrogenase/chemistry/metabolism ; Iron-Sulfur Proteins/*chemistry/*metabolism ; Mitochondrial Membranes/enzymology/metabolism ; Models, Molecular ; Origin of Life ; Oxidation-Reduction ; Oxidoreductases/*chemistry/*metabolism ; Proton Pumps/chemistry ; Pyrococcus furiosus/chemistry/enzymology ; Sodium-Hydrogen Exchangers/chemistry ; Sulfur/*metabolism ; }, abstract = {Modern day aerobic respiration in mitochondria involving complex I converts redox energy into chemical energy and likely evolved from a simple anaerobic system now represented by hydrogen gas-evolving hydrogenase (MBH) where protons are the terminal electron acceptor. Here we present the cryo-EM structure of an early ancestor in the evolution of complex I, the elemental sulfur (S[0])-reducing reductase MBS. Three highly conserved protein loops linking cytoplasmic and membrane domains enable scalable energy conversion in all three complexes. MBS contains two proton pumps compared to one in MBH and likely conserves twice the energy. The structure also reveals evolutionary adaptations of MBH that enabled S[0] reduction by MBS catalyzed by a site-differentiated iron-sulfur cluster without participation of protons or amino acid residues. This is the simplest mechanism proposed for reduction of inorganic or organic disulfides. It is of fundamental significance in the iron and sulfur-rich volcanic environments of early earth and possibly the origin of life. MBS provides a new perspective on the evolution of modern-day respiratory complexes and of catalysis by biological iron-sulfur clusters.}, } @article {pmid33231829, year = {2021}, author = {Mirahmadi, H and Behravan, M and Raz, A and Tasa, D and Namaei, MH and Solgi, R}, title = {Genotyping of the Echinococcus granulosus in Paraffin-Embedded Human Tissue Samples from Iran.}, journal = {Acta parasitologica}, volume = {66}, number = {2}, pages = {535-542}, pmid = {33231829}, issn = {1896-1851}, support = {5303//Birjand University of Medical Sciences/ ; }, mesh = {Animals ; *Echinococcus granulosus/genetics ; Genotype ; Humans ; Iran/epidemiology ; Paraffin Embedding ; Phylogeny ; Sheep ; }, abstract = {PURPOSE: Cystic Echinococcosis (CE) is a medically important disease that is caused by the metacestodes of Echinococcus granulosus. Human hydatid is considered an endemic disease in specific regions of Iran. The goal of the present study was to determine the genetic diversity of E. granulosus from the paraffin-embedded human tissue samples which were collected from the endemic regions of Iran.

METHODS: Fifty-five formalin-fixed and paraffin-embedded hydatid cysts (FFPE) of humans, which had been removed surgically, were obtained from the South Khorasan and Sistan and Baluchistan provinces. These regions are related to the East and Southeast regions of Iran, respectively. The cox1 and nad1 genes from mitochondria were amplified from the extracted DNA and sequenced. The sequences were edited using the BioEdit software. Furthermore, phylogenetic and genetic diversity analyses were performed.

RESULTS: Sequencing of the cox1 and nad1 genes from the 44 CE samples was done successfully. Genetic analysis revealed that 38 (86.3%) and 6 (13.6%) of the isolates were G1- and G6-genotypes, respectively. In general, eight and six haplotypes were identified by cox1 and nad1 genes analysis, respectively. For G1 strains, the haplotype diversity index was higher for the cox1 gene (0.6 ± 0.07) in comparison with the nad1 gene (0.4 ± 0.09).

CONCLUSION: The findings of the present study showed that the sheep strain (G1) and the less important camel strain (G6) play the main roles in the transmission cycle of CE in the East and Southeast regions of Iran. Therefore, these results could be useful for managing the hydatid disease control programs in the studied and other similar areas.}, } @article {pmid33239750, year = {2020}, author = {Rees, DJ and Poulsen, JY and Sutton, TT and Costa, PAS and Landaeta, MF}, title = {Global phylogeography suggests extensive eucosmopolitanism in Mesopelagic Fishes (Maurolicus: Sternoptychidae).}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {20544}, pmid = {33239750}, issn = {2045-2322}, mesh = {Animals ; Biological Evolution ; DNA, Mitochondrial/*genetics ; Electron Transport Complex IV/genetics ; Evolution, Molecular ; Fishes/*genetics/metabolism ; Genetic Variation/genetics ; Genotype ; Haplotypes/genetics ; Mitochondria/genetics ; Phylogeny ; Phylogeography/methods ; Sequence Analysis, DNA/methods ; Species Specificity ; }, abstract = {Fishes in the mesopelagic zone (200-1000 m) have recently been highlighted for potential exploitation. Here we assess global phylogeography in Maurolicus, the Pearlsides, an ecologically important group. We obtained new sequences from mitochondrial COI and nuclear ITS-2 from multiple locations worldwide, representing 10 described species plus an unknown central South Pacific taxon. Phylogenetic analyses identified five geographically distinct groupings, three of which comprise multiple described species. Species delimitation analyses suggest these may represent four species. Maurolicus muelleri and M. australis are potentially a single species, although as no shared haplotypes are found between the two disjunct groups, we suggest maintenance of these as two species. Maurolicus australis is a predominantly southern hemisphere species found in the Pacific, Indian and southern South Atlantic Oceans, comprising five previously allopatric species. M. muelleri (previously two species) is distributed in the North Atlantic and Mediterranean Sea. Maurolicus weitzmani (previously two species) inhabits the eastern equatorial Atlantic, Gulf of Mexico and western North and South Atlantic. Maurolicus mucronatus is restricted to the Red Sea. No Maurolicus have previously been reported in the central South Pacific but we have identified a distinct lineage from this region, which forms a sister group to Maurolicus from the Red Sea.}, } @article {pmid33245800, year = {2021}, author = {Wang, W and Hou, S and Chen, G and Xia, L and Chen, J and Wang, Z and Lu, Y}, title = {Characterization and function study of a glutamyl endopeptidase homolog from Nocardia seriolae.}, journal = {Journal of fish diseases}, volume = {44}, number = {6}, pages = {813-821}, doi = {10.1111/jfd.13311}, pmid = {33245800}, issn = {1365-2761}, support = {KJYF202001-08//Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District/ ; JCYJ20180306173022502//Shenzhen Science and Technology Project/ ; JCYJ20180507183240459//Shenzhen Science and Technology Project/ ; 231419017//Research Projects of Guangdong Ocean University's Top-ranking Discipline Construction/ ; }, mesh = {Amino Acid Sequence ; Animals ; Bacterial Proteins/chemistry/*genetics/metabolism ; Base Sequence ; Fish Diseases/microbiology ; Nocardia/*genetics/metabolism ; Nocardia Infections/microbiology/veterinary ; Phylogeny ; Sequence Alignment ; Serine Endopeptidases/chemistry/*genetics/metabolism ; }, abstract = {Glutamic endopeptidases (Glu), belonging to the class of serine proteases, are a subfamily of chymotrypsin-like proteolytic enzymes, which are regarded as important virulence factors in bacteria. However, the roles of glutamic endopeptidases of Nocardia seriolae in pathogenic process still remain uncertain. Here, a glutamic endopeptidase homolog from N. seriolae (GluNS) was cloned and its function was elucidated. GluNS encoded a 414-aa protein which shared 93% identity to N. concava. In the phylogenetic tree, the glutamic endopeptidases of genus Nocardia clustered together firstly and then clustered with Streptomyces species. Moreover, GluNS was identified to be a secreted protein of N. seriolae and localized in the mitochondria of FHM cells. The transient overexpression of GluNS significantly induced increase in caspase-3 activity and decrease in ΔΨm values in FHM cells. The number of apoptotic bodies was remarkably higher than that in control group. Taken together, GluNS overexpression induced apoptotic characteristics in FHM cells. This study provided new insights into the function of glutamic endopeptidase from N. seriolae.}, } @article {pmid33247794, year = {2021}, author = {Bagherfard, S and Najafi, N and Gharzi, A and Akmali, V}, title = {Lack of intraspecific variations of the mitochondrial cytochrome b gene in the greater mouse-tailed bat Rhinopoma microphyllum (Chiroptera: Rhinopomatidae) in Iran.}, journal = {Genetica}, volume = {149}, number = {1}, pages = {37-45}, pmid = {33247794}, issn = {1573-6857}, mesh = {Animals ; Chiroptera/classification/*genetics ; Cytochromes b/*genetics ; DNA, Mitochondrial/*genetics ; *Genetic Speciation ; Genetic Variation/genetics ; Genetics, Population ; Haplotypes/genetics ; Mitochondria/genetics ; Phylogeography ; Species Specificity ; }, abstract = {Rhinopoma microphyllum is one of the species of bats that lives in arid and semi-arid areas of Iran. The initial suggestion of the presence of two subspecies R. m. microphyllum and R. m. harrisoni based on their morphological characteristics has been questioned on the basis of small differences between the populations. Later, other researchers assigned Iranian populations of this species to one or two subspecies based on their morphological and molecular characteristics. The present study provides a phylogeographical analysis of this species using 687 bp of the mitochondrial cytochrome b in 81 bats in Iran, Jordan, Levant and Ethiopia. Based on mtDNA sequences, we found a low degree of genetic diversity in the Iranian populations of R. microphyllum (π = 0.0025), which shows a close relationship between the haplotypes. The analysis of genetic distance (0.15-1.93%), phylogenetic trees, and statistical parsimony network showed that all Iranian samples were grouped in the same clade, while Levant, Jordan and Ethiopian samples belonged to a different clade. Molecular dating suggested the Iranian R. microphyllum lineage split from the R. microphyllum of the Levant and Jordan clade during the Pliocene 3.18 (2.11-4.32 Ma). Taking these results into consideration, we can conclude that all Iranian specimens belong to the same subspecies as R. m. harrisoni since molecular results indicate that Iranian samples are differ from Levant subspecies (R. m. microphyllum).}, } @article {pmid33248045, year = {2021}, author = {Song, L and Gao, C and Xue, T and Yang, N and Fu, Q and Zhu, Q and Ge, X and Li, C}, title = {Characterization and expression analysis of mitochondrial localization molecule: NOD-like receptor X1 (Nlrx1) in mucosal tissues of turbot (Scophthalmus maximus) following bacterial challenge.}, journal = {Developmental and comparative immunology}, volume = {116}, number = {}, pages = {103944}, doi = {10.1016/j.dci.2020.103944}, pmid = {33248045}, issn = {1879-0089}, mesh = {Amino Acid Sequence ; Animals ; Cytoplasm/metabolism ; Fish Diseases/immunology/microbiology ; Fish Proteins/genetics/metabolism ; Flatfishes/*immunology/microbiology ; Gene Expression Profiling ; HEK293 Cells ; Humans ; Mitochondrial Proteins/genetics/*immunology/metabolism ; Mucous Membrane/*immunology/microbiology ; Phylogeny ; Protein Interaction Maps ; RNA, Messenger/genetics/metabolism ; Sequence Alignment ; Streptococcus iniae/physiology ; Vibrio/physiology ; }, abstract = {The NOD-like receptor X1 (NLRX1) is a member of highly conserved nucleotide-binding domain (NBD)- and leucine-rich-repeat (LRR)-containing family (known as NLR), that localizes to the mitochondrial outer membrane and regulate the innate immunity by interacting with mitochondrial antiviral-signaling protein (MAVS). As one of cytoplasmic PRRs, NLRX1 plays key roles for pathogen recognition, autophagy and regulating of subsequent immune signaling pathways. In this study, we identified the nlrx1 in turbot as well as its expression profiles in mucosal surfaces following bacterial infection. In our results, the full-length nlrx1 transcript consists of an open reading frame (ORF) of 4,886 bp encoding the putative peptide of 966 amino acids. The phylogenetic analysis revealed the SmNlrx1 showed the closest relationship to Cynoglossus semilaevis. In addition, the Nlrx1 mRNA expression could be detected in all the examined tissues, with the most abundant expression level in head kidney, and the lowest expression level in liver. Moreover, Nlrx1 showed similar expression patterns following Vibrio anguillarum and Streptococcus iniae infection, that were both significantly up-regulated following challenge, especially post S. iniae challenge. Finally, fluorescence microscopy unveiled that the SmNlrx1 localized to mitochondria in HEK293T by N-terminal mitochondrial targeting sequence. Characterization of Nlrx1 might have an important implication in bioenergetic adaptation during metabolic stress, oncogenic transformation and innate immunity and will probably contribute to the development of novel intervention strategies for farming turbot.}, } @article {pmid33248204, year = {2021}, author = {Beldade, R and Longo, GC and Clements, KD and Robertson, DR and Perez-Matus, A and Itoi, S and Sugita, H and Bernardi, G}, title = {Evolutionary origin of the Atlantic Cabo Verde nibbler (Girella stuebeli), a member of a primarily Pacific Ocean family of antitropical herbivorous reef fishes.}, journal = {Molecular phylogenetics and evolution}, volume = {156}, number = {}, pages = {107021}, doi = {10.1016/j.ympev.2020.107021}, pmid = {33248204}, issn = {1095-9513}, mesh = {Animals ; Atlantic Ocean ; *Biological Evolution ; Cabo Verde ; Calibration ; *Coral Reefs ; Geography ; Mitochondria/genetics ; Pacific Ocean ; Perciformes/*physiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Time Factors ; }, abstract = {Nibblers (family Girellidae) are reef fishes that are mostly distributed in the Indo-Pacific, with one exception: Girella stuebeli, which is found in the Cabo Verde Archipelago, in the Atlantic Ocean. We capitalized on this unusual distribution to study the evolutionary history of the girellids, and determine the relationship between G. stuebeli and the remaining nibbler taxa. Based on thousands of genomic markers (RAD sequences), we identified the closest relatives of G. stuebeli as being a clade of three species endemic to the northwestern Pacific, restricted to the Sea of Japan and vicinity. This clade diverged from G. stuebeli approximately 2.2 Mya. Two alternative potential routes of migration may explain this affinity: a western route, from the Tropical Eastern Pacific and the Tropical Western Atlantic, and an eastern route via the Indian Ocean and Southern Africa. The geological history and oceanography of the regions combined with molecular data presented here, suggest that the eastern route of invasion (via the Indian Ocean and Southern Africa) is a more likely scenario.}, } @article {pmid33253201, year = {2020}, author = {Bjedov, I and Cochemé, HM and Foley, A and Wieser, D and Woodling, NS and Castillo-Quan, JI and Norvaisas, P and Lujan, C and Regan, JC and Toivonen, JM and Murphy, MP and Thornton, J and Kinghorn, KJ and Neufeld, TP and Cabreiro, F and Partridge, L}, title = {Fine-tuning autophagy maximises lifespan and is associated with changes in mitochondrial gene expression in Drosophila.}, journal = {PLoS genetics}, volume = {16}, number = {11}, pages = {e1009083}, pmid = {33253201}, issn = {1553-7404}, support = {MC_UP_1605/6/MRC_/Medical Research Council/United Kingdom ; 214589/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; 102532/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; MC_UP_1102/10/MRC_/Medical Research Council/United Kingdom ; 102531/Z/13/A/WT_/Wellcome Trust/United Kingdom ; MC-A654-5QC80/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/M02492X/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_00015/3/MRC_/Medical Research Council/United Kingdom ; C416/A25145/CRUK_/Cancer Research UK/United Kingdom ; 28990/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Aging/genetics ; Animals ; Autophagy/*genetics ; Autophagy-Related Protein-1 Homolog/genetics/metabolism ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/genetics ; Gene Expression/genetics ; Gene Expression Regulation/genetics ; Genes, Mitochondrial/genetics ; Insulin Receptor Substrate Proteins/genetics/metabolism ; Longevity/*genetics ; Mitochondria/*genetics ; Protein Serine-Threonine Kinases/genetics ; Receptor, Insulin/genetics ; Signal Transduction ; }, abstract = {Increased cellular degradation by autophagy is a feature of many interventions that delay ageing. We report here that increased autophagy is necessary for reduced insulin-like signalling (IIS) to extend lifespan in Drosophila and is sufficient on its own to increase lifespan. We first established that the well-characterised lifespan extension associated with deletion of the insulin receptor substrate chico was completely abrogated by downregulation of the essential autophagy gene Atg5. We next directly induced autophagy by over-expressing the major autophagy kinase Atg1 and found that a mild increase in autophagy extended lifespan. Interestingly, strong Atg1 up-regulation was detrimental to lifespan. Transcriptomic and metabolomic approaches identified specific signatures mediated by varying levels of autophagy in flies. Transcriptional upregulation of mitochondrial-related genes was the signature most specifically associated with mild Atg1 upregulation and extended lifespan, whereas short-lived flies, possessing strong Atg1 overexpression, showed reduced mitochondrial metabolism and up-regulated immune system pathways. Increased proteasomal activity and reduced triacylglycerol levels were features shared by both moderate and high Atg1 overexpression conditions. These contrasting effects of autophagy on ageing and differential metabolic profiles highlight the importance of fine-tuning autophagy levels to achieve optimal healthspan and disease prevention.}, } @article {pmid33255957, year = {2020}, author = {King, MS and Tavoulari, S and Mavridou, V and King, AC and Mifsud, J and Kunji, ERS}, title = {A Single Cysteine Residue in the Translocation Pathway of the Mitosomal ADP/ATP Carrier from Cryptosporidium parvum Confers a Broad Nucleotide Specificity.}, journal = {International journal of molecular sciences}, volume = {21}, number = {23}, pages = {}, pmid = {33255957}, issn = {1422-0067}, support = {MC_UU_00015/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_00015/7/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Atractyloside/analogs & derivatives/chemistry ; Bongkrekic Acid/chemistry ; Cryptosporidium parvum/*metabolism ; Cysteine/*metabolism ; Lactococcus lactis/metabolism ; Mitochondria/*metabolism ; Mitochondrial ADP, ATP Translocases/*chemistry/*metabolism ; Models, Molecular ; Mutant Proteins/chemistry/metabolism ; Nucleotides/*metabolism ; Phylogeny ; Protein Translocation Systems/*metabolism ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Structure-Activity Relationship ; Substrate Specificity ; }, abstract = {Cryptosporidiumparvum is a clinically important eukaryotic parasite that causes the disease cryptosporidiosis, which manifests with gastroenteritis-like symptoms. The protist has mitosomes, which are organelles of mitochondrial origin that have only been partially characterized. The genome encodes a highly reduced set of transport proteins of the SLC25 mitochondrial carrier family of unknown function. Here, we have studied the transport properties of one member of the C. parvum carrier family, demonstrating that it resembles the mitochondrial ADP/ATP carrier of eukaryotes. However, this carrier has a broader substrate specificity for nucleotides, transporting adenosine, thymidine, and uridine di- and triphosphates in contrast to its mitochondrial orthologues, which have a strict substrate specificity for ADP and ATP. Inspection of the putative translocation pathway highlights a cysteine residue, which is a serine in mitochondrial ADP/ATP carriers. When the serine residue is replaced by cysteine or larger hydrophobic residues in the yeast mitochondrial ADP/ATP carrier, the substrate specificity becomes broad, showing that this residue is important for nucleotide base selectivity in ADP/ATP carriers.}, } @article {pmid33257722, year = {2020}, author = {Mannen, H and Yonezawa, T and Murata, K and Noda, A and Kawaguchi, F and Sasazaki, S and Olivieri, A and Achilli, A and Torroni, A}, title = {Cattle mitogenome variation reveals a post-glacial expansion of haplogroup P and an early incorporation into northeast Asian domestic herds.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {20842}, pmid = {33257722}, issn = {2045-2322}, mesh = {Animals ; Base Sequence/genetics ; Breeding/methods ; Cattle/*genetics ; Chromosomes/genetics ; DNA, Mitochondrial/*genetics ; Evolution, Molecular ; Genetic Variation/genetics ; Genome, Mitochondrial/*genetics ; Haplotypes/genetics ; Japan ; Mitochondria/genetics ; Phylogeny ; }, abstract = {Surveys of mitochondrial DNA (mtDNA) variation have shown that worldwide domestic cattle are characterized by just a few major haplogroups. Two, T and I, are common and characterize Bos taurus and Bos indicus, respectively, while the other three, P, Q and R, are rare and are found only in taurine breeds. Haplogroup P is typical of extinct European aurochs, while intriguingly modern P mtDNAs have only been found in northeast Asian cattle. These Asian P mtDNAs are extremely rare with the exception of the Japanese Shorthorn breed, where they reach a frequency of 45.9%. To shed light on the origin of this haplogroup in northeast Asian cattle, we completely sequenced 14 Japanese Shorthorn mitogenomes belonging to haplogroup P. Phylogenetic and Bayesian analyses revealed: (1) a post-glacial expansion of aurochs carrying haplogroup P from Europe to Asia; (2) that all Asian P mtDNAs belong to a single sub-haplogroup (P1a), so far never detected in either European or Asian aurochs remains, which was incorporated into domestic cattle of continental northeastern Asia possibly ~ 3700 years ago; and (3) that haplogroup P1a mtDNAs found in the Japanese Shorthorn breed probably reached Japan about 650 years ago from Mongolia/Russia, in agreement with historical evidence.}, } @article {pmid33263876, year = {2020}, author = {Kaczanowski, S}, title = {Symbiotic Origin of Apoptosis.}, journal = {Results and problems in cell differentiation}, volume = {69}, number = {}, pages = {253-280}, pmid = {33263876}, issn = {0080-1844}, mesh = {Animals ; *Apoptosis ; *Biological Evolution ; *Eukaryota ; Mitochondria/*microbiology ; Phylogeny ; *Symbiosis ; }, abstract = {The progress of evolutionary biology has revealed that symbiosis played a basic role in the evolution of complex eukaryotic organisms, including humans. Mitochondria are actually simplified endosymbiotic bacteria currently playing the role of cellular organelles. Mitochondrial domestication occurred at the very beginning of eukaryotic evolution. Mitochondria have two different basic functions: they produce energy using oxidative respiration, and they initiate different forms of apoptotic programmed/regulated cell death. Apoptotic programmed cell death may have different cytological forms. Mechanisms of apoptotic programmed cell death exist even in the unicellular organisms, and they play a basic role in the development of complex multicellular organisms, such as fungi, green plants, and animals. Multicellularity was independently established many times among eukaryotes. There are indications that apoptotic programmed cell death is a trait required for the establishment of multicellularity. Regulated cell death is initiated by many different parallel biochemical pathways. It is generally accepted that apoptosis evolved during mitochondrial domestication. However, there are different hypothetical models of the origin of apoptosis. The phylogenetic studies of my group indicate that apoptosis probably evolved during an evolutionary arms race between host ancestral eukaryotic predators and ancestral prey mitochondria (named protomitochondria). Protomitochondrial prey produced many different toxins as a defense against predators. From these toxins evolved extant apoptotic factors. There are indications that aerobic respiration and apoptosis co-evolved and are functionally linked in extant organisms. Perturbations of apoptosis and oxidative respiration are frequently observed during neoplastic transition. Our group showed that perturbations of apoptosis in yeasts also cause perturbations of oxidative respiration.}, } @article {pmid33263877, year = {2020}, author = {Lupette, J and Maréchal, E}, title = {The Puzzling Conservation and Diversification of Lipid Droplets from Bacteria to Eukaryotes.}, journal = {Results and problems in cell differentiation}, volume = {69}, number = {}, pages = {281-334}, pmid = {33263877}, issn = {0080-1844}, mesh = {Bacteria/*chemistry/genetics ; Biological Evolution ; Eukaryota/*chemistry/genetics ; Lipid Droplets/*chemistry ; Organelles ; Plastids ; Symbiosis ; }, abstract = {Membrane compartments are amongst the most fascinating markers of cell evolution from prokaryotes to eukaryotes, some being conserved and the others having emerged via a series of primary and secondary endosymbiosis events. Membrane compartments comprise the system limiting cells (one or two membranes in bacteria, a unique plasma membrane in eukaryotes) and a variety of internal vesicular, subspherical, tubular, or reticulated organelles. In eukaryotes, the internal membranes comprise on the one hand the general endomembrane system, a dynamic network including organelles like the endoplasmic reticulum, the Golgi apparatus, the nuclear envelope, etc. and also the plasma membrane, which are linked via direct lateral connectivity (e.g. between the endoplasmic reticulum and the nuclear outer envelope membrane) or indirectly via vesicular trafficking. On the other hand, semi-autonomous organelles, i.e. mitochondria and chloroplasts, are disconnected from the endomembrane system and request vertical transmission following cell division. Membranes are organized as lipid bilayers in which proteins are embedded. The budding of some of these membranes, leading to the formation of the so-called lipid droplets (LDs) loaded with hydrophobic molecules, most notably triacylglycerol, is conserved in all clades. The evolution of eukaryotes is marked by the acquisition of mitochondria and simple plastids from Gram-positive bacteria by primary endosymbiosis events and the emergence of extremely complex plastids, collectively called secondary plastids, bounded by three to four membranes, following multiple and independent secondary endosymbiosis events. There is currently no consensus view of the evolution of LDs in the Tree of Life. Some features are conserved; others show a striking level of diversification. Here, we summarize the current knowledge on the architecture, dynamics, and multitude of functions of the lipid droplets in prokaryotes and in eukaryotes deriving from primary and secondary endosymbiosis events.}, } @article {pmid33266387, year = {2020}, author = {Schirrmacher, V}, title = {Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism.}, journal = {Biomedicines}, volume = {8}, number = {11}, pages = {}, pmid = {33266387}, issn = {2227-9059}, abstract = {Mitochondria are of great relevance to health, and their dysregulation is associated with major chronic diseases. Research on mitochondria-156 brand new publications from 2019 and 2020-have contributed to this review. Mitochondria have been fundamental for the evolution of complex organisms. As important and semi-autonomous organelles in cells, they can adapt their function to the needs of the respective organ. They can program their function to energy supply (e.g., to keep heart muscle cells going, life-long) or to metabolism (e.g., to support hepatocytes and liver function). The capacity of mitochondria to re-program between different options is important for all cell types that are capable of changing between a resting state and cell proliferation, such as stem cells and immune cells. Major chronic diseases are characterized by mitochondrial dysregulation. This will be exemplified by cardiovascular diseases, metabolic syndrome, neurodegenerative diseases, immune system disorders, and cancer. New strategies for intervention in chronic diseases will be presented. The tumor microenvironment can be considered a battlefield between cancer and immune defense, competing for energy supply and metabolism. Cancer cachexia is considered as a final stage of cancer progression. Nevertheless, the review will present an example of complete remission of cachexia via immune cell transfer. These findings should encourage studies along the lines of mitochondria, energy supply, and metabolism.}, } @article {pmid33270708, year = {2020}, author = {Dell, AC and Curry, MC and Yarnell, KM and Starbuck, GR and Wilson, PB}, title = {Mitochondrial D-loop sequence variation and maternal lineage in the endangered Cleveland Bay horse.}, journal = {PloS one}, volume = {15}, number = {12}, pages = {e0243247}, pmid = {33270708}, issn = {1932-6203}, mesh = {Animals ; Cluster Analysis ; DNA, Mitochondrial/*genetics ; Endangered Species ; Genetic Variation/genetics ; Haplotypes/genetics ; Horses/*genetics ; Maternal Inheritance/*genetics ; Mitochondria/genetics ; Phylogeny ; Sequence Analysis, DNA/methods/veterinary ; }, abstract = {Genetic diversity and maternal ancestry line relationships amongst a sample of 96 Cleveland Bay horses were investigated using a 479bp length of mitochondrial D-loop sequence. The analysis yielded at total of 11 haplotypes with 27 variable positions, all of which have been described in previous equine mitochondrial DNA d-loop studies. Four main haplotype clusters were present in the Cleveland Bay breed describing 89% of the total sample. This suggests that only four principal maternal ancestry lines exist in the present-day global Cleveland Bay population. Comparison of these sequences with other domestic horse haplotypes (Fig 2) shows a close association of the Cleveland Bay horse with Northern European (Clade C), Iberian (Clade A) and North African (Clade B) horse breeds. This indicates that the Cleveland Bay horse may not have evolved exclusively from the now extinct Chapman horse, as previous work as suggested. The Cleveland Bay horse remains one of only five domestic horse breeds classified as Critical on the Rare Breeds Survival Trust (UK) Watchlist and our results provide important information on the origins of this breed and represent a valuable tool for conservation purposes.}, } @article {pmid33278511, year = {2021}, author = {Rukavina-Mikusic, IA and Rey, M and Martinefski, M and Tripodi, V and Valdez, LB}, title = {Temporal evolution of cardiac mitochondrial dysfunction in a type 1 diabetes model. Mitochondrial complex I impairment, and H2O2 and NO productions as early subcellular events.}, journal = {Free radical biology & medicine}, volume = {162}, number = {}, pages = {129-140}, doi = {10.1016/j.freeradbiomed.2020.11.033}, pmid = {33278511}, issn = {1873-4596}, mesh = {Animals ; *Diabetes Mellitus, Experimental ; *Diabetes Mellitus, Type 1/chemically induced ; Hydrogen Peroxide ; Male ; Mitochondria, Heart ; Rats ; Rats, Wistar ; }, abstract = {The aim of this work was to study the early events that occur in heart mitochondria and to analyse the temporal evolution of cardiac mitochondrial dysfunction in a type 1 diabetes model. Male Wistar rats were injected with Streptozotocin (STZ, single dose, 60 mg × kg[-1], i.p.) and hyperglycemic state was confirmed 72 h later. The animals were sacrificed 10 or 14 days after STZ-injection. Heart mitochondrial state 3 O2 consumption sustained by malate-glutamate (21%) or by succinate (16%), and complexes I-III (27%), II-III (24%) and IV (22%) activities were lower in STZ group, when animals were sacrificed at day 14, i.e. ~11 days of hyperglycemia. In contrast, after 10 days of STZ-injection (~7 days of hyperglycemia), only the state 3 O2 consumption sustained by malate-glutamate (23%) and its corresponding respiratory control (30%) were lower in diabetic rats, in accordance with complex I-III activity reduction (17%). Therefore, this time (~7 days of hyperglycemia) has been considered as an "early stage" of cardiac mitochondrial dysfunction. At this point, mitochondrial production rates of H2O2 (117%), NO (30%) and ONOO[-] (~225%), and mtNOS expression (29%) were higher; and mitochondrial SOD activity (15%) and [GSH + GSSG] (28%) were lower in diabetic rats. Linear correlations between the modified mitochondrial parameters and glycemias were observed. PGC-1α expression was similar between groups, suggesting that mitochondrial biogenesis was not triggered in this initial phase of mitochondrial dysfunction. Consequently, complex I, H2O2 and NO could be considered early subcellular signals of cardiac mitochondrial dysfunction, with NO and H2O2 being located upstream de novo synthesis of mitochondria.}, } @article {pmid33278586, year = {2021}, author = {Lee, Y and Ni, G and Shin, J and Kim, T and Kern, EMA and Kim, Y and Kim, SC and Chan, B and Goto, R and Nakano, T and Park, JK}, title = {Phylogeography of Mytilisepta virgata (Mytilidae: Bivalvia) in the northwestern Pacific: Cryptic mitochondrial lineages and mito-nuclear discordance.}, journal = {Molecular phylogenetics and evolution}, volume = {157}, number = {}, pages = {107037}, doi = {10.1016/j.ympev.2020.107037}, pmid = {33278586}, issn = {1095-9513}, mesh = {Animals ; Cell Nucleus/*genetics ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/genetics ; Genes, Mitochondrial ; Genetic Variation ; Genetics, Population ; Haplotypes/genetics ; Mitochondria/*genetics ; Mytilidae/*genetics ; Pacific Ocean ; Phylogeny ; *Phylogeography ; Principal Component Analysis ; Time Factors ; }, abstract = {The purplish bifurcate mussel Mytilisepta virgata is widely distributed and represents one of the major components of the intertidal community in the northwestern Pacific (NWP). Here, we characterized population genetic structure of NWP populations throughout nearly their whole distribution range using both mitochondrial (mtDNA cox1) and nuclear (ITS1) markers. Population genetic analyses for mtDNA cox 1 sequences revealed two monophyletic lineages (i.e., southern and northern lineages) geographically distributed according to the two different surface water temperature zones in the NWP. The timing of the lineage split is estimated at the Pliocene- mid-Pleistocene (5.49-1.61 Mya), which is consistent with the timing of the historical isolation of the East Sea/Sea of Japan from the South and East China Seas due to sea level decline during glacial cycles. Historical sea level fluctuation during the Pliocene-Pleistocene and subsequent adaptation of mussels to different surface water temperature zones may have contributed to shaping the contemporary genetic diversity and deep divergence of the two mitochondrial lineages. In contrast to mtDNA sequences, a clear lineage split between the two mitochondrial lineages was not found in ITS1 sequences, which showed a star-like structure composed of a mixture of southern and northern mitochondrial lineages. Possible reasons for this type of mito-nuclear discordance include stochastic divergence in the coalescent processes of the two molecular markers, or balancing selection under different marine environments. Cryptic speciation cannot be ruled out from these results, and future work using genomic analyses is required to address whether the thermal physiology of these mussels corresponds to the deep divergence of their mitochondrial genes and to test for the existence of morphologically indistinguishable but genetically separate cryptic species.}, } @article {pmid33279689, year = {2021}, author = {Sun, D and Niu, Z and Zheng, HX and Wu, F and Jiang, L and Han, TQ and Wei, Y and Wang, J and Jin, L}, title = {A Mitochondrial DNA Variant Elevates the Risk of Gallstone Disease by Altering Mitochondrial Function.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {11}, number = {4}, pages = {1211-1226.e15}, pmid = {33279689}, issn = {2352-345X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asian People/*genetics ; Case-Control Studies ; China/epidemiology ; Cholesterol/metabolism ; DNA, Mitochondrial/analysis/*genetics ; Female ; Gallstones/epidemiology/genetics/*pathology ; *Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Mitochondria/genetics/*pathology ; *Polymorphism, Single Nucleotide ; Risk Factors ; Young Adult ; }, abstract = {BACKGROUND AND AIMS: Gallstone disease (cholelithiasis) is a cholesterol-related metabolic disorders with strong familial predisposition. Mitochondrial DNA (mtDNA) variants accumulated during human evolution are associated with some metabolic disorders related to modified mitochondrial function. The mechanistic links between mtDNA variants and gallstone formation need further exploration.

METHODS: In this study, we explored the possible associations of mtDNA variants with gallstone disease by comparing 104 probands and 300 controls in a Chinese population. We constructed corresponding cybrids using trans-mitochondrial technology to investigate the underlying mechanisms of these associations. Mitochondrial respiratory chain complex activity and function and cholesterol metabolism were assessed in the trans-mitochondrial cell models.

RESULTS: Here, we found a significant association of mtDNA 827A>G with an increased risk of familial gallstone disease in a Chinese population (odds ratio [OR]: 4.5, 95% confidence interval [CI]: 2.1-9.4, P=1.2×10[-4]). Compared with 827A cybrids (haplogroups B4a and B4c), 827G cybrids (haplogroups B4b and B4d) had impaired mitochondrial respiratory chain complex activity and function and activated JNK and AMPK signaling pathways. Additionally, the 827G cybrids showed disturbances in cholesterol transport and accelerated development of gallstones. Specifically, cholesterol transport through the transporter ABCG5/8 was increased via activation of the AMPK signaling pathway in 827G cybrids.

CONCLUSIONS: Our findings reveal that mtDNA 827A>G induces aberrant mitochondrial function and abnormal cholesterol transport, resulting in increased occurrence of gallstones. The results provide an important biological basis for the clinical diagnosis and prevention of gallstone disease in the future.}, } @article {pmid33280130, year = {2021}, author = {Dahuja, A and Kumar, RR and Sakhare, A and Watts, A and Singh, B and Goswami, S and Sachdev, A and Praveen, S}, title = {Role of ATP-binding cassette transporters in maintaining plant homeostasis under abiotic and biotic stresses.}, journal = {Physiologia plantarum}, volume = {171}, number = {4}, pages = {785-801}, doi = {10.1111/ppl.13302}, pmid = {33280130}, issn = {1399-3054}, support = {Sanction no. TG-3079//Indian Council of Agricultural Research/ ; sanction no. 21-56 TG3064//Indian Council of Agricultural Research/ ; }, mesh = {*ATP-Binding Cassette Transporters/genetics/metabolism ; Biological Transport ; Homeostasis ; *Plants/metabolism ; Stress, Physiological ; }, abstract = {The ATP-binding cassette (ABC) transporters belong to a large protein family predominantly present in diverse species. ABC transporters are driven by ATP hydrolysis and can act as exporters as well as importers. These proteins are localized in the membranes of chloroplasts, mitochondria, peroxisomes and vacuoles. ABC proteins are involved in regulating diverse biological processes in plants, such as growth, development, uptake of nutrients, tolerance to biotic and abiotic stresses, tolerance to metal toxicity, stomatal closure, shape and size of grains, protection of pollens, transport of phytohormones, etc. In mitochondria and chloroplast, the iron metabolism and its transport across the membrane are mediated by ABC transporters. Tonoplast-localized ABC transporters are involved in internal detoxification of metal ion; thus protecting against the DNA impairment and maintaining cell growth. ABC transporters are involved in the transport of secondary metabolites inside the cells. Microorganisms also engage a large number of ABC transporters to import and expel substrates decisive for their pathogenesis. ABC transporters also suppress the seed embryonic growth until favorable conditions come. This review aims at giving insights on ABC transporters, their evolution, structure, functions and roles in different biological processes for helping the terrestrial plants to survive under adverse environmental conditions. These specialized plant membrane transporters ensure a sustainable economic yield and high-quality products, especially under unfavorable conditions of growth. These transporters can be suitably manipulated to develop 'Plants for the Future'.}, } @article {pmid33287726, year = {2020}, author = {Urantówka, AD and Kroczak, A and Mackiewicz, P}, title = {New view on the organization and evolution of Palaeognathae mitogenomes poses the question on the ancestral gene rearrangement in Aves.}, journal = {BMC genomics}, volume = {21}, number = {1}, pages = {874}, pmid = {33287726}, issn = {1471-2164}, support = {2017/25/N/NZ8/01197//National Science Centre Poland (Narodowe Centrum Nauki, Polska)/ ; 307//Wroclawskie Centrum Sieciowo-Superkomputerowe, Politechnika Wroclawska/ ; }, mesh = {Animals ; Birds/genetics ; Evolution, Molecular ; Gene Rearrangement ; *Genome, Mitochondrial ; *Palaeognathae ; Phylogeny ; }, abstract = {BACKGROUND: Bird mitogenomes differ from other vertebrates in gene rearrangement. The most common avian gene order, identified first in Gallus gallus, is considered ancestral for all Aves. However, other rearrangements including a duplicated control region and neighboring genes have been reported in many representatives of avian orders. The repeated regions can be easily overlooked due to inappropriate DNA amplification or genome sequencing. This raises a question about the actual prevalence of mitogenomic duplications and the validity of the current view on the avian mitogenome evolution. In this context, Palaeognathae is especially interesting because is sister to all other living birds, i.e. Neognathae. So far, a unique duplicated region has been found in one palaeognath mitogenome, that of Eudromia elegans.

RESULTS: Therefore, we applied an appropriate PCR strategy to look for omitted duplications in other palaeognaths. The analyses revealed the duplicated control regions with adjacent genes in Crypturellus, Rhea and Struthio as well as ND6 pseudogene in three moas. The copies are very similar and were subjected to concerted evolution. Mapping the presence and absence of duplication onto the Palaeognathae phylogeny indicates that the duplication was an ancestral state for this avian group. This feature was inherited by early diverged lineages and lost two times in others. Comparison of incongruent phylogenetic trees based on mitochondrial and nuclear sequences showed that two variants of mitogenomes could exist in the evolution of palaeognaths. Data collected for other avian mitogenomes revealed that the last common ancestor of all birds and early diverging lineages of Neoaves could also possess the mitogenomic duplication.

CONCLUSIONS: The duplicated control regions with adjacent genes are more common in avian mitochondrial genomes than it was previously thought. These two regions could increase effectiveness of replication and transcription as well as the number of replicating mitogenomes per organelle. In consequence, energy production by mitochondria may be also more efficient. However, further physiological and molecular analyses are necessary to assess the potential selective advantages of the mitogenome duplications.}, } @article {pmid33289389, year = {2021}, author = {Sureka, R and Mishra, R}, title = {Identification of Evolutionarily Conserved Nuclear Matrix Proteins and Their Prokaryotic Origins.}, journal = {Journal of proteome research}, volume = {20}, number = {1}, pages = {518-530}, doi = {10.1021/acs.jproteome.0c00550}, pmid = {33289389}, issn = {1535-3907}, mesh = {Animals ; *Drosophila melanogaster/genetics ; Eukaryotic Cells ; *Evolution, Molecular ; Nuclear Matrix ; *Nuclear Matrix-Associated Proteins ; Phylogeny ; *Prokaryotic Cells ; }, abstract = {Compared to prokaryotic cells, a typical eukaryotic cell is much more complex along with its endomembrane system and membrane-bound organelles. Although the endosymbiosis theories convincingly explain the evolution of membrane-bound organelles such as mitochondria and chloroplasts, very little is understood about the evolutionary origins of the nucleus, the defining feature of eukaryotes. Most studies on nuclear evolution have not been able to take into consideration the underlying structural framework of the nucleus, attributed to the nuclear matrix (NuMat), a ribonucleoproteinaceous structure. This can largely be attributed to the lack of annotation of its core components. Since NuMat has been shown to provide a structural platform for facilitating a variety of nuclear functions such as replication, transcription, and splicing, it is important to identify its protein components to better understand these processes. In this study, we address this issue using the developing embryos of Drosophila melanogaster and Danio rerio and identify 362 core NuMat proteins that are conserved between the two organisms. We further compare our results with publicly available Mus musculus NuMat dataset and Homo sapiens cellular localization dataset to define the core homologous NuMat proteins consisting of 252 proteins. We find that of them, 86 protein groups have originated from pre-existing proteins in prokaryotes. While 36 were conserved across all eukaryotic supergroups, 14 new proteins evolved before the evolution of the last eukaryotic common ancestor and together, these 50 proteins out of the 252 core conserved NuMat proteins are conserved across all eukaryotes, indicating their indispensable nature for nuclear function for over 1.5 billion years of eukaryotic history. Our analysis paves the way to understand the evolution of the complex internal nuclear architecture and its functions.}, } @article {pmid33293686, year = {2020}, author = {West, KM and Richards, ZT and Harvey, ES and Susac, R and Grealy, A and Bunce, M}, title = {Under the karst: detecting hidden subterranean assemblages using eDNA metabarcoding in the caves of Christmas Island, Australia.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {21479}, pmid = {33293686}, issn = {2045-2322}, mesh = {Animals ; Australia ; *Biodiversity ; Cell Nucleus/genetics ; *DNA Barcoding, Taxonomic/methods ; DNA, Environmental/*genetics ; Eukaryota/genetics ; Indian Ocean ; *Metagenomics/methods ; Mitochondria/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Subterranean ecosystems are understudied and challenging to conventionally survey given the inaccessibility of underground voids and networks. In this study, we conducted a eukaryotic environmental DNA (eDNA) metabarcoding survey across the karst landscape of Christmas Island, (Indian Ocean, Australia) to evaluate the utility of this non-invasive technique to detect subterranean aquatic 'stygofauna' assemblages. Three metabarcoding assays targeting the mitochondrial 16S rRNA and nuclear 18S genes were applied to 159 water and sediment samples collected from 23 caves and springs across the island. Taken together, our assays detected a wide diversity of chordates, cnidarians, porifera, arthropods, molluscs, annelids and bryozoans from 71 families across 60 orders. We report a high level of variation between cave and spring subterranean community compositions which are significantly influenced by varying levels of salinity. Additionally, we show that dissolved oxygen and longitudinal gradients significantly affect biotic assemblages within cave communities. Lastly, we combined eDNA-derived community composition and environmental (water quality) data to predict potential underground interconnectivity across Christmas Island. We identified three cave and spring groups that showed a high degree of biotic and abiotic similarity indicating likely local connectivity. This study demonstrates the applicability of eDNA metabarcoding to detect subterranean eukaryotic communities and explore underground interconnectivity.}, } @article {pmid33296646, year = {2020}, author = {Van Keuren, AM and Tsai, CW and Balderas, E and Rodriguez, MX and Chaudhuri, D and Tsai, MF}, title = {Mechanisms of EMRE-Dependent MCU Opening in the Mitochondrial Calcium Uniporter Complex.}, journal = {Cell reports}, volume = {33}, number = {10}, pages = {108486}, pmid = {33296646}, issn = {2211-1247}, support = {R01 GM129345/GM/NIGMS NIH HHS/United States ; R01 HL141353/HL/NHLBI NIH HHS/United States ; }, mesh = {Calcium/metabolism ; Calcium Channels/*metabolism/physiology/ultrastructure ; Calcium-Binding Proteins/*metabolism/physiology/ultrastructure ; Cation Transport Proteins/*metabolism/physiology/ultrastructure ; HEK293 Cells ; Humans ; Mitochondria/metabolism ; Mitochondrial Membrane Transport Proteins/*metabolism/physiology/ultrastructure ; Mitochondrial Membranes/metabolism ; }, abstract = {The mitochondrial calcium uniporter is a multi-subunit Ca[2+]-activated Ca[2+] channel, made up of the pore-forming MCU protein, a metazoan-specific EMRE subunit, and MICU1/MICU2, which mediate Ca[2+] activation. It has been established that metazoan MCU requires EMRE binding to conduct Ca[2+], but how EMRE promotes MCU opening remains unclear. Here, we demonstrate that EMRE controls MCU activity via its transmembrane helix, while using an N-terminal PKP motif to strengthen binding with MCU. Opening of MCU requires hydrophobic interactions mediated by MCU residues near the pore's luminal end. Enhancing these interactions by single mutation allows human MCU to transport Ca[2+] without EMRE. We further show that EMRE may facilitate MCU opening by stabilizing the open state in a conserved MCU gating mechanism, present also in non-metazoan MCU homologs. These results provide insights into the evolution of the uniporter machinery and elucidate the mechanism underlying the physiologically crucial EMRE-dependent MCU activation process.}, } @article {pmid33297963, year = {2020}, author = {Ren, RC and Yan, XW and Zhao, YJ and Wei, YM and Lu, X and Zang, J and Wu, JW and Zheng, GM and Ding, XH and Zhang, XS and Zhao, XY}, title = {The novel E-subgroup pentatricopeptide repeat protein DEK55 is responsible for RNA editing at multiple sites and for the splicing of nad1 and nad4 in maize.}, journal = {BMC plant biology}, volume = {20}, number = {1}, pages = {553}, pmid = {33297963}, issn = {1471-2229}, support = {91735301//National Natural Science Foundation of China/ ; 2016ZX08003-003//The National Plant Transgenic Program/ ; ts201712024//Taishan Scholar Project of Shandong Province/ ; SYL2017YSTD03//Shandong "Double Tops" Program/ ; dxkt201707//the project from State Key Laboratory of Crop Biology/ ; }, mesh = {Base Sequence ; Binding Sites/genetics ; Electron Transport Complex I/*genetics/metabolism ; Gene Expression Regulation, Plant ; Introns/genetics ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/classification/genetics/metabolism ; Mutation ; NADH Dehydrogenase/*genetics/metabolism ; Phylogeny ; Plant Proteins/classification/*genetics/metabolism ; Plants, Genetically Modified ; *RNA Editing ; *RNA Splicing ; Reverse Transcriptase Polymerase Chain Reaction ; Seeds/genetics/metabolism ; Zea mays/*genetics/metabolism ; }, abstract = {BACKGROUND: Pentatricopeptide repeat (PPR) proteins compose a large protein family whose members are involved in both RNA processing in organelles and plant growth. Previous reports have shown that E-subgroup PPR proteins are involved in RNA editing. However, the additional functions and roles of the E-subgroup PPR proteins are unknown.

RESULTS: In this study, we developed and identified a new maize kernel mutant with arrested embryo and endosperm development, i.e., defective kernel (dek) 55 (dek55). Genetic and molecular evidence suggested that the defective kernels resulted from a mononucleotide alteration (C to T) at + 449 bp within the open reading frame (ORF) of Zm00001d014471 (hereafter referred to as DEK55). DEK55 encodes an E-subgroup PPR protein within the mitochondria. Molecular analyses showed that the editing percentage of 24 RNA editing sites decreased and that of seven RNA editing sites increased in dek55 kernels, the sites of which were distributed across 14 mitochondrial gene transcripts. Moreover, the splicing efficiency of nad1 introns 1 and 4 and nad4 intron 1 significantly decreased in dek55 compared with the wild type (WT). These results indicate that DEK55 plays a crucial role in RNA editing at multiple sites as well as in the splicing of nad1 and nad4 introns. Mutation in the DEK55 gene led to the dysfunction of mitochondrial complex I. Moreover, yeast two-hybrid assays showed that DEK55 interacts with two multiple organellar RNA-editing factors (MORFs), i.e., ZmMORF1 (Zm00001d049043) and ZmMORF8 (Zm00001d048291).

CONCLUSIONS: Our results demonstrated that a mutation in the DEK55 gene affects the mitochondrial function essential for maize kernel development. Our results also provide novel insight into the molecular functions of E-subgroup PPR proteins involved in plant organellar RNA processing.}, } @article {pmid33301090, year = {2021}, author = {Duminil, J and Besnard, G}, title = {Utility of the Mitochondrial Genome in Plant Taxonomic Studies.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2222}, number = {}, pages = {107-118}, pmid = {33301090}, issn = {1940-6029}, mesh = {*DNA Barcoding, Taxonomic ; *Genome, Mitochondrial ; *Genomics/methods ; Phylogeny ; Phylogeography ; Plants/*classification/*genetics ; Polymorphism, Genetic ; Recombination, Genetic ; Sequence Analysis, DNA ; }, abstract = {Size, structure, and sequence content lability of plant mitochondrial genome (mtDNA) across species has sharply limited its use in taxonomic studies. Historically, mtDNA variation has been first investigated with RFLPs, while the development of universal primers then allowed studying sequence polymorphisms within short genomic regions (<3 kb). The recent advent of NGS technologies now offers new opportunities by greatly facilitating the assembly of longer mtDNA regions, and even full mitogenomes. Phylogenetic works aiming at comparing signals from different genomic compartments (i.e., nucleus, chloroplast, and mitochondria) have been developed on a few plant lineages, and have been shown especially relevant in groups with contrasted inheritance of organelle genomes. This chapter first reviews the main characteristics of mtDNA and the application offered in taxonomic studies. It then presents tips for best sequencing protocol based on NGS data to be routinely used in mtDNA-based phylogenetic studies.}, } @article {pmid33301801, year = {2021}, author = {Cortassa, S and Juhaszova, M and Aon, MA and Zorov, DB and Sollott, SJ}, title = {Mitochondrial Ca[2+], redox environment and ROS emission in heart failure: Two sides of the same coin?.}, journal = {Journal of molecular and cellular cardiology}, volume = {151}, number = {}, pages = {113-125}, pmid = {33301801}, issn = {1095-8584}, support = {Z99 AG999999/ImNIH/Intramural NIH HHS/United States ; ZIA AG000250/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Heart Failure/*metabolism ; Humans ; Mitochondria, Heart/*metabolism ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species/*metabolism ; Sodium/metabolism ; }, abstract = {Heart failure (HF) is a progressive, debilitating condition characterized, in part, by altered ionic equilibria, increased ROS production and impaired cellular energy metabolism, contributing to variable profiles of systolic and diastolic dysfunction with significant functional limitations and risk of premature death. We summarize current knowledge concerning changes of intracellular Na[+] and Ca[2+] control mechanisms during the disease progression and their consequences on mitochondrial Ca[2+] homeostasis and the shift in redox balance. Absent existing biological data, our computational modeling studies advance a new 'in silico' analysis to reconcile existing opposing views, based on different experimental HF models, regarding variations in mitochondrial Ca[2+] concentration that participate in triggering and perpetuating oxidative stress in the failing heart and their impact on cardiac energetics. In agreement with our hypothesis and the literature, model simulations demonstrate the possibility that the heart's redox status together with cytoplasmic Na[+] concentrations act as regulators of mitochondrial Ca[2+] levels in HF and of the bioenergetics response that will ultimately drive ATP supply and oxidative stress. The resulting model predictions propose future directions to study the evolution of HF as well as other types of heart disease, and to develop novel testable mechanistic hypotheses that may lead to improved therapeutics.}, } @article {pmid33301927, year = {2021}, author = {Jaimes Díaz, H and Martínez Covarrubias, EI and Murcia Garzón, JE and Flores Valdez, M and Muñoz Ramírez, ZY and Ramírez Calzada, CA and Bohra, R and Méndez Tenorio, A}, title = {Phylogenomic study and classification of mitochondrial DNA through virtual genomic fingerprints.}, journal = {Mitochondrion}, volume = {57}, number = {}, pages = {294-299}, doi = {10.1016/j.mito.2020.11.016}, pmid = {33301927}, issn = {1872-8278}, mesh = {Animals ; Computer Simulation ; DNA Fingerprinting/*methods ; DNA, Mitochondrial/classification/*genetics ; Genomics/*methods ; Haplotypes ; Humans ; Mitochondria/*classification/genetics ; Neanderthals/genetics ; Pan paniscus/genetics ; Pan troglodytes/genetics ; Phylogeny ; }, abstract = {In the present study, we evaluated the ability of the Virtual Analysis Method for Phylogenomic fingerprint Estimation (VAMPhyRE) toolkit to classify human mitochondrial DNA (mtDNA) haplogroups. In total, 357 random mtDNA sequences were obtained from different haplogroups, based on the classification of PhyloTree. Additionally, we included a control group of five sequences (Pan paniscus, Pan troglodytes, Homo sapiens neanderthalensis, Yoruba15, and the revised Cambridge reference sequence). VAMPhyRE employs a virtual hybridization technique, using probes that specifically bind to their complementary sequences in the genome. We used 65,536 probes of 8 nucleotides to identify potential sites where hybridization occurs between the mtDNA and the specific probe, forming different heteroduplexes and thus, creating a unique and specific genomic fingerprint for each sequence. Genomic fingerprints were compared, and a table of distances was calculated to obtain a mitochondrial phylogenomic tree with the macrohaplogroups, L, N, M, and R, and their corresponding haplogroups, according to universal nomenclature. The results obtained suggest an accuracy of 97.25% for the distribution of the 357 mtDNA sequences in the four macrohaplogroups and their corresponding haplogroups when compared with other mtDNA classification tools that require reference sequences and do not offer an analysis based on an evolutionary approach. These data are available online at http://biomedbiotec.encb.ipn.mx/VAMPhyRE/.}, } @article {pmid33302466, year = {2020}, author = {Geary, DC}, title = {Mitochondrial Functions, Cognition, and the Evolution of Intelligence: Reply to Commentaries and Moving Forward.}, journal = {Journal of Intelligence}, volume = {8}, number = {4}, pages = {}, pmid = {33302466}, issn = {2079-3200}, abstract = {In response to commentaries, I address questions regarding the proposal that general intelligence (g) is a manifestation of the functioning of intramodular and intermodular brain networks undergirded by the efficiency of mitochondrial functioning (Geary 2018). The core issues include the relative contribution of mitochondrial functioning to individual differences in g; studies that can be used to test associated hypotheses; and, the adaptive function of intelligence from an evolutionary perspective. I attempt to address these and related issues, as well as note areas in which other issues remain to be addressed.}, } @article {pmid33306962, year = {2021}, author = {Namba, T and Nardelli, J and Gressens, P and Huttner, WB}, title = {Metabolic Regulation of Neocortical Expansion in Development and Evolution.}, journal = {Neuron}, volume = {109}, number = {3}, pages = {408-419}, doi = {10.1016/j.neuron.2020.11.014}, pmid = {33306962}, issn = {1097-4199}, mesh = {Animals ; *Biological Evolution ; Cell Proliferation/*physiology ; Humans ; Metabolic Networks and Pathways/*physiology ; Neocortex/*metabolism ; Neural Stem Cells/*metabolism ; Neurogenesis/*physiology ; Neurons/physiology ; }, abstract = {The neocortex, the seat of our higher cognitive abilities, has expanded in size during the evolution of certain mammals such as primates, including humans. This expansion occurs during development and is linked to the proliferative capacity of neural stem and progenitor cells (NPCs) in the neocortex. A number of cell-intrinsic and cell-extrinsic factors have been implicated in increasing NPC proliferative capacity. However, NPC metabolism has only recently emerged as major regulator of NPC proliferation. In this Perspective, we summarize recent insights into the role of NPC metabolism in neocortical development and neurodevelopmental disorders and its relevance for neocortex evolution. We discuss certain human-specific genes and microcephaly-implicated genes that operate in, or at, the mitochondria of NPCs and stimulate their proliferation by promoting glutaminolysis. We also discuss other metabolic pathways and develop a perspective on how metabolism mechanistically regulates NPC proliferation in neocortical development and how this contributed to neocortex evolution.}, } @article {pmid33307391, year = {2021}, author = {Harshkova, D and Majewska, M and Pokora, W and Baścik-Remisiewicz, A and Tułodziecki, S and Aksmann, A}, title = {Diclofenac and atrazine restrict the growth of a synchronous Chlamydomonas reinhardtii population via various mechanisms.}, journal = {Aquatic toxicology (Amsterdam, Netherlands)}, volume = {230}, number = {}, pages = {105698}, doi = {10.1016/j.aquatox.2020.105698}, pmid = {33307391}, issn = {1879-1514}, mesh = {Antioxidants/metabolism ; Atrazine/*toxicity ; Catalase/metabolism ; Chlamydomonas reinhardtii/*drug effects/*growth & development/metabolism ; Chlorophyll A/metabolism ; Chloroplasts/metabolism ; Diclofenac/*toxicity ; Electron Transport ; Hydrogen Peroxide/metabolism ; Mitochondria/drug effects/metabolism ; Oxidative Stress/drug effects ; Photosynthesis/drug effects ; Water Pollutants, Chemical/*toxicity ; }, abstract = {Non-steroidal anti-inflammatory drug diclofenac (DCF) is commonly found in freshwater bodies and can have adverse effects on non-target organisms. Among the studies on DCF toxicity, several ones have reported its harmful effects on plants and algae. To gain a better understanding of the mechanisms of DCF toxicity towards green algae, we used a synchronous Chlamydomonas reinhardtii cc-1690 culture and compared DCF (135 mg/L) effects with effects caused by atrazine (ATR; 77.6 μg/L), an herbicide with a well-known mechanism of toxic action. To achieve our goal, cell number and size, photosynthetic oxygen consumption/evolution, chlorophyll a fluorescence in vivo, H2O2 production by the cells, antioxidative enzymes encoding genes expression were analyzed during light phase of the cell cycle. We have found, that DCF and ATR affect C. reinhardtii through different mechanisms. ATR inhibited the photosynthetic electron transport chain and induced oxidative stress in chloroplast. Such chloroplastic energetics disruption indirectly influenced respiration, the intensification of which could partially mitigate low efficiency of photosynthetic energy production. As a result, ATR inhibited the growth of single cell leading to limitation in C. reinhardtii population development. In contrast to ATR-treated algae, in DCF-treated cells the fraction of active PSII reaction centers was diminished without drastic changes in electron transport or oxidative stress symptoms in chloroplast. However, significant increase in transcript level of gene encoding for mitochondria-located catalase indicates respiratory processes as a source of H2O2 overproduced in the DCF-treated cells. Because the single cell growth was not strongly affected by DCF, its adverse effect on progeny cell number seemed to be related rather to arresting of cell divisions. Concluding, although the DCF phytotoxic action appeared to be different from the action of the typical herbicide ATR, it can act as algal growth-inhibiting factor in the environment.}, } @article {pmid33310361, year = {2021}, author = {Bi, YH and Du, AY and Li, JL and Zhou, ZG}, title = {Isolation and characterization of a γ-carbonic anhydrase localized in the mitochondria of Saccharina japonica.}, journal = {Chemosphere}, volume = {266}, number = {}, pages = {129162}, doi = {10.1016/j.chemosphere.2020.129162}, pmid = {33310361}, issn = {1879-1298}, mesh = {Carbon Dioxide ; *Carbonic Anhydrases/genetics ; Escherichia coli ; Mitochondria ; Phylogeny ; }, abstract = {Saccharina japonica is an ecologically and economically important seaweed that is dominant in the rocky shores of cold-temperate regions, forms the major component of productive beds, and affects marine environments. S. japonica exhibits a high photosynthetic efficiency in natural seawater with low dissolved CO2 concentration, thus suggesting the presence of its carbon-concentrating mechanism (CCM). However, the genes, proteins, and pathways involved in the CCM of S. japonica have not been fully identified and characterized. Carbonic anhydrase (CA) is a crucial component of CCM in macroalgae. In this study, the cloning, characterization, and subcellular localization of a specific CA were described. Multisequence alignment and phylogenetic analysis indicated that this CA belonged to the gamma (Sjγ-CA) class. This enzyme has a full-length cDAN of 1370 bp, encodes a protein with 246 amino acids (aa; ca. 25.7 kDa), and contains the mitochondrial transit peptide of 16 aa and LbH_gama_CA_like domain of 159 aa that defined the γ-CA region. The Sjγ-CA was successfully expressed in E. coli BL21 and purified as an active recombinant CA. Immunogold electron microscopy and fluorescence localization illustrated that this enzyme is localized in the mitochondria, and its transcription level is up-regulated by low CO2 concentration. These findings showed that Sjγ-CA is a possible component of the CCM in S. japonica. This work is the first to report about the mtCA of macroalgae and provides a basis for further analysis on seaweed CCM.}, } @article {pmid33311144, year = {2020}, author = {Vasconcelos, R and KÖhler, G and Geniez, P and Crochet, PA}, title = {A new endemic species of Hemidactylus (Squamata: Gekkonidae) from São Nicolau Island, Cabo Verde.}, journal = {Zootaxa}, volume = {4878}, number = {3}, pages = {zootaxa.4878.3.4}, doi = {10.11646/zootaxa.4878.3.4}, pmid = {33311144}, issn = {1175-5334}, mesh = {Animals ; Cabo Verde ; Islands ; *Lizards ; Mitochondria ; Phylogeny ; }, abstract = {A new species of gecko of the genus Hemidactylus (Squamata: Gekkonidae) is described from São Nicolau Island, Cabo Verde Archipelago, and the Sal and Boavista island populations of Hemidactylus boavistensis (i.e., Hemidactylus boavistensis boavistensis comb. nov. and Hemidactylus boavistensis chevalieri comb. nov.) are recognized as subspecies. Hemidactylus nicolauensis sp. nov. is genetically distinct from H. bouvieri, to which it has previously been referred, and from all other closely related endemic Hemidactylus from Cabo Verde Islands in mitochondrial (12S cyt b) and nuclear (RAG2, MC1R) markers. It is characterized morphologically by its distinct colouration and a diagnostically different arrangement of digital lamellae. With the description of this new species, São Nicolau is now known to harbour three single-island endemic gecko species, and the documented reptile diversity in Cabo Verde is raised to 23 endemic species. As a result of our taxonomic changes, existing conservation regulations should be updated and the conservation status of these taxa should be re-evaluated.}, } @article {pmid33314045, year = {2021}, author = {Filograna, R and Mennuni, M and Alsina, D and Larsson, NG}, title = {Mitochondrial DNA copy number in human disease: the more the better?.}, journal = {FEBS letters}, volume = {595}, number = {8}, pages = {976-1002}, pmid = {33314045}, issn = {1873-3468}, mesh = {Animals ; *DNA Copy Number Variations ; *DNA, Mitochondrial/genetics/metabolism ; *DNA, Neoplasm/genetics/metabolism ; Humans ; *Mitochondria/genetics/metabolism ; *Mitochondrial Diseases/genetics/metabolism ; *Neoplasms/genetics/metabolism ; *Neurodegenerative Diseases/genetics/metabolism ; }, abstract = {Most of the genetic information has been lost or transferred to the nucleus during the evolution of mitochondria. Nevertheless, mitochondria have retained their own genome that is essential for oxidative phosphorylation (OXPHOS). In mammals, a gene-dense circular mitochondrial DNA (mtDNA) of about 16.5 kb encodes 13 proteins, which constitute only 1% of the mitochondrial proteome. Mammalian mtDNA is present in thousands of copies per cell and mutations often affect only a fraction of them. Most pathogenic human mtDNA mutations are recessive and only cause OXPHOS defects if present above a certain critical threshold. However, emerging evidence strongly suggests that the proportion of mutated mtDNA copies is not the only determinant of disease but that also the absolute copy number matters. In this review, we critically discuss current knowledge of the role of mtDNA copy number regulation in various types of human diseases, including mitochondrial disorders, neurodegenerative disorders and cancer, and during ageing. We also provide an overview of new exciting therapeutic strategies to directly manipulate mtDNA to restore OXPHOS in mitochondrial diseases.}, } @article {pmid33314286, year = {2021}, author = {Mutti, LD and Ivanov, VA}, title = {Ultrastructure of the rhyncheal apparatus and other structures of the scolex of Grillotia (Christianella) carvajalregorum (Cestoda: Trypanorhyncha).}, journal = {Journal of morphology}, volume = {282}, number = {2}, pages = {309-324}, doi = {10.1002/jmor.21305}, pmid = {33314286}, issn = {1097-4687}, mesh = {Animals ; Cestoda/*anatomy & histology/cytology/*ultrastructure ; Histocytochemistry ; Phylogeny ; Sensory Receptor Cells/cytology/ultrastructure ; }, abstract = {The scolex ultrastructure was studied in Grillotia (Christianella) carvajalregorum (Cestoda: Trypanorhyncha) using histochemistry and transmission electron microscopy. We show for the first time the presence of scolex glands arranged in two longitudinal acini at the pars vaginalis parenchyma. These glands, along with those scattered in bothrial parenchyma, produce potentially adhesive glycoprotein secretions that are discharged via ducts to the bothrial grooves and apex. A particular type of sensory receptor was found around frontal gland pores, with a possible function in regulating their secretion activity. The internal structure of microtriches varies according to their morphotype and distribution on the scolex, this study providing the first description of the ultrastructure of serrate lanceolate spinitriches. The projections that form serrate margins are an extension of the medulla, differing from similar projections of other spinitriches. The large caps observed in serrate lanceolate spinitriches may reflect their specialization in attachment to and abrasion of intestinal mucosa, while the short caps and large bases of acicular filitriches may reflect their involvement in nutrient absorption. We also describe the rhyncheal apparatus ultrastructure, showing a similar basic structure of tentacular walls than that of other trypanorhynchs. Some differences among species in the number of fibrous layers, composition of the apical cytoplasm and presence of microvilli-like projections were discussed. Finally, our study describes in detail the internal ultrastructure of hollow hooks, evidencing the presence of cytoplasm, mitochondria and fibrils. The location of these fibrils may increase the area of contact surface of hooks on tentacles, possibly allowing for a higher tensile strength than that of solid hooks. We consider that gland location and shape, composition of tentacular wall layers, and hook internal structure may serve as useful characters for the taxonomy and phylogeny of Trypanorhyncha. RESEARCH HIGHLIGHTS: This is the first description of scolex internal ultrastructure in Grillotia carvajalregorum, showing the presence of glands arranged in two longitudinal acini at the pars vaginalis parenchyma, with potentially adhesive functions. The internal ultrastructure of serrate lanceolate spinitriches and acicular filitriches may reflect their specialization in attachment to the host intestinal mucosa and their involvement in nutrient absorption, respectively. Internally, hollow hooks have cytoplasm with mitochondria and fibrils, which are more widely distributed than in solid hooks, possibly increasing their tensile strength.}, } @article {pmid33329499, year = {2020}, author = {Oberleitner, L and Poschmann, G and Macorano, L and Schott-Verdugo, S and Gohlke, H and Stühler, K and Nowack, ECM}, title = {The Puzzle of Metabolite Exchange and Identification of Putative Octotrico Peptide Repeat Expression Regulators in the Nascent Photosynthetic Organelles of Paulinella chromatophora.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {607182}, pmid = {33329499}, issn = {1664-302X}, abstract = {The endosymbiotic acquisition of mitochondria and plastids more than one billion years ago was central for the evolution of eukaryotic life. However, owing to their ancient origin, these organelles provide only limited insights into the initial stages of organellogenesis. The cercozoan amoeba Paulinella chromatophora contains photosynthetic organelles-termed chromatophores-that evolved from a cyanobacterium ∼100 million years ago, independently from plastids in plants and algae. Despite the more recent origin of the chromatophore, it shows tight integration into the host cell. It imports hundreds of nucleus-encoded proteins, and diverse metabolites are continuously exchanged across the two chromatophore envelope membranes. However, the limited set of chromatophore-encoded solute transporters appears insufficient for supporting metabolic connectivity or protein import. Furthermore, chromatophore-localized biosynthetic pathways as well as multiprotein complexes include proteins of dual genetic origin, suggesting that mechanisms evolved that coordinate gene expression levels between chromatophore and nucleus. These findings imply that similar to the situation in mitochondria and plastids, also in P. chromatophora nuclear factors evolved that control metabolite exchange and gene expression in the chromatophore. Here we show by mass spectrometric analyses of enriched insoluble protein fractions that, unexpectedly, nucleus-encoded transporters are not inserted into the chromatophore inner envelope membrane. Thus, despite the apparent maintenance of its barrier function, canonical metabolite transporters are missing in this membrane. Instead we identified several expanded groups of short chromatophore-targeted orphan proteins. Members of one of these groups are characterized by a single transmembrane helix, and others contain amphipathic helices. We hypothesize that these proteins are involved in modulating membrane permeability. Thus, the mechanism generating metabolic connectivity of the chromatophore fundamentally differs from the one for mitochondria and plastids, but likely rather resembles the poorly understood mechanism in various bacterial endosymbionts in plants and insects. Furthermore, our mass spectrometric analysis revealed an expanded family of chromatophore-targeted helical repeat proteins. These proteins show similar domain architectures as known organelle-targeted expression regulators of the octotrico peptide repeat type in algae and plants. Apparently these chromatophore-targeted proteins evolved convergently to plastid-targeted expression regulators and are likely involved in gene expression control in the chromatophore.}, } @article {pmid33330486, year = {2020}, author = {Zeng, M and He, Y and Du, H and Yang, J and Wan, H}, title = {Output Regulation and Function Optimization of Mitochondria in Eukaryotes.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {598112}, pmid = {33330486}, issn = {2296-634X}, abstract = {The emergence of endosymbiosis between aerobic alpha-proteobacterium and anaerobic eukaryotic cell precursors opened the chapter of eukaryotic evolution. Multiple functions of mitochondria originated from the ancient precursors of mitochondria and underwent remodeling in eukaryotic cells. Due to the dependence on mitochondrial functions, eukaryotic cells need to constantly adjust mitochondrial output based on energy demand and cellular stress. Meanwhile, eukaryotes conduct the metabolic cooperation between different cells through the involvement of mitochondria. Under some conditions, mitochondria might also be transferred to nearby cells to provide a protective mechanism. However, the endosymbiont relationship determines the existence of various types of mitochondrial injury, such as proteotoxic stress, mutational meltdown, oxidative injure, and immune activation caused by released mitochondrial contents. Eukaryotes have a repertoire of mitochondrial optimization processes, including various mitochondrial quality-control proteins, regulation of mitochondrial dynamics and activation of mitochondrial autophagy. When these quality-control processes fail, eukaryotic cells can activate apoptosis to intercept uncontrolled cell death, thereby minimizing the damage to extracellular tissue. In this review, we describe the intracellular and extracellular context-based regulation of mitochondrial output in eukaryotic cells, and introduce new findings on multifaceted quality-control processes to deal with mitochondrial defects.}, } @article {pmid33338660, year = {2021}, author = {Cairns, NA and Cicchino, AS and Stewart, KA and Austin, JD and Lougheed, SC}, title = {Cytonuclear discordance, reticulation and cryptic diversity in one of North America's most common frogs.}, journal = {Molecular phylogenetics and evolution}, volume = {156}, number = {}, pages = {107042}, doi = {10.1016/j.ympev.2020.107042}, pmid = {33338660}, issn = {1095-9513}, mesh = {Animals ; Anura/*genetics ; Base Sequence ; Cell Nucleus/*genetics ; DNA, Mitochondrial/genetics ; *Genetic Variation ; Geography ; Linear Models ; Male ; Mitochondria/genetics ; North America ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Species Specificity ; }, abstract = {Complicated phylogenetic histories benefit from diverse sources of inference. Pseudacris crucifer (spring peeper) spans most of eastern North America and comprises six mtDNA lineages that form multiple contact zones. The putative Miocene or early Pliocene origins of the oldest lineages within Pseudacris crucifer imply sufficient time for species-level divergence. To understand why this species appears unified while congeners have radiated, we analyze and compare male advertisement calls, mitochondrial, and nuclear markers and speak to the complex processes that have potentially influenced its contemporary patterns. We find extensive geographic and topological mitonuclear discordance, with three nuclear lineages containing 6 more-structured mtDNA lineages, and nuclear introgression at some contact zones. Male advertisement call differentiation is incongruent with the genetic structure as only one lineage appears differentiated. Occupying the Interior Highlands of the central United States, this Western lineage also has the most concordant mitochondrial and nuclear geographic patterns. Based on our findings we suggest that the antiquity of common ancestors was not as important as the maintenance of allopatry in the divergence in P. crucifer genetic lineages. We use multiple lines of evidence to generate hypotheses of isolation, reticulation, and discordance within this species and to expand our understanding of the early stages of speciation.}, } @article {pmid33359125, year = {2021}, author = {Liu, H and Ju, Y and Tamate, H and Wang, T and Xing, X}, title = {Phylogeography of sika deer (Cervus nippon) inferred from mitochondrial cytochrome-b gene and microsatellite DNA.}, journal = {Gene}, volume = {772}, number = {}, pages = {145375}, doi = {10.1016/j.gene.2020.145375}, pmid = {33359125}, issn = {1879-0038}, mesh = {Animals ; Cell Nucleus/genetics ; China ; Cytochromes b/*genetics ; Deer/*classification/genetics ; *Genetic Variation ; Genetics, Population ; Haplotypes ; Japan ; *Microsatellite Repeats ; Mitochondria/genetics ; Phylogeny ; Phylogeography ; }, abstract = {The genetic diversity and phylogenetic relationships of sika deer of different subspecies are uncertain. In order to explore the phylogenetic relationship of different sika deer subspecies, this study used a wider sample collection to analyze mitochondrial sequences and nuclear microsatellites of sika deer. The full lengths of cytochrome-b gene of 134 sika deer were sequenced, and 16 haplotypes were obtained. Based on phylogenetic and haplotype networks analysis, the sika deer was not clustered according to subspecies but was divided into four lineages. Lineage I includes individuals from C.n.kopschi, C.n.sichuanicus, and C.n.hortulorum subspecies; Lineage II includes individuals from C.n.hortulorum subspecies; Lineage III includes individuals from C.n.centralis, C.n.yakushime, C.n.mageshimae, and C.n.keramae subspecies, namely southern Japanese population; Lineage IV includes individuals from C.n.centralis and C.n.yesoensis subspecies, namely northern Japanese population. The microsatellite analysis showed that the sika deer in China and Japan originated independently. The three subspecies of China have significant genetic differentiation, while the three subspecies of Japan have no significant differentiation. This study provides reference for the research of genetic diversity and phylogenetic relationship of sika deer, and also provides scientific data for the evaluation, protection, and utilization of sika deer resources.}, } @article {pmid33359769, year = {2021}, author = {Else, PL}, title = {Mammals to membranes: A reductionist story.}, journal = {Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology}, volume = {253}, number = {}, pages = {110552}, doi = {10.1016/j.cbpb.2020.110552}, pmid = {33359769}, issn = {1879-1107}, mesh = {Animals ; Cell Membrane/*metabolism ; Energy Metabolism ; Humans ; Mammals/*metabolism ; Oxygen Consumption ; }, abstract = {This is the story of a series of reductionist studies that started with an attempt to explain what underpins the high-level of aerobic metabolism in mammals (i.e. associated with the evolution of endothermy) and almost forty years later had led to investigations into the role of membrane lipids in determining metabolism. Initial studies showed that the increase in aerobic metabolism in mammals was driven by a combination of increases in mitochondrial volume and membrane densities, organ size and changes in the molecular activity of enzymes. The increase in the capacity to produce energy was matched by an increase in energy use, notably driven by increases in H[+], Na[+] and K[+] fluxes. In the case of increased Na[+] flux, it was found this was matched by increases in Na[+]-dependent metabolism at the tissue level and increases in enzyme activity at a cellular level but not by an increase in the number of sodium pumps. To maintain Na[+] gradient across cell membranes, increased Na[+] flux is not controlled by an increase in sodium pump number but rather by an increase in sodium pump molecular activity (i.e. an increase the substrate turnover rate of each sodium pump) in tissues of endotherms. This increase in molecular activity is coupled to an increase in the level of highly unsaturated polyunsaturated fatty acids (PUFA) in membranes, a mechanism similar to that used by ectotherms to ameliorate decreasing activities of metabolic processes in the cold. Determination of how changes in membrane fatty acid composition can change the activities of proteins in membranes will be the next step in this story.}, } @article {pmid33362740, year = {2020}, author = {Li, X and Li, L and Bao, Z and Tu, W and He, X and Zhang, B and Ye, L and Wang, X and Li, Q}, title = {The 287,403 bp Mitochondrial Genome of Ectomycorrhizal Fungus Tuber calosporum Reveals Intron Expansion, tRNA Loss, and Gene Rearrangement.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {591453}, pmid = {33362740}, issn = {1664-302X}, abstract = {In the present study, the mitogenome of Tuber calosporum was assembled and analyzed. The mitogenome of T. calosporum comprises 15 conserved protein-coding genes, two rRNA genes, and 14 tRNAs, with a total size of 287,403 bp. Fifty-eight introns with 170 intronic open reading frames were detected in the T. calosporum mitogenome. The intronic region occupied 69.41% of the T. calosporum mitogenome, which contributed to the T. calosporum mitogenome significantly expand relative to most fungal species. Comparative mitogenomic analysis revealed large-scale gene rearrangements occurred in the mitogenome of T. calosporum, involving gene relocations and position exchanges. The mitogenome of T. calosporum was found to have lost several tRNA genes encoding for cysteine, aspartate, histidine, etc. In addition, a pair of fragments with a total length of 32.91 kb in both the nuclear and mitochondrial genomes of T. calosporum was detected, indicating possible gene transfer events. A total of 12.83% intragenomic duplications were detected in the T. calosporum mitogenome. Phylogenetic analysis based on mitochondrial gene datasets obtained well-supported tree topologies, indicating that mitochondrial genes could be reliable molecular markers for phylogenetic analyses of Ascomycota. This study served as the first report on mitogenome in the family Tuberaceae, thereby laying the groundwork for our understanding of the evolution, phylogeny, and population genetics of these important ectomycorrhizal fungi.}, } @article {pmid33365705, year = {2019}, author = {Salas-Castañeda, MR and Castillo-Páez, A and Rocha-Olivares, A and Cruz-Barraza, JA}, title = {The complete mitogenome of the Eastern Pacific sponge Aplysina gerardogreeni (Demospongiae, Verongida, Aplysinidae).}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {4}, number = {2}, pages = {2734-2735}, pmid = {33365705}, issn = {2380-2359}, abstract = {We report the first mitochondrial genome of a Verongid sponge, Aplysina gerardogreeni from the Pacific Ocean. This has 19,620 bp and includes 14 protein-coding genes, 2 rRNAs genes, and 25 tRNAs genes. The gene arrangement was similar to the one found in two Caribbean Aplysina mitogenomes previously reported. Comparative analyses revealed a few substitutions among congeneric mitogenomes. The mitogenome of A. gerardogreeni could be useful to study the evolution of Verongimorpha group and also to identify adequate genes for its molecular systematics.}, } @article {pmid33366868, year = {2020}, author = {Yang, RS and Chen, YT}, title = {The complete mitochondrial genome of the freshwater fairy shrimp Branchinella kugenumaensis Ishikawa 1894 (Crustacea: Anostraca: Thamnocephalidae).}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {5}, number = {1}, pages = {1048-1049}, pmid = {33366868}, issn = {2380-2359}, abstract = {In this study, we determined and analyzed the complete mitochondrial genome of the freshwater fairy shrimp Branchinella kugenumaensis Ishikawa 1894 (Crustacea: Anostraca: Thamnocephalidae). The mitogenome is 15,127 bp in length, consisted of 37 genes that participate in protein production and energy metabolism of mitochondria. The gene order of the B. kugenumaensis mtDNA exhibits major rearrangements compared with the pancrustacean ancestral pattern or other known anostracan mitogenomes, representing a novel mitochondrial genomic organization within the Crustacea. A maximum-likelihood phylogenetic analysis based on concatenated nucleotide sequences of protein-coding genes places B. kugenumaensis next to Streptocephalus sirindhornae, inside the Anostraca clade. Our study will provide new evidence to the less sampled anostracan evolution and take a further step to the completion of the Branchiopoda tree of life.}, } @article {pmid33367059, year = {2020}, author = {Huang, X and Shi, Y and Shen, X and Huang, D and Wang, Y and Chen, J and Cai, Y}, title = {Characterization of the complete mitochondrial DNA sequence of the Lagocephalus gloveri (Tetraodontidae, Tetraodontiformes).}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {5}, number = {3}, pages = {3683-3684}, pmid = {33367059}, issn = {2380-2359}, abstract = {The complete mitochondrial genome of Lagocephalus gloveri is reported in the present study, which is 16,446 bp in length. It consists of 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes and a non-coding control region. The overall base composition of the genome is 27.58% for A, 25.07% for T, 30.83% for C and 16.52% for G. The phylogenetic tree, which is based on 12 protein coding gene sequences, suggested that L. gloveri was closest to L. lagocephalus. This study could give impetus to studies focused on population structure and molecular evolution of L. gloveri.}, } @article {pmid33369015, year = {2021}, author = {Lechuga-Vieco, AV and Justo-Méndez, R and Enríquez, JA}, title = {Not all mitochondrial DNAs are made equal and the nucleus knows it.}, journal = {IUBMB life}, volume = {73}, number = {3}, pages = {511-529}, pmid = {33369015}, issn = {1521-6551}, mesh = {Animals ; Cell Nucleus/*genetics ; Cytoplasm/genetics/metabolism ; *DNA, Mitochondrial/genetics/metabolism ; Evolution, Molecular ; Gene Expression Regulation ; Genome ; Haplotypes ; Humans ; Mitochondria/genetics ; *Oxidative Phosphorylation ; }, abstract = {The oxidative phosphorylation (OXPHOS) system is the only structure in animal cells with components encoded by two genomes, maternally transmitted mitochondrial DNA (mtDNA), and biparentally transmitted nuclear DNA (nDNA). MtDNA-encoded genes have to physically assemble with their counterparts encoded in the nucleus to build together the functional respiratory complexes. Therefore, structural and functional matching requirements between the protein subunits of these molecular complexes are rigorous. The crosstalk between nDNA and mtDNA needs to overcome some challenges, as the nuclear-encoded factors have to be imported into the mitochondria in a correct quantity and match the high number of organelles and genomes per mitochondria that encode and synthesize their own components locally. The cell is able to sense the mito-nuclear match through changes in the activity of the OXPHOS system, modulation of the mitochondrial biogenesis, or reactive oxygen species production. This implies that a complex signaling cascade should optimize OXPHOS performance to the cellular-specific requirements, which will depend on cell type, environmental conditions, and life stage. Therefore, the mitochondria would function as a cellular metabolic information hub integrating critical information that would feedback the nucleus for it to respond accordingly. Here, we review the current understanding of the complex interaction between mtDNA and nDNA.}, } @article {pmid33370271, year = {2020}, author = {Sorouri, M and Chang, T and Jesudhasan, P and Pinkham, C and Elde, NC and Hancks, DC}, title = {Signatures of host-pathogen evolutionary conflict reveal MISTR-A conserved MItochondrial STress Response network.}, journal = {PLoS biology}, volume = {18}, number = {12}, pages = {e3001045}, pmid = {33370271}, issn = {1545-7885}, support = {R00 GM119126/GM/NIGMS NIH HHS/United States ; R01 GM114514/GM/NIGMS NIH HHS/United States ; T32 AI005284/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Electron Transport Chain Complex Proteins/genetics/metabolism ; Electron Transport Complex IV/genetics/metabolism ; Evolution, Molecular ; Gene Regulatory Networks/genetics ; Host-Pathogen Interactions/*genetics/physiology ; Humans ; MicroRNAs/genetics ; Mitochondria/*genetics/metabolism ; Phylogeny ; Stress, Physiological/*genetics/physiology ; Viruses/genetics ; }, abstract = {Host-pathogen conflicts leave genetic signatures in genes that are critical for host defense functions. Using these "molecular scars" as a guide to discover gene functions, we discovered a vertebrate-specific MItochondrial STress Response (MISTR) circuit. MISTR proteins are associated with electron transport chain (ETC) factors and activated by stress signals such as interferon gamma (IFNγ) and hypoxia. Upon stress, ultraconserved microRNAs (miRNAs) down-regulate MISTR1(NDUFA4) followed by replacement with paralogs MItochondrial STress Response AntiViral (MISTRAV) and/or MItochondrial STress Response Hypoxia (MISTRH). While cells lacking MISTR1(NDUFA4) are more sensitive to chemical and viral apoptotic triggers, cells lacking MISTRAV or expressing the squirrelpox virus-encoded vMISTRAV exhibit resistance to the same insults. Rapid evolution signatures across primate genomes for MISTR1(NDUFA4) and MISTRAV indicate recent and ongoing conflicts with pathogens. MISTR homologs are also found in plants, yeasts, a fish virus, and an algal virus indicating ancient origins and suggesting diverse means of altering mitochondrial function under stress. The discovery of MISTR circuitry highlights the use of evolution-guided studies to reveal fundamental biological processes.}, } @article {pmid33372159, year = {2021}, author = {Chen, C and Mahar, R and Merritt, ME and Denlinger, DL and Hahn, DA}, title = {ROS and hypoxia signaling regulate periodic metabolic arousal during insect dormancy to coordinate glucose, amino acid, and lipid metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {1}, pages = {}, pmid = {33372159}, issn = {1091-6490}, support = {P41 GM122698/GM/NIGMS NIH HHS/United States ; R01 DK105346/DK/NIDDK NIH HHS/United States ; S10 OD028753/OD/NIH HHS/United States ; }, mesh = {Amino Acids/metabolism ; Animals ; Cell Respiration ; Citric Acid Cycle ; Diapause/physiology ; Energy Metabolism ; Glucose/metabolism ; Glycolysis/physiology ; Hypoxia/*metabolism ; Insecta/metabolism ; Lipid Metabolism/physiology ; Lipids/physiology ; Mitochondria/metabolism ; Phosphorylation ; Reactive Oxygen Species/*metabolism ; Sarcophagidae/metabolism ; Signal Transduction ; Torpor/*physiology ; }, abstract = {Metabolic suppression is a hallmark of animal dormancy that promotes overall energy savings. Some diapausing insects and some mammalian hibernators have regular cyclic patterns of substantial metabolic depression alternating with periodic arousal where metabolic rates increase dramatically. Previous studies, largely in mammalian hibernators, have shown that periodic arousal is driven by an increase in aerobic mitochondrial metabolism and that many molecules related to energy metabolism fluctuate predictably across periodic arousal cycles. However, it is still not clear how these rapid metabolic shifts are regulated. We first found that diapausing flesh fly pupae primarily use anaerobic glycolysis during metabolic depression but engage in aerobic respiration through the tricarboxylic acid cycle during periodic arousal. Diapausing pupae also clear anaerobic by-products and regenerate many metabolic intermediates depleted in metabolic depression during arousal, consistent with patterns in mammalian hibernators. We found that decreased levels of reactive oxygen species (ROS) induced metabolic arousal and elevated ROS extended the duration of metabolic depression. Our data suggest ROS regulates the timing of metabolic arousal by changing the activity of two critical metabolic enzymes, pyruvate dehydrogenase and carnitine palmitoyltransferase I by modulating the levels of hypoxia inducible transcription factor (HIF) and phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK). Our study shows that ROS signaling regulates periodic arousal in our insect diapasue system, suggesting the possible importance ROS for regulating other types of of metabolic cycles in dormancy as well.}, } @article {pmid33383174, year = {2021}, author = {Mamos, T and Uit de Weerd, D and von Oheimb, PV and Sulikowska-Drozd, A}, title = {Evolution of reproductive strategies in the species-rich land snail subfamily Phaedusinae (Stylommatophora: Clausiliidae).}, journal = {Molecular phylogenetics and evolution}, volume = {158}, number = {}, pages = {107060}, doi = {10.1016/j.ympev.2020.107060}, pmid = {33383174}, issn = {1095-9513}, mesh = {Animals ; *Biological Evolution ; Female ; Mitochondria/genetics ; Oviparity/genetics ; Phylogeny ; Reproduction/*genetics ; Snails/classification/*physiology ; *Viviparity, Nonmammalian/genetics ; }, abstract = {Most of the present knowledge on animal reproductive mode evolution, and possible factors driving transitions between oviparity and viviparity is based on studies on vertebrates. The species rich door snail (Clausiliidae) subfamily Phaedusinae represents a suitable and unique model for further examining parity evolution, as three different strategies, oviparity, viviparity, and the intermediate mode of embryo-retention, occur in this group. The present study reconstructs the evolution of reproductive strategies in Phaedusinae based on time-calibrated molecular phylogenetics, reproductive mode examinations and ancestral state reconstruction. Our phylogenetic analysis employing multiple mitochondrial and nuclear markers identified a well-supported clade (including the tribes Phaedusini and Serrulinini) that contains species exhibiting various reproductive strategies. This clade evolved from an oviparous most recent common ancestor according to our reconstruction. All non-oviparous taxa are confined to a highly supported subclade, coinciding with the tribe Phaedusini. Both oviparity and viviparity occur frequently in different lineages of this subclade that are not closely related. During Phaedusini diversification, multiple transitions in reproductive strategy must have taken place, which could have been promoted by a high fitness of embryo-retaining species. The evolutionary success of this group might result from the maintenance of various strategies.}, } @article {pmid33396191, year = {2020}, author = {Shimakawa, G and Kohara, A and Miyake, C}, title = {Characterization of Light-Enhanced Respiration in Cyanobacteria.}, journal = {International journal of molecular sciences}, volume = {22}, number = {1}, pages = {}, pmid = {33396191}, issn = {1422-0067}, support = {JPMJCR1503//Core Research for Evolutional Science and Technology/ ; 16J03443//Japan Society for the Promotion of Science/ ; A20J001050//Japan Society for the Promotion of Science/ ; }, mesh = {*Cell Respiration ; Cyanobacteria/*growth & development/metabolism/physiology ; Electron Transport ; *Light ; Oxidation-Reduction ; Oxygen/*metabolism ; *Photosynthesis ; }, abstract = {In eukaryotic algae, respiratory O2 uptake is enhanced after illumination, which is called light-enhanced respiration (LER). It is likely stimulated by an increase in respiratory substrates produced during photosynthetic CO2 assimilation and function in keeping the metabolic and redox homeostasis in the light in eukaryotic cells, based on the interactions among the cytosol, chloroplasts, and mitochondria. Here, we first characterize LER in photosynthetic prokaryote cyanobacteria, in which respiration and photosynthesis share their metabolisms and electron transport chains in one cell. From the physiological analysis, the cyanobacterium Synechocystis sp. PCC 6803 performs LER, similar to eukaryotic algae, which shows a capacity comparable to the net photosynthetic O2 evolution rate. Although the respiratory and photosynthetic electron transports share the interchain, LER was uncoupled from photosynthetic electron transport. Mutant analyses demonstrated that LER is motivated by the substrates directly provided by photosynthetic CO2 assimilation, but not by glycogen. Further, the light-dependent activation of LER was observed even with exogenously added glucose, implying a regulatory mechanism for LER in addition to the substrate amounts. Finally, we discuss the physiological significance of the large capacity of LER in cyanobacteria and eukaryotic algae compared to those in plants that normally show less LER.}, } @article {pmid33396901, year = {2020}, author = {Cucini, C and Fanciulli, PP and Frati, F and Convey, P and Nardi, F and Carapelli, A}, title = {Re-Evaluating the Internal Phylogenetic Relationships of Collembola by Means of Mitogenome Data.}, journal = {Genes}, volume = {12}, number = {1}, pages = {}, pmid = {33396901}, issn = {2073-4425}, mesh = {Animals ; Antarctic Regions ; Arthropods/classification/*genetics ; Bayes Theorem ; Biological Evolution ; DNA, Mitochondrial/*genetics ; Gene Order ; *Genome, Mitochondrial ; Mitochondria/genetics ; *Models, Genetic ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Collembola are an ancient and early diverging lineage of basal hexapods that occur in virtually all terrestrial habitats on Earth. Phylogenetic relationships between the different orders of Collembola are fiercely debated. Despite a range of studies and the application of both morphological and genetic approaches (singly or in combination) to assess the evolutionary relationships of major lineages in the group, no consensus has been reached. Several mitogenome sequences have been published for key taxa of the class (and their number is increasing rapidly). Here, we describe two new Antarctic Collembola mitogenomes and compare all complete or semi-complete springtail mitogenome sequences available on GenBank in terms of both gene order and DNA sequence analyses in a genome evolution and molecular phylogenetic framework. With minor exceptions, we confirm the monophyly of Poduromorpha and Symphypleona sensu stricto (the latter placed at the most basal position in the springtail phylogenetic tree), whereas monophyly of Neelipleona and Entomobryomorpha is only supported when a handful of critical taxa in these two lineages are excluded. Finally, we review gene order models observed in the class, as well as the overall mitochondrial nucleotide composition.}, } @article {pmid33404103, year = {2021}, author = {Lee, DW and Hwang, I}, title = {Understanding the evolution of endosymbiotic organelles based on the targeting sequences of organellar proteins.}, journal = {The New phytologist}, volume = {230}, number = {3}, pages = {924-930}, doi = {10.1111/nph.17167}, pmid = {33404103}, issn = {1469-8137}, mesh = {*Chloroplasts/metabolism ; Mitochondria ; *Organelles ; Phylogeny ; Symbiosis ; }, abstract = {Organellogenesis, a key aspect of eukaryotic cell evolution, critically depends on the successful establishment of organellar protein import mechanisms. Phylogenetic analysis revealed that the evolution of the two endosymbiotic organelles, the mitochondrion and the chloroplast, is thought to have occurred at time periods far from each other. Despite this, chloroplasts and mitochondria have highly similar protein import mechanisms. This raises intriguing questions such as what underlies such similarity in the import mechanisms and how these similar mechanisms have evolved. In this review, we summarise the recent findings regarding sorting and specific targeting of these organellar proteins. Based on these findings, we propose possible evolutionary scenarios regarding how the signal sequences of chloroplasts and mitochondrial proteins ended up having such relationship.}, } @article {pmid33408226, year = {2021}, author = {Ferrarini, MG and Nisimura, LM and Girard, RMBM and Alencar, MB and Fragoso, MSI and Araújo-Silva, CA and Veiga, AA and Abud, APR and Nardelli, SC and Vommaro, RC and Silber, AM and France-Sagot, M and Ávila, AR}, title = {Dichloroacetate and Pyruvate Metabolism: Pyruvate Dehydrogenase Kinases as Targets Worth Investigating for Effective Therapy of Toxoplasmosis.}, journal = {mSphere}, volume = {6}, number = {1}, pages = {}, pmid = {33408226}, issn = {2379-5042}, mesh = {Antiprotozoal Agents/*pharmacology ; Apoptosis/*drug effects ; Dichloroacetic Acid/chemistry/*pharmacology ; Fibroblasts/*drug effects/parasitology ; Humans ; Metabolic Networks and Pathways/drug effects ; Mitochondria/metabolism ; Oxidation-Reduction ; Oxidoreductases ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/*antagonists & inhibitors ; Pyruvates/*metabolism ; Toxoplasma/*drug effects ; Toxoplasmosis/drug therapy ; }, abstract = {Toxoplasmosis, a protozoan infection caused by Toxoplasma gondii, is estimated to affect around 2.5 billion people worldwide. Nevertheless, the side effects of drugs combined with the long period of therapy usually result in discontinuation of the treatment. New therapies should be developed by exploring peculiarities of the parasite's metabolic pathways, similarly to what has been well described in cancer cell metabolism. An example is the switch in the metabolism of cancer that blocks the conversion of pyruvate into acetyl coenzyme A in mitochondria. In this context, dichloroacetate (DCA) is an anticancer drug that reverts the tumor proliferation by inhibiting the enzymes responsible for this switch: the pyruvate dehydrogenase kinases (PDKs). DCA has also been used in the treatment of certain symptoms of malaria; however, there is no evidence of how this drug affects apicomplexan species. In this paper, we studied the metabolism of T. gondii and demonstrate that DCA also inhibits T. gondii's in vitro infection with no toxic effects on host cells. DCA caused an increase in the activity of pyruvate dehydrogenase followed by an unbalanced mitochondrial activity. We also observed morphological alterations frequently in mitochondria and in a few apicoplasts, essential organelles for parasite survival. To date, the kinases that potentially regulate the activity of pyruvate metabolism in both organelles have never been described. Here, we confirmed the presence in the genome of two putative kinases (T. gondii PDK [TgPDK] and T. gondii branched-chain α-keto acid dehydrogenase kinase [TgBCKDK]), verified their cellular localization in the mitochondrion, and provided in silico data suggesting that they are potential targets of DCA.IMPORTANCE Currently, the drugs used for toxoplasmosis have severe toxicity to human cells, and the treatment still lacks effective and safer alternatives. The search for novel drug targets is timely. We report here that the treatment of T. gondii with an anticancer drug, dichloroacetate (DCA), was effective in decreasing in vitro infection without toxicity to human cells. It is known that PDK is the main target of DCA in mammals, and this inactivation increases the conversion of pyruvate into acetyl coenzyme A and reverts the proliferation of tumor cells. Moreover, we verified the mitochondrial localization of two kinases that possibly regulate the activity of pyruvate metabolism in T. gondii, which has never been studied. DCA increased pyruvate dehydrogenase (PDH) activity in T. gondii, followed by an unbalanced mitochondrial activity, in a manner similar to what was previously observed in cancer cells. Thus, we propose the conserved kinases as potential regulators of pyruvate metabolism and interesting targets for new therapies.}, } @article {pmid33409542, year = {2021}, author = {Yarus, M}, title = {Crick Wobble and Superwobble in Standard Genetic Code Evolution.}, journal = {Journal of molecular evolution}, volume = {89}, number = {1-2}, pages = {50-61}, pmid = {33409542}, issn = {1432-1432}, mesh = {*Anticodon/genetics ; Codon/genetics ; Evolution, Molecular ; *Genetic Code ; RNA ; }, abstract = {Wobble coding is inevitable during evolution of the Standard Genetic Code (SGC). It ultimately splits half of NN U/C/A/G coding boxes with different assignments. Further, it contributes to pervasive SGC order by reinforcing close spacing for identical SGC assignments. But wobble cannot appear too soon, or it will inhibit encoding and more decisively, obstruct evolution of full coding tables. However, these prior results assumed Crick wobble, NN U/C and NN A/G, read by a single adaptor RNA. Superwobble translates NN U/C/A/G codons, using one adaptor RNA with an unmodified 5' anticodon U (appropriate to earliest coding) in modern mitochondria, plastids, and mycoplasma. Assuming the SGC was selected when evolving codes most resembled it, characteristics of the critical selection events can be calculated. For example, continuous superwobble infrequently evolves SGC-like coding tables. So, continuous superwobble is a very improbable origin hypothesis. In contrast, late-arising superwobble shares late Crick wobble's frequent resemblance to SGC order. Thus late superwobble is possible, but yields SGC-like assignments less frequently than late Crick wobble. Ancient coding ambiguity, most simply, arose from Crick wobble alone. This is consistent with SGC assignments to NAN codons.}, } @article {pmid33412200, year = {2021}, author = {Wang, Q and Wang, J and Wu, Q and Xu, X and Wang, P and Wang, Z}, title = {Insights into the evolution of Brachyura (Crustacea: Decapoda) from mitochondrial sequences and gene order rearrangements.}, journal = {International journal of biological macromolecules}, volume = {170}, number = {}, pages = {717-727}, doi = {10.1016/j.ijbiomac.2020.12.210}, pmid = {33412200}, issn = {1879-0003}, mesh = {Animals ; Brachyura/*genetics ; Gene Order/*genetics ; Gene Rearrangement/*genetics ; Genes, Mitochondrial/*genetics ; Genome, Mitochondrial/genetics ; Mitochondria/*genetics ; Phylogeny ; }, abstract = {Brachyura is one of the most species rich and highly derived groups among extant crustaceans, with over 7250 known species. However, brachyuran phylogeny remains controversial and requires further study. Here, we combined 103 brachyuran mitogenomes from GenBank with 10 new mitogenomes to describe gene rearrangement patterns and explore the internal phylogenetic relationships of Brachyura. Most of the 10 novel mitogenomes had the typical 37 genes, except that of Longpotamon depressum, which lacked trnQ. We discovered 15 gene rearrangement patterns among Brachyura and preliminarily determined their rearrangement mechanisms with the help of CREx. We identified seven putative ancestral family gene orders among the 15 rearrangement patterns and expounded systematically upon the mechanisms of their rearrangement. In our phylogenetic analysis, Raninoida shared a sister relationship with an eubrachyuran clade ((Heterotremata [Potamoidea] + Thoracotremata) + Heterotremata) at maximum nodal support rather than Dromiacea, which did not support monophyly of Podotremata. In addition, Potamoidea (Parathelphusidae + Potamidae) retained a close relationship with Thoracotremata rather than their marine relatives in Heterotremata. Our study provides important information for the evolution of Brachyura by using the large taxon sampling currently available for systematic rearrangement and phylogenetic analyses.}, } @article {pmid33412336, year = {2021}, author = {Bartáková, V and Bryjová, A and Nicolas, V and Lavrenchenko, LA and Bryja, J}, title = {Mitogenomics of the endemic Ethiopian rats: looking for footprints of adaptive evolution in sky islands.}, journal = {Mitochondrion}, volume = {57}, number = {}, pages = {182-191}, doi = {10.1016/j.mito.2020.12.015}, pmid = {33412336}, issn = {1872-8278}, mesh = {Animals ; Evolution, Molecular ; Genetic Introgression ; Mitochondria/*genetics ; Mitochondrial Proteins/chemistry/*genetics ; Models, Molecular ; Murinae/classification/*genetics ; Oxidative Phosphorylation ; Phylogeny ; Selection, Genetic ; Sequence Analysis, DNA/*methods ; }, abstract = {Organisms living in high altitude must adapt to environmental conditions with hypoxia and low temperature, e.g. by changes in the structure and function of proteins associated with oxidative phosphorylation in mitochondria. Here we analysed the signs of adaptive evolution in 27 mitogenomes of endemic Ethiopian rats (Stenocephalemys), where individual species adapted to different elevation. Significant signals of positive selection were detected in 10 of the 13 mitochondrial protein-coding genes, with a majority of functional substitutions in the NADH dehydrogenase complex. Higher frequency of positively selected sites was found in phylogenetic lineages corresponding to Afroalpine specialists.}, } @article {pmid33422486, year = {2021}, author = {Austin, S and Nowikovsky, K}, title = {Mitochondrial osmoregulation in evolution, cation transport and metabolism.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1862}, number = {5}, pages = {148368}, doi = {10.1016/j.bbabio.2021.148368}, pmid = {33422486}, issn = {1879-2650}, mesh = {Animals ; Cations/*metabolism ; *Evolution, Molecular ; Humans ; Ion Transport ; Mitochondria/*metabolism ; *Osmoregulation ; }, abstract = {This review provides a retrospective on the role of osmotic regulation in the process of eukaryogenesis. Specifically, it focuses on the adjustments which must have been made by the original colonizing α-proteobacteria that led to the evolution of modern mitochondria. We focus on the cations that are fundamentally involved in volume determination and cellular metabolism and define the transporter landscape in relation to these ions in mitochondria as we know today. We provide analysis on how the cations interplay and together maintain osmotic balance that allows for effective ATP synthesis in the organelle.}, } @article {pmid33422563, year = {2021}, author = {Pabis, K}, title = {Triplex and other DNA motifs show motif-specific associations with mitochondrial DNA deletions and species lifespan.}, journal = {Mechanisms of ageing and development}, volume = {194}, number = {}, pages = {111429}, doi = {10.1016/j.mad.2021.111429}, pmid = {33422563}, issn = {1872-6216}, mesh = {Age Factors ; Aging/*genetics/metabolism/pathology ; Animals ; DNA/*genetics/metabolism ; DNA, Mitochondrial/*genetics/metabolism ; G-Quadruplexes ; *Gene Deletion ; Humans ; Longevity/*genetics ; Models, Genetic ; *Mutation ; Nucleic Acid Conformation ; *Nucleotide Motifs ; Phylogeny ; Species Specificity ; }, abstract = {The "theory of resistant biomolecules" posits that long-lived species show resistance to molecular damage at the level of their biomolecules. Here, we test this hypothesis in the context of mitochondrial DNA (mtDNA) as it implies that predicted mutagenic DNA motifs should be inversely correlated with species maximum lifespan (MLS). First, we confirmed that guanine-quadruplex and direct repeat (DR) motifs are mutagenic, as they associate with mtDNA deletions in the human major arc of mtDNA, while also adding mirror repeat (MR) and intramolecular triplex motifs to a growing list of potentially mutagenic features. What is more, triplex motifs showed disease-specific associations with deletions and an apparent interaction with guanine-quadruplex motifs. Surprisingly, even though DR, MR and guanine-quadruplex motifs were associated with mtDNA deletions, their correlation with MLS was explained by the biased base composition of mtDNA. Only triplex motifs negatively correlated with MLS even after adjusting for body mass, phylogeny, mtDNA base composition and effective number of codons. Taken together, our work highlights the importance of base composition for the comparative biogerontology of mtDNA and suggests that future research on mitochondrial triplex motifs is warranted.}, } @article {pmid33432342, year = {2021}, author = {Harada, R and Inagaki, Y}, title = {Phage Origin of Mitochondrion-Localized Family A DNA Polymerases in Kinetoplastids and Diplonemids.}, journal = {Genome biology and evolution}, volume = {13}, number = {2}, pages = {}, pmid = {33432342}, issn = {1759-6653}, mesh = {Bacteriophages/enzymology/*genetics ; DNA-Directed DNA Polymerase/classification/*genetics ; Euglenozoa/enzymology/*genetics ; *Gene Transfer, Horizontal ; Kinetoplastida/enzymology/*genetics ; Mitochondria/enzymology/genetics ; Phylogeny ; }, abstract = {Mitochondria retain their own genomes as other bacterial endosymbiont-derived organelles. Nevertheless, no protein for DNA replication and repair is encoded in any mitochondrial genomes (mtDNAs) assessed to date, suggesting that the nucleus primarily governs the maintenance of mtDNA. As the proteins of diverse evolutionary origins occupy a large proportion of the current mitochondrial proteomes, we anticipate finding the same evolutionary trend in the nucleus-encoded machinery for mtDNA maintenance. Indeed, none of the DNA polymerases (DNAPs) in the mitochondrial endosymbiont, a putative α-proteobacterium, seemingly had been inherited by their descendants (mitochondria), as none of the known types of mitochondrion-localized DNAP showed a specific affinity to the α-proteobacterial DNAPs. Nevertheless, we currently have no concrete idea of how and when the known types of mitochondrion-localized DNAPs emerged. We here explored the origins of mitochondrion-localized DNAPs after the improvement of the samplings of DNAPs from bacteria and phages/viruses. Past studies have revealed that a set of mitochondrion-localized DNAPs in kinetoplastids and diplonemids, namely PolIB, PolIC, PolID, PolI-Perk1/2, and PolI-dipl (henceforth designated collectively as "PolIBCD+") have emerged from a single DNAP. In this study, we recovered an intimate connection between PolIBCD+ and the DNAPs found in a particular group of phages. Thus, the common ancestor of kinetoplastids and diplonemids most likely converted a laterally acquired phage DNAP into a mitochondrion-localized DNAP that was ancestral to PolIBCD+. The phage origin of PolIBCD+ hints at a potentially large contribution of proteins acquired via nonvertical processes to the machinery for mtDNA maintenance in kinetoplastids and diplonemids.}, } @article {pmid33436278, year = {2021}, author = {Koch, RE and Buchanan, KL and Casagrande, S and Crino, O and Dowling, DK and Hill, GE and Hood, WR and McKenzie, M and Mariette, MM and Noble, DWA and Pavlova, A and Seebacher, F and Sunnucks, P and Udino, E and White, CR and Salin, K and Stier, A}, title = {Integrating Mitochondrial Aerobic Metabolism into Ecology and Evolution.}, journal = {Trends in ecology & evolution}, volume = {36}, number = {4}, pages = {321-332}, doi = {10.1016/j.tree.2020.12.006}, pmid = {33436278}, issn = {1872-8383}, mesh = {Adaptation, Physiological ; Adenosine Triphosphate/metabolism ; *Energy Metabolism ; Humans ; *Mitochondria ; Reactive Oxygen Species/metabolism ; }, abstract = {Biologists have long appreciated the critical role that energy turnover plays in understanding variation in performance and fitness among individuals. Whole-organism metabolic studies have provided key insights into fundamental ecological and evolutionary processes. However, constraints operating at subcellular levels, such as those operating within the mitochondria, can also play important roles in optimizing metabolism over different energetic demands and time scales. Herein, we explore how mitochondrial aerobic metabolism influences different aspects of organismal performance, such as through changing adenosine triphosphate (ATP) and reactive oxygen species (ROS) production. We consider how such insights have advanced our understanding of the mechanisms underpinning key ecological and evolutionary processes, from variation in life-history traits to adaptation to changing thermal conditions, and we highlight key areas for future research.}, } @article {pmid33436634, year = {2021}, author = {Bit, A and Thakur, M and Singh, SK and Joshi, BD and Singh, VK and Sharma, LK and Tripathy, B and Chandra, K}, title = {Assembling mitogenome of Himalayan Black Bear (U. t. laniger) from low depth reads and its application in drawing phylogenetic inferences.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {730}, pmid = {33436634}, issn = {2045-2322}, mesh = {Animals ; DNA, Mitochondrial/analysis/*genetics ; *Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing/*methods ; Mitochondria/*genetics ; *Phylogeny ; Ursidae/classification/*genetics ; }, abstract = {The complete mitogenome of Himalayan black bear (Ursus thibetanus laniger) from Indian Himalayan region was assembled following the modified approach of mitochondrial baiting and mapping using the next-generation sequencing reads. The complete mitogenome was of 16,556 bp long, consisted of 37 genes that contained 13 protein-coding genes, 22 tRNAs, 2 rRNAs and 1 control region. The complete base composition was 31.33% A, 15.24% G, 25.45%C, and 27.98%T and gene arrangement was similar to the other sub-species of Asiatic black bear. The relative synonymous codon usage analysis revealed the maximum abundance of Isoleucine, Tyrosine, Leucine and Threonine. The assembled mitogenome of U. t. laniger exhibited 99% similarity with the mitogenomes of Himalayan black bear available from Nepal and Tibetan Plateau-Himalaya region. The findings of the present study has proven low depth sequencing data, adequate and highly efficient in rapid recovering the mitochondrial genome by overcoming the conventional strategies of obtaining long-range PCR and subsequently drawing phylogenetic inferences.}, } @article {pmid33442829, year = {2021}, author = {Zhang, K and Liu, Y and Chen, J and Zhang, H and Gong, L and Jiang, L and Liu, L and Lü, Z and Liu, B}, title = {Characterization of the complete mitochondrial genome of Macrotocinclus affinis (Siluriformes; Loricariidae) and phylogenetic studies of Siluriformes.}, journal = {Molecular biology reports}, volume = {48}, number = {1}, pages = {677-689}, pmid = {33442829}, issn = {1573-4978}, support = {NO.41806156//National Natural Science Foundation of China/ ; LMB20201005//State Key Laboratory of Microbial Resources (CN)/ ; No.2019J00048//Starting Research Fund from the Zhejiang Ocean University; Fundamental Research Funds for Zhejiang Provincial Universities and Research Institutes/ ; 2020C21016//Science and Technology Project of Zhoushan/ ; 31702321//National Natural Science Foundation of China/ ; LY20C190008//Zhejiang Provincial Natural Science Foundation of China/ ; }, mesh = {Animals ; Base Composition ; Catfishes/classification/*genetics ; Chromosome Mapping ; DNA, Circular/genetics ; DNA, Mitochondrial/*genetics ; Genome Size ; *Genome, Mitochondrial ; Mitochondria/*genetics ; *Open Reading Frames ; Phylogeny ; RNA, Ribosomal/classification/genetics ; RNA, Transfer/classification/genetics ; Whole Genome Sequencing ; }, abstract = {The vertebrate mitochondrial genome is typically circular molecules made up of 14,000 to 16,000 bp, including 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (12 s rRNA and 16 s rRNA) and a control region. Compared with nuclear DNA, mitochondrial DNA has a higher mutation rate, so it is one of the most effective and reliable molecular markers in fish phylogeny. Macrotocinclus affinis was the only species in Macrotocinclus (it was classified as Otocinclus in the past) and currently lacks genetic information. Most of the current researches are based on the mitochondrial Cytb gene and RAG1 and RAG2 nuclear genes to study the phylogenetic analysis of Siluriformes. So, the study provides the characteristic features of the Macrotocinclus affinis mitochondrial genome and this is the first time that the phylogenetic relationship of Siluriformes has been reconstructed based on COI. We aimed to sequence the entire mitochondrial genome of Macrotocinclus affinis using conventional PCR techniques and to clarify its phylogenetic status in Siluriformes by using the COI sequence of mitochondria. In this study, we sequenced the whole mitochondrial genome of this species yielding a 16,632 bp circular assembly composed of the typical vertebrate mitochondrial features. It contains 13 protein-coding genes, two rRNA genes, 22 tRNA genes, a putative control region, and one origin of replication on the light-strand. The overall base composition includes A (30.07%), T (24.43%), C (29.43%) and G (16.01%). The genome composition is A + T biased (54.5%), and exhibits AT-skew (0.1036) and GC-skew (-0.2962). Moreover, the 13 PCGs encode 3850 amino acids in total. The result of the phylogenetic tree supports Macrotocinclus affinis has a closest relationship with Otocinclus cf. hoppei far. These results will help to understand the characteristics of the mitochondrial genome of Macrotocinclus affinis and provide molecular basis for the evolutionary relationship of Loricariidae.}, } @article {pmid33446906, year = {2021}, author = {Fachi, JL and Pral, LP and Dos Santos, JAC and Codo, AC and de Oliveira, S and Felipe, JS and Zambom, FFF and Câmara, NOS and Vieira, PMMM and Colonna, M and Vinolo, MAR}, title = {Hypoxia enhances ILC3 responses through HIF-1α-dependent mechanism.}, journal = {Mucosal immunology}, volume = {14}, number = {4}, pages = {828-841}, pmid = {33446906}, issn = {1935-3456}, support = {U01 AI095542/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Clostridium Infections/etiology/metabolism ; Disease Models, Animal ; Disease Susceptibility ; Hypoxia/*immunology/*metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; *Immunity, Innate ; Lymphocyte Activation/genetics/immunology ; Lymphocyte Subsets/*immunology/*metabolism ; Mice ; Mice, Knockout ; Mitochondria/metabolism ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; Protein Stability ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {Group 3 innate lymphoid cells (ILC3) have a prominent role in the maintenance of intestine mucosa homeostasis. The hypoxia-inducible factor (HIF) is an important modulator of immune cell activation and a key mechanism for cellular adaptation to oxygen deprivation. However, its role on ILC3 is not well known. In this study, we investigated how a hypoxic environment modulates ILC3 response and the subsequent participation of HIF-1 signaling in this process. We found increased proliferation and activation of intestinal ILC3 at low oxygen levels, a response that was phenocopied when HIF-1α was chemically stabilized and was reversed when HIF-1 was blocked. The increased activation of ILC3 relied on a HIF-1α-dependent transcriptional program, but not on mTOR-signaling or a switch to glycolysis. HIF-1α deficiency in RORyt compartment resulted in impaired IL-17 and IL-22 production by ILC3 in vivo, which reflected in a lower expression of their target genes in the intestinal epithelium and an increased susceptibility to Clostridiodes difficile infection. Taken together, our results show that HIF-1α activation in intestinal ILC3 is relevant for their functions in steady state and infectious conditions.}, } @article {pmid33452307, year = {2021}, author = {Cui, H and Ding, Z and Zhu, Q and Wu, Y and Qiu, B and Gao, P}, title = {Comparative analysis of nuclear, chloroplast, and mitochondrial genomes of watermelon and melon provides evidence of gene transfer.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {1595}, pmid = {33452307}, issn = {2045-2322}, mesh = {Biological Evolution ; Cell Nucleus/*genetics ; Citrullus/*genetics ; Cucurbitaceae/*genetics ; DNA, Plant/chemistry/metabolism ; Gene Transfer, Horizontal ; *Genome, Chloroplast ; *Genome, Mitochondrial ; Genome, Plant ; Whole Genome Sequencing ; }, abstract = {During plant evolution, there is genetic communication between organelle and nuclear genomes. A comparative analysis was performed on the organelle and nuclear genomes of the watermelon and melon. In the watermelon, chloroplast-derived sequences accounted for 7.6% of the total length of the mitochondrial genome. In the melon, chloroplast-derived sequences accounted for approximately 2.73% of the total mitochondrial genome. In watermelon and melon, the chloroplast-derived small-fragment sequences are either a subset of large-fragment sequences or appeared multiple times in the mitochondrial genome, indicating that these fragments may have undergone multiple independent migration integrations or emerged in the mitochondrial genome after migration, replication, and reorganization. There was no evidence of migration from the mitochondria to chloroplast genome. A sequence with a total length of about 73 kb (47%) in the watermelon chloroplast genome was homologous to a sequence of about 313 kb in the nuclear genome. About 33% of sequences in the watermelon mitochondrial genome was homologous with a 260 kb sequence in the nuclear genome. A sequence with a total length of about 38 kb (25%) in the melon chloroplast genome was homologous with 461 sequences in the nuclear genome, with a total length of about 301 kb. A 3.4 Mb sequence in the nuclear genome was homologous with a melon mitochondrial sequence. These results indicate that, during the evolution of watermelon and melon, a large amount of genetic material was exchanged between the nuclear genome and the two organelle genomes in the cytoplasm.}, } @article {pmid33453317, year = {2021}, author = {Slijepcevic, P}, title = {Serial Endosymbiosis Theory: From biology to astronomy and back to the origin of life.}, journal = {Bio Systems}, volume = {202}, number = {}, pages = {104353}, doi = {10.1016/j.biosystems.2021.104353}, pmid = {33453317}, issn = {1872-8324}, mesh = {Astronomy/methods/*trends ; *Biological Evolution ; Biology/methods/*trends ; Eukaryota/physiology ; Humans ; *Origin of Life ; Phylogeny ; Symbiosis/*physiology ; }, abstract = {Serial Endosymbiosis Theory, or SET, was conceived and developed by Lynn Margulis, to explain the greatest discontinuity in the history of life, the origin of eukaryotic cells. Some predictions of SET, namely the origin of mitochondria and chloroplasts, withstood the test of the most recent evidence from a variety of disciplines including phylogenetics, biochemistry, and cell biology. Even though some other predictions fared less well, SET remains a seminal theory in biology. In this paper, I focus on two aspects of SET. First, using the concept of "universal symbiogenesis", developed by Freeman Dyson to search for commonalities in astronomy and biology, I propose that SET can be extended beyond eukaryogenesis. The extension refers to the possibility that even prokaryotic organisms, themselves subject to the process of symbiogenesis in SET, could have emerged symbiotically. Second, I contrast a recent "viral eukaryogenesis" hypothesis, according to which the nucleus evolved from a complex DNA virus, with a view closer to SET, according to which the nucleus evolved through the interplay of the archaeal host, the eubacterial symbiont, and a non-LTR transposon, or telomerase. Viruses joined in later, through the process of viral endogenization, to shape eukaryotic chromosomes in the process of karyotype evolution. These two proposals based on SET are a testament to its longevity as a scientific theory.}, } @article {pmid33454277, year = {2021}, author = {Fuentealba, M and Fabian, DK and Dönertaş, HM and Thornton, JM and Partridge, L}, title = {Transcriptomic profiling of long- and short-lived mutant mice implicates mitochondrial metabolism in ageing and shows signatures of normal ageing in progeroid mice.}, journal = {Mechanisms of ageing and development}, volume = {194}, number = {}, pages = {111437}, pmid = {33454277}, issn = {1872-6216}, support = {WT098565/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Age Factors ; Aging/*genetics/metabolism ; Animals ; Databases, Genetic ; Disease Models, Animal ; Energy Metabolism/*genetics ; *Gene Expression Profiling ; Gene Regulatory Networks ; Mice, Mutant Strains ; Mitochondria/*genetics/metabolism ; Progeria/*genetics/metabolism ; *Transcriptome ; Mice ; }, abstract = {Genetically modified mouse models of ageing are the living proof that lifespan and healthspan can be lengthened or shortened, and provide a powerful context in which to unravel the molecular mechanisms at work. In this study, we analysed and compared gene expression data from 10 long-lived and 8 short-lived mouse models of ageing. Transcriptome-wide correlation analysis revealed that mutations with equivalent effects on lifespan induce more similar transcriptomic changes, especially if they target the same pathway. Using functional enrichment analysis, we identified 58 gene sets with consistent changes in long- and short-lived mice, 55 of which were up-regulated in long-lived mice and down-regulated in short-lived mice. Half of these sets represented genes involved in energy and lipid metabolism, among which Ppargc1a, Mif, Aldh5a1 and Idh1 were frequently observed. Based on the gene sets with consistent changes, and also the whole transcriptome, the gene expression changes during normal ageing resembled the transcriptome of short-lived models, suggesting that accelerated ageing models reproduce partially the molecular changes of ageing. Finally, we identified new genetic interventions that may ameliorate ageing, by comparing the transcriptomes of 51 mouse mutants not previously associated with ageing to expression signatures of long- and short-lived mice and ageing-related changes.}, } @article {pmid33455045, year = {2021}, author = {Pamplona, R and Jové, M and Mota-Martorell, N and Barja, G}, title = {Is the NDUFV2 subunit of the hydrophilic complex I domain a key determinant of animal longevity?.}, journal = {The FEBS journal}, volume = {288}, number = {23}, pages = {6652-6673}, doi = {10.1111/febs.15714}, pmid = {33455045}, issn = {1742-4658}, mesh = {Aging/*genetics/metabolism ; Animals ; Biological Evolution ; Electron Transport/genetics ; Electron Transport Complex I/*genetics/metabolism ; Energy Metabolism/*genetics ; Free Radicals/metabolism ; Longevity/*genetics ; Mitochondria/*genetics/metabolism ; Oxygen Consumption/genetics ; Protein Subunits/genetics/metabolism ; }, abstract = {Complex I, a component of the electron transport chain, plays a central functional role in cell bioenergetics and the biology of free radicals. The structural and functional N module of complex I is one of the main sites of the generation of free radicals. The NDUFV2 subunit/N1a cluster is a component of this module. Furthermore, the rate of free radical production is linked to animal longevity. In this review, we explore the hypothesis that NDUFV2 is the only conserved core subunit designed with a regulatory function to ensure correct electron transfer and free radical production, that low gene expression and protein abundance of the NDUFV2 subunit is an evolutionary adaptation needed to achieve a longevity phenotype, and that these features are determinants of the lower free radical generation at the mitochondrial level and a slower rate of aging of long-lived animals.}, } @article {pmid33457738, year = {2020}, author = {Han, X and Li, Y and Lu, C and Liang, G and Zhang, F}, title = {The complete mitochondrial genome of Epicauta ruficeps (Coleoptera: Meloidae).}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {5}, number = {3}, pages = {2049-2050}, pmid = {33457738}, issn = {2380-2359}, abstract = {Epicauta ruficeps is widely distributed in China and some countries in Southeast Asia, and plays an important role in medicine and biological control. The complete mitochondria genome of E. ruficeps was 15,813 bp in length, with 37 genes, including 13 PCGs, 22 tRNA genes (tRNAs), and two rRNA genes (rRNAs). The positions and sequences of genes were consistent with those of known Meloidae species. The nucleotide composition was highly A + T biased, accounting for ∼65% of the whole mitogenome. The complete mitogenome of E. ruficeps would help understand Meloidae evolution.}, } @article {pmid33457783, year = {2020}, author = {Cevallos, MA and Guerrero, G and Ríos, S and Arroyo, A and Villalobos, MA and Porta, H}, title = {The mitogenome of Pseudocrossidium replicatum, a desiccation-tolerant moss.}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {5}, number = {3}, pages = {2339-2341}, pmid = {33457783}, issn = {2380-2359}, abstract = {Bryophytes are the earliest plant group on Earth. They are a fundamental component of many ecosystems around the World. Some of their main roles are related to soil development, water retention, and biogeochemical cycling. Bryophytes include liverworts, hornworts, and mosses. The sequencing of chloroplast and mitochondria genomes has been useful to elucidate the taxonomy of this heterogeneous plant group. To date, despite their ecological importance only 41 mosses mitogenomes have been deposited in the GenBank. Here, the complete mitochondria genome sequence of Pseudocrossidium replicatum, a moss of the Pottiaceae family isolated in Tlaxcala, Mexico, is reported. The mitochondrial genome size of P. replicatum comprises 105,495 bp and contains the groups of genes described for other bryophytes mitogenomes. Our phylogenetic analysis shows that during the evolution of the mosses' mitogenome, nad7, rps4, rpl16, and rpl10 genes were lost independently in several lineages. The complete mitogenome sequence reported here would be a useful tool for our comprehension of the evolutionary and population genetics of this group of plants.}, } @article {pmid33457843, year = {2020}, author = {Chen, Z and Zhao, J and Qiao, J and Li, W and Li, J and Xu, R and Wang, H and Liu, Z and Xing, B and Wendel, JF and Grover, CE}, title = {Comparative analysis of codon usage between Gossypium hirsutum and G. barbadense mitochondrial genomes.}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {5}, number = {3}, pages = {2500-2506}, pmid = {33457843}, issn = {2380-2359}, abstract = {Gossypium hirsutum and G. barbadense mitochondrial genomes were analyzed to understand the factors shaping codon usage. While most analyses of codon usage suggest minimal to no bias, nucleotide composition, specifically GC content, was significantly correlated with codon usage. In general, both mitochondrial genomes favor codons that end in A or U, with a secondary preference for pyrimidine rich codons. These observations are similar to previous reports of codon usage in cotton nuclear genomes, possibly suggestive of a general bias spanning genomic compartment. Although evidence for codon usage bias is weak for most genes, we identified six genes (i.e. atp8, atp9, sdh3, sdh4, mttB and rpl2) with significant nonrandom codon usage. In general, we find multiple factors that influence cotton mitochondrial genome codon usage, which may include selection in a subset of genes.}, } @article {pmid33458207, year = {2020}, author = {Huang, X and Shi, Y and Huang, D and Shen, X and Wang, Y and Chen, J and Cai, Y}, title = {Characterization of the complete mitochondrial DNA sequence of the Lagocephalus guentheri (Tetraodontidae, Tetraodontiformes).}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {5}, number = {3}, pages = {3472-3473}, pmid = {33458207}, issn = {2380-2359}, abstract = {The complete mitochondrial genome of Lagocephalus guentheri was reported in the present study, which was 16,461 bp in length. It consists of 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes and a non-coding control region. The overall base composition of the genome is 27.54% for A, 24.80% for T, 31.23% for C and 16.43% for G. The phylogenetic tree, which is based on 12 protein-coding gene sequences, suggested that L. guentheri was closest to L. spadiceus. This study could give impetus to studies focused on population structure and molecular evolution of L. guentheri.}, } @article {pmid33473428, year = {2016}, author = {Dong, L and Maoliang, R and Li, Z and Chen, B}, title = {The complete mitochondrial genome sequence of Meishan pig (Sus Scrofa) and a phylogenetic study.}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {1}, number = {1}, pages = {112-113}, pmid = {33473428}, issn = {2380-2359}, abstract = {In this study, we cloned and sequenced the complete mitochondrial genome DNA of Chinese pig, the Meishan pig. The sample was taken from Yencheng City, Jiangsu province in China. The complete genome DNA is 16 708 bp in length. We also performed a comparative analysis of the Meishan pig mitochondrial to the mitogenome sequences of 21 pig breeds which have been deposited in GenBank. Phylogenetic analysis using neighbour-joining computational algorithms showed that the analyzed species are divided into four major clades; the results can be subsequently used to provide information for pig phylogenetic and insights into the evolution of genomes.}, } @article {pmid33473765, year = {2017}, author = {Gagat, P and Mackiewicz, D and Mackiewicz, P}, title = {Peculiarities within peculiarities - dinoflagellates and their mitochondrial genomes.}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {2}, number = {1}, pages = {191-195}, pmid = {33473765}, issn = {2380-2359}, abstract = {After the establishment of an endosymbiotic relationship between a proto-mitochondrion and its probable archaeal host, mitochondrial genomes underwent a spectacular reductive evolution. An interesting pathway was chosen by mitogenomes of unicellular protists called dinoflagellates, which experienced an additional wave of reduction followed by amplification and rearrangement leading to their secondary complexity. The former resulted in a mitogenome consisting of only three protein-coding genes, the latter in their multiple copies being scattered across numerous chromosomes and the evolution of complex processes for their expression. These stunning features raise a question about the future of the dinoflagellate mitochondrial genome.}, } @article {pmid33473993, year = {2017}, author = {Zeng, L and Liu, C and Lin, R and Kang, X and Xie, B and Xiong, X}, title = {Complete mitogenome of the high ethanol production fungus Fusarium oxysporum Mh2-2.}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {2}, number = {2}, pages = {814-815}, pmid = {33473993}, issn = {2380-2359}, abstract = {Fusarium spp. are significantly important plant pathogens, and some of them are ethanol-producing strains. During infection and/or ethanol production, Fusarium requires a plenty of energy that is mainly provided by mitochondria. Here we report the first mitogenome from a selected Fusarium oxysporum strain mh2-2 that produces ethanol from glucose and xylose. The size of this mitogenome, 46 kb, is different from the size of any reported Fusarium mitogenome. Our results provide insight into the functions and evolution of mitochondrial genes and genomes.}, } @article {pmid33474357, year = {2018}, author = {Li, J and Bi, C and Tu, J and Lu, Z}, title = {The complete mitochondrial genome sequence of Boechera stricta.}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {3}, number = {2}, pages = {896-897}, pmid = {33474357}, issn = {2380-2359}, abstract = {Boechera stricta (B. stricta) is a wild relative of Arabidopsis, occurring in mostly montane regions of western North America. In this article, we assembled the complete mitochondrial (mt) DNA sequence of B. stricta into a circular genome of length 271,601 bp, including 31 protein-coding genes, 21 tRNA genes, and 3 rRNA genes. From the neighbour-joining phylogenetic tree was constructed, based on the 23 conserved protein-coding genes of B. stricta and other 23 plant species, and the phylogenic relationship and evolution position of B. stricta were determined. The complete mt genome would be useful for further investigation of the genotype-by-environment interactions in mitochondria of Boechera.}, } @article {pmid33475472, year = {2021}, author = {Fukuda, T and Kanki, T}, title = {Atg43, a novel autophagy-related protein, serves as a mitophagy receptor to bridge mitochondria with phagophores in fission yeast.}, journal = {Autophagy}, volume = {17}, number = {3}, pages = {826-827}, pmid = {33475472}, issn = {1554-8635}, mesh = {Animals ; Autophagosomes ; Autophagy ; Autophagy-Related Proteins ; Mitochondria ; *Mitophagy ; *Schizosaccharomyces ; }, abstract = {Mitophagy is a selective type of autophagy in which damaged or unnecessary mitochondria are sequestered by double-membranous structures called phagophores and delivered to vacuoles/lysosomes for degradation. The molecular mechanisms underlying mitophagy have been studied extensively in budding yeast and mammalian cells. To gain more diverse insights, our recent study identified Atg43 as a mitophagy receptor in the fission yeast Schizosaccharomyces pombe. Atg43 is localized on the mitochondrial outer membrane through the Mim1-Mim2 complex and binds to Atg8, a ubiquitin-like protein conjugated to phagophore membranes. Artificial tethering of Atg8 to mitochondria can bypass the requirement of Atg43 for mitophagy, suggesting that the main role of Atg43 in mitophagy is to stabilize phagophore expansion on mitochondria by interacting with Atg8. Atg43 shares no sequence similarity with mitophagy receptors in other organisms and has a mitophagy-independent function, raising the possibility that Atg43 has acquired the mitophagic function by convergent evolution.}, } @article {pmid33476615, year = {2021}, author = {Li, Q and Wu, P and Li, L and Feng, H and Tu, W and Bao, Z and Xiong, C and Gui, M and Huang, W}, title = {The first eleven mitochondrial genomes from the ectomycorrhizal fungal genus (Boletus) reveal intron loss and gene rearrangement.}, journal = {International journal of biological macromolecules}, volume = {172}, number = {}, pages = {560-572}, doi = {10.1016/j.ijbiomac.2021.01.087}, pmid = {33476615}, issn = {1879-0003}, mesh = {Amino Acid Sequence ; Basidiomycota/classification/*genetics/metabolism ; Biological Evolution ; Exons ; Forests ; Fungal Proteins/classification/*genetics/metabolism ; Genome Size ; *Genome, Mitochondrial ; Introns ; Mitochondria/*genetics/metabolism ; Mitochondrial Proteins/classification/*genetics/metabolism ; Mycorrhizae/classification/*genetics/metabolism ; Phylogeny ; Sequence Alignment ; Sequence Homology, Amino Acid ; Trees/microbiology ; }, abstract = {In the present study, eleven novel complete mitogenomes of Boletus were assembled and compared. The eleven complete mitogenomes were all composed of circular DNA molecules, with sizes ranging from 32,883 bp to 48,298 bp. The mitochondrial gene arrangement of Boletus varied greatly from other Boletales mitogenomes, and gene position reversal were observed frequently in the evolution of Boletus. Across the 15 core protein-coding genes (PCGs) tested, atp9 had the least and rps3 had the largest genetic distances among the eleven Boletus species, indicating varied evolution rates of core PCGs. In addition, the Ka/Ks value for nad3 gene was >1, suggesting that this gene was subject to possible positive selection pressure. Comparative mitogenomic analysis indicated that the intronic region was significantly correlated with the size of mitogenomes in Boletales. Two large-scale intron loss events were detected in the evolution of Boletus. Phylogenetic analyses based on a combined mitochondrial gene dataset yielded a well-supported (BPP ≥ 0.99; BS =100) phylogenetic tree for 72 Agaricomycetes, and the Boletus species had a close relationship with Paxillus. This study served as the first report on complete mitogenomes in Boletus, which will further promote investigations of the genetics, evolution and phylogeny of the Boletus genus.}, } @article {pmid33477742, year = {2021}, author = {Sunagar, K and Khochare, S and Senji Laxme, RR and Attarde, S and Dam, P and Suranse, V and Khaire, A and Martin, G and Captain, A}, title = {A Wolf in Another Wolf's Clothing: Post-Genomic Regulation Dictates Venom Profiles of Medically-Important Cryptic Kraits in India.}, journal = {Toxins}, volume = {13}, number = {1}, pages = {}, pmid = {33477742}, issn = {2072-6651}, support = {IAVI/BES/KASU/0002//Department for International Development, UK Government/ ; SR/FST/LS-II/2018/233//DST-FIST/ ; }, mesh = {Animals ; Antivenins/chemistry ; Biological Evolution ; Bungarotoxins/*chemistry ; Bungarus/classification/*genetics/*metabolism ; Gene Expression Profiling ; Gene Regulatory Networks ; Humans ; India ; Male ; Mice ; Mitochondria/genetics ; Molecular Typing ; Pakistan ; Phylogeny ; *Proteome ; Proteomics ; Species Specificity ; }, abstract = {The Common Krait (Bungarus caeruleus) shares a distribution range with many other 'phenotypically-similar' kraits across the Indian subcontinent. Despite several reports of fatal envenomings by other Bungarus species, commercial Indian antivenoms are only manufactured against B. caeruleus. It is, therefore, imperative to understand the distribution of genetically distinct lineages of kraits, the compositional differences in their venoms, and the consequent impact of venom variation on the (pre)clinical effectiveness of antivenom therapy. To address this knowledge gap, we conducted phylogenetic and comparative venomics investigations of kraits in Southern and Western India. Phylogenetic reconstructions using mitochondrial markers revealed a new species of krait, Romulus' krait (Bungarus romulusi sp. nov.), in Southern India. Additionally, we found that kraits with 17 mid-body dorsal scale rows in Western India do not represent a subspecies of the Sind Krait (B. sindanus walli) as previously believed, but are genetically very similar to B. sindanus in Pakistan. Furthermore, venom proteomics and comparative transcriptomics revealed completely contrasting venom profiles. While the venom gland transcriptomes of all three species were highly similar, venom proteomes and toxicity profiles differed significantly, suggesting the prominent role of post-genomic regulatory mechanisms in shaping the venoms of these cryptic kraits. In vitro venom recognition and in vivo neutralisation experiments revealed a strong negative impact of venom variability on the preclinical performance of commercial antivenoms. While the venom of B. caeruleus was neutralised as per the manufacturer's claim, performance against the venoms of B. sindanus and B. romulusi was poor, highlighting the need for regionally-effective antivenoms in India.}, } @article {pmid33481018, year = {2021}, author = {Wazawa, T and Noma, R and Uto, S and Sugiura, K and Washio, T and Nagai, T}, title = {A photoswitchable fluorescent protein for hours-time-lapse and sub-second-resolved super-resolution imaging.}, journal = {Microscopy (Oxford, England)}, volume = {70}, number = {4}, pages = {340-352}, pmid = {33481018}, issn = {2050-5701}, support = {JPMJCR15N3//Core Research for Evolutional Science and Technology/ ; 23115003, 18H03987, 18H05410, 16K07322, 19K05226//Japan Society for the Promotion of Science/ ; }, mesh = {Luminescent Proteins/*chemistry ; Microscopy ; Time-Lapse Imaging/*methods ; }, abstract = {Reversibly photoswitchable fluorescent proteins (RSFPs) are a class of fluorescent proteins whose fluorescence can be turned on and off by light irradiation. RSFPs have become essential tools for super-resolution (SR) imaging. Because most SR imaging techniques require high-power-density illumination, mitigating phototoxicity in cells due to intense light irradiation has been a challenge. Although we previously developed an RSFP named Kohinoor to achieve SR imaging with low phototoxicity, the photoproperties were insufficient to move a step further to explore the cellular dynamics by SR imaging. Here, we show an improved version of RSFP, Kohinoor2.0, which is suitable for SR imaging of cellular processes. Kohinoor2.0 shows a 2.6-fold higher fluorescence intensity, 2.5-fold faster chromophore maturation and 1.5-fold faster off-switching than Kohinoor. The analysis of the pH dependence of the visible absorption band revealed that Kohinoor2.0 and Kohinoor were in equilibria among multiple fluorescently bright and dark states, with the mutations introduced into Kohinoor2.0 bringing about a higher stabilization of the fluorescently bright states compared to Kohinoor. Using Kohinoor2.0 with our SR imaging technique, super-resolution polarization demodulation/on-state polarization angle narrowing, we conducted 4-h time-lapse SR imaging of an actin filament network in mammalian cells with a total acquisition time of 480 s without a noticeable indication of phototoxicity. Furthermore, we demonstrated the SR imaging of mitochondria dynamics at a time resolution of 0.5 s, in which the fusion and fission processes were clearly visualized. Thus, Kohinoor2.0 is shown to be an invaluable RSFP for the SR imaging of cellular dynamics.}, } @article {pmid33482382, year = {2021}, author = {Irwin, AR and Strong, EE and Kano, Y and Harper, EM and Williams, ST}, title = {Eight new mitogenomes clarify the phylogenetic relationships of Stromboidea within the caenogastropod phylogenetic framework.}, journal = {Molecular phylogenetics and evolution}, volume = {158}, number = {}, pages = {107081}, doi = {10.1016/j.ympev.2021.107081}, pmid = {33482382}, issn = {1095-9513}, mesh = {Animals ; Gastropoda/classification/*genetics ; *Genome, Mitochondrial ; Mitochondria/classification/*genetics ; Mitochondrial Proteins/classification/genetics ; Nucleic Acid Conformation ; Phylogeny ; RNA, Ribosomal, 18S/classification/genetics ; RNA, Transfer/chemistry ; }, abstract = {Members of the gastropod superfamily Stromboidea (Littorinimorpha) are characterised by their elaborate shell morphologies, distinctive mode of locomotion, and often large and colourful eyes. This iconic group comprises over 130 species, including many large and charismatic species. The family Strombidae is of particular interest, largely due to its commercial importance and wide distribution in tropical and subtropical waters. Although a few strombid mitochondrial genomes have been sequenced, data for the other four Recent families in Stromboidea are lacking. In this study we report seven new stromboid mitogenomes obtained from transcriptomic and genomic data, with taxonomic representation from each Recent stromboid family, including the first mitogenomes for Aporrhaidae, Rostellariidae, Seraphsidae and Struthiolariidae. We also report a new mitogenome for the family Xenophoridae. We use these data, along with published sequences, to investigate the relationships among these and other caenogastropod groups. All analyses undertaken in this study support monophyly of Stromboidea as redefined here to include Xenophoridae, a finding consistent with morphological and behavioural data. Consistent with previous morphological and molecular analyses, including those based on mitogenomes, monophyly of Hypsogastropoda is confirmed but monophyly of Littorinimorpha is again rejected.}, } @article {pmid33482383, year = {2021}, author = {Phillips, MJ and Shazwani Zakaria, S}, title = {Enhancing mitogenomic phylogeny and resolving the relationships of extinct megafaunal placental mammals.}, journal = {Molecular phylogenetics and evolution}, volume = {158}, number = {}, pages = {107082}, doi = {10.1016/j.ympev.2021.107082}, pmid = {33482383}, issn = {1095-9513}, mesh = {Animals ; Biological Evolution ; DNA, Mitochondrial/classification/genetics ; Eutheria/genetics ; Female ; Genetic Heterogeneity ; Likelihood Functions ; Mammals/classification/*genetics ; Mitochondria/*genetics ; Phylogeny ; Pregnancy ; }, abstract = {Mitochondrial genomes provided the first widely used sequences that were sufficiently informative to resolve relationships among animals across a wide taxonomic domain, from within species to between phyla. However, mitogenome studies supported several anomalous relationships and fell partly out of favour as sequencing multiple, independent nuclear loci proved to be highly effective. A tendency to blame mitochondrial DNA (mtDNA) has overshadowed efforts to understand and ameliorate underlying model misspecification. Here we find that influential assessments of the infidelity of mitogenome phylogenies have often been overstated, but nevertheless, substitution saturation and compositional non-stationarity substantially mislead reconstruction. We show that RY coding the mtDNA, excluding protein-coding 3rd codon sites, partitioning models based on amino acid hydrophobicity and enhanced taxon sampling improve the accuracy of mitogenomic phylogeny reconstruction for placental mammals, almost to the level of multi-gene nuclear datasets. Indeed, combined analysis of mtDNA with 3-fold longer nuclear sequence data either maintained or improved upon the nuclear support for all generally accepted clades, even those that mtDNA alone did not favour, thus indicating "hidden support". Confident mtDNA phylogeny reconstruction is especially important for understanding the evolutionary dynamics of mitochondria themselves, and for merging extinct taxa into the tree of life, with ancient DNA often only accessible as mtDNA. Our ancient mtDNA analyses lend confidence to the relationships of three extinct megafaunal taxa: glyptodonts are nested within armadillos, the South American ungulate, Macrauchenia is sister to horses and rhinoceroses, and sabre-toothed and scimitar cats are the monophyletic sister-group of modern cats.}, } @article {pmid33486550, year = {2021}, author = {Christensen, AC}, title = {Plant Mitochondria are a Riddle Wrapped in a Mystery Inside an Enigma.}, journal = {Journal of molecular evolution}, volume = {89}, number = {3}, pages = {151-156}, pmid = {33486550}, issn = {1432-1432}, mesh = {*Cell Nucleus ; *Evolution, Molecular ; Mitochondria/genetics ; Mutation ; Phylogeny ; }, abstract = {A fundamental paradox motivates the study of plant mitochondrial genomics: the mutation rate is very low (lower than in the nucleus) but the rearrangement rate is high. A landmark paper published in Journal of Molecular Evolution in 1988 established these facts and revealed the paradox. Jeffrey Palmer and Laura Herbon did a prodigious amount of work in the pre-genome sequencing era to identify both the high frequency of rearrangements between closely related species, and the low frequency of mutations, observations that have now been confirmed many times by sequencing. This paper was also the first to use molecular data on rearrangements as a phylogenetic trait to build a parsimonious tree. The work was a technical tour-de-force, its findings are still at the heart of plant mitochondrial genomics, and the underlying molecular mechanisms that produce this paradox are still not completely understood.}, } @article {pmid33487111, year = {2021}, author = {Wan, KY and Jékely, G}, title = {Origins of eukaryotic excitability.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1820}, pages = {20190758}, pmid = {33487111}, issn = {1471-2970}, mesh = {*Biological Evolution ; Eukaryota/*physiology ; Eukaryotic Cells/*physiology ; }, abstract = {All living cells interact dynamically with a constantly changing world. Eukaryotes, in particular, evolved radically new ways to sense and react to their environment. These advances enabled new and more complex forms of cellular behaviour in eukaryotes, including directional movement, active feeding, mating, and responses to predation. But what are the key events and innovations during eukaryogenesis that made all of this possible? Here we describe the ancestral repertoire of eukaryotic excitability and discuss five major cellular innovations that enabled its evolutionary origin. The innovations include a vastly expanded repertoire of ion channels, the emergence of cilia and pseudopodia, endomembranes as intracellular capacitors, a flexible plasma membrane and the relocation of chemiosmotic ATP synthesis to mitochondria, which liberated the plasma membrane for more complex electrical signalling involved in sensing and reacting. We conjecture that together with an increase in cell size, these new forms of excitability greatly amplified the degrees of freedom associated with cellular responses, allowing eukaryotes to vastly outperform prokaryotes in terms of both speed and accuracy. This comprehensive new perspective on the evolution of excitability enriches our view of eukaryogenesis and emphasizes behaviour and sensing as major contributors to the success of eukaryotes. This article is part of the theme issue 'Basal cognition: conceptual tools and the view from the single cell'.}, } @article {pmid33490584, year = {2021}, author = {Eo, JK}, title = {The complete mitogenome of Diaporthe nobilis.}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {6}, number = {1}, pages = {6-7}, pmid = {33490584}, issn = {2380-2359}, abstract = {The complete mitogenome of Diaporthe nobilis NIE8444 (KCTC No. 56710) isolated from alpine conifer Abies nephrolepis is determined by the Illumina Hiseq4000 platform in this study. This mitogenome consists of 67,437 bp length with 31.45% G + C content. A total of 51 genes were predicted in this mitogenome: 21 protein-coding genes, 2 rRNAs and 28 tRNAs. Phylogenetic tree based on small subunit ribosomal RNA of mitochondria showed that D. nobilis was close to D. longicolla. This complete mitogenome of D. nobilis provides valuable information on the mitochondrial evolution of endophytic fungi.}, } @article {pmid33493156, year = {2021}, author = {Neverov, AD and Popova, AV and Fedonin, GG and Cheremukhin, EA and Klink, GV and Bazykin, GA}, title = {Episodic evolution of coadapted sets of amino acid sites in mitochondrial proteins.}, journal = {PLoS genetics}, volume = {17}, number = {1}, pages = {e1008711}, pmid = {33493156}, issn = {1553-7404}, mesh = {Amino Acid Substitution/genetics ; Amino Acids/genetics ; Animals ; *Epistasis, Genetic ; *Evolution, Molecular ; Fungi/genetics ; Genome, Mitochondrial/genetics ; Mitochondria/genetics ; Mitochondrial Proteins/*genetics ; Phylogeny ; Protein Conformation ; Protein Interaction Maps/genetics ; *Selection, Genetic ; }, abstract = {The rate of evolution differs between protein sites and changes with time. However, the link between these two phenomena remains poorly understood. Here, we design a phylogenetic approach for distinguishing pairs of amino acid sites that evolve concordantly, i.e., such that substitutions at one site trigger subsequent substitutions at the other; and also pairs of sites that evolve discordantly, so that substitutions at one site impede subsequent substitutions at the other. We distinguish groups of amino acid sites that undergo coordinated evolution and evolve discordantly from other such groups. In mitochondrion-encoded proteins of metazoans and fungi, we show that concordantly evolving sites are clustered in protein structures. By analysing the phylogenetic patterns of substitutions at concordantly and discordantly evolving site pairs, we find that concordant evolution has two distinct causes: epistatic interactions between amino acid substitutions and episodes of selection independently affecting substitutions at different sites. The rate of substitutions at concordantly evolving groups of protein sites changes in the course of evolution, indicating episodes of selection limited to some of the lineages. The phylogenetic positions of these changes are consistent between proteins, suggesting common selective forces underlying them.}, } @article {pmid33494532, year = {2021}, author = {Kirkland, C and Farré, M}, title = {Mitochondrial Genome Evolution, Genetic Diversity, and Population Structure in British Water Voles (Arvicola amphibius).}, journal = {Genes}, volume = {12}, number = {2}, pages = {}, pmid = {33494532}, issn = {2073-4425}, mesh = {Animals ; Arvicolinae/classification/*genetics ; *Evolution, Molecular ; *Genetic Variation ; Genetics, Population ; *Genome, Mitochondrial ; Haplotypes ; Mitochondria/*genetics ; Phylogeny ; }, abstract = {The European water vole (Arvicola amphibius) is a rodent within the subfamily Arvicolinae. In Britain, water voles have declined rapidly during the last century, making them a conservation priority. The relationship of Arvicola to other genera within Arvicolinae remains debated. Additionally, the impact that captive breeding programs in Britain are having on the genetic diversity of water voles is unknown. We use available mitochondrial genomes to construct the phylogeny of species within Arvicolinae, followed by sequencing the mitochondrial DNA control region of 17 individuals from a captive population of water voles in Britain to assess their genetic diversity and population structure. Our study first provides an updated phylogenetic tree of Arvicolinae using the mitochondrial genome of 31 species. Second, our results show considerable genetic diversity in the captive population of water voles, when compared with natural populations in Britain. We confirm the grouping of British water voles into two clades, with all captive individuals found in the English/Welsh clade. Moreover, captive water voles clustered closely with populations in the South East and East of England. The mitochondrial genome provides a useful marker to study the phylogenetics of this rodent clade and in addition, our study provides support for the breeding program at Wildwood Trust and provides a framework for future conservation genetics studies in this species.}, } @article {pmid33495511, year = {2021}, author = {Subramanian, V and Rodemoyer, B and Shastri, V and Rasmussen, LJ and Desler, C and Schmidt, KH}, title = {Bloom syndrome DNA helicase deficiency is associated with oxidative stress and mitochondrial network changes.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {2157}, pmid = {33495511}, issn = {2045-2322}, support = {R01 GM081425/GM/NIGMS NIH HHS/United States ; R01 GM139296/GM/NIGMS NIH HHS/United States ; }, mesh = {Autophagy ; Bloom Syndrome/*enzymology/*pathology ; Cyclin B1/metabolism ; DNA Damage ; DNA Replication ; DNA-Binding Proteins/metabolism ; Energy Metabolism ; Fibroblasts/enzymology/pathology ; G1 Phase ; Humans ; Mitochondria/*metabolism/ultrastructure ; Mitochondrial Proteins/metabolism ; Mitosis ; *Oxidative Stress ; Reactive Oxygen Species/metabolism ; RecQ Helicases/*deficiency/metabolism ; Transcription Factors/metabolism ; Up-Regulation ; }, abstract = {Bloom Syndrome (BS; OMIM #210900; ORPHA #125) is a rare genetic disorder that is associated with growth deficits, compromised immune system, insulin resistance, genome instability and extraordinary predisposition to cancer. Most efforts thus far have focused on understanding the role of the Bloom syndrome DNA helicase BLM as a recombination factor in maintaining genome stability and suppressing cancer. Here, we observed increased levels of reactive oxygen species (ROS) and DNA base damage in BLM-deficient cells, as well as oxidative-stress-dependent reduction in DNA replication speed. BLM-deficient cells exhibited increased mitochondrial mass, upregulation of mitochondrial transcription factor A (TFAM), higher ATP levels and increased respiratory reserve capacity. Cyclin B1, which acts in complex with cyclin-dependent kinase CDK1 to regulate mitotic entry and associated mitochondrial fission by phosphorylating mitochondrial fission protein Drp1, fails to be fully degraded in BLM-deficient cells and shows unscheduled expression in G1 phase cells. This failure to degrade cyclin B1 is accompanied by increased levels and persistent activation of Drp1 throughout mitosis and into G1 phase as well as mitochondrial fragmentation. This study identifies mitochondria-associated abnormalities in Bloom syndrome patient-derived and BLM-knockout cells and we discuss how these abnormalities may contribute to Bloom syndrome.}, } @article {pmid33498264, year = {2021}, author = {Gladyck, S and Aras, S and Hüttemann, M and Grossman, LI}, title = {Regulation of COX Assembly and Function by Twin CX9C Proteins-Implications for Human Disease.}, journal = {Cells}, volume = {10}, number = {2}, pages = {}, pmid = {33498264}, issn = {2073-4409}, support = {W81XWH-16-1-0516//U.S. Department of Defense/ ; R01 GM116807/GF/NIH HHS/United States ; HHSN275201300006C/HD/NICHD NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; *Disease ; Electron Transport Complex IV/*chemistry/*metabolism ; Humans ; Phylogeny ; Protein Binding ; Protein Subunits/chemistry/metabolism ; }, abstract = {Oxidative phosphorylation is a tightly regulated process in mammals that takes place in and across the inner mitochondrial membrane and consists of the electron transport chain and ATP synthase. Complex IV, or cytochrome c oxidase (COX), is the terminal enzyme of the electron transport chain, responsible for accepting electrons from cytochrome c, pumping protons to contribute to the gradient utilized by ATP synthase to produce ATP, and reducing oxygen to water. As such, COX is tightly regulated through numerous mechanisms including protein-protein interactions. The twin CX9C family of proteins has recently been shown to be involved in COX regulation by assisting with complex assembly, biogenesis, and activity. The twin CX9C motif allows for the import of these proteins into the intermembrane space of the mitochondria using the redox import machinery of Mia40/CHCHD4. Studies have shown that knockdown of the proteins discussed in this review results in decreased or completely deficient aerobic respiration in experimental models ranging from yeast to human cells, as the proteins are conserved across species. This article highlights and discusses the importance of COX regulation by twin CX9C proteins in the mitochondria via COX assembly and control of its activity through protein-protein interactions, which is further modulated by cell signaling pathways. Interestingly, select members of the CX9C protein family, including MNRR1 and CHCHD10, show a novel feature in that they not only localize to the mitochondria but also to the nucleus, where they mediate oxygen- and stress-induced transcriptional regulation, opening a new view of mitochondrial-nuclear crosstalk and its involvement in human disease.}, } @article {pmid33502469, year = {2021}, author = {Han, KL and Barreto, FS}, title = {Pervasive Mitonuclear Coadaptation Underlies Fast Development in Interpopulation Hybrids of a Marine Crustacean.}, journal = {Genome biology and evolution}, volume = {13}, number = {3}, pages = {}, pmid = {33502469}, issn = {1759-6653}, mesh = {Adenosine Triphosphate/metabolism ; Animals ; Biological Evolution ; Cell Nucleus/genetics ; Copepoda/*genetics ; *Evolution, Molecular ; Female ; Gene Frequency ; Gene Pool ; Genetic Fitness ; Genome, Mitochondrial/*genetics ; *Hybridization, Genetic ; Male ; Mitochondria/genetics ; Sequence Analysis ; }, abstract = {Cellular energy production requires coordinated interactions between genetic components from the nuclear and mitochondrial genomes. This coordination results in coadaptation of interacting elements within populations. Interbreeding between divergent gene pools can disrupt coadapted loci and result in hybrid fitness breakdown. While specific incompatible loci have been detected in multiple eukaryotic taxa, the extent of the nuclear genome that is influenced by mitonuclear coadaptation is not clear in any species. Here, we used F2 hybrids between two divergent populations of the copepod Tigriopus californicus to examine mitonuclear coadaptation across the nuclear genome. Using developmental rate as a measure of fitness, we found that fast-developing copepods had higher ATP synthesis capacity than slow developers, suggesting variation in developmental rates is at least partly associated with mitochondrial dysfunction. Using Pool-seq, we detected strong biases for maternal alleles across 7 (of 12) chromosomes in both reciprocal crosses in high-fitness hybrids, whereas low-fitness hybrids showed shifts toward the paternal population. Comparison with previous results on a different hybrid cross revealed largely different patterns of strong mitonuclear coadaptation associated with developmental rate. Our findings suggest that functional coadaptation between interacting nuclear and mitochondrial components is reflected in strong polygenic effects on this life-history phenotype, and reveal that molecular coadaptation follows independent evolutionary trajectories among isolated populations.}, } @article {pmid33507545, year = {2021}, author = {Li, J and Meng, Q and Fu, Y and Yu, X and Ji, T and Chao, Y and Chen, Q and Li, Y and Bian, H}, title = {Novel insights: Dynamic foam cells derived from the macrophage in atherosclerosis.}, journal = {Journal of cellular physiology}, volume = {236}, number = {9}, pages = {6154-6167}, doi = {10.1002/jcp.30300}, pmid = {33507545}, issn = {1097-4652}, mesh = {Animals ; Atherosclerosis/*pathology ; Cell Communication ; Cholesterol/metabolism ; Esterification ; Foam Cells/metabolism/*pathology ; Humans ; Metabolome ; }, abstract = {Atherosclerosis can be regarded as a chronic disease derived from the interaction between disordered lipoproteins and an unsuitable immune response. The evolution of foam cells is not only a significant pathological change in the early stage of atherosclerosis but also a key stage in the occurrence and development of atherosclerosis. The formation of foam cells is mainly caused by the imbalance among lipids uptake, lipids treatment, and reverse cholesterol transport. Although a large number of studies have summarized the source of foam cells and the mechanism of foam cells formation, we propose a new idea about foam cells in atherosclerosis. Rather than an isolated microenvironment, the macrophage multiple lipid uptake pathways, lipid internalization, lysosome, mitochondria, endoplasmic reticulum, neutral cholesterol ester hydrolase (NCEH), acyl-coenzyme A-cholesterol acyltransferase (ACAT), and reverse cholesterol transport are mutually influential, and form a dynamic process under multi-factor regulation. The macrophage takes on different uptake lipid statuses depending on multiple uptake pathways and intracellular lipids, lipid metabolites versus pro-inflammatory factors. Except for NCEH and ACAT, the lipid internalization of macrophages also depends on multicellular organelles including the lysosome, mitochondria, and endoplasmic reticulum, which are associated with each other. A dynamic balance between esterification and hydrolysis of cholesterol for macrophages is essential for physiology and pathology. Therefore, we propose that the foam cell in the process of atherosclerosis may be dynamic under multi-factor regulation, and collate this study to provide a holistic and dynamic idea of the foam cell.}, } @article {pmid33507977, year = {2021}, author = {Dryomov, SV and Nazhmidenova, AM and Starikovskaya, EB and Shalaurova, SA and Rohland, N and Mallick, S and Bernardos, R and Derevianko, AP and Reich, D and Sukernik, RI}, title = {Mitochondrial genome diversity on the Central Siberian Plateau with particular reference to the prehistory of northernmost Eurasia.}, journal = {PloS one}, volume = {16}, number = {1}, pages = {e0244228}, pmid = {33507977}, issn = {1932-6203}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {DNA, Mitochondrial/chemistry/classification/genetics/history ; Genetic Linkage ; Genetic Variation ; *Genome, Mitochondrial ; Haplotypes ; History, Ancient ; Human Migration ; Humans ; Mitochondria/*genetics ; Phylogeny ; Siberia ; }, abstract = {The Central Siberian Plateau was the last geographic area in Eurasia to become habitable by modern humans after the Last Glacial Maximum (LGM). Through a comprehensive dataset of mitochondrial DNA (mtDNA) genomes retained in the remnats of earlier ("Old") Siberians, primarily the Ket, Tofalar, and Todzhi, we explored genetic links between the Yenisei-Sayan region and Northeast Eurasia (best represented by the Yukaghir) over the last 10,000 years. We generated 218 new complete mtDNA sequences and placed them into compound phylogenies with 7 newly obtained and 70 published ancient mitochondrial genomes. We have considerably extended the mtDNA sequence diversity (at the entire mtDNA genome level) of autochthonous Siberians, which remain poorly sampled, and these new data may have a broad impact on the study of human migration. We compared present-day mtDNA diversity in these groups with complete mitochondrial genomes from ancient samples from the region and placed the samples into combined genealogical trees. The resulting components were used to clarify the origins and expansion history of mtDNA lineages that evolved in the refugia of south-central Siberia and beyond, as well as multiple phases of connection between this region and distant parts of Eurasia.}, } @article {pmid33510193, year = {2021}, author = {Zhang, K and Zhu, K and Liu, Y and Zhang, H and Gong, L and Jiang, L and Liu, L and Lü, Z and Liu, B}, title = {Novel gene rearrangement in the mitochondrial genome of Muraenesox cinereus and the phylogenetic relationship of Anguilliformes.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {2411}, pmid = {33510193}, issn = {2045-2322}, mesh = {Animals ; Base Sequence ; Codon ; Eels/*classification/*genetics ; *Gene Rearrangement ; Genes, Mitochondrial ; *Genome, Mitochondrial ; *Genomics/methods ; Nucleic Acid Conformation ; *Phylogeny ; }, abstract = {The structure and gene sequence of the fish mitochondrial genome are generally considered to be conservative. However, two types of gene arrangements are found in the mitochondrial genome of Anguilliformes. In this paper, we report a complete mitogenome of Muraenesox cinereus (Anguilliformes: Muraenesocidae) with rearrangement phenomenon. The total length of the M. cinereus mitogenome was 17,673 bp, and it contained 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNA genes, and two identical control regions (CRs). The mitochondrial genome of M. cinereus was obviously rearranged compared with the mitochondria of typical vertebrates. The genes ND6 and the conjoint trnE were translocated to the location between trnT and trnP, and one of the duplicated CR was translocated to the upstream of the ND6. The tandem duplication and random loss is most suitable for explaining this mitochondrial gene rearrangement. The Anguilliformes phylogenetic tree constructed based on the whole mitochondrial genome well supports Congridae non-monophyly. These results provide a basis for the future Anguilliformes mitochondrial gene arrangement characteristics and further phylogenetic research.}, } @article {pmid33510273, year = {2021}, author = {Park, HS and Lee, WK and Lee, SC and Lee, HO and Joh, HJ and Park, JY and Kim, S and Song, K and Yang, TJ}, title = {Inheritance of chloroplast and mitochondrial genomes in cucumber revealed by four reciprocal F1 hybrid combinations.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {2506}, pmid = {33510273}, issn = {2045-2322}, mesh = {Cucumis sativus/*genetics ; Evolution, Molecular ; Genetic Markers ; *Genome, Chloroplast ; *Genome, Mitochondrial ; Genomics/methods ; *Hybridization, Genetic ; *Inheritance Patterns ; Plant Breeding ; Polymorphism, Genetic ; }, abstract = {Both genomes in chloroplasts and mitochondria of plant cell are usually inherited from maternal parent, with rare exceptions. To characterize the inheritance patterns of the organelle genomes in cucumber (Cucumis sativus var. sativus), two inbred lines and their reciprocal F1 hybrids were analyzed using an next generation whole genome sequencing data. Their complete chloroplast genome sequences were de novo assembled, and a single SNP was identified between the parental lines. Two reciprocal F1 hybrids have the same chloroplast genomes with their maternal parents. Meanwhile, 292 polymorphic sites were identified between mitochondrial genomes of the two parental lines, which showed the same genotypes with their paternal parents in the two reciprocal F1 hybrids, without any recombination. The inheritance patterns of the chloroplast and mitochondria genomes were also confirmed in four additional cucumber accessions and their six reciprocal F1 hybrids using molecular markers derived from the identified polymorphic sites. Taken together, our results indicate that the cucumber chloroplast genome is maternally inherited, as is typically observed in other plant species, whereas the large cucumber mitochondrial genome is paternally inherited. The combination of DNA markers derived from the chloroplast and mitochondrial genomes will provide a convenient system for purity test of F1 hybrid seeds in cucumber breeding.}, } @article {pmid33513437, year = {2021}, author = {Li, W and Cao, Y and Chen, Z and Tan, Y and Dai, Y and Wei, J and Xiao, J and Feng, H}, title = {Black carp TRADD suppresses MAVS/IFN signaling during the innate immune activation.}, journal = {Fish & shellfish immunology}, volume = {111}, number = {}, pages = {83-93}, doi = {10.1016/j.fsi.2021.01.006}, pmid = {33513437}, issn = {1095-9947}, mesh = {Amino Acid Sequence ; Animals ; Carps/*genetics/*immunology ; Cell Line ; Fish Diseases/*immunology ; Fish Proteins/chemistry/genetics/immunology ; Gene Expression Profiling/veterinary ; Gene Expression Regulation/*immunology ; HEK293 Cells ; Humans ; Immunity, Innate/*genetics ; Lipopolysaccharides/pharmacology ; Phylogeny ; Poly I-C/pharmacology ; Rhabdoviridae/physiology ; Rhabdoviridae Infections/immunology/veterinary ; Sequence Alignment/veterinary ; TNF Receptor-Associated Death Domain Protein/chemistry/*genetics/*immunology ; }, abstract = {Tumor necrosis factor receptor 1 (TNFR1) associated death domain protein (TRADD) is a pivotal adaptor in TNF signaling pathway and up-regulates MAVS/IFN signaling pathway in human and mammal. However, the role of TRADD in teleost fish remains obscure. To reveal the function of teleost TRADD in the innate immune response, the TRADD homologue (bcTRADD) of black carp (Mylopharyngodon piceus) has been cloned and the function of bcTRADD is investigated in this study, which shares similar functional domain to its mammalian counterpart. bcTRADD mRNA expression level increased in response to different stimuli, including LPS, poly (I:C) and virus infection in host cells. bcTRADD activated the transcriptional activity of NF-κB promoter in the reporter assay; however, showed hardly any effect on the transcriptional activity of IFN promoter. It was interesting that black carp mitochondria antiviral signaling protein (bcMAVS)-activated IFN promoter transcription were dramatically depressed by bcTRADD and the C-terminal death domain of bcTRADD was indispensable for its regulation of bcMAVS. Accordingly, the plaque assay result showed that EPC cells co-expressing bcMAVS and bcTRADD presented much attenuated antiviral activity than EPC cells expressing bcMAVS alone. Knockdown of bcTRADD slightly promoted the antiviral ability of the host cells against SVCV. The current data support the conclusion that bcTRADD suppresses MAVS-mediated antiviral signaling, which is different to its mammalian counterpart.}, } @article {pmid33514857, year = {2021}, author = {Macey, JR and Pabinger, S and Barbieri, CG and Buring, ES and Gonzalez, VL and Mulcahy, DG and DeMeo, DP and Urban, L and Hime, PM and Prost, S and Elliott, AN and Gemmell, NJ}, title = {Evidence of two deeply divergent co-existing mitochondrial genomes in the Tuatara reveals an extremely complex genomic organization.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {116}, pmid = {33514857}, issn = {2399-3642}, mesh = {Acclimatization/genetics ; Animals ; Cold Temperature ; DNA, Mitochondrial/*genetics ; *Evolution, Molecular ; Female ; *Genome, Mitochondrial ; Male ; Phylogeny ; Reptiles/*genetics ; }, abstract = {Animal mitochondrial genomic polymorphism occurs as low-level mitochondrial heteroplasmy and deeply divergent co-existing molecules. The latter is rare, known only in bivalvian mollusks. Here we show two deeply divergent co-existing mt-genomes in a vertebrate through genomic sequencing of the Tuatara (Sphenodon punctatus), the sole-representative of an ancient reptilian Order. The two molecules, revealed using a combination of short-read and long-read sequencing technologies, differ by 10.4% nucleotide divergence. A single long-read covers an entire mt-molecule for both strands. Phylogenetic analyses suggest a 7-8 million-year divergence between genomes. Contrary to earlier reports, all 37 genes typical of animal mitochondria, with drastic gene rearrangements, are confirmed for both mt-genomes. Also unique to vertebrates, concerted evolution drives three near-identical putative Control Region non-coding blocks. Evidence of positive selection at sites linked to metabolically important transmembrane regions of encoded proteins suggests these two mt-genomes may confer an adaptive advantage for an unusually cold-tolerant reptile.}, } @article {pmid33521279, year = {2021}, author = {Kim, J and Jang, SM and Choi, E and Jo, E and Lee, SJ and Kim, SH and Chi, YM and Kim, JH and Park, H}, title = {The complete mitochondrial genome of Eaton's skate, Bathyraja eatonii (Rajiformes, Arhynchobatidae).}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {6}, number = {1}, pages = {91-92}, pmid = {33521279}, issn = {2380-2359}, abstract = {The complete mitochondrial genome of Eaton's skate Bathyraja eatonii was studied using the long-read technology, PacBio Sequel System. The complete mitochondrial genome form of B. eatonii was 16,698 bp and it's comprised of 13 protein-coding genes, 22 tRNA and 2 rRNA. The base composition of B. eatonii is analyzed 31.94% for A, 33.94% for T, 13.49% for G, 20.64% for C, the result of GC content was 33.94%. Phylogenetic analysis showed that B. eatonii was closely related to Bathyraja meridionalis in Arhynchobatidae family, and this first mitochondrial genome of Antarctic skate would provide fundamental information to the evolutional relationship of Antarctic fishes.}, } @article {pmid33521839, year = {2021}, author = {Schumm, YR and Bakaloudis, D and Barboutis, C and Cecere, JG and Eraud, C and Fischer, D and Hering, J and Hillerich, K and Lormée, H and Mader, V and Masello, JF and Metzger, B and Rocha, G and Spina, F and Quillfeldt, P}, title = {Prevalence and genetic diversity of avian haemosporidian parasites in wild bird species of the order Columbiformes.}, journal = {Parasitology research}, volume = {120}, number = {4}, pages = {1405-1420}, pmid = {33521839}, issn = {1432-1955}, mesh = {Animal Migration ; Animals ; Bird Diseases/*epidemiology/parasitology ; Columbidae/parasitology ; Columbiformes/*parasitology ; Cytochromes b/genetics ; Genetic Variation ; Global Warming ; Haemosporida/classification/*genetics/growth & development ; Host Specificity ; Mitochondria/genetics ; Multiplex Polymerase Chain Reaction/veterinary ; Phylogeny ; Plasmodium/genetics ; Polymerase Chain Reaction/veterinary ; Prevalence ; Protozoan Infections, Animal/*epidemiology/parasitology ; }, abstract = {Diseases can play a role in species decline. Among them, haemosporidian parasites, vector-transmitted protozoan parasites, are known to constitute a risk for different avian species. However, the magnitude of haemosporidian infection in wild columbiform birds, including strongly decreasing European turtle doves, is largely unknown. We examined the prevalence and diversity of haemosporidian parasites Plasmodium, Leucocytozoon and subgenera Haemoproteus and Parahaemoproteus in six species of the order Columbiformes during breeding season and migration by applying nested PCR, one-step multiplex PCR assay and microscopy. We detected infections in 109 of the 259 screened individuals (42%), including 15 distinct haemosporidian mitochondrial cytochrome b lineages, representing five H. (Haemoproteus), two H. (Parahaemoproteus), five Leucocytozoon and three Plasmodium lineages. Five of these lineages have never been described before. We discriminated between single and mixed infections and determined host species-specific prevalence for each parasite genus. Observed differences among sampled host species are discussed with reference to behavioural characteristics, including nesting and migration strategy. Our results support previous suggestions that migratory birds have a higher prevalence and diversity of blood parasites than resident or short-distance migratory species. A phylogenetic reconstruction provided evidence for H. (Haemoproteus) as well as H. (Parahaemoproteus) infections in columbiform birds. Based on microscopic examination, we quantified parasitemia, indicating the probability of negative effects on the host. This study provides a large-scale baseline description of haemosporidian infections of wild birds belonging to the order Columbiformes sampled in the northern hemisphere. The results enable the monitoring of future changes in parasite transmission areas, distribution and diversity associated with global change, posing a potential risk for declining avian species as the European turtle dove.}, } @article {pmid33524071, year = {2021}, author = {Hayward, JA and Rajendran, E and Zwahlen, SM and Faou, P and van Dooren, GG}, title = {Divergent features of the coenzyme Q:cytochrome c oxidoreductase complex in Toxoplasma gondii parasites.}, journal = {PLoS pathogens}, volume = {17}, number = {2}, pages = {e1009211}, pmid = {33524071}, issn = {1553-7374}, mesh = {Animals ; Blotting, Western ; Cells, Cultured ; Electron Transport Complex III/chemistry/*metabolism ; Fluorescent Antibody Technique ; Humans ; Mitochondria/metabolism ; Oxygen/metabolism ; Protein Subunits/chemistry/metabolism ; Smegmamorpha ; Toxoplasma/genetics/*metabolism ; }, abstract = {The mitochondrion is critical for the survival of apicomplexan parasites. Several major anti-parasitic drugs, such as atovaquone and endochin-like quinolones, act through inhibition of the mitochondrial electron transport chain at the coenzyme Q:cytochrome c oxidoreductase complex (Complex III). Despite being an important drug target, the protein composition of Complex III of apicomplexan parasites has not been elucidated. Here, we undertake a mass spectrometry-based proteomic analysis of Complex III in the apicomplexan Toxoplasma gondii. Along with canonical subunits that are conserved across eukaryotic evolution, we identify several novel or highly divergent Complex III components that are conserved within the apicomplexan lineage. We demonstrate that one such subunit, which we term TgQCR11, is critical for parasite proliferation, mitochondrial oxygen consumption and Complex III activity, and establish that loss of this protein leads to defects in Complex III integrity. We conclude that the protein composition of Complex III in apicomplexans differs from that of the mammalian hosts that these parasites infect.}, } @article {pmid33526678, year = {2021}, author = {Rout, S and Oeljeklaus, S and Makki, A and Tachezy, J and Warscheid, B and Schneider, A}, title = {Determinism and contingencies shaped the evolution of mitochondrial protein import.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {6}, pages = {}, pmid = {33526678}, issn = {1091-6490}, mesh = {Animals ; Carrier Proteins/genetics ; *Evolution, Molecular ; Mitochondria/*genetics/metabolism ; Mitochondrial Membrane Transport Proteins/*genetics ; Mitochondrial Precursor Protein Import Complex Proteins ; Mitochondrial Proteins/genetics ; Protein Binding ; Protein Precursors/genetics ; Protein Transport/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/*genetics ; Trypanosoma brucei brucei/genetics/metabolism/pathogenicity ; }, abstract = {Mitochondrial protein import requires outer membrane receptors that evolved independently in different lineages. Here we used quantitative proteomics and in vitro binding assays to investigate the substrate preferences of ATOM46 and ATOM69, the two mitochondrial import receptors of Trypanosoma brucei The results show that ATOM46 prefers presequence-containing, hydrophilic proteins that lack transmembrane domains (TMDs), whereas ATOM69 prefers presequence-lacking, hydrophobic substrates that have TMDs. Thus, the ATOM46/yeast Tom20 and the ATOM69/yeast Tom70 pairs have similar substrate preferences. However, ATOM46 mainly uses electrostatic, and Tom20 hydrophobic, interactions for substrate binding. In vivo replacement of T. brucei ATOM46 by yeast Tom20 did not restore import. However, replacement of ATOM69 by the recently discovered Tom36 receptor of Trichomonas hydrogenosomes, while not allowing for growth, restored import of a large subset of trypanosomal proteins that lack TMDs. Thus, even though ATOM69 and Tom36 share the same domain structure and topology, they have different substrate preferences. The study establishes complementation experiments, combined with quantitative proteomics, as a highly versatile and sensitive method to compare in vivo preferences of protein import receptors. Moreover, it illustrates the role determinism and contingencies played in the evolution of mitochondrial protein import receptors.}, } @article {pmid33529628, year = {2021}, author = {Yan, L and Xu, W and Zhang, D and Li, J}, title = {Comparative analysis of the mitochondrial genomes of flesh flies and their evolutionary implication.}, journal = {International journal of biological macromolecules}, volume = {174}, number = {}, pages = {385-391}, doi = {10.1016/j.ijbiomac.2021.01.188}, pmid = {33529628}, issn = {1879-0003}, mesh = {Animals ; Base Composition ; Evolution, Molecular ; Genome Size ; Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics ; Phylogeny ; Sarcophagidae/*classification/genetics ; Whole Genome Sequencing/*methods ; }, abstract = {Flesh flies (Diptera: Sarcophagidae) include a large and widely distributed rapid radiation within the Calyptratae. They are vital for the ecosystem, as well as economic, forensic, and evolutionary studies, because of their extremely diverse habits as larvae. Phylogenetic studies of Sarcophagidae have been reaching convergence, which leads the opportunity to elucidate the evolution of these fast-evolving insects from the perspective of mitochondrial genome. Complete mitochondrial genomes of eight species were sequenced, and comparative mitochondrial genomic analysis between subfamilies were conducted. Mitochondrial genomes of these flesh flies are conserved in gene content with gene arrangement, same as the inferred ancestral insect, and the nucleotide composition is highly biased towards A + T like other flesh flies. The evolutionary rates of Sarcophagidae vary considerably across subfamilies, with that of Miltogramminae higher than the other two subfamilies. Phylogenetic analysis strongly supports monophyly of Sarcophagidae and each subfamily, with subfamily-level relationship inferred as (Sarcophaginae, (Miltogramminae, Paramacronychiinae)). The main topological inconsistency of all reconstructions is the relationship within Miltogramminae and Sarcophaga, which might be caused by their rapid evolution. Our study indicates that the mitochondrial genomes of flesh flies are highly conserved, and they are practically useful for phylogenetic inference of calyptrates.}, } @article {pmid33536648, year = {2021}, author = {Kraus, F and Roy, K and Pucadyil, TJ and Ryan, MT}, title = {Function and regulation of the divisome for mitochondrial fission.}, journal = {Nature}, volume = {590}, number = {7844}, pages = {57-66}, pmid = {33536648}, issn = {1476-4687}, support = {/HHMI/Howard Hughes Medical Institute/United States ; /MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Biological Evolution ; Calcium Signaling ; Cell Death ; Disease ; Dynamins/chemistry/genetics/metabolism ; Health ; Humans ; Mitochondria/*chemistry/*metabolism/pathology ; Mitochondrial Dynamics/*physiology ; }, abstract = {Mitochondria form dynamic networks in the cell that are balanced by the flux of iterative fusion and fission events of the organelles. It is now appreciated that mitochondrial fission also represents an end-point event in a signalling axis that allows cells to sense and respond to external cues. The fission process is orchestrated by membrane-associated adaptors, influenced by organellar and cytoskeletal interactions and ultimately executed by the dynamin-like GTPase DRP1. Here we invoke the framework of the 'mitochondrial divisome', which is conceptually and operationally similar to the bacterial cell-division machinery. We review the functional and regulatory aspects of the mitochondrial divisome and, within this framework, parse the core from the accessory machinery. In so doing, we transition from a phenomenological to a mechanistic understanding of the fission process.}, } @article {pmid33540080, year = {2021}, author = {de Freitas Souza, C and Baldissera, MD and Barroso, D and de Lima, MCM and Baldisserotto, B and Val, AL}, title = {Involvement of purinergic system and electron transport chain in two species of cichlids from the Amazon basin exposed to hypoxia.}, journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology}, volume = {255}, number = {}, pages = {110918}, doi = {10.1016/j.cbpa.2021.110918}, pmid = {33540080}, issn = {1531-4332}, mesh = {Animals ; Cichlids/*metabolism ; Electron Transport ; Fresh Water ; Hydrocortisone/blood ; Hypoxia/*metabolism ; Mitochondria, Liver/metabolism ; Receptors, Purinergic/*metabolism ; South America ; Species Specificity ; }, abstract = {The Amazonian aquatic ecosystem undergoes seasonal variations and daily changes that directly affect the availability of oxygen. During the day the levels of oxygen can reach supersaturation, and at night can drop to zero. In this way, aquatic organisms are exposed daily to physiological challenges regarding the availability of oxygen. The present study revealed significant differences in the physiology and performance of two cichlids: Geophagus proximus (black water cichlid - from Negro River) and Chaetobranchopsis orbicularis (white water cichlid - from Amazon River), exposed to hypoxia. The white water cichlid showed lower value (1.99 ± 0.79 pKa) of critical pressure of oxygen (Pcrit) and a longer time (68.00 ± 14.11 min) for total loss of balance (LOE); however, this species showed 50% mortality during exposure to hypoxia, while the black water cichlid did not show mortality. Both cichlids presented a decrease in O2 consumption rate (OCR) during hypoxia.. In this sense, it was observed that the black water cichlid presented several physiological strategies during hypoxia, such as, a significant increase in plasma cortisol levels, nucleoside triphosphate diphosphohydrolase activity (for adenosine diphosphate (ADP) as a substrate) in the gills, and the activity of adenosine deaminase (ADA) in gills and liver, in addition to a significant increase in the activity of complexes (II-III) in the transporter chain of electrons in both analyzed tissues and succinate dehydrogenase activity of gills' mitochondria. On the other hand, the only physiological change observed in the white water cichlid was a significant reduction in the activity of complexes II-III in gills and liver. Based on our findings, we can hypothesize that the white water cichlid specie has less tolerant to hypoxia when compared to the black water cichlid.}, } @article {pmid33540360, year = {2021}, author = {Supaphon, P and Kerdpiboon, S and Vénien, A and Loison, O and Sicard, J and Rouel, J and Astruc, T}, title = {Structural changes in local Thai beef during sous-vide cooking.}, journal = {Meat science}, volume = {175}, number = {}, pages = {108442}, doi = {10.1016/j.meatsci.2021.108442}, pmid = {33540360}, issn = {1873-4138}, mesh = {Animals ; Cattle ; Cooking/*methods ; Microscopy, Electron, Transmission ; Muscle Fibers, Skeletal/*ultrastructure ; Red Meat/*analysis ; Temperature ; Time Factors ; }, abstract = {Thai beef (Bos indicus) samples were sous-vide-cooked at temperatures of 60°C, 70°C or 80°C for 2 to 36 hrs and prepared for microstructure characterization by light and electron microscopy. Muscle fibers showed a first phase of lateral shrinkage during the first 6 hrs of cooking at 60-70°C and the first 2 hrs at 80°C followed by a second phase of significant alternations of shrinkage and swelling independently of water transfers. Swelling peaked at 12 hrs. Microstructural changes were more variable for samples cooked at 60-70°C than for samples cooked at 80°C that showed a larger cross-sectional myofibrillar mass area (CSA). Hypercontracted fibers were evidenced at all temperature-time combinations and were associated with adjacent wavy fibers and a characteristic structural evolution in the mitochondria. The role of thermal denaturation of proteins and the ultrastructural analogy of hypercontracted fibers with cold-shortened fibers are discussed.}, } @article {pmid33542272, year = {2021}, author = {Sucháčková Bartoňová, A and Konvička, M and Marešová, J and Wiemers, M and Ignatev, N and Wahlberg, N and Schmitt, T and Faltýnek Fric, Z}, title = {Wolbachia affects mitochondrial population structure in two systems of closely related Palaearctic blue butterflies.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {3019}, pmid = {33542272}, issn = {2045-2322}, mesh = {Animals ; Butterflies/*genetics/microbiology/ultrastructure ; DNA, Mitochondrial/genetics ; Mitochondria/genetics/microbiology/*ultrastructure ; *Phylogeny ; Wolbachia/*genetics/pathogenicity ; }, abstract = {The bacterium Wolbachia infects many insect species and spreads by diverse vertical and horizontal means. As co-inherited organisms, these bacteria often cause problems in mitochondrial phylogeny inference. The phylogenetic relationships of many closely related Palaearctic blue butterflies (Lepidoptera: Lycaenidae: Polyommatinae) are ambiguous. We considered the patterns of Wolbachia infection and mitochondrial diversity in two systems: Aricia agestis/Aricia artaxerxes and the Pseudophilotes baton species complex. We sampled butterflies across their distribution ranges and sequenced one butterfly mitochondrial gene and two Wolbachia genes. Both butterfly systems had uninfected and infected populations, and harboured several Wolbachia strains. Wolbachia was highly prevalent in A. artaxerxes and the host's mitochondrial structure was shallow, in contrast to A. agestis. Similar bacterial alleles infected both Aricia species from nearby sites, pointing to a possible horizontal transfer. Mitochondrial history of the P. baton species complex mirrored its Wolbachia infection and not the taxonomical division. Pseudophilotes baton and P. vicrama formed a hybrid zone in Europe. Wolbachia could obscure mitochondrial history, but knowledge on the infection helps us to understand the observed patterns. Testing for Wolbachia should be routine in mitochondrial DNA studies.}, } @article {pmid33545275, year = {2021}, author = {Kimball, RT and Hosner, PA and Braun, EL}, title = {A phylogenomic supermatrix of Galliformes (Landfowl) reveals biased branch lengths.}, journal = {Molecular phylogenetics and evolution}, volume = {158}, number = {}, pages = {107091}, doi = {10.1016/j.ympev.2021.107091}, pmid = {33545275}, issn = {1095-9513}, mesh = {Animals ; Cell Nucleus/genetics ; Databases, Genetic ; Galliformes/*classification/genetics/physiology ; Introns ; Mitochondria/genetics ; Phylogeny ; }, abstract = {Building taxon-rich phylogenies is foundational for macroevolutionary studies. One approach to improve taxon sampling beyond individual studies is to build supermatricies of publicly available data, incorporating taxa sampled across different studies and utilizing different loci. Most existing supermatrix studies have focused on loci commonly sequenced with Sanger technology ("legacy" markers, such as mitochondrial data and small numbers of nuclear loci). However, incorporating phylogenomic studies into supermatrices allows problem nodes to be targeted and resolved with considerable amounts of data, while improving taxon sampling with legacy data. Here we estimate phylogeny from a galliform supermatrix which includes well-known model and agricultural species such as the chicken and turkey. We assembled a supermatrix comprising 4500 ultra-conserved elements (UCEs) collected as part of recent phylogenomic studies in this group and legacy mitochondrial and nuclear (intron and exon) sequences. Our resulting phylogeny included 88% of extant species and recovered well-accepted relationships with strong support. However, branch lengths, which are particularly important in down-stream macroevolutionary studies, appeared vastly skewed. Taxa represented only by rapidly evolving mitochondrial data had high proportions of missing data and exhibited long terminal branches. Conversely, taxa sampled for slowly evolving UCEs with low proportions of missing data exhibited substantially shorter terminal branches. We explored several branch length re-estimation methods with particular attention to terminal branches and conclude that re-estimation using well-sampled mitochondrial sequences may be a pragmatic approach to obtain trees suitable for macroevolutionary analysis.}, } @article {pmid33546419, year = {2021}, author = {Lee, K and Leister, D and Kleine, T}, title = {Arabidopsis Mitochondrial Transcription Termination Factor mTERF2 Promotes Splicing of Group IIB Introns.}, journal = {Cells}, volume = {10}, number = {2}, pages = {}, pmid = {33546419}, issn = {2073-4409}, support = {KL 2362/1-1 to T.K., and TRR175 to D.L. (project C05) and T.K. (project C01), and a Humboldt fellowship to K.L.//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Arabidopsis ; Arabidopsis Proteins/*metabolism ; Basic-Leucine Zipper Transcription Factors/*metabolism ; Chloroplasts/*metabolism ; Gene Expression Regulation, Plant/*genetics ; Humans ; Introns/*genetics ; Mitochondrial Proteins/*metabolism ; }, abstract = {Plastid gene expression (PGE) is essential for chloroplast biogenesis and function and, hence, for plant development. However, many aspects of PGE remain obscure due to the complexity of the process. A hallmark of nuclear-organellar coordination of gene expression is the emergence of nucleus-encoded protein families, including nucleic-acid binding proteins, during the evolution of the green plant lineage. One of these is the mitochondrial transcription termination factor (mTERF) family, the members of which regulate various steps in gene expression in chloroplasts and/or mitochondria. Here, we describe the molecular function of the chloroplast-localized mTERF2 in Arabidopsis thaliana. The complete loss of mTERF2 function results in embryo lethality, whereas directed, microRNA (amiR)-mediated knockdown of MTERF2 is associated with perturbed plant development and reduced chlorophyll content. Moreover, photosynthesis is impaired in amiR-mterf2 plants, as indicated by reduced levels of photosystem subunits, although the levels of the corresponding messenger RNAs are not affected. RNA immunoprecipitation followed by RNA sequencing (RIP-Seq) experiments, combined with whole-genome RNA-Seq, RNA gel-blot, and quantitative RT-PCR analyses, revealed that mTERF2 is required for the splicing of the group IIB introns of ycf3 (intron 1) and rps12.}, } @article {pmid33549602, year = {2021}, author = {Baluška, F and Lyons, S}, title = {Archaeal Origins of Eukaryotic Cell and Nucleus.}, journal = {Bio Systems}, volume = {203}, number = {}, pages = {104375}, doi = {10.1016/j.biosystems.2021.104375}, pmid = {33549602}, issn = {1872-8324}, mesh = {Actin Cytoskeleton ; Archaea/*cytology ; Biological Evolution ; Cell Biology ; *Cell Nucleus ; Cytoskeleton ; Eukaryota/*cytology ; *Mitochondria ; *Plastids ; *Symbiosis ; Trimethoprim, Sulfamethoxazole Drug Combination ; Tubulin ; }, abstract = {Symbiosis is a major evolutionary force, especially at the cellular level. Here we discuss several older and new discoveries suggesting that besides mitochondria and plastids, eukaryotic nuclei also have symbiotic origins. We propose an archaea-archaea scenario for the evolutionary origin of the eukaryotic cells. We suggest that two ancient archaea-like cells, one based on the actin cytoskeleton and another one based on the tubulin-centrin cytoskeleton, merged together to form the first nucleated eukaryotic cell. This archaeal endosymbiotic origin of eukaryotic cells and their nuclei explains several features of eukaryotic cells which are incompatible with the currently preferred autogenous scenarios of eukaryogenesis.}, } @article {pmid33550595, year = {2021}, author = {Cainzos, M and Marchetti, F and Popovich, C and Leonardi, P and Pagnussat, G and Zabaleta, E}, title = {Gamma carbonic anhydrases are subunits of the mitochondrial complex I of diatoms.}, journal = {Molecular microbiology}, volume = {116}, number = {1}, pages = {109-125}, doi = {10.1111/mmi.14694}, pmid = {33550595}, issn = {1365-2958}, mesh = {Amino Acid Sequence ; Carbonic Anhydrases/genetics/*metabolism ; Chloroplasts/genetics/metabolism ; Diatoms/genetics/*metabolism ; Electron Transport Complex I/genetics/*metabolism ; Evolution, Molecular ; Mitochondria/genetics/*metabolism ; Phylogeny ; RNA-Seq ; Rhodophyta/genetics ; Sequence Alignment ; Symbiosis/genetics ; }, abstract = {Diatoms are unicellular organisms containing red algal-derived plastids that probably originated as result of serial endosymbioses between an ancestral heterotrophic organism and a red alga or cryptophyta algae from which has only the chloroplast left. Diatom mitochondria are thus believed to derive from the exosymbiont. Unlike animals and fungi, diatoms seem to contain ancestral respiratory chains. In support of this, genes encoding gamma type carbonic anhydrases (CAs) whose products were shown to be intrinsic complex I subunits in plants, Euglena and Acanthamoeba were found in diatoms, a representative of Stramenopiles. In this work, we experimentally show that mitochondrial complex I in diatoms is a large complex containing gamma type CA subunits, supporting an ancestral origin. By using a bioinformatic approach, a complex I integrated CA domain with heterotrimeric subunit composition is proposed.}, } @article {pmid33554278, year = {2021}, author = {Ohari, Y and Matsuo, K and Yoshida, A and Nonaka, N and Sato, H and Itagaki, T}, title = {Genetic diversity and population structure analyses based on microsatellite DNA of parthenogenetic Fasciola flukes obtained from cattle and sika deer in Japan.}, journal = {Parasitology research}, volume = {120}, number = {4}, pages = {1341-1350}, pmid = {33554278}, issn = {1432-1955}, mesh = {Animals ; Cattle ; Cattle Diseases/epidemiology/*parasitology ; DNA, Helminth/*genetics ; DNA, Mitochondrial/genetics ; DNA, Ribosomal Spacer/genetics ; Deer/*parasitology ; Fasciola/*genetics/physiology ; Fascioliasis/parasitology/*veterinary ; *Genetic Variation ; Haplotypes ; Helminth Proteins/genetics ; Japan/epidemiology ; Microsatellite Repeats ; Mitochondria/enzymology ; NADH Dehydrogenase/genetics ; Parthenogenesis ; Phylogeny ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Sequence Analysis, DNA ; }, abstract = {Understanding the population structure of Fasciola flukes in domestic and wild animals is important for determining the extent of cross-infection between them. Although the parthenogenetic Fasciola flukes in Japan have been shown to comprise five genetic types based on the ribosomal internal transcribed spacer 1 (ITS1) and mitochondrial NADH dehydrogenase subunit 1 (nad1) regions, these genetic regions are not suitable for analyzing their population structure. In the present study, the genetic diversity and population structure of the parthenogenetic Fasciola flukes in Japan were studied using microsatellite DNA, ITS1, and nad1 regions. A total of 144 parthenogenetic Fasciola flukes, obtained from cattle and sika deer in 16 localities, were individually analyzed using PCR-RFLP for ITS1, PCR-direct sequence analysis for nad1, and post-labeling PCR and capillary electrophoresis for microsatellite DNA regions. The flukes showed higher genetic diversity in the microsatellite DNA regions than ITS1 and nad1. The population structures of parthenogenetic Fasciola flukes were unclear, however, it was suggested that the flukes are more diverse populations. We hypothesized that their distribution throughout Japan is closely related to livestock movement dependent on human activity. Moreover, it is considered that cross-infection of the flukes between cattle and sika deer possibly has occurred in the past.}, } @article {pmid33557932, year = {2021}, author = {Pilgrim, J and Siozios, S and Baylis, M and Venter, G and Garros, C and Hurst, GDD}, title = {Cardinium symbiosis as a potential confounder of mtDNA based phylogeographic inference in Culicoides imicola (Diptera: Ceratopogonidae), a vector of veterinary viruses.}, journal = {Parasites & vectors}, volume = {14}, number = {1}, pages = {100}, pmid = {33557932}, issn = {1756-3305}, support = {BB/M011186/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; H2020-MSCA-IF-2014//H2020 Marie Skłodowska-Curie Actions/ ; }, mesh = {Animals ; Bacterial Infections/*transmission ; Bacteroidetes/genetics ; Ceratopogonidae/*genetics/*microbiology ; DNA, Mitochondrial/chemistry/*genetics ; Gene Flow ; Horses ; Insect Vectors/*microbiology ; Mediterranean Region ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; South Africa ; *Symbiosis ; }, abstract = {BACKGROUND: Culicoides imicola (Diptera: Ceratopogonidae) is an important Afrotropical and Palearctic vector of disease, transmitting viruses of animal health and economic significance including African horse sickness and bluetongue viruses. Maternally inherited symbiotic bacteria (endosymbionts) of arthropods can alter the frequency of COI (cytochrome c oxidase subunit I) mitochondrial haplotypes (mitotypes) in a population, masking the true patterns of host movement and gene flow. Thus, this study aimed to assess the mtDNA structure of C. imicola in relation to infection with Candidatus Cardinum hertigii (Bacteroides), a common endosymbiont of Culicoides spp.

METHODS: Using haplotype network analysis, COI Sanger sequences from Cardinium-infected and -uninfected C. imicola individuals were first compared in a population from South Africa. The network was then extended to include mitotypes from a geographic range where Cardinium infection has previously been investigated.

RESULTS: The mitotype network of the South African population demonstrated the presence of two broad mitotype groups. All Cardinium-infected specimens fell into one group (Fisher's exact test, P = 0.00071) demonstrating a linkage disequilibrium between endosymbiont and mitochondria. Furthermore, by extending this haplotype network to include other C. imicola populations from the Mediterranean basin, we revealed mitotype variation between the Eastern and Western Mediterranean basins (EMB and WMB) mirrored Cardinium-infection heterogeneity.

CONCLUSIONS: These observations suggest that the linkage disequilibrium of Cardinium and mitochondria reflects endosymbiont gene flow within the Mediterranean basin but may not assist in elucidating host gene flow. Subsequently, we urge caution on the single usage of the COI marker to determine population structure and movement in C. imicola and instead suggest the complementary utilisation of additional molecular markers.}, } @article {pmid33561119, year = {2021}, author = {De, AK and Sawhney, S and Bhattacharya, D and Sujatha, T and Sunder, J and Ponraj, P and Ravi, SK and Mondal, S and Malakar, D and Kundu, A}, title = {Origin, genetic diversity and evolution of Andaman local duck, a native duck germplasm of an insular region of India.}, journal = {PloS one}, volume = {16}, number = {2}, pages = {e0245138}, pmid = {33561119}, issn = {1932-6203}, mesh = {Animals ; Animals, Domestic/genetics ; Biological Evolution ; DNA, Mitochondrial/analysis/*genetics ; Ducks/*genetics ; Genetic Variation/genetics ; Genetics, Population/methods ; Haplotypes/genetics ; India ; Mitochondria/genetics ; Phylogeny ; Sequence Analysis, DNA/methods ; }, abstract = {Domestic ducks are of paramount importance as a cheap source of protein in rural India. Andaman local duck (ALD) is an indigenous avian genetic resource of Andaman and Nicobar islands (ANI) and is mainly distributed in Middle and Northern parts of these islands. Negligence has brought this breed on the edge of extinction necessitating immediate conservation efforts. Here, we report the genetic diversity, population structure and matrilineal genetic root of ALD. Partial mtDNA D-loop sequences were analyzed in 71 ALD samples and analysis revealed 19 polymorphic sites and 13 haplotypes. Estimated haplotype (Hd ± SD) and nucleotide diversity (π ± SD) were 0.881 ± 0.017 and 0.00897 ± 0.00078 respectively. The high genetic diversity of ALD indicates introgression of genetic material from other local duck breeds. In addition, it can be postulated that ALD bearing high genetic diversity has strong ability to adapt to environmental changes and can withstand impending climate change. Phylogenetic and network analysis indicate that ALD falls under Eurasian clade of mallard and ALD forms three clusters; one cluster is phylogenetically close to Southeast Asian countries, one close to Southern part of mainland India and the third one forms an independent cluster. Therefore, ALD might have migrated either from Southeast Asian countries which enjoy a close cultural bondage with ANI from time immemorial or from Southern part of India. The independent cluster may have evolved locally in these islands and natural selection pressure imposed by environmental conditions might be the driving force for evaluation of these duck haplotypes; which mimics Darwin's theory of natural selection. The results of the study will be beneficial for formulating future breeding programme and conservation strategy towards sustainable development of the duck breed.}, } @article {pmid33565245, year = {2021}, author = {Shiiba, I and Takeda, K and Nagashima, S and Ito, N and Tokuyama, T and Yamashita, SI and Kanki, T and Komatsu, T and Urano, Y and Fujikawa, Y and Inatome, R and Yanagi, S}, title = {MITOL promotes cell survival by degrading Parkin during mitophagy.}, journal = {EMBO reports}, volume = {22}, number = {3}, pages = {e49097}, pmid = {33565245}, issn = {1469-3178}, mesh = {Cell Survival ; HeLa Cells ; Humans ; *Mitophagy ; *Ubiquitin-Protein Ligases/genetics/metabolism ; Ubiquitination ; }, abstract = {Parkin promotes cell survival by removing damaged mitochondria via mitophagy. However, although some studies have suggested that Parkin induces cell death, the regulatory mechanism underlying the dual role of Parkin remains unknown. Herein, we report that mitochondrial ubiquitin ligase (MITOL/MARCH5) regulates Parkin-mediated cell death through the FKBP38-dependent dynamic translocation from the mitochondria to the ER during mitophagy. Mechanistically, MITOL mediates ubiquitination of Parkin at lysine 220 residue, which promotes its proteasomal degradation, and thereby fine-tunes mitophagy by controlling the quantity of Parkin. Deletion of MITOL leads to accumulation of the phosphorylated active form of Parkin in the ER, resulting in FKBP38 degradation and enhanced cell death. Thus, we have shown that MITOL blocks Parkin-induced cell death, at least partially, by protecting FKBP38 from Parkin. Our findings unveil the regulation of the dual function of Parkin and provide a novel perspective on the pathogenesis of PD.}, } @article {pmid33567508, year = {2021}, author = {Mannella, CA}, title = {VDAC-A Primal Perspective.}, journal = {International journal of molecular sciences}, volume = {22}, number = {4}, pages = {}, pmid = {33567508}, issn = {1422-0067}, support = {P41 RR001219/RR/NCRR NIH HHS/United States ; P41RR01219/RR/NCRR NIH HHS/United States ; U01HLI16321/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Ion Channel Gating ; Lipid Bilayers/*metabolism ; *Membrane Potentials ; Mitochondria/*physiology ; Voltage-Dependent Anion Channels/*metabolism ; }, abstract = {The evolution of the eukaryotic cell from the primal endosymbiotic event involved a complex series of adaptations driven primarily by energy optimization. Transfer of genes from endosymbiont to host and concomitant expansion (by infolding) of the endosymbiont's chemiosmotic membrane greatly increased output of adenosine triphosphate (ATP) and placed selective pressure on the membrane at the host-endosymbiont interface to sustain the energy advantage. It is hypothesized that critical functions at this interface (metabolite exchange, polypeptide import, barrier integrity to proteins and DNA) were managed by a precursor β-barrel protein ("pβB") from which the voltage-dependent anion-selective channel (VDAC) descended. VDAC's role as hub for disparate and increasingly complex processes suggests an adaptability that likely springs from a feature inherited from pβB, retained because of important advantages conferred. It is proposed that this property is the remarkable structural flexibility evidenced in VDAC's gating mechanism, a possible origin of which is discussed.}, } @article {pmid33569374, year = {2020}, author = {Xu, D and Qian, J and Guan, X and Ren, L and Yang, K and Huang, X and Zhang, S and Chai, Y and Wu, X and Wu, H and Zhang, X and Yang, K and Yu, B}, title = {Copper-Containing Alloy as Immunoregulatory Material in Bone Regeneration via Mitochondrial Oxidative Stress.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {8}, number = {}, pages = {620629}, pmid = {33569374}, issn = {2296-4185}, abstract = {In the mammalian skeletal system, osteogenesis and angiogenesis are closely linked by type H vessels during bone regeneration and repair. Our previous studies confirmed the promotion of these processes by copper-containing metal (CCM) in vitro and in vivo. However, whether and how the coupling of angiogenesis and osteogenesis participates in the promotion of bone regeneration by CCM in vivo is unknown. In this study, M2a macrophages but not M2c macrophages were shown to be immunoregulated by CCM. A CCM, 316L-5Cu, was applied to drilling hole injuries of the tibia of C57/6 mice for comparison. We observed advanced formation of cortical bone and type H vessels beneath the new bone in the 316L-5Cu group 14 and 21 days postinjury. Moreover, the recruitment of CD206-positive M2a macrophages, which are regarded as the primary source of platelet-derived growth factor type BB (PDGF-BB), was significantly promoted at the injury site at days 14 and 21. Under the stimulation of CCM, mitochondria-derived reactive oxygen species were also found to be upregulated in CD206[hi] M2a macrophages in vitro, and this upregulation was correlated with the expression of PDGF-BB. In conclusion, our results indicate that CCM promotes the evolution of callus through the generation of type H vessels during the process of bone repair by upregulating the expression of PDGF-BB derived from M2a macrophages.}, } @article {pmid33581918, year = {2021}, author = {Zheng, X and Gao, X and Wang, J and Du, C and Hou, C and Xie, Q and Lou, B and Liu, F and Zhu, J}, title = {KIFC1 functions in nuclear reshaping and midpiece formation during the spermatogenesis of small yellow croaker Larimichthys polyactis.}, journal = {Animal reproduction science}, volume = {226}, number = {}, pages = {106702}, doi = {10.1016/j.anireprosci.2021.106702}, pmid = {33581918}, issn = {1873-2232}, mesh = {Amino Acid Sequence ; Animals ; Cell Nucleus/physiology ; Cloning, Molecular ; DNA, Complementary/genetics ; Fishes/genetics/*physiology ; Gene Expression Regulation/physiology ; Kinesins/genetics/*metabolism ; Male ; Microtubules/physiology ; Mitochondria/physiology ; Phylogeny ; Protein Conformation ; Protein Transport ; RNA, Messenger/genetics/metabolism ; Spermatogenesis/*physiology ; Spermatozoa/*cytology/*physiology ; Testis/*physiology ; Tubulin/genetics/metabolism ; }, abstract = {The C-terminal kinesin motor protein (KIFC1) has essential functions in spermatogenesis. To evaluate molecular mechanisms of KIFC1 during teleost fish spermatogenesis, there was cloning and sequencing the kifc1 cDNA in the testis of Larimichthys polyactis. Quantitative PCR results indicated there were Lp-kifc1 mRNA transcripts in the testes. Results from conducting fluorescence in situ hybridization and immunofluorescence procedures indicated there were trends in relative abundance changes in Lp-kifc1 mRNA transcripts that were associated with abundance of Lp-KIFC1 protein during spermatogenesis. The Lp-KIFC1 protein was detected at all stages of spermatogenesis. There was minimal Lp-KIFC1 in the cytoplasm of spermatogonia, with content being greater and concentrated in the perinuclear region in spermatocytes and during early/mid-stages of development of spermatids. There were large abundances of Lp-KIFC1 in spermatids at the mid-developmental stage. In late-developing spermatids, Lp-KIFC1 content was less and concentrated in the bottom of the nucleus, where the midpiece formed. There was a small Lp-KIFC1 in the midpiece of mature sperm. These findings indicate Lp-KIFC1 may have functions in L. polyactis spermatogenesis. Results from conducting immunofluorescence procedures indicated Lp-KIFC1 was co-localized microtubules and mitochondria throughout spermatogenesis. There were large abundances of Lp-KIFC1 and tubulin in spermatids during the mid-developmental stage, when there is a decrease in size and reshaping of the nucleus. During midpiece formation, there was co-localization of the Lp-KIFC1 and mitochondria in the spermatid perinuclear region to the midpiece. These findings indicate Lp-KIFC1 is involved in nuclear reshaping and midpiece formation during spermatogenesis in L. polyactis.}, } @article {pmid33591272, year = {2021}, author = {Zhu, X and Boulet, A and Buckley, KM and Phillips, CB and Gammon, MG and Oldfather, LE and Moore, SA and Leary, SC and Cobine, PA}, title = {Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33591272}, issn = {2050-084X}, support = {R01 GM120211/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Cell Line ; Copper Transport Proteins/genetics/metabolism ; Eukaryota ; Mice ; Mitochondria ; Mitochondrial Proteins/*genetics/metabolism ; Mutagenesis, Site-Directed ; Phosphate Transport Proteins/genetics/metabolism ; Phylogeny ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/*genetics/metabolism ; }, abstract = {The mitochondrial carrier family protein SLC25A3 transports both copper and phosphate in mammals, yet in Saccharomyces cerevisiae the transport of these substrates is partitioned across two paralogs: PIC2 and MIR1. To understand the ancestral state of copper and phosphate transport in mitochondria, we explored the evolutionary relationships of PIC2 and MIR1 orthologs across the eukaryotic tree of life. Phylogenetic analyses revealed that PIC2-like and MIR1-like orthologs are present in all major eukaryotic supergroups, indicating an ancient gene duplication created these paralogs. To link this phylogenetic signal to protein function, we used structural modeling and site-directed mutagenesis to identify residues involved in copper and phosphate transport. Based on these analyses, we generated an L175A variant of mouse SLC25A3 that retains the ability to transport copper but not phosphate. This work highlights the utility of using an evolutionary framework to uncover amino acids involved in substrate recognition by mitochondrial carrier family proteins.}, } @article {pmid33594064, year = {2021}, author = {Uwizeye, C and Decelle, J and Jouneau, PH and Flori, S and Gallet, B and Keck, JB and Bo, DD and Moriscot, C and Seydoux, C and Chevalier, F and Schieber, NL and Templin, R and Allorent, G and Courtois, F and Curien, G and Schwab, Y and Schoehn, G and Zeeman, SC and Falconet, D and Finazzi, G}, title = {Morphological bases of phytoplankton energy management and physiological responses unveiled by 3D subcellular imaging.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {1049}, pmid = {33594064}, issn = {2041-1723}, mesh = {Acclimatization/radiation effects ; *Energy Metabolism/radiation effects ; *Imaging, Three-Dimensional ; Light ; Microalgae/metabolism/radiation effects/ultrastructure ; Mitochondria/metabolism/radiation effects/ultrastructure ; Phytoplankton/*cytology/*physiology/radiation effects/ultrastructure ; Plastids/metabolism ; Subcellular Fractions/metabolism ; }, abstract = {Eukaryotic phytoplankton have a small global biomass but play major roles in primary production and climate. Despite improved understanding of phytoplankton diversity and evolution, we largely ignore the cellular bases of their environmental plasticity. By comparative 3D morphometric analysis across seven distant phytoplankton taxa, we observe constant volume occupancy by the main organelles and preserved volumetric ratios between plastids and mitochondria. We hypothesise that phytoplankton subcellular topology is modulated by energy-management constraints. Consistent with this, shifting the diatom Phaeodactylum from low to high light enhances photosynthesis and respiration, increases cell-volume occupancy by mitochondria and the plastid CO2-fixing pyrenoid, and boosts plastid-mitochondria contacts. Changes in organelle architectures and interactions also accompany Nannochloropsis acclimation to different trophic lifestyles, along with respiratory and photosynthetic responses. By revealing evolutionarily-conserved topologies of energy-managing organelles, and their role in phytoplankton acclimation, this work deciphers phytoplankton responses at subcellular scales.}, } @article {pmid33606008, year = {2021}, author = {Omarjee, O and Mathieu, AL and Quiniou, G and Moreews, M and Ainouze, M and Frachette, C and Melki, I and Dumaine, C and Gerfaud-Valentin, M and Duquesne, A and Kallinich, T and Tahir Turanli, E and Malcus, C and Viel, S and Pescarmona, R and Georgin-Lavialle, S and Jamilloux, Y and Larbre, JP and Sarrabay, G and Magnotti, F and Rice, GI and Bleicher, F and Reboulet, J and Merabet, S and Henry, T and Crow, YJ and Faure, M and Walzer, T and Belot, A}, title = {LACC1 deficiency links juvenile arthritis with autophagy and metabolism in macrophages.}, journal = {The Journal of experimental medicine}, volume = {218}, number = {3}, pages = {}, pmid = {33606008}, issn = {1540-9538}, mesh = {Adenylate Kinase/metabolism ; Adolescent ; Amino Acid Sequence ; Apoptosis/drug effects ; Arthritis, Juvenile/genetics/*metabolism/*pathology ; *Autophagy/drug effects/genetics ; Autophagy-Related Proteins/metabolism ; Bacteria/metabolism ; Cell Differentiation/drug effects ; Child ; Exome/genetics ; Female ; Homozygote ; Humans ; Inflammasomes/metabolism ; Inflammation/complications/pathology ; Interferons/metabolism ; Intracellular Signaling Peptides and Proteins/chemistry/*deficiency/genetics ; Lipid Droplets/drug effects/metabolism ; Loss of Function Mutation/genetics ; Lysosomes/drug effects/metabolism ; Macrophage Colony-Stimulating Factor/pharmacology ; Macrophages/drug effects/*metabolism ; Male ; Mitochondria/drug effects/metabolism ; Monocytes/drug effects/pathology ; NF-kappa B/metabolism ; Pedigree ; Proteomics ; Receptors for Activated C Kinase/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; Young Adult ; }, abstract = {Juvenile idiopathic arthritis is the most common chronic rheumatic disease in children, and its etiology remains poorly understood. Here, we explored four families with early-onset arthritis carrying homozygous loss-of-expression mutations in LACC1. To understand the link between LACC1 and inflammation, we performed a functional study of LACC1 in human immune cells. We showed that LACC1 was primarily expressed in macrophages upon mTOR signaling. We found that LACC1 deficiency had no obvious impact on inflammasome activation, type I interferon response, or NF-κB regulation. Using bimolecular fluorescence complementation and biochemical assays, we showed that autophagy-inducing proteins, RACK1 and AMPK, interacted with LACC1. Autophagy blockade in macrophages was associated with LACC1 cleavage and degradation. Moreover, LACC1 deficiency reduced autophagy flux in primary macrophages. This was associated with a defect in the accumulation of lipid droplets and mitochondrial respiration, suggesting that LACC1-dependent autophagy fuels macrophage bioenergetics metabolism. Altogether, LACC1 deficiency defines a novel form of genetically inherited juvenile arthritis associated with impaired autophagy in macrophages.}, } @article {pmid33612083, year = {2022}, author = {Ma, ZJ and Li, GZ and Chen, SM and Han, JL and Hanif, Q}, title = {Rich maternal and paternal genetic diversity and divergent lineage composition in wild yak (Bos mutus).}, journal = {Animal biotechnology}, volume = {33}, number = {6}, pages = {1382-1386}, doi = {10.1080/10495398.2021.1884567}, pmid = {33612083}, issn = {1532-2378}, mesh = {Cattle/genetics ; Animals ; Phylogeny ; Haplotypes/genetics ; *DNA, Mitochondrial/genetics ; *Mitochondria/genetics ; Genetic Variation/genetics ; }, abstract = {Wild yak (Bos mutus) is a vulnerable bovine species on the Qinghai-Tibetan Plateau (QTP). So far, most studies on molecular genetic diversity of wild yak have focused on autosomal and mtDNA variations based on small number of samples. In this study, we analyzed 84 D-loop and 24 whole mitogenome sequences of wild yak to further comprehensively explore its maternal genetic diversity and lineage composition. Meanwhile, using six yak Y-specific polymorphic markers (i.e., SRY4, USP9Y, UTY19, AMELY3, OFD1Y10 and INRA189), we assessed the paternal genetic diversity and lineage composition based on eight wild yak. Our results showed that wild yak exhibited abundant maternal genetic diversity with haplotype diversities of 0.9621 ± 0.0078 and 0.9928 ± 0.0144 in the D-loop and whole mitogenome sequences, respectively. Maternal phylogenetic analysis of wild yak uncovered three defined lineages (mt-I, mt-II and mt-III). Similarly, profuse paternal genetic diversity was observed in wild yak with Y-haplotype diversity (Hd) at 0.8214 ± 0.1007. Two Y-haplogroups (Y1 and Y2) with four Y-haplotypes (yH1-yH4) were identified in paternal phylogenetic analysis, indicating wild yak to be of two paternal lineages. This study of genetic diversity and lineage composition of wild yak would provide useful information for the genetic resource conservation and utilization of this vulnerable wild species.}, } @article {pmid33616531, year = {2021}, author = {Zarin, T and Strome, B and Peng, G and Pritišanac, I and Forman-Kay, JD and Moses, AM}, title = {Identifying molecular features that are associated with biological function of intrinsically disordered protein regions.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33616531}, issn = {2050-084X}, support = {PJT-148532//CIHR/Canada ; FDN-148375//CIHR/Canada ; }, mesh = {Amino Acid Sequence ; Hydrophobic and Hydrophilic Interactions ; Intrinsically Disordered Proteins/chemistry/*metabolism ; Isoelectric Point ; Mitochondria/metabolism ; Models, Statistical ; Proteome/chemistry/*metabolism ; Saccharomyces cerevisiae/metabolism ; }, abstract = {In previous work, we showed that intrinsically disordered regions (IDRs) of proteins contain sequence-distributed molecular features that are conserved over evolution, despite little sequence similarity that can be detected in alignments (Zarin et al., 2019). Here, we aim to use these molecular features to predict specific biological functions for individual IDRs and identify the molecular features within them that are associated with these functions. We find that the predictable functions are diverse. Examining the associated molecular features, we note some that are consistent with previous reports and identify others that were previously unknown. We experimentally confirm that elevated isoelectric point and hydrophobicity, features that are positively associated with mitochondrial localization, are necessary for mitochondrial targeting function. Remarkably, increasing isoelectric point in a synthetic IDR restores weak mitochondrial targeting. We believe feature analysis represents a new systematic approach to understand how biological functions of IDRs are specified by their protein sequences.}, } @article {pmid33616640, year = {2021}, author = {Piccinini, G and Iannello, M and Puccio, G and Plazzi, F and Havird, JC and Ghiselli, F}, title = {Mitonuclear Coevolution, but not Nuclear Compensation, Drives Evolution of OXPHOS Complexes in Bivalves.}, journal = {Molecular biology and evolution}, volume = {38}, number = {6}, pages = {2597-2614}, pmid = {33616640}, issn = {1537-1719}, mesh = {Animals ; *Biological Evolution ; Bivalvia/*genetics ; *Genome, Mitochondrial ; *Oxidative Phosphorylation ; }, abstract = {In Metazoa, four out of five complexes involved in oxidative phosphorylation (OXPHOS) are formed by subunits encoded by both the mitochondrial (mtDNA) and nuclear (nuDNA) genomes, leading to the expectation of mitonuclear coevolution. Previous studies have supported coadaptation of mitochondria-encoded (mtOXPHOS) and nuclear-encoded OXPHOS (nuOXPHOS) subunits, often specifically interpreted with regard to the "nuclear compensation hypothesis," a specific form of mitonuclear coevolution where nuclear genes compensate for deleterious mitochondrial mutations due to less efficient mitochondrial selection. In this study, we analyzed patterns of sequence evolution of 79 OXPHOS subunits in 31 bivalve species, a taxon showing extraordinary mtDNA variability and including species with "doubly uniparental" mtDNA inheritance. Our data showed strong and clear signals of mitonuclear coevolution. NuOXPHOS subunits had concordant topologies with mtOXPHOS subunits, contrary to previous phylogenies based on nuclear genes lacking mt interactions. Evolutionary rates between mt and nuOXPHOS subunits were also highly correlated compared with non-OXPHO-interacting nuclear genes. Nuclear subunits of chimeric OXPHOS complexes (I, III, IV, and V) also had higher dN/dS ratios than Complex II, which is formed exclusively by nuDNA-encoded subunits. However, we did not find evidence of nuclear compensation: mitochondria-encoded subunits showed similar dN/dS ratios compared with nuclear-encoded subunits, contrary to most previously studied bilaterian animals. Moreover, no site-specific signals of compensatory positive selection were detected in nuOXPHOS genes. Our analyses extend the evidence for mitonuclear coevolution to a new taxonomic group, but we propose a reconsideration of the nuclear compensation hypothesis.}, } @article {pmid33618020, year = {2021}, author = {Shinde, P and Whitwell, HJ and Verma, RK and Ivanchenko, M and Zaikin, A and Jalan, S}, title = {Impact of modular mitochondrial epistatic interactions on the evolution of human subpopulations.}, journal = {Mitochondrion}, volume = {58}, number = {}, pages = {111-122}, doi = {10.1016/j.mito.2021.02.004}, pmid = {33618020}, issn = {1872-8278}, support = {MR/R02524X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Epistasis, Genetic ; *Evolution, Molecular ; *Genes, Mitochondrial ; Humans ; Mutation ; Population Groups/*genetics ; }, abstract = {Investigation of human mitochondrial (mt) genome variation has been shown to provide insights to the human history and natural selection. By analyzing 24,167 human mt-genome samples, collected for five continents, we have developed a co-mutation network model to investigate characteristic human evolutionary patterns. The analysis highlighted richer co-mutating regions of the mt-genome, suggesting the presence of epistasis. Specifically, a large portion of COX genes was found to co-mutate in Asian and American populations, whereas, in African, European, and Oceanic populations, there was greater co-mutation bias in hypervariable regions. Interestingly, this study demonstrated hierarchical modularity as a crucial agent for these co-mutation networks. More profoundly, our ancestry-based co-mutation module analyses showed that mutations cluster preferentially in known mitochondrial haplogroups. Contemporary human mt-genome nucleotides most closely resembled the ancestral state, and very few of them were found to be ancestral-variants. Overall, these results demonstrated that subpopulation-based biases may favor mitochondrial gene specific epistasis.}, } @article {pmid33631347, year = {2021}, author = {Kutyumov, VA and Predeus, AV and Starunov, VV and Maltseva, AL and Ostrovsky, AN}, title = {Mitochondrial gene order of the freshwater bryozoan Cristatella mucedo retains ancestral lophotrochozoan features.}, journal = {Mitochondrion}, volume = {59}, number = {}, pages = {96-104}, doi = {10.1016/j.mito.2021.02.003}, pmid = {33631347}, issn = {1872-8278}, mesh = {Animals ; Bryozoa/anatomy & histology/*classification/genetics ; Evolution, Molecular ; Gene Order ; Genome Size ; Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA/*methods ; }, abstract = {Bryozoans are aquatic colonial suspension-feeders abundant in many marine and freshwater benthic communities. At the same time, the phylum is under studied on both morphological and molecular levels, and its position on the metazoan tree of life is still disputed. Bryozoa include the exclusively marine Stenolaemata, predominantly marine Gymnolaemata and exclusively freshwater Phylactolaemata. Here we report the mitochondrial genome of the phylactolaemate bryozoan Cristatella mucedo. This species has the largest (21,008 bp) of all currently known bryozoan mitogenomes, containing a typical metazoan gene compendium as well as a number of non-coding regions, three of which are longer than 1500 bp. The trnS1/trnG/nad3 region is presumably duplicated in this species. Comparative analysis of the gene order in C. mucedo and another phylactolaemate bryozoan, Pectinatella magnifica, confirmed their close relationships, and revealed a stronger similarity to mitogenomes of phoronids and other lophotrochozoan species than to marine bryozoans, indicating the ancestral nature of their gene arrangement. We suggest that the ancestral gene order underwent substantial changes in different bryozoan cladesshowing mosaic distribution of conservative gene blocks regardless of their phylogenetic position. Altogether, our results support the early divergence of Phylactolaemata from the rest of Bryozoa.}, } @article {pmid33643304, year = {2020}, author = {Kumar, V}, title = {The Trinity of cGAS, TLR9, and ALRs Guardians of the Cellular Galaxy Against Host-Derived Self-DNA.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {624597}, pmid = {33643304}, issn = {1664-3224}, mesh = {Autoimmune Diseases/immunology/pathology ; DNA/*immunology ; DNA-Binding Proteins/*immunology ; Humans ; *Immunity, Innate ; Inflammation/immunology/pathology ; Nucleotidyltransferases/*immunology ; Toll-Like Receptor 9/*immunology ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; }, abstract = {The immune system has evolved to protect the host from the pathogens and allergens surrounding their environment. The immune system develops in such a way to recognize self and non-self and develops self-tolerance against self-proteins, nucleic acids, and other larger molecules. However, the broken immunological self-tolerance leads to the development of autoimmune or autoinflammatory diseases. Pattern-recognition receptors (PRRs) are expressed by immunological cells on their cell membrane and in the cytosol. Different Toll-like receptors (TLRs), Nod-like receptors (NLRs) and absent in melanoma-2 (AIM-2)-like receptors (ALRs) forming inflammasomes in the cytosol, RIG (retinoic acid-inducible gene)-1-like receptors (RLRs), and C-type lectin receptors (CLRs) are some of the PRRs. The DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) is another PRR present in the cytosol and the nucleus. The present review describes the role of ALRs (AIM2), TLR9, and cGAS in recognizing the host cell DNA as a potent damage/danger-associated molecular pattern (DAMP), which moves out to the cytosol from its housing organelles (nucleus and mitochondria). The introduction opens with the concept that the immune system has evolved to recognize pathogens, the idea of horror autotoxicus, and its failure due to the emergence of autoimmune diseases (ADs), and the discovery of PRRs revolutionizing immunology. The second section describes the cGAS-STING signaling pathway mediated cytosolic self-DNA recognition, its evolution, characteristics of self-DNAs activating it, and its role in different inflammatory conditions. The third section describes the role of TLR9 in recognizing self-DNA in the endolysosomes during infections depending on the self-DNA characteristics and various inflammatory diseases. The fourth section discusses about AIM2 (an ALR), which also binds cytosolic self-DNA (with 80-300 base pairs or bp) that inhibits cGAS-STING-dependent type 1 IFN generation but induces inflammation and pyroptosis during different inflammatory conditions. Hence, this trinity of PRRs has evolved to recognize self-DNA as a potential DAMP and comes into action to guard the cellular galaxy. However, their dysregulation proves dangerous to the host and leads to several inflammatory conditions, including sterile-inflammatory conditions autoinflammatory and ADs.}, } @article {pmid33644926, year = {2021}, author = {Radzvilavicius, A and Layh, S and Hall, MD and Dowling, DK and Johnston, IG}, title = {Sexually antagonistic evolution of mitochondrial and nuclear linkage.}, journal = {Journal of evolutionary biology}, volume = {34}, number = {5}, pages = {757-766}, doi = {10.1111/jeb.13776}, pmid = {33644926}, issn = {1420-9101}, mesh = {Animals ; *Biological Evolution ; Female ; *Genetic Linkage ; *Genome, Mitochondrial ; Male ; *Models, Genetic ; Mutation ; Recombination, Genetic ; Selection, Genetic ; *Sex Characteristics ; }, abstract = {Across eukaryotes, genes encoding bioenergetic machinery are located in both mitochondrial and nuclear DNA, and incompatibilities between the two genomes can be devastating. Mitochondria are often inherited maternally, and theory predicts sex-specific fitness effects of mitochondrial mutational diversity. Yet how evolution acts on linkage patterns between mitochondrial and nuclear genomes is poorly understood. Using novel mito-nuclear population-genetic models, we show that the interplay between nuclear and mitochondrial genes maintains mitochondrial haplotype diversity within populations, and selects both for sex-independent segregation of mitochondrion-interacting genes and for paternal leakage. These effects of genetic linkage evolution can eliminate male-harming fitness effects of mtDNA mutational diversity. With maternal mitochondrial inheritance, females maintain a tight mitochondrial-nuclear match, but males accumulate mismatch mutations because of the weak statistical associations between the two genomic components. Sex-independent segregation of mitochondria-interacting loci improves the mito-nuclear match. In a sexually antagonistic evolutionary process, male nuclear alleles evolve to increase the rate of recombination, whereas females evolve to suppress it. Paternal leakage of mitochondria can evolve as an alternative mechanism to improve the mito-nuclear linkage. Our modelling framework provides an evolutionary explanation for the observed paucity of mitochondrion-interacting genes on mammalian sex chromosomes and for paternal leakage in protists, plants, fungi and some animals.}, } @article {pmid33648457, year = {2021}, author = {Bizouerne, E and Buitink, J and Vu, BL and Vu, JL and Esteban, E and Pasha, A and Provart, N and Verdier, J and Leprince, O}, title = {Gene co-expression analysis of tomato seed maturation reveals tissue-specific regulatory networks and hubs associated with the acquisition of desiccation tolerance and seed vigour.}, journal = {BMC plant biology}, volume = {21}, number = {1}, pages = {124}, pmid = {33648457}, issn = {1471-2229}, support = {RFI Objectif Végétal//Conseil Régional des Pays de la Loire/ ; }, mesh = {Acclimatization/genetics ; Droughts ; Endosperm/genetics/growth & development ; *Gene Expression Regulation, Plant ; *Gene Regulatory Networks ; Genetic Association Studies ; Solanum lycopersicum/embryology/*genetics/growth & development ; Seeds/*genetics/growth & development ; Transcriptome ; }, abstract = {BACKGROUND: During maturation seeds acquire several physiological traits to enable them to survive drying and disseminate the species. Few studies have addressed the regulatory networks controlling acquisition of these traits at the tissue level particularly in endospermic seeds such as tomato, which matures in a fully hydrated environment and does not undergo maturation drying. Using temporal RNA-seq analyses of the different seed tissues during maturation, gene network and trait-based correlations were used to explore the transcriptome signatures associated with desiccation tolerance, longevity, germination under water stress and dormancy.

RESULTS: During maturation, 15,173 differentially expressed genes were detected, forming a gene network representing 21 expression modules, with 3 being specific to seed coat and embryo and 5 to the endosperm. A gene-trait significance measure identified a common gene module between endosperm and embryo associated with desiccation tolerance and conserved with non-endospermic seeds. In addition to genes involved in protection such LEA and HSP and ABA response, the module included antioxidant and repair genes. Dormancy was released concomitantly with the increase in longevity throughout fruit ripening until 14 days after the red fruit stage. This was paralleled by an increase in SlDOG1-2 and PROCERA transcripts. The progressive increase in seed vigour was captured by three gene modules, one in common between embryo and endosperm and two tissue-specific. The common module was enriched with genes associated with mRNA processing in chloroplast and mitochondria (including penta- and tetratricopeptide repeat-containing proteins) and post-transcriptional regulation, as well several flowering genes. The embryo-specific module contained homologues of ABI4 and CHOTTO1 as hub genes associated with seed vigour, whereas the endosperm-specific module revealed a diverse set of processes that were related to genome stability, defence against pathogens and ABA/GA response genes.

CONCLUSION: The spatio-temporal co-expression atlas of tomato seed maturation will serve as a valuable resource for the in-depth understanding of the dynamics of gene expression associated with the acquisition of seed vigour at the tissue level.}, } @article {pmid33649061, year = {2021}, author = {Fajardo, RG and Fariña, FO and Rey, AM and Rego-Pérez, I and Blanco, FJ and García, JLF}, title = {Relationship Between the Dynamics of Telomere Loss in Peripheral Blood Leukocytes From Knee Osteoarthritis Patients and Mitochondrial DNA Haplogroups.}, journal = {The Journal of rheumatology}, volume = {48}, number = {10}, pages = {1603-1607}, doi = {10.3899/jrheum.201316}, pmid = {33649061}, issn = {1499-2752}, mesh = {DNA, Mitochondrial/genetics ; Haplotypes ; Humans ; Leukocytes ; Mitochondria ; *Osteoarthritis, Knee/diagnostic imaging/genetics ; Telomere/genetics ; }, abstract = {OBJECTIVE: To evaluate the evolution of telomere length from peripheral blood leukocytes (PBLs) in subjects from the Osteoarthritis Initiative (OAI) cohort in relation to the incidence of osteoarthritis (OA), and to explore its possible interactive influence with the mitochondrial DNA (mtDNA) haplogroup.

METHODS: Dynamics of telomere sequence loss were quantified in PBLs from initially healthy individuals (without symptoms or radiological signs), 78 carrying the mtDNA cluster HV, and 47 with cluster JT, from the OAI, during a 72-month follow-up period. The incidence of knee OA during this period (n = 39) was radiographically established when Kellgren-Lawrence (KL) score increased from < 2 at recruitment, to ≥ 2 at the end of 72 months of follow-up. Multivariate analysis using binary logistic regression was performed to assess PBL telomere loss and mtDNA haplogroups as associated risk factors of incidence of knee OA.

RESULTS: Carriers of cluster HV showed knee OA incidence twice that of the JT carriers (n = 30 vs 9). The rate of PBL telomere loss was higher in cluster HV carriers and in individuals with incident knee OA. Multivariate analysis showed that the dynamics of PBL telomere shortening can be a consistent risk marker of knee OA incidence. Subjects with nonincident knee OA showed a slower telomere loss than those with incident knee OA; the difference was more significant in carriers of cluster JT than in HV.

CONCLUSION: An increased rate of telomere loss in PBLs may reflect a systemic accelerated senescence phenotype that could be potentiated by the mitochondrial function, increasing the susceptibility of developing knee OA.}, } @article {pmid33652602, year = {2021}, author = {Prieto, C and Montecinos, J and Jiménez, G and Riquelme, C and Garrido, D and Hernández, S and Loyola, A and Villanueva, RA}, title = {Phosphorylation of Phylogenetically Conserved Amino Acid Residues Confines HBx within Different Cell Compartments of Human Hepatocarcinoma Cells.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {5}, pages = {}, pmid = {33652602}, issn = {1420-3049}, mesh = {Amino Acid Sequence/genetics ; Carcinoma, Hepatocellular/*genetics/pathology/virology ; Conserved Sequence/genetics ; Gene Expression Regulation, Viral/genetics ; Genome, Viral/genetics ; Hep G2 Cells ; Hepatitis B/*genetics/pathology/virology ; Hepatitis B virus/genetics/pathogenicity ; Humans ; Liver Neoplasms/*genetics/pathology/virology ; Phosphorylation/genetics ; Phylogeny ; Trans-Activators/*genetics ; Viral Regulatory and Accessory Proteins/*genetics ; }, abstract = {Hepatitis B virus (HBV) is a circular, and partially double-stranded DNA virus. Upon infection, the viral genome is translocated into the cell nucleus, generating the covalently closed circular DNA (cccDNA) intermediate, and forming a mini chromosome. HBV HBx is a small protein displaying multiple roles in HBV-infected cells, and in different subcellular locations. In the nucleus, the HBx protein is required to initiate and maintain viral transcription from the viral mini chromosome. In contrast, HBx also functions in the cytoplasm, where it is able to alter multiple cellular functions such as mitochondria metabolism, apoptosis and signal transduction pathways. It has been reported that in cultured cells, at low expression levels, the HBx protein is localized in the nucleus, whereas at high expression levels, it accumulates in the cytoplasm. This dynamic subcellular distribution of HBx might be essential to exert its multiple roles during viral infection. However, the mechanism that regulates different subcellular localizations of the HBx protein is unknown. We have previously taken a bioinformatics approach to investigate whether HBx might be regulated via post-translational modification, and we have proposed that the multiple nucleocytoplasmic functions of HBx might be regulated by an evolutionarily conserved mechanism via phosphorylation. In the current study, phylogenetically conserved amino acids of HBx with a high potential of phosphorylation were targeted for site-directed mutagenesis. Two conserved serine (Ser25 and Ser41), and one conserved threonine (Thr81) amino acids were replaced by either alanine or aspartic acid residues to simulate an unphosphorylated or phosphorylated state, respectively. Human hepatoma cells were transfected with increasing amounts of the HBx DNA constructs, and the cells were analyzed by fluorescence microscopy. Together, our results show that the nucleocytoplasmic distribution of the HBx protein could be regulated by phosphorylation since some of the modified proteins were mainly confined to distinct subcellular compartments. Remarkably, both HBx Ser41A, and HBx Thr81D proteins were predominantly localized within the nuclear compartment throughout the different expression levels of HBx mutants.}, } @article {pmid33658608, year = {2021}, author = {Cabrera, VM}, title = {Human molecular evolutionary rate, time dependency and transient polymorphism effects viewed through ancient and modern mitochondrial DNA genomes.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {5036}, pmid = {33658608}, issn = {2045-2322}, mesh = {DNA, Ancient/analysis ; DNA, Mitochondrial/*genetics/history ; *Evolution, Molecular ; Genetics, Population/*history ; *Genome, Mitochondrial ; Haplotypes ; History, 21st Century ; History, Ancient ; Humans ; Mitochondria/genetics ; *Mutation Rate ; Population Density ; Time Factors ; }, abstract = {Human evolutionary genetics gives a chronological framework to interpret the human history. It is based on the molecular clock hypothesis that suppose a straightforward relationship between the mutation rate and the substitution rate with independence of other factors as demography dynamics. Analyzing ancient and modern human complete mitochondrial genomes we show here that, along the time, the substitution rate can be significantly slower or faster than the average germline mutation rate confirming a time dependence effect mainly attributable to changes in the effective population size of the human populations, with an exponential growth in recent times. We also detect that transient polymorphisms play a slowdown role in the evolutionary rate deduced from haplogroup intraspecific trees. Finally, we propose the use of the most divergent lineages within haplogroups as a practical approach to correct these molecular clock mismatches.}, } @article {pmid33658670, year = {2021}, author = {Lewis, WH and Ettema, TJG}, title = {A microbial marriage reminiscent of mitochondrial evolution.}, journal = {Nature}, volume = {591}, number = {7850}, pages = {375-376}, pmid = {33658670}, issn = {1476-4687}, mesh = {*Biological Evolution ; *Marriage ; Mitochondria/genetics ; }, } @article {pmid33658719, year = {2021}, author = {Graf, JS and Schorn, S and Kitzinger, K and Ahmerkamp, S and Woehle, C and Huettel, B and Schubert, CJ and Kuypers, MMM and Milucka, J}, title = {Anaerobic endosymbiont generates energy for ciliate host by denitrification.}, journal = {Nature}, volume = {591}, number = {7850}, pages = {445-450}, pmid = {33658719}, issn = {1476-4687}, mesh = {Adenosine Triphosphate/metabolism ; *Anaerobiosis ; Bacteria/genetics/*metabolism ; Biological Evolution ; Cell Respiration ; Ciliophora/chemistry/cytology/*metabolism ; Citric Acid Cycle/genetics ; *Denitrification ; Electron Transport/genetics ; *Energy Metabolism ; Genome, Bacterial/genetics ; *Host Microbial Interactions/genetics ; Mitochondria ; Nitrates/metabolism ; Oxygen/metabolism ; Phylogeny ; *Symbiosis ; }, abstract = {Mitochondria are specialized eukaryotic organelles that have a dedicated function in oxygen respiration and energy production. They evolved about 2 billion years ago from a free-living bacterial ancestor (probably an alphaproteobacterium), in a process known as endosymbiosis[1,2]. Many unicellular eukaryotes have since adapted to life in anoxic habitats and their mitochondria have undergone further reductive evolution[3]. As a result, obligate anaerobic eukaryotes with mitochondrial remnants derive their energy mostly from fermentation[4]. Here we describe 'Candidatus Azoamicus ciliaticola', which is an obligate endosymbiont of an anaerobic ciliate and has a dedicated role in respiration and providing energy for its eukaryotic host. 'Candidatus A. ciliaticola' contains a highly reduced 0.29-Mb genome that encodes core genes for central information processing, the electron transport chain, a truncated tricarboxylic acid cycle, ATP generation and iron-sulfur cluster biosynthesis. The genome encodes a respiratory denitrification pathway instead of aerobic terminal oxidases, which enables its host to breathe nitrate instead of oxygen. 'Candidatus A. ciliaticola' and its ciliate host represent an example of a symbiosis that is based on the transfer of energy in the form of ATP, rather than nutrition. This discovery raises the possibility that eukaryotes with mitochondrial remnants may secondarily acquire energy-providing endosymbionts to complement or replace functions of their mitochondria.}, } @article {pmid33659825, year = {2020}, author = {Poroshina, AA and Sherbakov, DY and Peretolchina, TE}, title = {Diagnosis of the mechanisms of different types of discordances between phylogenies inferred from nuclear and mitochondrial markers.}, journal = {Vavilovskii zhurnal genetiki i selektsii}, volume = {24}, number = {4}, pages = {420-426}, doi = {10.18699/VJ20.634}, pmid = {33659825}, issn = {2500-0462}, abstract = {In ancient freshwater lakes, an abnormally large species diversity is observed. The mechanisms that generated extremely high biodiversity in the ancient lakes have not been sufficiently studied and remain only partially known. Sequences of environmental changes in highly complex ecosystems such as Lake Baikal, may induce sophisticated combinations of microevolutionary processes. These processes are likely to result in unusual "patterns" of genetic variability of species. The most unusual patterns include the ones when speciation is followed by incomplete lineage sorting as well as mitochondrial or nuclear introgression. All these phenomena are diagnosed by comparing the topologies of phylogenetic trees inferred from molecular markers of evolution located in mitochondria and nuclei. Mitochondrial and nuclear introgression is a particularly interesting and complex case, which is the process of incorporating the gene alleles of one species into the gene pool of a sister species due to interspecific hybridization (introgressive hybridization). In many cases, existing methods for molecular phylogenetic analysis do not automatically allow the observed patterns of polymorphism to be explained and, therefore, cannot provide hypotheses that would explain the mechanisms which resulted to these patterns. Here we use adaptive dynamics models to study neutral molecular evolution under various scenarios of interaction between sister species and the environment. We propose and justify a set of criteria for detecting how two evolutionary trees may differ, with a special focus on comparing a tree inferred from nuclear DNA to one from mitochondrial DNA. The criteria react to branching pattern and branch lengths, including relative distances from ancestral lineages. Simulations show that the criteria allow fast and automated detection of various types of introgression, secondary breaches of reproductive barriers, and incomplete lineage sorting.}, } @article {pmid33659931, year = {2021}, author = {Ji, LL and Yeo, D}, title = {Oxidative stress: an evolving definition.}, journal = {Faculty reviews}, volume = {10}, number = {}, pages = {13}, pmid = {33659931}, issn = {2732-432X}, abstract = {Thirty-five years ago, Sies and colleagues insightfully described the universal phenomenon that the generation of reactive oxygen species could modify macromolecules in living organisms, resulting in a wide range of measurable damage. They used the term "oxidative stress" to define the loss of the balance between oxidants and antioxidants in favor of the former. After decades of research, it became increasingly clear that cells are not simply passive receivers of oxidative modification but can act dynamically to resist and adapt to oxidants. Furthermore, many redox-sensitive pathways have been identified wherein certain oxidants (mainly hydrogen peroxide and nitric oxide) are used as messenger molecules to transduce the signals required for these adaptations. Since the turn of the century, redox signaling has developed into a vibrant multidisciplinary field of biology. To reflect the evolution of the study in this field, the definition of oxidative stress is postulated to define a state in which the pro-oxidative processes overwhelm cellular antioxidant defense due to the disruption of redox signaling and adaptation.}, } @article {pmid33666295, year = {2021}, author = {Salinas-Giegé, T and Ubrig, E and Drouard, L}, title = {Cyanophora paradoxa mitochondrial tRNAs play a double game.}, journal = {The Plant journal : for cell and molecular biology}, volume = {106}, number = {4}, pages = {1105-1115}, doi = {10.1111/tpj.15222}, pmid = {33666295}, issn = {1365-313X}, mesh = {Cyanophora/*genetics ; Genome, Mitochondrial/*genetics ; Mitochondria/genetics ; *RNA Processing, Post-Transcriptional ; RNA, Messenger/*genetics ; RNA, Mitochondrial/*genetics ; RNA, Transfer/*genetics ; }, abstract = {Present-day mitochondria derive from a single endosymbiosis of an α-proteobacterium into a proto-eukaryotic cell. Since this monophyletic event, mitochondria have evolved considerably, and unique traits have been independently acquired in the different eukaryotic kingdoms. Mitochondrial genome expression and RNA metabolism have diverged greatly. Here, Cyanophora paradoxa, a freshwater alga considered as a living fossil among photosynthetic organisms, represents an exciting model for studying the evolution of mitochondrial gene expression. As expected, fully mature tRNAs are released from primary transcripts to function in mitochondrial translation. We also show that these tRNAs take part in an mRNA processing punctuation mechanism in a non-conventional manner, leading to mRNA-tRNA hybrids with a CCA triplet at their 3'-extremities. In this case, tRNAs are probably used as stabilizing structures impeding the degradation of mRNA by exonucleases. From our data we propose that the present-day tRNA-like elements (t-elements) found at the 3'-terminals of mitochondrial mRNAs in land plants originate from true tRNAs like those observed in the mitochondria of this basal photosynthetic glaucophyte.}, } @article {pmid33669879, year = {2021}, author = {Zapelloni, F and Jurado-Rivera, JA and Jaume, D and Juan, C and Pons, J}, title = {Comparative Mitogenomics in Hyalella (Amphipoda: Crustacea).}, journal = {Genes}, volume = {12}, number = {2}, pages = {}, pmid = {33669879}, issn = {2073-4425}, mesh = {Amphipoda/classification/*genetics ; Animals ; Codon/genetics ; Codon Usage/genetics ; DNA, Mitochondrial/*genetics ; *Evolution, Molecular ; Genome, Mitochondrial/*genetics ; Mitochondria/genetics ; Phylogeny ; RNA, Transfer/genetics ; }, abstract = {We present the sequencing and comparative analysis of 17 mitochondrial genomes of Nearctic and Neotropical amphipods of the genus Hyalella, most from the Andean Altiplano. The mitogenomes obtained comprised the usual 37 gene-set of the metazoan mitochondrial genome showing a gene rearrangement (a reverse transposition and a reversal) between the North and South American Hyalella mitogenomes. Hyalella mitochondrial genomes show the typical AT-richness and strong nucleotide bias among codon sites and strands of pancrustaceans. Protein-coding sequences are biased towards AT-rich codons, with a preference for leucine and serine amino acids. Numerous base changes (539) were found in tRNA stems, with 103 classified as fully compensatory, 253 hemi-compensatory and the remaining base mismatches and indels. Most compensatory Watson-Crick switches were AU -> GC linked in the same haplotype, whereas most hemi-compensatory changes resulted in wobble GU and a few AC pairs. These results suggest a pairing fitness increase in tRNAs after crossing low fitness valleys. Branch-site level models detected positive selection for several amino acid positions in up to eight mitochondrial genes, with atp6 and nad5 as the genes displaying more sites under selection.}, } @article {pmid33671025, year = {2021}, author = {Ramzan, R and Kadenbach, B and Vogt, S}, title = {Multiple Mechanisms Regulate Eukaryotic Cytochrome C Oxidase.}, journal = {Cells}, volume = {10}, number = {3}, pages = {}, pmid = {33671025}, issn = {2073-4409}, mesh = {Animals ; Electron Transport Complex IV/*metabolism ; Eukaryota/*metabolism ; Rats ; }, abstract = {Cytochrome c oxidase (COX), the rate-limiting enzyme of mitochondrial respiration, is regulated by various mechanisms. Its regulation by ATP (adenosine triphosphate) appears of particular importance, since it evolved early during evolution and is still found in cyanobacteria, but not in other bacteria. Therefore the "allosteric ATP inhibition of COX" is described here in more detail. Most regulatory properties of COX are related to "supernumerary" subunits, which are largely absent in bacterial COX. The "allosteric ATP inhibition of COX" was also recently described in intact isolated rat heart mitochondria.}, } @article {pmid33678114, year = {2021}, author = {Huang, F and Ye, X and Wang, Z and Ding, Y and Cai, X and Yu, L and Waseem, M and Abbas, F and Ashraf, U and Chen, X and Ke, Y}, title = {The prohibitins (PHB) gene family in tomato: Bioinformatic identification and expression analysis under abiotic and phytohormone stresses.}, journal = {GM crops & food}, volume = {12}, number = {1}, pages = {535-550}, pmid = {33678114}, issn = {2164-5701}, mesh = {Computational Biology ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Genome, Plant ; *Solanum lycopersicum/genetics/metabolism ; Multigene Family ; Phylogeny ; Plant Growth Regulators ; Plant Proteins/genetics/metabolism ; Prohibitins ; Stress, Physiological/genetics ; }, abstract = {The prohibitins (PHB) are SPFH domain-containing proteins found in the prokaryotes to eukaryotes. The plant PHBs are associated with a wide range of biological processes, including senescence, development, and responses to biotic and abiotic stresses. The PHB proteins are identified and characterized in the number of plant species, such as Arabidopsis, rice, maize, and soybean. However, no systematic identification of PHB proteins was performed in Solanum lycopersicum. In this study, we identified 16 PHB proteins in the tomato genome. The analysis of conserved motifs and gene structure validated the phylogenetic classification of tomato PHB proteins. It was observed that various members of tomato PHB proteins undergo purifying selection based on the Ka/Ks ratio and are targeted by four families of miRNAs. Moreover, SlPHB proteins displayed a very unique expression pattern in different plant parts including fruits at various development stages. It was found that SlPHBs processed various development-related and phytohormone responsive cis-regulatory elements in their promoter regions. Furthermore, the exogenous phytohormones treatments (Abscisic acid, indole-3-acetic acid, gibberellic acid, methyl jasmonate) salt and drought stresses induce the expression of SlPHB. Moreover, the subcellular localization assay revealed that SlPHB5 and SlPHB10 were located in the mitochondria. This study systematically summarized the general characterization of SlPHBs in the tomato genome and provides a foundation for the functional characterization of PHB genes in tomato and other plant species.}, } @article {pmid33683754, year = {2021}, author = {Shevtsov-Tal, S and Best, C and Matan, R and Chandran, SA and Brown, GG and Ostersetzer-Biran, O}, title = {nMAT3 is an essential maturase splicing factor required for holo-complex I biogenesis and embryo development in Arabidopsis thaliana plants.}, journal = {The Plant journal : for cell and molecular biology}, volume = {106}, number = {4}, pages = {1128-1147}, doi = {10.1111/tpj.15225}, pmid = {33683754}, issn = {1365-313X}, mesh = {Arabidopsis/embryology/*genetics ; Arabidopsis Proteins/genetics/*metabolism ; Cell Nucleus/genetics ; Deoxyribonucleases/genetics/*metabolism ; Electron Transport Complex I/*metabolism ; Introns/genetics ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Phenotype ; RNA Splicing ; RNA Splicing Factors/genetics/metabolism ; RNA-Directed DNA Polymerase/genetics/metabolism ; }, abstract = {Group-II introns are self-splicing mobile genetic elements consisting of catalytic intron-RNA and its related intron-encoded splicing maturase protein cofactor. Group-II sequences are particularly plentiful within the mitochondria of land plants, where they reside within many critical gene loci. During evolution, the plant organellar introns have degenerated, such as they lack regions that are are required for splicing, and also lost their evolutionary related maturase proteins. Instead, for their splicing the organellar introns in plants rely on different host-acting protein cofactors, which may also provide a means to link cellular signals with respiratory functions. The nuclear genome of Arabidopsis thaliana encodes four maturase-related factors. Previously, we showed that three of the maturases, nMAT1, nMAT2 and nMAT4, function in the excision of different group-II introns in Arabidopsis mitochondria. The function of nMAT3 (encoded by the At5g04050 gene locus) was found to be essential during early embryogenesis. Using a modified embryo-rescue method, we show that nMAT3-knockout plants are strongly affected in the splicing of nad1 introns 1, 3 and 4 in Arabidopsis mitochondria, resulting in complex-I biogenesis defects and altered respiratory activities. Functional complementation of nMAT3 restored the organellar defects and embryo-arrested phenotypes associated with the nmat3 mutant line. Notably, nMAT3 and nMA4 were found to act on the same RNA targets but have no redundant functions in the splicing of nad1 transcripts. The two maturases, nMAT3 and nMAT4 are likely to cooperate together in the maturation of nad1 pre-RNAs. Our results provide important insights into the roles of maturases in mitochondria gene expression and the biogenesis of the respiratory system during early plant life.}, } @article {pmid33684529, year = {2021}, author = {Bogdanova, VS and Shatskaya, NV and Mglinets, AV and Kosterin, OE and Vasiliev, GV}, title = {Discordant evolution of organellar genomes in peas (Pisum L.).}, journal = {Molecular phylogenetics and evolution}, volume = {160}, number = {}, pages = {107136}, doi = {10.1016/j.ympev.2021.107136}, pmid = {33684529}, issn = {1095-9513}, mesh = {Cell Nucleus/genetics ; Cytoplasm/genetics ; Europe ; *Evolution, Molecular ; Genome, Mitochondrial/*genetics ; Hybridization, Genetic ; Pisum sativum/*cytology/*genetics ; *Phylogeny ; Plastids/*genetics ; }, abstract = {Plastids and mitochondria have their own small genomes, which do not undergo meiotic recombination and may have evolutionary fates different from each other and that of the nuclear genome. For the first time, we sequenced mitochondrial genomes of pea (Pisum L.) from 42 accessions mostly representing diverse wild germplasm from throughout the wild pea geographical range. Six structural types of the pea mitochondrial genome were revealed. From the same accessions, plastid genomes were sequenced. Phylogenetic trees based on the plastid and mitochondrial genomes were compared. The topologies of these trees were highly discordant, implying not less than six events of hybridisation between diverged wild peas in the past, with plastids and mitochondria differently inherited by the descendants. Such discordant inheritance of organelles could have been driven by plastid-nuclear incompatibility, which is known to be widespread in crosses involving wild peas and affects organellar inheritance. The topology of the phylogenetic tree based on nucleotide sequences of a nuclear gene, His5, encoding a histone H1 subtype, corresponded to the current taxonomy and resembled that based on the plastid genome. Wild peas (Pisum sativum subsp. elatius s.l.) inhabiting Southern Europe were shown to be of hybrid origin, resulting from crosses of peas related to those presently inhabiting the eastern Mediterranean in a broad sense. These results highlight the roles of hybridisation and cytonuclear conflict in shaping plant microevolution.}, } @article {pmid33684992, year = {2021}, author = {Song, JY and Kim, KY and Choi, SW}, title = {Occurrence and Molecular Identification of Microcotyle sebastis Isolated from Fish Farms of the Korean Rockfish, Sebastes schlegelii.}, journal = {The Korean journal of parasitology}, volume = {59}, number = {1}, pages = {89-95}, pmid = {33684992}, issn = {1738-0006}, support = {R2021065//National Institute of Fisheries Science/ ; }, mesh = {Animals ; Electron Transport Complex IV/genetics ; Fish Diseases/*epidemiology/*parasitology ; *Fisheries ; Microscopy, Electron, Scanning ; Mitochondria/enzymology/genetics ; Phylogeny ; RNA, Ribosomal, 28S ; Republic of Korea/epidemiology ; Trematoda/*genetics/*isolation & purification/ultrastructure ; Trematode Infections/epidemiology/*parasitology/*veterinary ; }, abstract = {Microcotyle sebastis is a gill monogenean ectoparasite that causes serious problems in the mariculture of the Korean rockfish, Sebastes schlegelii. In this study, we isolated the parasite from fish farms along the coasts of Tongyeong, South Korea in 2016, and characterized its infection, morphology and molecular phylogeny. The prevalence of M. sebastis infection during the study period ranged from 46.7% to 96.7%, and the mean intensity was 2.3 to 31.4 ind./fish, indicating that the fish was constantly exposed to parasitic infections throughout the year. Morphological observations under light and scanning electron microscopes of the M. sebastis isolates in this study showed the typical characteristics of the anterior prohaptor and posterior opisthaptor of monogenean parasites. In phylogenetic trees reconstructed using the nuclear 28S ribosomal RNA gene and the mitochondrial cytochrome c oxidase I gene (cox1), they consistently clustered together with their congeneric species, and showed the closest phylogenetic relationships to M. caudata and M. kasago in the cox1 tree.}, } @article {pmid33684994, year = {2021}, author = {Yang, Y and Tong, J and Ruan, H and Yang, M and Sang, C and Liu, G and Hazihan, W and Xu, B and Hornok, S and Rizabek, K and Gulzhan, K and Liu, Z and Wang, Y}, title = {Genetic Diversity of Hard Ticks (Acari: Ixodidae) in the South and East Regions of Kazakhstan and Northwestern China.}, journal = {The Korean journal of parasitology}, volume = {59}, number = {1}, pages = {103-108}, pmid = {33684994}, issn = {1738-0006}, support = {2018ZX10101002-007//National Key Research & Development Program of China/ ; 2018ZX10101002-003//National Key Research & Development Program of China/ ; 81960379//National Natural Science Foundation of China/ ; 31960709//National Natural Science Foundation of China/ ; 18YJCZH220//Humanities and Social Sciences Research Projects/ ; RCZK2018C04//Shihezi University/ ; 2020E01008//International Cooperation Projects of Xinjiang Uygur Autonomous Region/ ; }, mesh = {Acari/*genetics ; Animals ; China ; Electron Transport Complex IV/genetics ; Evolution, Molecular ; Genetic Variation/*genetics ; Kazakhstan ; Mitochondria/enzymology/genetics ; Phylogeny ; }, abstract = {To date, there is no report on the genetic diversity of ticks in these regions. A total of 370 representative ticks from the south and east regions of Kazakhstan (SERK) and Xinjiang Uygur Autonomous Region (XUAR) were selected for molecular comparison. A fragment of the mitochondrial cytochrome c oxidase subunit I (cox1) gene, ranging from 631 bp to 889 bp, was used to analyze genetic diversity among these ticks. Phylogenetic analyses indicated 7 tick species including Hyalomma asiaticum, Hyalomma detritum, Hyalomma anatolicum, Dermacentor marginatus, Rhipicephalus sanguineus, Rhipicephalus turanicus and Haemaphysalis erinacei from the SERK clustered together with conspecific ticks from the XUAR. The network diagram of haplotypes showed that i) Hy. asiaticum from Almaty and Kyzylorda Oblasts together with that from Yuli County of XUAR constituted haplogroup H-2, and the lineage from Chimkent City of South Kazakhstan was newly evolved; and ii) the R. turanicus ticks sampled in Israel, Almaty, South Kazakhstan, Usu City, Ulugqat and Baicheng Counties of XUAR were derivated from an old lineage in Alataw City of XUAR. These findings indicate that: i) Hy. asiaticum, R. turanicus and Ha. erinacei shared genetic similarities between the SERK and XUAR; and ii) Hy. marginatum and D. reticulatus show differences in their evolution.}, } @article {pmid33689939, year = {2021}, author = {Dallai, R and Fanciulli, PP and Lupetti, P and Mercati, D}, title = {The ultrastructure of sperm and female sperm storage organs in the water strider Gerris lacustris L. (Heteroptera) and a possible example of genital coevolution.}, journal = {Arthropod structure & development}, volume = {61}, number = {}, pages = {101043}, doi = {10.1016/j.asd.2021.101043}, pmid = {33689939}, issn = {1873-5495}, mesh = {Animals ; *Biological Evolution ; Female ; Genitalia/physiology/ultrastructure ; *Heteroptera/classification/ultrastructure ; Insemination ; Male ; Spermatozoa/ultrastructure ; }, abstract = {The fine structural organization of the male and the female inner reproductive apparatuses of the water-strider Gerris lacustris was studied. The sperm of the species shows a long helicoidal acrosome provided with longitudinal tubules, and a short nucleus. The flagellum is characterized by crescent mitochondrial derivatives and a 9 + 9 + 2 axoneme, as occurs in all Heteroptera. The female reproductive apparatus is characterized by an extremely long spermathecal duct, filled with sperm, which plays the role of the main sperm storage organ. The duct has a thin epithelium surrounded by a complex of secretory and duct-forming cells. The spermathecal duct flows into the gynatrial sac. This region, together with the fertilization chamber, exhibits a simple epithelium with deep apical plasma membrane invaginations, and it does not show conspicuous secretions. The basal cell region shows plasma membrane infoldings forming thin cytoplasmic bands hosting mitochondria and large intercellular spaces. This organization is typical of epithelia active in fluid reabsorption. Two lateral large gynatrial glands open into the gynatrial sac. Such glands also exhibit secretory and duct forming cells. The same structure of these glands is also present along the proximal region of the fecundation canal. The duct forming cells of these regions have very wide ducts with peculiar cuticular finger-like structures at their opening into the gland duct lumen. The results of the present study suggest the occurrence of a coevolution between the sperm and the spermathecal duct lengths.}, } @article {pmid33704433, year = {2021}, author = {Broz, AK and Waneka, G and Wu, Z and Fernandes Gyorfy, M and Sloan, DB}, title = {Detecting de novo mitochondrial mutations in angiosperms with highly divergent evolutionary rates.}, journal = {Genetics}, volume = {218}, number = {1}, pages = {}, pmid = {33704433}, issn = {1943-2631}, support = {R01 GM118046/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Biological/genetics ; Biological Evolution ; DNA/genetics ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Genome/genetics ; Genome, Mitochondrial/genetics ; Genome, Plant/genetics ; Magnoliopsida/genetics ; Mitochondria/*genetics ; Mutation/genetics ; Mutation Rate ; Phylogeny ; Sequence Analysis, DNA/*methods ; Silene/*genetics ; }, abstract = {Although plant mitochondrial genomes typically show low rates of sequence evolution, levels of divergence in certain angiosperm lineages suggest anomalously high mitochondrial mutation rates. However, de novo mutations have never been directly analyzed in such lineages. Recent advances in high-fidelity DNA sequencing technologies have enabled detection of mitochondrial mutations when still present at low heteroplasmic frequencies. To date, these approaches have only been performed on a single plant species (Arabidopsis thaliana). Here, we apply a high-fidelity technique (Duplex Sequencing) to multiple angiosperms from the genus Silene, which exhibits extreme heterogeneity in rates of mitochondrial sequence evolution among close relatives. Consistent with phylogenetic evidence, we found that Silene latifolia maintains low mitochondrial variant frequencies that are comparable with previous measurements in Arabidopsis. Silene noctiflora also exhibited low variant frequencies despite high levels of historical sequence divergence, which supports other lines of evidence that this species has reverted to lower mitochondrial mutation rates after a past episode of acceleration. In contrast, S. conica showed much higher variant frequencies in mitochondrial (but not in plastid) DNA, consistent with an ongoing bout of elevated mitochondrial mutation rates. Moreover, we found an altered mutational spectrum in S. conica heavily biased towards AT→GC transitions. We also observed an unusually low number of mitochondrial genome copies per cell in S. conica, potentially pointing to reduced opportunities for homologous recombination to accurately repair mismatches in this species. Overall, these results suggest that historical fluctuations in mutation rates are driving extreme variation in rates of plant mitochondrial sequence evolution.}, } @article {pmid33707777, year = {2021}, author = {Zhang, J and Hou, L and Zuo, Z and Ji, P and Zhang, X and Xue, Y and Zhao, F}, title = {Comprehensive profiling of circular RNAs with nanopore sequencing and CIRI-long.}, journal = {Nature biotechnology}, volume = {39}, number = {7}, pages = {836-845}, pmid = {33707777}, issn = {1546-1696}, mesh = {Animals ; Base Sequence ; Computer Simulation ; Gene Expression Regulation ; Humans ; Mice ; *Nanopore Sequencing ; RNA Isoforms ; RNA, Circular/*genetics ; Reproducibility of Results ; }, abstract = {Reconstructing the sequence of circular RNAs (circRNAs) from short RNA sequencing reads has proved challenging given the similarity of circRNAs and their corresponding linear messenger RNAs. Previous sequencing methods were unable to achieve high-throughput detection of full-length circRNAs. Here we describe a protocol for enrichment and full-length sequencing of circRNA isoforms using nanopore technology. Circular reverse transcription and size selection achieves a 20-fold higher enrichment of circRNAs from total RNA compared to previous methods. We developed an algorithm, called circRNA identifier using long-read sequencing data (CIRI-long), to reconstruct the sequence of circRNAs. The workflow was validated with simulated data and by comparison to Illumina sequencing as well as quantitative real-time RT-PCR. We used CIRI-long to analyze adult mouse brain samples and systematically profile circRNAs, including mitochondria-derived and transcriptional read-through circRNAs. We identified a new type of intronic self-ligated circRNA that exhibits special splicing and expression patterns. Our method takes advantage of nanopore long reads and enables unbiased reconstruction of full-length circRNA sequences.}, } @article {pmid33711786, year = {2021}, author = {Srivastava, PN and Narwal, SK and Mishra, S}, title = {Mitochondrial apurinic/apyrimidinic endonuclease Apn1 is not critical for the completion of the Plasmodium berghei life cycle.}, journal = {DNA repair}, volume = {101}, number = {}, pages = {103078}, doi = {10.1016/j.dnarep.2021.103078}, pmid = {33711786}, issn = {1568-7856}, mesh = {Amino Acid Sequence ; DNA Damage ; DNA Repair ; DNA, Mitochondrial/metabolism ; DNA-(Apurinic or Apyrimidinic Site) Lyase/chemistry/genetics/*metabolism ; *Life Cycle Stages ; Mitochondria/*enzymology ; Models, Molecular ; Phylogeny ; Plasmodium berghei/*enzymology/growth & development ; Protein Conformation ; Sequence Alignment ; Sequence Analysis, Protein ; }, abstract = {Mitochondrion is an essential organelle in malaria parasite and its DNA must be maintained for optimal function during its complex life cycle. Base excision repair is one of the major pathways by which this is achieved. Apurinic/apyrimidinic (AP) endonucleases are important components of this pathway as they create a nick at the 5'-phosphodiester bond in the AP site and generate free 5'-phosphate and 3'-hydroxyl groups. Two class II AP endonucleases (Apn1 and Ape1) have been annotated in the Plasmodium berghei genome. Using reverse genetic approaches, we provide direct evidence that Apn1 is exclusively localized to the mitochondria of P. berghei. Surprisingly, our gene deletion study revealed a completely dispensable role of Apn1 for the entirety of the P. berghei life cycle. Apn1[-] parasites were found to successfully grow in the blood. They were transmitted normally to the mosquito midguts and salivary glands. Sporozoites obtained from the salivary glands were infective and achieved similar patency as WT. Our results help emphasize the non-availability of this enzyme as a plausible drug target. We also emphasize the importance of genetic validation of antimalarial drug targets before furthering them down the drug discovery pipeline.}, } @article {pmid33713675, year = {2021}, author = {Dumoulin, B and Ufer, C and Kuhn, H and Sofi, S}, title = {Expression Regulation, Protein Chemistry and Functional Biology of the Guanine-Rich Sequence Binding Factor 1 (GRSF1).}, journal = {Journal of molecular biology}, volume = {433}, number = {13}, pages = {166922}, doi = {10.1016/j.jmb.2021.166922}, pmid = {33713675}, issn = {1089-8638}, mesh = {Amino Acid Sequence ; Animals ; Evolution, Molecular ; *Gene Expression Regulation ; Guanine/*metabolism ; Humans ; Poly(A)-Binding Proteins/*chemistry/*genetics ; Protein Binding ; RNA/metabolism ; }, abstract = {In eukaryotic cells RNA-binding proteins have been implicated in virtually all post-transcriptional mechanisms of gene expression regulation. Based on the structural features of their RNA binding domains these proteins have been divided into several subfamilies. The presence of at least two RNA recognition motifs defines the group of heterogenous nuclear ribonucleoproteins H/F and one of its members is the guanine-rich sequence binding factor 1 (GRSF1). GRSF1 was first described 25 years ago and is widely distributed in eukaryotic cells. It is present in the nucleus, the cytoplasm and in mitochondria and has been implicated in a variety of physiological processes (embryogenesis, erythropoiesis, redox homeostasis, RNA metabolism) but also in the pathogenesis of various diseases. This review summarizes our current understanding on GRSF1 biology, critically discusses the literature reports and gives an outlook of future developments in the field.}, } @article {pmid33720930, year = {2021}, author = {Londoño-Burbano, A and Reis, RE}, title = {A combined molecular and morphological phylogeny of the Loricariinae (Siluriformes: Loricariidae), with emphasis on the Harttiini and Farlowellini.}, journal = {PloS one}, volume = {16}, number = {3}, pages = {e0247747}, pmid = {33720930}, issn = {1932-6203}, mesh = {Animals ; Bayes Theorem ; Catfishes/anatomy & histology/classification/*genetics ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Fish Proteins/*genetics ; Genetic Markers ; Mitochondria/genetics ; *Phylogeny ; }, abstract = {We present a combined molecular and morphological phylogenetic analysis of the Loricariinae, with emphasis on the Harttiini (Cteniloricaria, Harttia, and Harttiella) and Farlowellini (Aposturisoma, Farlowella, Lamontichthys, Pterosturisoma, Sturisoma, and Sturisomatichthys). Character sampling comprised seven molecular markers (the mitochondrial Cytb, nd2, 12S and 16S, and the nuclear MyH6, RAG1 and RAG2) and 196 morphological characters. A total of 1,059 specimens, and 159 tissue samples were analized, representing 100 species. A Bayesian Inference analysis was performed using the concatenated data matrix, which is comprised of 6,819 characters. The Loricariinae were found to comprise the tribes (Hartiini (Loricariini, Farlowellini)), the latter two elevated from subtribes. A Maximum Parsimony analysis was also performed using the same data matrix in order to reveal phenotypical synapomorphies to diagnose each clade. Two MP trees were found with a length of 14,704 steps, consistency index of 0.29 and retention index of 0.61, which were summarized in a strict consensus tree. Harttiini includes (Harttiella (Cteniloricaria, Harttia), and Farlowellini includes (Lamontichthys (Pterosturisoma (Sturisoma (Sturisomatichthys, Farlowella)))). Aposturisoma was recovered nested within Farlowella and is synonymyzed to the latter. Sturisoma was corroborated as strictly cis-Andean, while Sturisomatichthys encompasses, besides the valid species already included in the genus, the trans-Andean species once belonging to Sturisoma sensu lato. Identification keys and phylogenetic diagnoses of family-group taxa and genera of both the Harttiini and the Farlowellini are provided.}, } @article {pmid33729620, year = {2021}, author = {Radzvilavicius, A}, title = {Beyond the "selfish mitochondrion" theory of uniparental inheritance: A unified theory based on mutational variance redistribution.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {5}, pages = {e2100009}, doi = {10.1002/bies.202100009}, pmid = {33729620}, issn = {1521-1878}, mesh = {Eukaryota/genetics ; Genome ; *Heredity ; *Mitochondria/genetics ; Mutation/genetics ; }, abstract = {"Selfish" gene theories have offered invaluable insight into eukaryotic genome evolution, but they can also be misleading. The "selfish mitochondrion" hypothesis, developed in the 90s explained uniparental organelle inheritance as a mechanism of conflict resolution, improving cooperation between genetically distinct compartments of the cell. But modern population genetic models provided a more general explanation for uniparental inheritance based on mutational variance redistribution, modulating the efficiency of both purifying and adaptive selection. Nevertheless, as reviewed here, "selfish" conflict theories still dominate the literature. While these hypotheses are rich in metaphor and highly intuitive, selective focus on only one type of mitochondrial mutation limits the generality of our understanding and hinders progress in mito-nuclear evolution theory. Recognizing that uniparental inheritance may have evolved-and is maintained across the eukaryotic tree of life-because of its influence on mutational variance and improved selection will only increase the generality of our evolutionary reasoning, retaining "selfish" conflict explanations as a special case of a much broader theory.}, } @article {pmid33730185, year = {2021}, author = {Arab, DA and Lo, N}, title = {Evolutionary Rates are Correlated Between Buchnera Endosymbionts and the Mitochondrial Genomes of Their Aphid Hosts.}, journal = {Journal of molecular evolution}, volume = {89}, number = {4-5}, pages = {238-248}, pmid = {33730185}, issn = {1432-1432}, mesh = {Animals ; *Aphids/genetics ; Bacteroidetes ; *Buchnera/genetics ; Evolution, Molecular ; *Genome, Mitochondrial/genetics ; Phylogeny ; }, abstract = {The evolution of bacterial endosymbiont genomes is strongly influenced by host-driven selection. Factors affecting host genome evolution will potentially affect endosymbiont genomes in similar ways. One potential outcome is correlations in molecular rates between the genomes of the symbiotic partners. Recently, we presented the first evidence of such correlations between the mitochondrial genomes of cockroaches and the genomes of their endosymbiont (Blattabacterium cuenoti). Here we investigate whether similar patterns are found in additional host-symbiont partners. We use partial genome data from multiple strains of the bacterial endosymbionts Buchnera aphidicola and Sulcia muelleri, and the mitochondrial genomes of their sap-feeding insect hosts. Both endosymbionts show phylogenetic congruence with the mitochondria of their hosts, a result that is expected due to their identical mode of inheritance. We compared root-to-tip distances and branch lengths of phylogenetically independent species pairs. Both analyses showed a highly significant correlation of molecular rates between the genomes of Buchnera and the mitochondrial genomes of their hosts. A similar correlation was detected between Sulcia and their hosts, but was not statistically significant. Our results indicate that evolutionary rate correlations between hosts and long-term symbionts may be a widespread phenomenon.}, } @article {pmid33732288, year = {2021}, author = {Cruz, JO and Silva, AO and Ribeiro, JM and Luizon, MR and Ceron, CS}, title = {Epigenetic Regulation of the N-Terminal Truncated Isoform of Matrix Metalloproteinase-2 (NTT-MMP-2) and Its Presence in Renal and Cardiac Diseases.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {637148}, pmid = {33732288}, issn = {1664-8021}, abstract = {Several clinical and experimental studies have documented a compelling and critical role for the full-length matrix metalloproteinase-2 (FL-MMP-2) in ischemic renal injury, progressive renal fibrosis, and diabetic nephropathy. A novel N-terminal truncated isoform of MMP-2 (NTT-MMP-2) was recently discovered, which is induced by hypoxia and oxidative stress by the activation of a latent promoter located in the first intron of the MMP2 gene. This NTT-MMP-2 isoform is enzymatically active but remains intracellular in or near the mitochondria. In this perspective article, we first present the findings about the discovery of the NTT-MMP-2 isoform, and its functional and structural differences as compared with the FL-MMP-2 isoform. Based on publicly available epigenomics data from the Encyclopedia of DNA Elements (ENCODE) project, we provide insights into the epigenetic regulation of the latent promoter located in the first intron of the MMP2 gene, which support the activation of the NTT-MMP-2 isoform. We then focus on its functional assessment by covering the alterations found in the kidney of transgenic mice expressing the NTT-MMP-2 isoform. Next, we highlight recent findings regarding the presence of the NTT-MMP-2 isoform in renal dysfunction, in kidney and cardiac diseases, including damage observed in aging, acute ischemia-reperfusion injury (IRI), chronic kidney disease, diabetic nephropathy, and human renal transplants with delayed graft function. Finally, we briefly discuss how our insights may guide further experimental and clinical studies that are needed to elucidate the underlying mechanisms and the role of the NTT-MMP-2 isoform in renal dysfunction, which may help to establish it as a potential therapeutic target in kidney diseases.}, } @article {pmid33735257, year = {2021}, author = {Liu, Y and Yao, L and Ci, Y and Cao, X and Zhao, M and Li, Y and Zhang, X}, title = {Genetic differentiation of geographic populations of Rattus tanezumi based on the mitochondrial Cytb gene.}, journal = {PloS one}, volume = {16}, number = {3}, pages = {e0248102}, pmid = {33735257}, issn = {1932-6203}, mesh = {Animals ; Cytochromes b/*genetics ; *Gene Flow ; Genes, Mitochondrial ; *Genetic Drift ; Genetic Variation ; Genetics, Population ; Haplotypes ; Mitochondria/*genetics ; Rats/*genetics ; }, abstract = {Rattus tanezumi is a common domestic rat and host of the bubonic plague pathogen in China and Southeast Asia (SEA). The origin, genetic differentiation and dispersal of R. tanezumi have received increasing attention from researchers. The population genetics of R. tanezumi based on its mitochondrial cytochrome b gene have been studied to explain the origin, relationships and dispersal of populations. In this study, we captured a total of 229 rats; morphological and molecular biological identification cytochrome oxidase subunit I (COI) confirmed 131 R. tanezumi individuals collected from 6 provincial areas, and their Cytb gene sequences were analyzed. The results showed that the population in Mohan (MH), Yunnan, had the highest genetic diversity, while that in Ningde (ND), Fujian, had the lowest. Tajima's D statistic for all populations was negative and nonsignificant, indicating the possible expansion of R. tanezumi populations. Low gene flow occurred between the Zhangmu (ZM) R. tanezumi population and other populations, and the genetic differentiation among them was high. Furthermore, our analyses revealed the ZM lineage was the oldest lineage among the groups and diverged ~1.06 Mya, followed by the Luoyang (LY) lineages (~0.51 Mya) and Yunnan lineage (~0.33 Mya). In southeastern Yunnan, the Jinshuihe (JSH) and MH populations were more closely related to the populations in southeastern China (Fuzhou (FZ), ND, Quanzhou (QZ), Nanchang (NC)) and inland areas (Chongqing (CQ), LY) than to those in other areas of Yunnan (Jiegao (JG) and Qingshuihe (QSH)), indicating that R. tanezumi may have spread from southeastern Yunnan to the interior of China. In summary, R. tanezumi may have originated in ZM and adjacent areas, spread to Yunnan, and then spread from the southeast of Yunnan inland or directly eastward from ZM to inland China.}, } @article {pmid33735765, year = {2021}, author = {Wu, G and Wei, P and Chen, X and Zhang, Z and Jin, Z and Liu, J and Liu, L}, title = {Less is more: biological effects of NiSe2/rGO nanocomposites with low dose provide new insight for risk assessment.}, journal = {Journal of hazardous materials}, volume = {415}, number = {}, pages = {125605}, doi = {10.1016/j.jhazmat.2021.125605}, pmid = {33735765}, issn = {1873-3336}, mesh = {Animals ; *Graphite ; *Nanocomposites/toxicity ; Oxidative Stress ; Rats ; Risk Assessment ; }, abstract = {Nickel selenide nanomaterials (NiSe2 NMs) with different vacancies demonstrated high catalytic activity as electrocatalyst in oxygen evolution reaction. As the growing needs of the industrial applications in electrocatalyst, the increased occupational exposure and environmental releasing of NMs would be unavoidable. While, much efforts have been made to evaluate the ecological safety of such engineered NMs at unrealistically high concentrations, failed to provide the comprehensively guideline for exposure thresholds. To supplement the current knowledge gap, we testified the cytotoxicity of NiSe2/rGO nanocomposites with different surface defects under more realistic exposure mode. Compared with the short-term exposure and repetitive exposure, rat lung macrophages exhibited the augmented oxidative stress, dysfunction of mitochondria, damage of DNA and disorder of calcium homeostasis under the long-term NiSe2/rGO exposure. Noteworthily, no significant differences could be found between the NiSe2/rGO with different surface defects, indicated that the defect type of NMs were not the accurate predictor for real risk assessment. Collectively, the study provided the real potential toxic effects and exposure thresholds of NMs that might be highly possible industrial produced, and appealed the new insight for risk assessments of engineered NMs under the long-term exposure, which exhibited difference from the traditional evaluation of short-term and repetitive exposure.}, } @article {pmid33735859, year = {2021}, author = {Kuwana, C and Fujita, H and Tagami, M and Matsuo, T and Miura, I}, title = {Evolution of Sex Chromosome Heteromorphy in Geographic Populations of the Japanese Tago's Brown Frog Complex.}, journal = {Cytogenetic and genome research}, volume = {161}, number = {1-2}, pages = {23-31}, doi = {10.1159/000512964}, pmid = {33735859}, issn = {1424-859X}, mesh = {Animals ; Chromosome Banding ; DNA, Mitochondrial/genetics ; Female ; Geography ; Japan ; Karyotyping ; Likelihood Functions ; Mitochondria/*genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Ranidae/*genetics ; *Sex Chromosomes ; Species Specificity ; Y Chromosome ; }, abstract = {The sex chromosomes of most anuran amphibians are characterized by homomorphy in both sexes, and evolution to heteromorphy rarely occurs at the species or geographic population level. Here, we report sex chromosome heteromorphy in geographic populations of the Japanese Tago's brown frog complex (2n = 26), comprising Rana sakuraii and R. tagoi. The sex chromosomes of R. sakuraii from the populations in western Japan were homomorphic in both sexes, whereas chromosome 7 from the populations in eastern Japan were heteromorphic in males. Chromosome 7 of R. tagoi, which is distributed close to R. sakuraii in eastern Japan, was highly similar in morphology to the Y chromosome of R. sakuraii. Based on this and on mitochondrial gene sequence analysis, we hypothesize that in the R. sakuraii populations from eastern Japan the XY heteromorphic sex chromosome system was established by the introduction of chromosome 7 from R. tagoi via interspecies hybridization. In contrast, chromosome 13 of R. tagoi from the 2 large islands in western Japan, Shikoku and Kyushu, showed a heteromorphic pattern of constitutive heterochromatin distribution in males, while this pattern was homomorphic in females. Our study reveals that sex chromosome heteromorphy evolved independently at the geographic lineage level in this species complex.}, } @article {pmid33739376, year = {2021}, author = {Tria, FDK and Brueckner, J and Skejo, J and Xavier, JC and Kapust, N and Knopp, M and Wimmer, JLE and Nagies, FSP and Zimorski, V and Gould, SB and Garg, SG and Martin, WF}, title = {Gene Duplications Trace Mitochondria to the Onset of Eukaryote Complexity.}, journal = {Genome biology and evolution}, volume = {13}, number = {5}, pages = {}, pmid = {33739376}, issn = {1759-6653}, mesh = {*Biological Evolution ; Eukaryota/*genetics ; Evolution, Molecular ; *Gene Duplication ; Gene Transfer, Horizontal ; Genes, Archaeal ; Genes, Bacterial ; Mitochondria/*genetics ; }, abstract = {The last eukaryote common ancestor (LECA) possessed mitochondria and all key traits that make eukaryotic cells more complex than their prokaryotic ancestors, yet the timing of mitochondrial acquisition and the role of mitochondria in the origin of eukaryote complexity remain debated. Here, we report evidence from gene duplications in LECA indicating an early origin of mitochondria. Among 163,545 duplications in 24,571 gene trees spanning 150 sequenced eukaryotic genomes, we identify 713 gene duplication events that occurred in LECA. LECA's bacterial-derived genes include numerous mitochondrial functions and were duplicated significantly more often than archaeal-derived and eukaryote-specific genes. The surplus of bacterial-derived duplications in LECA most likely reflects the serial copying of genes from the mitochondrial endosymbiont to the archaeal host's chromosomes. Clustering, phylogenies and likelihood ratio tests for 22.4 million genes from 5,655 prokaryotic and 150 eukaryotic genomes reveal no evidence for lineage-specific gene acquisitions in eukaryotes, except from the plastid in the plant lineage. That finding, and the functions of bacterial genes duplicated in LECA, suggests that the bacterial genes in eukaryotes are acquisitions from the mitochondrion, followed by vertical gene evolution and differential loss across eukaryotic lineages, flanked by concomitant lateral gene transfer among prokaryotes. Overall, the data indicate that recurrent gene transfer via the copying of genes from a resident mitochondrial endosymbiont to archaeal host chromosomes preceded the onset of eukaryotic cellular complexity, favoring mitochondria-early over mitochondria-late hypotheses for eukaryote origin.}, } @article {pmid33740894, year = {2021}, author = {Pyrih, J and Žárský, V and Fellows, JD and Grosche, C and Wloga, D and Striepen, B and Maier, UG and Tachezy, J}, title = {The iron-sulfur scaffold protein HCF101 unveils the complexity of organellar evolution in SAR, Haptista and Cryptista.}, journal = {BMC ecology and evolution}, volume = {21}, number = {1}, pages = {46}, pmid = {33740894}, issn = {2730-7182}, mesh = {Animals ; *Cryptosporidiosis ; *Cryptosporidium ; Iron ; *Iron-Sulfur Proteins/genetics ; Phylogeny ; Sulfur ; }, abstract = {BACKGROUND: Nbp35-like proteins (Nbp35, Cfd1, HCF101, Ind1, and AbpC) are P-loop NTPases that serve as components of iron-sulfur cluster (FeS) assembly machineries. In eukaryotes, Ind1 is present in mitochondria, and its function is associated with the assembly of FeS clusters in subunits of respiratory Complex I, Nbp35 and Cfd1 are the components of the cytosolic FeS assembly (CIA) pathway, and HCF101 is involved in FeS assembly of photosystem I in plastids of plants (chHCF101). The AbpC protein operates in Bacteria and Archaea. To date, the cellular distribution of these proteins is considered to be highly conserved with only a few exceptions.

RESULTS: We searched for the genes of all members of the Nbp35-like protein family and analyzed their targeting sequences. Nbp35 and Cfd1 were predicted to reside in the cytoplasm with some exceptions of Nbp35 localization to the mitochondria; Ind1was found in the mitochondria, and HCF101 was predicted to reside in plastids (chHCF101) of all photosynthetically active eukaryotes. Surprisingly, we found a second HCF101 paralog in all members of Cryptista, Haptista, and SAR that was predicted to predominantly target mitochondria (mHCF101), whereas Ind1 appeared to be absent in these organisms. We also identified a few exceptions, as apicomplexans possess mHCF101 predicted to localize in the cytosol and Nbp35 in the mitochondria. Our predictions were experimentally confirmed in selected representatives of Apicomplexa (Toxoplasma gondii), Stramenopila (Phaeodactylum tricornutum, Thalassiosira pseudonana), and Ciliophora (Tetrahymena thermophila) by tagging proteins with a transgenic reporter. Phylogenetic analysis suggested that chHCF101 and mHCF101 evolved from a common ancestral HCF101 independently of the Nbp35/Cfd1 and Ind1 proteins. Interestingly, phylogenetic analysis supports rather a lateral gene transfer of ancestral HCF101 from bacteria than its acquisition being associated with either α-proteobacterial or cyanobacterial endosymbionts.

CONCLUSION: Our searches for Nbp35-like proteins across eukaryotic lineages revealed that SAR, Haptista, and Cryptista possess mitochondrial HCF101. Because plastid localization of HCF101 was only known thus far, the discovery of its mitochondrial paralog explains confusion regarding the presence of HCF101 in organisms that possibly lost secondary plastids (e.g., ciliates, Cryptosporidium) or possess reduced nonphotosynthetic plastids (apicomplexans).}, } @article {pmid33741537, year = {2021}, author = {Bober, S and Glaubrecht, M and Hausdorf, B and Neiber, MT}, title = {One, two or three? Integrative species delimitation of short-range endemic Hemicycla species (Gastropoda: Helicidae) from the Canary Islands based on morphology, barcoding, AFLP and ddRADseq data.}, journal = {Molecular phylogenetics and evolution}, volume = {161}, number = {}, pages = {107153}, doi = {10.1016/j.ympev.2021.107153}, pmid = {33741537}, issn = {1095-9513}, mesh = {*Amplified Fragment Length Polymorphism Analysis ; Animals ; *DNA Barcoding, Taxonomic ; Mitochondria/genetics ; *Phylogeny ; Polymorphism, Single Nucleotide/*genetics ; Snails/*anatomy & histology/classification/*genetics ; Spain ; }, abstract = {Hemicycla mascaensis and H. diegoi are short-range endemics that occur allopatrically in small areas in the Teno Mountains in the western part of Tenerife (Canary Islands). Both taxa have been recognised as distinct species based on differences in shell morphology and genital anatomy. Preliminary molecular analyses using mitochondrial markers suggested a potential paraphyly of H. diegoi with regard to H. mascaensis. We here use multilocus AFLP data and ddRADseq data as well as distribution data, data on shell morphology and genital anatomy to assess the status of these taxa using phylogenetic analyses, species tree reconstruction and molecular species delimitation based on the multispecies coalescent as implemented in BFD* and BPP in an integrative approach. Our analyses show that, based on the analysis of multilocus data, the two taxa are reciprocally monophyletic. Species delimitation methods, however, tend to recognise all investigated populations as distinct species, albeit neither lending unambiguous support to any of the species hypotheses. The comparison of the anatomy of distal genital organs further suggests differentiation within H. mascaensis. This highlights the need for a balanced weighting of arguments from different lines of evidence to determine species status and calls for cautious interpretations of the results of molecular species delimitation analyses, especially in organisms with low active dispersal capacities and expected distinct population structuring such as land snails. Taking all available evidence into account, we favour to recognise H. mascaensis and H. diegoi as distinct species, acknowledging, though, that the recognition of both taxa as subspecies (with possibly a third yet undescribed) would also be an option as morphological differentiation is within the limits of other land snail species that are traditionally subdivided into subspecies.}, } @article {pmid33743014, year = {2021}, author = {Zheng, K and Li, T}, title = {Prediction of ATPase cation transporting 13A2 molecule in Petromyzon marinus and pan-cancer analysis into human tumors from an evolutionary perspective.}, journal = {Immunogenetics}, volume = {73}, number = {4}, pages = {277-289}, pmid = {33743014}, issn = {1432-1211}, mesh = {Amino Acid Sequence ; Animals ; Computational Biology ; *Evolution, Molecular ; Fish Proteins/genetics/*metabolism ; Humans ; Neoplasms/genetics/*metabolism/pathology ; Petromyzon/genetics/*metabolism ; *Phylogeny ; Prognosis ; Proton-Translocating ATPases/genetics/*metabolism ; Sequence Homology, Amino Acid ; Survival Rate ; }, abstract = {The ATPase cation transporting 13A2 protein (ATP13A2), which maintains the homeostasis of mitochondria and lysosomes, plays a significant role in human neurodegenerative diseases and cancer. Through constructing a lamprey proteome database, employing multiple sequence alignment and phylogenetic analysis, 5 ATP13A2 proteins from Petromyzon marinus (Pm-ATP13A2) were identified based on the evolutionary perspective. The motif and domain analysis showed that the ATP13A2 protein was conserved. The multiple phosphorylation sites and transmembrane structures highlighted the characteristics of ATP13A2 as the P-ATPase-V cation transporting protein. Based on the information provided by the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, this study was conducted as a preliminary investigation of the carcinogenic effects of the ATP13A2 gene in a variety of tumors. The ATP13A2 was strongly expressed in most tumors, except in two types of nervous system tumors glioblastoma multiforme (GBM) and brain lower grade glioma (LGG). Moreover, the expression of ATP13A2 was strongly correlated with the prognosis of tumor patients. The high expression of ATP13A2 was obviously related to the poor prognosis of LGG. The poor prognosis of LGG patients may affect the ATP13A2 expression through the immune cells and radiotherapy. Also, cancer-related fibroblast infiltration was observed. All in all, this work offers more insights into the molecular evolution of the ATP13A2 protein and facilitates the understanding of the carcinogenic effects of the ATP13A2 in different tumors. Our discussion also promotes the study into the successful evolution of the vertebrate brain and the mechanism of clinical brain-related diseases.}, } @article {pmid33743097, year = {2021}, author = {Ressaissi, Y and Amills, M and Noce, A and Ben Hamouda, M}, title = {Characterizing the Mitochondrial Diversity of Arbi Goats from Tunisia.}, journal = {Biochemical genetics}, volume = {59}, number = {5}, pages = {1225-1232}, pmid = {33743097}, issn = {1573-4927}, support = {AGL2016-76108-R//Ministerio de Economía y Competitividad/ ; }, mesh = {Animals ; DNA, Mitochondrial/analysis/*genetics ; *Genetic Variation ; Goats ; *Haplotypes ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA/*methods ; Tunisia ; }, abstract = {Arbi is one of the main local goat breeds in Tunisia, representing an important economic resource in arid and hot areas where cattle and sheep cannot thrive successfully. In the current work, we have characterized the mitochondrial diversity of 26 Arbi goats by partially sequencing the mitochondrial D-loop region. These sequences plus 10 retrieved from GenBank were analyzed with the DnaSP v.5.10.1, evidencing the existence of 12 different haplotypes. Nucleotide and haplotype diversities were 0.02 and 0.96. Moreover, median-joining network analysis showed that all D-loop sequences from Arbi goats correspond to haplogroup A and that in general they do not cluster with sequences from other goat breeds. The high diversity that has been observed in North African goats is compatible with the maritime diffusion of the Neolithic package 10,000-7000 YBP. Moreover, there are evidences that local Tunisian breeds have been extensively crossed with highly productive transboundary breeds in order to improve meat and milk yields. These uncontrolled crossing practices may lead to the loss of alleles that play key roles in the adaptation of Tunisian local breeds to a harsh environment.}, } @article {pmid33744400, year = {2021}, author = {Lazcano, A and Peretó, J}, title = {Prokaryotic symbiotic consortia and the origin of nucleated cells: A critical review of Lynn Margulis hypothesis.}, journal = {Bio Systems}, volume = {204}, number = {}, pages = {104408}, doi = {10.1016/j.biosystems.2021.104408}, pmid = {33744400}, issn = {1872-8324}, mesh = {Basal Bodies ; *Biological Evolution ; Cell Movement ; Centromere ; *Eukaryotic Cells ; Flagella ; Genome, Mitochondrial ; Genome, Plastid ; Microbial Consortia ; Organelles/genetics ; *Prokaryotic Cells ; *Symbiosis ; }, abstract = {The publication in the late 1960s of Lynn Margulis endosymbiotic proposal is a scientific milestone that brought to the fore of evolutionary discussions the issue of the origin of nucleated cells. Although it is true that the times were ripe, the timely publication of Lynn Margulis' original paper was the product of an intellectually bold 29-years old scientist, who based on the critical analysis of the available scientific information produced an all-encompassing, sophisticated narrative scheme on the origin of eukaryotic cells as a result of the evolution of prokaryotic consortia and, in bold intellectual stroke, put it all in the context of planetary evolution. A critical historical reassessment of her original proposal demonstrates that her hypothesis was not a simple archival outline of past schemes, but a renewed historical narrative of prokaryotic evolution and the role of endosymbiosis in the origin of eukaryotes. Although it is now accepted that the closest bacterial relatives of mitochondria and plastids are α-proteobacteria and cyanobacteria, respectively, comparative genomics demonstrates the mosaic character of the organelle genomes. The available evidence has completely refuted Margulis' proposal of an exogenous origin for eukaryotic flagella, the (9 + 2) basal bodies, and centromeres, but we discuss in detail the reasons that led her to devote considerable efforts to argue for a symbiotic origin of the eukaryotic motility. An analysis of the arguments successfully employed by Margulis in her persuasive advocacy of endosymbiosis, combined with the discussions of her flaws and the scientific atmosphere during the period in which she formulated her proposals, are critical for a proper appraisal of the historical conditions that shaped her theory and its acceptance.}, } @article {pmid33746976, year = {2021}, author = {Shariq, M and Quadir, N and Sharma, N and Singh, J and Sheikh, JA and Khubaib, M and Hasnain, SE and Ehtesham, NZ}, title = {Mycobacterium tuberculosis RipA Dampens TLR4-Mediated Host Protective Response Using a Multi-Pronged Approach Involving Autophagy, Apoptosis, Metabolic Repurposing, and Immune Modulation.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {636644}, pmid = {33746976}, issn = {1664-3224}, mesh = {Animals ; Apoptosis ; Autophagy ; Bacterial Proteins/genetics/*metabolism ; Cell Differentiation ; HEK293 Cells ; Host-Pathogen Interactions ; Humans ; Immunity, Innate ; Immunomodulation ; Macrophages/*immunology ; Mice ; Mitochondria/*metabolism ; Mycobacterium tuberculosis/*physiology ; NF-kappa B/metabolism ; RAW 264.7 Cells ; Signal Transduction ; Toll-Like Receptor 4/*metabolism ; }, abstract = {Reductive evolution has endowed Mycobacterium tuberculosis (M. tb) with moonlighting in protein functions. We demonstrate that RipA (Rv1477), a peptidoglycan hydrolase, activates the NFκB signaling pathway and elicits the production of pro-inflammatory cytokines, TNF-α, IL-6, and IL-12, through the activation of an innate immune-receptor, toll-like receptor (TLR)4. RipA also induces an enhanced expression of macrophage activation markers MHC-II, CD80, and CD86, suggestive of M1 polarization. RipA harbors LC3 (Microtubule-associated protein 1A/1B-light chain 3) motifs known to be involved in autophagy regulation and indeed alters the levels of autophagy markers LC3BII and P62/SQSTM1 (Sequestosome-1), along with an increase in the ratio of P62/Beclin1, a hallmark of autophagy inhibition. The use of pharmacological agents, rapamycin and bafilomycin A1, reveals that RipA activates PI3K-AKT-mTORC1 signaling cascade that ultimately culminates in the inhibition of autophagy initiating kinase ULK1 (Unc-51 like autophagy activating kinase). This inhibition of autophagy translates into efficient intracellular survival, within macrophages, of recombinant Mycobacterium smegmatis expressing M. tb RipA. RipA, which also localizes into mitochondria, inhibits the production of oxidative phosphorylation enzymes to promote a Warburg-like phenotype in macrophages that favors bacterial replication. Furthermore, RipA also inhibited caspase-dependent programed cell death in macrophages, thus hindering an efficient innate antibacterial response. Collectively, our results highlight the role of an endopeptidase to create a permissive replication niche in host cells by inducing the repression of autophagy and apoptosis, along with metabolic reprogramming, and pointing to the role of RipA in disease pathogenesis.}, } @article {pmid33750312, year = {2021}, author = {Cheng, Y and He, X and Priyadarshani, SVGN and Wang, Y and Ye, L and Shi, C and Ye, K and Zhou, Q and Luo, Z and Deng, F and Cao, L and Zheng, P and Aslam, M and Qin, Y}, title = {Assembly and comparative analysis of the complete mitochondrial genome of Suaeda glauca.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {167}, pmid = {33750312}, issn = {1471-2164}, support = {31671267//National Natural Science Foundation of China/ ; 31970333//National Natural Science Foundation of China/ ; }, mesh = {*Chenopodiaceae/genetics ; Genome Size ; *Genome, Chloroplast ; *Genome, Mitochondrial ; Phylogeny ; }, abstract = {BACKGROUND: Suaeda glauca (S. glauca) is a halophyte widely distributed in saline and sandy beaches, with strong saline-alkali tolerance. It is also admired as a landscape plant with high development prospects and scientific research value. The S. glauca chloroplast (cp) genome has recently been reported; however, the mitochondria (mt) genome is still unexplored.

RESULTS: The mt genome of S. glauca were assembled based on the reads from Pacbio and Illumina sequencing platforms. The circular mt genome of S. glauca has a length of 474,330 bp. The base composition of the S. glauca mt genome showed A (28.00%), T (27.93%), C (21.62%), and G (22.45%). S. glauca mt genome contains 61 genes, including 27 protein-coding genes, 29 tRNA genes, and 5 rRNA genes. The sequence repeats, RNA editing, and gene migration from cp to mt were observed in S. glauca mt genome. Phylogenetic analysis based on the mt genomes of S. glauca and other 28 taxa reflects an exact evolutionary and taxonomic status of S. glauca. Furthermore, the investigation on mt genome characteristics, including genome size, GC contents, genome organization, and gene repeats of S. gulaca genome, was investigated compared to other land plants, indicating the variation of the mt genome in plants. However, the subsequently Ka/Ks analysis revealed that most of the protein-coding genes in mt genome had undergone negative selections, reflecting the importance of those genes in the mt genomes.

CONCLUSIONS: In this study, we reported the mt genome assembly and annotation of a halophytic model plant S. glauca. The subsequent analysis provided us a comprehensive understanding of the S. glauca mt genome, which might facilitate the research on the salt-tolerant plant species.}, } @article {pmid33751391, year = {2021}, author = {Yi, CH and Yoon, M and Kim, JM and Kim, IH and Cho, IY and An, HS}, title = {Genetic analysis and population genetic structure of hard-shelled mussel, Mytilus coruscus Gould 1861 (Mytiloida: Mytilidae) from the coasts of South Korea based on mitochondrial cytochrome oxidase (COI) gene sequences.}, journal = {Genes & genomics}, volume = {43}, number = {6}, pages = {577-585}, pmid = {33751391}, issn = {2092-9293}, mesh = {Animals ; Bivalvia/enzymology/*genetics ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/*genetics ; Genetic Variation/genetics ; Genetics, Population ; Haplotypes/genetics ; Humans ; Microsatellite Repeats/genetics ; Mitochondria/*enzymology ; Mytilus/enzymology/*genetics ; Phylogeny ; Republic of Korea ; }, abstract = {BACKGROUND: Mytilus coruscus Gould, 1861 is a mussel species in the family Mytilidae, native to the Northwest Pacific Ocean, ranging from the East China Sea, the Yellow Sea, and as far as the Peter the Great Gulf in the East Sea. In Korea, this species has been heavily exploited for nutrient-rich food resources and experienced severe reduction in their population.

OBJECTIVE: The aim of this study was to investigate the genetic diversity and population structure and to provide baseline data to facilitate the conservation and sustainable use of the vulnerable species M. coruscus in South Korea.

METHODS: Mitochondrial DNA (mtDNA) cytochrome c oxidase I (COI) sequences of 91 adult individuals from four islands and one coastal localities in South Korea were sequenced. We then compared genetic diversity and haplotype data with previously published Chinese wild populations.

RESULTS: Mytilus coruscus populations on Korean coasts were found to exhibit high genetic diversity despite concerns regarding recent population reduction. A total of 42 haplotypes were defined by 56 polymorphic sites. High-level genetic diversity was observed on four Island sites (Hd = 0.906-0.955, π = 0.0068-0.0090). The other seashore site represented relatively lower genetic diversity (Hd = 0.529, π = 0.0011) and was genetically differentiated from the others. In a previous study, wild populations on the East China Sea exhibited similarly high genetic diversity as that observed in our study. Additionally, Chinese M. coruscus populations exhibit a distinct regional haplotype distribution pattern while sharing six haplotypes with Korean populations.

CONCLUSIONS: The results of this study provide insights that further the current understanding regarding the evolution of M. coruscus species and provides comprehensive genetic data to facilitate the development of an effective conservation strategy.}, } @article {pmid33770399, year = {2021}, author = {Bazer, FW and Seo, H and Johnson, GA and Wu, G}, title = {One-Carbon Metabolism and Development of the Conceptus During Pregnancy: Lessons from Studies with Sheep and Pigs.}, journal = {Advances in experimental medicine and biology}, volume = {1285}, number = {}, pages = {1-15}, pmid = {33770399}, issn = {0065-2598}, mesh = {Animals ; Carbon ; *Embryo, Mammalian ; Endometrium ; Female ; Fetal Development ; *Interferon Type I ; Placenta ; Pregnancy ; Sheep ; Swine ; Uterus ; }, abstract = {The pregnancy recognition signal from the conceptus (embryo/fetus and associated membranes) to the mother is interferon tau (IFNT) in ruminants and estradiol, possibly in concert with interferons gamma and delta in pigs. Those pregnancy recognition signals silence expression of interferon stimulated genes (ISG) in uterine luminal (LE) and superficial glandular (sGE) epithelia while inducing expression of genes for transport of nutrients, including glucose and amino acids, into the uterine lumen to support growth and development of the conceptus. In sheep and pigs, glucose not utilized immediately by the conceptus is converted to fructose. Glucose, fructose, serine and glycine in uterine histotroph can contribute to one carbon (1C) metabolism that provides one-carbon groups for the synthesis of purines and thymidylate, as well as S-adenosylmethionine for epigenetic methylation reactions. Serine and glycine are transported into the mitochondria of cells and metabolized to formate that is transported into the cytoplasm for the synthesis of purines, thymidine and S-adenosylmethionine. The unique aspects of one-carbon metabolism are discussed in the context of the hypoxic uterine environment, aerobic glycolysis, and similarities in metabolism between cancer cells and cells of the rapidly developing fetal-placental tissues during pregnancy. Further, the evolution of anatomical and functional aspects of the placentae of sheep and pigs versus primates is discussed in the context of mechanisms to efficiently obtain, store and utilize nutrients required for rapid fetal growth in the last one-half of gestation.}, } @article {pmid33791336, year = {2021}, author = {Mortz, M and Levivier, A and Lartillot, N and Dufresne, F and Blier, PU}, title = {Long-Lived Species of Bivalves Exhibit Low MT-DNA Substitution Rates.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {626042}, pmid = {33791336}, issn = {2296-889X}, abstract = {Bivalves represent valuable taxonomic group for aging studies given their wide variation in longevity (from 1-2 to >500 years). It is well known that aging is associated to the maintenance of Reactive Oxygen Species homeostasis and that mitochondria phenotype and genotype dysfunctions accumulation is a hallmark of these processes. Previous studies have shown that mitochondrial DNA mutation rates are linked to lifespan in vertebrate species, but no study has explored this in invertebrates. To this end, we performed a Bayesian Phylogenetic Covariance model of evolution analysis using 12 mitochondrial protein-coding genes of 76 bivalve species. Three life history traits (maximum longevity, generation time and mean temperature tolerance) were tested against 1) synonymous substitution rates (dS), 2) conservative amino acid replacement rates (Kc) and 3) ratios of radical over conservative amino acid replacement rates (Kr/Kc). Our results confirm the already known correlation between longevity and generation time and show, for the first time in an invertebrate class, a significant negative correlation between dS and longevity. This correlation was not as strong when generation time and mean temperature tolerance variations were also considered in our model (marginal correlation), suggesting a confounding effect of these traits on the relationship between longevity and mtDNA substitution rate. By confirming the negative correlation between dS and longevity previously documented in birds and mammals, our results provide support for a general pattern in substitution rates.}, } @article {pmid33793863, year = {2021}, author = {Considine, MJ and Foyer, CH}, title = {Oxygen and reactive oxygen species-dependent regulation of plant growth and development.}, journal = {Plant physiology}, volume = {186}, number = {1}, pages = {79-92}, pmid = {33793863}, issn = {1532-2548}, mesh = {Oxygen/*metabolism ; Plant Development/*physiology ; Reactive Oxygen Species/*metabolism ; }, abstract = {Oxygen and reactive oxygen species (ROS) have been co-opted during evolution into the regulation of plant growth, development, and differentiation. ROS and oxidative signals arising from metabolism or phytohormone-mediated processes control almost every aspect of plant development from seed and bud dormancy, liberation of meristematic cells from the quiescent state, root and shoot growth, and architecture, to flowering and seed production. Moreover, the phytochrome and phytohormone-dependent transmissions of ROS waves are central to the systemic whole plant signaling pathways that integrate root and shoot growth. The sensing of oxygen availability through the PROTEOLYSIS 6 (PRT6) N-degron pathway functions alongside ROS production and signaling but how these pathways interact in developing organs remains poorly understood. Considerable progress has been made in our understanding of the nature of hydrogen peroxide sensors and the role of thiol-dependent signaling networks in the transmission of ROS signals. Reduction/oxidation (redox) changes in the glutathione (GSH) pool, glutaredoxins (GRXs), and thioredoxins (TRXs) are important in the control of growth mediated by phytohormone pathways. Although, it is clear that the redox states of proteins involved in plant growth and development are controlled by the NAD(P)H thioredoxin reductase (NTR)/TRX and reduced GSH/GRX systems of the cytosol, chloroplasts, mitochondria, and nucleus, we have only scratched the surface of this multilayered control and how redox-regulated processes interact with other cell signaling systems.}, } @article {pmid33798681, year = {2021}, author = {Ennis, CC and Haeffner, NN and Keyser, CD and Leonard, ST and Macdonald-Shedd, AC and Savoie, AM and Cronin, TJ and Veldsman, WP and Barden, P and Chak, STC and Baeza, JA}, title = {Comparative mitochondrial genomics of sponge-dwelling snapping shrimps in the genus Synalpheus: Exploring differences between eusocial and non-eusocial species and insights into phylogenetic relationships in caridean shrimps.}, journal = {Gene}, volume = {786}, number = {}, pages = {145624}, doi = {10.1016/j.gene.2021.145624}, pmid = {33798681}, issn = {1879-0038}, mesh = {Animals ; Codon Usage ; Decapoda/*classification/genetics ; Genome Size ; Genome, Mitochondrial ; Genomics/*methods ; Mitochondria/*genetics ; Phylogeny ; RNA, Transfer/genetics ; Selection, Genetic ; }, abstract = {The genus Synalpheus is a cosmopolitan clade of marine shrimps found in most tropical regions. Species in this genus exhibit a range of social organizations, including pair-forming, communal breeding, and eusociality, the latter only known to have evolved within this genus in the marine realm. This study examines the complete mitochondrial genomes of seven species of Synalpheus and explores differences between eusocial and non-eusocial species considering that eusociality has been shown before to affect the strength of purifying selection in mitochondrial protein coding genes. The AT-rich mitochondrial genomes of Synalpheus range from 15,421 bp to 15,782 bp in length and comprise, invariably, 13 protein-coding genes (PCGs), two ribosomal RNA genes, and 22 transfer RNA genes. A 648 bp to 994 bp long intergenic space is assumed to be the D-loop. Mitochondrial gene synteny is identical among the studied shrimps. No major differences occur between eusocial and non-eusocial species in nucleotide composition and codon usage profiles of PCGs and in the secondary structure of tRNA genes. Maximum likelihood phylogenetic analysis of the complete concatenated PCG complement of 90 species supports the monophyly of the genus Synalpheus and its family Alpheidae. Moreover, the monophyletic status of the caridean families Alvinocaridae, Atyidae, Thoridae, Lysmatidae, Palaemonidae, and Pandalidae within caridean shrimps are fully or highly supported by the analysis. We therefore conclude that mitochondrial genomes contain sufficient phylogenetic information to resolve relationships at high taxonomic levels within the Caridea. Our analysis of mitochondrial genomes in the genus Synalpheus contributes to the understanding of the coevolution between genomic architecture and sociality in caridean shrimps and other marine organisms.}, } @article {pmid33802618, year = {2021}, author = {Zhang, T and Li, C and Zhang, X and Wang, C and Roger, AJ and Gao, F}, title = {Characterization and Comparative Analyses of Mitochondrial Genomes in Single-Celled Eukaryotes to Shed Light on the Diversity and Evolution of Linear Molecular Architecture.}, journal = {International journal of molecular sciences}, volume = {22}, number = {5}, pages = {}, pmid = {33802618}, issn = {1422-0067}, support = {31922013//National Natural Science Foundation of China/ ; 32030015//National Natural Science Foundation of China/ ; 31772428//National Natural Science Foundation of China/ ; 201841013//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Amino Acid Sequence ; Cells, Cultured ; Eukaryota/*genetics ; Eukaryotic Cells/physiology ; Evolution, Molecular ; Genome, Mitochondrial/*genetics ; Mitogens/genetics ; Phylogeny ; Plankton/genetics ; Replication Origin/genetics ; }, abstract = {Determination and comparisons of complete mitochondrial genomes (mitogenomes) are important to understand the origin and evolution of mitochondria. Mitogenomes of unicellular protists are particularly informative in this regard because they are gene-rich and display high structural diversity. Ciliates are a highly diverse assemblage of protists and their mitogenomes (linear structure with high A+T content in general) were amongst the first from protists to be characterized and have provided important insights into mitogenome evolution. Here, we report novel mitogenome sequences from three representatives (Strombidium sp., Strombidium cf. sulcatum, and Halteria grandinella) in two dominant ciliate lineages. Comparative and phylogenetic analyses of newly sequenced and previously published ciliate mitogenomes were performed and revealed a number of important insights. We found that the mitogenomes of these three species are linear molecules capped with telomeric repeats that differ greatly among known species. The genomes studied here are highly syntenic, but larger in size and more gene-rich than those of other groups. They also all share an AT-rich tandem repeat region which may serve as the replication origin and modulate initiation of bidirectional transcription. More generally we identified a split version of ccmf, a cytochrome c maturation-related gene that might be a derived character uniting taxa in the subclasses Hypotrichia and Euplotia. Finally, our mitogenome comparisons and phylogenetic analyses support to reclassify Halteria grandinella from the subclass Oligotrichia to the subclass Hypotrichia. These results add to the growing literature on the unique features of ciliate mitogenomes, shedding light on the diversity and evolution of their linear molecular architecture.}, } @article {pmid33803147, year = {2021}, author = {Arcila-Galvis, JE and Arango, RE and Torres-Bonilla, JM and Arias, T}, title = {The Mitochondrial Genome of a Plant Fungal Pathogen Pseudocercospora fijiensis (Mycosphaerellaceae), Comparative Analysis and Diversification Times of the Sigatoka Disease Complex Using Fossil Calibrated Phylogenies.}, journal = {Life (Basel, Switzerland)}, volume = {11}, number = {3}, pages = {}, pmid = {33803147}, issn = {2075-1729}, support = {221356934854//Instituto para el desarrollo de la Ciencia y la Tecnología "Francisco José de Caldas/ ; 755-2017//Jovenes Investigadores e Innovadores por la Paz convocatoria/ ; }, abstract = {Mycosphaerellaceae is a highly diverse fungal family containing a variety of pathogens affecting many economically important crops. Mitochondria play a crucial role in fungal metabolism and in the study of fungal evolution. This study aims to: (i) describe the mitochondrial genome of Pseudocercospora fijiensis, and (ii) compare it with closely related species (Sphaerulina musiva, S. populicola, P. musae and P. eumusae) available online, paying particular attention to the Sigatoka disease's complex causal agents. The mitochondrial genome of P. fijiensis is a circular molecule of 74,089 bp containing typical genes coding for the 14 proteins related to oxidative phosphorylation, 2 rRNA genes and a set of 38 tRNAs. P. fijiensis mitogenome has two truncated cox1 copies, and bicistronic transcription of nad2-nad3 and atp6-atp8 confirmed experimentally. Comparative analysis revealed high variability in size and gene order among selected Mycosphaerellaceae mitogenomes likely to be due to rearrangements caused by mobile intron invasion. Using fossil calibrated Bayesian phylogenies, we found later diversification times for Mycosphaerellaceae (66.6 MYA) and the Sigatoka disease complex causal agents, compared to previous strict molecular clock studies. An early divergent Pseudocercospora fijiensis split from the sister species P. musae + P. eumusae 13.31 MYA while their sister group, the sister species P. eumusae and P. musae, split from their shared common ancestor in the late Miocene 8.22 MYA. This newly dated phylogeny suggests that species belonging to the Sigatoka disease complex originated after wild relatives of domesticated bananas (section Eumusae; 27.9 MYA). During this time frame, mitochondrial genomes expanded significantly, possibly due to invasions of introns into different electron transport chain genes.}, } @article {pmid33803683, year = {2021}, author = {Proulex, GCR and Meade, MJ and Manoylov, KM and Cahoon, AB}, title = {Mitochondrial mRNA Processing in the Chlorophyte Alga Pediastrum duplex and Streptophyte Alga Chara vulgaris Reveals an Evolutionary Branch in Mitochondrial mRNA Processing.}, journal = {Plants (Basel, Switzerland)}, volume = {10}, number = {3}, pages = {}, pmid = {33803683}, issn = {2223-7747}, abstract = {Mitochondria carry the remnant of an ancestral bacterial chromosome and express those genes with a system separate and distinct from the nucleus. Mitochondrial genes are transcribed as poly-cistronic primary transcripts which are post-transcriptionally processed to create individual translationally competent mRNAs. Algae post-transcriptional processing has only been explored in Chlamydomonas reinhardtii (Class: Chlorophyceae) and the mature mRNAs are different than higher plants, having no 5' UnTranslated Regions (UTRs), much shorter and more variable 3' UTRs and polycytidylated mature mRNAs. In this study, we analyzed transcript termini using circular RT-PCR and PacBio Iso-Seq to survey the 3' and 5' UTRs and termini for two green algae, Pediastrum duplex (Class: Chlorophyceae) and Chara vulgaris (Class: Charophyceae). This enabled the comparison of processing in the chlorophyte and charophyte clades of green algae to determine if the differences in mitochondrial mRNA processing pre-date the invasion of land by embryophytes. We report that the 5' mRNA termini and non-template 3' termini additions in P. duplex resemble those of C. reinhardtii, suggesting a conservation of mRNA processing among the chlorophyceae. We also report that C. vulgaris mRNA UTRs are much longer than chlorophytic examples, lack polycytidylation, and are polyadenylated similar to embryophytes. This demonstrates that some mitochondrial mRNA processing events diverged with the split between chlorophytic and streptophytic algae.}, } @article {pmid33805166, year = {2021}, author = {Lyu, D and Zajonc, J and Pagé, A and Tanney, CAS and Shah, A and Monjezi, N and Msimbira, LA and Antar, M and Nazari, M and Backer, R and Smith, DL}, title = {Plant Holobiont Theory: The Phytomicrobiome Plays a Central Role in Evolution and Success.}, journal = {Microorganisms}, volume = {9}, number = {4}, pages = {}, pmid = {33805166}, issn = {2076-2607}, support = {G250030 AAFC BioFuelNet//Agriculture and Agri-Food Canada/ ; RGPIN 2020-07047.//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {Under natural conditions, plants are always associated with a well-orchestrated community of microbes-the phytomicrobiome. The nature and degree of microbial effect on the plant host can be positive, neutral, or negative, and depends largely on the environment. The phytomicrobiome is integral for plant growth and function; microbes play a key role in plant nutrient acquisition, biotic and abiotic stress management, physiology regulation through microbe-to-plant signals, and growth regulation via the production of phytohormones. Relationships between the plant and phytomicrobiome members vary in intimacy, ranging from casual associations between roots and the rhizosphere microbial community, to endophytes that live between plant cells, to the endosymbiosis of microbes by the plant cell resulting in mitochondria and chloroplasts. If we consider these key organelles to also be members of the phytomicrobiome, how do we distinguish between the two? If we accept the mitochondria and chloroplasts as both members of the phytomicrobiome and the plant (entrained microbes), the influence of microbes on the evolution of plants becomes so profound that without microbes, the concept of the "plant" is not viable. This paper argues that the holobiont concept should take greater precedence in the plant sciences when referring to a host and its associated microbial community. The inclusivity of this concept accounts for the ambiguous nature of the entrained microbes and the wide range of functions played by the phytomicrobiome in plant holobiont homeostasis.}, } @article {pmid33805626, year = {2021}, author = {Schirrmacher, V}, title = {Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications.}, journal = {Biomedicines}, volume = {9}, number = {3}, pages = {}, pmid = {33805626}, issn = {2227-9059}, abstract = {A dose-response relationship to stressors, according to the hormesis theory, is characterized by low-dose stimulation and high-dose inhibition. It is non-linear with a low-dose optimum. Stress responses by cells lead to adapted vitality and fitness. Physical stress can be exerted through heat, radiation, or physical exercise. Chemical stressors include reactive species from oxygen (ROS), nitrogen (RNS), and carbon (RCS), carcinogens, elements, such as lithium (Li) and silicon (Si), and metals, such as silver (Ag), cadmium (Cd), and lead (Pb). Anthropogenic chemicals are agrochemicals (phytotoxins, herbicides), industrial chemicals, and pharmaceuticals. Biochemical stress can be exerted through toxins, medical drugs (e.g., cytostatics, psychopharmaceuticals, non-steroidal inhibitors of inflammation), and through fasting (dietary restriction). Key-lock interactions between enzymes and substrates, antigens and antibodies, antigen-presenting cells, and cognate T cells are the basics of biology, biochemistry, and immunology. Their rules do not obey linear dose-response relationships. The review provides examples of biologic stressors: oncolytic viruses (e.g., immuno-virotherapy of cancer) and hormones (e.g., melatonin, stress hormones). Molecular mechanisms of cellular stress adaptation involve the protein quality control system (PQS) and homeostasis of proteasome, endoplasmic reticulum, and mitochondria. Important components are transcription factors (e.g., Nrf2), micro-RNAs, heat shock proteins, ionic calcium, and enzymes (e.g., glutathion redox enzymes, DNA methyltransferases, and DNA repair enzymes). Cellular growth control, intercellular communication, and resistance to stress from microbial infections involve growth factors, cytokines, chemokines, interferons, and their respective receptors. The effects of hormesis during evolution are multifarious: cell protection and survival, evolutionary flexibility, and epigenetic memory. According to the hormesis theory, this is true for the entire biosphere, e.g., archaia, bacteria, fungi, plants, and the animal kingdoms.}, } @article {pmid33807111, year = {2021}, author = {Maár, K and Varga, GIB and Kovács, B and Schütz, O and Maróti, Z and Kalmár, T and Nyerki, E and Nagy, I and Latinovics, D and Tihanyi, B and Marcsik, A and Pálfi, G and Bernert, Z and Gallina, Z and Varga, S and Költő, L and Raskó, I and Török, T and Neparáczki, E}, title = {Maternal Lineages from 10-11th Century Commoner Cemeteries of the Carpathian Basin.}, journal = {Genes}, volume = {12}, number = {3}, pages = {}, pmid = {33807111}, issn = {2073-4425}, mesh = {Cemeteries ; DNA, Mitochondrial/*genetics ; Genetics, Population ; Haplotypes ; High-Throughput Nucleotide Sequencing ; History, Medieval ; Humans ; Hungary/ethnology ; Maternal Inheritance ; Mitochondria/*genetics ; Phylogeny ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/*methods ; Transients and Migrants/*history ; }, abstract = {Nomadic groups of conquering Hungarians played a predominant role in Hungarian prehistory, but genetic data are available only from the immigrant elite strata. Most of the 10-11th century remains in the Carpathian Basin belong to common people, whose origin and relation to the immigrant elite have been widely debated. Mitogenome sequences were obtained from 202 individuals with next generation sequencing combined with hybridization capture. Median joining networks were used for phylogenetic analysis. The commoner population was compared to 87 ancient Eurasian populations with sequence-based (Fst) and haplogroup-based population genetic methods. The haplogroup composition of the commoner population markedly differs from that of the elite, and, in contrast to the elite, commoners cluster with European populations. Alongside this, detectable sub-haplogroup sharing indicates admixture between the elite and the commoners. The majority of the 10-11th century commoners most likely represent local populations of the Carpathian Basin, which admixed with the eastern immigrant groups (which included conquering Hungarians).}, } @article {pmid33807810, year = {2021}, author = {S Ten, V and Stepanova, AA and Ratner, V and Neginskaya, M and Niatsetskaya, Z and Sosunov, S and Starkov, A}, title = {Mitochondrial Dysfunction and Permeability Transition in Neonatal Brain and Lung Injuries.}, journal = {Cells}, volume = {10}, number = {3}, pages = {}, pmid = {33807810}, issn = {2073-4409}, support = {P01 AG014930/AG/NIA NIH HHS/United States ; R01 NS099109/NS/NINDS NIH HHS/United States ; R01 NS100850/NS/NINDS NIH HHS/United States ; }, mesh = {Brain Injuries/*physiopathology ; Humans ; Infant, Newborn ; Lung Injury/*physiopathology ; Mitochondria/*metabolism/pathology ; Permeability ; }, abstract = {This review discusses the potential mechanistic role of abnormally elevated mitochondrial proton leak and mitochondrial bioenergetic dysfunction in the pathogenesis of neonatal brain and lung injuries associated with premature birth. Providing supporting evidence, we hypothesized that mitochondrial dysfunction contributes to postnatal alveolar developmental arrest in bronchopulmonary dysplasia (BPD) and cerebral myelination failure in diffuse white matter injury (WMI). This review also analyzes data on mitochondrial dysfunction triggered by activation of mitochondrial permeability transition pore(s) (mPTP) during the evolution of perinatal hypoxic-ischemic encephalopathy. While the still cryptic molecular identity of mPTP continues to be a subject for extensive basic science research efforts, the translational significance of mitochondrial proton leak received less scientific attention, especially in diseases of the developing organs. This review is focused on the potential mechanistic relevance of mPTP and mitochondrial dysfunction to neonatal diseases driven by developmental failure of organ maturation or by acute ischemia-reperfusion insult during development.}, } @article {pmid33808521, year = {2021}, author = {Gînguță, A and Rusu, I and Mircea, C and Ioniță, A and Banciu, HL and Kelemen, B}, title = {Mitochondrial DNA Profiles of Individuals from a 12th Century Necropolis in Feldioara (Transylvania).}, journal = {Genes}, volume = {12}, number = {3}, pages = {}, pmid = {33808521}, issn = {2073-4425}, mesh = {Asia/ethnology ; DNA, Ancient/*analysis ; DNA, Mitochondrial/genetics/*history ; Genetics, Population ; History, Medieval ; Humans ; Mitochondria/*genetics ; Phylogeny ; Population Dynamics ; Romania/ethnology ; White People/*genetics ; }, abstract = {The genetic signature of modern Europeans is the cumulated result of millennia of discrete small-scale exchanges between multiple distinct population groups that performed a repeated cycle of movement, settlement, and interactions with each other. In this study we aimed to highlight one such minute genetic cycle in a sea of genetic interactions by reconstructing part of the genetic story of the migration, settlement, interaction, and legacy of what is today the Transylvanian Saxon. The analysis of the mitochondrial DNA control region of 13 medieval individuals from Feldioara necropolis (Transylvania region, Romania) reveals a genetically heterogeneous group where all identified haplotypes are different. Most of the perceived maternal lineages are of Western Eurasian origin, except for the Central Asiatic haplogroup C seen in only one sample. Comparisons with historical and modern populations describe the contribution of the investigated Saxon settlers to the genetic history of this part of Europe.}, } @article {pmid33809280, year = {2021}, author = {Kusliy, MA and Vorobieva, NV and Tishkin, AA and Makunin, AI and Druzhkova, AS and Trifonov, VA and Iderkhangai, TO and Graphodatsky, AS}, title = {Traces of Late Bronze and Early Iron Age Mongolian Horse Mitochondrial Lineages in Modern Populations.}, journal = {Genes}, volume = {12}, number = {3}, pages = {}, pmid = {33809280}, issn = {2073-4425}, mesh = {Animals ; China ; DNA, Mitochondrial/genetics ; Genetic Variation/genetics ; Genome, Mitochondrial/genetics ; Haplotypes/genetics ; Horses/*genetics ; Italy ; Middle East ; Mitochondria/*genetics ; Mongolia ; }, abstract = {The Mongolian horse is one of the most ancient and relatively unmanaged horse breeds. The population history of the Mongolian horse remains poorly understood due to a lack of information on ancient and modern DNA. Here, we report nearly complete mitochondrial genome data obtained from five ancient Mongolian horse samples of the Khereksur and Deer Stone culture (late 2nd to 1st third of the 1st millennium BC) and one ancient horse specimen from the Xiongnu culture (1st century BC to 1st century AD) using target enrichment and high-throughput sequencing methods. Phylogenetic analysis involving ancient, historical, and modern mitogenomes of horses from Mongolia and other regions showed the presence of three mitochondrial haplogroups in the ancient Mongolian horse populations studied here and similar haplotype composition of ancient and modern horse populations of Mongolia. Our results revealed genetic continuity between the Mongolian horse populations of the Khereksur and Deer Stone culture and those of the Xiongnu culture owing to the presence of related mitotypes. Besides, we report close phylogenetic relationships between haplotypes of the Khereksur and Deer Stone horses and the horses of indigenous breeds of the Middle East (Caspian and Iranian), China (Naqu, Yunnan, and Jinjiang), and Italy (Giara) as well as genetic similarity between the Xiongnu Mongolian horses and those of the most ancient breeds of the Middle East (Arabian) and Central Asia (Akhal-Teke). Despite all the migrations of the Mongolian peoples over the past 3000 years, mitochondrial haplogroup composition of Mongolian horse populations remains almost unchanged.}, } @article {pmid33811236, year = {2021}, author = {Alqahtani, AA and Jansen, RK}, title = {The evolutionary fate of rpl32 and rps16 losses in the Euphorbia schimperi (Euphorbiaceae) plastome.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {7466}, pmid = {33811236}, issn = {2045-2322}, mesh = {Amino Acid Sequence ; Cell Nucleus/genetics ; Euphorbia/*genetics ; *Evolution, Molecular ; Gene Expression Regulation, Plant ; *Genome, Plastid ; Likelihood Functions ; Phylogeny ; Plant Proteins/chemistry/*genetics ; Ribosomal Proteins/chemistry/*genetics ; Transcriptome/genetics ; }, abstract = {Gene transfers from mitochondria and plastids to the nucleus are an important process in the evolution of the eukaryotic cell. Plastid (pt) gene losses have been documented in multiple angiosperm lineages and are often associated with functional transfers to the nucleus or substitutions by duplicated nuclear genes targeted to both the plastid and mitochondrion. The plastid genome sequence of Euphorbia schimperi was assembled and three major genomic changes were detected, the complete loss of rpl32 and pseudogenization of rps16 and infA. The nuclear transcriptome of E. schimperi was sequenced to investigate the transfer/substitution of the rpl32 and rps16 genes to the nucleus. Transfer of plastid-encoded rpl32 to the nucleus was identified previously in three families of Malpighiales, Rhizophoraceae, Salicaceae and Passifloraceae. An E. schimperi transcript of pt SOD-1-RPL32 confirmed that the transfer in Euphorbiaceae is similar to other Malpighiales indicating that it occurred early in the divergence of the order. Ribosomal protein S16 (rps16) is encoded in the plastome in most angiosperms but not in Salicaceae and Passifloraceae. Substitution of the E. schimperi pt rps16 was likely due to a duplication of nuclear-encoded mitochondrial-targeted rps16 resulting in copies dually targeted to the mitochondrion and plastid. Sequences of RPS16-1 and RPS16-2 in the three families of Malpighiales (Salicaceae, Passifloraceae and Euphorbiaceae) have high sequence identity suggesting that the substitution event dates to the early divergence within Malpighiales.}, } @article {pmid33813887, year = {2021}, author = {Ghiselli, F and Gomes-Dos-Santos, A and Adema, CM and Lopes-Lima, M and Sharbrough, J and Boore, JL}, title = {Molluscan mitochondrial genomes break the rules.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1825}, pages = {20200159}, pmid = {33813887}, issn = {1471-2970}, mesh = {Animals ; *Gene Duplication ; *Gene Rearrangement ; *Genome, Mitochondrial ; Heredity ; Mollusca/*genetics ; }, abstract = {The first animal mitochondrial genomes to be sequenced were of several vertebrates and model organisms, and the consistency of genomic features found has led to a 'textbook description'. However, a more broad phylogenetic sampling of complete animal mitochondrial genomes has found many cases where these features do not exist, and the phylum Mollusca is especially replete with these exceptions. The characterization of full mollusc mitogenomes required considerable effort involving challenging molecular biology, but has created an enormous catalogue of surprising deviations from that textbook description, including wide variation in size, radical genome rearrangements, gene duplications and losses, the introduction of novel genes, and a complex system of inheritance dubbed 'doubly uniparental inheritance'. Here, we review the extraordinary variation in architecture, molecular functioning and intergenerational transmission of molluscan mitochondrial genomes. Such features represent a great potential for the discovery of biological history, processes and functions that are novel for animal mitochondrial genomes. This provides a model system for studying the evolution and the manifold roles that mitochondria play in organismal physiology, and many ways that the study of mitochondrial genomes are useful for phylogeny and population biology. This article is part of the Theo Murphy meeting issue 'Molluscan genomics: broad insights and future directions for a neglected phylum'.}, } @article {pmid33818247, year = {2021}, author = {Schwartz, JH}, title = {Evolution, systematics, and the unnatural history of mitochondrial DNA.}, journal = {Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis}, volume = {32}, number = {4}, pages = {126-151}, doi = {10.1080/24701394.2021.1899165}, pmid = {33818247}, issn = {2470-1408}, mesh = {*DNA, Mitochondrial/genetics ; *Evolution, Molecular ; *Genome, Mitochondrial ; Mitochondria ; Phylogeny ; }, abstract = {The tenets underlying the use of mtDNA in phylogenetic and systematic analyses are strict maternal inheritance, clonality, homoplasmy, and difference due to mutation: that is, there are species-specific mtDNA sequences and phylogenetic reconstruction is a matter of comparing these sequences and inferring closeness of relatedness from the degree of sequence similarity. Yet, how mtDNA behavior became so defined is mysterious. Even though early studies of fertilization demonstrated for most animals that not only the head, but the sperm's tail and mitochondria-bearing midpiece penetrate the egg, the opposite - only the head enters the egg - became fact, and mtDNA conceived as maternally transmitted. When midpiece/tail penetration was realized as true, the conceptions 'strict maternal inheritance', etc., and their application to evolutionary endeavors, did not change. Yet there is mounting evidence of paternal mtDNA transmission, paternal and maternal combination, intracellular recombination, and intra- and intercellular heteroplasmy. Clearly, these phenomena impact the systematic and phylogenetic analysis of mtDNA sequences.}, } @article {pmid33825987, year = {2021}, author = {Eyenga, P and Roussel, D and Rey, B and Ndille, P and Teulier, L and Eyenga, F and Romestaing, C and Morel, J and Gueguen-Chaignon, V and Sheu, SS}, title = {Mechanical ventilation preserves diaphragm mitochondrial function in a rat sepsis model.}, journal = {Intensive care medicine experimental}, volume = {9}, number = {1}, pages = {19}, pmid = {33825987}, issn = {2197-425X}, abstract = {BACKGROUND: To describe the effect of mechanical ventilation on diaphragm mitochondrial oxygen consumption, ATP production, reactive oxygen species (ROS) generation, and cytochrome c oxidase activity and content, and their relationship to diaphragm strength in an experimental model of sepsis.

METHODS: A cecal ligation and puncture (CLP) protocol was performed in 12 rats while 12 controls underwent sham operation. Half of the rats in each group were paralyzed and mechanically ventilated. We performed blood gas analysis and lactic acid assays 6 h after surgery. Afterwards, we measured diaphragm strength and mitochondrial oxygen consumption, ATP and ROS generation, and cytochrome c oxidase activity. We also measured malondialdehyde (MDA) content as an index of lipid peroxidation, and mRNA expression of the proinflammatory interleukin-1β (IL-1β) in diaphragms.

RESULTS: CLP rats showed severe hypotension, metabolic acidosis, and upregulation of diaphragm IL-1β mRNA expression. Compared to sham controls, spontaneously breathing CLP rats showed lower diaphragm force and increased susceptibility to fatigue, along with depressed mitochondrial oxygen consumption and ATP production and cytochrome c oxidase activity. These rats also showed increased mitochondrial ROS generation and MDA content. Mechanical ventilation markedly restored mitochondrial oxygen consumption and ATP production in CLP rats; lowered mitochondrial ROS production by the complex 3; and preserved cytochrome c oxidase activity.

CONCLUSION: In an experimental model of sepsis, early initiation of mechanical ventilation restores diaphragm mitochondrial function.}, } @article {pmid33829092, year = {2021}, author = {Lee, SH and Lee, SH}, title = {Complete mitochondrial genome of Oregonia gracilis Dana, 1851 (Crustacea: Decapoda: Majoidea).}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {6}, number = {3}, pages = {1236-1237}, pmid = {33829092}, issn = {2380-2359}, abstract = {The complete mitochondrial genome of the majoid crab, Oregonia gracilis, was determined from a specimen collected in Korea. The mitochondrial genome is 15,737 bp long and contains 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, and two ribosomal RNA (rRNA) genes. A maximum-likelihood phylogenetic tree based on the 13 PCGs of the mitochondria showed that O. gracilis is closely related to the genus Chinoecetes. The complete mitochondrial genome of O. gracilis provides valuable information on the mitochondrial evolution of majoid crabs.}, } @article {pmid33836001, year = {2021}, author = {Dey, P and Sharma, SK and Sarkar, I and Ray, SD and Pramod, P and Kochiganti, VHS and Quadros, G and Rathore, SS and Singh, V and Singh, RP}, title = {Complete mitogenome of endemic plum-headed parakeet Psittacula cyanocephala - characterization and phylogenetic analysis.}, journal = {PloS one}, volume = {16}, number = {4}, pages = {e0241098}, pmid = {33836001}, issn = {1932-6203}, mesh = {Animals ; Codon Usage/genetics ; Gene Order/genetics ; Genome, Mitochondrial/*genetics ; Mitochondria/*genetics ; Mitogens/*genetics ; Phylogeny ; Psittacula/*genetics ; RNA, Ribosomal/genetics ; RNA, Transfer/genetics ; Selection, Genetic/genetics ; }, abstract = {Psittacula cyanocephala is an endemic parakeet from the Indian sub-continent that is widespread in the illegal bird trade. Previous studies on Psittacula parakeets have highlighted taxonomic ambiguities, warranting studies to resolve the issues. Since the mitochondrial genome provides useful information concerning the species evolution and phylogenetics, we sequenced the complete mitogenome of P. cyanocephala using NGS, validated 38.86% of the mitogenome using Sanger Sequencing and compared it with other available whole mitogenomes of Psittacula. The complete mitogenome of the species was 16814 bp in length with 54.08% AT composition. P. cyanocephala mitogenome comprises of 13 protein-coding genes, 2 rRNAs and 22 tRNAs. P. cyanocephala mitogenome organization was consistent with other Psittacula mitogenomes. Comparative codon usage analysis indicated the role of natural selection on Psittacula mitogenomes. Strong purifying selection pressure was observed maximum on nad1 and nad4l genes. The mitochondrial control region of all Psittacula species displayed the ancestral avian CR gene order. Phylogenetic analyses revealed the Psittacula genus as paraphyletic nature, containing at least 4 groups of species within the same genus, suggesting its taxonomic reconsideration. Our results provide useful information for developing forensic tests to control the illegal trade of the species and scientific basis for phylogenetic revision of the genus Psittacula.}, } @article {pmid33837704, year = {2020}, author = {Chihade, J}, title = {Mitochondrial aminoacyl-tRNA synthetases.}, journal = {The Enzymes}, volume = {48}, number = {}, pages = {175-206}, doi = {10.1016/bs.enz.2020.07.003}, pmid = {33837704}, issn = {0423-2607}, mesh = {*Amino Acyl-tRNA Synthetases/genetics ; Cytosol ; Eukaryotic Cells ; Humans ; Mitochondria/genetics ; RNA, Transfer ; }, abstract = {In all eukaryotic cells, protein synthesis occurs not only in the cytosol, but also in the mitochondria. Translation of mitochondrial genes requires a set of aminoacyl-tRNA synthetases, many of which are often specialized for organellar function. These enzymes have evolved unique mechanisms for tRNA recognition and for ensuring fidelity of translation. Mutations of human mitochondrial synthetases are associated with a wide range of pathogenic phenotypes, both highlighting the importance of their role in maintaining the cellular "powerhouse" and suggesting additional cellular roles.}, } @article {pmid33837778, year = {2021}, author = {Pyrih, J and Pánek, T and Durante, IM and Rašková, V and Cimrhanzlová, K and Kriegová, E and Tsaousis, AD and Eliáš, M and Lukeš, J}, title = {Vestiges of the Bacterial Signal Recognition Particle-Based Protein Targeting in Mitochondria.}, journal = {Molecular biology and evolution}, volume = {38}, number = {8}, pages = {3170-3187}, pmid = {33837778}, issn = {1537-1719}, mesh = {Bacterial Proteins/*genetics ; *Biological Evolution ; Escherichia coli Proteins/*genetics ; *Genome, Mitochondrial ; Naegleria/*genetics ; Receptors, Cytoplasmic and Nuclear/*genetics ; Sequence Homology, Nucleic Acid ; Signal Recognition Particle/*genetics ; }, abstract = {The main bacterial pathway for inserting proteins into the plasma membrane relies on the signal recognition particle (SRP), composed of the Ffh protein and an associated RNA component, and the SRP-docking protein FtsY. Eukaryotes use an equivalent system of archaeal origin to deliver proteins into the endoplasmic reticulum, whereas a bacteria-derived SRP and FtsY function in the plastid. Here we report on the presence of homologs of the bacterial Ffh and FtsY proteins in various unrelated plastid-lacking unicellular eukaryotes, namely Heterolobosea, Alveida, Goniomonas, and Hemimastigophora. The monophyly of novel eukaryotic Ffh and FtsY groups, predicted mitochondrial localization experimentally confirmed for Naegleria gruberi, and a strong alphaproteobacterial affinity of the Ffh group, collectively suggest that they constitute parts of an ancestral mitochondrial signal peptide-based protein-targeting system inherited from the last eukaryotic common ancestor, but lost from the majority of extant eukaryotes. The ability of putative signal peptides, predicted in a subset of mitochondrial-encoded N. gruberi proteins, to target a reporter fluorescent protein into the endoplasmic reticulum of Trypanosoma brucei, likely through their interaction with the cytosolic SRP, provided further support for this notion. We also illustrate that known mitochondrial ribosome-interacting proteins implicated in membrane protein targeting in opisthokonts (Mba1, Mdm38, and Mrx15) are broadly conserved in eukaryotes and nonredundant with the mitochondrial SRP system. Finally, we identified a novel mitochondrial protein (MAP67) present in diverse eukaryotes and related to the signal peptide-binding domain of Ffh, which may well be a hitherto unrecognized component of the mitochondrial membrane protein-targeting machinery.}, } @article {pmid33839167, year = {2021}, author = {García-Catalán, S and González-Moreno, L and Del Arco, A}, title = {Ca[2+]-regulated mitochondrial carriers of ATP-Mg[2+]/Pi: Evolutionary insights in protozoans.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {1868}, number = {7}, pages = {119038}, doi = {10.1016/j.bbamcr.2021.119038}, pmid = {33839167}, issn = {1879-2596}, mesh = {Adenosine Triphosphate/metabolism ; Amino Acid Sequence/genetics ; Animals ; Antiporters/*genetics/*metabolism/physiology ; Calcium/metabolism ; Calcium-Binding Proteins/metabolism ; Calmodulin/metabolism ; Databases, Genetic ; Evolution, Molecular ; Membrane Transport Proteins/metabolism ; Mitochondria/metabolism ; Mitochondrial Membrane Transport Proteins/genetics/metabolism ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/*genetics/*metabolism/physiology ; Phylogeny ; Protozoan Proteins/genetics/metabolism ; Sequence Homology ; }, abstract = {In addition to its uptake across the Ca[2+] uniporter, intracellular calcium signals can stimulate mitochondrial metabolism activating metabolite exchangers of the inner mitochondrial membrane belonging to the mitochondrial carrier family (SLC25). One of these Ca[2+]-regulated mitochondrial carriers (CaMCs) are the reversible ATP-Mg[2+]/Pi transporters, or SCaMCs, required for maintaining optimal adenine nucleotide (AdN) levels in the mitochondrial matrix representing an alternative transporter to the ADP/ATP translocases (AAC). This CaMC has a distinctive Calmodulin-like (CaM-like) domain fused to the carrier domain that makes its transport activity strictly dependent on cytosolic Ca[2+] signals. Here we investigate about its origin analysing its distribution and features in unicellular eukaryotes. Unexpectedly, we find two types of ATP-Mg[2+]/Pi carriers, the canonical ones and shortened variants lacking the CaM-like domain. Phylogenetic analysis shows that both SCaMC variants have a common origin, unrelated to AACs, suggesting in turn that recurrent losses of the regulatory module have occurred in the different phyla. They are excluding variants that show a more limited distribution and less conservation than AACs. Interestingly, these truncated variants of SCaMC are found almost exclusively in parasitic protists, such as apicomplexans, kinetoplastides or animal-patogenic oomycetes, and in green algae, suggesting that its lost could be related to certain life-styles. In addition, we find an intricate structural diversity in these variants that may be associated with their pathogenicity. The consequences on SCaMC functions of these new SCaMC-b variants are discussed.}, } @article {pmid33846476, year = {2021}, author = {Elfekih, S and Tay, WT and Polaszek, A and Gordon, KHJ and Kunz, D and Macfadyen, S and Walsh, TK and Vyskočilová, S and Colvin, J and De Barro, PJ}, title = {On species delimitation, hybridization and population structure of cassava whitefly in Africa.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {7923}, pmid = {33846476}, issn = {2045-2322}, mesh = {Africa ; Animals ; Base Sequence ; Electron Transport Complex IV/genetics ; Gene Flow ; Geography ; Hemiptera/*genetics ; *Hybridization, Genetic ; Manihot/*parasitology ; Mitochondria/genetics ; Phylogeny ; Population Dynamics ; Principal Component Analysis ; Species Specificity ; }, abstract = {The Bemisia cassava whitefly complex includes species that cause severe crop damage through vectoring cassava viruses in eastern Africa. Currently, this whitefly complex is divided into species and subgroups (SG) based on very limited molecular markers that do not allow clear definition of species and population structure. Based on 14,358 genome-wide SNPs from 62 Bemisia cassava whitefly individuals belonging to sub-Saharan African species (SSA1, SSA2 and SSA4), and using a well-curated mtCOI gene database, we show clear incongruities in previous taxonomic approaches underpinned by effects from pseudogenes. We show that the SSA4 species is nested within SSA2, and that populations of the SSA1 species comprise well-defined south-eastern (Madagascar, Tanzania) and north-western (Nigeria, Democratic Republic of Congo, Burundi) putative sub-species. Signatures of allopatric incipient speciation, and the presence of a 'hybrid zone' separating the two putative sub-species were also detected. These findings provide insights into the evolution and molecular ecology of a highly cryptic hemipteran insect complex in African, and allow the systematic use of genomic data to be incorporated in the development of management strategies for this cassava pest.}, } @article {pmid33848308, year = {2021}, author = {de Meeûs d'Argenteuil, C and Boshuizen, B and Oosterlinck, M and van de Winkel, D and De Spiegelaere, W and de Bruijn, CM and Goethals, K and Vanderperren, K and Delesalle, CJG}, title = {Flexibility of equine bioenergetics and muscle plasticity in response to different types of training: An integrative approach, questioning existing paradigms.}, journal = {PloS one}, volume = {16}, number = {4}, pages = {e0249922}, pmid = {33848308}, issn = {1932-6203}, mesh = {Amino Acids, Aromatic/metabolism ; Amino Acids, Branched-Chain/metabolism ; Animals ; Citric Acid Cycle ; *Energy Metabolism ; Female ; Glycolysis ; Heart Rate ; Horses ; Lipid Peroxidation ; Male ; Metabolomics ; Mitochondria/metabolism ; Muscle Fibers, Skeletal/physiology ; Muscle, Skeletal/metabolism/pathology/*physiology ; Pentose Phosphate Pathway ; Physical Conditioning, Animal ; }, abstract = {Equine bioenergetics have predominantly been studied focusing on glycogen and fatty acids. Combining omics with conventional techniques allows for an integrative approach to broadly explore and identify important biomolecules. Friesian horses were aquatrained (n = 5) or dry treadmill trained (n = 7) (8 weeks) and monitored for: evolution of muscle diameter in response to aquatraining and dry treadmill training, fiber type composition and fiber cross-sectional area of the M. pectoralis, M. vastus lateralis and M. semitendinosus and untargeted metabolomics of the M. pectoralis and M. vastus lateralis in response to dry treadmill training. Aquatraining was superior to dry treadmill training to increase muscle diameter in the hindquarters, with maximum effect after 4 weeks. After dry treadmill training, the M. pectoralis showed increased muscle diameter, more type I fibers, decreased fiber mean cross sectional area, and an upregulated oxidative metabolic profile: increased β-oxidation (key metabolites: decreased long chain fatty acids and increased long chain acylcarnitines), TCA activity (intermediates including succinyl-carnitine and 2-methylcitrate), amino acid metabolism (glutamine, aromatic amino acids, serine, urea cycle metabolites such as proline, arginine and ornithine) and xenobiotic metabolism (especially p-cresol glucuronide). The M. vastus lateralis expanded its fast twitch profile, with decreased muscle diameter, type I fibers and an upregulation of glycolytic and pentose phosphate pathway activity, and increased branched-chain and aromatic amino acid metabolism (cis-urocanate, carnosine, homocarnosine, tyrosine, tryptophan, p-cresol-glucuronide, serine, methionine, cysteine, proline and ornithine). Trained Friesians showed increased collagen and elastin turn-over. Results show that branched-chain amino acids, aromatic amino acids and microbiome-derived xenobiotics need further study in horses. They feed the TCA cycle at steps further downstream from acetyl CoA and most likely, they are oxidized in type IIA fibers, the predominant fiber type of the horse. These study results underline the importance of reviewing existing paradigms on equine bioenergetics.}, } @article {pmid33848317, year = {2021}, author = {Postic, E and Outreman, Y and Derocles, S and Granado, C and Le Ralec, A}, title = {Genetics of wild and mass-reared populations of a generalist aphid parasitoid and improvement of biological control.}, journal = {PloS one}, volume = {16}, number = {4}, pages = {e0249893}, pmid = {33848317}, issn = {1932-6203}, mesh = {Animals ; Aphids/classification/*genetics ; Discriminant Analysis ; Electron Transport Complex IV/genetics ; Fragaria/parasitology ; Genetic Variation ; Genetics, Population ; Haplotypes ; Host-Parasite Interactions ; Microsatellite Repeats/genetics ; Mitochondria/genetics ; *Pest Control, Biological ; Phylogeny ; Principal Component Analysis ; }, abstract = {Due to their ability to parasitize various insect species, generalist parasitoids are widely used as biological control agents. They can be mass-reared and released in agroecosystems to control several pest species in various crops. However, the existence of genetic differentiation among populations of generalist parasitoid species is increasingly recognized and this can be associated with an adaptation to local conditions or to a reduced range of host species. Moreover, constraints of mass-rearing conditions can alter genetic variation within parasitoid populations released. These features could be associated with a reduced efficiency of the control of targeted pest species. Here, we focused on strawberry greenhouses where the control of aphids with the generalist parasitoid Aphidius ervi appears to be inefficient. We investigated whether this inefficiency may have both genetic and ecological bases comparing wild and commercial populations of A. ervi. We used two complementary genetic approaches: one based on the mitochondrial marker COI and one based on microsatellite markers. COI analysis showed a genetic differentiation within the A. ervi species, but the structure was neither associated with the commercial/wild status nor with host species factors. On the other hand, using microsatellite markers, we showed a genetic differentiation between commercial and wild A. ervi populations associated with a loss of genetic diversity within the mass-reared populations. Our ecological genetics study may potentially explain the weak efficiency of biological control of aphids in protected strawberry crops and enable to provide some insights to improve biological control.}, } @article {pmid33857516, year = {2021}, author = {Dores-Silva, PR and Kiraly, VTR and Moritz, MNO and Serrão, VHB and Dos Passos, PMS and Spagnol, V and Teixeira, FR and Gava, LM and Cauvi, DM and Ramos, CHI and De Maio, A and Borges, JC}, title = {New insights on human Hsp70-escort protein 1: Chaperone activity, interaction with liposomes, cellular localizations and HSPA's self-assemblies remodeling.}, journal = {International journal of biological macromolecules}, volume = {182}, number = {}, pages = {772-784}, doi = {10.1016/j.ijbiomac.2021.04.048}, pmid = {33857516}, issn = {1879-0003}, mesh = {Active Transport, Cell Nucleus ; Cell Line, Tumor ; Cell Nucleus/*metabolism ; HSP70 Heat-Shock Proteins/metabolism ; Humans ; Intracellular Membranes/metabolism ; Liposomes/*metabolism ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; Molecular Chaperones/*metabolism ; Protein Binding ; Protein Multimerization ; }, abstract = {The 70 kDa heat shock proteins (Hsp70) are prone to self-assembly under thermal stress conditions, forming supramolecular assemblies (SMA), what may have detrimental consequences for cellular viability. In mitochondria, the cochaperone Hsp70-escort protein 1 (Hep1) maintains mitochondrial Hsp70 (mtHsp70) in a soluble and functional state, contributing to preserving proteostasis. Here we investigated the interaction between human Hep1 (hHep1) and HSPA9 (human mtHsp70) or HSPA1A (Hsp70-1A) in monomeric and thermic SMA states to unveil further information about the involved mechanisms. hHep1 was capable of blocking the formation of HSPA SMAs under a thermic treatment and stimulated HSPA ATPase activity in both monomeric and preformed SMA. The interaction of hHep1 with both monomeric and SMA HSPAs displayed a stoichiometric ratio close to 1, suggesting that hHep1 has access to most protomers within the SMA. Interestingly, hHep1 remodeled HSPA9 and HSPA1A SMAs into smaller forms. Furthermore, hHep1 was detected in the mitochondria and nucleus of cells transfected with the respective coding DNA and interacted with liposomes resembling mitochondrial membranes. Altogether, these new features reinforce that hHep1 act as a "chaperone for a chaperone", which may play a critical role in cellular proteostasis.}, } @article {pmid33857537, year = {2021}, author = {Deonath, A}, title = {Evolution of eukaryotes as a story of survival and growth of mitochondrial DNA over two billion years.}, journal = {Bio Systems}, volume = {206}, number = {}, pages = {104426}, doi = {10.1016/j.biosystems.2021.104426}, pmid = {33857537}, issn = {1872-8324}, mesh = {Animals ; *Biological Evolution ; Cell Survival/physiology ; DNA, Mitochondrial/*physiology ; Eukaryota/genetics/*growth & development ; Eukaryotic Cells/*physiology ; *Evolution, Molecular ; Humans ; Mitochondria/physiology ; Time Factors ; }, abstract = {Mitochondria's significance in human diseases and in functioning, health and death of eukaryotic cell has been acknowledged widely. Yet our perspective in cell biology and evolution remains nucleocentric. Mitochondrial DNA, by virtue of its omnipresence and species-level conservation, is used as a barcode in animal taxonomy. This article analyses various levels of containment structures that enclose mitochondrial DNA and advocates a fresh perspective wherein evolution of organic structures of the eukarya domain seem to support and facilitate survival and proliferation of mitochondrial DNA by splitting containers as they age and by directing them along two distinct pathways: destruction of containers with more mutant mitochondrial DNA and rejuvenation of containers with less mutant mitochondrial DNA.}, } @article {pmid33859247, year = {2021}, author = {Louro, M and Kuzmina, TA and Bredtmann, CM and Diekmann, I and de Carvalho, LMM and von Samson-Himmelstjerna, G and Krücken, J}, title = {Genetic variability, cryptic species and phylogenetic relationship of six cyathostomin species based on mitochondrial and nuclear sequences.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {8245}, pmid = {33859247}, issn = {2045-2322}, mesh = {Animals ; Cell Nucleus/*genetics ; DNA, Helminth/analysis/genetics ; DNA, Mitochondrial/analysis ; Genetic Variation ; Germany ; Horse Diseases/parasitology ; Horses/parasitology ; Intestinal Diseases, Parasitic ; Mitochondria/*genetics ; Parasite Egg Count/veterinary ; Phylogeny ; Sequence Analysis, DNA ; *Strongyloidea/classification/genetics ; Ukraine ; }, abstract = {Cyathostomins are important intestinal nematode parasites of equines and include 50 accepted species. Their taxonomy has been frequently revised and the presence of cryptic species suggested. Furthermore, usually molecular- and morphology-based phylogenetic analyses give divergent results. In this study, the nucleotide sequences of the nuclear second internal transcribed spacer (ITS-2) and the mitochondrial partial cytochrome c oxidase subunit I (COI) were determined for adults of six cyathostomin species (Coronocyclus coronatus, Coronocyclus labiatus, Cylicocyclus nassatus, Cylicostephanus calicatus, Cylicostephanus longibursatus, Cylicostephanus minutus) collected from different equine species within two geographic regions. Maximum likelihood trees were calculated for ITS-2, COI, and concatenated data. No obvious differentiation was observed between geographic regions or equine host species. As previously reported, Coronocyclus coronatus and Cylicostephanus calicatus revealed a close relationship. Cryptic species were detected in Cylicostephanus minutus and Cylicostephanus calicatus. Cylicocyclus nassatus and Coronocyclus labiatus showed diverse mitochondrial and nuclear haplotypes occurring in different combinations, while Cylicostephanus longibursatus was comparatively homogenous. In conclusion, a combined analysis of nuclear and mitochondrial haplotypes improved resolution of the phylogeny and should be applied to the remaining cyathostomin species and across additional equine host species and geographic regions.}, } @article {pmid33860546, year = {2021}, author = {Brandeis, M}, title = {Were eukaryotes made by sex?: Sex might have been vital for merging endosymbiont and host genomes giving rise to eukaryotes.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {6}, pages = {e2000256}, doi = {10.1002/bies.202000256}, pmid = {33860546}, issn = {1521-1878}, mesh = {Archaea/genetics ; *Biological Evolution ; *Eukaryota/genetics ; Eukaryotic Cells ; Phylogeny ; Symbiosis/genetics ; }, abstract = {I hypothesize that the appearance of sex facilitated the merging of the endosymbiont and host genomes during early eukaryote evolution. Eukaryotes were formed by symbiosis between a bacterium that entered an archaeon, eventually giving rise to mitochondria. This entry was followed by the gradual transfer of most bacterial endosymbiont genes into the archaeal host genome. I argue that the merging of the mitochondrial genes into the host genome was vital for the evolution of genuine eukaryotes. At the time this process commenced it was unprecedented and required a novel mechanism. I suggest that this mechanism was meiotic sex, and that its appearance might have been THE crucial step that enabled the evolution of proper eukaryotes from early endosymbiont containing proto-eukaryotes. Sex might continue to be essential today for keeping genome insertions in check. Also see the video abstract here: https://youtu.be/aVMvWMpomac.}, } @article {pmid33863338, year = {2021}, author = {Salomaki, ED and Terpis, KX and Rueckert, S and Kotyk, M and Varadínová, ZK and Čepička, I and Lane, CE and Kolisko, M}, title = {Gregarine single-cell transcriptomics reveals differential mitochondrial remodeling and adaptation in apicomplexans.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {77}, pmid = {33863338}, issn = {1741-7007}, support = {CZ.02.2.69/0.0/0.0/16_027/0008357//Ministerstvo Školství, Mládeže a Tělovýchovy (CZ)/ ; CZ.02.2.69/0.0/0.0/20_079/0017809//Ministerstvo Školství, Mládeže a Tělovýchovy/ ; CZ.02.1.01/0.0/0.0/16_019/0000759//Ministerstvo Školství, Mládeže a Tělovýchovy/ ; 1541510//Directorate for Biological Sciences/ ; 1158119//Grantová Agentura, Univerzita Karlova/ ; 19-19297S//Grantová Agentura České Republiky/ ; 18-28103S//Grantová Agentura České Republiky/ ; Fellowship Purkyne//Akademie Věd České Republiky/ ; OIA-1655221//National Science Foundation/ ; GBMF9327//Gordon and Betty Moore Foundation/ ; }, mesh = {Animals ; *Apicomplexa/genetics ; Humans ; *Mitochondria/genetics ; Phylogeny ; Single-Cell Analysis ; Transcriptome ; }, abstract = {BACKGROUND: Apicomplexa is a diverse phylum comprising unicellular endobiotic animal parasites and contains some of the most well-studied microbial eukaryotes including the devastating human pathogens Plasmodium falciparum and Cryptosporidium hominis. In contrast, data on the invertebrate-infecting gregarines remains sparse and their evolutionary relationship to other apicomplexans remains obscure. Most apicomplexans retain a highly modified plastid, while their mitochondria remain metabolically conserved. Cryptosporidium spp. inhabit an anaerobic host-gut environment and represent the known exception, having completely lost their plastid while retaining an extremely reduced mitochondrion that has lost its genome. Recent advances in single-cell sequencing have enabled the first broad genome-scale explorations of gregarines, providing evidence of differential plastid retention throughout the group. However, little is known about the retention and metabolic capacity of gregarine mitochondria.

RESULTS: Here, we sequenced transcriptomes from five species of gregarines isolated from cockroaches. We combined these data with those from other apicomplexans, performed detailed phylogenomic analyses, and characterized their mitochondrial metabolism. Our results support the placement of Cryptosporidium as the earliest diverging lineage of apicomplexans, which impacts our interpretation of evolutionary events within the phylum. By mapping in silico predictions of core mitochondrial pathways onto our phylogeny, we identified convergently reduced mitochondria. These data show that the electron transport chain has been independently lost three times across the phylum, twice within gregarines.

CONCLUSIONS: Apicomplexan lineages show variable functional restructuring of mitochondrial metabolism that appears to have been driven by adaptations to parasitism and anaerobiosis. Our findings indicate that apicomplexans are rife with convergent adaptations, with shared features including morphology, energy metabolism, and intracellularity.}, } @article {pmid33871031, year = {2021}, author = {de Melo Teixeira, M and Lang, BF and Matute, DR and Stajich, JE and Barker, BM}, title = {Mitochondrial genomes of the human pathogens Coccidioides immitis and Coccidioides posadasii.}, journal = {G3 (Bethesda, Md.)}, volume = {11}, number = {7}, pages = {}, pmid = {33871031}, issn = {2160-1836}, support = {R01 AI153523/AI/NIAID NIH HHS/United States ; R21 AI128536/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Coccidioides/genetics ; Phylogeny ; *Genome, Mitochondrial ; *Coccidioidomycosis/epidemiology/genetics/microbiology ; }, abstract = {Fungal mitochondrial genomes encode genes involved in crucial cellular processes, such as oxidative phosphorylation and mitochondrial translation, and the molecule has been used as a molecular marker for population genetics studies. Coccidioides immitis and C. posadasii are endemic fungal pathogens that cause coccidioidomycosis in arid regions across both American continents. To date, approximately 150 Coccidioides isolates have been sequenced to infer patterns of variation in nuclear genomes. However, less attention has been given to the mitochondrial genomes of Coccidioides. In this report, we describe the assembly and annotation of mitochondrial reference genomes for two representative strains of C. posadasii and C. immitis, as well as assess population variation among 77 selected genomes. The sizes of the circular-mapping molecules are 68.2 Kb in C. immitis and 75.1 Kb in C. posadasii. We identify 14 mitochondrial protein-coding genes common to most fungal mitochondria, which are largely syntenic across different populations and species of Coccidioides. Both Coccidioides species are characterized by a large number of group I and II introns, harboring twice the number of elements as compared to closely related Onygenales. The introns contain complete or truncated ORFs with high similarity to homing endonucleases of the LAGLIDADG and GIY-YIG families. Phylogenetic comparisons of mitochondrial and nuclear genomes show extensive phylogenetic discordance suggesting that the evolution of the two types of genetic material is not identical. This work represents the first assessment of mitochondrial genomes among isolates of both species of Coccidioides, and provides a foundation for future functional work.}, } @article {pmid33871590, year = {2021}, author = {Helfenrath, K and Sauer, M and Kamga, M and Wisniewsky, M and Burmester, T and Fabrizius, A}, title = {The More, the Merrier? Multiple Myoglobin Genes in Fish Species, Especially in Gray Bichir (Polypterus senegalus) and Reedfish (Erpetoichthys calabaricus).}, journal = {Genome biology and evolution}, volume = {13}, number = {7}, pages = {}, pmid = {33871590}, issn = {1759-6653}, mesh = {Animals ; Evolution, Molecular ; *Fishes/genetics ; *Myoglobin/genetics ; Phylogeny ; Vertebrates/genetics ; }, abstract = {The members of the globin superfamily are a classical model system to investigate gene evolution and their fates as well as the diversity of protein function. One of the best-known globins is myoglobin (Mb), which is mainly expressed in heart muscle and transports oxygen from the sarcolemma to the mitochondria. Most vertebrates harbor a single copy of the myoglobin gene, but some fish species have multiple myoglobin genes. Phylogenetic analyses indicate an independent emergence of multiple myoglobin genes, whereby the origin is mostly the last common ancestor of each order. By analyzing different transcriptome data sets, we found at least 15 multiple myoglobin genes in the polypterid gray bichir (Polypterus senegalus) and reedfish (Erpetoichthys calabaricus). In reedfish, the myoglobin genes are expressed in a broad range of tissues but show very different expression values. In contrast, the Mb genes of the gray bichir show a rather scattered expression pattern; only a few Mb genes were found expressed in the analyzed tissues. Both, gray bichir and reedfish possess lungs which enable them to inhabit shallow and swampy waters throughout tropical Africa with frequently fluctuating and low oxygen concentrations. The myoglobin repertoire probably reflects the molecular adaptation to these conditions. The sequence divergence, the substitution rate, and the different expression pattern of multiple myoglobin genes in gray bichir and reedfish imply different functions, probably through sub- and neofunctionalization during evolution.}, } @article {pmid33873653, year = {2003}, author = {Logan, DC}, title = {Mitochondrial dynamics.}, journal = {The New phytologist}, volume = {160}, number = {3}, pages = {463-478}, pmid = {33873653}, issn = {1469-8137}, abstract = {Mitochondria cannot be created de novo but instead must arise from the fission (division) of a parental organelle. In addition to fission, mitochondria also fuse with one another and it is thought that a co-ordinated balance of these two processes controls mitochondrial shape, size and number. In the past 5-7 yr, molecular genetics coupled to state-of-the-art cell biology, in particular the use of mitochondrial-targeted green fluorescent protein (GFP), has enabled identification of proteins controlling mitochondrial shape, size and number in yeast and mammalian cells. Little is known about higher plant mitochondrial dynamics. Recently, however, several genes involved in the control of plant mitochondrial dynamics have been identified. The aim of this article is to bring together what is known about mitochondrial dynamics in any organisms and to relate this to our recent knowledge of the underlying processes in higher plants. Contents Summary 463 I. Introduction 464 II. Mitochondrial evolution 464 III. Mitochondria and the cytoskeleton 465 IV. Mitochondrial morphology, biogenesis, proliferation and inheritance 466 V. Mitochondrial fission and fusion 468 VI. Mitochondrial distribution 470 VII. Plant specific proteins playing a role in mitochondrial dynamics 470 VIII. Conclusions 471 Acknowledgements 475 References 475.}, } @article {pmid33873942, year = {1988}, author = {Fahn, A}, title = {Secretory tissues in vascular plants.}, journal = {The New phytologist}, volume = {108}, number = {3}, pages = {229-257}, doi = {10.1111/j.1469-8137.1988.tb04159.x}, pmid = {33873942}, issn = {1469-8137}, abstract = {Secretory tissues occur in most vascular plants. Some of these tissues, such as hydathodes, salt glands and nectaries, secrete unmodified or only slightly modified substances supplied directly or indirectly by the vascular tissues. Other tissues secreting, for instance, polysaccharides, proteins and lipophilic material, produce these substances in their cells. The cells of secretory tissues usually contain numerous mitochondria. The frequency of other cell organelles varies according to the material secreted. In most glandular trichomes the side wall of the lowest stalk cell is completely cutinized. This prevents the secreted material from flowing back into the plant. The salt glands in Atriplex eliminate salt into the central vacuole of the bladder cell but, in other plants, the glands secrete salt to the outside. Different views exist as to the manner in which salt is eliminated from the cytoplasm. According to some authors, the mode of elimination is an eccrine one, while others suggest the involvement of membrane-bound vesicles. Nectar is of phloem origin. The pre-nectar moves to the secretory cells through numerous plasmodesmata present in the nectariferous tissue. Nectar is eliminated from the secretory cells by vesicles of either KR or dictyosomal origin. In some cases, both organelles may be involved but an eccrine mode of nectar secretion has also been suggested by some authors. Carbohydrate mucilages and gums are synthesized by dictyosomes but virtually every cell compartment has been suggested as having a role on the secretion of lipophilic substances. Most commonly, plastids are implicated in the synthesis of lipophilic materials but KR may also play a part. In some cases lipophilic materials may be transported towards the plasmalemma in the KR. Resin and gum ducts of some plants develop normally or in response to external stimuli, such as microorganisms or growth substances. Among the latter, ethylene is the most effective. During the course of evolution, secretory tissues seem to have developed from secretory idioblasts scattered among the cells of the ordinary tissues. Subsequently ducts and cavities developed and finally secretory trichomes. CONTENTS Summary 229 I. Introduction 230 II. Salt glands 231 III. Nectaries 236 IV. Mucilages and gums 241 V. Tissues secreting lipophilic material 242 VI. Factors influencing the development of certain secretory tissues 246 VII. Evolutionary considerations 248 References 250.}, } @article {pmid33878294, year = {2021}, author = {Kummer, E and Schubert, KN and Schoenhut, T and Scaiola, A and Ban, N}, title = {Structural basis of translation termination, rescue, and recycling in mammalian mitochondria.}, journal = {Molecular cell}, volume = {81}, number = {12}, pages = {2566-2582.e6}, doi = {10.1016/j.molcel.2021.03.042}, pmid = {33878294}, issn = {1097-4164}, mesh = {Animals ; Carboxylic Ester Hydrolases ; Codon, Terminator ; Cryoelectron Microscopy/methods ; Humans ; Mitochondria/metabolism/*physiology ; Mitochondrial Proteins/metabolism ; Mitochondrial Ribosomes/*metabolism ; Peptide Chain Termination, Translational/genetics/*physiology ; Peptide Elongation Factor G/metabolism ; Peptide Termination Factors/metabolism ; Protein Biosynthesis ; Ribosomal Proteins/metabolism/physiology ; Ribosomes/metabolism ; }, abstract = {The mitochondrial translation system originates from a bacterial ancestor but has substantially diverged in the course of evolution. Here, we use single-particle cryo-electron microscopy (cryo-EM) as a screening tool to identify mitochondrial translation termination mechanisms and to describe them in molecular detail. We show how mitochondrial release factor 1a releases the nascent chain from the ribosome when it encounters the canonical stop codons UAA and UAG. Furthermore, we define how the peptidyl-tRNA hydrolase ICT1 acts as a rescue factor on mitoribosomes that have stalled on truncated messages to recover them for protein synthesis. Finally, we present structural models detailing the process of mitochondrial ribosome recycling to explain how a dedicated elongation factor, mitochondrial EFG2 (mtEFG2), has specialized for cooperation with the mitochondrial ribosome recycling factor to dissociate the mitoribosomal subunits at the end of the translation process.}, } @article {pmid33891583, year = {2021}, author = {Edwards, DM and Røyrvik, EC and Chustecki, JM and Giannakis, K and Glastad, RC and Radzvilavicius, AL and Johnston, IG}, title = {Avoiding organelle mutational meltdown across eukaryotes with or without a germline bottleneck.}, journal = {PLoS biology}, volume = {19}, number = {4}, pages = {e3001153}, pmid = {33891583}, issn = {1545-7885}, support = {/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Arabidopsis ; DNA, Mitochondrial/genetics ; Drosophila ; Eukaryota/classification/*genetics ; Gene Expression Regulation, Developmental ; Genetic Speciation ; Germ Cells/*metabolism ; Germ-Line Mutation/physiology ; Humans ; Mice ; Mitochondria/genetics ; Mitochondrial Dynamics/genetics ; Models, Genetic ; Mutagenesis/physiology ; Mutation/*physiology ; Mutation Rate ; Organelle Biogenesis ; Organelles/*genetics/physiology ; }, abstract = {Mitochondrial DNA (mtDNA) and plastid DNA (ptDNA) encode vital bioenergetic apparatus, and mutations in these organelle DNA (oDNA) molecules can be devastating. In the germline of several animals, a genetic "bottleneck" increases cell-to-cell variance in mtDNA heteroplasmy, allowing purifying selection to act to maintain low proportions of mutant mtDNA. However, most eukaryotes do not sequester a germline early in development, and even the animal bottleneck remains poorly understood. How then do eukaryotic organelles avoid Muller's ratchet-the gradual buildup of deleterious oDNA mutations? Here, we construct a comprehensive and predictive genetic model, quantitatively describing how different mechanisms segregate and decrease oDNA damage across eukaryotes. We apply this comprehensive theory to characterise the animal bottleneck with recent single-cell observations in diverse mouse models. Further, we show that gene conversion is a particularly powerful mechanism to increase beneficial cell-to-cell variance without depleting oDNA copy number, explaining the benefit of observed oDNA recombination in diverse organisms which do not sequester animal-like germlines (for example, sponges, corals, fungi, and plants). Genomic, transcriptomic, and structural datasets across eukaryotes support this mechanism for generating beneficial variance without a germline bottleneck. This framework explains puzzling oDNA differences across taxa, suggesting how Muller's ratchet is avoided in different eukaryotes.}, } @article {pmid33891594, year = {2021}, author = {Milner, DS and Wideman, JG and Stairs, CW and Dunn, CD and Richards, TA}, title = {A functional bacteria-derived restriction modification system in the mitochondrion of a heterotrophic protist.}, journal = {PLoS biology}, volume = {19}, number = {4}, pages = {e3001126}, pmid = {33891594}, issn = {1545-7885}, mesh = {Bacteria/*genetics ; Base Sequence ; DNA Restriction-Modification Enzymes/*genetics ; DNA, Mitochondrial/analysis/genetics ; Escherichia coli/genetics ; Eukaryota/classification/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal ; Genome, Mitochondrial/genetics ; Mitochondria/*genetics ; Organisms, Genetically Modified ; Phylogeny ; Repetitive Sequences, Nucleic Acid/genetics ; Saccharomyces cerevisiae/genetics ; Sequence Analysis, DNA ; }, abstract = {The overarching trend in mitochondrial genome evolution is functional streamlining coupled with gene loss. Therefore, gene acquisition by mitochondria is considered to be exceedingly rare. Selfish elements in the form of self-splicing introns occur in many organellar genomes, but the wider diversity of selfish elements, and how they persist in the DNA of organelles, has not been explored. In the mitochondrial genome of a marine heterotrophic katablepharid protist, we identify a functional type II restriction modification (RM) system originating from a horizontal gene transfer (HGT) event involving bacteria related to flavobacteria. This RM system consists of an HpaII-like endonuclease and a cognate cytosine methyltransferase (CM). We demonstrate that these proteins are functional by heterologous expression in both bacterial and eukaryotic cells. These results suggest that a mitochondrion-encoded RM system can function as a toxin-antitoxin selfish element, and that such elements could be co-opted by eukaryotic genomes to drive biased organellar inheritance.}, } @article {pmid33892099, year = {2021}, author = {Wood, AW and Duda, TF}, title = {Reticulate evolution in Conidae: Evidence of nuclear and mitochondrial introgression.}, journal = {Molecular phylogenetics and evolution}, volume = {161}, number = {}, pages = {107182}, doi = {10.1016/j.ympev.2021.107182}, pmid = {33892099}, issn = {1095-9513}, mesh = {Animals ; Cell Nucleus/*genetics ; *Evolution, Molecular ; Gastropoda/classification/*genetics ; Genes, Mitochondrial/genetics ; *Genetic Introgression ; Mitochondria/*genetics ; Phylogeny ; }, abstract = {Conidae is a hyperdiverse family of marine snails that has many hallmarks of adaptive radiation. Hybridization and introgression may contribute to such instances of rapid diversification by generating novel gene combinations that facilitate exploitation of distinct niches. Here we evaluated whether or not these mechanisms may have contributed to the evolutionary history of a subgenus of Conidae (Virroconus). Several observations hint at evidence of past introgression for members of this group, including incongruence between phylogenetic relationships inferred from mitochondrial gene sequences and morphology and widespread sympatry of many Virroconus species in the Indo-West Pacific. We generated and analyzed transcriptome data of Virroconus species to (i) infer a robust nuclear phylogeny, (ii) assess mitochondrial and nuclear gene tree discordance, and (iii) formally test for introgression of nuclear loci. We identified introgression of mitochondrial genomes and nuclear gene regions between ancestors of one pair of Virroconus species, and mitochondrial introgression between another pair. We also found evidence of adaptive introgression of conotoxin venom loci between a third pair of species. Together, our results demonstrate that hybridization and introgression impacted the evolutionary history of Virroconus and hence may have contributed to the adaptive radiation of Conidae.}, } @article {pmid33892508, year = {2021}, author = {Breton, S and Ghiselli, F and Milani, L}, title = {Mitochondrial Short-Term Plastic Responses and Long-Term Evolutionary Dynamics in Animal Species.}, journal = {Genome biology and evolution}, volume = {13}, number = {7}, pages = {}, pmid = {33892508}, issn = {1759-6653}, mesh = {Animals ; DNA, Mitochondrial/genetics ; Epigenesis, Genetic ; Epigenomics ; *Genome, Mitochondrial ; *Mitochondria/genetics ; }, abstract = {How do species respond or adapt to environmental changes? The answer to this depends partly on mitochondrial epigenetics and genetics, new players in promoting adaptation to both short- and long-term environmental changes. In this review, we explore how mitochondrial epigenetics and genetics mechanisms, such as mtDNA methylation, mtDNA-derived noncoding RNAs, micropeptides, mtDNA mutations, and adaptations, can contribute to animal plasticity and adaptation. We also briefly discuss the challenges in assessing mtDNA adaptive evolution. In sum, this review covers new advances in the field of mitochondrial genomics, many of which are still controversial, and discusses processes still somewhat obscure, and some of which are still quite speculative and require further robust experimentation.}, } @article {pmid33901335, year = {2021}, author = {Bilcke, G and Osuna-Cruz, CM and Santana Silva, M and Poulsen, N and D'hondt, S and Bulankova, P and Vyverman, W and De Veylder, L and Vandepoele, K}, title = {Diurnal transcript profiling of the diatom Seminavis robusta reveals adaptations to a benthic lifestyle.}, journal = {The Plant journal : for cell and molecular biology}, volume = {107}, number = {1}, pages = {315-336}, doi = {10.1111/tpj.15291}, pmid = {33901335}, issn = {1365-313X}, mesh = {*Adaptation, Physiological ; Cell Cycle/genetics ; Cell Wall/genetics/metabolism ; Chloroplasts/genetics ; Circadian Rhythm/*genetics ; Diatoms/*cytology/*physiology ; Enzymes/genetics/metabolism ; Evolution, Molecular ; *Gene Expression ; Mitochondria/genetics ; Phylogeny ; Plankton/genetics/physiology ; RNA, Long Noncoding ; }, abstract = {Coastal regions contribute an estimated 20% of annual gross primary production in the oceans, despite occupying only 0.03% of their surface area. Diatoms frequently dominate coastal sediments, where they experience large variations in light regime resulting from the interplay of diurnal and tidal cycles. Here, we report on an extensive diurnal transcript profiling experiment of the motile benthic diatom Seminavis robusta. Nearly 90% (23 328) of expressed protein-coding genes and 66.9% (1124) of expressed long intergenic non-coding RNAs showed significant expression oscillations and are predominantly phasing at night with a periodicity of 24 h. Phylostratigraphic analysis found that rhythmic genes are enriched in highly conserved genes, while diatom-specific genes are predominantly associated with midnight expression. Integration of genetic and physiological cell cycle markers with silica depletion data revealed potential new silica cell wall-associated gene families specific to diatoms. Additionally, we observed 1752 genes with a remarkable semidiurnal (12-h) periodicity, while the expansion of putative circadian transcription factors may reflect adaptations to cope with highly unpredictable external conditions. Taken together, our results provide new insights into the adaptations of diatoms to the benthic environment and serve as a valuable resource for the study of diurnal regulation in photosynthetic eukaryotes.}, } @article {pmid33906412, year = {2021}, author = {Schikora-Tamarit, MÀ and Marcet-Houben, M and Nosek, J and Gabaldón, T}, title = {Shared evolutionary footprints suggest mitochondrial oxidative damage underlies multiple complex I losses in fungi.}, journal = {Open biology}, volume = {11}, number = {4}, pages = {200362}, pmid = {33906412}, issn = {2046-2441}, mesh = {*Biological Evolution ; Computational Biology/methods ; Electron Transport Complex I/*genetics/*metabolism ; Eukaryota/genetics/metabolism ; Fungi/classification/*physiology ; Genome, Fungal ; Genomics ; Mitochondria/*genetics/*metabolism ; *Oxidative Phosphorylation ; *Oxidative Stress ; Phylogeny ; }, abstract = {Oxidative phosphorylation is among the most conserved mitochondrial pathways. However, one of the cornerstones of this pathway, the multi-protein complex NADH : ubiquinone oxidoreductase (complex I) has been lost multiple independent times in diverse eukaryotic lineages. The causes and consequences of these convergent losses remain poorly understood. Here, we used a comparative genomics approach to reconstruct evolutionary paths leading to complex I loss and infer possible evolutionary scenarios. By mining available mitochondrial and nuclear genomes, we identified eight independent events of mitochondrial complex I loss across eukaryotes, of which six occurred in fungal lineages. We focused on three recent loss events that affect closely related fungal species, and inferred genomic changes convergently associated with complex I loss. Based on these results, we predict novel complex I functional partners and relate the loss of complex I with the presence of increased mitochondrial antioxidants, higher fermentative capabilities, duplications of alternative dehydrogenases, loss of alternative oxidases and adaptation to antifungal compounds. To explain these findings, we hypothesize that a combination of previously acquired compensatory mechanisms and exposure to environmental triggers of oxidative stress (such as hypoxia and/or toxic chemicals) induced complex I loss in fungi.}, } @article {pmid33909617, year = {2021}, author = {Gurke, M and Vidal-Gorosquieta, A and Pajimans, JLA and Wȩcek, K and Barlow, A and González-Fortes, G and Hartmann, S and Grandal-d'Anglade, A and Hofreiter, M}, title = {Insight into the introduction of domestic cattle and the process of Neolithization to the Spanish region Galicia by genetic evidence.}, journal = {PloS one}, volume = {16}, number = {4}, pages = {e0249537}, pmid = {33909617}, issn = {1932-6203}, mesh = {Animals ; Animals, Domestic/*classification/*genetics ; Breeding ; Cattle ; Domestication ; Evolution, Molecular ; Female ; Fossils/*history ; High-Throughput Nucleotide Sequencing ; History, Ancient ; Introduced Species/*history ; Male ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA/*methods ; Spain ; }, abstract = {Domestic cattle were brought to Spain by early settlers and agricultural societies. Due to missing Neolithic sites in the Spanish region of Galicia, very little is known about this process in this region. We sampled 18 cattle subfossils from different ages and different mountain caves in Galicia, of which 11 were subject to sequencing of the mitochondrial genome and phylogenetic analysis, to provide insight into the introduction of cattle to this region. We detected high similarity between samples from different time periods and were able to compare the time frame of the first domesticated cattle in Galicia to data from the connecting region of Cantabria to show a plausible connection between the Neolithization of these two regions. Our data shows a close relationship of the early domesticated cattle of Galicia and modern cow breeds and gives a general insight into cattle phylogeny. We conclude that settlers migrated to this region of Spain from Europe and introduced common European breeds to Galicia.}, } @article {pmid33921106, year = {2021}, author = {Bonora, M and Missiroli, S and Perrone, M and Fiorica, F and Pinton, P and Giorgi, C}, title = {Mitochondrial Control of Genomic Instability in Cancer.}, journal = {Cancers}, volume = {13}, number = {8}, pages = {}, pmid = {33921106}, issn = {2072-6694}, support = {IG-23670//Associazione Italiana per la Ricerca sul Cancro/ ; IG-19803//Associazione Italiana per la Ricerca sul Cancro/ ; GGP11139B//Fondazione Telethon/ ; GR-2013-02356747//Ministero della Salute/ ; PRIN2017E5L5P3//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; PRIN20177E9EPY//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; 853057-InflaPML/ERC_/European Research Council/International ; }, abstract = {Mitochondria are well known to participate in multiple aspects of tumor formation and progression. They indeed can alter the susceptibility of cells to engage regulated cell death, regulate pro-survival signal transduction pathways and confer metabolic plasticity that adapts to specific tumor cell demands. Interestingly, a relatively poorly explored aspect of mitochondria in neoplastic disease is their contribution to the characteristic genomic instability that underlies the evolution of the disease. In this review, we summarize the known mechanisms by which mitochondrial alterations in cancer tolerate and support the accumulation of DNA mutations which leads to genomic instability. We describe recent studies elucidating mitochondrial responses to DNA damage as well as the direct contribution of mitochondria to favor the accumulation of DNA alterations.}, } @article {pmid33923118, year = {2021}, author = {Filip, E and Skuza, L}, title = {Horizontal Gene Transfer Involving Chloroplasts.}, journal = {International journal of molecular sciences}, volume = {22}, number = {9}, pages = {}, pmid = {33923118}, issn = {1422-0067}, mesh = {Cell Nucleus/*genetics ; Chloroplasts/*genetics ; Endophytes/genetics ; *Gene Transfer, Horizontal ; Genome ; Mitochondria/*genetics ; Plants/genetics ; Plastids/genetics ; }, abstract = {Horizontal gene transfer (HGT)- is defined as the acquisition of genetic material from another organism. However, recent findings indicate a possible role of HGT in the acquisition of traits with adaptive significance, suggesting that HGT is an important driving force in the evolution of eukaryotes as well as prokaryotes. It has been noted that, in eukaryotes, HGT is more prevalent than originally thought. Mitochondria and chloroplasts lost a large number of genes after their respective endosymbiotic events occurred. Even after this major content loss, organelle genomes still continue to lose their own genes. Many of these are subsequently acquired by intracellular gene transfer from the original plastid. The aim of our review was to elucidate the role of chloroplasts in the transfer of genes. This review also explores gene transfer involving mitochondrial and nuclear genomes, though recent studies indicate that chloroplast genomes are far more active in HGT as compared to these other two DNA-containing cellular compartments.}, } @article {pmid33924228, year = {2021}, author = {Kolchanova, S and Komissarov, A and Kliver, S and Mazo-Vargas, A and Afanador, Y and Velez-Valentín, J and de la Rosa, RV and Castro-Marquez, S and Rivera-Colon, I and Majeske, AJ and Wolfsberger, WW and Hains, T and Corvelo, A and Martinez-Cruzado, JC and Glenn, TC and Robinson, O and Koepfli, KP and Oleksyk, TK}, title = {Molecular Phylogeny and Evolution of Amazon Parrots in the Greater Antilles.}, journal = {Genes}, volume = {12}, number = {4}, pages = {}, pmid = {33924228}, issn = {2073-4425}, mesh = {Amazona/*classification/genetics ; Animals ; Brazil ; Cuba ; DNA, Mitochondrial/*genetics ; Evolution, Molecular ; High-Throughput Nucleotide Sequencing ; Jamaica ; Mitochondria/*genetics ; Molecular Sequence Annotation ; Phylogeny ; Puerto Rico ; Sequence Analysis, DNA/*methods ; }, abstract = {Amazon parrots (Amazona spp.) colonized the islands of the Greater Antilles from the Central American mainland, but there has not been a consensus as to how and when this happened. Today, most of the five remaining island species are listed as endangered, threatened, or vulnerable as a consequence of human activity. We sequenced and annotated full mitochondrial genomes of all the extant Amazon parrot species from the Greater Antillean (A. leucocephala (Cuba), A. agilis, A. collaria (both from Jamaica), A. ventralis (Hispaniola), and A. vittata (Puerto Rico)), A. albifrons from mainland Central America, and A. rhodocorytha from the Atlantic Forest in Brazil. The assembled and annotated mitogenome maps provide information on sequence organization, variation, population diversity, and evolutionary history for the Caribbean species including the critically endangered A. vittata. Despite the larger number of available samples from the Puerto Rican Parrot Recovery Program, the sequence diversity of the A. vittata population in Puerto Rico was the lowest among all parrot species analyzed. Our data support the stepping-stone dispersal and speciation hypothesis that has started approximately 3.47 MYA when the ancestral population arrived from mainland Central America and led to diversification across the Greater Antilles, ultimately reaching the island of Puerto Rico 0.67 MYA. The results are presented and discussed in light of the geological history of the Caribbean and in the context of recent parrot evolution, island biogeography, and conservation. This analysis contributes to understating evolutionary history and empowers subsequent assessments of sequence variation and helps design future conservation efforts in the Caribbean.}, } @article {pmid33929506, year = {2021}, author = {Liao, Z and Schelcher, C and Smirnov, A}, title = {YbeY, éminence grise of ribosome biogenesis.}, journal = {Biochemical Society transactions}, volume = {49}, number = {2}, pages = {727-745}, doi = {10.1042/BST20200669}, pmid = {33929506}, issn = {1470-8752}, mesh = {Amino Acid Sequence ; Animals ; GTP-Binding Proteins/*metabolism ; Humans ; Phylogeny ; Protein Binding ; RNA-Binding Proteins/*metabolism ; Ribonucleases/classification/genetics/*metabolism ; Ribosomal Proteins/*metabolism ; Ribosomes/*metabolism ; Sequence Homology, Amino Acid ; }, abstract = {YbeY is an ultraconserved small protein belonging to the unique heritage shared by most existing bacteria and eukaryotic organelles of bacterial origin, mitochondria and chloroplasts. Studied in more than a dozen of evolutionarily distant species, YbeY is invariably critical for cellular physiology. However, the exact mechanisms by which it exerts such penetrating influence are not completely understood. In this review, we attempt a transversal analysis of the current knowledge about YbeY, based on genetic, structural, and biochemical data from a wide variety of models. We propose that YbeY, in association with the ribosomal protein uS11 and the assembly GTPase Era, plays a critical role in the biogenesis of the small ribosomal subunit, and more specifically its platform region, in diverse genetic systems of bacterial type.}, } @article {pmid33931054, year = {2021}, author = {Li, F and Lv, Y and Wen, Z and Bian, C and Zhang, X and Guo, S and Shi, Q and Li, D}, title = {The complete mitochondrial genome of the intertidal spider (Desis jiaxiangi) provides novel insights into the adaptive evolution of the mitogenome and the evolution of spiders.}, journal = {BMC ecology and evolution}, volume = {21}, number = {1}, pages = {72}, pmid = {33931054}, issn = {2730-7182}, mesh = {Animals ; Base Sequence ; *Genome, Mitochondrial/genetics ; Phylogeny ; Silk/genetics ; *Spiders/genetics ; }, abstract = {BACKGROUND: Although almost all extant spider species live in terrestrial environments, a few species live fully submerged in freshwater or seawater. The intertidal spiders (genus Desis) built silk nests within coral crevices can survive submerged in high tides. The diving bell spider, Argyroneta aquatica, resides in a similar dynamic environment but exclusively in freshwater. Given the pivotal role played by mitochondria in supplying most energy for physiological activity via oxidative phosphorylation and the environment, herein we sequenced the complete mitogenome of Desis jiaxiangi to investigate the adaptive evolution of the aquatic spider mitogenomes and the evolution of spiders.

RESULTS: We assembled a complete mitogenome of the intertidal spider Desis jiaxiangi and performed comparative mitochondrial analyses of data set comprising of Desis jiaxiangi and other 45 previously published spider mitogenome sequences, including that of Argyroneta aquatica. We found a unique transposition of trnL2 and trnN genes in Desis jiaxiangi. Our robust phylogenetic topology clearly deciphered the evolutionary relationships between Desis jiaxiangi and Argyroneta aquatica as well as other spiders. We dated the divergence of Desis jiaxiangi and Argyroneta aquatica to the late Cretaceous at ~ 98 Ma. Our selection analyses detected a positive selection signal in the nd4 gene of the aquatic branch comprising both Desis jiaxiangi and Argyroneta aquatica. Surprisingly, Pirata subpiraticus, Hypochilus thorelli, and Argyroneta aquatica each had a higher Ka/Ks value in the 13 PCGs dataset among 46 taxa with complete mitogenomes, and these three species also showed positive selection signal in the nd6 gene.

CONCLUSIONS: Our finding of the unique transposition of trnL2 and trnN genes indicates that these genes may have experienced rearrangements in the history of intertidal spider evolution. The positive selection signals in the nd4 and nd6 genes might enable a better understanding of the spider metabolic adaptations in relation to different environments. Our construction of a novel mitogenome for the intertidal spider thus sheds light on the evolutionary history of spiders and their mitogenomes.}, } @article {pmid33946769, year = {2021}, author = {Oborník, M}, title = {Enigmatic Evolutionary History of Porphobilinogen Deaminase in Eukaryotic Phototrophs.}, journal = {Biology}, volume = {10}, number = {5}, pages = {}, pmid = {33946769}, issn = {2079-7737}, support = {21-03224S//Czech Science Foundation/ ; CZ.02.1.01/0.0/0.0/16_019/0000759//European Regional Development Fund/ ; }, abstract = {In most eukaryotic phototrophs, the entire heme synthesis is localized to the plastid, and enzymes of cyanobacterial origin dominate the pathway. Despite that, porphobilinogen deaminase (PBGD), the enzyme responsible for the synthesis of hydroxymethybilane in the plastid, shows phylogenetic affiliation to α-proteobacteria, the supposed ancestor of mitochondria. Surprisingly, no PBGD of such origin is found in the heme pathway of the supposed partners of the primary plastid endosymbiosis, a primarily heterotrophic eukaryote, and a cyanobacterium. It appears that α-proteobacterial PBGD is absent from glaucophytes but is present in rhodophytes, chlorophytes, plants, and most algae with complex plastids. This may suggest that in eukaryotic phototrophs, except for glaucophytes, either the gene from the mitochondrial ancestor was retained while the cyanobacterial and eukaryotic pseudoparalogs were lost in evolution, or the gene was acquired by non-endosymbiotic gene transfer from an unspecified α-proteobacterium and functionally replaced its cyanobacterial and eukaryotic counterparts.}, } @article {pmid33951769, year = {2021}, author = {Ndosi, BA and Park, H and Lee, D and Choe, S and Kang, Y and Nath, TC and Bia, MM and Eamudomkarn, C and Jeon, HK and Eom, KS}, title = {Mitochondrial Genome of Spirometra theileri Compared with Other Spirometra Species.}, journal = {The Korean journal of parasitology}, volume = {59}, number = {2}, pages = {139-148}, pmid = {33951769}, issn = {1738-0006}, support = {//International Parasite Resource Bank/ ; 2020-0042//Inclusive Business Solution (IBS) project, Korea/ ; }, mesh = {Animals ; Genome, Helminth ; *Genome, Mitochondrial ; Male ; Panthera/parasitology ; Phylogeny ; Spirometra/classification/*genetics/isolation & purification ; Tanzania ; }, abstract = {This study was carried out to provide information on the taxonomic classification and analysis of mitochondrial genomes of Spirometra theileri. One strobila of S. theileri was collected from the intestine of an African leopard (Panthera pardus) in the Maswa Game Reserve, Tanzania. The complete mtDNA sequence of S. theileri was 13,685 bp encoding 36 genes including 12 protein genes, 22 tRNAs and 2 rRNAs with absence of atp8. Divergences of 12 protein-coding genes were as follow: 14.9% between S. theileri and S. erinaceieuropaei, 14.7% between S. theileri and S. decipiens, and 14.5% between S. theileri with S. ranarum. Divergences of 12 proteins of S. theileri and S. erinaceieuropaei ranged from 2.3% in cox1 to 15.7% in nad5, while S. theileri varied from S. decipiens and S. ranarum by 1.3% in cox1 to 15.7% in nad3. Phylogenetic relationship of S. theileri with eucestodes inferred using the maximum likelihood and Bayesian inferences exhibited identical tree topologies. A clade composed of S. decipiens and S. ranarum formed a sister species to S. erinaceieuropaei, and S. theileri formed a sister species to all species in this clade. Within the diphyllobothridean clade, Dibothriocephalus, Diphyllobothrium and Spirometra formed a monophyletic group, and sister genera were well supported.}, } @article {pmid33952640, year = {2021}, author = {Fujino, K and Horie, M and Kojima, S and Shimizu, S and Nabekura, A and Kobayashi, H and Makino, A and Honda, T and Tomonaga, K}, title = {A Human Endogenous Bornavirus-Like Nucleoprotein Encodes a Mitochondrial Protein Associated with Cell Viability.}, journal = {Journal of virology}, volume = {95}, number = {14}, pages = {e0203020}, pmid = {33952640}, issn = {1098-5514}, mesh = {Bornaviridae/*genetics ; Cell Survival/*genetics ; Genome, Human ; HEK293 Cells ; HeLa Cells ; Humans ; Mitochondria/*genetics/metabolism ; Mitochondrial Proteins/*genetics/physiology ; Nucleoproteins/genetics ; RNA, Viral ; RNA-Seq ; Transcriptome ; }, abstract = {Endogenous retroviruses (ERVs) are sequences in animal genomes that originated from ancient retrovirus infections; they provide genetic novelty in hosts by being coopted as functional genes or elements during evolution. Recently, we demonstrated that endogenous elements from not only from retroviruses but also nonretroviral RNA viruses are a possible source of functional genes in host animals. The remnants of ancient bornavirus infections, called endogenous bornavirus-like elements (EBLs), are present in the genomes of a wide variety of vertebrate species, and some express functional products in host cells. Previous studies have predicted that the human EBL locus derived from bornavirus nucleoprotein, termed hsEBLN-2, expresses mRNA encoding a protein, suggesting that hsEBLN-2 has acquired a cellular function during evolution. However, the detailed function of the hsEBLN-2-derived product remains to be elucidated. In this study, we show that the hsEBLN-2-derived protein E2 acts as a mitochondrial protein that interacts with mitochondrial host factors associated with apoptosis, such as HAX-1. We also demonstrate that knockdown of hsEBLN-2-derived RNA increased the levels of PARP and caspase-3 cleavage and markedly decreased cell viability. In contrast, overexpression of E2 enhanced cell viability, as well as the intracellular stability of HAX-1, under stress conditions. Our results suggest that hsEBLN-2 has been coopted as a host gene, the product of which is involved in cell viability by interacting with mitochondrial proteins. IMPORTANCE Our genomes contain molecular fossils of ancient viruses, called endogenous virus elements (EVEs). Mounting evidence suggests that EVEs derived from nonretroviral RNA viruses have acquired functions in host cells during evolution. Previous studies have revealed that a locus encoding a bornavirus-derived EVE, hsEBLN-2, which was generated approximately 43 million years ago in a human ancestor, may be linked to the development of some tumors. However, the function of hsEBLN-2 has not been determined. In this study, we found that the E2 protein, an expression product of hsEBLN-2, interacts with apoptosis-related host proteins as a mitochondrial protein and affects cell viability. This study suggests that nonretroviral RNA viral EVEs have been coopted by hosts with more diverse functions than previously thought, showing a pivotal role for RNA virus infection in evolution.}, } @article {pmid33952666, year = {2021}, author = {Reinke, AW}, title = {mSphere of Influence: Where the Pathogen Proteins Are.}, journal = {mSphere}, volume = {6}, number = {3}, pages = {}, pmid = {33952666}, issn = {2379-5042}, mesh = {Animals ; Fungal Proteins/chemistry/*genetics ; *Host-Pathogen Interactions ; Microsporidia/chemistry/*pathogenicity ; Proteomics ; }, abstract = {Aaron Reinke studies microsporidian evolution and how microsporidia interact with their hosts. In this mSphere of Influence article, he reflects on how the papers "A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells" (K. J. Roux, D. I. Kim, M. Raida, and B. Burke, J Cell Biol 196:801-810, 2012, https://doi.org/10.1083/jcb.201112098) and "Proteomic mapping of mitochondria in living cells via spatially restricted enzymatic tagging" (H.-W. Rhee, P. Zou, N. D. Udeshi, J. D. Martell, et al., Science 339:1328-1331, 2013, https://doi.org/10.1126/science.1230593) impacted his thinking on how to determine where proteins from intracellular pathogens are located within host cells.}, } @article {pmid33956890, year = {2021}, author = {Caccavale, F and Osca, D and D'Aniello, S and Crocetta, F}, title = {Molecular taxonomy confirms that the northeastern Atlantic and Mediterranean Sea harbor a single lancelet, Branchiostoma lanceolatum (Pallas, 1774) (Cephalochordata: Leptocardii: Branchiostomatidae).}, journal = {PloS one}, volume = {16}, number = {5}, pages = {e0251358}, pmid = {33956890}, issn = {1932-6203}, mesh = {Animals ; Atlantic Ocean ; DNA/genetics ; Lancelets/classification/*genetics ; Mediterranean Sea ; Mitochondria/genetics ; Multilocus Sequence Typing ; Phylogeny ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {Branchiostomatidae (lancelets or amphioxus) comprises about 30 species, several of which are well-established models in evolutionary development. Our zoological and ecological knowledge of the family is nonetheless limited. Despite evident differences can be found among known populations, the taxonomy of Branchiostoma lanceolatum (type species of the genus Branchiostoma) has never been investigated with modern methods through its range in the northeastern Atlantic and Mediterranean Sea. We address this via a multilocus molecular approach and comparing specimens collected from different European populations. Results obtained here confirm the presence of a single species inhabiting the range between the topotypical localities of B. lanceolatum (Atlantic Ocean) and of its junior synonym B. lubricum (Mediterranean Sea), without evincing geographical structure between populations. This suggests that environment most likely drives the characteristics observed in different geographic areas. The long larval phase and the slow mutation rate in lancelets may have played a key role in the evolutionary history of this iconic species.}, } @article {pmid33958611, year = {2021}, author = {Tuda, M and Iwase, SI and Kébé, K and Haran, J and Skuhrovec, J and Sanaei, E and Tsuji, N and Podlussány, A and Merkl, O and El-Heneidy, AH and Morimoto, K}, title = {Diversification, selective sweep, and body size in the invasive Palearctic alfalfa weevil infected with Wolbachia.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {9664}, pmid = {33958611}, issn = {2045-2322}, mesh = {Animals ; Asia ; Body Size ; Europe ; Female ; Genetic Variation/genetics ; Haplotypes/genetics ; Introduced Species ; Male ; Mitochondria/genetics ; Phylogeny ; Phylogeography ; Weevils/genetics/*microbiology ; *Wolbachia ; }, abstract = {The alfalfa weevil Hypera postica, native to the Western Palearctic, is an invasive legume pest with two divergent mitochondrial clades in its invading regions, the Western clade and the Eastern/Egyptian clade. However, knowledge regarding the native populations is limited. The Western clade is infected with the endosymbiotic bacteria Wolbachia that cause cytoplasmic incompatibility in host weevils. Our aim was to elucidate the spatial genetic structure of this insect and the effect of Wolbachia on its population diversity. We analyzed two mitochondrial and two nuclear genes of the weevil from its native ranges. The Western clade was distributed in western/central Europe, whereas the Eastern/Egyptian clade was distributed from the Mediterranean basin to central Asia. Intermediate mitotypes were found from the Balkans to central Asia. Most Western clade individuals in western Europe were infected with an identical Wolbachia strain. Mitochondrial genetic diversity of the infected individuals was minimal. The infected clades demonstrated a higher nonsynonymous/synonymous substitution rate ratio than the uninfected clades, suggesting a higher fixation of nonsynonymous mutations due to a selective sweep by Wolbachia. Trans-Mediterranean and within-European dispersal routes were supported. We suggest that the ancestral populations diversified by geographic isolation due to glaciations and that the diversity was reduced in the west by a recent Wolbachia-driven sweep(s). The intermediate clade exhibited a body size and host plant that differed from the other clades. Pros and cons of the possible use of infected-clade males to control uninfected populations are discussed.}, } @article {pmid33963405, year = {2021}, author = {Skejo, J and Garg, SG and Gould, SB and Hendriksen, M and Tria, FDK and Bremer, N and Franjević, D and Blackstone, NW and Martin, WF}, title = {Evidence for a Syncytial Origin of Eukaryotes from Ancestral State Reconstruction.}, journal = {Genome biology and evolution}, volume = {13}, number = {7}, pages = {}, pmid = {33963405}, issn = {1759-6653}, mesh = {Archaea/genetics ; *Biological Evolution ; *Eukaryota/genetics ; Eukaryotic Cells ; Phylogeny ; Prokaryotic Cells ; }, abstract = {Modern accounts of eukaryogenesis entail an endosymbiotic encounter between an archaeal host and a proteobacterial endosymbiont, with subsequent evolution giving rise to a unicell possessing a single nucleus and mitochondria. The mononucleate state of the last eukaryotic common ancestor (LECA) is seldom, if ever, questioned, even though cells harboring multiple (syncytia, coenocytes, and polykaryons) are surprisingly common across eukaryotic supergroups. Here, we present a survey of multinucleated forms. Ancestral character state reconstruction for representatives of 106 eukaryotic taxa using 16 different possible roots and supergroup sister relationships, indicate that LECA, in addition to being mitochondriate, sexual, and meiotic, was multinucleate. LECA exhibited closed mitosis, which is the rule for modern syncytial forms, shedding light on the mechanics of its chromosome segregation. A simple mathematical model shows that within LECA's multinucleate cytosol, relationships among mitochondria and nuclei were neither one-to-one, nor one-to-many, but many-to-many, placing mitonuclear interactions and cytonuclear compatibility at the evolutionary base of eukaryotic cell origin. Within a syncytium, individual nuclei and individual mitochondria function as the initial lower-level evolutionary units of selection, as opposed to individual cells, during eukaryogenesis. Nuclei within a syncytium rescue each other's lethal mutations, thereby postponing selection for viable nuclei and cytonuclear compatibility to the generation of spores, buffering transitional bottlenecks at eukaryogenesis. The prokaryote-to-eukaryote transition is traditionally thought to have left no intermediates, yet if eukaryogenesis proceeded via a syncytial common ancestor, intermediate forms have persisted to the present throughout the eukaryotic tree as syncytia but have so far gone unrecognized.}, } @article {pmid33965538, year = {2021}, author = {Neiber, MT and Chueca, LJ and Caro, A and Teixeira, D and Schlegel, KA and Gómez-Moliner, BJ and Walther, F and Glaubrecht, M and Hausdorf, B}, title = {Incorporating palaeogeography into ancestral area estimation can explain the disjunct distribution of land snails in Macaronesia and the Balearic Islands (Helicidae: Allognathini).}, journal = {Molecular phylogenetics and evolution}, volume = {162}, number = {}, pages = {107196}, doi = {10.1016/j.ympev.2021.107196}, pmid = {33965538}, issn = {1095-9513}, mesh = {Animals ; Cell Nucleus/genetics ; *Islands ; Mitochondria/genetics ; *Phylogeny ; *Phylogeography ; Snails/*genetics ; Spain ; }, abstract = {The systematics and biogeographical history of the Eastern Mediterranean and Macaronesian land snail tribe Allognathini (Helicidae: Helicinae) is investigated based on mitochondrial and nuclear DNA sequence data. Our molecular phylogenetic analyses indicate that the genus-group systematics of the tribe needs to be revised. We show for the first time that the narrow-range endemics Lampadia and Idiomela from the Madeira Archipelago belong to Allognathini and represent together the sister group of the diverse Canary Island Hemicycla radiation. We therefore suggest synonymising Lampadiini with Allognathini. Sister to these Macaronesian genera was the Balearic Island Allognathus radiation. Pseudotachea was not recovered as a monophyletic group and the two currently recognised species clustered in Iberus. Similarly, Adiverticula was not recovered as a monophyletic group and clustered in Hemicycla. We therefore suggest synonymising Pseudotachea with Iberus and Adiverticula with Hemicycla. The six genera in Allognathini, which we distinguish here (Cepaea, Iberus, Allognathus, Hemicycla, Idiomela and Lampadia), originated in Western to South-western Europe according to our ancestral area estimation and the fossil record. The disjunct distribution of the Balearic Islands and Macaronesian sister clades and the mainly Iberian Iberus clade that separated earlier can be explained by the separation of the Betic-Rif System from the Iberian Peninsula during the late Oligocene to early Miocene, along with independent Miocene dispersals to the Balearic Islands and Macaronesia from the Iberian Peninsula, where the ancestral lineage became extinct.}, } @article {pmid33974849, year = {2021}, author = {Mathur, V and Wakeman, KC and Keeling, PJ}, title = {Parallel functional reduction in the mitochondria of apicomplexan parasites.}, journal = {Current biology : CB}, volume = {31}, number = {13}, pages = {2920-2928.e4}, doi = {10.1016/j.cub.2021.04.028}, pmid = {33974849}, issn = {1879-0445}, mesh = {Animals ; Energy Metabolism ; Genome, Mitochondrial ; Mitochondria/genetics/*metabolism ; Parasites/*cytology/genetics/*metabolism ; *Phylogeny ; Toxoplasma ; }, abstract = {Gregarines are an early-diverging lineage of apicomplexan parasites that hold many clues into the origin and evolution of the group, a remarkable transition from free-living phototrophic algae into obligate parasites of animals.[1] Using single-cell transcriptomics targeting understudied lineages to complement available sequencing data, we characterized the mitochondrial metabolic repertoire across the tree of apicomplexans. In contrast to the large suite of proteins involved in aerobic respiration in well-studied parasites like Toxoplasma or Plasmodium,[2] we find that gregarine trophozoites have significantly reduced energy metabolism: most lack respiratory complexes III and IV, and some lack the electron transport chains (ETCs) and tricarboxylic acid (TCA) cycle entirely. Phylogenomic analyses show that these reductions took place several times in parallel, resulting in a functional range from fully aerobic organelles to extremely reduced "mitosomes" restricted to Fe-S cluster biosynthesis. The mitochondrial genome has also been lost repeatedly: in species with severe functional reduction simply by gene loss but in one species with a complete ETC by relocating cox1 to the nuclear genome. Severe functional reduction of mitochondria is generally associated with structural reduction, resulting in small, nondescript mitochondrial-related organelles (MROs).[3] By contrast, gregarines retain distinctive mitochondria with tubular cristae, even the most functionally reduced cases that also lack genes associated with cristae formation. Overall, the parallel, severe reduction of gregarine mitochondria expands the diversity of organisms that contain MROs and further emphasizes the role of parallel transitions in apicomplexan evolution.}, } @article {pmid33975946, year = {2021}, author = {Takusagawa, M and Kobayashi, Y and Fukao, Y and Hidaka, K and Endo, M and Sugiyama, H and Hamaji, T and Kato, Y and Miyakawa, I and Misumi, O and Shikanai, T and Nishimura, Y}, title = {HBD1 protein with a tandem repeat of two HMG-box domains is a DNA clip to organize chloroplast nucleoids in Chlamydomonas reinhardtii.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {20}, pages = {}, pmid = {33975946}, issn = {1091-6490}, mesh = {Chlamydomonas reinhardtii/*genetics/metabolism ; Chloroplast Proteins/classification/*genetics/metabolism ; DNA, Chloroplast/*genetics/metabolism ; Gene Expression Regulation ; Genome, Chloroplast/*genetics ; HMG-Box Domains/*genetics ; Mass Spectrometry/methods ; Mutation ; Phylogeny ; Protein Binding ; Proteomics/methods ; Tandem Repeat Sequences/*genetics ; }, abstract = {Compaction of bulky DNA is a universal issue for all DNA-based life forms. Chloroplast nucleoids (chloroplast DNA-protein complexes) are critical for chloroplast DNA maintenance and transcription, thereby supporting photosynthesis, but their detailed structure remains enigmatic. Our proteomic analysis of chloroplast nucleoids of the green alga Chlamydomonas reinhardtii identified a protein (HBD1) with a tandem repeat of two DNA-binding high mobility group box (HMG-box) domains, which is structurally similar to major mitochondrial nucleoid proteins transcription factor A, mitochondrial (TFAM), and ARS binding factor 2 protein (Abf2p). Disruption of the HBD1 gene by CRISPR-Cas9-mediated genome editing resulted in the scattering of chloroplast nucleoids. This phenotype was complemented when intact HBD1 was reintroduced, whereas a truncated HBD1 with a single HMG-box domain failed to complement the phenotype. Furthermore, ectopic expression of HBD1 in the mitochondria of yeast Δabf2 mutant successfully complemented the defects, suggesting functional similarity between HBD1 and Abf2p. Furthermore, in vitro assays of HBD1, including the electrophoretic mobility shift assay and DNA origami/atomic force microscopy, showed that HBD1 is capable of introducing U-turns and cross-strand bridges, indicating that proteins with two HMG-box domains would function as DNA clips to compact DNA in both chloroplast and mitochondrial nucleoids.}, } @article {pmid33983431, year = {2021}, author = {Dellière, S and Hamane, S and Aissaoui, N and Gits-Muselli, M and Bretagne, S and Alanio, A}, title = {Increased sensitivity of a new commercial reverse transcriptase-quantitative PCR for the detection of Pneumocystis jirovecii in respiratory specimens.}, journal = {Medical mycology}, volume = {59}, number = {8}, pages = {845-848}, doi = {10.1093/mmy/myab029}, pmid = {33983431}, issn = {1460-2709}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Opportunistic Infections/microbiology ; Pneumocystis carinii/genetics/*isolation & purification ; Pneumonia, Pneumocystis/*diagnosis/microbiology ; Real-Time Polymerase Chain Reaction/methods/*standards ; Respiratory System/*microbiology ; Reverse Transcriptase Polymerase Chain Reaction/methods/*standards ; Sensitivity and Specificity ; }, abstract = {UNLABELLED: Optimal sensitivity to detect low Pneumocystis loads is of importance to take individual and collective measures to avoid evolution towards Pneumocystis pneumonia and outbreaks in immunocompromised patients. This study compares two qPCR procedures, a new automated RTqPCR using the GeneLEAD VIII extractor/thermocycler (GLVIII; ∼2.2 h workflow) and a previously validated in-house qPCR assays (IH; ∼5 h workflow) both targeting mtSSU and mtLSU for detecting P. jirovecii in 213 respiratory samples. GLVIII was found to be more sensitive than IH, detecting eight more specimens. Bland-Altman analysis between the two procedures showed a Cq bias of 1.17 ± 0.07 in favor of GLVIII.

LAY SUMMARY: The fungus Pneumocystis needs to be detected early in respiratory samples to prevent pneumonia in immunocompromised hosts. We evaluated a new commercial RTqPCR on 213 respiratory samples to detect Pneumocystis and found it more sensitive and faster than our routine sensitive in-house qPCR assay.}, } @article {pmid33984441, year = {2021}, author = {Lim, LWK and Chung, HH and Lau, MML and Aziz, F and Gan, HM}, title = {Improving the phylogenetic resolution of Malaysian and Javan mahseer (Cyprinidae), Tor tambroides and Tor tambra: Whole mitogenomes sequencing, phylogeny and potential mitogenome markers.}, journal = {Gene}, volume = {791}, number = {}, pages = {145708}, doi = {10.1016/j.gene.2021.145708}, pmid = {33984441}, issn = {1879-0038}, mesh = {Animals ; Base Sequence/genetics ; Biomarkers ; Cyprinidae/*classification/*genetics ; DNA, Mitochondrial/genetics ; Genes, Mitochondrial/genetics ; Genome, Mitochondrial/*genetics ; Haplotypes/genetics ; Indonesia ; Malaysia ; Mitochondria/genetics ; Phylogeny ; Sequence Analysis, DNA/methods ; }, abstract = {The true mahseer (Tor spp.) is one of the highest valued fish in the world due to its high nutritional value and great unique taste. Nevertheless, its morphological characterization and single mitochondrial gene phylogeny in the past had yet to resolve the ambiguity in its taxonomical classification. In this study, we sequenced and assembled 11 complete mahseer mitogenomes collected from Java of Indonesia, Pahang and Terengganu of Peninsular Malaysia as well as Sarawak of East Malaysia. The mitogenome evolutionary relationships among closely related Tor spp. samples were investigated based on maximum likelihood phylogenetic tree construction. Compared to the commonly used COX1 gene fragment, the complete COX1, Cytb, ND2, ND4 and ND5 genes appear to be better phylogenetic markers for genetic differentiation at the population level. In addition, a total of six population-specific mitolineage haplotypes were identified among the mahseer samples analyzed, which this offers hints towards its taxonomical landscape.}, } @article {pmid33991648, year = {2021}, author = {Moreno-Carmona, M and Cameron, SL and Prada Quiroga, CF}, title = {How are the mitochondrial genomes reorganized in Hexapoda? Differential evolution and the first report of convergences within Hexapoda.}, journal = {Gene}, volume = {791}, number = {}, pages = {145719}, doi = {10.1016/j.gene.2021.145719}, pmid = {33991648}, issn = {1879-0038}, mesh = {Animals ; Databases, Genetic ; Evolution, Molecular ; Gene Order/genetics ; Gene Rearrangement/genetics ; Genes, Mitochondrial/*genetics ; Genome, Mitochondrial/*genetics ; Insecta/classification/*genetics ; Mitochondria/classification/genetics ; Phylogeny ; Sequence Analysis, DNA/methods ; }, abstract = {The evolution of the Hexapoda mitochondrial genome has been the focus of several genetic and evolutionary studies over the last decades. However, they have concentrated on certain taxonomic orders of economic or health importance. The recent increase of mitochondrial genomes sequencing of diverse taxonomic orders generates an important opportunity to clarify the evolution of this group of organisms. However, there is no comparative study that investigates the evolution of the Hexapoda mitochondrial genome. In order to verify the level of rearrangement and the mitochondrial genome evolution, we performed a comparative genomic analysis of the Hexapoda mitochondrial genome available in the NCBI database. Using a combination of bioinformatics methods to carefully examine the mitochondrial gene rearrangements in 1198 Hexapoda species belonging to 32 taxonomic orders, we determined that there is a great variation in the rate of rearrangement by gene and by taxonomic order. A higher rate of genetic reassortment is observed in Phthiraptera, Thysanoptera, Protura, and Hymenoptera; compared to other taxonomic orders. Twenty-four events of convergence in the genetic order between different taxonomic orders were determined, most of them not previously reported; which proves the great evolutionary dynamics within Hexapoda.}, } @article {pmid34001130, year = {2021}, author = {Záhonová, K and Lax, G and Sinha, SD and Leonard, G and Richards, TA and Lukeš, J and Wideman, JG}, title = {Single-cell genomics unveils a canonical origin of the diverse mitochondrial genomes of euglenozoans.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {103}, pmid = {34001130}, issn = {1741-7007}, support = {20-07186S//Grantová Agentura České Republiky/ ; ERC CZ LL1601//Ministerstvo Školství, Mládeže a Tělovýchovy/ ; URF\R\191005//Royal Society/ ; 16_019/0000759//Czech Ministry of Education/ ; }, mesh = {DNA, Mitochondrial ; *Euglenida/genetics ; Euglenozoa/genetics ; Europium ; *Genome, Mitochondrial/genetics ; Genomics ; Phylogeny ; RNA, Transfer ; }, abstract = {BACKGROUND: The supergroup Euglenozoa unites heterotrophic flagellates from three major clades, kinetoplastids, diplonemids, and euglenids, each of which exhibits extremely divergent mitochondrial characteristics. Mitochondrial genomes (mtDNAs) of euglenids comprise multiple linear chromosomes carrying single genes, whereas mitochondrial chromosomes are circular non-catenated in diplonemids, but circular and catenated in kinetoplastids. In diplonemids and kinetoplastids, mitochondrial mRNAs require extensive and diverse editing and/or trans-splicing to produce mature transcripts. All known euglenozoan mtDNAs exhibit extremely short mitochondrial small (rns) and large (rnl) subunit rRNA genes, and absence of tRNA genes. How these features evolved from an ancestral bacteria-like circular mitochondrial genome remains unanswered.

RESULTS: We sequenced and assembled 20 euglenozoan single-cell amplified genomes (SAGs). In our phylogenetic and phylogenomic analyses, three SAGs were placed within kinetoplastids, 14 within diplonemids, one (EU2) within euglenids, and two SAGs with nearly identical small subunit rRNA gene (18S) sequences (EU17/18) branched as either a basal lineage of euglenids, or as a sister to all euglenozoans. Near-complete mitochondrial genomes were identified in EU2 and EU17/18. Surprisingly, both EU2 and EU17/18 mitochondrial contigs contained multiple genes and one tRNA gene. Furthermore, EU17/18 mtDNA possessed several features unique among euglenozoans including full-length rns and rnl genes, six mitoribosomal genes, and nad11, all likely on a single chromosome.

CONCLUSIONS: Our data strongly suggest that EU17/18 is an early-branching euglenozoan with numerous ancestral mitochondrial features. Collectively these data contribute to untangling the early evolution of euglenozoan mitochondria.}, } @article {pmid34003535, year = {2021}, author = {Pereira, RJ and Lima, TG and Pierce-Ward, NT and Chao, L and Burton, RS}, title = {Recovery from hybrid breakdown reveals a complex genetic architecture of mitonuclear incompatibilities.}, journal = {Molecular ecology}, volume = {30}, number = {23}, pages = {6403-6416}, doi = {10.1111/mec.15985}, pmid = {34003535}, issn = {1365-294X}, support = {//US National Science Foundation/ ; IOS1754347//Division of Integrative Organismal Systems/ ; DEB1556466//Division of Environmental Biology/ ; //Ludwig-Maximilians-Universitaet Muenchen/ ; }, mesh = {Alleles ; Animals ; Cell Nucleus/genetics ; *Copepoda/genetics ; Hybridization, Genetic ; Mitochondria/genetics ; *Reproductive Isolation ; }, abstract = {Reproductive isolation is often achieved when genes that are neutral or beneficial in their genomic background become functionally incompatible in a foreign genomic background, causing inviability, sterility or other forms of low fitness in hybrids. Recent studies suggest that mitonuclear interactions are among the initial incompatibilities to evolve at early stages of population divergence across taxa. Yet, the genomic architecture of mitonuclear incompatibilities has rarely been elucidated. We employ an experimental evolution approach starting with low-fitness F2 interpopulation hybrids of the copepod Tigriopus californicus, in which frequencies of compatible and incompatible nuclear alleles change in response to an alternative mitochondrial background. After about nine generations, we observe a generalized increase in population size and in survivorship, suggesting efficiency of selection against maladaptive phenotypes. Whole genome sequencing of evolved populations showed some consistent allele frequency changes across three replicates of each reciprocal cross, but markedly different patterns between mitochondrial backgrounds. In only a few regions (~6.5% of the genome), the same parental allele was overrepresented irrespective of the mitochondrial background. About 33% of the genome showed allele frequency changes consistent with divergent selection, with the location of these genomic regions strongly differing between mitochondrial backgrounds. In 87% and 89% of these genomic regions, the dominant nuclear allele matched the associated mitochondrial background, consistent with mitonuclear co-adaptation. These results suggest that mitonuclear incompatibilities have a complex polygenic architecture that differs between populations, potentially generating genome-wide barriers to gene flow between closely related taxa.}, } @article {pmid34006275, year = {2021}, author = {Hirakawa, Y and Senda, M and Fukuda, K and Yu, HY and Ishida, M and Taira, M and Kinbara, K and Senda, T}, title = {Characterization of a novel type of carbonic anhydrase that acts without metal cofactors.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {105}, pmid = {34006275}, issn = {1741-7007}, support = {18K06358//Japan Society for the Promotion of Science/ ; 18H05419//Japan Society for the Promotion of Science/ ; JP20am0101071//Japan Agency for Medical Research and Development/ ; 19H03280//Japan Society for the Promotion of Science/ ; 18H05419//Japan Society for the Promotion of Science/ ; }, mesh = {Bacteria/metabolism ; Carbon Dioxide ; Carbonic Anhydrases/genetics/*metabolism ; Eukaryota ; Humans ; Photosynthesis ; Plants/metabolism ; Recombinant Proteins ; }, abstract = {BACKGROUND: Carbonic anhydrases (CAs) are universal metalloenzymes that catalyze the reversible conversion of carbon dioxide (CO2) and bicarbonate (HCO3[-]). They are involved in various biological processes, including pH control, respiration, and photosynthesis. To date, eight evolutionarily unrelated classes of CA families (α, β, γ, δ, ζ, η, θ, and ι) have been identified. All are characterized by an active site accommodating the binding of a metal cofactor, which is assumed to play a central role in catalysis. This feature is thought to be the result of convergent evolution.

RESULTS: Here, we report that a previously uncharacterized protein group, named "COG4337," constitutes metal-independent CAs from the newly discovered ι-class. Genes coding for COG4337 proteins are found in various bacteria and photosynthetic eukaryotic algae. Biochemical assays demonstrated that recombinant COG4337 proteins from a cyanobacterium (Anabaena sp. PCC7120) and a chlorarachniophyte alga (Bigelowiella natans) accelerated CO2 hydration. Unexpectedly, these proteins exhibited their activity under metal-free conditions. Based on X-ray crystallography and point mutation analysis, we identified a metal-free active site within the cone-shaped α+β barrel structure. Furthermore, subcellular localization experiments revealed that COG4337 proteins are targeted into plastids and mitochondria of B. natans, implicating their involvement in CO2 metabolism in these organelles.

CONCLUSIONS: COG4337 proteins shared a short sequence motif and overall structure with ι-class CAs, whereas they were characterized by metal independence, unlike any known CAs. Therefore, COG4337 proteins could be treated as a variant type of ι-class CAs. Our findings suggested that this novel type of ι-CAs can function even in metal-poor environments (e.g., the open ocean) without competition with other metalloproteins for trace metals. Considering the widespread prevalence of ι-CAs across microalgae, this class of CAs may play a role in the global carbon cycle.}, } @article {pmid34008202, year = {2021}, author = {Speijer, D}, title = {Zombie ideas about early endosymbiosis: Which entry mechanisms gave us the "endo" in different endosymbionts?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {7}, pages = {e2100069}, doi = {10.1002/bies.202100069}, pmid = {34008202}, issn = {1521-1878}, mesh = {Bacteria/genetics ; Biological Evolution ; Eukaryota ; *Eukaryotic Cells ; Phylogeny ; *Symbiosis ; }, abstract = {Recently, a review regarding the mechanics and evolution of mitochondrial fission appeared in Nature. Surprisingly, it stated authoritatively that the mitochondrial outer membrane, in contrast with the inner membrane of bacterial descent, was acquired from the host, presumably during uptake. However, it has been known for quite some time that this membrane was also derived from the Gram-negative, alpha-proteobacterium related precursor of present-day mitochondria. The zombie idea of the host membrane still surrounding the endosymbiont is not only wrong, but more importantly, might hamper the proper conception of possible scenarios of eukaryogenesis. Why? Because it steers the imagination not only with regard to possible uptake mechanisms, but also regarding what went on before. Here I critically discuss both the evidence for the continuity of the bacterial outer membrane, the reasons for the persistence of the erroneous host membrane hypothesis and the wider implications of these misconceptions for the ideas regarding events occurring during the first steps towards the evolution of the eukaryotes and later major eukaryotic differentiations. I will also highlight some of the latest insights regarding different instances of endosymbiont evolution.}, } @article {pmid34009087, year = {2022}, author = {Ma, ZJ and Li, GZ and Chen, SM and Han, JL and Hanif, Q}, title = {Rich maternal and paternal genetic diversity and divergent lineage composition in wild yak (Bos mutus).}, journal = {Animal biotechnology}, volume = {33}, number = {6}, pages = {1318-1321}, doi = {10.1080/10495398.2021.1895187}, pmid = {34009087}, issn = {1532-2378}, mesh = {Cattle/genetics ; Animals ; Phylogeny ; Haplotypes/genetics ; *DNA, Mitochondrial/genetics ; *Mitochondria/genetics ; Genetic Variation/genetics ; }, abstract = {Wild yak (Bos mutus) is a vulnerable bovine species on the Qinghai-Tibetan Plateau. So far, most studies on the molecular genetic diversity of wild yak have focused on autosomal and mtDNA variations based on the small number of samples. In this study, we analyzed 84 D-loop and 24 whole mitogenome sequences of wild yak to further comprehensively explore its maternal genetic diversity and lineage composition. Meanwhile, using six yak Y-specific polymorphic markers (i.e., SRY4, USP9Y, UTY19, AMELY3, OFD1Y10 and INRA189), we assessed the paternal genetic diversity and lineage composition based on eight wild yak. Our results showed that wild yak exhibited abundant maternal genetic diversity with haplotype diversities of 0.9621 ± 0.0078 and 0.9928 ± 0.0144 in the D-loop and whole mitogenome sequences, respectively. Maternal phylogenetic analysis of wild yak uncovered three defined lineages (mt-I, mt-II and mt-III). Similarly, profuse paternal genetic diversity was observed in wild yak with Y-haplotype diversity at 0.8214 ± 0.1007. Two Y-haplogroups (Y1 and Y2) and four Y-haplotypes (yH1-yH4) were identified in paternal phylogenetic analysis, indicating wild yak to be of two paternal lineages. The present study of genetic diversity and lineage composition of wild yak would provide useful information for the genetic resource conservation and utilization of this vulnerable wild species.}, } @article {pmid34009340, year = {2021}, author = {Phua, SY and De Smet, B and Remacle, C and Chan, KX and Van Breusegem, F}, title = {Reactive oxygen species and organellar signaling.}, journal = {Journal of experimental botany}, volume = {72}, number = {16}, pages = {5807-5824}, doi = {10.1093/jxb/erab218}, pmid = {34009340}, issn = {1460-2431}, mesh = {Cell Nucleus/metabolism ; Photosynthesis ; *Plant Cells ; Reactive Oxygen Species/metabolism ; *Signal Transduction ; }, abstract = {The evolution of photosynthesis and its associated metabolic pathways has been crucial to the successful establishment of plants, but has also challenged plant cells in the form of production of reactive oxygen species (ROS). Intriguingly, multiple forms of ROS are generated in virtually every plant cell compartment through diverse pathways. As a result, a sophisticated network of ROS detoxification and signaling that is simultaneously tailored to individual organelles and safeguards the entire cell is necessary. Here we take an organelle-centric view on the principal sources and sinks of ROS across the plant cell and provide insights into the ROS-induced organelle to nucleus retrograde signaling pathways needed for operational readjustments during environmental stresses.}, } @article {pmid34011275, year = {2021}, author = {Porter, TM and Hajibabaei, M}, title = {Profile hidden Markov model sequence analysis can help remove putative pseudogenes from DNA barcoding and metabarcoding datasets.}, journal = {BMC bioinformatics}, volume = {22}, number = {1}, pages = {256}, pmid = {34011275}, issn = {1471-2105}, mesh = {Cell Nucleus ; *DNA Barcoding, Taxonomic ; DNA, Mitochondrial ; Mitochondria/genetics ; Phylogeny ; *Pseudogenes/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Pseudogenes are non-functional copies of protein coding genes that typically follow a different molecular evolutionary path as compared to functional genes. The inclusion of pseudogene sequences in DNA barcoding and metabarcoding analysis can lead to misleading results. None of the most widely used bioinformatic pipelines used to process marker gene (metabarcode) high throughput sequencing data specifically accounts for the presence of pseudogenes in protein-coding marker genes. The purpose of this study is to develop a method to screen for nuclear mitochondrial DNA segments (nuMTs) in large COI datasets. We do this by: (1) describing gene and nuMT characteristics from an artificial COI barcode dataset, (2) show the impact of two different pseudogene removal methods on perturbed community datasets with simulated nuMTs, and (3) incorporate a pseudogene filtering step in a bioinformatic pipeline that can be used to process Illumina paired-end COI metabarcode sequences. Open reading frame length and sequence bit scores from hidden Markov model (HMM) profile analysis were used to detect pseudogenes.

RESULTS: Our simulations showed that it was more difficult to identify nuMTs from shorter amplicon sequences such as those typically used in metabarcoding compared with full length DNA barcodes that are used in the construction of barcode libraries. It was also more difficult to identify nuMTs in datasets where there is a high percentage of nuMTs. Existing bioinformatic pipelines used to process metabarcode sequences already remove some nuMTs, especially in the rare sequence removal step, but the addition of a pseudogene filtering step can remove up to 5% of sequences even when other filtering steps are in place.

CONCLUSIONS: Open reading frame length filtering alone or combined with hidden Markov model profile analysis can be used to effectively screen out apparent pseudogenes from large datasets. There is more to learn from COI nuMTs such as their frequency in DNA barcoding and metabarcoding studies, their taxonomic distribution, and evolution. Thus, we encourage the submission of verified COI nuMTs to public databases to facilitate future studies.}, } @article {pmid34011950, year = {2021}, author = {Horváthová, L and Žárský, V and Pánek, T and Derelle, R and Pyrih, J and Motyčková, A and Klápšťová, V and Vinopalová, M and Marková, L and Voleman, L and Klimeš, V and Petrů, M and Vaitová, Z and Čepička, I and Hryzáková, K and Harant, K and Gray, MW and Chami, M and Guilvout, I and Francetic, O and Franz Lang, B and Vlček, Č and Tsaousis, AD and Eliáš, M and Doležal, P}, title = {Analysis of diverse eukaryotes suggests the existence of an ancestral mitochondrial apparatus derived from the bacterial type II secretion system.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2947}, pmid = {34011950}, issn = {2041-1723}, mesh = {Amino Acid Sequence ; Conserved Sequence ; Eukaryota/classification/genetics/metabolism ; *Evolution, Molecular ; Gram-Negative Bacteria/classification/genetics/metabolism ; Mitochondria/*genetics/*metabolism ; Mitochondrial Proteins/classification/genetics/metabolism ; Models, Biological ; Models, Molecular ; Naegleria/classification/genetics/metabolism ; Peroxisomes/metabolism ; Phylogeny ; Protozoan Proteins/classification/genetics/metabolism ; Sequence Homology, Amino Acid ; Type II Secretion Systems/classification/*genetics/*metabolism ; }, abstract = {The type 2 secretion system (T2SS) is present in some Gram-negative eubacteria and used to secrete proteins across the outer membrane. Here we report that certain representative heteroloboseans, jakobids, malawimonads and hemimastigotes unexpectedly possess homologues of core T2SS components. We show that at least some of them are present in mitochondria, and their behaviour in biochemical assays is consistent with the presence of a mitochondrial T2SS-derived system (miT2SS). We additionally identified 23 protein families co-occurring with miT2SS in eukaryotes. Seven of these proteins could be directly linked to the core miT2SS by functional data and/or sequence features, whereas others may represent different parts of a broader functional pathway, possibly also involving the peroxisome. Its distribution in eukaryotes and phylogenetic evidence together indicate that the miT2SS-centred pathway is an ancestral eukaryotic trait. Our findings thus have direct implications for the functional properties of the early mitochondrion.}, } @article {pmid34017941, year = {2021}, author = {Kamrad, S and Rodríguez-López, M and Dey, S and Hoti, M and Wallace, H and Ralser, M and Bähler, J}, title = {Recombination and biased segregation of mitochondrial genomes during crossing and meiosis of different Schizosaccharomyces pombe strains.}, journal = {microPublication biology}, volume = {2021}, number = {}, pages = {}, pmid = {34017941}, issn = {2578-9430}, support = {FC001134/WT_/Wellcome Trust/United Kingdom ; }, abstract = {During meiosis, tethering of parental mitochondria to opposite cell poles inhibits the mixing of mitochondria with different genomes and ensures uniparental inheritance in thestandard laboratory strain of fission yeast. We here investigate mitochondrial inheritance in crosses between natural isolates using tetrad dissection and next-generation sequencing. We find that colonies grown from single spores can sometimes carry a mix of mitochondrial genotypes, that mitochondrial genomes can recombine during meiosis, that in some cases tetrads do not follow the 2:2 segregation pattern, and that certain crosses may feature a weak bias towards one of the parents. Together, these findings paint a more nuanced picture of mitochondrial inheritance in the wild.}, } @article {pmid34018613, year = {2021}, author = {Stephens, TG and Gabr, A and Calatrava, V and Grossman, AR and Bhattacharya, D}, title = {Why is primary endosymbiosis so rare?.}, journal = {The New phytologist}, volume = {231}, number = {5}, pages = {1693-1699}, pmid = {34018613}, issn = {1469-8137}, support = {80NSSC19K0462/NSSC/Shared Services Center NASA/United States ; }, mesh = {*Amoeba ; Biological Evolution ; Eukaryota ; Phylogeny ; Plastids ; *Symbiosis ; }, abstract = {Endosymbiosis is a relationship between two organisms wherein one cell resides inside the other. This affiliation, when stable and beneficial for the 'host' cell, can result in massive genetic innovation with the foremost examples being the evolution of eukaryotic organelles, the mitochondria and plastids. Despite its critical evolutionary role, there is limited knowledge about how endosymbiosis is initially established and how host-endosymbiont biology is integrated. Here, we explore this issue, using as our model the rhizarian amoeba Paulinella, which represents an independent case of primary plastid origin that occurred c. 120 million yr ago. We propose the 'chassis and engine' model that provides a theoretical framework for understanding primary plastid endosymbiosis, potentially explaining why it is so rare.}, } @article {pmid34027666, year = {2021}, author = {Zheng, Y and Ye, Z and Liu, Z and Yang, W and Zhang, X and Yang, Y and Xiao, Y}, title = {Nitroso-Caged Rhodamine: A Superior Green Light-Activatable Fluorophore for Single-Molecule Localization Super-Resolution Imaging.}, journal = {Analytical chemistry}, volume = {93}, number = {22}, pages = {7833-7842}, doi = {10.1021/acs.analchem.1c00175}, pmid = {34027666}, issn = {1520-6882}, mesh = {*Fluorescent Dyes ; Ionophores ; Microscopy, Fluorescence ; Rhodamines ; *Single Molecule Imaging ; }, abstract = {The evolution of super-resolution imaging techniques, especially single-molecule localization microscopy, demands the engineering of switchable fluorophores with labeling functionality. Yet, the switching of these fluorophores depends on the exterior conditions of UV light and enhancing buffers, which is bioincompatible for living-cell applications. Herein, to surpass these limitations, a nitroso-caging strategy is employed to cage rhodamines into leuco forms, which for the first time, is discovered to uncage highly bright zwitterions by green light. Further, clickable construction grants the specificity and versatility for labeling various components in living cells. The simultaneous photoactivation and excitation of these novel probes allow for single-laser super-resolution imaging without any harmful additives. Super-resolution imaging of microtubules in fixed cells or mitochondria and the distribution of glycans and H2B proteins in living cells are achieved at a molecular scale with robust integrity. We envision that our nitroso-caging probes would set a platform for the development of future visible-activatable probes.}, } @article {pmid34029916, year = {2021}, author = {Zhu, D and Liu, Z and Li, Y and Huang, Q and Xia, L and Li, K}, title = {Delivery of manganese carbonyl to the tumor microenvironment using Tumor-Derived exosomes for cancer gas therapy and low dose radiotherapy.}, journal = {Biomaterials}, volume = {274}, number = {}, pages = {120894}, doi = {10.1016/j.biomaterials.2021.120894}, pmid = {34029916}, issn = {1878-5905}, mesh = {Cell Line, Tumor ; *Exosomes ; Manganese ; *Nanoparticles ; *Neoplasms/radiotherapy ; Tumor Microenvironment ; }, abstract = {The development of novel radiosensitizer with high selectivity and controllability is highly desirable. CO gas could cause damage to mitochondria and thus enhance RT effect. Controlled delivery of CO in tumor is important both to achieve high-efficiency of CO gas therapy and to decrease the risk of CO poisoning. In this study, manganese carbonyl (MnCO) loaded exosome nano-vesicles (MMV) to overcome this conundrum for tumor therapy is developed. After administration, MMV showed its admirable performance in active tumor-targeting, mitochondria damage and radiosensitization therapy. These MMV nanoparticles were able to facilitate robust CO evolution and consequent ROS generation in response to X-ray irradiation both in vitro and in vivo. Significantly, MMV could facilitate a 90% inhibition effect of tumor growth under very low dose (only 2Gy) RT, which is better than high dose (6Gy) radiotherapy. Overall, this study highlights a novel and practical approach to enhancing the efficacy of tumor RT, underscoring the value of future research in the field of CO medicine.}, } @article {pmid34031453, year = {2021}, author = {Kloss-Brandstätter, A and Summerer, M and Horst, D and Horst, B and Streiter, G and Raschenberger, J and Kronenberg, F and Sanguansermsri, T and Horst, J and Weissensteiner, H}, title = {An in-depth analysis of the mitochondrial phylogenetic landscape of Cambodia.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {10816}, pmid = {34031453}, issn = {2045-2322}, mesh = {Asian People/ethnology/*genetics ; Cambodia/ethnology ; Female ; Genome, Mitochondrial ; Haplotypes ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Maternal Inheritance ; Mitochondria/*classification/genetics ; Phylogeny ; Refugees/*classification ; Whole Genome Sequencing/*methods ; }, abstract = {Cambodia harbours a variety of human aboriginal populations that have scarcely been studied in terms of genetic diversity of entire mitochondrial genomes. Here we present the matrilineal gene pool of 299 Cambodian refugees from three different ethnic groups (Cham, Khmer, and Khmer Loeu) deriving from 16 Cambodian districts. After establishing a DNA-saving high-throughput strategy for mitochondrial whole-genome Sanger sequencing, a HaploGrep based workflow was used for quality control, haplogroup classification and phylogenetic reconstruction. The application of diverse phylogenetic algorithms revealed an exciting picture of the genetic diversity of Cambodia, especially in relation to populations from Southeast Asia and from the whole world. A total of 224 unique haplotypes were identified, which were mostly classified under haplogroups B5a1, F1a1, or categorized as newly defined basal haplogroups or basal sub-branches of R, N and M clades. The presence of autochthonous maternal lineages could be confirmed as reported in previous studies. The exceptional homogeneity observed between and within the three investigated Cambodian ethnic groups indicates genetic isolation of the whole population. Between ethnicities, genetic barriers were not detected. The mtDNA data presented here increases the phylogenetic resolution in Cambodia significantly, thereby highlighting the need for an update of the current human mtDNA phylogeny.}, } @article {pmid34034879, year = {2021}, author = {Chowrasia, S and Nishad, J and Pandey, R and Mondal, TK}, title = {Oryza coarctata is a triploid plant with initial events of C4 photosynthesis evolution.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {308}, number = {}, pages = {110878}, doi = {10.1016/j.plantsci.2021.110878}, pmid = {34034879}, issn = {1873-2259}, mesh = {*Biological Evolution ; *Carbon Cycle ; Oryza/*anatomy & histology/genetics ; *Photosynthesis ; Plant Leaves/anatomy & histology ; *Triploidy ; }, abstract = {Oryza coarctata is an obligate halophyte of wild species of rice which thrives well under high saline as well as submerged conditions. We report here for the first time that O. coarctata is triploid (2n = 3x = 36), though it was previously known as tetraploid (2n = 4x = 48). The chromosome number of O. coarctata was determined from mitotic plates of root tips and ploidy level was determined by flow cytometer, where it was found to be triploid (2n = 3x = 36). In addition, this species was found to possess several unique anatomical features in leaves such as presence of Kranz-anatomy, increased vein density and higher ratio of bundle sheath to mesophyll cell area as compared to rice variety (IR-29). Ultra-structure of leaf showed the presence of bundle sheath cells with significant number of chloroplasts and mitochondria which were arranged centrifugally. Chloroplasts lack grana in bundle sheath cell whereas, mesophyll cell contain well-developed grana. These anatomical and ultra structural characteristics indicate that this plant is in initial stage of evolving towards C4 photosynthesis due to high selection pressure which might help it to survive in wide range of ecological conditions i.e. from submerged saline to non-saline terrestrial condition.}, } @article {pmid34037779, year = {2021}, author = {Burskaia, V and Artyushin, I and Potapova, NA and Konovalov, K and Bazykin, GA}, title = {Convergent Adaptation in Mitochondria of Phylogenetically Distant Birds: Does it Exist?.}, journal = {Genome biology and evolution}, volume = {13}, number = {7}, pages = {}, pmid = {34037779}, issn = {1759-6653}, mesh = {Adaptation, Physiological/genetics ; Animals ; Birds/genetics ; *Evolution, Molecular ; *Genome, Mitochondrial ; Mitochondria/genetics ; }, abstract = {In a wide range of taxa, proteins encoded by mitochondrial genomes are involved in adaptation to lifestyle that requires oxygen starvation or elevation of metabolism rate. It remains poorly understood to what extent adaptation to similar conditions is associated with parallel changes in these proteins. We search for a genetic signal of parallel or convergent evolution in recurrent molecular adaptation to high altitude, migration, diving, wintering, unusual flight abilities, or loss of flight in mitochondrial genomes of birds. Developing on previous work, we design an approach for the detection of recurrent coincident changes in genotype and phenotype, indicative of an association between the two. We describe a number of candidate sites involved in recurrent adaptation in ND genes. However, we find that the majority of convergence events can be explained by random coincidences without invoking adaptation.}, } @article {pmid34038740, year = {2021}, author = {Wong, HH and Seet, SH and Maier, M and Gurel, A and Traspas, RM and Lee, C and Zhang, S and Talim, B and Loh, AYT and Chia, CY and Teoh, TS and Sng, D and Rensvold, J and Unal, S and Shishkova, E and Cepni, E and Nathan, FM and Sirota, FL and Liang, C and Yarali, N and Simsek-Kiper, PO and Mitani, T and Ceylaner, S and Arman-Bilir, O and Mbarek, H and Gumruk, F and Efthymiou, S and Uğurlu Çi Men, D and Georgiadou, D and Sotiropoulou, K and Houlden, H and Paul, F and Pehlivan, D and Lainé, C and Chai, G and Ali, NA and Choo, SC and Keng, SS and Boisson, B and Yılmaz, E and Xue, S and Coon, JJ and Ly, TTN and Gilani, N and Hasbini, D and Kayserili, H and Zaki, MS and Isfort, RJ and Ordonez, N and Tripolszki, K and Bauer, P and Rezaei, N and Seyedpour, S and Khotaei, GT and Bascom, CC and Maroofian, R and Chaabouni, M and Alsubhi, A and Eyaid, W and Işıkay, S and Gleeson, JG and Lupski, JR and Casanova, JL and Pagliarini, DJ and Akarsu, NA and Maurer-Stroh, S and Cetinkaya, A and Bertoli-Avella, A and Mathuru, AS and Ho, L and Bard, FA and Reversade, B}, title = {Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy.}, journal = {American journal of human genetics}, volume = {108}, number = {7}, pages = {1301-1317}, pmid = {34038740}, issn = {1537-6605}, support = {R35 GM131795/GM/NIGMS NIH HHS/United States ; U54 HG006542/HG/NHGRI NIH HHS/United States ; UM1 HG006542/HG/NHGRI NIH HHS/United States ; R35 NS105078/NS/NINDS NIH HHS/United States ; P41 GM108538/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; CRISPR-Cas Systems ; Cell Line ; Encephalitis/*genetics/mortality ; Female ; Genes, Recessive ; Glycogen/metabolism ; Humans ; Inflammation/genetics ; Male ; Membrane Proteins/genetics ; Mitochondrial Diseases/*genetics/mortality ; Pedigree ; Seizures/genetics/mortality ; Zebrafish/genetics ; }, abstract = {Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. C2ORF69 bears homology to esterase enzymes, and orthologs can be found in most eukaryotic genomes, including that of unicellular phytoplankton. We found that endogenous C2ORF69 (1) is loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. We show that CRISPR-Cas9-mediated inactivation of zebrafish C2orf69 results in lethality by 8 months of age due to spontaneous epileptic seizures, which is preceded by persistent brain inflammation. Collectively, our results delineate an autoinflammatory Mendelian disorder of C2orf69 deficiency that disrupts the development/homeostasis of the immune and central nervous systems.}, } @article {pmid34039261, year = {2021}, author = {Awadi, A and Ben Slimen, H and Schaschl, H and Knauer, F and Suchentrunk, F}, title = {Positive selection on two mitochondrial coding genes and adaptation signals in hares (genus Lepus) from China.}, journal = {BMC ecology and evolution}, volume = {21}, number = {1}, pages = {100}, pmid = {34039261}, issn = {2730-7182}, mesh = {Animals ; China ; DNA, Mitochondrial/genetics ; Genes, Mitochondrial ; *Hares/genetics ; Phylogeny ; }, abstract = {BACKGROUND: Animal mitochondria play a central role in energy production in the cells through the oxidative phosphorylation (OXPHOS) pathway. Recent studies of selection on different mitochondrial OXPHOS genes have revealed the adaptive implications of amino acid changes in these subunits. In hares, climatic variation and/or introgression were suggested to be at the origin of such adaptation. Here we looked for evidence of positive selection in three mitochondrial OXPHOS genes, using tests of selection, protein structure modelling and effects of amino acid substitutions on the protein function and stability. We also used statistical models to test for climate and introgression effects on sites under positive selection.

RESULTS: Our results revealed seven sites under positive selection in ND4 and three sites in Cytb. However, no sites under positive selection were observed in the COX1 gene. All three subunits presented a high number of codons under negative selection. Sites under positive selection were mapped on the tridimensional structure of the predicted models for the respective mitochondrial subunit. Of the ten amino acid replacements inferred to have evolved under positive selection for both subunits, six were located in the transmembrane domain. On the other hand, three codons were identified as sites lining proton translocation channels. Furthermore, four codons were identified as destabilizing with a significant variation of Δ vibrational entropy energy between wild and mutant type. Moreover, our PROVEAN analysis suggested that among all positively selected sites two fixed amino acid replacements altered the protein functioning. Our statistical models indicated significant effects of climate on the presence of ND4 and Cytb protein variants, but no effect by trans-specific mitochondrial DNA introgression, which is not uncommon in a number of hare species.

CONCLUSIONS: Positive selection was observed in several codons in two OXPHOS genes. We found that substitutions in the positively selected codons have structural and functional impacts on the encoded proteins. Our results are concordantly suggesting that adaptations have strongly affected the evolution of mtDNA of hare species with potential effects on the protein function. Environmental/climatic changes appear to be a major trigger of this adaptation, whereas trans-specific introgressive hybridization seems to play no major role for the occurrence of protein variants.}, } @article {pmid34061590, year = {2021}, author = {Siscar-Lewin, S and Gabaldón, T and Aldejohann, AM and Kurzai, O and Hube, B and Brunke, S}, title = {Transient Mitochondria Dysfunction Confers Fungal Cross-Resistance against Phagocytic Killing and Fluconazole.}, journal = {mBio}, volume = {12}, number = {3}, pages = {e0112821}, pmid = {34061590}, issn = {2150-7511}, mesh = {Antifungal Agents/*pharmacology ; Candida glabrata/*drug effects/*genetics/growth & development/pathogenicity ; Candidiasis/microbiology ; Drug Resistance, Fungal/*genetics ; Fluconazole/*pharmacology ; Gene Expression Regulation, Fungal ; Humans ; Macrophages/microbiology ; Microbial Sensitivity Tests ; Mitochondria/metabolism/*pathology ; Phagocytes ; Phagocytosis ; Virulence/genetics ; }, abstract = {Loss or inactivation of antivirulence genes is an adaptive strategy in pathogen evolution. Candida glabrata is an important opportunistic pathogen related to baker's yeast, with the ability to both quickly increase its intrinsic high level of azole resistance and persist within phagocytes. During C. glabrata's evolution as a pathogen, the mitochondrial DNA polymerase CgMip1 has been under positive selection. We show that CgMIP1 deletion not only triggers loss of mitochondrial function and a petite phenotype, but increases C. glabrata's azole and endoplasmic reticulum (ER) stress resistance and, importantly, its survival in phagocytes. The same phenotype is induced by fluconazole and by exposure to macrophages, conferring a cross-resistance between antifungals and immune cells, and can be found in clinical isolates despite a slow growth of petite strains. This suggests that petite constitutes a bet-hedging strategy of C. glabrata and, potentially, a relevant cause of azole resistance. Mitochondrial function may therefore be considered a potential antivirulence factor. IMPORTANCE Candida glabrata is an opportunistic pathogen whose incidence has been increasing in the last 40 years. It has risen to become the most prominent non-Candida albicans Candida (NCAC) species to cause candidemia, constituting about one-third of isolates in the United States, and steadily increasing in European countries and in Australia. Despite its clinical importance, C. glabrata's pathogenicity strategies remain poorly understood. Our research shows that loss of mitochondrial function and the resulting petite phenotype is advantageous for C. glabrata to cope with infection-related stressors, such as antifungals and host immune defenses. The (cross-)resistance against both these factors may have major implications in the clinical outcome of infections with this major fungal pathogen.}, } @article {pmid34061855, year = {2021}, author = {Cai, C and Gu, K and Zhao, H and Steinhagen, S and He, P and Wichard, T}, title = {Screening and verification of extranuclear genetic markers in green tide algae from the Yellow Sea.}, journal = {PloS one}, volume = {16}, number = {6}, pages = {e0250968}, pmid = {34061855}, issn = {1932-6203}, mesh = {*Phylogeny ; *Ulva/genetics ; *Genome, Chloroplast/genetics ; Genetic Markers ; *Genome, Mitochondrial ; Evolution, Molecular ; China ; Oceans and Seas ; Chlorophyta/genetics ; }, abstract = {Over the past decade, Ulva compressa, a cosmopolitan green algal species, has been identified as a component of green tides in the Yellow Sea, China. In the present study, we sequenced and annotated the complete chloroplast genome of U. compressa (alpha-numeric code: RD9023) and focused on the assessment of genome length, homology, gene order and direction, intron size, selection strength, and substitution rate. We compared the chloroplast genome with the mitogenome. The generated phylogenetic tree was analyzed based on single and aligned genes in the chloroplast genome of Ulva compared to mitogenome genes to detect evolutionary trends. U. compressa and U. mutabilis chloroplast genomes had similar gene queues, with individual genes exhibiting high homology levels. Chloroplast genomes were clustered together in the entire phylogenetic tree and shared several forward/palindromic/tandem repetitions, similar to those in U. prolifera and U. linza. However, U. fasciata and U. ohnoi were more divergent, especially in sharing complementary/palindromic repetitions. In addition, phylogenetic analyses of the aligned genes from their chloroplast genomes and mitogenomes confirmed the evolutionary trends of the extranuclear genomes. From phylogenetic analysis, we identified the petA chloroplast genes as potential genetic markers that are similar to the tufA marker. Complementary/forward/palindromic interval repetitions were more abundant in chloroplast genomes than in mitogenomes. Interestingly, a few tandem repetitions were significant for some Ulva subspecies and relatively more evident in mitochondria than in chloroplasts. Finally, the tandem repetition [GAAATATATAATAATA × 3, abbreviated as TRg)] was identified in the mitogenome of U. compressa and the conspecific strain U. mutabilis but not in other algal species of the Yellow Sea. Owing to the high morphological plasticity of U. compressa, the findings of this study have implications for the rapid non-sequencing detection of this species during the occurrence of green tides in the region.}, } @article {pmid34064566, year = {2021}, author = {Jacome Burbano, MS and Gilson, E}, title = {The Power of Stress: The Telo-Hormesis Hypothesis.}, journal = {Cells}, volume = {10}, number = {5}, pages = {}, pmid = {34064566}, issn = {2073-4409}, support = {ANR-18-CE13-0029-01//Agence Nationale de la Recherche (ANR)/ ; AgeMed//Inserm/ ; }, mesh = {Adaptation, Physiological ; Animals ; DNA ; Hormesis ; Humans ; Hydrogen-Ion Concentration ; Inflammation ; Karyotyping ; Mice ; Mitochondria/metabolism ; *Mutation ; Signal Transduction ; *Stress, Physiological ; Stress, Psychological ; Telomerase/metabolism ; Telomere/*ultrastructure ; Temperature ; }, abstract = {Adaptative response to stress is a strategy conserved across evolution to promote survival. In this context, the groundbreaking findings of Miroslav Radman on the adaptative value of changing mutation rates opened new avenues in our understanding of stress response. Inspired by this work, we explore here the putative beneficial effects of changing the ends of eukaryotic chromosomes, the telomeres, in response to stress. We first summarize basic principles in telomere biology and then describe how various types of stress can alter telomere structure and functions. Finally, we discuss the hypothesis of stress-induced telomere signaling with hormetic effects.}, } @article {pmid34065848, year = {2021}, author = {Lyu, D and Msimbira, LA and Nazari, M and Antar, M and Pagé, A and Shah, A and Monjezi, N and Zajonc, J and Tanney, CAS and Backer, R and Smith, DL}, title = {The Coevolution of Plants and Microbes Underpins Sustainable Agriculture.}, journal = {Microorganisms}, volume = {9}, number = {5}, pages = {}, pmid = {34065848}, issn = {2076-2607}, support = {RGPIN 2020-07047.//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {Terrestrial plants evolution occurred in the presence of microbes, the phytomicrobiome. The rhizosphere microbial community is the most abundant and diverse subset of the phytomicrobiome and can include both beneficial and parasitic/pathogenic microbes. Prokaryotes of the phytomicrobiome have evolved relationships with plants that range from non-dependent interactions to dependent endosymbionts. The most extreme endosymbiotic examples are the chloroplasts and mitochondria, which have become organelles and integral parts of the plant, leading to some similarity in DNA sequence between plant tissues and cyanobacteria, the prokaryotic symbiont of ancestral plants. Microbes were associated with the precursors of land plants, green algae, and helped algae transition from aquatic to terrestrial environments. In the terrestrial setting the phytomicrobiome contributes to plant growth and development by (1) establishing symbiotic relationships between plant growth-promoting microbes, including rhizobacteria and mycorrhizal fungi, (2) conferring biotic stress resistance by producing antibiotic compounds, and (3) secreting microbe-to-plant signal compounds, such as phytohormones or their analogues, that regulate aspects of plant physiology, including stress resistance. As plants have evolved, they recruited microbes to assist in the adaptation to available growing environments. Microbes serve themselves by promoting plant growth, which in turn provides microbes with nutrition (root exudates, a source of reduced carbon) and a desirable habitat (the rhizosphere or within plant tissues). The outcome of this coevolution is the diverse and metabolically rich microbial community that now exists in the rhizosphere of terrestrial plants. The holobiont, the unit made up of the phytomicrobiome and the plant host, results from this wide range of coevolved relationships. We are just beginning to appreciate the many ways in which this complex and subtle coevolution acts in agricultural systems.}, } @article {pmid34067626, year = {2021}, author = {Yamaguchi, K and Kitamura, S and Furutake, Y and Murakami, R and Yamanoi, K and Taki, M and Ukita, M and Hamanishi, J and Mandai, M}, title = {Acquired Evolution of Mitochondrial Metabolism Regulated by HNF1B in Ovarian Clear Cell Carcinoma.}, journal = {Cancers}, volume = {13}, number = {10}, pages = {}, pmid = {34067626}, issn = {2072-6694}, abstract = {Clear cell carcinoma (CCC) of the ovary exhibits a unique morphology and clinically malignant behavior. The eosinophilic cytoplasm includes abundant glycogen. Although the growth is slow, the prognosis is poor owing to resistance to conventional chemotherapies. CCC often arises in endometriotic cysts and is accompanied by endometriosis. Based on these characteristics, three clinical questions are considered: why does ovarian cancer, especially CCC and endometrioid carcinoma, frequently occur in endometriotic cysts, why do distinct histological subtypes (CCC and endometrioid carcinoma) arise in the endometriotic cyst, and why does ovarian CCC possess unique characteristics? Mutations in AT-rich interacting domain-containing protein 1A and phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit alpha genes may contribute to the carcinogenesis of ovarian CCC, whereas hepatocyte nuclear factor-1-beta (HNF1B) plays crucial roles in sculpting the unique characteristics of ovarian CCC through metabolic alterations. HNF1B increases glutathione synthesis, activates anaerobic glycolysis called the Warburg effect, and suppresses mitochondria. These metabolic changes may be induced in stressful environments. Life has evolved to utilize and control energy; eukaryotes require mitochondria to transform oxygen reduction into useful energy. Because mitochondrial function is suppressed in ovarian CCC, these cancer cells probably acquired further metabolic evolution during the carcinogenic process in order to survive stressful environments.}, } @article {pmid34070384, year = {2021}, author = {Di Gregorio, E and Miolo, G and Saorin, A and Steffan, A and Corona, G}, title = {From Metabolism to Genetics and Vice Versa: The Rising Role of Oncometabolites in Cancer Development and Therapy.}, journal = {International journal of molecular sciences}, volume = {22}, number = {11}, pages = {}, pmid = {34070384}, issn = {1422-0067}, mesh = {Cell Transformation, Neoplastic/*metabolism/pathology ; Humans ; Metabolic Diseases/*metabolism/pathology ; Mitochondria/*metabolism/pathology ; Neoplasms/*metabolism/pathology ; *Signal Transduction ; }, abstract = {Over the last decades, the study of cancer metabolism has returned to the forefront of cancer research and challenged the role of genetics in the understanding of cancer development. One of the major impulses of this new trend came from the discovery of oncometabolites, metabolic intermediates whose abnormal cellular accumulation triggers oncogenic signalling and tumorigenesis. These findings have led to reconsideration and support for the long-forgotten hypothesis of Warburg of altered metabolism as oncogenic driver of cancer and started a novel paradigm whereby mitochondrial metabolites play a pivotal role in malignant transformation. In this review, we describe the evolution of the cancer metabolism research from a historical perspective up to the oncometabolites discovery that spawned the new vision of cancer as a metabolic disease. The oncometabolites' mechanisms of cellular transformation and their contribution to the development of new targeted cancer therapies together with their drawbacks are further reviewed and discussed.}, } @article {pmid34070437, year = {2021}, author = {Ai, D and Peng, L and Qin, D and Zhang, Y}, title = {Characterization of Three Complete Mitogenomes of Flatidae (Hemiptera: Fulgoroidea) and Compositional Heterogeneity Analysis in the Planthoppers' Mitochondrial Phylogenomics.}, journal = {International journal of molecular sciences}, volume = {22}, number = {11}, pages = {}, pmid = {34070437}, issn = {1422-0067}, support = {31420103911//National Natural Science Foundation of China/ ; 2015FY210300//Ministry of Science and Technology of the People's Republic of China/ ; 2005DKA21402//Ministry of Science and Technology of the People's Republic of China/ ; }, mesh = {Animals ; Base Composition ; Codon Usage ; Gene Order ; *Genome, Mitochondrial ; Hemiptera/*genetics ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics ; Mitochondrial Proteins/genetics ; Phylogeny ; RNA, Ribosomal/genetics ; RNA, Transfer/genetics ; Sequence Alignment ; Tandem Repeat Sequences/genetics ; }, abstract = {Although sequences of mitogenomes have been widely used for investigating phylogenetic relationship, population genetics, and biogeography in many members of Fulgoroidea, only one complete mitogenome of a member of Flatidae has been sequenced. Here, the complete mitogenomes of Cerynia lineola, Cromna sinensis, and Zecheuna tonkinensis are sequenced. The gene arrangements of the three new mitogenomes are consistent with ancestral insect mitogenomes. The strategy of using mitogenomes in phylogenetics remains in dispute due to the heterogeneity in base composition and the possible variation in evolutionary rates. In this study, we found compositional heterogeneity and variable evolutionary rates among planthopper mitogenomes. Phylogenetic analysis based on site-homogeneous models showed that the families (Delphacidae and Derbidae) with high values of Ka/Ks and A + T content tended to fall together at a basal position on the trees. Using a site-heterogeneous mixture CAT + GTR model implemented in PhyloBayes yielded almost the same topology. Our results recovered the monophyly of Fulgoroidea. In this study, we apply the heterogeneous mixture model to the planthoppers' phylogenetic analysis for the first time. Our study is based on a large sample and provides a methodological reference for future phylogenetic studies of Fulgoroidea.}, } @article {pmid34072215, year = {2021}, author = {Dür, A and Huber, N and Parson, W}, title = {Fine-Tuning Phylogenetic Alignment and Haplogrouping of mtDNA Sequences.}, journal = {International journal of molecular sciences}, volume = {22}, number = {11}, pages = {}, pmid = {34072215}, issn = {1422-0067}, mesh = {Algorithms ; Computational Biology/methods ; DNA, Mitochondrial/chemistry/*genetics ; Genome, Mitochondrial ; Genomics/methods ; *Haplotypes ; Humans ; Mitochondria/genetics ; *Phylogeny ; Regulatory Sequences, Nucleic Acid ; }, abstract = {In this paper, we present a new algorithm for alignment and haplogroup estimation of mitochondrial DNA (mtDNA) sequences. Based on 26,011 vetted full mitogenome sequences, we refined the 5435 original haplogroup motifs of Phylotree Build 17 without changing the haplogroup nomenclature. We adapted 430 motifs (about 8%) and added 966 motifs for yet undetermined subclades. In summary, this led to an 18% increase of haplogroup defining motifs for full mitogenomes and a 30% increase for the mtDNA control region that is of interest for a variety of scientific disciplines, such as medical, population and forensic genetics. The new algorithm is implemented in the EMPOP mtDNA database and is freely accessible.}, } @article {pmid34073133, year = {2021}, author = {Cramer, ERA and Garcia-Del-Rey, E and Johannessen, LE and Laskemoen, T and Marthinsen, G and Johnsen, A and Lifjeld, JT}, title = {Longer Sperm Swim More Slowly in the Canary Islands Chiffchaff.}, journal = {Cells}, volume = {10}, number = {6}, pages = {}, pmid = {34073133}, issn = {2073-4409}, support = {301592//Norges Forskningsråd/ ; 196554//Norges Forskningsråd/ ; }, mesh = {Animals ; Male ; Mammals/metabolism ; Passeriformes/anatomy & histology/*metabolism ; *Phenotype ; Phylogeny ; Spain ; Sperm Motility/*physiology ; Spermatozoa/*cytology ; }, abstract = {Sperm swimming performance affects male fertilization success, particularly in species with high sperm competition. Understanding how sperm morphology impacts swimming performance is therefore important. Sperm swimming speed is hypothesized to increase with total sperm length, relative flagellum length (with the flagellum generating forward thrust), and relative midpiece length (as the midpiece contains the mitochondria). We tested these hypotheses and tested for divergence in sperm traits in five island populations of Canary Islands chiffchaff (Phylloscopus canariensis). We confirmed incipient mitochondrial DNA differentiation between Gran Canaria and the other islands. Sperm swimming speed correlated negatively with total sperm length, did not correlate with relative flagellum length, and correlated negatively with relative midpiece length (for Gran Canaria only). The proportion of motile cells increased with relative flagellum length on Gran Canaria only. Sperm morphology was similar across islands. We thus add to a growing number of studies on passerine birds that do not support sperm morphology-swimming speed hypotheses. We suggest that the swimming mechanics of passerine sperm are sufficiently different from mammalian sperm that predictions from mammalian hydrodynamic models should no longer be applied for this taxon. While both sperm morphology and sperm swimming speed are likely under selection in passerines, the relationship between them requires further elucidation.}, } @article {pmid34077418, year = {2021}, author = {Castro-Pereira, D and Peres, EA and Pinto-da-Rocha, R}, title = {Systematics and phylogeography of the Brazilian Atlantic Forest endemic harvestmen Neosadocus Mello-Leitão, 1926 (Arachnida: Opiliones: Gonyleptidae).}, journal = {PloS one}, volume = {16}, number = {6}, pages = {e0249746}, pmid = {34077418}, issn = {1932-6203}, mesh = {*Animal Distribution ; Animals ; Arachnida/*classification ; *Biological Evolution ; Brazil ; Cell Nucleus/metabolism ; *Forests ; Mitochondria/metabolism ; Phylogeography ; Reproduction ; }, abstract = {Neosadocus harvestmen are endemic to the Southern Brazilian Atlantic Forest. Although they are conspicuous and display great morphological variation, their evolutionary history and the biogeographical events underlying their diversification and distribution are still unknown. This contribution about Neosadocus includes the following: a taxonomic revision; a molecular phylogenetic analysis using mitochondrial and nuclear markers; an investigation of the genetic structure and species' diversity in a phylogeographical framework. Our results show that Neosadocus is a monophyletic group and comprises four species: N. bufo, N. maximus, N. robustus and N. misandrus (which we did not find on fieldwork and only studied the female holotype). There is astonishing male polymorphism in N. robustus, mostly related to reproductive strategies. The following synonymies have resulted from this work: "Bunoweyhia" variabilis Mello-Leitão, 1935 = Neosadocus bufo (Mello-Leitão, 1926); and "Bunoweyhia" minor Mello-Leitão, 1935 = Neosadocus maximus (Giltay, 1928). Most divergences occurred during the Miocene, a geological epoch marked by intense orogenic and climatic events in the Brazilian Atlantic Forest. Intraspecific analyses indicate strong population structure, a pattern congruent with the general behavior and physiological constraints of Neotropical harvestmen.}, } @article {pmid34082186, year = {2021}, author = {Singh, L and Atilano, SR and Jager, MJ and Kenney, MC}, title = {Mitochondrial DNA polymorphisms and biogenesis genes in primary and metastatic uveal melanoma cell lines.}, journal = {Cancer genetics}, volume = {256-257}, number = {}, pages = {91-99}, doi = {10.1016/j.cancergen.2021.05.002}, pmid = {34082186}, issn = {2210-7762}, mesh = {Cell Line, Tumor ; DNA, Mitochondrial/*genetics ; Gene Dosage ; *Genes, Neoplasm ; Genome, Human ; Haplotypes/genetics ; Heteroplasmy/genetics ; Humans ; Melanoma/*genetics/*pathology ; Neoplasm Metastasis ; *Organelle Biogenesis ; Phylogeny ; *Polymorphism, Genetic ; Polymorphism, Single Nucleotide/genetics ; Uveal Neoplasms/*genetics/*pathology ; Uveal Melanoma ; }, abstract = {PURPOSE: This study was designed to identify mitochondrial (mt) DNA variations in primary and metastatic uveal melanoma (UM) cell lines and their relation with cell metabolism to gain insight into metastatic progression.

METHOD: The entire mtDNA genomes were sequenced using Sanger sequencing from two primary UM cell lines (92.1 and MEL270) and two cell lines (OMM2.3 and OMM2.5) derived from liver metastases of the MEL270 patient. The mtDNA copy numbers determined by the ratio of nDNA versus mtDNA. qRT-PCR was used to evaluate expression levels of mitochondrial biogenesis genes.

RESULTS: Sequencing showed that cell line MEL270 and metastases-derived OMM2.3 and OMM2.5 cell lines had homoplasmic single nucleotide polymorphisms (SNPs) representing J1c7a haplogroup, whereas 92.1 cells had mtDNA H31a haplogroup. mtDNA copy numbers were significantly higher in primary cell lines. The metastatic UM cells showed down-regulation of POLG, TFAM, NRF-1 and SIRT1 compared to their primary MEL270 cells. PGC-1α was downregulated in 92.1 and upregulated in MEL270, OMM2.3 and OMM2.5.

CONCLUSIONS: Our finding suggests that within metastatic cells, the heteroplasmic SNPs, copy numbers and mitochondrial biogenesis genes are modulated differentially compared to their primary UM cells. Therefore, investigating pathogenic mtDNA variants associated with cancer metabolic susceptibility may provide future therapeutic strategies in metastatic UM.}, } @article {pmid34083540, year = {2021}, author = {Wang, S and Luo, H}, title = {Dating Alphaproteobacteria evolution with eukaryotic fossils.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {3324}, pmid = {34083540}, issn = {2041-1723}, mesh = {Alphaproteobacteria/*classification/*genetics ; Animals ; Cyanobacteria/classification/genetics ; Eukaryota/*classification/*genetics ; *Evolution, Molecular ; *Fossils/history/microbiology ; Genome, Bacterial ; Genome, Mitochondrial ; History, Ancient ; Mitochondria/genetics/microbiology ; Models, Biological ; Models, Genetic ; Phylogeny ; Rickettsiales/classification/genetics ; Symbiosis/genetics ; Time Factors ; }, abstract = {Elucidating the timescale of the evolution of Alphaproteobacteria, one of the most prevalent microbial lineages in marine and terrestrial ecosystems, is key to testing hypotheses on their co-evolution with eukaryotic hosts and Earth's systems, which, however, is largely limited by the scarcity of bacterial fossils. Here, we incorporate eukaryotic fossils to date the divergence times of Alphaproteobacteria, based on the mitochondrial endosymbiosis that mitochondria evolved from an alphaproteobacterial lineage. We estimate that Alphaproteobacteria arose ~1900 million years (Ma) ago, followed by rapid divergence of their major clades. We show that the origin of Rickettsiales, an order of obligate intracellular bacteria whose hosts are mostly animals, predates the emergence of animals for ~700 Ma but coincides with that of eukaryotes. This, together with reconstruction of ancestral hosts, strongly suggests that early Rickettsiales lineages had established previously underappreciated interactions with unicellular eukaryotes. Moreover, the mitochondria-based approach displays higher robustness to uncertainties in calibrations compared with the traditional strategy using cyanobacterial fossils. Further, our analyses imply the potential of dating the (bacterial) tree of life based on endosymbiosis events, and suggest that previous applications using divergence times of the modern hosts of symbiotic bacteria to date bacterial evolution might need to be revisited.}, } @article {pmid34083683, year = {2021}, author = {Feng, JT and Xia, LP and Yan, CR and Miao, J and Ye, YY and Li, JJ and Guo, BY and Lü, ZM}, title = {Characterization of four mitochondrial genomes of family Neritidae (Gastropoda: Neritimorpha) and insight into its phylogenetic relationships.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {11748}, pmid = {34083683}, issn = {2045-2322}, mesh = {Animals ; Base Composition ; Codon ; Computational Biology/methods ; Gastropoda/*classification/*genetics ; Gene Rearrangement ; Genes, Mitochondrial ; *Genome, Mitochondrial ; Genomics/methods ; Mitochondria/*genetics ; Molecular Sequence Annotation ; *Phylogeny ; Selection, Genetic ; }, abstract = {Neritidae is one of the most diverse families of Neritimorpha and possesses euryhaline properties. Members of this family usually live on tropical and subtropical coasts and are mainly gregarious. The phylogenetic relationships between several subclasses of Gastropoda have been controversial for many years. With an increase in the number of described species of Neritidae, the knowledge of the evolutionary relationships in this family has improved. In the present study, we sequenced four complete mitochondrial genomes from two genera (Clithon and Nerita) and compared them with available complete mitochondrial genomes of Neritidae. Gene order exhibited a highly conserved pattern among three genera in the Neritidae family. Our results improved the phylogenetic resolution within Neritidae, and more comprehensive taxonomic sampling of subclass Neritimorpha was proposed. Furthermore, we reconstructed the divergence among the main lineages of 19 Neritimorpha taxa under an uncorrelated relaxed molecular clock.}, } @article {pmid34087289, year = {2021}, author = {Lu, Z and Tang, M and Zhang, M and Li, Y and Shi, F and Zhan, F and Zhao, L and Li, J and Lin, L and Qin, Z}, title = {Expression and functional analysis of the BCL2-Associated agonist of cell death (BAD) gene in grass carp (Ctenopharyngodon idella) during bacterial infection.}, journal = {Developmental and comparative immunology}, volume = {123}, number = {}, pages = {104160}, doi = {10.1016/j.dci.2021.104160}, pmid = {34087289}, issn = {1879-0089}, mesh = {Aeromonas hydrophila/*physiology ; Amino Acid Sequence ; Animals ; Apoptosis ; Carps/*immunology ; Cell Line ; Cloning, Molecular ; Fish Proteins/genetics/*metabolism ; Gram-Negative Bacterial Infections/*immunology ; Immunity, Innate ; Lipopolysaccharides/immunology ; Phylogeny ; Spleen ; Staphylococcal Infections/*immunology ; Staphylococcus aureus/*physiology ; Transcriptome ; Up-Regulation ; bcl-Associated Death Protein/genetics/*metabolism ; }, abstract = {The BCL2-associated agonist of cell death protein is a key participant in apoptosis dependent on mitochondria and in disease progression that involves the regulation of cell death, such as tumorigenesis, diabetes, sepsis shock, and epilepsy. Nevertheless, the mechanisms underlying the immune responses to teleost BAD bacterial infection and mitochondrial-dependent apoptosis remains unclear. In order to elucidate the mechanisms involved, in this study, a Ctenopharyngodon idella (grass carp) BAD gene named GcBAD1 was firstly cloned and characterized. The results indicated that the ORF (open reading frame) of GcBAD1 was 438 bp in length, encoding a 145-amino acid putative protein of 16.66 kDa. This deduced amino acid sequence has a better identity than another teleost species according to a phylogenetic analysis, and contains a Bcl2-BAD-1 domain. In healthy grass carp fish, the mRNA transcripts of GcBAD1 were widely present in the studied tissues, which could be ranked as follows; spleen > brain > middle-kidney > head-kidney > liver > gills > intestines > heart and muscle. In addition, during infection by Aeromonas hydrophila and Staphylococcus aureus, the mRNA transcription and protein levels expression of GcBAD1 in the head-kidney, spleen, and liver tissues of the fish were significantly up-regulated. Moreover, when the C. idellus kidney cell line (CIK) cells were incubated with Lipopolysaccharide (LPS) and lipoteichoic acid (LTA), the GcBAD1 expression transcripts were also significantly up-regulated. Additionally, overexpression of GcBAD1 in CIK cells was able to activate apoptosis-related genes, including those encoding p53, Cytochrome C (CytoC), caspase-3, and caspase-9. Besides, in the TUNEL assays, when pEGFP-BAD1 was over-expressed, the number of red signals associated with apoptosis were significantly increased in the CIK cells infected with LPS or LTA at 12 h. This study demonstrates that GcBAD1 has a significant role in the mitochondrial apoptosis pathway of grass carp's innate immunity. Our findings provide new insight into the potential mechanisms of teleost antibacterial immunity.}, } @article {pmid34087614, year = {2021}, author = {Mazzocca, A and Fais, S}, title = {New hypotheses for cancer generation and progression.}, journal = {Medical hypotheses}, volume = {152}, number = {}, pages = {110614}, doi = {10.1016/j.mehy.2021.110614}, pmid = {34087614}, issn = {1532-2777}, mesh = {Biological Evolution ; Carcinogenesis ; Humans ; Mutation ; *Neoplasms ; Phenotype ; Tumor Microenvironment ; }, abstract = {Since Nixon famously declared war on cancer in 1971, trillions of dollars have been spent on cancer research but the life expectancy for most forms of cancer is still poor. There are many reasons for the partial success of cancer translational research. One of these can be the predominance of certain paradigms that potentially narrowed the vision in interpreting cancer. The main paradigm to explain carcinogenesis is based on DNA mutations, which is well interpreted by the somatic mutation theory (SMT). However, a different theory claims that cancer is instead a tissue disease as proposed by the Tissue Organization Field Theory (TOFT). Here, we propose new hypotheses to explain the origin and pathogenesis of cancer. In this perspective, the systemic-evolutionary theory of cancer (SETOC) is discussed as well as how the microenvironment affects the adaptation of transformed cells and the reversion to a unicellular-like or embryo-like phenotype.}, } @article {pmid34089318, year = {2021}, author = {Vrzoňová, R and Tóth, R and Siváková, B and Moťovská, A and Gaplovská-Kyselá, K and Baráth, P and Tomáška, Ľ and Gácser, A and Gabaldón, T and Nosek, J and Neboháčová, M}, title = {OCT1 - a yeast mitochondrial thiolase involved in the 3-oxoadipate pathway.}, journal = {FEMS yeast research}, volume = {21}, number = {5}, pages = {}, doi = {10.1093/femsyr/foab034}, pmid = {34089318}, issn = {1567-1364}, mesh = {Acetyl-CoA C-Acetyltransferase/genetics ; Acetyl-CoA C-Acyltransferase/genetics ; Animals ; Chromatography, Liquid ; Mitochondria ; Phylogeny ; *Saccharomyces cerevisiae/genetics ; *Tandem Mass Spectrometry ; }, abstract = {The 3-oxoacyl-CoA thiolases catalyze the last step of the fatty acid β-oxidation pathway. In yeasts and plants, this pathway takes place exclusively in peroxisomes, whereas in animals it occurs in both peroxisomes and mitochondria. In contrast to baker's yeast Saccharomyces cerevisiae, yeast species from the Debaryomycetaceae family also encode a thiolase with predicted mitochondrial localization. These yeasts are able to utilize a range of hydroxyaromatic compounds via the 3-oxoadipate pathway the last step of which is catalyzed by 3-oxoadipyl-CoA thiolase and presumably occurs in mitochondria. In this work, we studied Oct1p, an ortholog of this enzyme from Candida parapsilosis. We found that the cells grown on a 3-oxoadipate pathway substrate exhibit increased levels of the OCT1 mRNA. Deletion of both OCT1 alleles impairs the growth of C. parapsilosis cells on 3-oxoadipate pathway substrates and this defect can be rescued by expression of the OCT1 gene from a plasmid vector. Subcellular localization experiments and LC-MS/MS analysis of enriched organellar fraction-proteins confirmed the presence of Oct1p in mitochondria. Phylogenetic profiling of Oct1p revealed an intricate evolutionary pattern indicating multiple horizontal gene transfers among different fungal groups.}, } @article {pmid34097987, year = {2021}, author = {Capitanio, G and Papa, F and Papa, S}, title = {The allosteric protein interactions in the proton-motive function of mammalian redox enzymes of the respiratory chain.}, journal = {Biochimie}, volume = {189}, number = {}, pages = {1-12}, doi = {10.1016/j.biochi.2021.05.018}, pmid = {34097987}, issn = {1638-6183}, mesh = {Allosteric Regulation ; Animals ; Cytochromes b/*metabolism ; Cytochromes c1/*metabolism ; Electron Transport Complex I/*metabolism ; Electron Transport Complex IV/*metabolism ; Humans ; *Proton-Motive Force ; }, abstract = {Insight into mammalian respiratory complexes defines the role of allosteric protein interactions in their proton-motive activity. In cytochrome c oxidase (CxIV) conformational change of subunit I, caused by O2 binding to heme a3[2+]-CuB[+] and reduction, and stereochemical transitions coupled to oxidation/reduction of heme a and CuA, combined with electrostatic effects, determine the proton pumping activity. In ubiquinone-cytochrome c oxidoreductase (CxIII) conformational movement of Fe-S protein between cytochromes b and c1 is the key element of the proton-motive activity. In NADH-ubiquinone oxidoreductase (CxI) ubiquinone binding and reduction result in conformational changes of subunits in the quinone reaction structure which initiate proton pumping.}, } @article {pmid34098144, year = {2021}, author = {Spinelli, S and Begani, G and Guida, L and Magnone, M and Galante, D and D'Arrigo, C and Scotti, C and Iamele, L and De Jonge, H and Zocchi, E and Sturla, L}, title = {LANCL1 binds abscisic acid and stimulates glucose transport and mitochondrial respiration in muscle cells via the AMPK/PGC-1α/Sirt1 pathway.}, journal = {Molecular metabolism}, volume = {53}, number = {}, pages = {101263}, pmid = {34098144}, issn = {2212-8778}, mesh = {AMP-Activated Protein Kinases/*metabolism ; Abscisic Acid/*metabolism ; Glucose/metabolism ; HeLa Cells ; Humans ; Mitochondria/metabolism ; Muscle, Skeletal/cytology/metabolism ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/*metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Sirtuin 1/*metabolism ; }, abstract = {OBJECTIVE: Abscisic acid (ABA) is a plant hormone also present and active in animals. In mammals, ABA regulates blood glucose levels by stimulating insulin-independent glucose uptake and metabolism in adipocytes and myocytes through its receptor LANCL2. The objective of this study was to investigate whether another member of the LANCL protein family, LANCL1, also behaves as an ABA receptor and, if so, which functional effects are mediated by LANCL1.

METHODS: ABA binding to human recombinant LANCL1 was explored by equilibrium-binding experiments with [[3]H]ABA, circular dichroism, and surface plasmon resonance. Rat L6 myoblasts overexpressing either LANCL1 or LANCL2, or silenced for the expression of both proteins, were used to investigate the basal and ABA-stimulated transport of a fluorescent glucose analog (NBDG) and the signaling pathway downstream of the LANCL proteins using Western blot and qPCR analysis. Finally, glucose tolerance and sensitivity to ABA were compared in LANCL2[-/-] and wild-type (WT) siblings.

RESULTS: Human recombinant LANCL1 binds ABA with a Kd between 1 and 10 μM, depending on the assay (i.e., in a concentration range that lies between the low and high-affinity ABA binding sites of LANCL2). In L6 myoblasts, LANCL1 and LANCL2 similarly, i) stimulate both basal and ABA-triggered NBDG uptake (4-fold), ii) activate the transcription and protein expression of the glucose transporters GLUT4 and GLUT1 (4-6-fold) and the signaling proteins AMPK/PGC-1α/Sirt1 (2-fold), iii) stimulate mitochondrial respiration (5-fold) and the expression of the skeletal muscle (SM) uncoupling proteins sarcolipin (3-fold) and UCP3 (12-fold). LANCL2[-/-] mice have a reduced glucose tolerance compared to WT. They spontaneously overexpress LANCL1 in the SM and respond to chronic ABA treatment (1 μg/kg body weight/day) with an improved glycemia response to glucose load and an increased SM transcription of GLUT4 and GLUT1 (20-fold) of the AMPK/PGC-1α/Sirt1 pathway and sarcolipin, UCP3, and NAMPT (4- to 6-fold).

CONCLUSIONS: LANCL1 behaves as an ABA receptor with a somewhat lower affinity for ABA than LANCL2 but with overlapping effector functions: stimulating glucose uptake and the expression of muscle glucose transporters and mitochondrial uncoupling and respiration via the AMPK/PGC-1α/Sirt1 pathway. Receptor redundancy may have been advantageous in animal evolution, given the role of the ABA/LANCL system in the insulin-independent stimulation of cell glucose uptake and energy metabolism.}, } @article {pmid34099752, year = {2021}, author = {Machkour-M'Rabet, S and Hanes, MM and Martínez-Noguez, JJ and Cruz-Medina, J and García-De León, FJ}, title = {The queen conch mitogenome: intra- and interspecific mitogenomic variability in Strombidae and phylogenetic considerations within the Hypsogastropoda.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {11972}, pmid = {34099752}, issn = {2045-2322}, mesh = {Animals ; Base Sequence ; Caribbean Region ; Cell Extracts/genetics ; Gastropoda/*classification/*genetics ; Mitochondria/genetics/metabolism ; NAD/metabolism ; Phylogeny ; RNA, Ribosomal/metabolism ; RNA, Transfer/metabolism ; }, abstract = {Aliger gigas is an economically important and vulnerable marine species. We present a new mitogenome of A. gigas from the Mexican Caribbean and use the eight publicly available Strombidae mitogenomes to analyze intra- and interspecific variation. We present the most complete phylogenomic understanding of Hypsogastropoda to date (17 superfamilies, 39 families, 85 genera, 109 species) to revisit the phylogenetic position of the Stromboidea and evaluate divergence times throughout the phylogeny. The A. gigas mitogenome comprises 15,460 bp including 13 PCGs, 22 tRNAs, and two rRNAs. Nucleotide diversity suggested divergence between the Mexican and Colombian lineages of A. gigas. Interspecific divergence showed high differentiation among Strombidae species and demonstrated a close relationship between A. gigas and Strombus pugilis, between Lambis lambis and Harpago chiragra, and among Tridentarius dentatus/Laevistrombus canarium/Ministrombus variabilis. At the intraspecific level, the gene showing the highest differentiation is ATP8 and the lowest is NAD4L, whereas at the interspecific level the NAD genes show the highest variation and the COX genes the lowest. Phylogenomic analyses confirm that Stromboidea belongs in the non-Latrogastropoda clade and includes Xenophoridea. The phylogenomic position of other superfamilies, including those of previously uncertain affiliation, is also discussed. Finally, our data indicated that Stromboidea diverged into two principal clades in the early Cretaceous while Strombidae diversified in the Paleocene, and lineage diversification within A. gigas took place in the Pleistocene.}, } @article {pmid34109499, year = {2021}, author = {Riyaz, M and Shah, RA and Savarimuthu, I and Kuppusamy, S}, title = {Comparative mitochondrial genome analysis of Eudocima salaminia (Cramer, 1777) (Lepidoptera: Noctuoidea), novel gene rearrangement and phylogenetic relationship within the superfamily Noctuoidea.}, journal = {Molecular biology reports}, volume = {48}, number = {5}, pages = {4449-4463}, pmid = {34109499}, issn = {1573-4978}, support = {EMR/2017/000566//DST/ ; }, mesh = {Animals ; Base Pairing/genetics ; Gene Order ; *Gene Rearrangement ; *Genes, Insect ; *Genome, Mitochondrial ; India ; Insect Proteins/genetics ; Microsatellite Repeats/genetics ; Mitochondria/*genetics ; Moths/*classification/*genetics ; *Phylogeny ; RNA, Ribosomal/genetics ; RNA, Transfer/genetics ; }, abstract = {The species Eudocima salaminia (Cramer, 1777) commonly known as the fruit-piercing moth belongs to family Erebidae. Its distribution varies from India and across South-east Asia, pacific islands and parts of Australia. The insect is a devastating pest of citrus, longans and lychees. In the present study, complete mitochondrial genome of Eudocima salaminia was sequenced and analyzed using Illumina sequencer. The phylogenetic tree was reconstructed based on nucleotide sequences of 13 PCGs using Maximum likelihood method-General Reversible mitochondrial (mtREV) model. The mitogenome has 15,597 base pairs (bp) in length, comprising of 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes and A + T-rich region. All protein-coding genes (PCGs) initiate with canonical start codon ATN. The gene order (trnQ-trnI-trnM) of tRNA shows a different rearrangement compared to ancestral insect gene order (trnI-trnQ-trnM). Almost all tRNAs have a typical cloverleaf secondary structure except for trnS1 (AGN) which lacks the dihydrouridine arm. At the beginning of the control region, we observed a conserved polyT", motif "ATTTA" and microsatellite (TA)n element. There are 21 intergenic regions and five overlapping regions ranging from 1 to 73 bp and 1 to 8 bp, respectively. The phylogenetic relationships based on nucleotide sequences of 13 PCGs using Maximum likelihood method showed the family level relationships as (Notodontidae + (Euteliidae + Noctuidae + (Erebidae + Nolidae))). The present study represents the similarity to phylogenetic analysis of Noctuoidea mitogenome. Moreover, the family Erebidae is the sister to the families of (Euteliidae + Noctuidae + Nolidae).}, } @article {pmid34111145, year = {2021}, author = {Horoiwa, M and Mandagi, IF and Sutra, N and Montenegro, J and Tantu, FY and Masengi, KWA and Nagano, AJ and Kusumi, J and Yasuda, N and Yamahira, K}, title = {Mitochondrial introgression by ancient admixture between two distant lacustrine fishes in Sulawesi Island.}, journal = {PloS one}, volume = {16}, number = {6}, pages = {e0245316}, pmid = {34111145}, issn = {1932-6203}, mesh = {Animals ; *Haplotypes ; *DNA, Mitochondrial/genetics ; Islands ; Phylogeny ; Polymorphism, Single Nucleotide ; Genetic Introgression ; Mitochondria/genetics ; Genetics, Population ; Fishes/genetics/classification ; Ecosystem ; }, abstract = {Sulawesi, an island located in a biogeographical transition zone between Indomalaya and Australasia, is famous for its high levels of endemism. Ricefishes (family Adrianichthyidae) are an example of taxa that have uniquely diversified on this island. It was demonstrated that habitat fragmentation due to the Pliocene juxtaposition among tectonic subdivisions of this island was the primary factor that promoted their divergence; however, it is also equally probable that habitat fusions and resultant admixtures between phylogenetically distant species may have frequently occurred. Previous studies revealed that some individuals of Oryzias sarasinorum endemic to a tectonic lake in central Sulawesi have mitochondrial haplotypes that are similar to the haplotypes of O. eversi, which is a phylogenetically related but geologically distant (ca. 190 km apart) adrianichthyid endemic to a small fountain. In this study, we tested if this reflects ancient admixture of O. eversi and O. sarasinorum. Population genomic analyses of genome-wide single-nucleotide polymorphisms revealed that O. eversi and O. sarasinorum are substantially reproductively isolated from each other. Comparison of demographic models revealed that the models assuming ancient admixture from O. eversi to O. sarasinorum was more supported than the models assuming no admixture; this supported the idea that the O. eversi-like mitochondrial haplotype in O. sarasinorum was introgressed from O. eversi. This study is the first to demonstrate ancient admixture of lacustrine or pond organisms in Sulawesi beyond 100 km. The complex geological history of this island enabled such island-wide admixture of lacustrine organisms, which usually experience limited migration.}, } @article {pmid34118265, year = {2021}, author = {Manoj, KM and Bazhin, NM}, title = {The murburn precepts for aerobic respiration and redox homeostasis.}, journal = {Progress in biophysics and molecular biology}, volume = {167}, number = {}, pages = {104-120}, doi = {10.1016/j.pbiomolbio.2021.05.010}, pmid = {34118265}, issn = {1873-1732}, mesh = {*Adenosine Triphosphate/metabolism ; *Cell Respiration ; Energy Metabolism ; Homeostasis ; Oxidation-Reduction ; Oxidative Phosphorylation ; Respiration ; }, abstract = {Murburn concept is a new perspective to metabolism which posits that certain redox enzymes/proteins mediate catalysis outside their active site, via diffusible reactive oxygen species (DROS, usually deemed as toxic wastes). We have recently questioned the proton-centric chemiosmotic rotary ATP synthesis (CRAS) explanation for mitochondrial oxidative phosphorylation (mOxPhos) and proposed an oxygen-centric murburn model in lieu. Herein, the chemical equations and thermodynamic foundations for this new model of mOxPhos are detailed. Standard transformed Gibbs free energy values of respiratory reactions are calculated to address the spontaneity, control, and efficiency of oxidative phosphorylation. Unlike the deterministic/multi-molecular and 'irreducibly complex' CRAS model, the stochastic/bimolecular and parsimonious murburn reactions afford a more viable precept for the variable and non-integral stoichiometry, higher yield for NADH than FADH2, and origin/evolution of oxygen-centric cellular life. Also, we present tangible DROS-based explanations for the multiple roles of various reaction components, HCN > H2S order of cellular toxicity in aerobes, and explain why oxygen inhibits anaerobes. We highlight the thermodynamic significance of proton deficiency in NADH/mitochondria and link the 'oxygen → DROS → water' metabolic pathway to the macroscopic physiologies of ATP-synthesis, trans-membrane potential, thermogenesis, and homeostasis. We also provide arguments for the extension of the murburn bioenergetics model to life under anoxic and extreme/unique habitats. In the context of mOxPhos, our findings imply that DROS should be seen as an essential requisite for life, and not merely as pathophysiological manifestations.}, } @article {pmid34129020, year = {2021}, author = {Mixão, V and Hegedűsová, E and Saus, E and Pryszcz, LP and Cillingová, A and Nosek, J and Gabaldón, T}, title = {Genome analysis of Candida subhashii reveals its hybrid nature and dual mitochondrial genome conformations.}, journal = {DNA research : an international journal for rapid publication of reports on genes and genomes}, volume = {28}, number = {3}, pages = {}, pmid = {34129020}, issn = {1756-1663}, support = {//European Union's Horizon 2020 Research and Innovation/ ; }, mesh = {Candida/*genetics/metabolism ; Cell Nucleus/*genetics ; *Genome, Fungal ; *Genome, Mitochondrial ; *Metabolic Networks and Pathways ; Phenols/*metabolism ; Whole Genome Sequencing ; }, abstract = {Candida subhashii belongs to the CUG-Ser clade, a group of phylogenetically closely related yeast species that includes some human opportunistic pathogens, such as Candida albicans. Despite being present in the environment, C. subhashii was initially described as the causative agent of a case of peritonitis. Considering the relevance of whole-genome sequencing and analysis for our understanding of genome evolution and pathogenicity, we sequenced, assembled and annotated the genome of C. subhashii type strain. Our results show that C. subhashii presents a highly heterozygous genome and other signatures that point to a hybrid ancestry. The presence of functional pathways for assimilation of hydroxyaromatic compounds goes in line with the affiliation of this yeast with soil microbial communities involved in lignin decomposition. Furthermore, we observed that different clones of this strain may present circular or linear mitochondrial DNA. Re-sequencing and comparison of strains with differential mitochondrial genome topology revealed five candidate genes potentially associated with this conformational change: MSK1, SSZ1, ALG5, MRPL9 and OYE32.}, } @article {pmid34131078, year = {2021}, author = {Hoshino, Y and Gaucher, EA}, title = {Evolution of bacterial steroid biosynthesis and its impact on eukaryogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {25}, pages = {}, pmid = {34131078}, issn = {1091-6490}, support = {R01 AR069137/AR/NIAMS NIH HHS/United States ; }, mesh = {Archaea/genetics ; Bacteria/genetics/*metabolism ; Bayes Theorem ; *Biosynthetic Pathways/genetics ; Cell Membrane/metabolism ; Eukaryotic Cells/*metabolism ; *Evolution, Molecular ; Genes, Bacterial ; Phylogeny ; Steroids/*biosynthesis ; }, abstract = {Steroids are components of the eukaryotic cellular membrane and have indispensable roles in the process of eukaryotic endocytosis by regulating membrane fluidity and permeability. In particular, steroids may have been a structural prerequisite for the acquisition of mitochondria via endocytosis during eukaryogenesis. While eukaryotes are inferred to have evolved from an archaeal lineage, there is little similarity between the eukaryotic and archaeal cellular membranes. As such, the evolution of eukaryotic cellular membranes has limited our understanding of eukaryogenesis. Despite evolving from archaea, the eukaryotic cellular membrane is essentially a fatty acid bacterial-type membrane, which implies a substantial bacterial contribution to the evolution of the eukaryotic cellular membrane. Here, we address the evolution of steroid biosynthesis in eukaryotes by combining ancestral sequence reconstruction and comprehensive phylogenetic analyses of steroid biosynthesis genes. Contrary to the traditional assumption that eukaryotic steroid biosynthesis evolved within eukaryotes, most steroid biosynthesis genes are inferred to be derived from bacteria. In particular, aerobic deltaproteobacteria (myxobacteria) seem to have mediated the transfer of key genes for steroid biosynthesis to eukaryotes. Analyses of resurrected steroid biosynthesis enzymes suggest that the steroid biosynthesis pathway in early eukaryotes may have been similar to the pathway seen in modern plants and algae. These resurrected proteins also experimentally demonstrate that molecular oxygen was required to establish the modern eukaryotic cellular membrane during eukaryogenesis. Our study provides unique insight into relationships between early eukaryotes and other bacteria in addition to the well-known endosymbiosis with alphaproteobacteria.}, } @article {pmid34133204, year = {2021}, author = {Cadena, LR and Gahura, O and Panicucci, B and Zíková, A and Hashimi, H}, title = {Mitochondrial Contact Site and Cristae Organization System and F1FO-ATP Synthase Crosstalk Is a Fundamental Property of Mitochondrial Cristae.}, journal = {mSphere}, volume = {6}, number = {3}, pages = {e0032721}, pmid = {34133204}, issn = {2379-5042}, support = {OPVVV16_019/0000759//Ministry of Education, Youth and Sports of the Czech Republic/ ; LM2015062//Ministry of Education, Youth and Sports of the Czech Republic/ ; 20-23513S//Grantová Agentura České Republiky (GAČR)/ ; 18-17529S//Grantová Agentura České Republiky (GAČR)/ ; 20-01450Y//Grantová Agentura České Republiky (GAČR)/ ; }, abstract = {Mitochondrial cristae are polymorphic invaginations of the inner membrane that are the fabric of cellular respiration. Both the mitochondrial contact site and cristae organization system (MICOS) and the F1FO-ATP synthase are vital for sculpting cristae by opposing membrane-bending forces. While MICOS promotes negative curvature at crista junctions, dimeric F1FO-ATP synthase is crucial for positive curvature at crista rims. Crosstalk between these two complexes has been observed in baker's yeast, the model organism of the Opisthokonta supergroup. Here, we report that this property is conserved in Trypanosoma brucei, a member of the Discoba clade that separated from the Opisthokonta ∼2 billion years ago. Specifically, one of the paralogs of the core MICOS subunit Mic10 interacts with dimeric F1FO-ATP synthase, whereas the other core Mic60 subunit has a counteractive effect on F1FO-ATP synthase oligomerization. This is evocative of the nature of MICOS-F1FO-ATP synthase crosstalk in yeast, which is remarkable given the diversification that these two complexes have undergone during almost 2 eons of independent evolution. Furthermore, we identified a highly diverged, putative homolog of subunit e, which is essential for the stability of F1FO-ATP synthase dimers in yeast. Just like subunit e, it is preferentially associated with dimers and interacts with Mic10, and its silencing results in severe defects to cristae and the disintegration of F1FO-ATP synthase dimers. Our findings indicate that crosstalk between MICOS and dimeric F1FO-ATP synthase is a fundamental property impacting crista shape throughout eukaryotes. IMPORTANCE Mitochondria have undergone profound diversification in separate lineages that have radiated since the last common ancestor of eukaryotes some eons ago. Most eukaryotes are unicellular protists, including etiological agents of infectious diseases, like Trypanosoma brucei. Thus, the study of a broad range of protists can reveal fundamental features shared by all eukaryotes and lineage-specific innovations. Here, we report that two different protein complexes, MICOS and F1FO-ATP synthase, known to affect mitochondrial architecture, undergo crosstalk in T. brucei, just as in baker's yeast. This is remarkable considering that these complexes have otherwise undergone many changes during their almost 2 billion years of independent evolution. Thus, this crosstalk is a fundamental property needed to maintain proper mitochondrial structure even if the constituent players considerably diverged.}, } @article {pmid34136489, year = {2021}, author = {Gažová, I and Lefevre, L and Bush, SJ and Rojo, R and Hume, DA and Lengeling, A and Summers, KM}, title = {CRISPR-Cas9 Editing of Human Histone Deubiquitinase Gene USP16 in Human Monocytic Leukemia Cell Line THP-1.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {679544}, pmid = {34136489}, issn = {2296-634X}, abstract = {USP16 is a histone deubiquitinase which facilitates G2/M transition during the cell cycle, regulates DNA damage repair and contributes to inducible gene expression. We mutated the USP16 gene in a high differentiation clone of the acute monocytic leukemia cell line THP-1 using the CRISPR-Cas9 system and generated four homozygous knockout clones. All were able to proliferate and to differentiate in response to phorbol ester (PMA) treatment. One line was highly proliferative prior to PMA treatment and shut down proliferation upon differentiation, like wild type. Three clones showed sustained expression of the progenitor cell marker MYB, indicating that differentiation had not completely blocked proliferation in these clones. Network analysis of transcriptomic differences among wild type, heterozygotes and homozygotes showed clusters of genes that were up- or down-regulated after differentiation in all cell lines. Prior to PMA treatment, the homozygous clones had lower levels than wild type of genes relating to metabolism and mitochondria, including SRPRB, encoding an interaction partner of USP16. There was also apparent loss of interferon signaling. In contrast, a number of genes were up-regulated in the homozygous cells compared to wild type at baseline, including other deubiquitinases (USP12, BAP1, and MYSM1). However, three homozygotes failed to fully induce USP3 during differentiation. Other network clusters showed effects prior to or after differentiation in the homozygous clones. Thus the removal of USP16 affected the transcriptome of the cells, although all these lines were able to survive, which suggests that the functions attributed to USP16 may be redundant. Our analysis indicates that the leukemic line can adapt to the extreme selection pressure applied by the loss of USP16, and the harsh conditions of the gene editing and selection protocol, through different compensatory pathways. Similar selection pressures occur during the evolution of a cancer in vivo, and our results can be seen as a case study in leukemic cell adaptation. USP16 has been considered a target for cancer chemotherapy, but our results suggest that treatment would select for escape mutants that are resistant to USP16 inhibitors.}, } @article {pmid34140474, year = {2021}, author = {Jin, L and Tang, Q and Hu, S and Chen, Z and Zhou, X and Zeng, B and Wang, Y and He, M and Li, Y and Gui, L and Shen, L and Long, K and Ma, J and Wang, X and Chen, Z and Jiang, Y and Tang, G and Zhu, L and Liu, F and Zhang, B and Huang, Z and Li, G and Li, D and Gladyshev, VN and Yin, J and Gu, Y and Li, X and Li, M}, title = {A pig BodyMap transcriptome reveals diverse tissue physiologies and evolutionary dynamics of transcription.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {3715}, pmid = {34140474}, issn = {2041-1723}, mesh = {Adipose Tissue/*metabolism ; Alternative Splicing ; Animals ; Biological Evolution ; Cell Line ; Cell Lineage ; Cell Nucleus/genetics/metabolism ; Enhancer Elements, Genetic ; Evolution, Molecular ; Gene Expression Profiling ; Gene Regulatory Networks ; MicroRNAs/genetics/*metabolism ; Mitochondria/metabolism ; Molecular Conformation ; Muscle, Skeletal/*metabolism ; Myofibrils/genetics/metabolism ; Phylogeny ; Promoter Regions, Genetic ; RNA, Circular/genetics/*metabolism ; RNA, Long Noncoding/genetics/*metabolism ; RNA, Messenger/genetics/*metabolism ; Spatial Analysis ; Swine ; Transcriptome/*genetics ; }, abstract = {A comprehensive transcriptomic survey of pigs can provide a mechanistic understanding of tissue specialization processes underlying economically valuable traits and accelerate their use as a biomedical model. Here we characterize four transcript types (lncRNAs, TUCPs, miRNAs, and circRNAs) and protein-coding genes in 31 adult pig tissues and two cell lines. We uncover the transcriptomic variability among 47 skeletal muscles, and six adipose depots linked to their different origins, metabolism, cell composition, physical activity, and mitochondrial pathways. We perform comparative analysis of the transcriptomes of seven tissues from pigs and nine other vertebrates to reveal that evolutionary divergence in transcription potentially contributes to lineage-specific biology. Long-range promoter-enhancer interaction analysis in subcutaneous adipose tissues across species suggests evolutionarily stable transcription patterns likely attributable to redundant enhancers buffering gene expression patterns against perturbations, thereby conferring robustness during speciation. This study can facilitate adoption of the pig as a biomedical model for human biology and disease and uncovers the molecular bases of valuable traits.}, } @article {pmid34145919, year = {2021}, author = {Dymek, AM and Pecio, A and Piprek, RP}, title = {Diversity of Balbiani body formation in internally and externally fertilizing representatives of Osteoglossiformes (Teleostei: Osteoglossomorpha).}, journal = {Journal of morphology}, volume = {282}, number = {9}, pages = {1313-1329}, doi = {10.1002/jmor.21387}, pmid = {34145919}, issn = {1097-4687}, mesh = {Animals ; Fertilization ; Germ Cells ; Male ; Mitochondria ; *Oocytes/metabolism ; *Oogenesis ; }, abstract = {During the early stages of oogenesis, the Balbiani body is formed in the primary oocytes. It consists of the Golgi apparatus, endoplasmic reticulum (ER), and numerous mitochondria aggregated with germ plasm, but its form may differ among animals. Hypothetically, during oogenesis oocytes become adapted to future development in two different environments depending on internal or external fertilization. We aimed to investigate, using light and transmission electron microscopy, the development of the Balbiani body during oogenesis in representatives of Osteoglossiformes, one of the most basal Teleostei groups. We analyzed the structure of oogonia and primary oocytes in the internally fertilizing butterflyfish Pantodon buchholzi and the externally fertilizing Osteoglossum bicirrhosum and Arapaima gigas to compare formation of the Balbiani body in relation to modes of fertilization. We demonstrated that the presence of the germ plasm as well as the fusion and fission of mitochondria are the conserved features of the Bb. However, each species exhibited also some peculiar features, including the presence of three types of ooplasm with different electron density and mitochondria-associated membranes in P. buchholzi; annulate lamellae, complexes of the Golgi apparatus, ER network, and lysosome-like bodies in O. bicirrhosum; as well as karmellae and whorls formed by the lamellae of the ER in A. gigas. Moreover, the form of the germ plasm observed in close contact with mitochondria differed between osteoglossiforms, with a "net-like" structure in P. buchholzi, the presence of numerous strings in O. bicirrhosum, and irregular accumulations in A. gigas. These unique features indicate that the extreme diversity of gamete structure observed so far only in the spermatozoa of osteoglossiforms is also characteristic for oocyte development in these basal teleosts. Possible reason of this variability is a period of about 150 million years of independent evolution of the lineages.}, } @article {pmid34154402, year = {2021}, author = {Comandatore, F and Radaelli, G and Montante, S and Sacchi, L and Clementi, E and Epis, S and Cafiso, A and Serra, V and Pajoro, M and Di Carlo, D and Floriano, AM and Stavru, F and Bandi, C and Sassera, D}, title = {Modeling the Life Cycle of the Intramitochondrial Bacterium "Candidatus Midichloria mitochondrii" Using Electron Microscopy Data.}, journal = {mBio}, volume = {12}, number = {3}, pages = {e0057421}, pmid = {34154402}, issn = {2150-7511}, mesh = {Alphaproteobacteria/*growth & development/*ultrastructure ; Animals ; DNA, Bacterial ; Ixodes/*microbiology ; *Life Cycle Stages ; Microscopy, Electron/*methods ; Mitochondria/microbiology ; Phylogeny ; Symbiosis ; }, abstract = {"Candidatus Midichloria mitochondrii" is a Gram-negative bacterium that lives in strict intracellular symbiosis with the hard tick Ixodes ricinus, forming one of the most intriguing endosymbiosis described to date. The bacterium is capable of durably colonizing the host mitochondria, a peculiar tropism that makes "Ca. Midichloria mitochondrii" a very interesting tool to study the physiology of these cellular organelles. The interaction between the symbiont and the organelle has, however, been difficult to characterize. A parallelism with the predatory bacterium Bdellovibrio bacteriovorus has been drawn, suggesting the hypothesis that "Ca. Midichloria mitochondrii" could prey on mitochondria and consume them to multiply. We studied the life cycle of the bacterium within the host oocytes using a multidisciplinary approach, including electron microscopy, molecular biology, statistics, and systems biology. Our results were not coherent with a predatory-like behavior by "Ca. Midichloria mitochondrii" leading us to propose a novel hypothesis for its life cycle. Based on our results, we here present a novel model called the "mitochondrion-to-mitochondrion hypothesis." Under this model, the bacterium would be able to move from mitochondrion to mitochondrion, possibly within a mitochondrial network. We show that this model presents a good fit with quantitative electron microscopy data. IMPORTANCE Our results suggest that "Candidatus Midichloria mitochondrii," the intramitochondrial bacterium, does not invade mitochondria like predatory bacteria do but instead moves from mitochondrion to mitochondrion within the oocytes of Ixodes ricinus. A better understanding of the lifestyle of "Ca. Midichloria mitochondrii" will allow us to better define the role of this bacterial symbiont in the host physiology.}, } @article {pmid34155201, year = {2021}, author = {Evers, F and Cabrera-Orefice, A and Elurbe, DM and Kea-Te Lindert, M and Boltryk, SD and Voss, TS and Huynen, MA and Brandt, U and Kooij, TWA}, title = {Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {3820}, pmid = {34155201}, issn = {2041-1723}, mesh = {Electron Transport Chain Complex Proteins/metabolism/ultrastructure ; Evolution, Molecular ; *Life Cycle Stages ; Mitochondria/*metabolism/ultrastructure ; Mitochondrial Proteins/metabolism/ultrastructure ; Multiprotein Complexes/metabolism/ultrastructure ; Oxidative Phosphorylation ; Plasmodium falciparum/growth & development/*metabolism/ultrastructure ; Protozoan Proteins/metabolism/ultrastructure ; Species Specificity ; }, abstract = {Our current understanding of mitochondrial functioning is largely restricted to traditional model organisms, which only represent a fraction of eukaryotic diversity. The unusual mitochondrion of malaria parasites is a validated drug target but remains poorly understood. Here, we apply complexome profiling to map the inventory of protein complexes across the pathogenic asexual blood stages and the transmissible gametocyte stages of Plasmodium falciparum. We identify remarkably divergent composition and clade-specific additions of all respiratory chain complexes. Furthermore, we show that respiratory chain complex components and linked metabolic pathways are up to 40-fold more prevalent in gametocytes, while glycolytic enzymes are substantially reduced. Underlining this functional switch, we find that cristae are exclusively present in gametocytes. Leveraging these divergent properties and stage dynamics for drug development presents an attractive opportunity to discover novel classes of antimalarials and increase our repertoire of gametocytocidal drugs.}, } @article {pmid34158556, year = {2021}, author = {Soukal, P and Hrdá, Š and Karnkowska, A and Milanowski, R and Szabová, J and Hradilová, M and Strnad, H and Vlček, Č and Čepička, I and Hampl, V}, title = {Heterotrophic euglenid Rhabdomonas costata resembles its phototrophic relatives in many aspects of molecular and cell biology.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {13070}, pmid = {34158556}, issn = {2045-2322}, mesh = {Biological Evolution ; Chromatium/genetics/*metabolism ; Euglenida/*genetics/metabolism ; Exons/genetics ; Genome ; Heterotrophic Processes ; Introns/genetics ; Mitochondria/genetics ; Phylogeny ; Sequence Analysis, DNA/methods ; Transcriptome/genetics ; }, abstract = {Euglenids represent a group of protists with diverse modes of feeding. To date, only a partial genomic sequence of Euglena gracilis and transcriptomes of several phototrophic and secondarily osmotrophic species are available, while primarily heterotrophic euglenids are seriously undersampled. In this work, we begin to fill this gap by presenting genomic and transcriptomic drafts of a primary osmotroph, Rhabdomonas costata. The current genomic assembly length of 100 Mbp is 14× smaller than that of E. gracilis. Despite being too fragmented for comprehensive gene prediction it provided fragments of the mitochondrial genome and comparison of the transcriptomic and genomic data revealed features of its introns, including several candidates for nonconventional types. A set of 39,456 putative R. costata proteins was predicted from the transcriptome. Annotation of the mitochondrial core metabolism provides the first data on the facultatively anaerobic mitochondrion of R. costata, which in most respects resembles the mitochondrion of E. gracilis with a certain level of streamlining. R. costata can synthetise thiamine by enzymes of heterogenous provenances and haem by a mitochondrial-cytoplasmic C4 pathway with enzymes orthologous to those found in E. gracilis. The low percentage of green algae-affiliated genes supports the ancestrally osmotrophic status of this species.}, } @article {pmid34166699, year = {2021}, author = {Xu, XD and Guan, JY and Zhang, ZY and Cao, YR and Storey, KB and Yu, DN and Zhang, JY}, title = {Novel tRNA gene rearrangements in the mitochondrial genomes of praying mantises (Mantodea: Mantidae): Translocation, duplication and pseudogenization.}, journal = {International journal of biological macromolecules}, volume = {185}, number = {}, pages = {403-411}, doi = {10.1016/j.ijbiomac.2021.06.096}, pmid = {34166699}, issn = {1879-0003}, mesh = {Animals ; Evolution, Molecular ; Gene Duplication ; Gene Order ; *Gene Rearrangement ; Genome, Mitochondrial ; Mantodea/*genetics ; Mitochondria/*genetics ; Nucleic Acid Conformation ; Phylogeny ; Pseudogenes ; RNA, Plant/genetics ; RNA, Transfer/chemistry/*genetics ; Sequence Analysis, DNA ; Translocation, Genetic ; }, abstract = {Gene rearrangements have been found in several mitochondrial genomes of Mantodea, located in the gene blocks CR-I-Q-M-ND2, COX1-K-D-ATP8 and ND3-A-R-N-S-E-F-ND5. We have sequenced one mitogenome of Amelidae (Yersinia mexicana) and six mitogenomes of Mantidae to discuss the mitochondrial gene rearrangement and the phylogenetic relationship within Mantidae. These mitogenomes showed rearrangements of tRNA genes except for Asiadodis yunnanensis and Hierodula zhangi. These novel gene rearrangements of Mantidae were primarily concentrated in the region of CR-I-Q-M-ND2, including gene translocation, duplication and pseudogenization. For the occurrences of these rearrangements, the tandem duplication-random loss (TDRL) model and slipped-strand mispairing model were suitable to explain. Large non-coding regions (LNCRs) located in the region of CR-I-Q-M-ND2 were detected in most Mantidae species, whereas some LNCRs had high similarity to the control region (CR). Both BI and ML phylogenetic analyses supported the monophyly of Mantidae and the paraphyly of Mantinae. The phylogenetic results with the gene order and the location of NCRs acted as forceful evidence that specific gene rearrangements and special LNCRs may be synapomorphies for several groups of mantises.}, } @article {pmid34171617, year = {2021}, author = {Iwata, R and Vanderhaeghen, P}, title = {Regulatory roles of mitochondria and metabolism in neurogenesis.}, journal = {Current opinion in neurobiology}, volume = {69}, number = {}, pages = {231-240}, pmid = {34171617}, issn = {1873-6882}, mesh = {Cell Differentiation ; Cell Proliferation ; Humans ; Mitochondria ; *Neural Stem Cells/metabolism ; *Neurogenesis ; }, abstract = {Neural stem cells (NSCs) undergo massive molecular and cellular changes during neuronal differentiation. These include mitochondria and metabolism remodelling, which were thought to be mostly permissive cues, but recent work indicates that they are causally linked to neurogenesis. Striking remodelling of mitochondria occurs right after mitosis of NSCs, which influences the postmitotic daughter cells towards self-renewal or differentiation. The transitioning to neuronal fate requires metabolic rewiring including increased oxidative phosphorylation activity, which drives transcriptional and epigenetic effects to influence cell fate. Mitochondria metabolic pathways also contribute in an essential way to the regulation of NSC proliferation and self-renewal. The influence of mitochondria and metabolism on neurogenesis is conserved from fly to human systems, but also displays striking differences linked to cell context or species. These new findings have important implications for our understanding of neurodevelopmental diseases and possibly human brain evolution.}, } @article {pmid34175310, year = {2021}, author = {Parrot, C and Moulinier, L and Bernard, F and Hashem, Y and Dupuy, D and Sissler, M}, title = {Peculiarities of aminoacyl-tRNA synthetases from trypanosomatids.}, journal = {The Journal of biological chemistry}, volume = {297}, number = {2}, pages = {100913}, pmid = {34175310}, issn = {1083-351X}, mesh = {Amino Acid Sequence ; Amino Acids/*metabolism ; Amino Acyl-tRNA Synthetases/chemistry/genetics/*metabolism ; Animals ; Cytosol/metabolism ; Humans ; Leishmania/*enzymology/isolation & purification ; Leishmaniasis/enzymology/parasitology/*pathology ; Mitochondria/metabolism ; Phylogeny ; RNA, Transfer/*genetics/metabolism ; Sequence Homology, Amino Acid ; }, abstract = {Trypanosomatid parasites are responsible for various human diseases, such as sleeping sickness, animal trypanosomiasis, or cutaneous and visceral leishmaniases. The few available drugs to fight related parasitic infections are often toxic and present poor efficiency and specificity, and thus, finding new molecular targets is imperative. Aminoacyl-tRNA synthetases (aaRSs) are essential components of the translational machinery as they catalyze the specific attachment of an amino acid onto cognate tRNA(s). In trypanosomatids, one gene encodes both cytosolic- and mitochondrial-targeted aaRSs, with only three exceptions. We identify here a unique specific feature of aaRSs from trypanosomatids, which is that most of them harbor distinct insertion and/or extension sequences. Among the 26 identified aaRSs in the trypanosome Leishmania tarentolae, 14 contain an additional domain or a terminal extension, confirmed in mature mRNAs by direct cDNA nanopore sequencing. Moreover, these RNA-Seq data led us to address the question of aaRS dual localization and to determine splice-site locations and the 5'-UTR lengths for each mature aaRS-encoding mRNA. Altogether, our results provided evidence for at least one specific mechanism responsible for mitochondrial addressing of some L. tarentolae aaRSs. We propose that these newly identified features of trypanosomatid aaRSs could be developed as relevant drug targets to combat the diseases caused by these parasites.}, } @article {pmid34175396, year = {2021}, author = {Lin, C and Tang, D and Gao, X and Jiang, H and Du, C and Zhu, J}, title = {Molecular characterization, dynamic transcription, and potential function of KIF3A/KIF3B during spermiogenesis in Opsariichthys bidens.}, journal = {Gene}, volume = {798}, number = {}, pages = {145795}, doi = {10.1016/j.gene.2021.145795}, pmid = {34175396}, issn = {1879-0038}, mesh = {Animals ; Cyprinidae/genetics/*physiology ; Kinesins/chemistry/genetics/*physiology ; Male ; Microtubules/metabolism ; Mitochondria/metabolism ; Phylogeny ; Protein Conformation ; RNA, Messenger/metabolism ; Sequence Alignment ; Sequence Analysis, DNA ; Sperm Tail/physiology ; Spermatids/physiology/ultrastructure ; Spermatogenesis/genetics/*physiology ; Testis/metabolism ; Transcription, Genetic ; }, abstract = {Spermiogenesis is the final phase of spermatogenesis, wherein the spermatids differentiate into mature spermatozoa via complex morphological transformation. In this process, kinesin plays an important role. Here, we observed the morphological transformation of spermatids and analyzed the characterization, dynamic transcription, and potential function of kinesin KIF3A/KIF3B during spermiogenesis in Chinese hook snout carp (Opsariichthys bidens). We found that the full-length cDNAs of O. bidens kif3a and kif3b were 2544 and 2806 bp in length comprising 119 bp and 259 bp 5' untranslated region (UTR), 313 bp and 222 bp 3' UTR, and 2112 bp and 2325 bp open reading frame encoding 703 and 774 amino acids, respectively. Ob-KIF3A/KIF3B proteins have three domains, namely N-terminal head, coiled-coil stalk, and C-terminal tail, and exhibit high similarity with homologous proteins in vertebrates and invertebrates. Ob-kif3a/kif3b mRNAs were ubiquitously expressed in all tissues examined, with the highest expression in the brain and stage-IV testis. Immunofluorescence results showed that Ob-KIF3A was co-localized with tubulin and the mitochondria. Particularly, in early spermatids, Ob-KIF3A, tubulin, and the mitochondrial signals were evenly distributed in the cytoplasm, whereas in middle spermatids, they were distributed around the nucleus. In the late stage, the signals were concentrated on one side of the nucleus, where the tail is formed, whereas in mature sperms, they were detected in the midpiece and flagellum. These results indicate that Ob-KIF3A/KIF3B may participate in nuclear reshaping, flagellum formation, and mitochondrial aggregation in the midpiece during spermiogenesis.}, } @article {pmid34188831, year = {2021}, author = {Yang, M and Dong, D and Li, X}, title = {The complete mitogenome of Phymorhynchus sp. (Neogastropoda, Conoidea, Raphitomidae) provides insights into the deep-sea adaptive evolution of Conoidea.}, journal = {Ecology and evolution}, volume = {11}, number = {12}, pages = {7518-7531}, pmid = {34188831}, issn = {2045-7758}, abstract = {The deep-sea environment is characterized by darkness, hypoxia, and high hydrostatic pressure. Mitochondria play a vital role in energy metabolism; thus, they may endure the selection process during the adaptive evolution of deep-sea organisms. In the present study, the mitogenome of Phymorhynchus sp. from the Haima methane seep was completely assembled and characterized. This mitogenome is 16,681 bp in length and contains 13 protein-coding genes, 2 rRNAs, and 22 tRNAs. The gene order and orientation were identical to those of most sequenced conoidean gastropods. Some special elements, such as tandem repeat sequences and AT-rich sequences, which are involved in the regulation of the replication and transcription of the mitogenome, were observed in the control region. Phylogenetic analysis revealed that Conoidea is divided into two separate clades with high nodal support. Positive selection analysis revealed evidence of adaptive changes in the mitogenomes of deep-sea conoidean gastropods. Eight residues located in atp6, cox1, cytb, nad1, nad4, and nad5 were determined to have undergone positive selection. This study explores the adaptive evolution of deep-sea conoidean gastropods and provides valuable clues at the mitochondrial level regarding the exceptional adaptive ability of organisms in deep-sea environments.}, } @article {pmid34192514, year = {2021}, author = {Amine, AAA and Liao, CW and Hsu, PC and Opoc, FJG and Leu, JY}, title = {Experimental evolution improves mitochondrial genome quality control in Saccharomyces cerevisiae and extends its replicative lifespan.}, journal = {Current biology : CB}, volume = {31}, number = {16}, pages = {3663-3670.e4}, doi = {10.1016/j.cub.2021.06.026}, pmid = {34192514}, issn = {1879-0445}, mesh = {DNA, Mitochondrial/genetics ; *Directed Molecular Evolution ; *Genome, Mitochondrial ; Longevity ; *Saccharomyces cerevisiae/genetics ; }, abstract = {The mitochondrion is an ancient endosymbiotic organelle that performs many essential functions in eukaryotic cells.[1-3] Mitochondrial impairment often results in physiological defects or diseases.[2-8] Since most mitochondrial genes have been copied into the nuclear genome during evolution,[9] the regulatory and interaction mechanisms between the mitochondrial and nuclear genomes are very complex. Multiple mechanisms, including antioxidant, DNA repair, mitophagy, and mitochondrial biogenesis pathways, have been shown to monitor the quality and quantity of mitochondria.[10-12] Nonetheless, it remains unclear if these pathways can be further modified to enhance mitochondrial stability. Previously, experimental evolution has been used to adapt cells to novel growth conditions. By analyzing the resulting evolved populations, insights have been gained into the underlying molecular mechanisms.[13] Here, we experimentally evolved yeast cells under conditions that selected for efficient respiration while continuously assaulting the mitochondrial genome (mtDNA) with ethidium bromide (EtBr). We found that the ability to maintain functional mtDNA was enhanced in most of the evolved lines when challenged with mtDNA-damaging reagents. We identified mutations of the mitochondrial NADH dehydrogenase NDE1 in most of the evolved lines, but other pathways are also involved. Finally, we show that cells displaying enhanced mtDNA retention also exhibit a prolonged replicative lifespan. Our work reveals potential evolutionary trajectories by which cells can maintain functional mitochondria in response to mtDNA stress, as well as the physiological implications of such adaptations.}, } @article {pmid34193932, year = {2021}, author = {Ye, L and Yao, T and Lu, J and Jiang, J and Bai, C}, title = {Mitochondrial genomes of two Polydora (Spionidae) species provide further evidence that mitochondrial architecture in the Sedentaria (Annelida) is not conserved.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {13552}, pmid = {34193932}, issn = {2045-2322}, mesh = {Animals ; Annelida/*genetics ; *Evolution, Molecular ; *Gene Order ; *Genome, Mitochondrial ; Mitochondria/*genetics ; *Phylogeny ; }, abstract = {Contrary to the early evidence, which indicated that the mitochondrial architecture in one of the two major annelida clades, Sedentaria, is relatively conserved, a handful of relatively recent studies found evidence that some species exhibit elevated rates of mitochondrial architecture evolution. We sequenced complete mitogenomes belonging to two congeneric shell-boring Spionidae species that cause considerable economic losses in the commercial marine mollusk aquaculture: Polydora brevipalpa and Polydora websteri. The two mitogenomes exhibited very similar architecture. In comparison to other sedentarians, they exhibited some standard features, including all genes encoded on the same strand, uncommon but not unique duplicated trnM gene, as well as a number of unique features. Their comparatively large size (17,673 bp) can be attributed to four non-coding regions larger than 500 bp. We identified an unusually large (putative) overlap of 14 bases between nad2 and cox1 genes in both species. Importantly, the two species exhibited completely rearranged gene orders in comparison to all other available mitogenomes. Along with Serpulidae and Sabellidae, Polydora is the third identified sedentarian lineage that exhibits disproportionally elevated rates of mitogenomic architecture rearrangements. Selection analyses indicate that these three lineages also exhibited relaxed purifying selection pressures.}, } @article {pmid34202821, year = {2021}, author = {Purnomo, GA and Mitchell, KJ and O'Connor, S and Kealy, S and Taufik, L and Schiller, S and Rohrlach, A and Cooper, A and Llamas, B and Sudoyo, H and Teixeira, JC and Tobler, R}, title = {Mitogenomes Reveal Two Major Influxes of Papuan Ancestry across Wallacea Following the Last Glacial Maximum and Austronesian Contact.}, journal = {Genes}, volume = {12}, number = {7}, pages = {}, pmid = {34202821}, issn = {2073-4425}, mesh = {Animals ; Archaeology/history ; Asia ; Australia ; Coleoptera/genetics ; Female ; *Genetics, Population ; Genome, Mitochondrial/*genetics ; Haplotypes/genetics ; History, Ancient ; Humans ; Male ; New Guinea ; Oceania ; *Phylogeny ; *Phylogeography ; }, abstract = {The tropical archipelago of Wallacea contains thousands of individual islands interspersed between mainland Asia and Near Oceania, and marks the location of a series of ancient oceanic voyages leading to the peopling of Sahul-i.e., the former continent that joined Australia and New Guinea at a time of lowered sea level-by 50,000 years ago. Despite the apparent deep antiquity of human presence in Wallacea, prior population history research in this region has been hampered by patchy archaeological and genetic records and is largely concentrated upon more recent history that follows the arrival of Austronesian seafarers ~3000-4000 years ago (3-4 ka). To shed light on the deeper history of Wallacea and its connections with New Guinea and Australia, we performed phylogeographic analyses on 656 whole mitogenomes from these three regions, including 186 new samples from eight Wallacean islands and three West Papuan populations. Our results point to a surprisingly dynamic population history in Wallacea, marked by two periods of extensive demographic change concentrated around the Last Glacial Maximum ~15 ka and post-Austronesian contact ~3 ka. These changes appear to have greatly diminished genetic signals informative about the original peopling of Sahul, and have important implications for our current understanding of the population history of the region.}, } @article {pmid34204357, year = {2021}, author = {Richtová, J and Sheiner, L and Gruber, A and Yang, SM and Kořený, L and Striepen, B and Oborník, M}, title = {Using Diatom and Apicomplexan Models to Study the Heme Pathway of Chromera velia.}, journal = {International journal of molecular sciences}, volume = {22}, number = {12}, pages = {}, pmid = {34204357}, issn = {1422-0067}, support = {21-03224S//Grantová Agentura České Republiky/ ; CZ.02.1.01/0.0/0.0/16_019/0000759//ERDF/ESF, Centre for Research of Pathogenicity and Virulence of Parasites/ ; }, mesh = {Alveolata/*physiology ; Amino Acid Sequence ; Apicomplexa/*metabolism ; Biological Transport ; Diatoms/*metabolism ; Evolution, Molecular ; Gene Expression Regulation, Enzymologic ; Heme/*metabolism ; *Metabolic Networks and Pathways ; Mitochondria/genetics/metabolism/ultrastructure ; Protozoan Proteins/chemistry/genetics/metabolism ; }, abstract = {Heme biosynthesis is essential for almost all living organisms. Despite its conserved function, the pathway's enzymes can be located in a remarkable diversity of cellular compartments in different organisms. This location does not always reflect their evolutionary origins, as might be expected from the history of their acquisition through endosymbiosis. Instead, the final subcellular localization of the enzyme reflects multiple factors, including evolutionary origin, demand for the product, availability of the substrate, and mechanism of pathway regulation. The biosynthesis of heme in the apicomonad Chromera velia follows a chimeric pathway combining heme elements from the ancient algal symbiont and the host. Computational analyses using different algorithms predict complex targeting patterns, placing enzymes in the mitochondrion, plastid, endoplasmic reticulum, or the cytoplasm. We employed heterologous reporter gene expression in the apicomplexan parasite Toxoplasma gondii and the diatom Phaeodactylum tricornutum to experimentally test these predictions. 5-aminolevulinate synthase was located in the mitochondria in both transfection systems. In T. gondii, the two 5-aminolevulinate dehydratases were located in the cytosol, uroporphyrinogen synthase in the mitochondrion, and the two ferrochelatases in the plastid. In P. tricornutum, all remaining enzymes, from ALA-dehydratase to ferrochelatase, were placed either in the endoplasmic reticulum or in the periplastidial space.}, } @article {pmid34211040, year = {2021}, author = {Sarkar, BK and Sharma, AR and Bhattacharya, M and Sharma, G and Lee, SS and Chakraborty, C}, title = {Determination of k-mer density in a DNA sequence and subsequent cluster formation algorithm based on the application of electronic filter.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {13701}, pmid = {34211040}, issn = {2045-2322}, mesh = {*Algorithms ; Animals ; Base Sequence ; Cluster Analysis ; DNA/genetics ; DNA, Mitochondrial/genetics ; Genome, Mitochondrial ; Humans ; Phylogeny ; Principal Component Analysis ; Sequence Analysis, DNA/*methods ; beta-Globins/genetics ; }, abstract = {We describe a novel algorithm for information recovery from DNA sequences by using a digital filter. This work proposes a three-part algorithm to decide the k-mer or q-gram word density. Employing a finite impulse response digital filter, one can calculate the sequence's k-mer or q-gram word density. Further principal component analysis is used on word density distribution to analyze the dissimilarity between sequences. A dissimilarity matrix is thus formed and shows the appearance of cluster formation. This cluster formation is constructed based on the alignment-free sequence method. Furthermore, the clusters are used to build phylogenetic relations. The cluster algorithm is in good agreement with alignment-based algorithms. The present algorithm is simple and requires less time for computation than other currently available algorithms. We tested the algorithm using beta hemoglobin coding sequences (HBB) of 10 different species and 18 primate mitochondria genome (mtDNA) sequences.}, } @article {pmid34211399, year = {2021}, author = {García-Casas, P and Alvarez-Illera, P and Gómez-Orte, E and Cabello, J and Fonteriz, RI and Montero, M and Alvarez, J}, title = {The Mitochondrial Na[+]/Ca[2+] Exchanger Inhibitor CGP37157 Preserves Muscle Structure and Function to Increase Lifespan and Healthspan in Caenorhabditis elegans.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {695687}, pmid = {34211399}, issn = {1663-9812}, abstract = {We have reported recently that the mitochondrial Na[+]/Ca[2+] exchanger inhibitor CGP37157 extends lifespan in Caenorhabditis elegans by a mechanism involving mitochondria, the TOR pathway and the insulin/IGF1 pathway. Here we show that CGP37157 significantly improved the evolution with age of the sarcomeric regular structure, delaying development of sarcopenia in C. elegans body wall muscle and increasing the average and maximum speed of the worms. Similarly, CGP37157 favored the maintenance of a regular mitochondrial structure during aging. We have also investigated further the mechanism of the effect of CGP37157 by studying its effect in mutants of aak-1;aak-2/AMP-activated kinase, sir-2.1/sirtuin, rsks-1/S6 kinase and daf-16/FOXO. We found that this compound was still effective increasing lifespan in all these mutants, indicating that these pathways are not involved in the effect. We have then monitored pharynx cytosolic and mitochondrial Ca[2+] signalling and our results suggest that CGP37157 is probably inhibiting not only the mitochondrial Na[+]/Ca[2+] exchanger, but also Ca[2+] entry through the plasma membrane. Finally, a transcriptomic study detected that CGP37157 induced changes in lipid metabolism enzymes and a four-fold increase in the expression of ncx-6, one of the C. elegans mitochondrial Na[+]/Ca[2+] exchangers. In summary, CGP37157 increases both lifespan and healthspan by a mechanism involving changes in cytosolic and mitochondrial Ca[2+] homeostasis. Thus, Ca[2+] signalling could be a promising target to act on aging.}, } @article {pmid34211444, year = {2021}, author = {Degli Esposti, M and Moya-Beltrán, A and Quatrini, R and Hederstedt, L}, title = {Respiratory Heme A-Containing Oxidases Originated in the Ancestors of Iron-Oxidizing Bacteria.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {664216}, pmid = {34211444}, issn = {1664-302X}, abstract = {Respiration is a major trait shaping the biology of many environments. Cytochrome oxidase containing heme A (COX) is a common terminal oxidase in aerobic bacteria and is the only one in mammalian mitochondria. The synthesis of heme A is catalyzed by heme A synthase (CtaA/Cox15), an enzyme that most likely coevolved with COX. The evolutionary origin of COX in bacteria has remained unknown. Using extensive sequence and phylogenetic analysis, we show that the ancestral type of heme A synthases is present in iron-oxidizing Proteobacteria such as Acidithiobacillus spp. These bacteria also contain a deep branching form of the major COX subunit (COX1) and an ancestral variant of CtaG, a protein that is specifically required for COX biogenesis. Our work thus suggests that the ancestors of extant iron-oxidizers were the first to evolve COX. Consistent with this conclusion, acidophilic iron-oxidizing prokaryotes lived on emerged land around the time for which there is the earliest geochemical evidence of aerobic respiration on earth. Hence, ecological niches of iron oxidation have apparently promoted the evolution of aerobic respiration.}, } @article {pmid34212085, year = {2021}, author = {Sheng, L and Zhou, T and Shi, Z and Pan, X and Weng, X and Ma, J and Wu, S}, title = {The complete mitochondrial genome of Trictenotoma davidi Deyrolle, 1875 (Coleoptera: Trictenotomidae).}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {6}, number = {7}, pages = {2026-2027}, pmid = {34212085}, issn = {2380-2359}, abstract = {Trictenotoma davidi Deyrolle, 1875 is a beetle of the Trictenotomidae family. The length of the complete mitochondria genome of T. davidi was 15,910 bp with 24.1% GC content, including 39.9% A, 15.1% C, 9.0% G, and 36.0% T. The genome encoded 13 protein-coding genes, 22 tRNAs, and 2 rRNAs. Phylogenetic analysis showed that T. davidi was closely related to Vincenzellus ruficollis. This study provided useful genetic information for the evolution of T. davidi and Trictenotomidae insects.}, } @article {pmid34222053, year = {2021}, author = {Li, T and Fang, Z and He, Q and Wang, C and Meng, X and Yu, B and Zhou, Z}, title = {Characterizing the Xenoma of Vairimorpha necatrix Provides Insights Into the Most Efficient Mode of Microsporidian Proliferation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {699239}, pmid = {34222053}, issn = {2235-2988}, mesh = {Animals ; Cell Proliferation ; Humans ; In Situ Hybridization, Fluorescence ; *Microsporidia/genetics ; Phylogeny ; }, abstract = {Microsporidia are a group of obligated intracellular parasites that can infect nearly all vertebrates and invertebrates, including humans and economic animals. Microsporidian Vairimorpha necatrix is a natural pathogen of multiple insects and can massively proliferate by making tumor-like xenoma in host tissue. However, little is known about the subcellular structures of this xenoma and the proliferation features of the pathogens inside. Here, we characterized the V. necatrix xenoma produced in muscle cells of silkworm midgut. In result, the whitish xenoma was initially observed on the 12[th] day post infection on the outer surface of the midgut and later became larger and numerous. The observation by scanning electronic microscopy showed that the xenoma is mostly elliptical and spindle with dense pathogen-containing protrusions and spores on the surface, which were likely shedding off the xenoma through exocytosis and could be an infection source of other tissues. Demonstrated with transmission electron microscopy and fluorescent staining, the xenoma was enveloped by a monolayer membrane, and full of vesicle structures, mitochondria, and endoplasmic reticulum around parasites in development, suggesting that high level of energy and nutrients were produced to support the massive proliferation of the parasites. Multiple hypertrophic nuclei were found in one single xenoma, indicating that the cyst was probably formed by fusion of multiple muscle cells. Observed by fluorescence in situ hybridization, pathogens in the xenoma were in merongony, sporogony, and octosporogony, and mature stages. And mature spores were pushed to the center while vegetative pathogens were in the surface layer of the xenoma. The V. necatrix meront usually contained two to three nuclei, and sporont contained two nuclei and was wrapped by a thick membrane with high electron density. The V. necatrix sporogony produces two types of spores, the ordinary dikaryotic spore and unicellular octospores, the latter of which were smaller in size and packed in a sporophorous vesicle. In summary, V. necatrix xenoma is a specialized cyst likely formed by fusion of multiple muscle cells and provides high concentration of energy and nutrients with increased number of mitochondria and endoplasmic reticulum for the massive proliferation of pathogens inside.}, } @article {pmid34233163, year = {2021}, author = {Allouche, J and Rachmin, I and Adhikari, K and Pardo, LM and Lee, JH and McConnell, AM and Kato, S and Fan, S and Kawakami, A and Suita, Y and Wakamatsu, K and Igras, V and Zhang, J and Navarro, PP and Lugo, CM and Noonan, HR and Christie, KA and Itin, K and Mujahid, N and Lo, JA and Won, CH and Evans, CL and Weng, QY and Wang, H and Osseiran, S and Lovas, A and Németh, I and Cozzio, A and Navarini, AA and Hsiao, JJ and Nguyen, N and Kemény, LV and Iliopoulos, O and Berking, C and Ruzicka, T and Gonzalez-José, R and Bortolini, MC and Canizales-Quinteros, S and Acuna-Alonso, V and Gallo, C and Poletti, G and Bedoya, G and Rothhammer, F and Ito, S and Schiaffino, MV and Chao, LH and Kleinstiver, BP and Tishkoff, S and Zon, LI and Nijsten, T and Ruiz-Linares, A and Fisher, DE and Roider, E}, title = {NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism.}, journal = {Cell}, volume = {184}, number = {16}, pages = {4268-4283.e20}, pmid = {34233163}, issn = {1097-4172}, support = {R01 AR072304/AR/NIAMS NIH HHS/United States ; R00 CA218870/CA/NCI NIH HHS/United States ; T32 AR007098/AR/NIAMS NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; P01 CA163222/CA/NCI NIH HHS/United States ; R01 AR076241/AR/NIAMS NIH HHS/United States ; R01 CA103846/CA/NCI NIH HHS/United States ; P30 DK057521/DK/NIDDK NIH HHS/United States ; R35 GM134957/GM/NIGMS NIH HHS/United States ; BB/I021213/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; P01 HL142494/HL/NHLBI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; R01 CA222871/CA/NCI NIH HHS/United States ; R01 AR043369/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Cohort Studies ; Cyclic AMP/metabolism ; DNA Damage ; Enzyme Inhibitors/chemistry/pharmacology ; Genetic Predisposition to Disease ; Humans ; Melanocytes/drug effects/metabolism ; Melanosomes/drug effects/metabolism/radiation effects ; Mice ; Mice, Inbred C57BL ; Microphthalmia-Associated Transcription Factor/*metabolism ; Mitochondria/drug effects/metabolism ; Monophenol Monooxygenase/genetics/metabolism ; NADP Transhydrogenases/antagonists & inhibitors/*metabolism ; Oxidation-Reduction/drug effects/radiation effects ; Polymorphism, Single Nucleotide/genetics ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis/drug effects/radiation effects ; RNA, Messenger/genetics/metabolism ; Skin Pigmentation/drug effects/genetics/*radiation effects ; Ubiquitin/metabolism ; *Ultraviolet Rays ; Zebrafish ; }, abstract = {Ultraviolet (UV) light and incompletely understood genetic and epigenetic variations determine skin color. Here we describe an UV- and microphthalmia-associated transcription factor (MITF)-independent mechanism of skin pigmentation. Targeting the mitochondrial redox-regulating enzyme nicotinamide nucleotide transhydrogenase (NNT) resulted in cellular redox changes that affect tyrosinase degradation. These changes regulate melanosome maturation and, consequently, eumelanin levels and pigmentation. Topical application of small-molecule inhibitors yielded skin darkening in human skin, and mice with decreased NNT function displayed increased pigmentation. Additionally, genetic modification of NNT in zebrafish alters melanocytic pigmentation. Analysis of four diverse human cohorts revealed significant associations of skin color, tanning, and sun protection use with various single-nucleotide polymorphisms within NNT. NNT levels were independent of UVB irradiation and redox modulation. Individuals with postinflammatory hyperpigmentation or lentigines displayed decreased skin NNT levels, suggesting an NNT-driven, redox-dependent pigmentation mechanism that can be targeted with NNT-modifying topical drugs for medical and cosmetic purposes.}, } @article {pmid34235856, year = {2022}, author = {Mori, MP and Penjweini, R and Knutson, JR and Wang, PY and Hwang, PM}, title = {Mitochondria and oxygen homeostasis.}, journal = {The FEBS journal}, volume = {289}, number = {22}, pages = {6959-6968}, pmid = {34235856}, issn = {1742-4658}, support = {ZIA HL006051/ImNIH/Intramural NIH HHS/United States ; }, mesh = {*Mitochondria/metabolism ; Free Radicals/metabolism ; *Oxygen/metabolism ; Homeostasis ; Reactive Oxygen Species/metabolism ; Oxidative Stress ; }, abstract = {Molecular oxygen possesses a dual nature due to its highly reactive free radical property: it is capable of oxidizing metabolic substrates to generate cellular energy, but can also serve as a substrate for genotoxic reactive oxygen species generation. As a labile substance upon which aerobic life depends, the mechanisms for handling cellular oxygen have been fine-tuned and orchestrated in evolution. Protection from atmospheric oxygen toxicity as originally posited by the Endosymbiotic Theory of the Mitochondrion is likely to be one basic principle underlying oxygen homeostasis. We briefly review the literature on oxygen homeostasis both in vitro and in vivo with a focus on the role of the mitochondrion where the majority of cellular oxygen is consumed. The insights gleaned from these basic mechanisms are likely to be important for understanding disease pathogenesis and developing strategies for maintaining health.}, } @article {pmid34237359, year = {2021}, author = {Zhang, B and Havird, JC and Wang, E and Lv, J and Xu, X}, title = {Massive gene rearrangement in mitogenomes of phytoseiid mites.}, journal = {International journal of biological macromolecules}, volume = {186}, number = {}, pages = {33-39}, pmid = {34237359}, issn = {1879-0003}, support = {R35 GM142836/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Diet ; *Evolution, Molecular ; Feeding Behavior ; *Gene Order ; *Gene Rearrangement ; *Genome, Mitochondrial ; Mites/*genetics ; Mitochondria/*genetics ; Phylogeny ; }, abstract = {Mitochondrial (mt) gene sequences have been widely used to infer phylogeny in animals. The relative order of mt genes in the mitogenome can also be a useful marker for evolution, but the propensity of mt gene rearrangements vary tremendously among taxa. Ticks and mites in Acari exemplify this trend as some families retain the ancestral arthropod gene order, while others show highly divergent gene orders. Mites in Phytoseiidae, many of which are effective biological control agents, show some of the most divergent gene orders. However, the diversity of mitogenome order within this family is little known. We thus sequenced three mt genomes of phytoseiid mites from two of the most speciose genera: Amblyseius swirskii (Athias-Henriot), Amblyseius tsugawai (Ehara) and Neoseiulus womersleyi (Schicha). We find differences in mt GC skew and nucleotide composition, especially between N. womersleyi and the two Amblyseius species. Each species within Phytoseiidae (including three previously available sequences) present a unique gene order. Phytoseiid mitogenomes show some of the highest numbers of breakpoints when compared to the ancestral arthropod order (up to 33), as well as high numbers of breakpoints within the family (14-30). This suggests a history of massive, ongoing mitogenome rearrangements in the family. Phylogenetic analyses of mt sequences confirm that the degree of gene rearrangements follows phylogenetic relatedness. We discuss possible causes for the high degree of mt gene rearrangement within phytoseiid mites as well as selection in the mt and nuclear genome tied to the independent evolution of many diverse feeding strategies in the family. Finally, we suggest N. womersleyi should be used instead of the synonym Amblyseius pseudolongispinosus.}, } @article {pmid34252921, year = {2021}, author = {Anselmetti, Y and El-Mabrouk, N and Lafond, M and Ouangraoua, A}, title = {Gene tree and species tree reconciliation with endosymbiotic gene transfer.}, journal = {Bioinformatics (Oxford, England)}, volume = {37}, number = {Suppl_1}, pages = {i120-i132}, pmid = {34252921}, issn = {1367-4811}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; //Fonds de recherche Nature et Technologie, Québec/ ; }, mesh = {Algorithms ; *Evolution, Molecular ; Gene Duplication ; *Gene Transfer, Horizontal ; Genome ; Phylogeny ; Symbiosis/genetics ; }, abstract = {MOTIVATION: It is largely established that all extant mitochondria originated from a unique endosymbiotic event integrating an α-proteobacterial genome into an eukaryotic cell. Subsequently, eukaryote evolution has been marked by episodes of gene transfer, mainly from the mitochondria to the nucleus, resulting in a significant reduction of the mitochondrial genome, eventually completely disappearing in some lineages. However, in other lineages such as in land plants, a high variability in gene repertoire distribution, including genes encoded in both the nuclear and mitochondrial genome, is an indication of an ongoing process of Endosymbiotic Gene Transfer (EGT). Understanding how both nuclear and mitochondrial genomes have been shaped by gene loss, duplication and transfer is expected to shed light on a number of open questions regarding the evolution of eukaryotes, including rooting of the eukaryotic tree.

RESULTS: We address the problem of inferring the evolution of a gene family through duplication, loss and EGT events, the latter considered as a special case of horizontal gene transfer occurring between the mitochondrial and nuclear genomes of the same species (in one direction or the other). We consider both EGT events resulting in maintaining (EGTcopy) or removing (EGTcut) the gene copy in the source genome. We present a linear-time algorithm for computing the DLE (Duplication, Loss and EGT) distance, as well as an optimal reconciled tree, for the unitary cost, and a dynamic programming algorithm allowing to output all optimal reconciliations for an arbitrary cost of operations. We illustrate the application of our EndoRex software and analyze different costs settings parameters on a plant dataset and discuss the resulting reconciled trees.

EndoRex implementation and supporting data are available on the GitHub repository via https://github.com/AEVO-lab/EndoRex.}, } @article {pmid34253188, year = {2021}, author = {Gélvez, APC and Diniz Junior, JAP and Brígida, RTSS and Rodrigues, APD}, title = {AgNP-PVP-meglumine antimoniate nanocomposite reduces Leishmania amazonensis infection in macrophages.}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {211}, pmid = {34253188}, issn = {1471-2180}, mesh = {Animals ; Antiprotozoal Agents/*pharmacology/*therapeutic use ; Cells, Cultured ; In Vitro Techniques ; Leishmania/*drug effects/physiology/ultrastructure ; Macrophages/parasitology ; Meglumine Antimoniate/chemistry/pharmacology/therapeutic use ; Metal Nanoparticles/chemistry/therapeutic use ; Mice ; Mice, Inbred BALB C ; Nanocomposites/*therapeutic use ; Povidone/chemistry/pharmacology/therapeutic use ; Silver/chemistry/pharmacology/therapeutic use ; }, abstract = {BACKGROUND: Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania and presents different clinical manifestations. The adverse effects, immunosuppression and resistant strains associated with this disease necessitate the development of new drugs. Nanoparticles have shown potential as alternative antileishmanial drugs. We showed in a previous study the biosynthesis, characterization and ideal concentration of a nanocomposite that promoted leishmanicidal activity. In the present study, we conducted a specific analysis to show the mechanism of action of AgNP-PVP-MA (silver nanoparticle-polyvinylpyrrolidone-[meglumine antimoniate (Glucantime®)]) nanocomposite during Leishmania amazonensis infection in vitro.

RESULTS: Through ultrastructural analysis, we observed significant alterations, such as the presence of small vesicles in the flagellar pocket and in the extracellular membrane, myelin-like structure formation in the Golgi complex and mitochondria, flagellum and plasma membrane rupture, and electrodense material deposition at the edges of the parasite nucleus in both evolutive forms. Furthermore, the Leishmania parasite infection index in macrophages decreased significantly after treatment, and nitric oxide and reactive oxygen species production levels were determined. Additionally, inflammatory, and pro-inflammatory cytokine and chemokine production levels were evaluated. The IL-4, TNF-α and MIP-1α levels increased significantly, while the IL-17 A level decreased significantly after treatment.

CONCLUSIONS: Thus, we demonstrate in this study that the AgNP-PVP-MA nanocomposite has leishmanial potential, and the mechanism of action was demonstrated for the first time, showing that this bioproduct seems to be a potential alternative treatment for leishmaniasis.}, } @article {pmid34254168, year = {2021}, author = {Igloi, GL}, title = {The Evolutionary Fate of Mitochondrial Aminoacyl-tRNA Synthetases in Amitochondrial Organisms.}, journal = {Journal of molecular evolution}, volume = {89}, number = {7}, pages = {484-493}, pmid = {34254168}, issn = {1432-1432}, mesh = {Amino Acid Sequence ; *Amino Acyl-tRNA Synthetases/genetics/metabolism ; *Arginine-tRNA Ligase/metabolism ; Mitochondria/genetics/metabolism ; RNA, Transfer ; }, abstract = {During the endosymbiotic evolution of mitochondria, the genes for aminoacyl-tRNA synthetases were transferred to the ancestral nucleus. A further reduction of mitochondrial function resulted in mitochondrion-related organisms (MRO) with a loss of the organelle genome. The fate of the now redundant ancestral mitochondrial aminoacyl-tRNA synthetase genes is uncertain. The derived protein sequence for arginyl-tRNA synthetase from thirty mitosomal organisms have been classified as originating from the ancestral nuclear or mitochondrial gene and compared to the identity element at position 20 of the cognate tRNA that distinguishes the two enzyme forms. The evolutionary choice between loss and retention of the ancestral mitochondrial gene for arginyl-tRNA synthetase reflects the coevolution of arginyl-tRNA synthetase and tRNA identity elements.}, } @article {pmid34256922, year = {2021}, author = {Husnik, F and Tashyreva, D and Boscaro, V and George, EE and Lukeš, J and Keeling, PJ}, title = {Bacterial and archaeal symbioses with protists.}, journal = {Current biology : CB}, volume = {31}, number = {13}, pages = {R862-R877}, doi = {10.1016/j.cub.2021.05.049}, pmid = {34256922}, issn = {1879-0445}, mesh = {Animals ; *Archaea ; *Bacteria ; *Eukaryota ; *Prokaryotic Cells ; *Symbiosis ; }, abstract = {Most of the genetic, cellular, and biochemical diversity of life rests within single-celled organisms - the prokaryotes (bacteria and archaea) and microbial eukaryotes (protists). Very close interactions, or symbioses, between protists and prokaryotes are ubiquitous, ecologically significant, and date back at least two billion years ago to the origin of mitochondria. However, most of our knowledge about the evolution and functions of eukaryotic symbioses comes from the study of animal hosts, which represent only a small subset of eukaryotic diversity. Here, we take a broad view of bacterial and archaeal symbioses with protist hosts, focusing on their evolution, ecology, and cell biology, and also explore what functions (if any) the symbionts provide to their hosts. With the immense diversity of protist symbioses starting to come into focus, we can now begin to see how these systems will impact symbiosis theory more broadly.}, } @article {pmid34257835, year = {2021}, author = {Cheung, NJ and John Peter, AT and Kornmann, B}, title = {Leri: A web-server for identifying protein functional networks from evolutionary couplings.}, journal = {Computational and structural biotechnology journal}, volume = {19}, number = {}, pages = {3556-3563}, pmid = {34257835}, issn = {2001-0370}, abstract = {Information on the co-evolution of amino acid pairs in a protein can be used for endeavors such as protein engineering, mutation design, and structure prediction. Here we report a method that captures significant determinants of proteins using estimated co-evolution information to identify networks of residues, termed "residue communities", relevant to protein function. On the benchmark dataset (67 proteins with both catalytic and allosteric residues), the Pearson's correlation between the identified residues in the communities at functional sites is 0.53, and it is higher than 0.8 by taking account of conserved residues derived from the method. On the endoplasmic reticulum-mitochondria encounter structure complex, the results indicate three distinguishable residue communities that are relevant to functional roles in the protein family, suggesting that the residue communities could be general evolutionary signatures in proteins. Based on the method, we provide a webserver for the scientific community to explore the signatures in protein families, which establishes a powerful tool to analyze residue-level profiling for the discovery of functional sites and biological pathway identification. This web-server is freely available for non-commercial users at https://kornmann.bioch.ox.ac.uk/leri/services/ecs.html, neither login nor e-mail required.}, } @article {pmid34274481, year = {2021}, author = {Kimball, RT and Guido, M and Hosner, PA and Braun, EL}, title = {When good mitochondria go bad: Cyto-nuclear discordance in landfowl (Aves: Galliformes).}, journal = {Gene}, volume = {801}, number = {}, pages = {145841}, doi = {10.1016/j.gene.2021.145841}, pmid = {34274481}, issn = {1879-0038}, mesh = {Animals ; Cell Nucleus/genetics ; Galliformes/*genetics ; Genome, Mitochondrial/*genetics ; *Phylogeny ; }, abstract = {Mitochondrial sequences were among the first molecular data collected for phylogenetic studies and they are plentiful in DNA sequence archives. However, the future value of mitogenomic data in phylogenetics is uncertain, because its phylogenetic signal sometimes conflicts with that of the nuclear genome. A thorough understanding of the causes and prevalence of cyto-nuclear discordance would aid in reconciling different results owing to sequence data type, and provide a framework for interpreting megaphylogenies when taxa which lack substantial nuclear data are placed using mitochondrial data. Here, we examine the prevalence and possible causes of cyto-nuclear discordance in the landfowl (Aves: Galliformes), leveraging 47 new mitogenomes assembled from off-target reads recovered as part of a target-capture study. We evaluated two hypotheses, that cyto-nuclear discordance is "genuine" and a result of biological processes such as incomplete lineage sorting or introgression, and that cyto-nuclear discordance is an artifact of inaccurate mitochondrial tree estimation (the "inaccurate estimation" hypothesis). We identified seven well-supported topological differences between the mitogenomic tree and trees based on nuclear data. These well-supported topological differences were robust to model selection. An examination of sites suggests these differences were driven by small number of sites, particularly from third-codon positions, suggesting that they were not confounded by convergent directional selection. Hence, the hypothesis of genuine discordance was supported.}, } @article {pmid34277616, year = {2021}, author = {Xu, X and Ma, A and Li, T and Cui, W and Wang, X and Li, J and Li, Q and Pang, Y}, title = {Genetic and Functional Characterization of Novel Brown-Like Adipocytes Around the Lamprey Brain.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {674939}, pmid = {34277616}, issn = {2296-634X}, abstract = {During the process of vertebrate evolution, many thermogenic organs and mechanisms have appeared. Mammalian brown adipose tissue (BAT) generates heat through the uncoupling oxidative phosphorylation of mitochondria, acts as a natural defense against hypothermia and inhibits the development of obesity. Although the existence, cellular origin and molecular identity of BAT in humans have been well studied, the genetic and functional characteristics of BAT from lampreys remain unknown. Here, we identified and characterized a novel, naturally existing brown-like adipocytes at the lamprey brain periphery. Similar to human BAT, the lamprey brain periphery contains brown-like adipocytes that maintain the same morphology as human brown adipocytes, containing multilocular lipid droplets and high mitochondrion numbers. Furthermore, we found that brown-like adipocytes in the periphery of lamprey brains responded to thermogenic reagent treatment and cold exposure and that lamprey UCP2 promoted precursor adipocyte differentiation. Molecular mapping by RNA-sequencing showed that inflammation in brown-like adipocytes treated with LPS and 25HC was enhanced compared to controls. The results of this study provide new evidence for human BAT research and demonstrate the multilocular adipose cell functions of lampreys, including: (1) providing material energy and protecting structure, (2) generating additional heat and contributing to adaptation to low-temperature environments, and (3) resisting external pathogens.}, } @article {pmid34279226, year = {2021}, author = {Colnaghi, M and Pomiankowski, A and Lane, N}, title = {The need for high-quality oocyte mitochondria at extreme ploidy dictates mammalian germline development.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34279226}, issn = {2050-084X}, support = {BB/S003681/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/V003542/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Biological Evolution ; Cell Death ; Cell Proliferation ; DNA, Mitochondrial/genetics ; Female ; Follicular Atresia ; Germ Cells/*metabolism ; Humans ; Mammals/genetics ; Mice ; Mitochondria/*genetics/*metabolism ; Mutation ; Oocytes/*metabolism ; Oogenesis ; *Ploidies ; }, abstract = {Selection against deleterious mitochondrial mutations is facilitated by germline processes, lowering the risk of genetic diseases. How selection works is disputed: experimental data are conflicting and previous modeling work has not clarified the issues; here, we develop computational and evolutionary models that compare the outcome of selection at the level of individuals, cells and mitochondria. Using realistic de novo mutation rates and germline development parameters from mouse and humans, the evolutionary model predicts the observed prevalence of mitochondrial mutations and diseases in human populations. We show the importance of organelle-level selection, seen in the selective pooling of mitochondria into the Balbiani body, in achieving high-quality mitochondria at extreme ploidy in mature oocytes. Alternative mechanisms debated in the literature, bottlenecks and follicular atresia, are unlikely to account for the clinical data, because neither process effectively eliminates mitochondrial mutations under realistic conditions. Our findings explain the major features of female germline architecture, notably the longstanding paradox of over-proliferation of primordial germ cells followed by massive loss. The near-universality of these processes across animal taxa makes sense in light of the need to maintain mitochondrial quality at extreme ploidy in mature oocytes, in the absence of sex and recombination.}, } @article {pmid34287642, year = {2021}, author = {Vendramin, R and Katopodi, V and Cinque, S and Konnova, A and Knezevic, Z and Adnane, S and Verheyden, Y and Karras, P and Demesmaeker, E and Bosisio, FM and Kucera, L and Rozman, J and Gladwyn-Ng, I and Rizzotto, L and Dassi, E and Millevoi, S and Bechter, O and Marine, JC and Leucci, E}, title = {Activation of the integrated stress response confers vulnerability to mitoribosome-targeting antibiotics in melanoma.}, journal = {The Journal of experimental medicine}, volume = {218}, number = {9}, pages = {}, pmid = {34287642}, issn = {1540-9538}, mesh = {Aged ; Animals ; Antibiotics, Antineoplastic/*pharmacology ; Cell Line, Tumor ; Doxycycline/pharmacology ; Drug Resistance, Neoplasm/drug effects ; Female ; Humans ; Male ; Melanoma/*drug therapy/genetics/mortality/*pathology ; Mice, Inbred C57BL ; Mice, Nude ; Mitochondrial Ribosomes/*drug effects ; Protein Kinase Inhibitors/pharmacology ; Stress, Physiological/drug effects ; Tigecycline/pharmacology ; Uveal Neoplasms/drug therapy/pathology ; Xenograft Model Antitumor Assays ; Mice ; Uveal Melanoma ; }, abstract = {The ability to adapt to environmental stress, including therapeutic insult, contributes to tumor evolution and drug resistance. In suboptimal conditions, the integrated stress response (ISR) promotes survival by dampening cytosolic translation. We show that ISR-dependent survival also relies on a concomitant up-regulation of mitochondrial protein synthesis, a vulnerability that can be exploited using mitoribosome-targeting antibiotics. Accordingly, such agents sensitized to MAPK inhibition, thus preventing the development of resistance in BRAFV600E melanoma models. Additionally, this treatment compromised the growth of melanomas that exhibited elevated ISR activity and resistance to both immunotherapy and targeted therapy. In keeping with this, pharmacological inactivation of ISR, or silencing of ATF4, rescued the antitumoral response to the tetracyclines. Moreover, a melanoma patient exposed to doxycycline experienced complete and long-lasting response of a treatment-resistant lesion. Our study indicates that the repurposing of mitoribosome-targeting antibiotics offers a rational salvage strategy for targeted therapy in BRAF mutant melanoma and a therapeutic option for NRAS-driven and immunotherapy-resistant tumors.}, } @article {pmid34290263, year = {2021}, author = {Yang, H and Li, W and Yu, X and Zhang, X and Zhang, Z and Liu, Y and Wang, W and Tian, X}, title = {Insights into molecular structure, genome evolution and phylogenetic implication through mitochondrial genome sequence of Gleditsia sinensis.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {14850}, pmid = {34290263}, issn = {2045-2322}, mesh = {*Evolution, Molecular ; Fabaceae/genetics ; Genome, Plant/*genetics ; Gleditsia/*genetics/ultrastructure ; Mitochondria/*genetics ; *Phylogeny ; Species Specificity ; *Whole Genome Sequencing ; }, abstract = {Gleditsia sinensis is an endemic species widely distributed in China with high economic and medicinal value. To explore the genomic evolution and phylogenetic relationships of G. sinensis, the complete mitochondrial (mt) genome of G. sinensis was sequenced and assembled, which was firstly reported in Gleditsia. The mt genome was circular and 594,121 bp in length, including 37 protein-coding genes (PCGs), 19 transfer RNA (tRNA) genes and 3 ribosomal RNA (rRNA) genes. The overall base composition of the G. sinensis mt genome was 27.4% for A, 27.4% for T, 22.6% for G, 22.7% for C. The comparative analysis of PCGs in Fabaceae species showed that most of the ribosomal protein genes and succinate dehydrogenase genes were lost. In addition, we found that the rps4 gene was only lost in G. sinensis, whereas it was retained in other Fabaceae species. The phylogenetic analysis based on shared PCGs of 24 species (22 Fabaceae and 2 Solanaceae) showed that G. sinensis is evolutionarily closer to Senna species. In general, this research will provide valuable information for the evolution of G. sinensis and provide insight into the phylogenetic relationships within the family Fabaceae.}, } @article {pmid34302870, year = {2021}, author = {Costa, JH and Roque, ALM and Aziz, S and Dos Santos, CP and Germano, TA and Batista, MC and Thiers, KLL and da Cruz Saraiva, KD and Arnholdt-Schmitt, B}, title = {Genome-wide identification of ascorbate-glutathione cycle gene families in soybean (Glycine max) reveals gene duplication events and specificity of gene members linked to development and stress conditions.}, journal = {International journal of biological macromolecules}, volume = {187}, number = {}, pages = {528-543}, doi = {10.1016/j.ijbiomac.2021.07.103}, pmid = {34302870}, issn = {1879-0003}, mesh = {Ascorbate Peroxidases/genetics/metabolism ; Ascorbic Acid/*metabolism ; *Evolution, Molecular ; *Gene Duplication ; Gene Expression Regulation, Plant ; Germination ; Glutathione/*metabolism ; Glutathione Reductase/genetics/metabolism ; Glutathione Transferase/genetics/metabolism ; NADH, NADPH Oxidoreductases/genetics/metabolism ; *Oxidative Stress ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Reactive Oxygen Species/*metabolism ; Glycine max/*genetics/growth & development/metabolism ; }, abstract = {Ascorbate-glutathione (AsA-GSH) cycle plays an important role in tuning beneficial ROS accumulation for intracellular signals and imparts plant tolerance to oxidative stress by detoxifying excess of ROS. Here, we present genome-wide identification of AsA-GSH cycle genes (APX, MDHAR, DHAR, and GR) in several leguminous species and expression analyses in G. max during stress, germination and tissue development. Our data revealed 24 genes in Glycine genus against the maximum of 15 in other leguminous species, which was due to 9 pars of duplicated genes mostly originated from sub/neofunctionalization. Cytosolic APX and MDHAR genes were highly expressed in different tissues and physiological conditions. Germination induced genes encoding AsA-GSH proteins from different cell compartments, whereas vegetative phase (leaves) stimulated predominantly genes related to chloroplast/mitochondria proteins. Moreover, cytosolic APX-1, 2, MDHAR-1a, 1b and GR genes were the primary genes linked to senescence and biotic stresses, while stAPX-a, b and GR (from organelles) were the most abiotic stress related genes. Biotic and abiotic stress tolerant genotypes generally showed increased MDHAR, DHAR and/or GR mRNA levels compared to susceptible genotypes. Overall, these data clarified evolutionary events in leguminous plants and point to the functional specificity of duplicated genes of the AsA-GSH cycle in G. max.}, } @article {pmid34309123, year = {2021}, author = {Fernandes Gyorfy, M and Miller, ER and Conover, JL and Grover, CE and Wendel, JF and Sloan, DB and Sharbrough, J}, title = {Nuclear-cytoplasmic balance: whole genome duplications induce elevated organellar genome copy number.}, journal = {The Plant journal : for cell and molecular biology}, volume = {108}, number = {1}, pages = {219-230}, doi = {10.1111/tpj.15436}, pmid = {34309123}, issn = {1365-313X}, mesh = {Arabidopsis/*genetics ; Cell Nucleus/genetics ; Chloroplasts/genetics ; Cytoplasm/genetics ; *DNA Copy Number Variations ; Diploidy ; Gene Duplication ; Genome, Plant/*genetics ; Genome, Plastid/*genetics ; Mitochondria/genetics ; Plastids/genetics ; Polyploidy ; Triticum/*genetics ; }, abstract = {The plant genome is partitioned across three distinct subcellular compartments: the nucleus, mitochondria, and plastids. Successful coordination of gene expression among these organellar genomes and the nuclear genome is critical for plant function and fitness. Whole genome duplication (WGD) events in the nucleus have played a major role in the diversification of land plants and are expected to perturb the relative copy number (stoichiometry) of nuclear, mitochondrial, and plastid genomes. Thus, elucidating the mechanisms whereby plant cells respond to the cytonuclear stoichiometric imbalance that follows WGDs represents an important yet underexplored question in understanding the evolutionary consequences of genome doubling. We used droplet digital PCR to investigate the relationship between nuclear and organellar genome copy numbers in allopolyploids and their diploid progenitors in both wheat and Arabidopsis. Polyploids exhibit elevated organellar genome copy numbers per cell, largely preserving the cytonuclear stoichiometry observed in diploids despite the change in nuclear genome copy number. To investigate the timescale over which cytonuclear stoichiometry may respond to WGD, we also estimated the organellar genome copy number in Arabidopsis synthetic autopolyploids and in a haploid-induced diploid line. We observed corresponding changes in organellar genome copy number in these laboratory-generated lines, indicating that at least some of the cellular response to cytonuclear stoichiometric imbalance is immediate following WGD. We conclude that increases in organellar genome copy numbers represent a common response to polyploidization, suggesting that maintenance of cytonuclear stoichiometry is an important component in establishing polyploid lineages.}, } @article {pmid34320951, year = {2021}, author = {Kan, SL and Shen, TT and Ran, JH and Wang, XQ}, title = {Both Conifer II and Gnetales are characterized by a high frequency of ancient mitochondrial gene transfer to the nuclear genome.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {146}, pmid = {34320951}, issn = {1741-7007}, mesh = {Cycadopsida/genetics ; Evolution, Molecular ; *Genes, Mitochondrial ; *Genome, Mitochondrial/genetics ; Mitochondria/genetics ; Phylogeny ; Tracheophyta/genetics ; }, abstract = {BACKGROUND: Mitochondrial gene transfer/loss is common in land plants, and therefore the fate of missing mitochondrial genes has attracted more and more attention. The gene content of gymnosperm mitochondria varies greatly, supplying a system for studying the evolutionary fate of missing mitochondrial genes.

RESULTS: Here, we studied the tempo and pattern of mitochondrial gene transfer/loss in gymnosperms represented by all 13 families, using high-throughput sequencing of both DNA and cDNA. All 41 mitochondrial protein-coding genes were found in cycads, Ginkgo and Pinaceae, whereas multiple mitochondrial genes were absent in Conifer II and Gnetales. In Conifer II, gene transfer from mitochondria to the nucleus followed by loss of the mitochondrial copy was common, but complete loss of a gene in both mitochondrial and nuclear genomes was rare. In contrast, both gene transfer and loss were commonly found in Gnetales. Notably, in Conifer II and Gnetales, the same five mitochondrial genes were transferred to the nuclear genome, and these gene transfer events occurred, respectively, in ancestors of the two lineages. A two-step transfer mechanism (retroprocessing and subsequent DNA-mediated gene transfer) may be responsible for mitochondrial gene transfer in Conifer II and Gnetales. Moreover, the mitochondrial gene content variation is correlated with gene length, GC content, hydrophobicity, and nucleotide substitution rates in land plants.

CONCLUSIONS: This study reveals a complete evolutionary scenario for variations of mitochondrial gene transferring in gymnosperms, and the factors responsible for mitochondrial gene content variation in land plants.}, } @article {pmid34321495, year = {2021}, author = {Scarpassa, VM and Cunha-Machado, AS and Alencar, RB}, title = {Multiple evolutionary lineages for the main vector of Leishmania guyanensis, Lutzomyia umbratilis (Diptera: Psychodidae), in the Brazilian Amazon.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {15323}, pmid = {34321495}, issn = {2045-2322}, mesh = {Animals ; *Biological Evolution ; Brazil/epidemiology ; Cytochromes b/genetics ; Electron Transport Complex IV/genetics ; Female ; Gene Expression ; Genetic Variation ; Haplotypes ; Humans ; Insect Proteins/genetics ; Insect Vectors/classification/*genetics ; Leishmania guyanensis/growth & development/*pathogenicity ; Leishmaniasis, Mucocutaneous/epidemiology/parasitology/*transmission ; Mitochondria/enzymology/genetics ; *Phylogeny ; Phylogeography ; Psychodidae/classification/*genetics ; Rivers/parasitology ; }, abstract = {Lutzomyia umbratilis is the main vector of Leishmania guyanensis in the Brazilian Amazon and in neighboring countries. Previous biological and molecular investigations have revealed significant differences between L. umbratilis populations from the central Brazilian Amazon region. Here, a phylogeographic survey of L. umbratilis populations collected from nine localities in the Brazilian Amazon was conducted using two mitochondrial genes. Statistical analyses focused on population genetics, phylogenetic relationships and species delimitations. COI genetic diversity was very high, whereas Cytb diversity was moderate. COI genealogical haplotypes, population structure and phylogenetic analyses identified a deep genetic differentiation and three main genetic groups. Cytb showed a shallower genetic structure, two main haplogroups and poorly resolved phylogenetic trees. These findings, allied to absence of isolation by distance, support the hypothesis that the Amazon and Negro Rivers and interfluves are the main evolutionary forces driving L. umbratilis diversification. The main three genetic groups observed represent three evolutionary lineages, possibly species. The first lineage occurs north of the Amazon River and east of Negro River, where Le. guyanensis transmission is intense, implying that L. umbratilis is an important vector there. The second lineage is in the interfluve between north of Amazon River and west of Negro River, an area reported to be free of Le. guyanensis transmission. The third lineage, first recorded in this study, is in the interfluve between south of Amazonas River and west of Madeira River, and its involvement in the transmission of this parasite remains to be elucidated.}, } @article {pmid34341532, year = {2021}, author = {Zhang, Q and Wang, Z and Zhang, W and Wen, Q and Li, X and Zhou, J and Wu, X and Guo, Y and Liu, Y and Wei, C and Qian, W and Tian, Y}, title = {The memory of neuronal mitochondrial stress is inherited transgenerationally via elevated mitochondrial DNA levels.}, journal = {Nature cell biology}, volume = {23}, number = {8}, pages = {870-880}, pmid = {34341532}, issn = {1476-4679}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Caenorhabditis elegans Proteins/*genetics ; DNA, Mitochondrial/*metabolism ; *Genes, Mitochondrial ; HEK293 Cells ; Humans ; Longevity/genetics ; *Maternal Inheritance ; Neurons/*metabolism ; Organelle Biogenesis ; Stress, Physiological/*genetics ; Unfolded Protein Response/*genetics ; Wnt Signaling Pathway ; }, abstract = {The memory of stresses experienced by parents can be passed on to descendants as a forecast of the challenges to come. Here, we discovered that the neuronal mitochondrial perturbation-induced systemic mitochondrial unfolded protein response (UPR[mt]) in Caenorhabditis elegans can be transmitted to offspring over multiple generations. The transgenerational activation of UPR[mt] is mediated by maternal inheritance of elevated levels of mitochondrial DNA (mtDNA), which causes the proteostasis stress within mitochondria. Furthermore, results from intercrossing studies using wild C. elegans strains further support that maternal inheritance of higher levels of mtDNA can induce the UPR[mt] in descendants. The mitokine Wnt signalling pathway is required for the transmission of elevated mtDNA levels across generations, thereby conferring lifespan extension and stress resistance to offspring. Collectively, our results reveal that the nervous system can transmit stress signals across generations by increasing mtDNA in the germline, enabling descendants to better cope with anticipated challenges.}, } @article {pmid34343017, year = {2021}, author = {Gabaldón, T}, title = {Origin and Early Evolution of the Eukaryotic Cell.}, journal = {Annual review of microbiology}, volume = {75}, number = {}, pages = {631-647}, doi = {10.1146/annurev-micro-090817-062213}, pmid = {34343017}, issn = {1545-3251}, mesh = {*Biological Evolution ; Eukaryota/genetics ; *Eukaryotic Cells/metabolism ; Phylogeny ; Prokaryotic Cells/metabolism ; Symbiosis ; }, abstract = {The origin of eukaryotes has been defined as the major evolutionary transition since the origin of life itself. Most hallmark traits of eukaryotes, such as their intricate intracellular organization, can be traced back to a putative common ancestor that predated the broad diversity of extant eukaryotes. However, little is known about the nature and relative order of events that occurred in the path from preexisting prokaryotes to this already sophisticated ancestor. The origin of mitochondria from the endosymbiosis of an alphaproteobacterium is one of the few robustly established events to which most hypotheses on the origin of eukaryotes are anchored, but the debate is still open regarding the time of this acquisition, the nature of the host, and the ecological and metabolic interactions between the symbiotic partners. After the acquisition of mitochondria, eukaryotes underwent a fast radiation into several major clades whose phylogenetic relationships have been largely elusive. Recent progress in the comparative analyses of a growing number of genomes is shedding light on the early events of eukaryotic evolution as well as on the root and branching patterns of the tree of eukaryotes. Here I discuss current knowledge and debates on the origin and early evolution of eukaryotes. I focus particularly on how phylogenomic analyses have challenged some of the early assumptions about eukaryotic evolution, including the widespread idea that mitochondrial symbiosis in an archaeal host was the earliest event in eukaryogenesis.}, } @article {pmid34344905, year = {2021}, author = {Collado, GA and Torres-Díaz, C and Valladares, MA}, title = {Phylogeography and molecular species delimitation reveal cryptic diversity in Potamolithus (Caenogastropoda: Tateidae) of the southwest basin of the Andes.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {15735}, pmid = {34344905}, issn = {2045-2322}, mesh = {Animals ; Bayes Theorem ; *Biodiversity ; Chile ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/genetics/*metabolism ; Gastropoda/classification/*physiology ; *Genetic Speciation ; *Genetic Variation ; Mitochondria/enzymology/genetics ; *Phylogeography ; }, abstract = {The species of the genus Potamolithus inhabiting the southwestern basin of the Andes are difficult to distinguish due to small size and similar shell morphology. Only Potamolithus australis and Potamolithus santiagensis have been traditionally recognized in this region, but the occurrence of several morphologically similar undescribed populations could increase the regional richness. Here we delimit described and potentially undescribed cryptic species of the genus using partial sequences of the mitochondrial cytochrome c oxidase subunit I (COI) gene. Network analysis and diversity indices inferred six highly differentiated haplogroups, many of them sympatric and widespread in the study area. Phylogeographic analyses suggest a scenario of recent diversification and the occurrence of multiple refuges during the successive Pleistocene glaciations. Phylogenetic analysis also recovered six major clades that showed no relationship with physiography. Species delimitation analyses consistently recognized three or four candidate species apart from P. australis and P. santiagensis. Divergence times indicate that speciation of Chilean Potamolithus began at the end of the Pliocene, probably driven by climatic rather than geographic events. Considering the high inter- and intra-basin genetic diversity, conservation efforts should be focused on protecting sympatric taxa in the basins with the highest species richness.}, } @article {pmid34356526, year = {2021}, author = {Prieto-Carrasco, R and Silva-Palacios, A and Rojas-Morales, P and Aparicio-Trejo, OE and Medina-Reyes, EI and Hernández-Cruz, EY and Sánchez-Garibay, C and Salinas-Lara, C and Pavón, N and Roldán, FJ and Zazueta, C and Tapia, E and Pedraza-Chaverri, J}, title = {Unilateral Ureteral Obstruction for 28 Days in Rats Is Not Associated with Changes in Cardiac Function or Alterations in Mitochondrial Function.}, journal = {Biology}, volume = {10}, number = {7}, pages = {}, pmid = {34356526}, issn = {2079-7737}, support = {A1-S-7495//Consejo Nacional de Ciencia y Tecnología/ ; 281967//Consejo Nacional de Ciencia y Tecnología/ ; IN202219//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; 5000-9105//Programa de Apoyo a la Invstigación y el Posgrado-Facultad de Química/ ; 2020//Fondos de Gasto Directo Autorizado a la Subdirección de Investigación Básica-Instituto Nacional de Cardioloigía Ignacio Chávez/ ; }, abstract = {Our work evaluated cardiac function and mitochondrial bioenergetics parameters in hearts from male Wistar rats subjected to the UUO model during 28 days of progression. We measured markers of kidney damage and inflammation in plasma and renal fibrosis by histological analysis and Western blot. Cardiac function was evaluated by echocardiography and proteins involved in cardiac damage by Western blot. Oxygen consumption and transmembrane potential were monitored in cardiac mitochondria using high-resolution respirometry. We also determined the activity of ATP synthase and antioxidant enzymes such as glutathione peroxidase, glutathione reductase, and catalase. Our results show that, although renal dysfunction is established in animals subjected to ureteral obstruction, cardiac function is maintained along with mitochondrial function and antioxidant enzymes activity after 28 days of injury evolution. Our results suggest that renocardiac syndrome might develop but belatedly in obstruction-induced renal damage, opening the opportunity for treatment to prevent this condition.}, } @article {pmid34356863, year = {2021}, author = {Cooper, ID and Brookler, KH and Kyriakidou, Y and Elliott, BT and Crofts, CAP}, title = {Metabolic Phenotypes and Step by Step Evolution of Type 2 Diabetes: A New Paradigm.}, journal = {Biomedicines}, volume = {9}, number = {7}, pages = {}, pmid = {34356863}, issn = {2227-9059}, abstract = {Unlike bolus insulin secretion mechanisms, basal insulin secretion is poorly understood. It is essential to elucidate these mechanisms in non-hyperinsulinaemia healthy persons. This establishes a baseline for investigation into pathologies where these processes are dysregulated, such as in type 2 diabetes (T2DM), cardiovascular disease (CVD), certain cancers and dementias. Chronic hyperinsulinaemia enforces glucose fueling, depleting the NAD+ dependent antioxidant activity that increases mitochondrial reactive oxygen species (mtROS). Consequently, beta-cell mitochondria increase uncoupling protein expression, which decreases the mitochondrial ATP surge generation capacity, impairing bolus mediated insulin exocytosis. Excessive ROS increases the Drp1:Mfn2 ratio, increasing mitochondrial fission, which increases mtROS; endoplasmic reticulum-stress and impaired calcium homeostasis ensues. Healthy individuals in habitual ketosis have significantly lower glucagon and insulin levels than T2DM individuals. As beta-hydroxybutyrate rises, hepatic gluconeogenesis and glycogenolysis supply extra-hepatic glucose needs, and osteocalcin synthesis/release increases. We propose insulin's primary role is regulating beta-hydroxybutyrate synthesis, while the role of bone regulates glucose uptake sensitivity via osteocalcin. Osteocalcin regulates the alpha-cell glucagon secretory profile via glucagon-like peptide-1 and serotonin, and beta-hydroxybutyrate synthesis via regulating basal insulin levels. Establishing metabolic phenotypes aids in resolving basal insulin secretion regulation, enabling elucidation of the pathological changes that occur and progress into chronic diseases associated with ageing.}, } @article {pmid34378290, year = {2021}, author = {Liu, X and Xu, L and Hu, K and Ren, S and Weng, M and Yu, J and Li, D and Zhang, J}, title = {New isolate of Loma psittaca (Microsporidia: Glugeidae) infecting the stomach wall of cultured hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀) in South China.}, journal = {The Journal of eukaryotic microbiology}, volume = {68}, number = {6}, pages = {e12868}, doi = {10.1111/jeu.12868}, pmid = {34378290}, issn = {1550-7408}, mesh = {Animals ; *Bass ; *Fish Diseases ; *Loma ; *Microsporidia ; *Microsporidiosis/veterinary ; Phylogeny ; Stomach ; }, abstract = {Loma psittaca, previously described as inhabiting the intestinal mucosa of an anadromous fish, Colomesus pisttacus, from the Amazon Basin, is reported as being found for the first time in a marine fish, the hybrid grouper (Epinephelus lanceolatus♂×Epinephelus fuscoguttatus♀), from Lingshui city, Hainan Province, China, expanding the geographical distribution and host range of this parasite. Numerous whitish xenomas (0.5-0.7 mm in diameter) of this new isolate of L. psittaca were found distinctly in the muscle layer of the host stomach wall. Electron microscopic observations showed a monokaryotic nucleus in all developmental stages. Round or elongated multinucleate merogonial plasmodia surrounded by numerous mitochondria were observed initially, subsequently transforming into uninucleate sporonts through multiple fissions. Sporonts, each with a large centrally positioned nucleus, further developed into sporoblasts. Each sporoblast mother cell gave rise to two uninucleate sporoblasts by binary fission. Mature spores were ellipsoidal, measuring 4.0 ± 0.3 (3.7-4.3) μm in length and 2.2 ± 0.2 (2.1-2.5) μm in width. Spores possessed a mushroom-like anchoring disk, a bipartite polarplast, isofilar polar filaments arranged in 12-14 turns in one row, and a trilaminar spore wall. The obtained partial SSU rRNA gene sequence of the new isolate was 1330 bp in length and showed 99.4% sequence similarity with an estuary isolate of L. psittaca previously reported in South America. SSU rRNA gene-based phylogenetic analyses demonstrated that the two L. psittaca isolates first clustered together and then formed a dichotomy that included the digestive-tract-infecting Loma species, L. acerinae, with high support values within group I.}, } @article {pmid34378417, year = {2021}, author = {Yap, KN and Zhang, Y}, title = {Revisiting the question of nucleated versus enucleated erythrocytes in birds and mammals.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {321}, number = {4}, pages = {R547-R557}, doi = {10.1152/ajpregu.00276.2020}, pmid = {34378417}, issn = {1522-1490}, mesh = {Animals ; *Biological Evolution ; Birds/*blood ; Cell Size ; *Energy Metabolism ; Erythroblasts/*metabolism ; Erythrocytes/*metabolism ; Hemoglobins/metabolism ; Organelles/*physiology ; Oxidative Stress ; Phylogeny ; Species Specificity ; }, abstract = {Erythrocyte enucleation is thought to have evolved in mammals to support their energetic cost of high metabolic activities. However, birds face similar selection pressure yet possess nucleated erythrocytes. Current hypotheses on the mammalian erythrocyte enucleation claim that the absence of cell organelles allows erythrocytes to 1) pack more hemoglobin into the cells to increase oxygen carrying capacity and 2) decrease erythrocyte size for increased surface area-to-volume ratio, and improved ability to traverse small capillaries. In this article, we first empirically tested current hypotheses using both conventional and phylogenetically informed analysis comparing literature values of mean cell hemoglobin concentration (MCHC) and mean cell volume (MCV) between 181 avian and 194 mammalian species. We found no difference in MCHC levels between birds and mammals using both conventional and phylogenetically corrected analysis. MCV was higher in birds than mammals according to conventional analysis, but the difference was lost when we controlled for phylogeny. These results suggested that avian and mammalian erythrocytes may employ different strategies to solve a common problem. To further investigate existing hypotheses or develop new hypothesis, we need to understand the functions of various organelles in avian erythrocytes. Consequently, we covered potential physiological functions of various cell organelles in avian erythrocytes based on current knowledge, while making explicit comparisons with their mammalian counterparts. Finally, we proposed by taking an integrative and comparative approach, using tools from molecular biology to evolutionary biology, would allow us to better understand the fundamental physiological functions of various components of avian and mammalian erythrocytes.}, } @article {pmid34384346, year = {2021}, author = {Schäffer, AA and McVeigh, R and Robbertse, B and Schoch, CL and Johnston, A and Underwood, BA and Karsch-Mizrachi, I and Nawrocki, EP}, title = {Ribovore: ribosomal RNA sequence analysis for GenBank submissions and database curation.}, journal = {BMC bioinformatics}, volume = {22}, number = {1}, pages = {400}, pmid = {34384346}, issn = {1471-2105}, mesh = {DNA, Ribosomal ; *Databases, Nucleic Acid ; Phylogeny ; *RNA, Ribosomal ; RNA, Ribosomal, 16S/genetics ; RNA, Ribosomal, 18S/genetics ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: The DNA sequences encoding ribosomal RNA genes (rRNAs) are commonly used as markers to identify species, including in metagenomics samples that may combine many organismal communities. The 16S small subunit ribosomal RNA (SSU rRNA) gene is typically used to identify bacterial and archaeal species. The nuclear 18S SSU rRNA gene, and 28S large subunit (LSU) rRNA gene have been used as DNA barcodes and for phylogenetic studies in different eukaryote taxonomic groups. Because of their popularity, the National Center for Biotechnology Information (NCBI) receives a disproportionate number of rRNA sequence submissions and BLAST queries. These sequences vary in quality, length, origin (nuclear, mitochondria, plastid), and organism source and can represent any region of the ribosomal cistron.

RESULTS: To improve the timely verification of quality, origin and loci boundaries, we developed Ribovore, a software package for sequence analysis of rRNA sequences. The ribotyper and ribosensor programs are used to validate incoming sequences of bacterial and archaeal SSU rRNA. The ribodbmaker program is used to create high-quality datasets of rRNAs from different taxonomic groups. Key algorithmic steps include comparing candidate sequences against rRNA sequence profile hidden Markov models (HMMs) and covariance models of rRNA sequence and secondary-structure conservation, as well as other tests. Nine freely available blastn rRNA databases created and maintained with Ribovore are used for checking incoming GenBank submissions and used by the blastn browser interface at NCBI. Since 2018, Ribovore has been used to analyze more than 50 million prokaryotic SSU rRNA sequences submitted to GenBank, and to select at least 10,435 fungal rRNA RefSeq records from type material of 8350 taxa.

CONCLUSION: Ribovore combines single-sequence and profile-based methods to improve GenBank processing and analysis of rRNA sequences. It is a standalone, portable, and extensible software package for the alignment, classification and validation of rRNA sequences. Researchers planning on submitting SSU rRNA sequences to GenBank are encouraged to download and use Ribovore to analyze their sequences prior to submission to determine which sequences are likely to be automatically accepted into GenBank.}, } @article {pmid34384891, year = {2021}, author = {Aboouf, MA and Armbruster, J and Thiersch, M and Gassmann, M and Gödecke, A and Gnaiger, E and Kristiansen, G and Bicker, A and Hankeln, T and Zhu, H and Gorr, TA}, title = {Myoglobin, expressed in brown adipose tissue of mice, regulates the content and activity of mitochondria and lipid droplets.}, journal = {Biochimica et biophysica acta. Molecular and cell biology of lipids}, volume = {1866}, number = {12}, pages = {159026}, doi = {10.1016/j.bbalip.2021.159026}, pmid = {34384891}, issn = {1879-2618}, mesh = {Adipocytes, Brown/metabolism ; Adipose Tissue, Brown/metabolism ; Animals ; Apoptosis Regulatory Proteins/genetics ; Disease Models, Animal ; Energy Metabolism/genetics ; Humans ; Lipid Droplets/*metabolism ; Mice ; Mice, Knockout ; Mitochondria/genetics/*metabolism ; Muscle, Skeletal/metabolism ; Myoglobin/*genetics/metabolism ; Oxygen/*metabolism ; PPAR alpha/genetics ; Palmitates/metabolism ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics ; Proteins/genetics ; Thermogenesis/genetics ; Uncoupling Protein 1/genetics ; }, abstract = {The identification of novel physiological regulators that stimulate energy expenditure through brown adipose tissue (BAT) activity in substrate catalysis is of utmost importance to understand and treat metabolic diseases. Myoglobin (MB), known to store or transport oxygen in heart and skeletal muscles, has recently been found to bind fatty acids with physiological constants in its oxygenated form (i.e., MBO2). Here, we investigated the in vivo effect of MB expression on BAT activity. In particular, we studied mitochondrial function and lipid metabolism as essential determinants of energy expenditure in this tissue. We show in a MB-null (MBko) mouse model that MB expression in BAT impacts on the activity of brown adipocytes in a twofold manner: i) by elevating mitochondrial density plus maximal respiration capacity, and through that, by stimulating BAT oxidative metabolism along with the organelles` uncoupled respiration; and ii) by influencing the free fatty acids pool towards a palmitate-enriched composition and shifting the lipid droplet (LD) equilibrium towards higher counts of smaller droplets. These metabolic changes were accompanied by the up-regulated expression of thermogenesis markers UCP1, CIDEA, CIDEC, PGC1-α and PPAR-α in the BAT of MB wildtype (MBwt) mice. Along with the emergence of the "browning" BAT morphology, MBwt mice exhibited a leaner phenotype when compared to MBko littermates at 20 weeks of age. Our data shed novel insights into MB's role in linking oxygen and lipid-based thermogenic metabolism. The findings suggest potential new strategies of targeting the MB pathway to treat metabolic disorders related to diminishing energy expenditure.}, } @article {pmid34387318, year = {2021}, author = {Scott, GR and Dalziel, AC}, title = {Physiological insight into the evolution of complex phenotypes: aerobic performance and the O2 transport pathway of vertebrates.}, journal = {The Journal of experimental biology}, volume = {224}, number = {16}, pages = {}, doi = {10.1242/jeb.210849}, pmid = {34387318}, issn = {1477-9145}, mesh = {*Acclimatization ; Adaptation, Physiological ; *Altitude ; Animals ; Mammals ; Oxygen Consumption ; Phenotype ; }, abstract = {Evolutionary physiology strives to understand how the function and integration of physiological systems influence the way in which organisms evolve. Studies of the O2 transport pathway - the integrated physiological system that transports O2 from the environment to mitochondria - are well suited to this endeavour. We consider the mechanistic underpinnings across the O2 pathway for the evolution of aerobic capacity, focusing on studies of artificial selection and naturally selected divergence among wild populations of mammals and fish. We show that evolved changes in aerobic capacity do not require concerted changes across the O2 pathway and can arise quickly from changes in one or a subset of pathway steps. Population divergence in aerobic capacity can be associated with the evolution of plasticity in response to environmental variation or activity. In some cases, initial evolutionary divergence of aerobic capacity arose exclusively from increased capacities for O2 diffusion and/or utilization in active O2-consuming tissues (muscle), which may often constitute first steps in adaptation. However, continued selection leading to greater divergence in aerobic capacity is often associated with increased capacities for circulatory and pulmonary O2 transport. Increases in tissue O2 diffusing capacity may augment the adaptive benefit of increasing circulatory O2 transport owing to their interactive influence on tissue O2 extraction. Theoretical modelling of the O2 pathway suggests that O2 pathway steps with a disproportionately large influence over aerobic capacity have been more likely to evolve, but more work is needed to appreciate the extent to which such physiological principles can predict evolutionary outcomes.}, } @article {pmid34388165, year = {2021}, author = {Gul, S and Shah, KN and Rana, RM and Khan, MA and El-Shehawi, AM and Elseehy, MM}, title = {Phylogenetic and expression dynamics of tomato ClpB/Hsp100 gene under heat stress.}, journal = {PloS one}, volume = {16}, number = {8}, pages = {e0255847}, pmid = {34388165}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Chloroplasts/metabolism ; Cluster Analysis ; Endopeptidase Clp/classification/*metabolism ; Hot Temperature ; Solanum lycopersicum/*metabolism ; Phylogeny ; Plant Leaves/metabolism ; Plant Proteins/classification/*metabolism ; Seedlings/metabolism ; Sequence Alignment ; }, abstract = {Heat shock proteins (Hsps) are stress-responsive molecular chaperones, which uphold proper protein folding in response to external and internal stresses. The Hsp100 gene family plays a substantial role in thermos-tolerance of plants. This study investigated evolutionary relationship and expression of ClpB/Hsp100 gene family in tomato under heat stress. Six SlHsp100 genes were identified using bioinformatics tools. In silico sub-cellular localization indicated that of these 6 ClpB/Hsp100 members, 4 are found in chloroplast, 1 in mitochondria and 1 in the cytoplasm. For evolutionary study, 36 SlHsp100 genes were included in the phylogenetic tree showing a hierarchical clustering shared by the members of the kingdoms Plantae, Archaea, Chromista, Fungi and Bacteria. A total 4 pairs of orthologous and 5 pairs of paralogous genes were identified. Functional divergence between different Hsp100 clusters showed considerable functional homology. Thermo-tolerance measured in terms of cell viability, cell membrane stability and pollen viability indicated that it was paralleled by thermal resistance of Hsps. Reverse transcriptase polymerase chain reaction was used to analyze gene expression in leaves of five-week-old tomato seedlings following exposure to heat stress (45°C) and control (25°C). Chloroplastic LeHSP110/ClpB gene was upregulated in all tomato genotypes after exposure to heat stress highlighting the crucial role of this gene family in acquired thermo-tolerance.}, } @article {pmid34388986, year = {2021}, author = {Morrow, JL and Riegler, M}, title = {Genome analyses of four Wolbachia strains and associated mitochondria of Rhagoletis cerasi expose cumulative modularity of cytoplasmic incompatibility factors and cytoplasmic hitchhiking across host populations.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {616}, pmid = {34388986}, issn = {1471-2164}, mesh = {Animals ; Biological Evolution ; Cytoplasm ; Humans ; Mitochondria ; Symbiosis/genetics ; *Tephritidae ; *Wolbachia/genetics ; }, abstract = {BACKGROUND: The endosymbiont Wolbachia can manipulate arthropod reproduction and invade host populations by inducing cytoplasmic incompatibility (CI). Some host species are coinfected with multiple Wolbachia strains which may have sequentially invaded host populations by expressing different types of modular CI factor (cif) genes. The tephritid fruit fly Rhagoletis cerasi is a model for CI and Wolbachia population dynamics. It is associated with at least four Wolbachia strains in various combinations, with demonstrated (wCer2, wCer4), predicted (wCer1) or unknown (wCer5) CI phenotypes.

RESULTS: We sequenced and assembled the draft genomes of the Wolbachia strains wCer1, wCer4 and wCer5, and compared these with the previously sequenced genome of wCer2 which currently invades R. cerasi populations. We found complete cif gene pairs in all strains: four pairs in wCer2 (three Type I; one Type V), two pairs in wCer1 (both Type I) and wCer4 (one Type I; one Type V), and one pair in wCer5 (Type IV). Wolbachia genome variant analyses across geographically and genetically distant host populations revealed the largest diversity of single nucleotide polymorphisms (SNPs) in wCer5, followed by wCer1 and then wCer2, indicative of their different lengths of host associations. Furthermore, mitogenome analyses of the Wolbachia genome-sequenced individuals in combination with SNP data from six European countries revealed polymorphic mitogenome sites that displayed reduced diversity in individuals infected with wCer2 compared to those without.

CONCLUSIONS: Coinfections with Wolbachia are common in arthropods and affect options for Wolbachia-based management strategies of pest and vector species already infected by Wolbachia. Our analyses of Wolbachia genomes of a host naturally coinfected by several strains unravelled signatures of the evolutionary dynamics in both Wolbachia and host mitochondrial genomes as a consequence of repeated invasions. Invasion of already infected populations by new Wolbachia strains requires new sets of functionally different cif genes and thereby may select for a cumulative modularity of cif gene diversity in invading strains. Furthermore, we demonstrated at the mitogenomic scale that repeated CI-driven Wolbachia invasions of hosts result in reduced mitochondrial diversity and hitchhiking effects. Already resident Wolbachia strains may experience similar cytoplasmic hitchhiking effects caused by the invading Wolbachia strain.}, } @article {pmid34390927, year = {2021}, author = {Calderon, RH and Strand, Å}, title = {How retrograde signaling is intertwined with the evolution of photosynthetic eukaryotes.}, journal = {Current opinion in plant biology}, volume = {63}, number = {}, pages = {102093}, doi = {10.1016/j.pbi.2021.102093}, pmid = {34390927}, issn = {1879-0356}, mesh = {Biological Evolution ; *Eukaryota ; Photosynthesis/genetics ; Phylogeny ; *Plastids/genetics ; Symbiosis/genetics ; }, abstract = {Chloroplasts and mitochondria evolved from free-living prokaryotic organisms that entered the eukaryotic cell through endosymbiosis. The gradual conversion from endosymbiont to organelle during the course of evolution was accompanied by the development of a communication system between the host and the endosymbiont, referred to as retrograde signaling or organelle-to-nucleus signaling. In higher plants, plastid-to-nucleus signaling involves multiple signaling pathways necessary to coordinate plastid function and cellular responses to developmental and environmental stimuli. Phylogenetic reconstructions using sequence information from evolutionarily diverse photosynthetic eukaryotes have begun to provide information about how retrograde signaling pathways were adopted and modified in different lineages over time. A tight communication system was likely a major facilitator of plants conquest of the land because it would have enabled the algal ancestors of land plants to better allocate their cellular resources in response to high light and desiccation, the major stressor for streptophyte algae in a terrestrial habitat. In this review, we aim to give an evolutionary perspective on plastid-to-nucleus signaling.}, } @article {pmid34397079, year = {2021}, author = {Wang, T and He, T and Ding, X and Zhang, Q and Yang, L and Nie, Z and Zhao, T and Gai, J and Yang, S}, title = {Confirmation of GmPPR576 as a fertility restorer gene of cytoplasmic male sterility in soybean.}, journal = {Journal of experimental botany}, volume = {72}, number = {22}, pages = {7729-7742}, doi = {10.1093/jxb/erab382}, pmid = {34397079}, issn = {1460-2431}, mesh = {Cytoplasm ; Fertility/genetics ; Phylogeny ; *Plant Infertility/genetics ; *Glycine max/genetics ; }, abstract = {In soybean, heterosis achieved through the three-line system has been gradually applied in breeding to increase yield, but the underlying molecular mechanism remains unknown. We conducted a genetic analysis using the pollen fertility of offspring of the cross NJCMS1A×NJCMS1C. All the pollen of F1 plants was semi-sterile; in F2, the ratio of pollen-fertile plants to pollen-semi-sterile plants was 208:189. This result indicates that NJCMS1A is gametophyte sterile, and the fertility restoration of NJCMS1C to NJCMS1A is a quality trait controlled by a single gene locus. Using bulked segregant analysis, the fertility restorer gene Rf in NJCMS1C was located on chromosome 16 between the markers BARCSOYSSR_16_1067 and BARCSOYSSR_16_1078. Sequence analysis of genes in that region showed that GmPPR576 was non-functional in rf cultivars. GmPPR576 has one functional allele in Rf cultivars but three non-functional alleles in rf cultivars. Phylogenetic analysis showed that the GmPPR576 locus evolved rapidly with the presence of male-sterile cytoplasm. GmPPR576 belongs to the RFL fertility restorer gene family and is targeted to the mitochondria. GmPPR576 was knocked out in soybean N8855 using CRISPR/Cas9. The T1 plants showed sterile pollen, and T2 plants produced few pods at maturity. The results indicate that GmPPR576 is the fertility restorer gene of NJCMS1A.}, } @article {pmid34397090, year = {2021}, author = {Kowalczyk, A and Gbadamosi, O and Kolor, K and Sosa, J and Andrzejczuk, L and Gibson, G and St Croix, C and Chikina, M and Aizenman, E and Clark, N and Kiselyov, K}, title = {Evolutionary rate covariation identifies SLC30A9 (ZnT9) as a mitochondrial zinc transporter.}, journal = {The Biochemical journal}, volume = {478}, number = {17}, pages = {3205-3220}, pmid = {34397090}, issn = {1470-8728}, support = {R01 HG009299/HG/NHGRI NIH HHS/United States ; R21 NS111944/NS/NINDS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Carrier Proteins/*genetics/*metabolism ; Cation Transport Proteins/*genetics/*metabolism ; Cell Cycle Proteins/*genetics/*metabolism ; Computational Biology/*methods ; *Evolution, Molecular ; Gene Knockdown Techniques ; HeLa Cells ; Humans ; Mitochondria/*metabolism ; Mitochondrial Proteins/metabolism ; Phylogeny ; Signal Transduction/*genetics ; Transcription Factors/*genetics/*metabolism ; Transfection ; Whole Genome Sequencing/methods ; Zinc/metabolism ; }, abstract = {Recent advances in genome sequencing have led to the identification of new ion and metabolite transporters, many of which have not been characterized. Due to the variety of subcellular localizations, cargo and transport mechanisms, such characterization is a daunting task, and predictive approaches focused on the functional context of transporters are very much needed. Here we present a case for identifying a transporter localization using evolutionary rate covariation (ERC), a computational approach based on pairwise correlations of amino acid sequence evolutionary rates across the mammalian phylogeny. As a case study, we find that poorly characterized transporter SLC30A9 (ZnT9) coevolves with several components of the mitochondrial oxidative phosphorylation chain, suggesting mitochondrial localization. We confirmed this computational finding experimentally using recombinant human SLC30A9. SLC30A9 loss caused zinc mishandling in the mitochondria, suggesting that under normal conditions it acts as a zinc exporter. We therefore propose that ERC can be used to predict the functional context of novel transporters and other poorly characterized proteins.}, } @article {pmid34402879, year = {2021}, author = {Muthye, V and Lavrov, DV}, title = {Multiple Losses of MSH1, Gain of mtMutS, and Other Changes in the MutS Family of DNA Repair Proteins in Animals.}, journal = {Genome biology and evolution}, volume = {13}, number = {9}, pages = {}, pmid = {34402879}, issn = {1759-6653}, mesh = {Animals ; DNA Repair ; DNA-Binding Proteins/genetics/metabolism ; Fungal Proteins/genetics ; MutS DNA Mismatch-Binding Protein/genetics/metabolism ; Saccharomyces cerevisiae/genetics ; *Saccharomyces cerevisiae Proteins/genetics ; }, abstract = {MutS is a key component of the mismatch repair (MMR) pathway. Members of the MutS protein family are present in prokaryotes, eukaryotes, and viruses. Six MutS homologs (MSH1-6) have been identified in yeast, of which three function in nuclear MMR, while MSH1 functions in mitochondrial DNA repair. MSH proteins are believed to be well conserved in animals, except for MSH1-which is thought to be lost. Two intriguing exceptions to this general picture have been found, both in the class Anthozoa within the phylum Cnidaria. First, an ortholog of the yeast-MSH1 was reported in one hexacoral species. Second, a MutS homolog (mtMutS) has been found in the mitochondrial genome of all octocorals. To understand the origin and potential functional implications of these exceptions, we investigated the evolution of the MutS family both in Cnidaria and in animals in general. Our study confirmed the acquisition of octocoral mtMutS by horizontal gene transfer from a giant virus. Surprisingly, we identified MSH1 in all hexacorals and several sponges and placozoans. By contrast, MSH1 orthologs were lacking in other cnidarians, ctenophores, and bilaterian animals. Furthermore, while we identified MSH2 and MSH6 in nearly all animals, MSH4, MSH5, and, especially, MSH3 were missing in multiple species. Overall, our analysis revealed a dynamic evolution of the MutS family in animals, with multiple losses of MSH1, MSH3, some losses of MSH4 and MSH5, and a gain of the octocoral mtMutS. We propose that octocoral mtMutS functionally replaced MSH1 that was present in the common ancestor of Anthozoa.}, } @article {pmid34403637, year = {2021}, author = {Bettinazzi, S and Milani, L and Blier, PU and Breton, S}, title = {Bioenergetic consequences of sex-specific mitochondrial DNA evolution.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1957}, pages = {20211585}, pmid = {34403637}, issn = {1471-2954}, mesh = {Animals ; *Bivalvia/genetics ; DNA, Mitochondrial/genetics ; Female ; *Genome, Mitochondrial ; Male ; Mitochondria/genetics ; Oxidative Phosphorylation ; }, abstract = {Doubly uniparental inheritance (DUI) represents a notable exception to the general rule of strict maternal inheritance (SMI) of mitochondria in metazoans. This system entails the coexistence of two mitochondrial lineages (F- and M-type) transmitted separately through oocytes and sperm, thence providing an unprecedented opportunity for the mitochondrial genome to evolve adaptively for male functions. In this study, we explored the impact of a sex-specific mitochondrial evolution upon gamete bioenergetics of DUI and SMI bivalve species, comparing the activity of key enzymes of glycolysis, fermentation, fatty acid metabolism, tricarboxylic acid cycle, oxidative phosphorylation and antioxidant metabolism. Our findings suggest reorganized bioenergetic pathways in DUI gametes compared to SMI gametes. This generally results in a decreased enzymatic capacity in DUI sperm with respect to DUI oocytes, a limitation especially prominent at the terminus of the electron transport system. This bioenergetic remodelling fits a reproductive strategy that does not require high energy input and could potentially link with the preservation of the paternally transmitted mitochondrial genome in DUI species. Whether this phenotype may derive from positive or relaxed selection acting on DUI sperm is still uncertain.}, } @article {pmid34407123, year = {2021}, author = {Su, HJ and Liang, SL and Nickrent, DL}, title = {Plastome variation and phylogeny of Taxillus (Loranthaceae).}, journal = {PloS one}, volume = {16}, number = {8}, pages = {e0256345}, pmid = {34407123}, issn = {1932-6203}, mesh = {DNA, Ribosomal/chemistry/classification/metabolism ; Evolution, Molecular ; Genome, Plastid ; Loranthaceae/*classification/genetics ; Mitochondria/genetics ; NADH Dehydrogenase/classification/genetics ; Phylogeny ; Plastids/*genetics ; RNA, Transfer/genetics ; Ribosomal Proteins/classification/genetics ; }, abstract = {Several molecular phylogenetic studies of the mistletoe family Loranthaceae have been published such that now the general pattern of relationships among the genera and their biogeographic histories are understood. Less is known about species relationships in the larger (> 10 species) genera. This study examines the taxonomically difficult genus Taxillus composed of 35-40 Asian species. The goal was to explore the genetic diversity present in Taxillus plastomes, locate genetically variable hotspots, and test these for their utility as potential DNA barcodes. Using genome skimming, complete plastomes, as well as nuclear and mitochondrial rDNA sequences, were newly generated for eight species. The plastome sequences were used in conjunction with seven publicly available Taxillus sequences and three sequences of Scurrula, a close generic relative. The Taxillus plastomes ranged from 121 to 123 kbp and encoded 90-93 plastid genes. In addition to all of the NADH dehydrogenase complex genes, four ribosomal genes, infA and four intron-containing tRNA genes were lost or pseudogenized in all of the Taxillus and Scurrula plastomes. The topologies of the plastome, mitochondrial rDNA and nuclear rDNA trees were generally congruent, though with discordance at the position of T. chinensis. Several variable regions in the plastomes were identified that have sufficient numbers of parsimony informative sites as to recover the major clades seen in the complete plastome tree. Instead of generating complete plastome sequences, our study showed that accD alone or the concatenation of accD and rbcL can be used in future studies to facilitate identification of Taxillus samples and to generate a molecular phylogeny with robust sampling within the genus.}, } @article {pmid34409658, year = {2021}, author = {Karia, P and Yoshioka, K and Moeder, W}, title = {Multiple phosphorylation events of the mitochondrial membrane protein TTM1 regulate cell death during senescence.}, journal = {The Plant journal : for cell and molecular biology}, volume = {108}, number = {3}, pages = {766-780}, doi = {10.1111/tpj.15470}, pmid = {34409658}, issn = {1365-313X}, mesh = {Abscisic Acid/metabolism/pharmacology ; Acid Anhydride Hydrolases/genetics/*metabolism ; Arabidopsis/*cytology/drug effects/*physiology ; Arabidopsis Proteins/genetics/*metabolism ; Cell Death ; Darkness ; Mitochondrial Proteins/genetics/metabolism ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Phosphorylation ; Plant Leaves/drug effects/metabolism ; Plant Senescence/*physiology ; Plants, Genetically Modified ; Serine/metabolism ; }, abstract = {The role of mitochondria in programmed cell death (PCD) during animal growth and development is well documented, but much less is known for plants. We previously showed that the Arabidopsis thaliana triphosphate tunnel metalloenzyme (TTM) proteins TTM1 and TTM2 are tail-anchored proteins that localize in the mitochondrial outer membrane and participate in PCD during senescence and immunity, respectively. Here, we show that TTM1 is specifically involved in senescence induced by abscisic acid (ABA). Moreover, phosphorylation of TTM1 by multiple mitogen-activated protein (MAP) kinases regulates its function and turnover. A combination of proteomics and in vitro kinase assays revealed three major phosphorylation sites of TTM1 (Ser10, Ser437, and Ser490). Ser437, which is phosphorylated upon perception of senescence cues such as ABA and prolonged darkness, is phosphorylated by the MAP kinases MPK3 and MPK4, and Ser437 phosphorylation is essential for TTM1 function in senescence. These MPKs, together with three additional MAP kinases (MPK1, MPK7, and MPK6), also phosphorylate Ser10 and Ser490, marking TTM1 for protein turnover, which likely prevents uncontrolled cell death. Taken together, our results show that multiple MPKs regulate the function and turnover of the mitochondrial protein TTM1 during senescence-associated cell death, revealing a novel link between mitochondria and PCD.}, } @article {pmid34410224, year = {2021}, author = {Bandini, G and Damerow, S and Sempaio Guther, ML and Guo, H and Mehlert, A and Paredes Franco, JC and Beverley, S and Ferguson, MA}, title = {An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34410224}, issn = {2050-084X}, support = {101842/WT_/Wellcome Trust/United Kingdom ; R01 AI031078/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Cloning, Molecular ; Fucosyltransferases/genetics/*metabolism ; Gene Expression Regulation, Enzymologic ; Humans ; Mitochondria/*enzymology ; Phylogeny ; Trypanosoma brucei brucei/enzymology/*metabolism ; Galactoside 2-alpha-L-fucosyltransferase ; }, abstract = {Fucose is a common component of eukaryotic cell-surface glycoconjugates, generally added by Golgi-resident fucosyltransferases. Whereas fucosylated glycoconjugates are rare in kinetoplastids, the biosynthesis of the nucleotide sugar GDP-Fuc has been shown to be essential in Trypanosoma brucei. Here we show that the single identifiable T. brucei fucosyltransferase (TbFUT1) is a GDP-Fuc: β-D-galactose α-1,2-fucosyltransferase with an apparent preference for a Galβ1,3GlcNAcβ1-O-R acceptor motif. Conditional null mutants of TbFUT1 demonstrated that it is essential for both the mammalian-infective bloodstream form and the insect vector-dwelling procyclic form. Unexpectedly, TbFUT1 was localized in the mitochondrion of T. brucei and found to be required for mitochondrial function in bloodstream form trypanosomes. Finally, the TbFUT1 gene was able to complement a Leishmania major mutant lacking the homologous fucosyltransferase gene (Guo et al., 2021). Together these results suggest that kinetoplastids possess an unusual, conserved and essential mitochondrial fucosyltransferase activity that may have therapeutic potential across trypanosomatids.}, } @article {pmid34417525, year = {2021}, author = {Jenkins, EC and O'Connell, MJ and Manfredi, G and Germain, D}, title = {Doxycycline promotes proteasome fitness in the central nervous system.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {17003}, pmid = {34417525}, issn = {2045-2322}, support = {R01 NS084486/NS/NINDS NIH HHS/United States ; R01 GM124079/GM/NIGMS NIH HHS/United States ; R01 NS062055/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Central Nervous System/drug effects/*metabolism ; Cyclic AMP/metabolism ; Doxycycline/*pharmacology ; Estrogen Receptor alpha/metabolism ; Female ; Gene Expression Regulation/drug effects ; Male ; Mice ; Proteasome Endopeptidase Complex/genetics/*metabolism ; Saccharomyces cerevisiae/metabolism ; Transcription, Genetic/drug effects ; Unfolded Protein Response/drug effects ; }, abstract = {Several studies reported that mitochondrial stress induces cytosolic proteostasis in yeast and C. elegans. Notably, inhibition of mitochondrial translation with doxcycyline decreases the toxicity of β-amyloid aggregates, in a C. elegans. However, how mitochondrial stress activates cytosolic proteostasis remains unclear. Further whether doxycycline has this effect in mammals and in disease relevant tissues also remains unclear. We show here that doxycycline treatment in mice drastically reduces the accumulation of proteins destined for degradation by the proteasome in a CNS region-specific manner. This effect is associated with the activation of the ERα axis of the mitochondrial unfolded protein response (UPR[mt]), in both males and females. However, sexually dimorphic mechanisms of proteasome activation were observed. Doxycycline also activates the proteasome in fission yeast, where ERα is not expressed. Rather, the ancient ERα-coactivator Mms19 regulates this response in yeast. Our results suggest that the UPR[mt] initiates a conserved mitochondria-to-cytosol stress signal, resulting in proteasome activation, and that this signal has adapted during evolution, in a sex and tissue specific-manner. Therefore, while our results support the use of doxycycline in the prevention of proteopathic diseases, they also indicate that sex is an important variable to consider in the design of future clinical trials using doxycycline.}, } @article {pmid34418213, year = {2021}, author = {Jakovlić, I and Zou, H and Chen, JH and Lei, HP and Wang, GT and Liu, J and Zhang, D}, title = {Slow crabs - fast genomes: Locomotory capacity predicts skew magnitude in crustacean mitogenomes.}, journal = {Molecular ecology}, volume = {30}, number = {21}, pages = {5488-5502}, doi = {10.1111/mec.16138}, pmid = {34418213}, issn = {1365-294X}, support = {BP0719040//International Collaboration 111 Programme/ ; 31970408//National Natural Science Foundation of China/ ; lzujbky-2019//Fundamental Research Funds for the Central Universities/ ; XDB31010300//Strategic Priority Research Program of Chinese Academy of Sciences/ ; 561120206//Start-up Funds of Introduced Talent in Lanzhou University/ ; }, mesh = {Animals ; Base Composition ; *Brachyura ; Evolution, Molecular ; *Genome, Mitochondrial/genetics ; Mutation ; Phylogeny ; }, abstract = {Base composition skews (G-C/G+C) of mitochondrial genomes are believed to be primarily driven by mutational pressure, which is positively correlated with metabolic rate. In marine animals, metabolic rate is also positively correlated with locomotory capacity. Given the central role of mitochondria in energy metabolism, we hypothesised that selection for locomotory capacity should be positively correlated with the strength of purifying selection (dN/dS), and thus be negatively correlated with the skew magnitude. Therefore, these two models assume diametrically opposite associations between the metabolic rate and skew magnitude: positive correlation in the prevailing paradigm, and negative in our working hypothesis. We examined correlations between the skew magnitude, metabolic rate, locomotory capacity, and several other variables previously associated with mitochondrial evolution on 287 crustacean mitogenomes. Weakly locomotory taxa had higher skew magnitude and ω (dN/dS) values, but not the gene order rearrangement rate. Skew and ω magnitudes were correlated. Multilevel regression analyses indicated that three competing variables, body size, gene order rearrangement rate, and effective population size, had negligible impacts on the skew magnitude. In most crustacean lineages selection for locomotory capacity appears to be the primary factor determining the skew magnitude. Contrary to the prevailing paradigm, this implies that adaptive selection outweighs nonadaptive selection (mutation pressure) in crustaceans. However, we found indications that effective population size (nonadaptive factor) may outweigh the impact of locomotory capacity in sessile crustaceans (Thecostraca). In conclusion, skew magnitude is a product of the interplay between adaptive and nonadaptive factors, the balance of which varies among lineages.}, } @article {pmid34419587, year = {2021}, author = {Lyra, GM and Iha, C and Grassa, CJ and Cai, L and Zhang, H and Lane, C and Blouin, N and Oliveira, MC and Nunes, JMC and Davis, CC}, title = {Phylogenomics, divergence time estimation and trait evolution provide a new look into the Gracilariales (Rhodophyta).}, journal = {Molecular phylogenetics and evolution}, volume = {165}, number = {}, pages = {107294}, doi = {10.1016/j.ympev.2021.107294}, pmid = {34419587}, issn = {1095-9513}, mesh = {Genes, Mitochondrial ; *Gracilaria/genetics ; Phylogeny ; Plastids/genetics ; *Rhodophyta/genetics ; }, abstract = {The Gracilariales is a highly diverse, widely distributed order of red algae (Rhodophyta) that forms a well-supported clade. Aside from their ecological importance, species of Gracilariales provide important sources of agarans and possess bioactive compounds with medicinal and pharmaceutical use. Recent phylogenetic analyses from a small number of genes have greatly advanced our knowledge of evolutionary relationships in this clade, yet several key nodes were not especially well resolved. We assembled a phylogenomic data set containing 79 nuclear genes, 195 plastid genes, and 24 mitochondrial genes from species representing all three major Gracilariales lineages, including: Melanthalia, Gracilariopsis, and Gracilaria sensu lato. This data set leads to a fully-resolved phylogeny of Gracilariales, which is highly-consistent across genomic compartments. In agreement with previous findings, Melanthalia obtusata was sister to a clade including Gracilaria s.l. and Gracilariopsis, which were each resolved as well-supported clades. Our results also clarified the long-standing uncertainty about relationships in Gracilaria s.l., not resolved in single and multi-genes approaches. We further characterized the divergence time, organellar genome architecture, and morphological trait evolution in Gracilarales to better facilitate its taxonomic treatment. Gracilariopsis and Gracilaria s.l. are comparable taxonomic ranks, based on the overlapping time range of their divergence. The genomic structure of plastid and mitochondria is highly conserved within each clade but differs slightly among these clades in gene contents. For example, the plastid gene petP is lost in Gracilaria s.l. and the mitochondrial gene trnH is in different positions in the genome of Gracilariopsis and Gracilaria s.l. Our analyses of ancestral character evolution provide evidence that the main characters used to delimitate genera in Gracilariales, such as spermatangia type and features of the cystocarp's anatomy, overlap in subclades of Gracilaria s.l. We discuss the taxonomy of Gracilariales in light of these results and propose an objective and practical classification, which is in agreement with the criteria of monophyly, exclusive characters, predictability and nomenclatural stability.}, } @article {pmid34428409, year = {2021}, author = {Cooper, LN}, title = {Metabolism: Evolution of dolphin sperm endurance.}, journal = {Current biology : CB}, volume = {31}, number = {16}, pages = {R1006-R1008}, doi = {10.1016/j.cub.2021.06.075}, pmid = {34428409}, issn = {1879-0445}, mesh = {Animals ; *Dolphins ; Glycolysis ; Male ; Mammals ; Mitochondria ; Spermatozoa ; }, abstract = {Mammalian sperm have long been known to use energy derived from the metabolism of sugars and fatty acids. A new study shows that sperm of dolphins and their relatives lost functionality of the glycolysis pathway and are fueled only by energy-rich fatty acids that are metabolized by extra-large mitochondria, giving them exceptional endurance.}, } @article {pmid34436602, year = {2021}, author = {Petrů, M and Dohnálek, V and Füssy, Z and Doležal, P}, title = {Fates of Sec, Tat, and YidC Translocases in Mitochondria and Other Eukaryotic Compartments.}, journal = {Molecular biology and evolution}, volume = {38}, number = {12}, pages = {5241-5254}, pmid = {34436602}, issn = {1537-1719}, mesh = {*Escherichia coli Proteins/genetics ; *Eukaryota/genetics/metabolism ; Evolution, Molecular ; Membrane Transport Proteins/genetics/metabolism ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; Protein Transport ; }, abstract = {Formation of mitochondria by the conversion of a bacterial endosymbiont was a key moment in the evolution of eukaryotes. It was made possible by outsourcing the endosymbiont's genetic control to the host nucleus, while developing the import machinery for proteins synthesized on cytosolic ribosomes. The original protein export machines of the nascent organelle remained to be repurposed or were completely abandoned. This review follows the evolutionary fates of three prokaryotic inner membrane translocases Sec, Tat, and YidC. Homologs of all three translocases can still be found in current mitochondria, but with different importance for mitochondrial function. Although the mitochondrial YidC homolog, Oxa1, became an omnipresent independent insertase, the other two remained only sporadically present in mitochondria. Only a single substrate is known for the mitochondrial Tat and no function has yet been assigned for the mitochondrial Sec. Finally, this review compares these ancestral mitochondrial proteins with their paralogs operating in the plastids and the endomembrane system.}, } @article {pmid34440385, year = {2021}, author = {Stewart, DT and Robicheau, BM and Youssef, N and Garrido-Ramos, MA and Chase, EE and Breton, S}, title = {Expanding the Search for Sperm Transmission Elements in the Mitochondrial Genomes of Bivalve Mollusks.}, journal = {Genes}, volume = {12}, number = {8}, pages = {}, pmid = {34440385}, issn = {2073-4425}, mesh = {Animals ; Bivalvia/*genetics ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial ; Inheritance Patterns ; Male ; Spermatozoa/*physiology ; }, abstract = {Doubly uniparental inheritance (DUI) of mitochondrial DNA (mtDNA) in bivalve mollusks is one of the most notable departures from the paradigm of strict maternal inheritance of mtDNA among metazoans. Recently, work on the Mediterranean mussel Mytilus galloprovincialis suggested that a nucleotide motif in the control region of this species, known as the sperm transmission element (STE), helps protect male-transmitted mitochondria from destruction during spermatogenesis. Subsequent studies found similar, yet divergent, STE motifs in other marine mussels. Here, we extend the in silico search for mtDNA signatures resembling known STEs. This search is carried out for the large unassigned regions of 157 complete mitochondrial genomes from within the Mytiloida, Veneroida, Unionoida, and Ostreoida bivalve orders. Based on a sliding window approach, we present evidence that there are additional putative STE signatures in the large unassigned regions of several marine clams and freshwater mussels with DUI. We discuss the implications of this finding for interpreting the origin of doubly uniparental inheritance in ancestral bivalve mollusks, as well as potential future in vitro and in silico studies that could further refine our understanding of the early evolution of this unusual system of mtDNA inheritance.}, } @article {pmid34442643, year = {2021}, author = {Kwak, Y}, title = {An Update on Trichoderma Mitogenomes: Complete De Novo Mitochondrial Genome of the Fungal Biocontrol Agent Trichoderma harzianum (Hypocreales, Sordariomycetes), an Ex-Neotype Strain CBS 226.95, and Tracing the Evolutionary Divergences of Mitogenomes in Trichoderma.}, journal = {Microorganisms}, volume = {9}, number = {8}, pages = {}, pmid = {34442643}, issn = {2076-2607}, support = {NRF-2018R1D1A1B07043042, NRF-2021R1I1A1A01042148//National Research Foundation of Korea/ ; }, abstract = {Members of the genus Trichoderma (Hypocreales), widely used as biofungicides, biofertilizers, and as model fungi for the industrial production of CAZymes, have actively been studied for the applications of their biological functions. Recently, the study of the nuclear genomes of Trichoderma has expanded in the directions of adaptation and evolution to gain a better understanding of their ecological traits. However, Trichoderma's mitochondria have received much less attention despite mitochondria being the most necessary element for sustaining cell life. In this study, a mitogenome of the fungus Trichoderma harzianum CBS 226.95 was assembled de novo. A 27,632 bp circular DNA molecule was revealed with specific features, such as the intronless of all core PCGs, one homing endonuclease, and a putative overlapping tRNA, on a closer phylogenetic relationship with T. reesei among hypocrealean fungi. Interestingly, the mitogenome of T. harzianum CBS 226.95 was predicted to have evolved earlier than those of other Trichoderma species and also assumed with a selection pressure in the cox3. Considering the bioavailability, both for the ex-neotype strain of the T. harzianum species complex and the most globally representative commercial fungal biocontrol agent, our results on the T. harzianum CBS 226.95 mitogenome provide crucial information which will be helpful criteria in future studies on Trichoderma.}, } @article {pmid34446347, year = {2021}, author = {Satoh, T}, title = {Bird evolution by insulin resistance.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {32}, number = {10}, pages = {803-813}, doi = {10.1016/j.tem.2021.07.007}, pmid = {34446347}, issn = {1879-3061}, mesh = {Animals ; Birds/metabolism ; Humans ; *Insulin Resistance/genetics ; *Insulins ; Kelch-Like ECH-Associated Protein 1 ; NF-E2-Related Factor 2 ; Oxygen ; Reactive Oxygen Species/metabolism ; }, abstract = {Drift of oxygen concentrations in the atmosphere was one of the main drivers of the evolution of vertebrates. The drop in oxygen concentrations at the Permian-Triassic (PT) boundary may have been the biggest challenge to vertebrates. This hypoxic condition forced theropods to lose certain genes to maximize their efficiency of oxygen usage. Recent studies show that omentin and insulin-sensitive glucose transporter 4 (GLUT4) are missing in the bird genome. Since these gene products play essential roles in maintaining insulin sensitivity, this loss forced theropods to become insulin resistant. Insulin resistance may have been the key to allowing theropods to become hyperathletic under hypoxic conditions and to outcompete mammals during the Triassic period. A second challenge was the gradual increase in oxygen concentrations during the late Jurassic, Cretaceous, and Tertiary periods when reactive oxygen species (ROS) leakage from mitochondria became a problem. Since the simplest solution was the expansion of body size, some theropods became bigger to reduce ROS leakage per volume. Another solution was the development of a constitutively active countermeasure against ROS. A recent study shows that Neoaves have constitutively active nuclear factor erythroid 2-related factor 2 (NRF2) due to deletion of the C-terminal part of the KEAP1 protein, thus allowing Neoaves to express antioxidant enzymes to overcome ROS leakage.}, } @article {pmid34447361, year = {2021}, author = {Rolland, C and Andreani, J and Sahmi-Bounsiar, D and Krupovic, M and La Scola, B and Levasseur, A}, title = {Clandestinovirus: A Giant Virus With Chromatin Proteins and a Potential to Manipulate the Cell Cycle of Its Host Vermamoeba vermiformis.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {715608}, pmid = {34447361}, issn = {1664-302X}, abstract = {For several decades, the vast world of DNA viruses has been expanding constantly. Various discoveries in this field have broadened our knowledge and revealed that DNA viruses encode many functional features, which were once thought to be exclusive to cellular life. Here, we report the isolation of a giant virus named "clandestinovirus," grown on the amoebal host Vermamoeba vermiformis. This virus was discovered in a mixed co-culture associated with another giant virus, Faustovirus ST1. Clandestinovirus possesses a linear dsDNA genome of 581,987 base pairs containing 617 genes. Phylogenetically, clandestinovirus is most closely related to Acanthamoeba castellanii medusavirus and was considered a member of the proposed Medusaviridae family. However, clandestinovirus genome is 65% larger than that of medusavirus, emphasizing the considerable genome size variation within this virus family. Functional annotation of the clandestinovirus genes suggests that the virus encodes four core histones. Furthermore, clandestinovirus appears to orchestrate the cell cycle and mitochondrial activities of the infected host by virtue of encoding a panel of protein kinases and phosphatases, and a suite of functionally diverse mitochondrial protein homologs, respectively. Collectively, these observations illuminate a strategy employed by clandestinovirus to optimize the intracellular environment for efficient virus propagation.}, } @article {pmid34447743, year = {2021}, author = {Mahapatra, K and Banerjee, S and De, S and Mitra, M and Roy, P and Roy, S}, title = {An Insight Into the Mechanism of Plant Organelle Genome Maintenance and Implications of Organelle Genome in Crop Improvement: An Update.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {671698}, pmid = {34447743}, issn = {2296-634X}, abstract = {Besides the nuclear genome, plants possess two small extra chromosomal genomes in mitochondria and chloroplast, respectively, which contribute a small fraction of the organelles' proteome. Both mitochondrial and chloroplast DNA have originated endosymbiotically and most of their prokaryotic genes were either lost or transferred to the nuclear genome through endosymbiotic gene transfer during the course of evolution. Due to their immobile nature, plant nuclear and organellar genomes face continuous threat from diverse exogenous agents as well as some reactive by-products or intermediates released from various endogenous metabolic pathways. These factors eventually affect the overall plant growth and development and finally productivity. The detailed mechanism of DNA damage response and repair following accumulation of various forms of DNA lesions, including single and double-strand breaks (SSBs and DSBs) have been well documented for the nuclear genome and now it has been extended to the organelles also. Recently, it has been shown that both mitochondria and chloroplast possess a counterpart of most of the nuclear DNA damage repair pathways and share remarkable similarities with different damage repair proteins present in the nucleus. Among various repair pathways, homologous recombination (HR) is crucial for the repair as well as the evolution of organellar genomes. Along with the repair pathways, various other factors, such as the MSH1 and WHIRLY family proteins, WHY1, WHY2, and WHY3 are also known to be involved in maintaining low mutation rates and structural integrity of mitochondrial and chloroplast genome. SOG1, the central regulator in DNA damage response in plants, has also been found to mediate endoreduplication and cell-cycle progression through chloroplast to nucleus retrograde signaling in response to chloroplast genome instability. Various proteins associated with the maintenance of genome stability are targeted to both nuclear and organellar compartments, establishing communication between organelles as well as organelles and nucleus. Therefore, understanding the mechanism of DNA damage repair and inter compartmental crosstalk mechanism in various sub-cellular organelles following induction of DNA damage and identification of key components of such signaling cascades may eventually be translated into strategies for crop improvement under abiotic and genotoxic stress conditions. This review mainly highlights the current understanding as well as the importance of different aspects of organelle genome maintenance mechanisms in higher plants.}, } @article {pmid34481840, year = {2021}, author = {Montes de Oca Balderas, P}, title = {Mitochondria-plasma membrane interactions and communication.}, journal = {The Journal of biological chemistry}, volume = {297}, number = {4}, pages = {101164}, pmid = {34481840}, issn = {1083-351X}, mesh = {Animals ; Cell Membrane/*metabolism ; Humans ; Mitochondria/*metabolism ; }, abstract = {Mitochondria are known as the powerhouses of eukaryotic cells; however, they perform many other functions besides oxidative phosphorylation, including Ca[2+] homeostasis, lipid metabolism, antiviral response, and apoptosis. Although other hypotheses exist, mitochondria are generally thought as descendants of an α-proteobacteria that adapted to the intracellular environment within an Asgard archaebacteria, which have been studied for decades as an organelle subdued by the eukaryotic cell. Nevertheless, several early electron microscopy observations hinted that some mitochondria establish specific interactions with certain plasma membrane (PM) domains in mammalian cells. Furthermore, recent findings have documented the direct physical and functional interaction of mitochondria and the PM, the organization of distinct complexes, and their communication through vesicular means. In yeast, some molecular players mediating this interaction have been elucidated, but only a few works have studied this interaction in mammalian cells. In addition, mitochondria can be translocated among cells through tunneling nanotubes or by other mechanisms, and free, intact, functional mitochondria have been reported in the blood plasma. Together, these findings challenge the conception of mitochondria as organelles subdued by the eukaryotic cell. This review discusses the evidence of the mitochondria interaction with the PM that has been long disregarded despite its importance in cell function, pathogenesis, and evolution. It also proposes a scheme of mitochondria-PM interactions with the intent to promote research and knowledge of this emerging pathway that promises to shift the current paradigms of cell biology.}, } @article {pmid34490275, year = {2021}, author = {Moroz, LL and Romanova, DY}, title = {Selective Advantages of Synapses in Evolution.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {726563}, pmid = {34490275}, issn = {2296-634X}, support = {R01 NS114491/NS/NINDS NIH HHS/United States ; }, } @article {pmid34492093, year = {2021}, author = {Phadungsaksawasdi, K and Sunantaraporn, S and Seatamanoch, N and Kongdachalert, S and Phumee, A and Kraivichian, K and Sawaswong, V and Payungporn, S and Brownell, N and Siriyasatien, P}, title = {Molecular analysis of mitochrondrial cytb of Pediculus humanus capitis in Thailand revealed potential historical connection with South Asia.}, journal = {PloS one}, volume = {16}, number = {9}, pages = {e0257024}, pmid = {34492093}, issn = {1932-6203}, mesh = {Animals ; Child ; Cytochromes b/*genetics ; Ectoparasitic Infestations/epidemiology/*genetics/parasitology ; Female ; Genetic Variation/genetics ; Haplotypes/genetics ; Human Migration ; Humans ; Lice Infestations/epidemiology/*genetics/parasitology ; Male ; Mitochondria/genetics ; Pediculus/classification/*genetics/pathogenicity ; Phylogeny ; Thailand/epidemiology ; }, abstract = {BACKGROUND: Pediculus humanus capitis or head louse is an obligate ectoparasite and its infestation remains a major public health issue worldwide. Molecular analysis divides head lice into six clades and intra-clade genetic differences have been identified. Several hypotheses have been formulated to elucidate the discrepancies of the variety of head lice among different regions of the world. It is currently concluded that head lice distribution might be associated with human migration history. This study aims to investigate genetic data of human head lice in Thailand. We believe that the analysis could help establish the correlation between local and global head lice populations.

METHOD: We investigated mitochondrial cytochrome b (cytb) gene of the collected 214 head lice to evaluate genetic diversity from 15 provinces among 6 regions of Thailand. The head lice genes were added to the global pool for the phylogenetic tree, Bayesian tree, Skyline plot, and median joining network construction. The biodiversity, neutrality tests, and population genetic differentiation among the 6 Thailand geographic regions were analyzed by DNAsp version 6.

RESULTS: The phylogenetic tree analysis of 214 collected head lice are of clade A and clade C accounting for roughly 65% and 35% respectively. The Bayesian tree revealed a correlation of clade diversification and ancient human dispersal timeline. In Thailand, clade A is widespread in the country. Clade C is confined to only the Central, Southern, and Northeastern regions. We identified 50 novel haplotypes. Statistical analysis showed congruent results between genetic differentiation and population migration especially with South Asia.

CONCLUSIONS: Pediculosis remains problematic among children in the rural areas in Thailand. Cytb gene analysis of human head lice illustrated clade distribution and intra-clade diversity of different areas. Our study reported novel haplotypes of head lice in Thailand. Moreover, the statistic calculation provided a better understanding of their relationship with human, as an obligate human parasite and might help provide a better insight into the history of human population migration. Determination of the correlation between phylogenetic data and pediculicide resistance gene as well as residing bacteria are of interest for future studies.}, } @article {pmid34493257, year = {2021}, author = {Tůmová, P and Voleman, L and Klingl, A and Nohýnková, E and Wanner, G and Doležal, P}, title = {Inheritance of the reduced mitochondria of Giardia intestinalis is coupled to the flagellar maturation cycle.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {193}, pmid = {34493257}, issn = {1741-7007}, mesh = {Databases, Genetic ; *Giardia lamblia/genetics ; Mitochondria/genetics ; Mitochondrial Dynamics ; Organelles ; }, abstract = {BACKGROUND: The presence of mitochondria is a distinguishing feature between prokaryotic and eukaryotic cells. It is currently accepted that the evolutionary origin of mitochondria coincided with the formation of eukaryotes and from that point control of mitochondrial inheritance was required. Yet, the way the mitochondrial presence has been maintained throughout the eukaryotic cell cycle remains a matter of study. Eukaryotes control mitochondrial inheritance mainly due to the presence of the genetic component; still only little is known about the segregation of mitochondria to daughter cells during cell division. Additionally, anaerobic eukaryotic microbes evolved a variety of genomeless mitochondria-related organelles (MROs), which could be theoretically assembled de novo, providing a distinct mechanistic basis for maintenance of stable mitochondrial numbers. Here, we approach this problem by studying the structure and inheritance of the protist Giardia intestinalis MROs known as mitosomes.

RESULTS: We combined 2D stimulated emission depletion (STED) microscopy and focused ion beam scanning electron microscopy (FIB/SEM) to show that mitosomes exhibit internal segmentation and conserved asymmetric structure. From a total of about forty mitosomes, a small, privileged population is harnessed to the flagellar apparatus, and their life cycle is coordinated with the maturation cycle of G. intestinalis flagella. The orchestration of mitosomal inheritance with the flagellar maturation cycle is mediated by a microtubular connecting fiber, which physically links the privileged mitosomes to both axonemes of the oldest flagella pair and guarantees faithful segregation of the mitosomes into the daughter cells.

CONCLUSION: Inheritance of privileged Giardia mitosomes is coupled to the flagellar maturation cycle. We propose that the flagellar system controls segregation of mitochondrial organelles also in other members of this supergroup (Metamonada) of eukaryotes and perhaps reflects the original strategy of early eukaryotic cells to maintain this key organelle before mitochondrial fusion-fission dynamics cycle as observed in Metazoa was established.}, } @article {pmid34498257, year = {2021}, author = {Miyake, T and Nakajima, J and Umemura, K and Onikura, N and Ueda, T and Smith, C and Kawamura, K}, title = {Genetic diversification of the Kanehira bitterling Acheilognathus rhombeus inferred from mitochondrial DNA, with comments on the phylogenetic relationship with its sister species Acheilognathus barbatulus.}, journal = {Journal of fish biology}, volume = {99}, number = {5}, pages = {1677-1695}, doi = {10.1111/jfb.14876}, pmid = {34498257}, issn = {1095-8649}, support = {12575009//Ministry of Education, Science, Sports and Culture, Japan/ ; 10041156//Ministry of Education, Science, Sports and Culture, Japan/ ; }, mesh = {Animals ; *Cypriniformes ; *DNA, Mitochondrial/genetics ; Mitochondria ; Phylogeny ; Phylogeography ; }, abstract = {The Kanehira bitterling, Acheilognathus rhombeus, is a freshwater fish, discontinuously distributed in western Japan and the Korean Peninsula. Unusually among bitterling it is an autumn-spawning species and shows developmental diapause. Consequently, the characterization of its evolutionary history is significant not only in the context of the fish assemblage of East Asia, but also for understanding life-history evolution. This study aimed to investigate the phylogeography of A. rhombeus and its sister species Acheilognathus barbatulus, distributed in China, using a mitochondrial analysis of the ND1 gene from 311 samples collected from 50 localities in Japan and continental Asia. Phylogenetic analysis revealed that A. barbatulus is included in A. rhombeus and genetically closer to Japanese A. rhombeus than to Korean A. rhombeus. Divergence of Korean A. rhombeus and A. barbatulus from Japanese A. rhombeus was estimated to be from the late Pliocene (3.44 Mya) and the early Pleistocene (1.98 Mya), respectively. Each event closely coincided with the time of the Japan Sea opening. Japanese A. rhombeus comprised seven lineages: three in Honshu and four in Kyushu. One lineage in central Kyushu was genetically closer to the Honshu lineages than to other lineages in northern Kyushu. Divergence of Japanese lineages was estimated to be from the early to middle Pleistocene (0.55-0.93 Mya), during a period of geological and paleoclimatic change, including volcanic activity. Population expansion in the late Pleistocene (<0.10 Ma) was suggested in many of the lineages, which accords with other freshwater fishes. Biogeographically the ancestral A. rhombeus/A. barbatulus was likely to have repeatedly colonized Japan from the continent through land bridges in the late Pliocene and the early Pleistocene. However, the close genetic relationship between Japanese A. rhombeus and A. barbatulus suggests another possibility, with the second colonization occurring in reverse, from Japan to China. The small genetic distance between them indicates that the colonization occurred later than colonization events of other freshwater fishes, including other bitterling species.}, } @article {pmid34504353, year = {2021}, author = {Li, L and Conradson, DM and Bharat, V and Kim, MJ and Hsieh, CH and Minhas, PS and Papakyrikos, AM and Durairaj, AS and Ludlam, A and Andreasson, KI and Partridge, L and Cianfrocco, MA and Wang, X}, title = {A mitochondrial membrane-bridging machinery mediates signal transduction of intramitochondrial oxidation.}, journal = {Nature metabolism}, volume = {3}, number = {9}, pages = {1242-1258}, pmid = {34504353}, issn = {2522-5812}, support = {R21 AG061315/AG/NIA NIH HHS/United States ; H-1105/PUK_/Parkinson's UK/United Kingdom ; S10 RR027425/RR/NCRR NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; S10 RR026780/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mitochondria/*metabolism ; Mitochondrial Membranes/*metabolism ; Oxidation-Reduction ; Protein Conformation ; Reactive Oxygen Species/metabolism ; *Signal Transduction ; }, abstract = {Mitochondria are the main site for generating reactive oxygen species, which are key players in diverse biological processes. However, the molecular pathways of redox signal transduction from the matrix to the cytosol are poorly defined. Here we report an inside-out redox signal of mitochondria. Cysteine oxidation of MIC60, an inner mitochondrial membrane protein, triggers the formation of disulfide bonds and the physical association of MIC60 with Miro, an outer mitochondrial membrane protein. The oxidative structural change of this membrane-crossing complex ultimately elicits cellular responses that delay mitophagy, impair cellular respiration and cause oxidative stress. Blocking the MIC60-Miro interaction or reducing either protein, genetically or pharmacologically, extends lifespan and health-span of healthy fruit flies, and benefits multiple models of Parkinson's disease and Friedreich's ataxia. Our discovery provides a molecular basis for common treatment strategies against oxidative stress.}, } @article {pmid34519912, year = {2022}, author = {Oono, J and Hatakeyama, Y and Yabiku, T and Ueno, O}, title = {Effects of growth temperature and nitrogen nutrition on expression of C3-C4 intermediate traits in Chenopodium album.}, journal = {Journal of plant research}, volume = {135}, number = {1}, pages = {15-27}, pmid = {34519912}, issn = {1618-0860}, support = {JP15K14638//Japan Society for the promotion of Science, KAKENHI/ ; }, mesh = {*Chenopodium album/metabolism ; Glycine Dehydrogenase (Decarboxylating)/metabolism ; Nitrogen ; Photosynthesis ; Plant Leaves/metabolism ; Temperature ; }, abstract = {Proto-Kranz plants represent an initial phase in the evolution from C3 to C3-C4 intermediate to C4 plants. The ecological and adaptive aspects of C3-C4 plants would provide an important clue to understand the evolution of C3-C4 plants. We investigated whether growth temperature and nitrogen (N) nutrition influence the expression of C3-C4 traits in Chenopodium album (proto-Kranz) in comparison with Chenopodium quinoa (C3). Plants were grown during 5 weeks at 20 or 30 °C under standard or low N supply levels (referred to as 20SN, 20LN, 30SN, and 30LN). Net photosynthetic rate and leaf N content were higher in 20SN and 30SN plants than in 20LN and 30LN plants of C. album but did not differ among growth conditions in C. quinoa. The CO2 compensation point (Γ) of C. album was lowest in 30LN plants (36 µmol mol[-1]), highest in 20SN plants (51 µmol mol[-1]), and intermediate in 20LN and 30SN plants, whereas Γ of C. quinoa did not differ among the growth conditions (51-52 µmol mol[-1]). The anatomical structure of leaves was not considerably affected by growth conditions in either species. However, ultrastructural observations in C. album showed that the number of mitochondria per mesophyll or bundle sheath (BS) cell was lower in 20LN and 30LN plants than in 20SN and 30SN plants. Immunohistochemical observations revealed that lower accumulation level of P-protein of glycine decarboxylase (GDC-P) in mesophyll mitochondria than in BS mitochondria is the major factor causing the decrease in Γ values in C. album plants grown under low N supply and high temperature. These results suggest that high growth temperature and low N supply lead to the expression of C3-C4 traits (the reduction of Γ) in the proto-Kranz plants of C. album through the regulation of GDC-P expression.}, } @article {pmid34523684, year = {2021}, author = {Mallo, N and Ovciarikova, J and Martins-Duarte, ES and Baehr, SC and Biddau, M and Wilde, ML and Uboldi, AD and Lemgruber, L and Tonkin, CJ and Wideman, JG and Harding, CR and Sheiner, L}, title = {Depletion of a Toxoplasma porin leads to defects in mitochondrial morphology and contacts with the endoplasmic reticulum.}, journal = {Journal of cell science}, volume = {134}, number = {20}, pages = {}, pmid = {34523684}, issn = {1477-9137}, support = {213455/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 217173/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; BB/N003675/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Endoplasmic Reticulum/genetics/metabolism ; Humans ; Mitochondria/metabolism ; Protein Transport ; *Toxoplasma/genetics/metabolism ; Voltage-Dependent Anion Channels/genetics/metabolism ; }, abstract = {The voltage-dependent anion channel (VDAC) is a ubiquitous channel in the outer membrane of the mitochondrion with multiple roles in protein, metabolite and small molecule transport. In mammalian cells, VDAC protein, as part of a larger complex including the inositol triphosphate receptor, has been shown to have a role in mediating contacts between the mitochondria and endoplasmic reticulum (ER). We identify VDAC of the pathogenic apicomplexan Toxoplasma gondii and demonstrate its importance for parasite growth. We show that VDAC is involved in protein import and metabolite transfer to mitochondria. Further, depletion of VDAC resulted in significant morphological changes in the mitochondrion and ER, suggesting a role in mediating contacts between these organelles in T. gondii. This article has an associated First Person interview with the first author of the paper.}, } @article {pmid34528296, year = {2021}, author = {Møller, IM and Rasmusson, AG and Van Aken, O}, title = {Plant mitochondria - past, present and future.}, journal = {The Plant journal : for cell and molecular biology}, volume = {108}, number = {4}, pages = {912-959}, doi = {10.1111/tpj.15495}, pmid = {34528296}, issn = {1365-313X}, mesh = {DNA, Mitochondrial/genetics ; DNA, Plant/*genetics ; Lipids/analysis ; Mitochondria/*metabolism/ultrastructure ; Mitochondrial Proteins/genetics/*metabolism ; NADH Dehydrogenase/genetics/metabolism ; Oxidation-Reduction ; Oxidoreductases/genetics/metabolism ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Plants/genetics/*metabolism/ultrastructure ; Proteomics ; Signal Transduction ; Alternative Oxidase ; }, abstract = {The study of plant mitochondria started in earnest around 1950 with the first isolations of mitochondria from animal and plant tissues. The first 35 years were spent establishing the basic properties of plant mitochondria and plant respiration using biochemical and physiological approaches. A number of unique properties (compared to mammalian mitochondria) were observed: (i) the ability to oxidize malate, glycine and cytosolic NAD(P)H at high rates; (ii) the partial insensitivity to rotenone, which turned out to be due to the presence of a second NADH dehydrogenase on the inner surface of the inner mitochondrial membrane in addition to the classical Complex I NADH dehydrogenase; and (iii) the partial insensitivity to cyanide, which turned out to be due to an alternative oxidase, which is also located on the inner surface of the inner mitochondrial membrane, in addition to the classical Complex IV, cytochrome oxidase. With the appearance of molecular biology methods around 1985, followed by genomics, further unique properties were discovered: (iv) plant mitochondrial DNA (mtDNA) is 10-600 times larger than the mammalian mtDNA, yet it only contains approximately 50% more genes; (v) plant mtDNA has kept the standard genetic code, and it has a low divergence rate with respect to point mutations, but a high recombinatorial activity; (vi) mitochondrial mRNA maturation includes a uniquely complex set of activities for processing, splicing and editing (at hundreds of sites); (vii) recombination in mtDNA creates novel reading frames that can produce male sterility; and (viii) plant mitochondria have a large proteome with 2000-3000 different proteins containing many unique proteins such as 200-300 pentatricopeptide repeat proteins. We describe the present and fairly detailed picture of the structure and function of plant mitochondria and how the unique properties make their metabolism more flexible allowing them to be involved in many diverse processes in the plant cell, such as photosynthesis, photorespiration, CAM and C4 metabolism, heat production, temperature control, stress resistance mechanisms, programmed cell death and genomic evolution. However, it is still a challenge to understand how the regulation of metabolism and mtDNA expression works at the cellular level and how retrograde signaling from the mitochondria coordinates all those processes.}, } @article {pmid34530136, year = {2021}, author = {Duncan, WP and Machado, RN and Fernandes, MN}, title = {Environmentally-induced osmoregulation in Neotropical freshwater stingrays (Myliobatiformes: Potamotrygoninae) after controlling for phylogeny.}, journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology}, volume = {262}, number = {}, pages = {111076}, doi = {10.1016/j.cbpa.2021.111076}, pmid = {34530136}, issn = {1531-4332}, mesh = {Animals ; Electrolytes/blood/*metabolism ; Fish Proteins/genetics/metabolism ; Fresh Water ; Gills/metabolism ; Kidney/metabolism ; Mitochondria/genetics/*metabolism ; *Osmoregulation ; Osmosis ; Phylogeny ; Renal Reabsorption ; Skates, Fish/blood/genetics/*metabolism ; Sodium-Potassium-Exchanging ATPase/genetics/metabolism ; *Tropical Climate ; }, abstract = {The osmotic physiology of freshwater stingrays was investigated in fifteen species from white (WW), black (BW), and clearwater (CW) rivers of Brazilian hydrographic basins. Regardless of phylogeny, potamotrygonids collected in the BW (Negro, Jutai, Nhamunda, and Manacapuru rivers), and CW (Tapajos, Parana, Mutum, Demeni, and Branco rivers) exhibited lower levels of osmolytes and plasma osmolality than those from WW (Amazon estuary, Solimoes, and Tarauaca rivers). However, the gill and kidney Na[+]/K[+]-ATPase activities were higher in the potamotrygonid species from BW and CW than those from WW. These results may be related to the ability of the potamotrygonids to achieve high ion uptake from ion-poor waters, such as those of BW and/or CW. Additionally, the high kidney Na[+]/K[+]-ATPase activity may help to minimize ion loss and generate diluted urine. Thus, diffusional losses of salts are balanced by uptake of ions in the gill, and reabsorption by the kidney. The physiological traits showed a weak phylogenetic signal, which indicates a strong evolutionary convergence. Multivariate analyses revealed that variations in physiological traits has a significant association with the type of water, as well as its physical and chemical characteristics such as electric conductivity and pH. Therefore, the South American Neotropical freshwater stingrays adjust their osmoregulatory mechanisms according to the environment in which they live.}, } @article {pmid34536995, year = {2021}, author = {Hong, Z and Liao, X and Ye, Y and Zhang, N and Yang, Z and Zhu, W and Gao, W and Sharbrough, J and Tembrock, LR and Xu, D and Wu, Z}, title = {A complete mitochondrial genome for fragrant Chinese rosewood (Dalbergia odorifera, Fabaceae) with comparative analyses of genome structure and intergenomic sequence transfers.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {672}, pmid = {34536995}, issn = {1471-2164}, mesh = {China ; Chloroplasts ; *Dalbergia/genetics ; *Fabaceae/genetics ; *Genome, Chloroplast ; *Genome, Mitochondrial ; Phylogeny ; Plant Breeding ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Dalbergia odorifera is an economically and culturally important species in the Fabaceae because of the high-quality lumber and traditional Chinese medicines made from this plant, however, overexploitation has increased the scarcity of D. odorifera. Given the rarity and the multiple uses of this species, it is important to expand the genomic resources for utilizing in applications such as tracking illegal logging, determining effective population size of wild stands, delineating pedigrees in marker assisted breeding programs, and resolving gene networks in functional genomics studies. Even the nuclear and chloroplast genomes have been published for D. odorifera, the complete mitochondrial genome has not been assembled or assessed for sequence transfer to other genomic compartments until now. Such work is essential in understanding structural and functional genome evolution in a lineage (Fabaceae) with frequent intergenomic sequence transfers.

RESULTS: We integrated Illumina short-reads and PacBio CLR long-reads to assemble and annotate the complete mitochondrial genome of D. odorifera. The mitochondrial genome was organized as a single circular structure of 435 Kb in length containing 33 protein coding genes, 4 rRNA and 17 tRNA genes. Nearly 4.0% (17,386 bp) of the genome was annotated as repetitive DNA. From the sequence transfer analysis, it was found that 114 Kb of DNA originating from the mitochondrial genome has been transferred to the nuclear genome, with most of the transfer events having taken place relatively recently. The high frequency of sequence transfers from the mitochondria to the nuclear genome was similar to that of sequence transfer from the chloroplast to the nuclear genome.

CONCLUSION: For the first-time, the complete mitochondrial genome of D. odorifera was assembled in this study, which will provide a baseline resource in understanding genomic evolution in the highly specious Fabaceae. In particular, the assessment of intergenomic sequence transfer suggests that transfers have been common and recent indicating a possible role in environmental adaptation as has been found in other lineages. The high turnover rate of genomic colinearly and large differences in mitochondrial genome size found in the comparative analyses herein providing evidence for the rapid evolution of mitochondrial genome structure compared to chloroplasts in Faboideae. While phylogenetic analyses using functional genes indicate that mitochondrial genes are very slowly evolving compared to chloroplast genes.}, } @article {pmid34545138, year = {2021}, author = {Ruíz-Rivero, O and Garcia-Lor, A and Rojas-Panadero, B and Franco, JC and Khamis, FM and Kruger, K and Cifuentes, D and Bielza, P and Tena, A and Urbaneja, A and Pérez-Hedo, M}, title = {Insights into the origin of the invasive populations of Trioza erytreae in Europe using microsatellite markers and mtDNA barcoding approaches.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {18651}, pmid = {34545138}, issn = {2045-2322}, mesh = {Animals ; Citrus/chemistry ; DNA Barcoding, Taxonomic/methods ; DNA, Mitochondrial/*genetics ; Europe ; Hemiptera/*genetics ; Insect Vectors ; Introduced Species/trends ; Microsatellite Repeats/*genetics ; Mitochondria/genetics ; Phylogeny ; Plant Diseases ; }, abstract = {The African citrus psyllid Trioza erytreae is one of the major threats to citrus industry as the vector of the incurable disease known as huanglongbing (HLB) or citrus greening. The psyllid invaded the northwest of the Iberian Peninsula 6 years ago. The invasion alarmed citrus growers in the Mediterranean basin, the largest citrus producing area in Europe, which is still free of HLB. Before our study, no research had been carried out on the genetic diversity of T. erytreae populations that have invaded the Iberian Peninsula and the archipelagos of the Macaronesia (Madeira and the Canary Islands). In this study, combining microsatellites markers and mtDNA barcoding analysis, we characterize the genetic diversity, structure and maternal relationship of these new invasive populations of T. erytreae and those from Africa. Our results suggest that the outbreaks of T. erytreae in the Iberian Peninsula may have derived from the Canary Islands. The populations of T. erytreae that invaded Macaronesia and the Iberian Peninsula are likely to have originated from southern Africa. We anticipate our results to be a starting point for tracking the spread of this invasive pest outside of Africa and to be important for optimizing contingency and eradication plans in newly invaded and free areas.}, } @article {pmid34545486, year = {2022}, author = {O'Leary, BM and Oh, GGK and Millar, AH}, title = {High-Throughput Oxygen Consumption Measurements in Leaf Tissue Using Oxygen Sensitive Fluorophores.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2363}, number = {}, pages = {63-75}, pmid = {34545486}, issn = {1940-6029}, mesh = {Carbon Dioxide/metabolism ; Fluorescent Dyes/metabolism ; Ionophores ; Mitochondria/metabolism ; Oxygen/metabolism ; *Oxygen Consumption ; Plant Leaves ; }, abstract = {Respiratory rate measurements are crucial assays to understand mitochondrial biochemistry as well as metabolic regulation within tissues. Several technologies currently exist that can measure plant respiratory oxygen consumption or carbon dioxide evolution rates over short durations by either isolated mitochondria or plant tissues. Here we describe recently developed alternative methods for measuring tissue oxygen consumption rates (OCRs) using systems reliant on oxygen sensitive fluorophores. The methods described have distinct experimental advantages: they can allow high-throughput and long-duration measurements; and they are particularly suited to investigating the metabolic regulation of respiration by comparing OCRs among treatments or genotypes.}, } @article {pmid34547233, year = {2021}, author = {Trefts, E and Shaw, RJ}, title = {AMPK: restoring metabolic homeostasis over space and time.}, journal = {Molecular cell}, volume = {81}, number = {18}, pages = {3677-3690}, pmid = {34547233}, issn = {1097-4164}, support = {R01 DK080425/DK/NIDDK NIH HHS/United States ; R01 CA234047/CA/NCI NIH HHS/United States ; R35 CA220538/CA/NCI NIH HHS/United States ; F32 DK126418/DK/NIDDK NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; P01 CA120964/CA/NCI NIH HHS/United States ; R01 CA172229/CA/NCI NIH HHS/United States ; }, mesh = {AMP-Activated Protein Kinases/genetics/*metabolism ; Animals ; Cytoplasm/metabolism ; Energy Metabolism ; Homeostasis ; Humans ; Mitochondria/metabolism ; Protein Domains ; Signal Transduction ; Structure-Activity Relationship ; }, abstract = {The evolution of AMPK and its homologs enabled exquisite responsivity and control of cellular energetic homeostasis. Recent work has been critical in establishing the mechanisms that determine AMPK activity, novel targets of AMPK action, and the distribution of AMPK-mediated control networks across the cellular landscape. The role of AMPK as a hub of metabolic control has led to intense interest in pharmacologic activation as a therapeutic avenue for a number of disease states, including obesity, diabetes, and cancer. As such, critical work on the compartmentalization of AMPK, its downstream targets, and the systems it influences has progressed in recent years. The variegated distribution of AMPK-mediated control of metabolic homeostasis has revealed key insights into AMPK in normal biology and future directions for AMPK-based therapeutic strategies.}, } @article {pmid34555943, year = {2022}, author = {Lima-Silva, LF and Lee, J and Moraes-Vieira, PM}, title = {Soluble Carrier Transporters and Mitochondria in the Immunometabolic Regulation of Macrophages.}, journal = {Antioxidants & redox signaling}, volume = {36}, number = {13-15}, pages = {906-919}, pmid = {34555943}, issn = {1557-7716}, support = {K01 DK114162/DK/NIDDK NIH HHS/United States ; }, mesh = {Drug Delivery Systems ; *Macrophages/metabolism ; *Mitochondria ; }, abstract = {Significance: Immunometabolic regulation of macrophages is a growing area of research across many fields. Here, we review the contribution of solute carriers (SLCs) in regulating macrophage metabolism. We also highlight key mechanisms that regulate SLC function, their effects on mitochondrial activity, and how these intracellular activities contribute to macrophage fitness in health and disease. Recent Advances: SLCs serve as a major drug absorption pathway and represent a novel category of therapeutic drug targets. SLC dynamics affect cellular nutritional sensors, such as AMP-activated protein kinase and mammalian target of rapamycin, and consequently alter the cellular metabolism and mitochondrial dynamics within macrophages to adapt to a new functional phenotype. Critical Issues: SLC function affects macrophage phenotype, but their mechanisms of action and how their functions contribute to host health remain incompletely defined. Future Directions: Few studies focus on the impact of solute transporters on macrophage function. Identifying which SLCs are present in macrophages and determining their functional roles may reveal novel therapeutic targets with which to treat metabolic and inflammatory diseases. Antioxid. Redox Signal. 36, 906-919.}, } @article {pmid34563127, year = {2021}, author = {Deng, J and Assandri, G and Chauhan, P and Futahashi, R and Galimberti, A and Hansson, B and Lancaster, LT and Takahashi, Y and Svensson, EI and Duplouy, A}, title = {Wolbachia-driven selective sweep in a range expanding insect species.}, journal = {BMC ecology and evolution}, volume = {21}, number = {1}, pages = {181}, pmid = {34563127}, issn = {2730-7182}, mesh = {Animals ; Cyprus ; *DNA, Mitochondrial/genetics ; Female ; Genetic Variation ; Odonata/*genetics/*microbiology ; Phylogeny ; *Wolbachia ; }, abstract = {BACKGROUND: Evolutionary processes can cause strong spatial genetic signatures, such as local loss of genetic diversity, or conflicting histories from mitochondrial versus nuclear markers. Investigating these genetic patterns is important, as they may reveal obscured processes and players. The maternally inherited bacterium Wolbachia is among the most widespread symbionts in insects. Wolbachia typically spreads within host species by conferring direct fitness benefits, and/or by manipulating its host reproduction to favour infected over uninfected females. Under sufficient selective advantage, the mitochondrial haplotype associated with the favoured maternally-inherited symbiotic strains will spread (i.e. hitchhike), resulting in low mitochondrial genetic variation across the host species range.

METHOD: The common bluetail damselfly (Ischnura elegans: van der Linden, 1820) has recently emerged as a model organism for genetics and genomic signatures of range expansion during climate change. Although there is accumulating data on the consequences of such expansion on the genetics of I. elegans, no study has screened for Wolbachia in the damselfly genus Ischnura. Here, we present the biogeographic variation in Wolbachia prevalence and penetrance across Europe and Japan (including samples from 17 populations), and from close relatives in the Mediterranean area (i.e. I. genei: Rambur, 1842; and I. saharensis: Aguesse, 1958).

RESULTS: Our data reveal (a) multiple Wolbachia-strains, (b) potential transfer of the symbiont through hybridization, (c) higher infection rates at higher latitudes, and (d) reduced mitochondrial diversity in the north-west populations, indicative of hitchhiking associated with the selective sweep of the most common strain. We found low mitochondrial haplotype diversity in the Wolbachia-infected north-western European populations (Sweden, Scotland, the Netherlands, Belgium, France and Italy) of I. elegans, and, conversely, higher mitochondrial diversity in populations with low penetrance of Wolbachia (Ukraine, Greece, Montenegro and Cyprus). The timing of the selective sweep associated with infected lineages was estimated between 20,000 and 44,000 years before present, which is consistent with the end of the last glacial period about 20,000 years.

CONCLUSIONS: Our findings provide an example of how endosymbiont infections can shape spatial variation in their host evolutionary genetics during postglacial expansion. These results also challenge population genetic studies that do not consider the prevalence of symbionts in many insects, which we show can impact geographic patterns of mitochondrial genetic diversity.}, } @article {pmid34565318, year = {2021}, author = {Baleva, MV and Piunova, UE and Chicherin, IV and Krasavina, DG and Levitskii, SA and Kamenski, PA}, title = {Yeast Translational Activator Mss51p and Human ZMYND17 - Two Proteins with a Common Origin, but Different Functions.}, journal = {Biochemistry. Biokhimiia}, volume = {86}, number = {9}, pages = {1151-1161}, doi = {10.1134/S0006297921090108}, pmid = {34565318}, issn = {1608-3040}, mesh = {Electron Transport Complex IV/metabolism ; Evolution, Molecular ; Gene Editing ; HeLa Cells ; Humans ; Mitochondria/enzymology/metabolism ; NADH Dehydrogenase/metabolism ; Phylogeny ; Protein Subunits/metabolism ; Proton-Translocating ATPases/metabolism ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/classification/genetics/*metabolism ; Transcription Factors/classification/deficiency/genetics/*metabolism ; RNA, Guide, CRISPR-Cas Systems ; }, abstract = {Despite its similarity to protein biosynthesis in bacteria, translation in the mitochondria of modern eukaryotes has several unique features, such as the necessity for coordination of translation of mitochondrial mRNAs encoding proteins of the electron transport chain complexes with translation of other protein components of these complexes in the cytosol. In the mitochondria of baker's yeast Saccharomyces cerevisiae, this coordination is carried out by a system of translational activators that predominantly interact with the 5'-untranslated regions of mitochondrial mRNAs. No such system has been found in human mitochondria, except a single identified translational activator, TACO1. Here, we studied the role of the ZMYND17 gene, an ortholog of the yeast gene for the translational activator Mss51p, on the mitochondrial translation in human cells. Deletion of the ZMYND17 gene did not affect translation in the mitochondria, but led to the decrease in the cytochrome c oxidase activity and increase in the amount of free F1 subunit of ATP synthase. We also investigated the evolutionary history of Mss51p and ZMYND17 and suggested a possible mechanism for the divergence of functions of these orthologous proteins.}, } @article {pmid34565456, year = {2021}, author = {Bunmee, K and Thaenkham, U and Saralamba, N and Ponlawat, A and Zhong, D and Cui, L and Sattabongkot, J and Sriwichai, P}, title = {Population genetic structure of the malaria vector Anopheles minimus in Thailand based on mitochondrial DNA markers.}, journal = {Parasites & vectors}, volume = {14}, number = {1}, pages = {496}, pmid = {34565456}, issn = {1756-3305}, support = {U19AI089672/NH/NIH HHS/United States ; D43 TW006571/TW/FIC NIH HHS/United States ; D43TW006571/NH/NIH HHS/United States ; U19 AI089672/AI/NIAID NIH HHS/United States ; P0108_19_AF_06.01//Armed Forces Health Surveillance Branch/ ; }, mesh = {Animals ; Anopheles/classification/*genetics/physiology ; Cytochromes b/genetics ; Electron Transport Complex IV/genetics/metabolism ; Gene Flow ; Genetic Markers ; Insect Proteins/*genetics ; Malaria/*transmission ; Mitochondria/*genetics ; Mosquito Vectors/classification/*genetics/physiology ; Phylogeny ; Thailand ; }, abstract = {BACKGROUND: The malaria vector Anopheles minimus has been influenced by external stresses affecting the survival rate and vectorial capacity of the population. Since An. minimus habitats have continuously undergone ecological changes, this study aimed to determine the population genetic structure and the potential gene flow among the An. minimus populations in Thailand.

METHODS: Anopheles minimus was collected from five malaria transmission areas in Thailand using Centers for Disease Control and Prevention (CDC) light traps. Seventy-nine females from those populations were used as representative samples. The partial mitochondrial cytochrome c oxidase subunit I (COI), cytochrome c oxidase subunit II (COII) and cytochrome b (Cytb) gene sequences were amplified and analyzed to identify species and determine the current population genetic structure. For the past population, we determined the population genetic structure from the 60 deposited COII sequences in GenBank of An. minimus collected from Thailand 20 years ago.

RESULTS: The current populations of An. minimus were genetically divided into two lineages, A and B. Lineage A has high haplotype diversity under gene flow similar to the population in the past. Neutrality tests suggested population expansion of An. minimus, with the detection of abundant rare mutations in all populations, which tend to arise from negative selection.

CONCLUSIONS: This study revealed that the population genetic structure of An. minimus lineage A was similar between the past and present populations, indicating high adaptability of the species. There was substantial gene flow between the eastern and western An. minimus populations without detection of significant gene flow barriers.}, } @article {pmid34577183, year = {2021}, author = {Koumpoura, CL and Robert, A and Athanassopoulos, CM and Baltas, M}, title = {Antimalarial Inhibitors Targeting Epigenetics or Mitochondria in Plasmodium falciparum: Recent Survey upon Synthesis and Biological Evaluation of Potential Drugs against Malaria.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {18}, pages = {}, pmid = {34577183}, issn = {1420-3049}, mesh = {Animals ; Antimalarials/*chemistry/pharmacology ; DNA/chemistry ; Dihydroorotate Dehydrogenase ; Drug Discovery ; Drug Resistance ; Enzyme Inhibitors/chemistry/pharmacology ; Epigenesis, Genetic ; Histone Deacetylases/metabolism ; Humans ; Malaria, Falciparum/*drug therapy ; Methyltransferases/antagonists & inhibitors ; Mitochondria/*metabolism ; Oxidoreductases Acting on CH-CH Group Donors/antagonists & inhibitors ; Plasmodium falciparum/*drug effects ; Quinazolines/chemistry/pharmacology ; Signal Transduction ; Structure-Activity Relationship ; }, abstract = {Despite many efforts, malaria remains among the most problematic infectious diseases worldwide, mainly due to the development of drug resistance by P. falciparum. Over the past decade, new essential pathways have been emerged to fight against malaria. Among them, epigenetic processes and mitochondrial metabolism appear to be important targets. This review will focus on recent evolutions concerning worldwide efforts to conceive, synthesize and evaluate new drug candidates interfering selectively and efficiently with these two targets and pathways. The focus will be on compounds/scaffolds that possess biological/pharmacophoric properties on DNA methyltransferases and HDAC's for epigenetics, and on cytochrome bc1 and dihydroorotate dehydrogenase for mitochondrion.}, } @article {pmid34582890, year = {2021}, author = {Weerth, RS and Medlock, AE and Dailey, HA}, title = {Ironing out the distribution of [2Fe-2S] motifs in ferrochelatases.}, journal = {The Journal of biological chemistry}, volume = {297}, number = {5}, pages = {101017}, pmid = {34582890}, issn = {1083-351X}, support = {R01 DK111653/DK/NIDDK NIH HHS/United States ; }, mesh = {*Actinobacteria/chemistry/genetics ; Amino Acid Motifs ; *Bacterial Proteins/chemistry/genetics ; *Ferrochelatase/chemistry/genetics ; Heme/chemistry/genetics ; Iron/*chemistry ; Sulfur/*chemistry ; }, abstract = {Heme, a near ubiquitous cofactor, is synthesized by most organisms. The essential step of insertion of iron into the porphyrin macrocycle is mediated by the enzyme ferrochelatase. Several ferrochelatases have been characterized, and it has been experimentally shown that a fraction of them contain [2Fe-2S] clusters. It has been suggested that all metazoan ferrochelatases have such clusters, but among bacteria, these clusters have been most commonly identified in Actinobacteria and a few other bacteria. Despite this, the function of the [2Fe-2S] cluster remains undefined. With the large number of sequenced genomes currently available, we comprehensively assessed the distribution of putative [2Fe-2S] clusters throughout the ferrochelatase protein family. We discovered that while rare within the bacterial ferrochelatase family, this cluster is prevalent in a subset of phyla. Of note is that genomic data show that the cluster is not common in Actinobacteria, as is currently thought based on the small number of actinobacterial ferrochelatases experimentally examined. With available physiological data for each genome included, we identified a correlation between the presence of the microbial cluster and aerobic metabolism. Additionally, our analysis suggests that Firmicute ferrochelatases are the most ancient and evolutionarily preceded the Alphaproteobacterial precursor to eukaryotic mitochondria. These findings shed light on distribution and evolution of the [2Fe-2S] cluster in ferrochelatases and will aid in determining the function of the cluster in heme synthesis.}, } @article {pmid34583583, year = {2021}, author = {Fenton, A and Camus, MF and Hurst, GDD}, title = {Positive selection on mitochondria may eliminate heritable microbes from arthropod populations.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1959}, pages = {20211735}, pmid = {34583583}, issn = {1471-2954}, mesh = {Animals ; *Arthropods/genetics ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Mitochondria/genetics ; Symbiosis ; }, abstract = {Diverse eukaryotic taxa carry facultative heritable symbionts, microbes that are passed from mother to offspring. These symbionts are coinherited with mitochondria, and selection favouring either new symbionts, or new symbiont variants, is known to drive loss of mitochondrial diversity as a correlated response. More recently, evidence has accumulated of episodic directional selection on mitochondria, but with currently unknown consequences for symbiont evolution. We therefore employed a population genetic mean field framework to model the impact of selection on mitochondrial DNA (mtDNA) upon symbiont frequency for three generic scenarios of host-symbiont interaction. Our models predict that direct selection on mtDNA can drive symbionts out of the population where a positively selected mtDNA mutation occurs initially in an individual that is uninfected with the symbiont, and the symbiont is initially at low frequency. When, by contrast, the positively selected mtDNA mutation occurs in a symbiont-infected individual, the mutation becomes fixed and in doing so removes symbiont variation from the population. We conclude that the molecular evolution of symbionts and mitochondria, which has previously been viewed from a perspective of selection on symbionts driving the evolution of a neutral mtDNA marker, should be reappraised in the light of positive selection on mtDNA.}, } @article {pmid34585988, year = {2021}, author = {Turra, GL and Liedgens, L and Sommer, F and Schneider, L and Zimmer, D and Vilurbina Perez, J and Koncarevic, S and Schroda, M and Mühlhaus, T and Deponte, M}, title = {In Vivo Structure-Function Analysis and Redox Interactomes of Leishmania tarentolae Erv.}, journal = {Microbiology spectrum}, volume = {9}, number = {2}, pages = {e0080921}, pmid = {34585988}, issn = {2165-0497}, mesh = {CRISPR-Cas Systems/genetics ; Leishmania/classification/genetics/*metabolism ; Mitochondria/*metabolism ; Mitochondrial Precursor Protein Import Complex Proteins/*metabolism ; Oxidation-Reduction ; Oxidoreductases Acting on Sulfur Group Donors/*metabolism ; Protein Domains/genetics ; Protein Folding ; Protein Transport/genetics ; Structure-Activity Relationship ; }, abstract = {Import and oxidative folding of proteins in the mitochondrial intermembrane space differ among eukaryotic lineages. While opisthokonts such as yeast rely on the receptor and oxidoreductase Mia40 in combination with the Mia40:cytochrome c oxidoreductase Erv, kinetoplastid parasites and other Excavata/Discoba lack Mia40 but have a functional Erv homologue. Whether excavate Erv homologues rely on a Mia40 replacement or directly interact with imported protein substrates remains controversial. Here, we used the CRISPR-Cas9 system to generate a set of tagged and untagged homozygous mutants of LTERV from the kinetoplastid model parasite Leishmania tarentolae. Modifications of the shuttle cysteine motif of LtErv were lethal, whereas replacement of clamp residue Cys[17] or removal of the kinetoplastida-specific second (KISS) domain had no impact on parasite viability under standard growth conditions. However, removal of the KISS domain rendered parasites sensitive to heat stress and led to the accumulation of homodimeric and mixed LtErv disulfides. We therefore determined and compared the redox interactomes of tagged wild-type LtErv and LtErv[ΔKISS] using stable isotope labeling by amino acids in cell culture (SILAC) and quantitative mass spectrometry. While the Mia40-replacement candidate Mic20 and all but one typical substrate with twin Cx3/9C-motifs were absent in both redox interactomes, we identified a small set of alternative potential interaction partners with putative redox-active cysteine residues. In summary, our study reveals parasite-specific intracellular structure-function relationships and redox interactomes of LtErv with implications for current hypotheses on mitochondrial protein import in nonopisthokonts. IMPORTANCE The discovery of the redox proteins Mia40/CHCHD4 and Erv1/ALR, as well as the elucidation of their relevance for oxidative protein folding in the mitochondrial intermembrane space of yeast and mammals, founded a new research topic in redox biology and mitochondrial protein import. The lack of Mia40/CHCHD4 in protist lineages raises fundamental and controversial questions regarding the conservation and evolution of this essential pathway. Do protist Erv homologues act alone, or do they use the candidate Mic20 or another protein as a Mia40 replacement? Furthermore, we previously showed that Erv homologues in L. tarentolae and the human pathogen L. infantum are not only essential but also differ structurally and mechanistically from yeast and human Erv1/ALR. Here, we analyzed the relevance of such structural differences in vivo and determined the first redox interactomes of a nonopisthokont Erv homologue. Our data challenge recent hypotheses on mitochondrial protein import in nonopisthokonts.}, } @article {pmid34592348, year = {2022}, author = {Li, Y and Wang, S and Zhou, J and Li, T and Jiang, K and Zhang, Y and Zheng, C and Liang, J and Bu, W}, title = {The phylogenic position of aschiphasmatidae in euphasmatodea based on mitochondrial genomic evidence.}, journal = {Gene}, volume = {808}, number = {}, pages = {145974}, doi = {10.1016/j.gene.2021.145974}, pmid = {34592348}, issn = {1879-0038}, mesh = {Animals ; Base Sequence/genetics ; Gene Order/genetics ; Gene Rearrangement/genetics ; Genome, Mitochondrial/*genetics ; Genomics/methods ; Mitochondria/*genetics ; Nematoda/*genetics ; Neoptera/genetics ; Phylogeny ; }, abstract = {The mitochondrial genome (mitogenome) has been regarded as significant source of data to better understand the phylogenetic relationships within the Euphasmatodea, but no mitogenome in Aschiphasmatoidea has been sequenced to date. In this study, two mitogenomes of Orthomeria smaragdinum and Nanhuaphasma hamicercum of Aschiphasmatidae were sequenced and annotated for the first time. The same mitochondrial gene rearrangement structure was present in the two mitogenomes sequenced, showing as the translocation of tRNA-Arg and tRNA-Asn, which conformed to the tandem duplication-random loss and could be used as a possible synapomorphy for Aschiphasmatidae. The phylogenetic results based on the maximum likelihood (ML) and bayesian inference (BI) methods both showed that Aschiphasmatidae and Neophasmatodea in Euphasmatodea are sister taxa. Although the monophyly of Oriophasmata, Occidophasmata, Diapheromeridae, Phasmatidae, Lonchodidae and Bacilloidea has not been solved, the monophyly of Neophasmatodea and Phyllioidea was well supported.}, } @article {pmid34599203, year = {2021}, author = {Klink, GV and O'Keefe, H and Gogna, A and Bazykin, GA and Elson, JL}, title = {A broad comparative genomics approach to understanding the pathogenicity of Complex I mutations.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {19578}, pmid = {34599203}, issn = {2045-2322}, mesh = {Alleles ; Amino Acid Substitution ; Electron Transport Complex I/*genetics/metabolism ; *Genetic Predisposition to Disease ; Genome-Wide Association Study ; *Genomics/methods ; Humans ; Mitochondria/*genetics/metabolism ; *Mutation ; Phylogeny ; Selection, Genetic ; }, abstract = {Disease caused by mutations of mitochondrial DNA (mtDNA) are highly variable in both presentation and penetrance. Over the last 30 years, clinical recognition of this group of diseases has increased. It has been suggested that haplogroup background could influence the penetrance and presentation of disease-causing mutations; however, to date there is only one well-established example of such an effect: the increased penetrance of two Complex I Leber's hereditary optic neuropathy mutations on a haplogroup J background. This paper conducts the most extensive investigation to date into the importance of haplogroup context in the pathogenicity of mtDNA mutations in Complex I. We searched for proven human point mutations across more than 900 metazoans finding human disease-causing mutations and potential masking variants. We found more than a half of human pathogenic variants as compensated pathogenic deviations (CPD) in at least in one animal species from our multiple sequence alignments. Some variants were found in many species, and some were even the most prevalent amino acids across our dataset. Variants were also found in other primates, and in such cases, we looked for non-human amino acids in sites with high probability to interact with the CPD in folded protein. Using this "local interactions" approach allowed us to find potential masking substitutions in other amino acid sites. We suggest that the masking variants might arise in humans, resulting in variability of mutation effect in our species.}, } @article {pmid34600050, year = {2022}, author = {Yu, X and Yang, H and Liu, J and Qi, Y and Sun, L and Tian, X}, title = {A strategy for a high enrichment of insect mitochondrial DNA for mitogenomic analysis.}, journal = {Gene}, volume = {808}, number = {}, pages = {145986}, doi = {10.1016/j.gene.2021.145986}, pmid = {34600050}, issn = {1879-0038}, mesh = {Animals ; DNA, Mitochondrial/*genetics/*isolation & purification ; Genome, Insect/genetics ; Genome, Mitochondrial/genetics ; Genomics ; High-Throughput Nucleotide Sequencing/methods ; Insecta/*genetics ; Mitochondria/genetics ; Phylogeny ; Sequence Analysis, DNA/methods ; }, abstract = {Next-generation sequencing has dramatically fostered insect mitogenomic research in recent years. However, studies on the insect mitochondrial genome (mitogenome) assembly mainly rely on the sequencing data from total DNA, which is not cost-effective as a huge data from nuclear DNA are wasted. Besides, many mitogenomic studies require genomic information from individual organisms, whereas the DNA yield from small individual insects is too low to meet the sequencing requirements. Here, we describe a strategy for a high enrichment of insect mitochondrial DNA (mtDNA) using rolling circle amplification (RCA) technique. This strategy consists of standard DNA extraction, RCA enrichment, next-generation sequencing and mitogenome assembly. We have evaluated the performance of this strategy on nine insect species representing eight families of insecta, three other invertebrates, and even two vertebrate specimens. Results show that our strategy is especially suitable for insects, which allows almost all tested insect mtDNA contents to reach 80% and above. A further examination of enrichment efficiency of our strategy among different taxa shows that it is also applicable to other invertebrates and even some vertebrates such as Rhacophorus and ptyas species, although its enrichment efficiency in these groups is lower than that of insects. After treatment with our strategy, small flux sequencing data can realize the assembly of mitogenome with deep coverage, providing a solid base for subsequent mitogenome-based studies.}, } @article {pmid34600156, year = {2021}, author = {Sahebnasagh, A and Hashemi, J and Khoshi, A and Saghafi, F and Avan, R and Faramarzi, F and Azimi, S and Habtemariam, S and Sureda, A and Khayatkashani, M and Safdari, M and Rezai Ghaleno, H and Soltani, H and Khayat Kashani, HR}, title = {Aromatic hydrocarbon receptors in mitochondrial biogenesis and function.}, journal = {Mitochondrion}, volume = {61}, number = {}, pages = {85-101}, doi = {10.1016/j.mito.2021.09.012}, pmid = {34600156}, issn = {1872-8278}, mesh = {Animals ; Cell Cycle ; Evolution, Molecular ; Humans ; Mitochondria/genetics/*metabolism ; Mitogen-Activated Protein Kinases/genetics/metabolism ; *Organelle Biogenesis ; }, abstract = {Mitochondria are ubiquitous membrane-bound organelles that not only play a key role in maintaining cellular energy homeostasis and metabolism but also in signaling and apoptosis. Aryl hydrocarbons receptors (AhRs) are ligand-activated transcription factors that recognize a wide variety of xenobiotics, including polyaromatic hydrocarbons and dioxins, and activate diverse detoxification pathways. These receptors are also activated by natural dietary compounds and endogenous metabolites. In addition, AhRs can modulate the expression of a diverse array of genes related to mitochondrial biogenesis and function. The aim of the present review is to analyze scientific data available on the AhR signaling pathway and its interaction with the intracellular signaling pathways involved in mitochondrial functions, especially those related to cell cycle progression and apoptosis. Various evidence have reported the crosstalk between the AhR signaling pathway and the nuclear factor κB (NF-κB), tyrosine kinase receptor signaling and mitogen-activated protein kinases (MAPKs). The AhR signaling pathway seems to promote cell cycle progression in the absence of exogenous ligands, whereas the presence of exogenous ligands induces cell cycle arrest. However, its effects on apoptosis are controversial since activation or overexpression of AhR has been observed to induce or inhibit apoptosis depending on the cell type. Regarding the mitochondria, although activation by endogenous ligands is related to mitochondrial dysfunction, the effects of endogenous ligands are not well understood but point towards antiapoptotic effects and inducers of mitochondrial biogenesis.}, } @article {pmid34603395, year = {2021}, author = {Rodríguez, E and Grover Thomas, F and Camus, MF and Lane, N}, title = {Mitonuclear Interactions Produce Diverging Responses to Mild Stress in Drosophila Larvae.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {734255}, pmid = {34603395}, issn = {1664-8021}, abstract = {Mitochondrial function depends on direct interactions between respiratory proteins encoded by genes in two genomes, mitochondrial and nuclear, which evolve in very different ways. Serious incompatibilities between these genomes can have severe effects on development, fitness and viability. The effect of subtle mitonuclear mismatches has received less attention, especially when subject to mild physiological stress. Here, we investigate how two distinct physiological stresses, metabolic stress (high-protein diet) and redox stress [the glutathione precursor N-acetyl cysteine (NAC)], affect development time, egg-to-adult viability, and the mitochondrial physiology of Drosophila larvae with an isogenic nuclear background set against three mitochondrial DNA (mtDNA) haplotypes: one coevolved (WT) and two slightly mismatched (COX and BAR). Larvae fed the high-protein diet developed faster and had greater viability in all haplotypes. The opposite was true of NAC-fed flies, especially those with the COX haplotype. Unexpectedly, the slightly mismatched BAR larvae developed fastest and were the most viable on both treatments, as well as control diets. These changes in larval development were linked to a shift to complex I-driven mitochondrial respiration in all haplotypes on the high-protein diet. In contrast, NAC increased respiration in COX larvae but drove a shift toward oxidation of proline and succinate. The flux of reactive oxygen species was increased in COX larvae treated with NAC and was associated with an increase in mtDNA copy number. Our results support the notion that subtle mitonuclear mismatches can lead to diverging responses to mild physiological stress, undermining fitness in some cases, but surprisingly improving outcomes in other ostensibly mismatched fly lines.}, } @article {pmid34610767, year = {2021}, author = {Evans, BJ and Peter, BM and Melnick, DJ and Andayani, N and Supriatna, J and Zhu, J and Tosi, AJ}, title = {Mitonuclear interactions and introgression genomics of macaque monkeys (Macaca) highlight the influence of behaviour on genome evolution.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1960}, pages = {20211756}, pmid = {34610767}, issn = {1471-2954}, mesh = {Animals ; Evolution, Molecular ; Female ; *Genome, Mitochondrial ; Genomics ; Haplorhini ; *Macaca/genetics ; Male ; }, abstract = {In most macaques, females are philopatric and males migrate from their natal ranges, which results in pronounced divergence of mitochondrial genomes within and among species. We therefore predicted that some nuclear genes would have to acquire compensatory mutations to preserve compatibility with diverged interaction partners from the mitochondria. We additionally expected that these sex-differences would have distinctive effects on gene flow in the X and autosomes. Using new genomic data from 29 individuals from eight species of Southeast Asian macaque, we identified evidence of natural selection associated with mitonuclear interactions, including extreme outliers of interspecies differentiation and metrics of positive selection, low intraspecies polymorphism and atypically long runs of homozygosity associated with nuclear-encoded genes that interact with mitochondria-encoded genes. In one individual with introgressed mitochondria, we detected a small but significant enrichment of autosomal introgression blocks from the source species of her mitochondria that contained genes which interact with mitochondria-encoded loci. Our analyses also demonstrate that sex-specific demography sculpts genetic exchange across multiple species boundaries. These findings show that behaviour can have profound but indirect effects on genome evolution by influencing how interacting components of different genomic compartments (mitochondria, the autosomes and the sex chromosomes) move through time and space.}, } @article {pmid34614167, year = {2021}, author = {Sanchez-Contreras, M and Sweetwyne, MT and Kohrn, BF and Tsantilas, KA and Hipp, MJ and Schmidt, EK and Fredrickson, J and Whitson, JA and Campbell, MD and Rabinovitch, PS and Marcinek, DJ and Kennedy, SR}, title = {A replication-linked mutational gradient drives somatic mutation accumulation and influences germline polymorphisms and genome composition in mitochondrial DNA.}, journal = {Nucleic acids research}, volume = {49}, number = {19}, pages = {11103-11118}, pmid = {34614167}, issn = {1362-4962}, support = {T32 AG066574/AG/NIA NIH HHS/United States ; T32 AG000057/AG/NIA NIH HHS/United States ; R21 HG011229/HG/NHGRI NIH HHS/United States ; R21 DK128540/DK/NIDDK NIH HHS/United States ; K01 AG062757/AG/NIA NIH HHS/United States ; R21 CA259780/CA/NCI NIH HHS/United States ; P01 AG001751/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*genetics/metabolism ; Animals ; Chromosome Mapping ; DNA Polymerase gamma/deficiency/genetics ; *DNA Replication ; DNA, Mitochondrial/*genetics/metabolism ; Genetic Speciation ; *Genome, Mitochondrial ; *Germ-Line Mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria/*genetics/metabolism ; *Mutation Accumulation ; Mutation Rate ; Polymorphism, Single Nucleotide ; }, abstract = {Mutations in mitochondrial DNA (mtDNA) cause maternally inherited diseases, while somatic mutations are linked to common diseases of aging. Although mtDNA mutations impact health, the processes that give rise to them are under considerable debate. To investigate the mechanism by which de novo mutations arise, we analyzed the distribution of naturally occurring somatic mutations across the mouse and human mtDNA obtained by Duplex Sequencing. We observe distinct mutational gradients in G→A and T→C transitions delimited by the light-strand origin and the mitochondrial Control Region (mCR). The gradient increases unequally across the mtDNA with age and is lost in the absence of DNA polymerase γ proofreading activity. In addition, high-resolution analysis of the mCR shows that important regulatory elements exhibit considerable variability in mutation frequency, consistent with them being mutational 'hot-spots' or 'cold-spots'. Collectively, these patterns support genome replication via a deamination prone asymmetric strand-displacement mechanism as the fundamental driver of mutagenesis in mammalian DNA. Moreover, the distribution of mtDNA single nucleotide polymorphisms in humans and the distribution of bases in the mtDNA across vertebrate species mirror this gradient, indicating that replication-linked mutations are likely the primary source of inherited polymorphisms that, over evolutionary timescales, influences genome composition during speciation.}, } @article {pmid34616376, year = {2021}, author = {Lin, R and Xia, Y and Liu, Y and Zhang, D and Xiang, X and Niu, X and Jiang, L and Wang, X and Zheng, A}, title = {Comparative Mitogenomic Analysis and the Evolution of Rhizoctonia solani Anastomosis Groups.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {707281}, pmid = {34616376}, issn = {1664-302X}, abstract = {Mitochondria are the major energy source for cell functions. However, for the plant fungal pathogens, mitogenome variations and their roles during the host infection processes remain largely unknown. Rhizoctonia solani, an important soil-borne pathogen, forms different anastomosis groups (AGs) and adapts to a broad range of hosts in nature. Here, we reported three complete mitogenomes of AG1-IA RSIA1, AG1-IB RSIB1, and AG1-IC, and performed a comparative analysis with nine published Rhizoctonia mitogenomes (AG1-IA XN, AG1-IB 7/3/14, AG3, AG4, and five Rhizoctonia sp. mitogenomes). These mitogenomes encoded 15 typical proteins (cox1-3, cob, atp6, atp8-9, nad1-6, nad4L, and rps3) and several LAGLIDADG/GIY-YIG endonucleases with sizes ranging from 109,017 bp (Rhizoctonia sp. SM) to 235,849 bp (AG3). We found that their large sizes were mainly contributed by repeat sequences and genes encoding endonucleases. We identified the complete sequence of the rps3 gene in 10 Rhizoctonia mitogenomes, which contained 14 positively selected sites. Moreover, we inferred a robust maximum-likelihood phylogeny of 32 Basidiomycota mitogenomes, representing that seven R. solani and other five Rhizoctonia sp. lineages formed two parallel branches in Agaricomycotina. The comparative analysis showed that mitogenomes of Basidiomycota pathogens had high GC content and mitogenomes of R. solani had high repeat content. Compared to other strains, the AG1-IC strain had low substitution rates, which may affect its mitochondrial phylogenetic placement in the R. solani clade. Additionally, with the published RNA-seq data, we investigated gene expression patterns from different AGs during host infection stages. The expressed genes from AG1-IA (host: rice) and AG3 (host: potato) mainly formed four groups by k-mean partitioning analysis. However, conserved genes represented varied expression patterns, and only the patterns of rps3-nad2 and nad1-m3g18/mag28 (an LAGLIDADG endonuclease) were conserved in AG1-IA and AG3 as shown by the correlation coefficient analysis, suggesting regulation of gene repertoires adapting to infect varied hosts. The results of variations in mitogenome characteristics and the gene substitution rates and expression patterns may provide insights into the evolution of R. solani mitogenomes.}, } @article {pmid34618964, year = {2020}, author = {Soto Gomez, M and Lin, Q and da Silva Leal, E and Gallaher, TJ and Scherberich, D and Mennes, CB and Smith, SY and Graham, SW}, title = {A bi-organellar phylogenomic study of Pandanales: inference of higher-order relationships and unusual rate-variation patterns.}, journal = {Cladistics : the international journal of the Willi Hennig Society}, volume = {36}, number = {5}, pages = {481-504}, doi = {10.1111/cla.12417}, pmid = {34618964}, issn = {1096-0031}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Genes, Plant ; *Genome, Mitochondrial ; *Genome, Plastid ; Magnoliopsida/*classification/*genetics ; Mitochondria/genetics ; Phylogeny ; Plastids/genetics ; }, abstract = {We used a bi-organellar phylogenomic approach to address higher-order relationships in Pandanales, including the first molecular phylogenetic study of the panama-hat family, Cyclanthaceae. Our genus-level study of plastid and mitochondrial gene sets includes a comprehensive sampling of photosynthetic lineages across the order, and provides a framework for investigating clade ages, biogeographic hypotheses and organellar molecular evolution. Using multiple inference methods and both organellar genomes, we recovered mostly congruent and strongly supported relationships within and between families, including the placement of fully mycoheterotrophic Triuridaceae. Cyclanthaceae and Pandanaceae plastomes have slow substitution rates, contributing to weakly supported plastid-based relationships in Cyclanthaceae. While generally slowly evolving, mitochondrial genomes exhibit sporadic rate elevation across the order. However, we infer well-supported relationships even for slower evolving mitochondrial lineages in Cyclanthaceae. Clade age estimates across photosynthetic lineages are largely consistent with previous studies, are well correlated between the two organellar genomes (with slightly younger inferences from mitochondrial data), and support several biogeographic hypotheses. We show that rapidly evolving non-photosynthetic lineages may bias age estimates upwards at neighbouring photosynthetic nodes, even using a relaxed clock model. Finally, we uncovered new genome structural variants in photosynthetic taxa at plastid inverted repeat boundaries that show promise as interfamilial phylogenetic markers.}, } @article {pmid34626646, year = {2021}, author = {Latimer, S and Keene, SA and Stutts, LR and Berger, A and Bernert, AC and Soubeyrand, E and Wright, J and Clarke, CF and Block, AK and Colquhoun, TA and Elowsky, C and Christensen, A and Wilson, MA and Basset, GJ}, title = {A dedicated flavin-dependent monooxygenase catalyzes the hydroxylation of demethoxyubiquinone into ubiquinone (coenzyme Q) in Arabidopsis.}, journal = {The Journal of biological chemistry}, volume = {297}, number = {5}, pages = {101283}, pmid = {34626646}, issn = {1083-351X}, support = {R01 GM139978/GM/NIGMS NIH HHS/United States ; RF1 AG061566/AG/NIA NIH HHS/United States ; }, mesh = {*Arabidopsis/enzymology/genetics ; *Arabidopsis Proteins/genetics/metabolism ; *Mitochondria/enzymology/genetics ; *Mixed Function Oxygenases/genetics/metabolism ; *Phylogeny ; *Ubiquinone/genetics/metabolism ; }, abstract = {Ubiquinone (Coenzyme Q) is a vital respiratory cofactor and liposoluble antioxidant. In plants, it is not known how the C-6 hydroxylation of demethoxyubiquinone, the penultimate step in ubiquinone biosynthesis, is catalyzed. The combination of cross-species gene network modeling along with mining of embryo-defective mutant databases of Arabidopsis thaliana identified the embryo lethal locus EMB2421 (At1g24340) as a top candidate for the missing plant demethoxyubiquinone hydroxylase. In marked contrast with prototypical eukaryotic demethoxyubiquinone hydroxylases, the catalytic mechanism of which depends on a carboxylate-bridged di-iron domain, At1g24340 is homologous to FAD-dependent oxidoreductases that instead use NAD(P)H as an electron donor. Complementation assays in Saccharomyces cerevisiae and Escherichia coli demonstrated that At1g24340 encodes a functional demethoxyubiquinone hydroxylase and that the enzyme displays strict specificity for the C-6 position of the benzoquinone ring. Laser-scanning confocal microscopy also showed that GFP-tagged At1g24340 is targeted to mitochondria. Silencing of At1g24340 resulted in 40 to 74% decrease in ubiquinone content and de novo ubiquinone biosynthesis. Consistent with the role of At1g24340 as a benzenoid ring modification enzyme, this metabolic blockage could not be bypassed by supplementation with 4-hydroxybenzoate, the immediate precursor of ubiquinone's ring. Unlike in yeast, in Arabidopsis overexpression of demethoxyubiquinone hydroxylase did not boost ubiquinone content. Phylogenetic reconstructions indicated that plant demethoxyubiquinone hydroxylase is most closely related to prokaryotic monooxygenases that act on halogenated aromatics and likely descends from an event of horizontal gene transfer between a green alga and a bacterium.}, } @article {pmid34633451, year = {2022}, author = {Valera-Calero, JA and Úbeda-D'Ocasar, E and Caballero-Corella, M and Fernández-de-Las-Peñas, C and Sendarrubias, GMG and Arias-Buría, JL}, title = {Cervical Multifidus Morphology and Quality Are Not Associated with Clinical Variables in Women with Fibromyalgia: An Observational Study.}, journal = {Pain medicine (Malden, Mass.)}, volume = {23}, number = {6}, pages = {1138-1143}, doi = {10.1093/pm/pnab297}, pmid = {34633451}, issn = {1526-4637}, mesh = {Cervical Vertebrae/diagnostic imaging ; Female ; *Fibromyalgia/diagnostic imaging ; Humans ; Neck ; Pain ; *Paraspinal Muscles ; }, abstract = {OBJECTIVE: Some studies have reported the presence of histological alterations, such as myofiber disorganization and abnormalities in the number and shape of mitochondria, in patients with fibromyalgia syndrome (FMS). Although Ultrasound imaging (US) is used to quantitatively characterize muscle tissues, US studies in patients with FMS are lacking. Therefore, we aimed to describe morphological and qualitative cervical multifidus (CM) muscle US features in women with FMS and to assess their correlation with clinical indicators.

DESIGN: Observational study.

SETTING: AFINSYFACRO Fibromyalgia Association (Madrid, Spain).

SUBJECTS: Forty-five women with FMS participated.

METHODS: Sociodemographic variables (e.g., age, height, weight, body mass index) and clinical outcomes (e.g., pain as assessed on a numerical pain rating scale, evolution time, pain-related disability as assessed by the Fibromyalgia Impact Questionnaire) were collected. Images were acquired bilaterally at the cervical spine (C4-C5 level) and measured by an experienced examiner for assessment of muscle morphology (e.g., cross-sectional area, perimeter, and shape) and quality (mean echo intensity and intramuscular fatty infiltration). Side-to-side comparisons and a correlational analysis were conducted.

RESULTS: No significant side-to-side differences were found for morphology or quality features (P > 0.05). None of the clinical indicators were associated with US characteristics (all, P > 0.05).

CONCLUSION: Our results showed no side-to-side differences for CM morphology and quality as assessed with US. No associations between CM muscle morphology or quality and Fibromyalgia Impact Questionnaire, pressure pain threshold, numerical pain rating scale score, or evolution time were observed. Our preliminary data suggest that muscle morphology is not directly related to pain and pain-related disability in women with FMS.}, } @article {pmid34643951, year = {2022}, author = {Adriano, EA and Zatti, SA and Okamura, B}, title = {How to build single-celled cnidarians with worm-like motility: Lessons from Myxozoa.}, journal = {Journal of anatomy}, volume = {240}, number = {3}, pages = {475-488}, pmid = {34643951}, issn = {1469-7580}, mesh = {Animals ; *Cnidaria ; *Fish Diseases/parasitology ; Gallbladder ; *Myxozoa/physiology/ultrastructure ; Phylogeny ; }, abstract = {Metazoans with worm-like morphologies across diverse and disparate groups typically demonstrate motility generated by hydrostatic skeletons involving tissue layers (muscles and epithelia). Here we present representative morphological, behavioural and molecular data for parasitic cnidarians (myxozoans) that demonstrate unprecedented variation in form and function, developing as cellular hydrostats. Motile elongate plasmodia characterise a remarkable radiation of species in the genus Ceratomyxa. The vermiform plasmodia inhabit gall bladders of a range of South American freshwater fish and exhibit undulatory motility reminiscent of nematodes but achieved at the cellular level. Collective insights from ultrastructure, confocal and light microscopy along with videos depicting movements highlight key features that we propose explain the unique motility of the plasmodia. These features include cytoskeletal elements (net forming microfilaments and microtubules), a large internal vacuole, a relatively rigid outer glycocalyx and peripherally arranged mitochondria. These constituents provide collective evidence for repurposing of the cnidarian epitheliomuscular cell to support worm-like motility at the cellular level. The apparent restriction of vermiform ceratomyxids to South American freshwaters suggests an origination via Cretaceous or Miocene marine transgressions and subsequent radiation.}, } @article {pmid34644400, year = {2021}, author = {Szoke, T and Nussbaum-Shochat, A and Amster-Choder, O}, title = {Evolutionarily conserved mechanism for membrane recognition from bacteria to mitochondria.}, journal = {FEBS letters}, volume = {595}, number = {22}, pages = {2805-2815}, doi = {10.1002/1873-3468.14203}, pmid = {34644400}, issn = {1873-3468}, mesh = {*Conserved Sequence ; Escherichia coli ; Escherichia coli Proteins/chemistry/*genetics/metabolism ; *Evolution, Molecular ; Membrane Proteins/chemistry/*genetics/metabolism ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/chemistry/*genetics/metabolism ; Protein Domains ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins/chemistry/*genetics/metabolism ; }, abstract = {The mechanisms controlling membrane recognition by proteins with one hydrophobic stretch at their carboxyl terminus (tail anchor, TA) are poorly defined. The Escherichia coli TAs of ElaB and YqjD, which share sequential and structural similarity with the Saccharomyces cerevisiae TA of Fis1, were shown to localize to mitochondria. We show that YqjD and ElaB are directed by their TAs to bacterial cell poles. Fis1(TA) expressed in E. coli localizes like the endogenous TAs. The yeast and bacterial TAs are inserted in the E. coli inner membrane, and they all show affiliation to phosphatidic acid (PA), found in the membrane of the bacterial cell poles and of the yeast mitochondria. Our results suggest a mechanism for TA membrane recognition conserved from bacteria to mitochondria and raise the possibility that through their interaction with PA, and TAs play a role across prokaryotes and eukaryotes in controlling cell/organelle fate.}, } @article {pmid34645790, year = {2021}, author = {Frye, RE and Lionnard, L and Singh, I and Karim, MA and Chajra, H and Frechet, M and Kissa, K and Racine, V and Ammanamanchi, A and McCarty, PJ and Delhey, L and Tippett, M and Rose, S and Aouacheria, A}, title = {Mitochondrial morphology is associated with respiratory chain uncoupling in autism spectrum disorder.}, journal = {Translational psychiatry}, volume = {11}, number = {1}, pages = {527}, pmid = {34645790}, issn = {2158-3188}, mesh = {*Autism Spectrum Disorder/metabolism ; Electron Transport ; Electron Transport Complex I ; Humans ; Mitochondria/metabolism ; Oxidation-Reduction ; }, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is associated with unique changes in mitochondrial metabolism, including elevated respiration rates and morphological alterations. We examined electron transport chain (ETC) complex activity in fibroblasts derived from 18 children with ASD as well as mitochondrial morphology measurements in fibroblasts derived from the ASD participants and four typically developing controls. In ASD participants, symptoms severity was measured by the Social Responsiveness Scale and Aberrant Behavior Checklist. Mixed-model regression demonstrated that alterations in mitochondrial morphology were associated with both ETC Complex I+III and IV activity as well as the difference between ETC Complex I+III and IV activity. The subgroup of ASD participants with relative elevation in Complex IV activity demonstrated more typical mitochondrial morphology and milder ASD related symptoms. This study is limited by sample size given the invasive nature of obtaining fibroblasts from children. Furthermore, since mitochondrial function is heterogenous across tissues, the result may be specific to fibroblast respiration. Previous studies have separately described elevated ETC Complex IV activity and changes in mitochondrial morphology in cells derived from children with ASD but this is the first study to link these two findings in mitochondrial metabolism. The association between a difference in ETC complex I+III and IV activity and normal morphology suggests that mitochondrial in individuals with ASD may require ETC uncoupling to function optimally. Further studies should assess the molecular mechanisms behind these unique metabolic changes.Trial registration: Protocols used in this study were registered in clinicaltrials.gov as NCT02000284 and NCT02003170.}, } @article {pmid34655689, year = {2022}, author = {do Amaral, MJ and de Andrade Rosa, I and Andrade, SA and Fang, X and Andrade, LR and Costa, ML and Mermelstein, C}, title = {The perinuclear region concentrates disordered proteins with predicted phase separation distributed in a 3D network of cytoskeletal filaments and organelles.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {1869}, number = {1}, pages = {119161}, pmid = {34655689}, issn = {1879-2596}, support = {R00 HL143210/HL/NHLBI NIH HHS/United States ; R01 HL157115/HL/NHLBI NIH HHS/United States ; R01 HL158761/HL/NHLBI NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/genetics/*metabolism/ultrastructure ; Animals ; Cells, Cultured ; Chick Embryo ; Intrinsically Disordered Proteins/metabolism ; Lysosomes/metabolism/ultrastructure ; Microscopy, Electron, Transmission/methods ; Mitochondria/metabolism/ultrastructure ; Nuclear Envelope/*metabolism/ultrastructure ; Proteome/genetics/metabolism ; Zebrafish ; }, abstract = {Membraneless organelles have emerged during the evolution of eukaryotic cells as intracellular domains in which multiple proteins organize into complex structures to perform specialized functions without the need of a lipid bilayer compartment. Here we describe the perinuclear space of eukaryotic cells as a highly organized network of cytoskeletal filaments that facilitates assembly of biomolecular condensates. Using bioinformatic analyses, we show that the perinuclear proteome is enriched in intrinsic disorder with several proteins predicted to undergo liquid-liquid phase separation. We also analyze immunofluorescence and transmission electron microscopy images showing the association between the nucleus and other organelles, such as mitochondria and lysosomes, or the labeling of specific proteins within the perinuclear region of cells. Altogether our data support the existence of a perinuclear dense sub-micron region formed by a well-organized three-dimensional network of structural and signaling proteins, including several proteins containing intrinsically disordered regions with phase behavior. This network of filamentous cytoskeletal proteins extends a few micrometers from the nucleus, contributes to local crowding, and organizes the movement of molecular complexes within the perinuclear space. Our findings take a key step towards understanding how membraneless regions within eukaryotic cells can serve as hubs for biomolecular condensates assembly, in particular the perinuclear space. Finally, evaluation of the disease context of the perinuclear proteins revealed that alterations in their expression can lead to several pathological conditions, and neurological disorders and cancer are among the most frequent.}, } @article {pmid34660591, year = {2021}, author = {Lim, HJ and Yoon, H and Kim, H and Kang, YW and Kim, JE and Kim, OY and Lee, EY and Twizere, JC and Rak, J and Kim, DK}, title = {Extracellular Vesicle Proteomes Shed Light on the Evolutionary, Interactive, and Functional Divergence of Their Biogenesis Mechanisms.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {734950}, pmid = {34660591}, issn = {2296-634X}, abstract = {Extracellular vesicles (EVs) are membranous structures containing bioactive molecules, secreted by most cells into the extracellular environment. EVs are classified by their biogenesis mechanisms into two major subtypes: ectosomes (enriched in large EVs; lEVs), budding directly from the plasma membrane, which is common in both prokaryotes and eukaryotes, and exosomes (enriched in small EVs; sEVs) generated through the multivesicular bodies via the endomembrane system, which is unique to eukaryotes. Even though recent proteomic analyses have identified key proteins associated with EV subtypes, there has been no systematic analysis, thus far, to support the general validity and utility of current EV subtype separation methods, still largely dependent on physical properties, such as vesicular size and sedimentation. Here, we classified human EV proteomic datasets into two main categories based on distinct centrifugation protocols commonly used for isolating sEV or lEV fractions. We found characteristic, evolutionarily conserved profiles of sEV and lEV proteins linked to their respective biogenetic origins. This may suggest that the evolutionary trajectory of vesicular proteins may result in a membership bias toward specific EV subtypes. Protein-protein interaction (PPI) network analysis showed that vesicular proteins formed distinct clusters with proteins in the same EV fraction, providing evidence for the existence of EV subtype-specific protein recruiters. Moreover, we identified functional modules enriched in each fraction, including multivesicular body sorting for sEV, and mitochondria cellular respiration for lEV proteins. Our analysis successfully captured novel features of EVs embedded in heterogeneous proteomics studies and suggests specific protein markers and signatures to be used as quality controllers in the isolation procedure for subtype-enriched EV fractions.}, } @article {pmid34662686, year = {2022}, author = {Omeka, WKM and Liyanage, DS and Jeong, T and Lee, S and Lee, J}, title = {Molecular characterization, immune responses, and functional activities of manganese superoxide dismutase in disk abalone (Haliotis discus discus).}, journal = {Developmental and comparative immunology}, volume = {127}, number = {}, pages = {104299}, doi = {10.1016/j.dci.2021.104299}, pmid = {34662686}, issn = {1879-0089}, mesh = {Animals ; *Gastropoda ; Gene Expression Regulation ; Hydrogen Peroxide ; Immunity, Innate ; Mammals ; Phylogeny ; Superoxide Dismutase/genetics ; *Vibrio parahaemolyticus ; }, abstract = {Superoxide dismutases (SODs) are metalloenzymes that convert superoxide radicals to H2O2 and O2. Although SODs have been extensively studied in mammals and other species, comparative studies in invertebrates, such as abalones, are lacking. Here, we aimed to characterize manganese superoxide dismutase in disk abalone (Haliotis discus discus) (AbMnSOD) by assessing its transcriptional levels at different embryonic developmental stages. Additionally, the temporal expression of AbMnSOD in different abalone tissues in response to bacterial, viral, and pathogen-associated molecular pattern (PAMP) stimuli was investigated. SOD activity was measured at various recombinant protein concentrations via the xanthine oxidase/WST-1 system. Cell viability upon exposure to H2O2, wound healing ability, and subcellular localization were determined in AbMnSOD-transfected cells. AbMnSOD was 681 bp long and contained the SOD-A domain. AbMnSOD expression was higher at the trochophore stage than at the other stages. When challenged with immune stimulants, AbMnSOD showed the highest expression at 6 h post-injection (p.i.) for all stimulants except lipopolysaccharides. In the gills, the highest AbMnSOD expression was observed at 6 h p.i., except for the Vibrio parahaemolyticus challenge. Recombinant AbMnSOD showed concentration-dependent xanthine oxidase activity. Furthermore, AbMnSOD-transfected cells survived H2O2-induced apoptosis and exhibited significant wound gap closure. As expected, AbMnSOD was localized in the mitochondria of the cells. Our findings suggest that AbMnSOD is an essential antioxidant enzyme that participates in regulating developmental processes and defense mechanisms against oxidative stress in hosts.}, } @article {pmid34669188, year = {2022}, author = {Fan, Y and Asao, S and Furbank, RT and von Caemmerer, S and Day, DA and Tcherkez, G and Sage, TL and Sage, RF and Atkin, OK}, title = {The crucial roles of mitochondria in supporting C4 photosynthesis.}, journal = {The New phytologist}, volume = {233}, number = {3}, pages = {1083-1096}, doi = {10.1111/nph.17818}, pmid = {34669188}, issn = {1469-8137}, mesh = {Carbon Dioxide/metabolism ; *Malate Dehydrogenase/metabolism ; Mitochondria/metabolism ; *Photosynthesis ; Plant Leaves/physiology ; }, abstract = {C4 photosynthesis involves a series of biochemical and anatomical traits that significantly improve plant productivity under conditions that reduce the efficiency of C3 photosynthesis. We explore how evolution of the three classical biochemical types of C4 photosynthesis (NADP-ME, NAD-ME and PCK types) has affected the functions and properties of mitochondria. Mitochondria in C4 NAD-ME and PCK types play a direct role in decarboxylation of metabolites for C4 photosynthesis. Mitochondria in C4 PCK type also provide ATP for C4 metabolism, although this role for ATP provision is not seen in NAD-ME type. Such involvement has increased mitochondrial abundance/size and associated enzymatic capacity, led to changes in mitochondrial location and ultrastructure, and altered the role of mitochondria in cellular carbon metabolism in the NAD-ME and PCK types. By contrast, these changes in mitochondrial properties are absent in the C4 NADP-ME type and C3 leaves, where mitochondria play no direct role in photosynthesis. From an eco-physiological perspective, rates of leaf respiration in darkness vary considerably among C4 species but does not differ systematically among the three C4 types. This review outlines further mitochondrial research in key areas central to the engineering of the C4 pathway into C3 plants and to the understanding of variation in rates of C4 dark respiration.}, } @article {pmid34671161, year = {2021}, author = {Wang, Y and Pedersen, MW and Alsos, IG and De Sanctis, B and Racimo, F and Prohaska, A and Coissac, E and Owens, HL and Merkel, MKF and Fernandez-Guerra, A and Rouillard, A and Lammers, Y and Alberti, A and Denoeud, F and Money, D and Ruter, AH and McColl, H and Larsen, NK and Cherezova, AA and Edwards, ME and Fedorov, GB and Haile, J and Orlando, L and Vinner, L and Korneliussen, TS and Beilman, DW and Bjørk, AA and Cao, J and Dockter, C and Esdale, J and Gusarova, G and Kjeldsen, KK and Mangerud, J and Rasic, JT and Skadhauge, B and Svendsen, JI and Tikhonov, A and Wincker, P and Xing, Y and Zhang, Y and Froese, DG and Rahbek, C and Bravo, DN and Holden, PB and Edwards, NR and Durbin, R and Meltzer, DJ and Kjær, KH and Möller, P and Willerslev, E}, title = {Late Quaternary dynamics of Arctic biota from ancient environmental genomics.}, journal = {Nature}, volume = {600}, number = {7887}, pages = {86-92}, pmid = {34671161}, issn = {1476-4687}, support = {207492/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; /ERC_/European Research Council/International ; 207492/WT_/Wellcome Trust/United Kingdom ; WT220023/WT_/Wellcome Trust/United Kingdom ; 069906/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Arctic Regions ; *Biota ; Climate Change/history ; DNA, Ancient/*analysis ; DNA, Environmental/*analysis ; Databases, Genetic ; Datasets as Topic ; Extinction, Biological ; Geologic Sediments ; Grassland ; Greenland ; Haplotypes/genetics ; Herbivory/genetics ; History, Ancient ; Humans ; Lakes ; Mammoths ; *Metagenomics ; Mitochondria/genetics ; Perissodactyla ; Permafrost ; Phylogeny ; Plants/genetics ; Population Dynamics ; Rain ; Siberia ; Spatio-Temporal Analysis ; Wetlands ; }, abstract = {During the last glacial-interglacial cycle, Arctic biotas experienced substantial climatic changes, yet the nature, extent and rate of their responses are not fully understood[1-8]. Here we report a large-scale environmental DNA metagenomic study of ancient plant and mammal communities, analysing 535 permafrost and lake sediment samples from across the Arctic spanning the past 50,000 years. Furthermore, we present 1,541 contemporary plant genome assemblies that were generated as reference sequences. Our study provides several insights into the long-term dynamics of the Arctic biota at the circumpolar and regional scales. Our key findings include: (1) a relatively homogeneous steppe-tundra flora dominated the Arctic during the Last Glacial Maximum, followed by regional divergence of vegetation during the Holocene epoch; (2) certain grazing animals consistently co-occurred in space and time; (3) humans appear to have been a minor factor in driving animal distributions; (4) higher effective precipitation, as well as an increase in the proportion of wetland plants, show negative effects on animal diversity; (5) the persistence of the steppe-tundra vegetation in northern Siberia enabled the late survival of several now-extinct megafauna species, including the woolly mammoth until 3.9 ± 0.2 thousand years ago (ka) and the woolly rhinoceros until 9.8 ± 0.2 ka; and (6) phylogenetic analysis of mammoth environmental DNA reveals a previously unsampled mitochondrial lineage. Our findings highlight the power of ancient environmental metagenomics analyses to advance understanding of population histories and long-term ecological dynamics.}, } @article {pmid34674637, year = {2021}, author = {Lankheet, I and Vicente, M and Barbieri, C and Schlebusch, C}, title = {The performance of common SNP arrays in assigning African mitochondrial haplogroups.}, journal = {BMC genomic data}, volume = {22}, number = {1}, pages = {43}, pmid = {34674637}, issn = {2730-6844}, mesh = {Black People/*genetics ; DNA, Mitochondrial/*genetics ; Datasets as Topic ; Haplotypes/*genetics ; Humans ; Mitochondria/*genetics ; Oligonucleotide Array Sequence Analysis/*standards ; Polymorphism, Single Nucleotide/*genetics ; Software/standards ; }, abstract = {BACKGROUND: Mitochondrial haplogroup assignment is an important tool for forensics and evolutionary genetics. African populations are known to display a high diversity of mitochondrial haplogroups. In this research we explored mitochondrial haplogroup assignment in African populations using commonly used genome-wide SNP arrays.

RESULTS: We show that, from eight commonly used SNP arrays, two SNP arrays outperform the other arrays when it comes to the correct assignment of African mitochondrial haplogroups. One array enables the recognition of 81% of the African mitochondrial haplogroups from our compiled dataset of full mitochondrial sequences. Other SNP arrays were able to assign 4-62% of the African mitochondrial haplogroups present in our dataset. We also assessed the performance of available software for assigning mitochondrial haplogroups from SNP array data.

CONCLUSIONS: These results provide the first cross-checked quantification of mitochondrial haplogroup assignment performance from SNP array data. Mitochondrial haplogroup frequencies inferred from most common SNP arrays used for human population analysis should be considered with caution.}, } @article {pmid34678134, year = {2023}, author = {Satyanarayana, DS and Ahlawat, S and Sharma, R and Arora, R and Sharma, A and Tantia, MS and Vijh, RK}, title = {Genetic differentiation of Indian dromedary and Bactrian camel populations based on mitochondrial ATP8 and ATP6 genes.}, journal = {Animal biotechnology}, volume = {34}, number = {3}, pages = {756-760}, doi = {10.1080/10495398.2021.1990079}, pmid = {34678134}, issn = {1532-2378}, mesh = {Animals ; *Camelus/genetics ; Phylogeny ; *Mitochondria/genetics ; Genetic Drift ; DNA, Mitochondrial/genetics ; }, abstract = {Camelids are acknowledged worldwide to endure hostile conditions prevalent in the hot as well cold deserts across the globe. Adaptations to climatic extremes have been associated with mitochondrial protein variants such as ATP8 and ATP6 in different species. The camel genetic resources of India are represented by 9 breeds of dromedary camels which inhabit hot arid and semi-arid zones of the country and a small population of Bactrian camels found in the cold desert of Ladakh. In this study, within and between breed genetic diversity in Indian dromedaries and their divergence from Bactrian camels was investigated based on ATP8/6 genes. Sequence analysis of a mitochondrial DNA fragment encompassing ATP8 and ATP6 genes identified 15 haplotypes in the dromedaries of India and 3 haplotypes in Bactrian camels. The values of haplotype diversity and nucleotide diversity were 0.647 and 0.00187 in the former and 0.679 and 0.00098, respectively in the latter. AMOVA analysis revealed 97.81% variance between the two species. Median-Joining network delineated three distinct mitochondrial haplogroups for Camelus dromedarius, Camelus ferus and Camelus bactrianus. Clear demarcation of the old world (Dromedary and Bactrian camels) and new world camelids (Alpaca, llama, guanaco and vicugna) was evident through the phylogenetic analysis.}, } @article {pmid34678428, year = {2022}, author = {Yu, M and Yu, Y and Song, T and Zhang, Y and Wei, F and Cheng, J and Zhang, B and Zhang, X}, title = {Characterization of the voltage-dependent anion channel (VDAC) gene family in wheat (Triticum aestivum L.) and its potential mechanism in response to drought and salinity stresses.}, journal = {Gene}, volume = {809}, number = {}, pages = {146031}, doi = {10.1016/j.gene.2021.146031}, pmid = {34678428}, issn = {1879-0038}, mesh = {Amino Acid Motifs ; Arabidopsis/genetics ; Chromosomes, Plant ; Droughts ; Gene Expression Regulation, Plant ; Multigene Family ; Oxidoreductases/genetics ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; Plants, Genetically Modified ; Promoter Regions, Genetic ; Salinity ; Stress, Physiological/*genetics ; Triticum/*genetics/physiology ; Voltage-Dependent Anion Channels/chemistry/*genetics/metabolism ; }, abstract = {Voltage-dependent anion channels (VDACs) are major transport proteins localized in the outer membrane of mitochondria and play critical roles in regulating plant growth and responding to stress. In this study, a total of 26 VDAC genes in common wheat (Triticum aestivum L.) were identified. TaVDACs that contained β-barrel structures were classified into three groups with phylogenetic and sequence alignment. Additionally, the gene structure and protein conserved motif composition varied among diverse subfamilies but were relatively conserved within the same subfamily. The basic elements that were stress- and hormone-related, including TATA-box, CAAT-box, MBS, LTR, TC-rich repeats, ABRE, P-box and TATC-box, were predicted within the promoter region of TaVDAC genes. TaVDAC expression patterns differed among tissues, organs and abiotic stress conditions. Overexpression (OE) of TaVDAC1-B conferred high tolerance to salinity and less resistance to drought stress in Arabidopsis thaliana. TaVDAC1-B interacted with Nucleoredoxin-D1 (TaNRX-D1) protein. Furthermore, compared with WT lines, salinity stress further upregulated the level of AtNRX1 (homologous gene of TaNRX-D1 in Arabidopsis) expression and the activity of superoxide dismutase in TaVDAC1-B OE lines, which led to a decrease in superoxide radical accumulation; drought stress further downregulated AtNRX1 expression and superoxide dismutase activity in TaVDAC1-B OE lines, resulting in the accumulation of superoxide radicals. Our study not only presents comprehensive information for understanding the VDAC gene family in wheat but also proposes a potential mechanism in response to drought and salinity stress.}, } @article {pmid34678674, year = {2021}, author = {Rothmann-Meyer, W and Naidoo, K and de Waal, PJ}, title = {Comparative mitogenomics of Spirocerca lupi from South Africa and China: Variation and possible heteroplasmy.}, journal = {Veterinary parasitology}, volume = {300}, number = {}, pages = {109595}, doi = {10.1016/j.vetpar.2021.109595}, pmid = {34678674}, issn = {1873-2550}, mesh = {Animals ; *Dog Diseases/epidemiology ; Dogs ; Heteroplasmy ; Phylogeny ; South Africa/epidemiology ; *Spirurida Infections/veterinary ; *Thelazioidea/genetics ; }, abstract = {The complete mitochondrial genome of Spirocerca lupi isolated from a dog in South Africa was sequenced using next generation sequencing (NGS) technology and the 12 protein coding genes along with the two rRNA genes were compared to 18 other nematode species as well as S. lupi from China. The mitochondrial genome of S. lupi South Africa had a mean genetic diversity of 6.1 % compared to S. lupi China with some variation in nucleotide composition, gene positioning and size. Pairwise distance results indicated slightly higher variation when compared to the pairwise distances of other closely related species, however, this variation was not high enough for it to be considered a cryptic species. Phylogenetic analysis indicated that S. lupi from the two continents are very similar. In addition, single nucleotide polymorphisms were detected in the nad2 gene with ten sequence variants identified from 10 clones from a single nematode, suggesting possible heteroplasmy. The origin of the heteroplasmy is currently unknown but it is speculated to have arisen from accumulated mutations in the mitochondria during somatic replication.}, } @article {pmid34680141, year = {2021}, author = {Picca, A and Guerra, F and Calvani, R and Romano, R and Coelho-Júnior, HJ and Bucci, C and Marzetti, E}, title = {Mitochondrial Dysfunction, Protein Misfolding and Neuroinflammation in Parkinson's Disease: Roads to Biomarker Discovery.}, journal = {Biomolecules}, volume = {11}, number = {10}, pages = {}, pmid = {34680141}, issn = {2218-273X}, mesh = {Biomarkers/metabolism ; Dopaminergic Neurons/metabolism/pathology ; Humans ; Lewy Bodies/genetics/pathology ; Mitochondria/*genetics/pathology ; Neuroinflammatory Diseases/genetics/pathology ; Parkinson Disease/*genetics/pathology ; Protein Aggregates/genetics ; Proteostasis Deficiencies/*genetics/pathology ; Reactive Oxygen Species/metabolism ; alpha-Synuclein/*genetics ; }, abstract = {Parkinson's Disease (PD) is a highly prevalent neurodegenerative disease among older adults. PD neuropathology is marked by the progressive loss of the dopaminergic neurons of the substantia nigra pars compacta and the widespread accumulation of misfolded intracellular α-synuclein (α-syn). Genetic mutations and post-translational modifications, such as α-syn phosphorylation, have been identified among the multiple factors supporting α-syn accrual during PD. A decline in the clearance capacity of the ubiquitin-proteasome and the autophagy-lysosomal systems, together with mitochondrial dysfunction, have been indicated as major pathophysiological mechanisms of PD neurodegeneration. The accrual of misfolded α-syn aggregates into soluble oligomers, and the generation of insoluble fibrils composing the core of intraneuronal Lewy bodies and Lewy neurites observed during PD neurodegeneration, are ignited by the overproduction of reactive oxygen species (ROS). The ROS activate the α-syn aggregation cascade and, together with the Lewy bodies, promote neurodegeneration. However, the molecular pathways underlying the dynamic evolution of PD remain undeciphered. These gaps in knowledge, together with the clinical heterogeneity of PD, have hampered the identification of the biomarkers that may be used to assist in diagnosis, treatment monitoring, and prognostication. Herein, we illustrate the main pathways involved in PD pathogenesis and discuss their possible exploitation for biomarker discovery.}, } @article {pmid34685491, year = {2021}, author = {Kurokawa, H and Taninaka, A and Shigekawa, H and Matsui, H}, title = {Dabigatran Etexilate Induces Cytotoxicity in Rat Gastric Epithelial Cell Line via Mitochondrial Reactive Oxygen Species Production.}, journal = {Cells}, volume = {10}, number = {10}, pages = {}, pmid = {34685491}, issn = {2073-4409}, support = {JP17H06088//Japan Society for the Promotion of Science/ ; JP19H02591//Japan Society for the Promotion of Science/ ; JP19K16854//Japan Society for the Promotion of Science/ ; JPMJCR1875//Core Research for Evolutional Science and Technology/ ; }, mesh = {Animals ; Anticoagulants/*pharmacology ; Benzimidazoles/pharmacology ; Dabigatran/*pharmacology ; Epithelial Cells/*drug effects ; Mitochondria/*drug effects ; Rats ; Reactive Oxygen Species/*metabolism ; Thrombin/metabolism ; }, abstract = {Dabigatran is a novel oral anticoagulant that directly inhibits free and fibrin-bound thrombins and exerts rapid and predictable anticoagulant effects. While the use of this reagent has been associated with an increased risk of gastrointestinal bleeding, the reason why dabigatran use increases gastrointestinal bleeding risk remains unknown. We investigated the cytotoxicity of dabigatran etexilate and tartaric acid, the two primary components of dabigatran. The cytotoxicity of dabigatran etexilate and tartaric acid was measured in a cell viability assay. Intracellular mitochondrial reactive oxygen species (mitROS) production and lipid peroxidation were measured using fluorescence dyes. Cell membrane viscosity was measured using atomic force microscopy. The potential of ascorbic acid as an inhibitor of dabigatran cytotoxicity was also evaluated. The cytotoxicity of dabigatran etexilate was higher than that of tartaric acid. Dabigatran etexilate induced mitROS production and lipid peroxidation and altered the cell membrane viscosity. Ascorbic acid inhibited the cytotoxicity and mitROS production induced by dabigatran etexilate. Therefore, we attributed the cytotoxicity of dabigatran to dabigatran etexilate, and proposed that the cytotoxic effects of dabigatran etexilate are mediated via mitROS production. Additionally, we demonstrated that dabigatran cytotoxicity can be prevented via antioxidant treatment.}, } @article {pmid34689722, year = {2022}, author = {Ahuja, P and Ng, CF and Pang, BPS and Chan, WS and Tse, MCL and Bi, X and Kwan, HR and Brobst, D and Herlea-Pana, O and Yang, X and Du, G and Saengnipanthkul, S and Noh, HL and Jiao, B and Kim, JK and Lee, CW and Ye, K and Chan, CB}, title = {Muscle-generated BDNF (brain derived neurotrophic factor) maintains mitochondrial quality control in female mice.}, journal = {Autophagy}, volume = {18}, number = {6}, pages = {1367-1384}, pmid = {34689722}, issn = {1554-8635}, support = {U2C DK093000/DK/NIDDK NIH HHS/United States ; }, mesh = {*AMP-Activated Protein Kinases/metabolism ; Animals ; Autophagy ; *Brain-Derived Neurotrophic Factor/metabolism ; Fatty Acids/metabolism ; Female ; Mice ; *Mitochondria, Muscle/metabolism ; *Muscle, Skeletal/physiology ; }, abstract = {Mitochondrial remodeling is dysregulated in metabolic diseases but the underlying mechanism is not fully understood. We report here that BDNF (brain derived neurotrophic factor) provokes mitochondrial fission and clearance in skeletal muscle via the PRKAA/AMPK-PINK1-PRKN/Parkin and PRKAA-DNM1L/DRP1-MFF pathways. Depleting Bdnf expression in myotubes reduced fatty acid-induced mitofission and mitophagy, which was associated with mitochondrial elongation and impaired lipid handling. Muscle-specific bdnf knockout (MBKO) mice displayed defective mitofission and mitophagy, and accumulation of dysfunctional mitochondria in the muscle when they were fed with a high-fat diet (HFD). These animals also have exacerbated body weight gain, increased intramyocellular lipid deposition, reduced energy expenditure, poor metabolic flexibility, and more insulin resistance. In contrast, consuming a BDNF mimetic (7,8-dihydroxyflavone) increased mitochondrial content, and enhanced mitofission and mitophagy in the skeletal muscles. Hence, BDNF is an essential myokine to maintain mitochondrial quality and function, and its repression in obesity might contribute to impaired metabolism.Abbreviation: 7,8-DHF: 7,8-dihydroxyflavone; ACACA/ACC: acetyl Coenzyme A carboxylase alpha; ACAD: acyl-Coenzyme A dehydrogenase family; ACADVL: acyl-Coenzyme A dehydrogenase, very long chain; ACOT: acyl-CoA thioesterase; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2, beta; BDNF: brain derived neurotrophic factor; BNIP3: BCL2/adenovirus E1B interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; CCL2/MCP-1: chemokine (C-C motif) ligand 2; CCL5: chemokine (C-C motif) ligand 5; CNS: central nervous system; CPT1B: carnitine palmitoyltransferase 1b, muscle; Cpt2: carnitine palmitoyltransferase 2; CREB: cAMP responsive element binding protein; DNM1L/DRP1: dynamin 1-like; E2: estrogen; EHHADH: enoyl-CoenzymeA hydratase/3-hydroxyacyl CoenzymeA dehydrogenase; ESR1/ER-alpha: estrogen receptor 1 (alpha); FA: fatty acid; FAO: fatty acid oxidation; FCCP: carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone; FFA: free fatty acids; FGF21: fibroblast growth factor 21; FUNDC1: FUN14 domain containing 1; HADHA: hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha; HFD: high-fat diet; iWAT: inguinal white adipose tissues; MAP1LC3A/LC3A: microtubule-associated protein 1 light chain 3 alpha; MBKO; muscle-specific bdnf knockout; IL6/IL-6: interleukin 6; MCEE: methylmalonyl CoA epimerase; MFF: mitochondrial fission factor; NTRK2/TRKB: neurotrophic tyrosine kinase, receptor, type 2; OPTN: optineurin; PA: palmitic acid; PARL: presenilin associated, rhomboid-like; PDH: pyruvate dehydrogenase; PINK1: PTEN induced putative kinase 1; PPARGC1A/PGC-1α: peroxisome proliferative activated receptor, gamma, coactivator 1 alpha; PRKAA/AMPK: protein kinase, AMP-activated, alpha 2 catalytic subunit; ROS: reactive oxygen species; TBK1: TANK-binding kinase 1; TG: triacylglycerides; TNF/TNFα: tumor necrosis factor; TOMM20: translocase of outer mitochondrial membrane 20; ULK1: unc-51 like kinase 1.}, } @article {pmid34704591, year = {2021}, author = {Kato, S and Arasaki, K and Tokutomi, N and Imai, Y and Inoshita, T and Hattori, N and Sasaki, T and Sato, M and Wakana, Y and Inoue, H and Tagaya, M}, title = {Syntaxin 17, an ancient SNARE paralog, plays different and conserved roles in different organisms.}, journal = {Journal of cell science}, volume = {134}, number = {22}, pages = {}, doi = {10.1242/jcs.258699}, pmid = {34704591}, issn = {1477-9137}, mesh = {Animals ; Autophagy ; HeLa Cells ; Humans ; *Membrane Fusion ; Qa-SNARE Proteins/genetics ; *SNARE Proteins ; }, abstract = {Mammalian syntaxin 17 (Stx17) has several roles in processes other than membrane fusion, including in mitochondrial division, autophagosome formation and lipid droplet expansion. In contrast to conventional syntaxins, Stx17 has a long C-terminal hydrophobic region with a hairpin-like structure flanked by a basic amino acid-enriched C-terminal tail. Although Stx17 is one of the six ancient SNAREs and is present in diverse eukaryotic organisms, it has been lost in multiple lineages during evolution. In the present study, we compared the localization and function of fly and nematode Stx17s expressed in HeLa cells with those of human Stx17. We found that fly Stx17 predominantly localizes to the cytosol and mediates autophagy, but not mitochondrial division. Nematode Stx17, on the other hand, is predominantly present in mitochondria and facilitates mitochondrial division, but is irrelevant to autophagy. These differences are likely due to different structures in the C-terminal tail. Non-participation of fly Stx17 and nematode Stx17 in mitochondrial division and autophagy, respectively, was demonstrated in individual organisms. Our results provide an insight into the evolution of Stx17 in metazoa. This article has an associated First Person interview with the first author of the paper.}, } @article {pmid34710348, year = {2021}, author = {Stairs, CW and Táborský, P and Salomaki, ED and Kolisko, M and Pánek, T and Eme, L and Hradilová, M and Vlček, Č and Jerlström-Hultqvist, J and Roger, AJ and Čepička, I}, title = {Anaeramoebae are a divergent lineage of eukaryotes that shed light on the transition from anaerobic mitochondria to hydrogenosomes.}, journal = {Current biology : CB}, volume = {31}, number = {24}, pages = {5605-5612.e5}, doi = {10.1016/j.cub.2021.10.010}, pmid = {34710348}, issn = {1879-0445}, mesh = {Anaerobiosis ; *Eukaryota/metabolism ; Mitochondria/genetics/metabolism ; *Organelles/genetics/metabolism ; Oxygen/metabolism ; Phylogeny ; }, abstract = {Discoveries of diverse microbial eukaryotes and their inclusion in comprehensive phylogenomic analyses have crucially re-shaped the eukaryotic tree of life in the 21st century.[1] At the deepest level, eukaryotic diversity comprises 9-10 "supergroups." One of these supergroups, the Metamonada, is particularly important to our understanding of the evolutionary dynamics of eukaryotic cells, including the remodeling of mitochondrial function. All metamonads thrive in low-oxygen environments and lack classical aerobic mitochondria, instead possessing mitochondrion-related organelles (MROs) with metabolisms that are adapted to low-oxygen conditions. These MROs lack an organellar genome, do not participate in the Krebs cycle and oxidative phosphorylation,[2] and often synthesize ATP by substrate-level phosphorylation coupled to hydrogen production.[3][,][4] The events that occurred during the transition from an oxygen-respiring mitochondrion to a functionally streamlined MRO early in metamonad evolution remain largely unknown. Here, we report transcriptomes of two recently described, enigmatic, anaerobic protists from the genus Anaeramoeba.[5] Using phylogenomic analysis, we show that these species represent a divergent, phylum-level lineage in the tree of metamonads, emerging as a sister group of the Parabasalia and reordering the deep branching order of the metamonad tree. Metabolic reconstructions of the Anaeramoeba MROs reveal many "classical" mitochondrial features previously not seen in metamonads, including a disulfide relay import system, propionate production, and amino acid metabolism. Our findings suggest that the cenancestor of Metamonada likely had MROs with more classical mitochondrial features than previously anticipated and demonstrate how discoveries of novel lineages of high taxonomic rank continue to transform our understanding of early eukaryote evolution.}, } @article {pmid34713507, year = {2022}, author = {Balparda, M and Elsässer, M and Badia, MB and Giese, J and Bovdilova, A and Hüdig, M and Reinmuth, L and Eirich, J and Schwarzländer, M and Finkemeier, I and Schallenberg-Rüdinger, M and Maurino, VG}, title = {Acetylation of conserved lysines fine-tunes mitochondrial malate dehydrogenase activity in land plants.}, journal = {The Plant journal : for cell and molecular biology}, volume = {109}, number = {1}, pages = {92-111}, doi = {10.1111/tpj.15556}, pmid = {34713507}, issn = {1365-313X}, mesh = {Acetylation ; Embryophyta/*enzymology/genetics ; Lysine/metabolism ; Malate Dehydrogenase/genetics/*metabolism ; Mitochondria/enzymology ; Mitochondrial Proteins/genetics/metabolism ; Plant Proteins/genetics/metabolism ; *Protein Processing, Post-Translational ; }, abstract = {Plants need to rapidly and flexibly adjust their metabolism to changes of their immediate environment. Since this necessity results from the sessile lifestyle of land plants, key mechanisms for orchestrating central metabolic acclimation are likely to have evolved early. Here, we explore the role of lysine acetylation as a post-translational modification to directly modulate metabolic function. We generated a lysine acetylome of the moss Physcomitrium patens and identified 638 lysine acetylation sites, mostly found in mitochondrial and plastidial proteins. A comparison with available angiosperm data pinpointed lysine acetylation as a conserved regulatory strategy in land plants. Focusing on mitochondrial central metabolism, we functionally analyzed acetylation of mitochondrial malate dehydrogenase (mMDH), which acts as a hub of plant metabolic flexibility. In P. patens mMDH1, we detected a single acetylated lysine located next to one of the four acetylation sites detected in Arabidopsis thaliana mMDH1. We assessed the kinetic behavior of recombinant A. thaliana and P. patens mMDH1 with site-specifically incorporated acetyl-lysines. Acetylation of A. thaliana mMDH1 at K169, K170, and K334 decreases its oxaloacetate reduction activity, while acetylation of P. patens mMDH1 at K172 increases this activity. We found modulation of the malate oxidation activity only in A. thaliana mMDH1, where acetylation of K334 strongly activated it. Comparative homology modeling of MDH proteins revealed that evolutionarily conserved lysines serve as hotspots of acetylation. Our combined analyses indicate lysine acetylation as a common strategy to fine-tune the activity of central metabolic enzymes with likely impact on plant acclimation capacity.}, } @article {pmid34715011, year = {2021}, author = {Hochberg, I and Demain, LAM and Richer, J and Thompson, K and Urquhart, JE and Rea, A and Pagarkar, W and Rodríguez-Palmero, A and Schlüter, A and Verdura, E and Pujol, A and Quijada-Fraile, P and Amberger, A and Deutschmann, AJ and Demetz, S and Gillespie, M and Belyantseva, IA and McMillan, HJ and Barzik, M and Beaman, GM and Motha, R and Ng, KY and O'Sullivan, J and Williams, SG and Bhaskar, SS and Lawrence, IR and Jenkinson, EM and Zambonin, JL and Blumenfeld, Z and Yalonetsky, S and Oerum, S and Rossmanith, W and , and Yue, WW and Zschocke, J and Munro, KJ and Battersby, BJ and Friedman, TB and Taylor, RW and O'Keefe, RT and Newman, WG}, title = {Bi-allelic variants in the mitochondrial RNase P subunit PRORP cause mitochondrial tRNA processing defects and pleiotropic multisystem presentations.}, journal = {American journal of human genetics}, volume = {108}, number = {11}, pages = {2195-2204}, pmid = {34715011}, issn = {1537-6605}, mesh = {Adult ; *Alleles ; Female ; *Genetic Pleiotropy ; Humans ; Male ; Mitochondria/*enzymology ; Pedigree ; RNA, Mitochondrial/*genetics ; RNA, Transfer/*genetics ; Ribonuclease P/*genetics ; }, abstract = {Human mitochondrial RNase P (mt-RNase P) is responsible for 5' end processing of mitochondrial precursor tRNAs, a vital step in mitochondrial RNA maturation, and is comprised of three protein subunits: TRMT10C, SDR5C1 (HSD10), and PRORP. Pathogenic variants in TRMT10C and SDR5C1 are associated with distinct recessive or x-linked infantile onset disorders, resulting from defects in mitochondrial RNA processing. We report four unrelated families with multisystem disease associated with bi-allelic variants in PRORP, the metallonuclease subunit of mt-RNase P. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes. Fibroblasts from affected individuals in two families demonstrated decreased steady state levels of PRORP, an accumulation of unprocessed mitochondrial transcripts, and decreased steady state levels of mitochondrial-encoded proteins, which were rescued by introduction of the wild-type PRORP cDNA. In mt-tRNA processing assays performed with recombinant mt-RNase P proteins, the disease-associated variants resulted in diminished mitochondrial tRNA processing. Identification of disease-causing variants in PRORP indicates that pathogenic variants in all three subunits of mt-RNase P can cause mitochondrial dysfunction, each with distinct pleiotropic clinical presentations.}, } @article {pmid34724985, year = {2021}, author = {Wu, Y and Wang, XH and Li, XH and Song, LY and Yu, SL and Fang, ZC and Liu, YQ and Yuan, LY and Peng, CY and Zhang, SY and Cheng, W and Ma, HC and Wang, LF and Tang, JM and Wang, YF and Ji, FY}, title = {Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China.}, journal = {Military Medical Research}, volume = {8}, number = {1}, pages = {57}, pmid = {34724985}, issn = {2054-9369}, support = {№:2020XGFYZR11//the Special Project of Contingency Research for COVID-19 at Hubei University of Medicine/ ; №:2020XGFYZR03//the Special Project of Contingency Research for COVID-19 at Hubei University of Medicine/ ; №: 2018QDJZR01//the Cultivating Project for Young Scholar at Hubei University of Medicine/ ; }, mesh = {*COVID-19/genetics ; Case-Control Studies ; China ; *DNA, Mitochondrial/genetics ; Humans ; Mitochondria/genetics ; Phylogeny ; Risk Factors ; }, abstract = {BACKGROUND: Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk.

METHODS: A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n = 615) and COVID-19 patients (n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student's t-test was used for continuous variables, and Pearson's chi-squared test or Fisher's exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations.

RESULTS: Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (> 10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1)/G10310A (in ND3) were associated with a reduced risk of severe COVID-19 (OR = 0.590, 95% CI 0.428-0.814, P = 0.001; and OR = 0.654, 95% CI 0.457-0.936, P = 0.020, respectively), while A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 (OR = 2.336, 95% CI 1.179-4.608, P = 0.015; OR = 2.033, 95% CI 1.242-3.322, P = 0.005; OR = 3.040, 95% CI 1.522-6.061, P = 0.002; and OR = 2.890, 95% CI 1.199-6.993, P = 0.018, respectively).

CONCLUSIONS: This is the first study to explore the association of mtDNA variants with individual's risk of developing severe COVID-19. Based on the case-control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual's resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual's risk of developing severe COVID-19.}, } @article {pmid34727288, year = {2022}, author = {Liu, K and Xie, N and Ma, HJ}, title = {Next-generation sequencing reveals the mitogenomic heteroplasmy in the topmouth culter (Culter alburnus Basilewsky, 1855).}, journal = {Molecular biology reports}, volume = {49}, number = {2}, pages = {943-950}, pmid = {34727288}, issn = {1573-4978}, support = {20162012A03//Hangzhou Agricultural & Social Development Research Program/ ; 2019HNCT-01//Science & Technology Innovation Program of Hangzhou Academy of Agricultural Sciences/ ; }, mesh = {Animals ; China ; Cyprinidae/*genetics ; Cypriniformes/genetics ; DNA, Mitochondrial/*genetics ; Fish Proteins/genetics ; Heteroplasmy/*genetics ; High-Throughput Nucleotide Sequencing/methods ; Mitogens/genetics ; Phylogeny ; }, abstract = {BACKGROUND: The mitogenomic heteroplasmy is the presence of multiple haplotypes in the mitochondria, which could cause genetic diseases and is also associated with many critical biological functions. The topmouth culter (Culter alburnus Basilewsky, 1855) is one of the most important freshwater fish in the family of Cyprinidae in China. At present, there are no reports on the topmouth culter's mtDNA heteroplasmy and the existence of which is not known.

METHODS AND RESULTS: This study aimed to analyze the mitogenomic heteroplasmy in the topmouth culter by the next-generation sequencing of the fins' total DNA. The results confirmed the existence of the heteroplasmy and indicated the presence of the extensive heteroplasmy in the topmouth culter's mitogenome. There were 38 heteroplasmic variations in the protein-coding genes from the three specimens, with 33 non-synonymous substitutions accounting for 86.84% and five synonymous substitutions accounting for 13.16%. Among them, the ND6 had the most heteroplasmic variations but only one synonymous substitution. After removing the putative nuclear mitochondrial DNA fragments, the ratio of primary haplotype in the three specimens was 43.89%, 74.72%, and 32.76%, respectively. The three specimens contained 21, 7, and 21 haplotypes of the mitogenomes, respectively. Due to the extensive heteroplasmy, we reconstructed the phylogenetic tree of the topmouth culter using the RY-coding method, which improved the performance of the phylogenetic tree to some extent.

CONCLUSIONS: This study reported the mitogenomic heteroplasmy in the topmouth culter and enhanced the knowledge regarding the mitogenomic heteroplasmy in phylogenetic studies. As the topmouth culter is a commercial species, the mitogenomic heteroplasmy is crucial for the fisheries management of the topmouth culter.}, } @article {pmid34728739, year = {2021}, author = {Wang, X and Li, LL and Xiao, Y and Chen, XY and Chen, JH and Hu, XS}, title = {A complete sequence of mitochondrial genome of Neolamarckia cadamba and its use for systematic analysis.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {21452}, pmid = {34728739}, issn = {2045-2322}, support = {2018-GDTK-08//Central Finance Forestry Reform and Development Fund/ ; 4400-K16013//South China Agricultural University/ ; }, mesh = {DNA, Mitochondrial/analysis/*genetics ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; *Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics/metabolism ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Rubiaceae/*genetics/growth & development ; *Transcriptome ; }, abstract = {Neolamarckia cadamba is an important tropical and subtropical tree for timber industry in southern China and is also a medicinal plant because of the secondary product cadambine. N. cadamba belongs to Rubiaceae family and its taxonomic relationships with other species are not fully evaluated based on genome sequences. Here, we report the complete sequences of mitochondrial genome of N. cadamba, which is 414,980 bp in length and successfully assembled in two genome circles (109,836 bp and 305,144 bp). The mtDNA harbors 83 genes in total, including 40 protein-coding genes (PCGs), 31 transfer RNA genes, 6 ribosomal RNA genes, and 6 other genes. The base composition of the whole genome is estimated as 27.26% for base A, 22.63% for C, 22.53% for G, and 27.56% for T, with the A + T content of 54.82% (54.45% in the small circle and 54.79% in the large circle). Repetitive sequences account for ~ 0.14% of the whole genome. A maximum likelihood (ML) tree based on DNA sequences of 24 PCGs supports that N. cadamba belongs to order Gentianales. A ML tree based on rps3 gene of 60 species in family Rubiaceae shows that N. cadamba is more related to Cephalanthus accidentalis and Hymenodictyon parvifolium and belongs to the Cinchonoideae subfamily. The result indicates that N. cadamba is genetically distant from the species and genera of Rubiaceae in systematic position. As the first sequence of mitochondrial genome of N. cadamba, it will provide a useful resource to investigate genetic variation and develop molecular markers for genetic breeding in the future.}, } @article {pmid34734993, year = {2022}, author = {Hüdig, M and Tronconi, MA and Zubimendi, JP and Sage, TL and Poschmann, G and Bickel, D and Gohlke, H and Maurino, VG}, title = {Respiratory and C4-photosynthetic NAD-malic enzyme coexist in bundle sheath cell mitochondria and evolved via association of differentially adapted subunits.}, journal = {The Plant cell}, volume = {34}, number = {1}, pages = {597-615}, pmid = {34734993}, issn = {1532-298X}, mesh = {Adaptation, Biological ; Capparaceae/*enzymology ; Cleome/enzymology ; *Evolution, Molecular ; Malate Dehydrogenase/*chemistry/metabolism ; Mitochondria/metabolism ; Plant Proteins/*chemistry/metabolism ; }, abstract = {In plant mitochondria, nicotinamide adenine dinucleotide-malic enzyme (NAD-ME) has a housekeeping function in malate respiration. In different plant lineages, NAD-ME was independently co-opted in C4 photosynthesis. In the C4 Cleome species, Gynandropsis gynandra and Cleome angustifolia, all NAD-ME genes (NAD-MEα, NAD-MEβ1, and NAD-MEβ2) were affected by C4 evolution and are expressed at higher levels than their orthologs in the C3 species Tarenaya hassleriana. In T. hassleriana, the NAD-ME housekeeping function is performed by two heteromers, NAD-MEα/β1 and NAD-MEα/β2, with similar biochemical properties. In both C4 species, this role is restricted to NAD-MEα/β2. In the C4 species, NAD-MEα/β1 is exclusively present in the leaves, where it accounts for most of the enzymatic activity. Gynandropsis gynandra NAD-MEα/β1 (GgNAD-MEα/β1) exhibits high catalytic efficiency and is differentially activated by the C4 intermediate aspartate, confirming its role as the C4-decarboxylase. During C4 evolution, NAD-MEβ1 lost its catalytic activity; its contribution to the enzymatic activity results from a stabilizing effect on the associated α-subunit and the acquisition of regulatory properties. We conclude that in bundle sheath cell mitochondria of C4 species, the functions of NAD-ME as C4 photosynthetic decarboxylase and as a housekeeping enzyme coexist and are performed by isoforms that combine the same α-subunit with differentially adapted β-subunits.}, } @article {pmid34746119, year = {2021}, author = {Thomas, LW and Ashcroft, M}, title = {The Contextual Essentiality of Mitochondrial Genes in Cancer.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {695351}, pmid = {34746119}, issn = {2296-634X}, support = {209749/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Mitochondria are key organelles in eukaryotic evolution that perform crucial roles as metabolic and cellular signaling hubs. Mitochondrial function and dysfunction are associated with a range of diseases, including cancer. Mitochondria support cancer cell proliferation through biosynthetic reactions and their role in signaling, and can also promote tumorigenesis via processes such as the production of reactive oxygen species (ROS). The advent of (nuclear) genome-wide CRISPR-Cas9 deletion screens has provided gene-level resolution of the requirement of nuclear-encoded mitochondrial genes (NEMGs) for cancer cell viability (essentiality). More recently, it has become apparent that the essentiality of NEMGs is highly dependent on the cancer cell context. In particular, key tumor microenvironmental factors such as hypoxia, and changes in nutrient (e.g., glucose) availability, significantly influence the essentiality of NEMGs. In this mini-review we will discuss recent advances in our understanding of the contribution of NEMGs to cancer from CRISPR-Cas9 deletion screens, and discuss emerging concepts surrounding the context-dependent nature of mitochondrial gene essentiality.}, } @article {pmid34748608, year = {2021}, author = {Powers, MJ and Martz, LD and Burton, RS and Hill, GE and Weaver, RJ}, title = {Evidence for hybrid breakdown in production of red carotenoids in the marine invertebrate Tigriopus californicus.}, journal = {PloS one}, volume = {16}, number = {11}, pages = {e0259371}, pmid = {34748608}, issn = {1932-6203}, mesh = {Animals ; Aquatic Organisms ; Carotenoids/*metabolism ; Cell Nucleus/genetics/metabolism ; Copepoda/*genetics/metabolism ; *Genetic Fitness ; Hybridization, Genetic ; Invertebrates ; Mitochondria/genetics/metabolism ; Oxidative Phosphorylation ; Xanthophylls/metabolism ; }, abstract = {The marine copepod, Tigriopus californicus, produces the red carotenoid pigment astaxanthin from yellow dietary precursors. This 'bioconversion' of yellow carotenoids to red is hypothesized to be linked to individual condition, possibly through shared metabolic pathways with mitochondrial oxidative phosphorylation. Experimental inter-population crosses of lab-reared T. californicus typically produces low-fitness hybrids is due in large part to the disruption of coadapted sets nuclear and mitochondrial genes within the parental populations. These hybrid incompatibilities can increase variability in life history traits and energy production among hybrid lines. Here, we tested if production of astaxanthin was compromised in hybrid copepods and if it was linked to mitochondrial metabolism and offspring development. We observed no clear mitonuclear dysfunction in hybrids fed a limited, carotenoid-deficient diet of nutritional yeast. However, when yellow carotenoids were restored to their diet, hybrid lines produced less astaxanthin than parental lines. We observed that lines fed a yeast diet produced less ATP and had slower offspring development compared to lines fed a more complete diet of algae, suggesting the yeast-only diet may have obscured effects of mitonuclear dysfunction. Astaxanthin production was not significantly associated with development among lines fed a yeast diet but was negatively related to development in early generation hybrids fed an algal diet. In lines fed yeast, astaxanthin was negatively related to ATP synthesis, but in lines fed algae, the relationship was reversed. Although the effects of the yeast diet may have obscured evidence of hybrid dysfunction, these results suggest that astaxanthin bioconversion may still be related to mitochondrial performance and reproductive success.}, } @article {pmid34748935, year = {2022}, author = {Boël, M and Veyrunes, F and Durieux, AC and Freyssenet, D and Voituron, Y and Roussel, D}, title = {Does high mitochondrial efficiency carry an oxidative cost? The case of the African pygmy mouse (Mus mattheyi).}, journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology}, volume = {264}, number = {}, pages = {111111}, doi = {10.1016/j.cbpa.2021.111111}, pmid = {34748935}, issn = {1531-4332}, mesh = {Adenosine Diphosphate/metabolism ; Animals ; Hydrogen Peroxide/metabolism ; Mice ; Mice, Inbred C57BL ; Mitochondria, Muscle/*metabolism ; Muscle, Skeletal/metabolism ; Oxidative Phosphorylation ; Oxidative Stress ; Oxygen Consumption ; Reactive Oxygen Species/metabolism ; Species Specificity ; }, abstract = {Skeletal muscle mitochondria of the African pygmy mouse Mus mattheyi exhibit markedly reduced oxygen consumption and ATP synthesis rates but a higher mitochondrial efficiency than what would be expected from allometric trends. In the present study, we assessed whether such reduction of mitochondrial activity in M. mattheyi can limit the oxidative stress associated with an increased generation of mitochondrial reactive oxygen species. We conducted a comparative study of mitochondrial oxygen consumption, H2O2 release, and electron leak (%H2O2/O) in skeletal muscle mitochondria isolated from the extremely small African pygmy mouse (M. mattheyi, ~5 g) and Mus musculus, which is a larger Mus species (~25 g). Mitochondria were energized with pyruvate, malate, and succinate, after which fluxes were measured at different steady-state rates of oxidative phosphorylation. Overall, M. mattheyi exhibited lower oxidative activity and higher electron leak than M. musculus, while the H2O2 release did not differ significantly between these two Mus species. We further found that the high coupling efficiency of skeletal muscle mitochondria from M. mattheyi was associated with high electron leak. Nevertheless, data also show that, despite the higher electron leak, the lower mitochondrial respiratory capacity of M. mattheyi limits the cost of a net increase in H2O2 release, which is lower than that expected for a mammals of this size.}, } @article {pmid34752746, year = {2021}, author = {Erinjeri, AP and Labbadia, J}, title = {The importance of long-lived proteins: Not just nuclear anymore.}, journal = {Developmental cell}, volume = {56}, number = {21}, pages = {2925-2927}, doi = {10.1016/j.devcel.2021.10.015}, pmid = {34752746}, issn = {1878-1551}, mesh = {*Electron Transport Complex IV/metabolism ; *Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; }, abstract = {The significance of mitochondrial long-lived proteins (mitoLLPs) to tissue health has remained mysterious for over a decade. In this issue of Developmental Cell, Krishna et al. demonstrate that mitochondrial lifetimes are highly heterogeneous and that mitoLLPs promote respiratory capacity by facilitating supercomplex assembly within the electron transport chain.}, } @article {pmid34773616, year = {2022}, author = {Skuza, L}, title = {Primer Design for the Analysis of Closely Related Species: Application of Noncoding mtDNA and cpDNA Sequences.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2392}, number = {}, pages = {83-91}, pmid = {34773616}, issn = {1940-6029}, mesh = {Chloroplasts/genetics ; DNA, Chloroplast/genetics ; DNA, Mitochondrial/genetics ; *Mitochondria/genetics ; Phylogeny ; Plants/genetics ; Secale/genetics ; }, abstract = {Noncoding regions of the chloroplast (cpDNA) and mitochondrial (mtDNA) genomes are commonly used in plant phylogenetic and population studies. Consensus primers, which are homologous to most coding regions, but amplify variable noncoding regions, are very useful for this purpose. However, high genetic diversity of plants poses a problem in developing molecular methods that require conserved DNA sequences between species.This chapter describes the protocol for designing PCR primers suitable for analysis of closely related plant species. As an example, we used PCR primer design for cpDNA noncoding regions of the rye (Secale).}, } @article {pmid34773990, year = {2021}, author = {Liu, Y and Qu, J and Shi, Z and Zhang, P and Ren, M}, title = {Comparative genomic analysis of the tricarboxylic acid cycle members in four Solanaceae vegetable crops and expression pattern analysis in Solanum tuberosum.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {821}, pmid = {34773990}, issn = {1471-2164}, mesh = {Citric Acid Cycle/genetics ; Genomics ; Phylogeny ; *Solanum tuberosum/genetics ; Vegetables ; }, abstract = {BACKGROUND: The tricarboxylic acid (TCA) cycle is crucial for energy supply in animal, plant, and microbial cells. It is not only the main pathway of carbohydrate catabolism but also the final pathway of lipid and protein catabolism. Some TCA genes have been found to play important roles in the growth and development of tomato and potato, but no comprehensive study of TCA cycle genes in Solanaceae crops has been reported.

RESULTS: In this study, we analyzed TCA cycle genes in four important Solanaceae vegetable crops (potato (Solanum tuberosum), tomato (Solanum lycopersicum), eggplant (Solanum melongena), and pepper (Capsicum annuum)) based on comparative genomics. The four Solanaceae crops had a total of 180 TCA cycle genes: 43 in potato, 44 in tomato, 40 in eggplant, and 53 in pepper. Phylogenetic analysis, collinearity analysis, and tissue expression patterns revealed the conservation of and differences in TCA cycle genes between the four Solanaceae crops and found that there were unique subgroup members in Solanaceae crops that were independent of Arabidopsis genes. The expression analysis of potato TCA cycle genes showed that (1) they were widely expressed in various tissues, and some transcripts like Soltu.DM.01G003320.1(SCoAL) and Soltu.DM.04G021520.1 (SDH) mainly accumulate in vegetative organs, and some transcripts such as Soltu.DM.12G005620.3 (SDH) and Soltu.DM.02G007400.4 (MDH) are preferentially expressed in reproductive organs; (2) several transcripts can be significantly induced by hormones, such as Soltu.DM.08G023870.2 (IDH) and Soltu.DM.06G029290.1 (SDH) under ABA treatment, and Soltu.DM.07G021850.2 (CSY) and Soltu.DM.09G026740.1 (MDH) under BAP treatment, and Soltu.DM.02G000940.1 (IDH) and Soltu.DM.01G031350.4 (MDH) under GA treatment; (3) Soltu.DM.11G024650.1 (SDH) can be upregulated by the three disease resistance inducers including Phytophthora infestans, acibenzolar-S-methyl (BTH), and DL-β-amino-n-butyric acid (BABA); and (4) the levels of Soltu.DM.01G045790.1 (MDH), Soltu.DM.01G028520.3 (CSY), and Soltu.DM.12G028700.1 (CSY) can be activated by both NaCl and mannitol. The subcellular localization results of three potato citrate synthases showed that Soltu.DM.01G028520.3 was localized in mitochondria, while Soltu.DM.12G028700.1 and Soltu.DM.07G021850.1 were localized in the cytoplasm.

CONCLUSIONS: This study provides a scientific foundation for the comprehensive understanding and functional studies of TCA cycle genes in Solanaceae crops and reveals their potential roles in potato growth, development, and stress response.}, } @article {pmid34781749, year = {2021}, author = {Benhamou, S and Rahioui, I and Henri, H and Charles, H and Da Silva, P and Heddi, A and Vavre, F and Desouhant, E and Calevro, F and Mouton, L}, title = {Cytotype Affects the Capability of the Whitefly Bemisia tabaci MED Species To Feed and Oviposit on an Unfavorable Host Plant.}, journal = {mBio}, volume = {12}, number = {6}, pages = {e0073021}, pmid = {34781749}, issn = {2150-7511}, mesh = {Amino Acids/chemistry ; Animals ; Feeding Behavior ; Fertility ; Hemiptera/classification/*physiology ; Hibiscus/chemistry/*parasitology/physiology ; Host Specificity ; Lantana/chemistry/*parasitology/physiology ; Mitochondria/metabolism ; Oviposition ; Symbiosis ; Nicotiana/chemistry/*parasitology/physiology ; }, abstract = {The acquisition of nutritional obligate primary endosymbionts (P-symbionts) allowed phloemo-phageous insects to feed on plant sap and thus colonize novel ecological niches. P-symbionts often coexist with facultative secondary endosymbionts (S-symbionts), which may also influence their hosts' niche utilization ability. The whitefly Bemisia tabaci is a highly diversified species complex harboring, in addition to the P-symbiont "Candidatus Portiera aleyrodidarum," seven S-symbionts whose roles remain poorly understood. Here, we compare the phenotypic and metabolic responses of three B. tabaci lines differing in their S-symbiont community, reared on three different host plants, hibiscus, tobacco, or lantana, and address whether and how S-symbionts influence insect capacity to feed and produce offspring on those plants. We first show that hibiscus, tobacco, and lantana differ in their free amino acid composition. Insects' performance, as well as free amino acid profile and symbiotic load, were shown to be plant dependent, suggesting a critical role for the plant nutritional properties. Insect fecundity was significantly lower on lantana, indicating that it is the least favorable plant. Remarkably, insects reared on this plant show a specific amino acid profile and a higher symbiont density compared to the two other plants. In addition, this plant was the only one for which fecundity differences were observed between lines. Using genetically homogeneous hybrids, we demonstrate that cytotype (mitochondria and symbionts), and not genotype, is a major determinant of females' fecundity and amino acid profile on lantana. As cytotypes differ in their S-symbiont community, we propose that these symbionts may mediate their hosts' suitable plant range. IMPORTANCE Microbial symbionts are universal in eukaryotes, and it is now recognized that symbiotic associations represent major evolutionary driving forces. However, the extent to which symbionts contribute to their hosts' ecological adaptation and subsequent diversification is far from being fully elucidated. The whitefly Bemisia tabaci is a sap feeder associated with multiple coinfecting intracellular facultative symbionts. Here, we show that plant species simultaneously affect whiteflies' performance, amino acid profile, and symbiotic density, which could be partially explained by differences in plant nutritional properties. We also demonstrate that, on lantana, the least favorable plant used in our study, whiteflies' performance is determined by their cytotype. We propose that the host plant utilization in B. tabaci is influenced by its facultative symbiont community composition, possibly through its impact on the host dietary requirements. Altogether, our data provide new insights into the impact of intracellular microorganisms on their animal hosts' ecological niche range and diversification.}, } @article {pmid34783988, year = {2022}, author = {López-Cuamatzi, IL and Ortega, J and Baeza, JA}, title = {The complete mitochondrial genome of the 'Zacatuche' Volcano rabbit (Romerolagus diazi), an endemic and endangered species from the Volcanic Belt of Central Mexico.}, journal = {Molecular biology reports}, volume = {49}, number = {2}, pages = {1141-1149}, pmid = {34783988}, issn = {1573-4978}, mesh = {Animals ; Conservation of Natural Resources/methods ; Endangered Species ; Gene Order ; Genome, Mitochondrial/*genetics ; Lagomorpha/*genetics ; Mexico ; Mitochondria/*genetics ; Phylogeny ; RNA, Transfer/genetics ; Rabbits/genetics ; }, abstract = {BACKGROUND: The 'Zacatuche', 'Teporingo', or Volcano rabbit (Romerolagus diazi) belongs to the family Leporidae, is an endemic species restricted to the Central part of the Trans-Mexican Volcanic Belt, and is considered 'endangered' by the IUCN Red List of Threatened Species.

METHODS AND RESULTS: This study reports, for the first time, the complete mitochondrial genome of R. diazi and examined the phylogenetic position of R. diazi among other closely related co-familiar species using mitochondrial protein-coding genes (PCGs). The mitogenome of R. diazi was assembled from short Illumina 150 bp pair-end reads with a coverage of 189x. The AT-rich mitochondrial genome of R. diazi is 17,400 bp in length and is comprised of 13 PCGs, two ribosomal RNA genes, and 22 transfer RNA genes. The gene order observed in the mitochondrial genome of R. diazi is identical to that reported for other leporids. Phylogenetic analyses based on PCGs support the basal position of Romerolagus within the Leporidae, at least when compared to the genera Oryctolagus and Lepus. Nonetheless, additional mitochondrial genomes from species belonging to the genera Bunolagus, Sylvilagus, and Pronolagus, among others, are needed before a more robust conclusion about the derived vs basal placement of Romerolagus within the family Leporidae can be reached based on mitochondrial PCGs.

CONCLUSIONS: This is the first genomic resource developed for R. diazi and it represents a tool to improve our understanding about the ecology and evolutionary biology of this iconic and endangered species.}, } @article {pmid34784177, year = {2021}, author = {Holehouse, AS and Ginell, GM and Griffith, D and Böke, E}, title = {Clustering of Aromatic Residues in Prion-like Domains Can Tune the Formation, State, and Organization of Biomolecular Condensates.}, journal = {Biochemistry}, volume = {60}, number = {47}, pages = {3566-3581}, pmid = {34784177}, issn = {1520-4995}, mesh = {Amino Acids, Aromatic/chemistry/genetics/metabolism ; Animals ; Biomolecular Condensates/*metabolism ; Cell Polarity ; Cells, Cultured ; Female ; Intravital Microscopy ; Oocytes/cytology/metabolism ; Phase Transition ; Primary Cell Culture ; Protein Domains/genetics ; Protein Engineering ; T-Box Domain Proteins/chemistry/genetics/*metabolism ; Xenopus Proteins/chemistry/genetics/*metabolism ; Xenopus laevis ; }, abstract = {In immature oocytes, Balbiani bodies are conserved membraneless condensates implicated in oocyte polarization, the organization of mitochondria, and long-term organelle and RNA storage. In Xenopus laevis, Balbiani body assembly is mediated by the protein Velo1. Velo1 contains an N-terminal prion-like domain (PLD) that is essential for Balbiani body formation. PLDs have emerged as a class of intrinsically disordered regions that can undergo various different types of intracellular phase transitions and are often associated with dynamic, liquid-like condensates. Intriguingly, the Velo1 PLD forms solid-like assemblies. Here we sought to understand why Velo1 phase behavior appears to be biophysically distinct from that of other PLD-containing proteins. Through bioinformatic analysis and coarse-grained simulations, we predict that the clustering of aromatic residues and the amino acid composition of residues between aromatics can influence condensate material properties, organization, and the driving forces for assembly. To test our predictions, we redesigned the Velo1 PLD to test the impact of targeted sequence changes in vivo. We found that the Velo1 design with evenly spaced aromatic residues shows rapid internal dynamics, as probed by fluorescent recovery after photobleaching, even when recruited into Balbiani bodies. Our results suggest that Velo1 might have been selected in evolution for distinctly clustered aromatic residues to maintain the structure of Balbiani bodies in long-lived oocytes. In general, our work identifies several tunable parameters that can be used to augment the condensate material state, offering a road map for the design of synthetic condensates.}, } @article {pmid34786732, year = {2022}, author = {Bykov, YS and Flohr, T and Boos, F and Zung, N and Herrmann, JM and Schuldiner, M}, title = {Widespread use of unconventional targeting signals in mitochondrial ribosome proteins.}, journal = {The EMBO journal}, volume = {41}, number = {1}, pages = {e109519}, pmid = {34786732}, issn = {1460-2075}, mesh = {Amino Acid Motifs ; Bacterial Proteins/chemistry ; Mitochondria/metabolism ; Mitochondrial Proteins/*metabolism ; Mitochondrial Ribosomes/*metabolism ; Models, Biological ; *Protein Sorting Signals ; Saccharomyces cerevisiae/*metabolism ; Sequence Homology, Amino Acid ; }, abstract = {Mitochondrial ribosomes are complex molecular machines indispensable for respiration. Their assembly involves the import of several dozens of mitochondrial ribosomal proteins (MRPs), encoded in the nuclear genome, into the mitochondrial matrix. Proteomic and structural data as well as computational predictions indicate that up to 25% of yeast MRPs do not have a conventional N-terminal mitochondrial targeting signal (MTS). We experimentally characterized a set of 15 yeast MRPs in vivo and found that five use internal MTSs. Further analysis of a conserved model MRP, Mrp17/bS6m, revealed the identity of the internal targeting signal. Similar to conventional MTS-containing proteins, the internal sequence mediates binding to TOM complexes. The entire sequence of Mrp17 contains positive charges mediating translocation. The fact that these sequence properties could not be reliably predicted by standard methods shows that mitochondrial protein targeting is more versatile than expected. We hypothesize that structural constraints imposed by ribosome assembly interfaces may have disfavored N-terminal presequences and driven the evolution of internal targeting signals in MRPs.}, } @article {pmid34789336, year = {2021}, author = {Proust, B and Radić, M and Vidaček, NŠ and Cottet, C and Attia, S and Lamarche, F and Ačkar, L and Mikulčić, VG and Tokarska-Schlattner, M and Ćetković, H and Schlattner, U and Bosnar, MH}, title = {NME6 is a phosphotransfer-inactive, monomeric NME/NDPK family member and functions in complexes at the interface of mitochondrial inner membrane and matrix.}, journal = {Cell & bioscience}, volume = {11}, number = {1}, pages = {195}, pmid = {34789336}, issn = {2045-3701}, support = {IP-2016-06-4021//Hrvatska Zaklada za Znanost/ ; IP-2019-04-5382//Hrvatska Zaklada za Znanost/ ; ANR-15-IDEX-02//French National Research Agency within the Investissements d'Avenir program/ ; }, abstract = {BACKGROUND: NME6 is a member of the nucleoside diphosphate kinase (NDPK/NME/Nm23) family which has key roles in nucleotide homeostasis, signal transduction, membrane remodeling and metastasis suppression. The well-studied NME1-NME4 proteins are hexameric and catalyze, via a phospho-histidine intermediate, the transfer of the terminal phosphate from (d)NTPs to (d)NDPs (NDP kinase) or proteins (protein histidine kinase). For the NME6, a gene/protein that emerged early in eukaryotic evolution, only scarce and partially inconsistent data are available. Here we aim to clarify and extend our knowledge on the human NME6.

RESULTS: We show that NME6 is mostly expressed as a 186 amino acid protein, but that a second albeit much less abundant isoform exists. The recombinant NME6 remains monomeric, and does not assemble into homo-oligomers or hetero-oligomers with NME1-NME4. Consequently, NME6 is unable to catalyze phosphotransfer: it does not generate the phospho-histidine intermediate, and no NDPK activity can be detected. In cells, we could resolve and extend existing contradictory reports by localizing NME6 within mitochondria, largely associated with the mitochondrial inner membrane and matrix space. Overexpressing NME6 reduces ADP-stimulated mitochondrial respiration and complex III abundance, thus linking NME6 to dysfunctional oxidative phosphorylation. However, it did not alter mitochondrial membrane potential, mass, or network characteristics. Our screen for NME6 protein partners revealed its association with NME4 and OPA1, but a direct interaction was observed only with RCC1L, a protein involved in mitochondrial ribosome assembly and mitochondrial translation, and identified as essential for oxidative phosphorylation.

CONCLUSIONS: NME6, RCC1L and mitoribosomes localize together at the inner membrane/matrix space where NME6, in concert with RCC1L, may be involved in regulation of the mitochondrial translation of essential oxidative phosphorylation subunits. Our findings suggest new functions for NME6, independent of the classical phosphotransfer activity associated with NME proteins.}, } @article {pmid34795357, year = {2021}, author = {Mishina, T and Takeshima, H and Takada, M and Iguchi, K and Zhang, C and Zhao, Y and Kawahara-Miki, R and Hashiguchi, Y and Tabata, R and Sasaki, T and Nishida, M and Watanabe, K}, title = {Interploidy gene flow involving the sexual-asexual cycle facilitates the diversification of gynogenetic triploid Carassius fish.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {22485}, pmid = {34795357}, issn = {2045-2322}, support = {18J00928//Japan Society for the Promotion of Science/ ; 21K14919//Japan Society for the Promotion of Science/ ; 15J02066//Japan Society for the Promotion of Science/ ; 26291079//Japan Society for the Promotion of Science/ ; 26250044//Japan Society for the Promotion of Science/ ; 17H03720//Japan Society for the Promotion of Science/ ; 18H01330//Japan Society for the Promotion of Science/ ; 20H03009//Japan Society for the Promotion of Science/ ; }, mesh = {Alleles ; Animals ; Asia ; Biological Evolution ; Cell Nucleus/metabolism ; DNA, Mitochondrial/genetics ; Diploidy ; Europe ; *Gene Flow ; Genetic Markers ; Genetics, Population ; Genotype ; Geography ; Goldfish/*genetics/*physiology ; Heterozygote ; Homozygote ; Japan/epidemiology ; Male ; Mitochondria/metabolism ; Models, Genetic ; Polymorphism, Single Nucleotide ; Principal Component Analysis ; Rivers ; Species Specificity ; Spermatozoa/physiology ; Transcriptome ; Triploidy ; }, abstract = {Asexual vertebrates are rare and at risk of extinction due to their restricted adaptability through the loss of genetic recombination. We explore the mechanisms behind the generation and maintenance of genetic diversity in triploid asexual (gynogenetic) Carassius auratus fish, which is widespread in East Asian fresh waters and exhibits one of the most extensive distribution among asexual vertebrates despite its dependence on host sperm. Our analyses of genetic composition using dozens of genetic markers and genome-wide transcriptome sequencing uncover admixed genetic composition of Japanese asexual triploid Carassius consisting of both the diverged Japanese and Eurasian alleles, suggesting the involvement of Eurasian lineages in its origin. However, coexisting sexual diploid relatives and asexual triploids in Japan show regional genetic similarity in both mitochondrial and nuclear markers. These results are attributed to a unique unidirectional gene flow from diploids to sympatric triploids, with the involvement of occasional sexual reproduction. Additionally, the asexual triploid shows a weaker population structure than the sexual diploid, and multiple triploid lineages coexist in most Japanese rivers. The generated diversity via repeated interploidy gene flow as well as an increased establishment of immigrants is assumed to offset the cost of asexual reproduction and might contribute to the successful broad distribution of this asexual vertebrate.}, } @article {pmid34797494, year = {2022}, author = {Yamazaki, D and Chiba, S}, title = {Comparing the genetic diversity and population structure of sister marine snails having contrasting habitat specificity.}, journal = {Molecular biology reports}, volume = {49}, number = {1}, pages = {393-401}, pmid = {34797494}, issn = {1573-4978}, mesh = {Animals ; DNA, Mitochondrial/*genetics ; Gene Flow ; Genetic Variation ; Genetics, Population ; Japan ; Mitochondria/*genetics ; Phylogeny ; Phylogeography ; Snails/*classification/genetics ; Species Specificity ; }, abstract = {BACKGROUND: To grasp the processes of spatial genetic structuring in open and connectable marine environments is the principal study goal in molecular biological studies. Comparative seascape genetics using multiple species are a powerful approach to understand the physical geographic and oceanographic effects on genetic variation. Besides, species-specific ecological traits such as dispersal abilities and habitat specificity are important factors for spatial genetic structuring.

METHODS AND RESULTS: We focused on the sister marine snail species Tegula kusairo and T. xanthostigma around the Japanese mainland, which have contrasting habitat specificities for wave strength. Tegula kusairo only inhabits sheltered coastal environments, while T. xanthostigma is found mainly on wave-exposed rocky shores facing the open sea. We estimated their genetic diversity indices and levels of population differentiation based on mtDNA. We found that the genetic diversity of T. kusairo was lower than that of T. xanthostigma, while their level of population genetic differentiation was higher than that of T. xanthostigma. Namely, the species specific to weak wave environments had a higher level of population genetic differentiation than the species specific to strong wave action.

CONCLUSION: Ecological traits linked not only to dispersal abilities but also to habitat specificity can influence genetic variation in a pair of closely related sister species distributed in the same seascape.}, } @article {pmid34798191, year = {2021}, author = {Lin, Y and Xiao, Q and Hao, Q and Qian, Z and Li, X and Li, P and Li, H and Chen, L}, title = {Genome-wide identification and functional analysis of the glutathione S-transferase (GST) family in Pomacea canaliculata.}, journal = {International journal of biological macromolecules}, volume = {193}, number = {Pt B}, pages = {2062-2069}, doi = {10.1016/j.ijbiomac.2021.11.038}, pmid = {34798191}, issn = {1879-0003}, mesh = {Animals ; Cold-Shock Response/genetics ; Gastropoda/*genetics ; Genome/*genetics ; Glutathione Transferase/*genetics ; Oxidative Stress/genetics ; Phylogeny ; Reactive Oxygen Species/metabolism ; }, abstract = {Cold causes oxidative stress in living organisms, mainly caused by the accumulation of reactive oxygen species (ROS). In the antioxidant defense systems, Glutathione S-transferases (GSTs) play a vital role in the regulation of detoxification and redox balance of ROS. In this study, the P. canaliculata GST gene family were characterized using a genome-wide search of the conserved domain. Phylogenetic tree and domain composition analysis revealed that 30 PcGSTs belong to seven classes, including five in MAPEG, two in Mu, nine in Omega, 11 in Sigma, one in Rho, Theta and Alpha class, respectively. RNA-seq analysis revealed that most PcGSTs localized in mitochondria highly expressed in hepatopancreas, and most PcGSTs localized in cytoplasm highly expressed in kidney. A total of 12 PcGST genes were significantly up-regulated and PcGST12 was significantly down-regulated after cold acclimation. Ten PcGSTs were identified as DEGs under cold stress after cold acclimation. qRT-PCR revealed that the expression level of five PcGST genes were significantly varied during the cold acclimation. The present study investigated the characterization of the P. canaliculata GST gene family, extending our understanding of GST mediated cold acclimation and cold stress-response mechanisms in this invasive snail.}, } @article {pmid34799698, year = {2021}, author = {Vowinckel, J and Hartl, J and Marx, H and Kerick, M and Runggatscher, K and Keller, MA and Mülleder, M and Day, J and Weber, M and Rinnerthaler, M and Yu, JSL and Aulakh, SK and Lehmann, A and Mattanovich, D and Timmermann, B and Zhang, N and Dunn, CD and MacRae, JI and Breitenbach, M and Ralser, M}, title = {The metabolic growth limitations of petite cells lacking the mitochondrial genome.}, journal = {Nature metabolism}, volume = {3}, number = {11}, pages = {1521-1535}, pmid = {34799698}, issn = {2522-5812}, support = {200829/WT_/Wellcome Trust/United Kingdom ; P 26713/FWF_/Austrian Science Fund FWF/Austria ; FC001134/WT_/Wellcome Trust/United Kingdom ; FC001134/CRUK_/Cancer Research UK/United Kingdom ; 260809/ERC_/European Research Council/International ; }, mesh = {Amino Acids/metabolism ; Biomass ; Cell Proliferation ; Citric Acid Cycle ; *Energy Metabolism ; Fungal Proteins/chemistry/genetics/metabolism ; *Genome, Mitochondrial ; Membrane Potential, Mitochondrial ; Mitochondria/*genetics/*metabolism ; Mutation ; Phenotype ; Structure-Activity Relationship ; Yeasts/*genetics/*metabolism ; }, abstract = {Eukaryotic cells can survive the loss of their mitochondrial genome, but consequently suffer from severe growth defects. 'Petite yeasts', characterized by mitochondrial genome loss, are instrumental for studying mitochondrial function and physiology. However, the molecular cause of their reduced growth rate remains an open question. Here we show that petite cells suffer from an insufficient capacity to synthesize glutamate, glutamine, leucine and arginine, negatively impacting their growth. Using a combination of molecular genetics and omics approaches, we demonstrate the evolution of fast growth overcomes these amino acid deficiencies, by alleviating a perturbation in mitochondrial iron metabolism and by restoring a defect in the mitochondrial tricarboxylic acid cycle, caused by aconitase inhibition. Our results hence explain the slow growth of mitochondrial genome-deficient cells with a partial auxotrophy in four amino acids that results from distorted iron metabolism and an inhibited tricarboxylic acid cycle.}, } @article {pmid34810731, year = {2021}, author = {Mousavi-Sabet, H and Eagderi, S and Vatandoust, S and Freyhof, J}, title = {Five new species of the sisorid catfish genus Glyptothorax from Iran (Teleostei: Sisoridae).}, journal = {Zootaxa}, volume = {5067}, number = {4}, pages = {451-484}, doi = {10.11646/zootaxa.5067.4.1}, pmid = {34810731}, issn = {1175-5334}, mesh = {Animals ; *Catfishes/genetics ; DNA, Mitochondrial ; Iran ; Mitochondria ; Rivers ; }, abstract = {Five new species of Glyptothorax are described from Iran. Glyptothorax alidaeii, new species, from the Seimare in the Karkheh drainage, G. galaxias, new species, from the upper Karun drainage, G. hosseinpanahii, new species, from the Zohreh drainage, G. pallens, new species, from the Sirvan drainage, and G. shapuri, new species, from Shapur in the Helleh drainage. Glyptothorax silviae from the Jarrahi drainage is re-diagnosed. All six species are morphologically distinguishable by the structure of the thoracic adhesive apparatus, as well as morphometric characters and details in the colour pattern. They form distinct mitochondrial clades between 1.2% and 4.1% minimum K2P distance based on the mitochondrial DNA barcode region.}, } @article {pmid34811145, year = {2021}, author = {Parrinha, D and Marques, MP and Heinicke, MP and Khalid, F and Parker, KL and Tolley, KA and Childers, JL and Conradie, W and Bauer, AM and Ceraco, LMP}, title = {A revision of Angolan species in the genus Pedioplanis Fitzinger (Squamata: Lacertidae), with the description of a new species.}, journal = {Zootaxa}, volume = {5032}, number = {1}, pages = {1-46}, doi = {10.11646/zootaxa.5032.1.1}, pmid = {34811145}, issn = {1175-5334}, mesh = {Animals ; Cell Nucleus ; *Lizards/genetics ; Mitochondria ; Phylogeny ; }, abstract = {The genus Pedioplanis reaches its northernmost limit in western Angola, where it is represented by three species, Pedioplanis benguelensis, P. haackei and P. huntleyi. The taxonomic status of P. benguelensis remains problematic, mainly due to the vague original description and the loss of the original type material. Here we provide a revision of the Angolan representatives of the genus, with the description of a new species, Pedioplanis serodioi sp. nov., from the lowlands of southwestern Angola. Phylogenetic analyses using a combination of mitochondrial (16S and ND2) and nuclear (RAG-1) markers, as well as morphological data, support the recognition of the new species. For purposes of nomenclatural stability, we designate a neotype for P. benguelensis and provide motivation to correct the spelling of the specific epithet to benguelensis. The clarification of the status of P. benguelensis and the description of a new species contribute to a better understanding of the taxonomy and biogeography of the genus Pedioplanis, as well as the general biogeographic context of southwestern Angola, adding to the growing evidence in favor of the recognition of this region as a hotspot of lizard diversity and endemism. An updated key to the genus is also provided.}, } @article {pmid34818432, year = {2022}, author = {Jiang, Y and Yue, L and Yang, F and Gillung, JP and Winterton, SL and Price, BW and Contreras-Ramos, A and Hayashi, F and Aspöck, U and Aspöck, H and Yeates, DK and Yang, D and Liu, X}, title = {Similar pattern, different paths: tracing the biogeographical history of Megaloptera (Insecta: Neuropterida) using mitochondrial phylogenomics.}, journal = {Cladistics : the international journal of the Willi Hennig Society}, volume = {38}, number = {3}, pages = {374-391}, doi = {10.1111/cla.12494}, pmid = {34818432}, issn = {1096-0031}, mesh = {Animals ; *Genome, Mitochondrial/genetics ; *Holometabola/genetics ; Insecta/genetics ; Mitochondria/genetics ; Phylogeny ; }, abstract = {The sequential breakup of the supercontinent Pangaea since the Middle Jurassic is one of the crucial factors that has driven the biogeographical patterns of terrestrial biotas. Despite decades of effort searching for concordant patterns between diversification and continental fragmentation among taxonomic groups, increasing evidence has revealed more complex and idiosyncratic scenarios resulting from a mixture of vicariance, dispersal and extinction. Aquatic insects with discreet ecological requirements, low vagility and disjunct distributions represent a valuable model for testing biogeographical hypotheses by reconstructing their distribution patterns and temporal divergences. Insects of the order Megaloptera have exclusively aquatic larvae, their adults have low vagility, and the group has a highly disjunct geographical distribution. Here we present a comprehensive phylogeny of Megaloptera based on a large-scale mitochondrial genome sequencing of 99 species representing >90% of the world genera from all major biogeographical regions. Molecular dating suggests that the deep divergence within Megaloptera pre-dates the breakup of Pangaea. Subsequently, the intergeneric divergences within Corydalinae (dobsonflies), Chauliodinae (fishflies) and Sialidae (alderflies) might have been driven by both vicariance and dispersal correlated with the shifting continent during the Cretaceous, but with strikingly different and incongruent biogeographical signals. The austral distribution of many corydalids appears to be a result of colonization from Eurasia through southward dispersal across Europe and Africa during the Cretaceous, whereas a nearly contemporaneous dispersal via northward rafting of Gondwanan landmasses may account for the colonization of extant Eurasian alderflies from the south.}, } @article {pmid34828378, year = {2021}, author = {Chen, F and Zou, H and Jin, X and Zhang, D and Li, W and Li, M and Wu, S and Wang, G}, title = {Sequencing of the Complete Mitochondrial Genome of Pingus sinensis (Spirurina: Quimperiidae): Gene Arrangements and Phylogenetic Implications.}, journal = {Genes}, volume = {12}, number = {11}, pages = {}, pmid = {34828378}, issn = {2073-4425}, mesh = {Animals ; Bayes Theorem ; Codon Usage ; Evolution, Molecular ; Gene Order ; Genome Size ; Genome, Mitochondrial ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA/*methods ; Spirurina/*genetics/isolation & purification ; }, abstract = {Despite several decades of intensive research on spirurine nematodes, molecular data on some of the main lineages are still absent, which makes taxonomic classification insufficiently resolved. In the present study, we sequenced the first complete mitogenome for the family Quimperiidae, belonging to P. sinensis (Spirurina: Quimperiidae), a parasite living in the intestines of snakehead (Ophiocephalus argus). The circular mitogenome is 13,874 bp long, and it contains the standard nematode gene set: 22 transfer RNAs, 2 ribosomal RNAs and 12 protein-coding genes. There are also two long non-coding regions (NCR), in addition to only 8 other intergenic regions, ranging in size from 1 to 58 bp. To investigate its phylogenetic position and study the relationships among other available Spirurina, we performed the phylogenetic analysis using Bayesian inference and maximum likelihood approaches by concatenating the nucleotide sequences of all 36 genes on a dataset containing all available mitogenomes of the suborder Spirurina from NCBI and compared with gene order phylogenies using the MLGO program. Both supported the closer relationship of Ascaridoidea to Seuratoidea than to Spiruroidea. Pingus formed a sister-group with the Cucullanus genus. The results provide a new insights into the relationships within Spirurina.}, } @article {pmid34829521, year = {2021}, author = {Olson, KR}, title = {A Case for Hydrogen Sulfide Metabolism as an Oxygen Sensing Mechanism.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {34829521}, issn = {2076-3921}, support = {IOS2012106//National Science Foundation USA/ ; }, abstract = {The ability to detect oxygen availability is a ubiquitous attribute of aerobic organisms. However, the mechanism(s) that transduce oxygen concentration or availability into appropriate physiological responses is less clear and often controversial. This review will make the case for oxygen-dependent metabolism of hydrogen sulfide (H2S) and polysulfides, collectively referred to as reactive sulfur species (RSS) as a physiologically relevant O2 sensing mechanism. This hypothesis is based on observations that H2S and RSS metabolism is inversely correlated with O2 tension, exogenous H2S elicits physiological responses identical to those produced by hypoxia, factors that affect H2S production or catabolism also affect tissue responses to hypoxia, and that RSS efficiently regulate downstream effectors of the hypoxic response in a manner consistent with a decrease in O2. H2S-mediated O2 sensing is then compared to the more generally accepted reactive oxygen species (ROS) mediated O2 sensing mechanism and a number of reasons are offered to resolve some of the confusion between the two.}, } @article {pmid34829656, year = {2021}, author = {Hernández-Camacho, JD and García-Corzo, L and Fernández-Ayala, DJM and Navas, P and López-Lluch, G}, title = {Coenzyme Q at the Hinge of Health and Metabolic Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {34829656}, issn = {2076-3921}, support = {P18-RT-4572//Regional Government of Andalusia/ ; UPO-126247//Regional Government of Andalusia/ ; UPO-1265673//Regional Government of Andalusia/ ; BIO-177//Regional Government of Andalusia/ ; FIS PI20/00541//Instituto de Salud Carlos III/ ; RED2018-102576-T//Centre for Biomedical Network Research on Rare Diseases/ ; FPU16/03264//Ministerio de Educación Cultura y Deporte/ ; }, abstract = {Coenzyme Q is a unique lipidic molecule highly conserved in evolution and essential to maintaining aerobic metabolism. It is endogenously synthesized in all cells by a very complex pathway involving a group of nuclear genes that share high homology among species. This pathway is tightly regulated at transcription and translation, but also by environment and energy requirements. Here, we review how coenzyme Q reacts within mitochondria to promote ATP synthesis and also integrates a plethora of metabolic pathways and regulates mitochondrial oxidative stress. Coenzyme Q is also located in all cellular membranes and plasma lipoproteins in which it exerts antioxidant function, and its reaction with different extramitochondrial oxidoreductases contributes to regulate the cellular redox homeostasis and cytosolic oxidative stress, providing a key factor in controlling various apoptosis mechanisms. Coenzyme Q levels can be decreased in humans by defects in the biosynthesis pathway or by mitochondrial or cytosolic dysfunctions, leading to a highly heterogeneous group of mitochondrial diseases included in the coenzyme Q deficiency syndrome. We also review the importance of coenzyme Q levels and its reactions involved in aging and age-associated metabolic disorders, and how the strategy of its supplementation has had benefits for combating these diseases and for physical performance in aging.}, } @article {pmid34831121, year = {2021}, author = {De Gaetano, A and Solodka, K and Zanini, G and Selleri, V and Mattioli, AV and Nasi, M and Pinti, M}, title = {Molecular Mechanisms of mtDNA-Mediated Inflammation.}, journal = {Cells}, volume = {10}, number = {11}, pages = {}, pmid = {34831121}, issn = {2073-4409}, support = {FAR di Dipartimento 2020//University of Modena and Reggio Emilia/ ; NA//Istituto Nazionale per le Ricerche Cardiovascolari/ ; }, mesh = {Biological Evolution ; Body Fluids/metabolism ; DNA, Mitochondrial/*genetics ; Extracellular Vesicles/metabolism ; Humans ; Inflammasomes/metabolism ; Inflammation/*genetics ; }, abstract = {Besides their role in cell metabolism, mitochondria display many other functions. Mitochondrial DNA (mtDNA), the own genome of the organelle, plays an important role in modulating the inflammatory immune response. When released from the mitochondrion to the cytosol, mtDNA is recognized by cGAS, a cGAMP which activates a pathway leading to enhanced expression of type I interferons, and by NLRP3 inflammasome, which promotes the activation of pro-inflammatory cytokines Interleukin-1beta and Interleukin-18. Furthermore, mtDNA can be bound by Toll-like receptor 9 in the endosome and activate a pathway that ultimately leads to the expression of pro-inflammatory cytokines. mtDNA is released in the extracellular space in different forms (free DNA, protein-bound DNA fragments) either as free circulating molecules or encapsulated in extracellular vesicles. In this review, we discussed the latest findings concerning the molecular mechanisms that regulate the release of mtDNA from mitochondria, and the mechanisms that connect mtDNA misplacement to the activation of inflammation in different pathophysiological conditions.}, } @article {pmid34833151, year = {2021}, author = {Vargas-Mendoza, N and Angeles-Valencia, M and Morales-González, Á and Madrigal-Santillán, EO and Morales-Martínez, M and Madrigal-Bujaidar, E and Álvarez-González, I and Gutiérrez-Salinas, J and Esquivel-Chirino, C and Chamorro-Cevallos, G and Cristóbal-Luna, JM and Morales-González, JA}, title = {Oxidative Stress, Mitochondrial Function and Adaptation to Exercise: New Perspectives in Nutrition.}, journal = {Life (Basel, Switzerland)}, volume = {11}, number = {11}, pages = {}, pmid = {34833151}, issn = {2075-1729}, abstract = {Cells have the ability to adapt to stressful environments as a part of their evolution. Physical exercise induces an increase of a demand for energy that must be met by mitochondria as the main (ATP) provider. However, this process leads to the increase of free radicals and the so-called reactive oxygen species (ROS), which are necessary for the maintenance of cell signaling and homeostasis. In addition, mitochondrial biogenesis is influenced by exercise in continuous crosstalk between the mitochondria and the nuclear genome. Excessive workloads may induce severe mitochondrial stress, resulting in oxidative damage. In this regard, the objective of this work was to provide a general overview of the molecular mechanisms involved in mitochondrial adaptation during exercise and to understand if some nutrients such as antioxidants may be implicated in blunt adaptation and/or an impact on the performance of exercise by different means.}, } @article {pmid34836918, year = {2023}, author = {Esteves, AR and Munoz-Pinto, MF and Nunes-Costa, D and Candeias, E and Silva, DF and Magalhães, JD and Pereira-Santos, AR and Ferreira, IL and Alarico, S and Tiago, I and Empadinhas, N and Cardoso, SM}, title = {Footprints of a microbial toxin from the gut microbiome to mesencephalic mitochondria.}, journal = {Gut}, volume = {72}, number = {1}, pages = {73-89}, pmid = {34836918}, issn = {1468-3288}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; Mesencephalon/metabolism/pathology ; *Parkinson Disease/metabolism ; Inflammation/metabolism ; Mitochondria/metabolism ; }, abstract = {OBJECTIVE: Idiopathic Parkinson's disease (PD) is characterised by alpha-synuclein (aSyn) aggregation and death of dopaminergic neurons in the midbrain. Recent evidence posits that PD may initiate in the gut by microbes or their toxins that promote chronic gut inflammation that will ultimately impact the brain. In this work, we sought to demonstrate that the effects of the microbial toxin β-N-methylamino-L-alanine (BMAA) in the gut may trigger some PD cases, which is especially worrying as this toxin is present in certain foods but not routinely monitored by public health authorities.

DESIGN: To test the hypothesis, we treated wild-type mice, primary neuronal cultures, cell lines and isolated mitochondria with BMAA, and analysed its impact on gut microbiota composition, barrier permeability, inflammation and aSyn aggregation as well as in brain inflammation, dopaminergic neuronal loss and motor behaviour. To further examine the key role of mitochondria, we also determined the specific effects of BMAA on mitochondrial function and on inflammasome activation.

RESULTS: BMAA induced extensive depletion of segmented filamentous bacteria (SFB) that regulate gut immunity, thus triggering gut dysbiosis, immune cell migration, increased intestinal inflammation, loss of barrier integrity and caudo-rostral progression of aSyn. Additionally, BMAA induced in vitro and in vivo mitochondrial dysfunction with cardiolipin exposure and consequent activation of neuronal innate immunity. These events primed neuroinflammation, dopaminergic neuronal loss and motor deficits.

CONCLUSION: Taken together, our results demonstrate that chronic exposure to dietary BMAA can trigger a chain of events that recapitulate the evolution of the PD pathology from the gut to the brain, which is consistent with 'gut-first' PD.}, } @article {pmid34847540, year = {2021}, author = {Fernández Casafuz, AB and De Rossi, MC and Bruno, L}, title = {Morphological fluctuations of individual mitochondria in living cells.}, journal = {Journal of physics. Condensed matter : an Institute of Physics journal}, volume = {34}, number = {9}, pages = {}, doi = {10.1088/1361-648X/ac3e9c}, pmid = {34847540}, issn = {1361-648X}, mesh = {*Cytoskeleton/metabolism ; Microscopy, Confocal ; *Microtubules/metabolism ; Mitochondria/physiology ; Organelles ; }, abstract = {Uncovering the link between mitochondrial morphology, dynamics, positioning and function is challenging. Mitochondria are very flexible organelles that are subject to tension and compression within cells. Recent findings highlighted the importance of these mechanical aspects in the regulation of mitochondria dynamics, arising the question on which are the processes and mechanisms involved in their shape remodeling. In this work we explored in detail the morphological changes and spatio-temporal fluctuations of these organelles in livingXenopus laevismelanophores, a well-characterized cellular model. We developed an automatic method for the classification of mitochondria shapes based on the analysis of the curvature of the contour shape from confocal microscopy images. A persistence length of 2.1μm was measured, quantifying, for the first time, the bending plasticity of mitochondria in their cellular environment. The shape evolution at the single organelle level was followed during a few minutes revealing that mitochondria can bend and unbend in the seconds timescale. Furthermore, the inspection of confocal movies simultaneously registering fluorescent mitochondria and microtubules suggests that the cytoskeleton network architecture and dynamics play a significant role in mitochondria shape remodeling and fluctuations. For instance changes from sinuous to elongated organelles related to transitions from confined behavior to fast directed motion along microtubule tracks were observed.}, } @article {pmid34858801, year = {2021}, author = {Dai, SD and Wang, S and Qin, YN and Zhu, JC}, title = {Multiomics Landscape Uncovers the Molecular Mechanism of the Malignant Evolution of Lung Adenocarcinoma Cells to Chronic Low Dose Cadmium Exposure.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {654687}, pmid = {34858801}, issn = {2234-943X}, abstract = {Cadmium (Cd) from cigarette smoke and polluted air can lead to lung adenocarcinoma after long-term inhalation. However, most studies are based on short-term exposure to this toxic metal at high concentrations. Here, we investigate the effects of long-term exposure of A549 cells (lung adenocarcinoma) to cadmium at low concentrations using morphological and multiomics analyses. First, we treated A549 cells continuously with CdCl2 at 1μM for 8 months and found that CdCl2 promoted cellular migration and invasion. After that, we applied transmission electron and fluorescence microscopies and did not observe significant morphological changes in Golgi apparatus, endoplasmic reticulum, lysosomes, or mitochondria on Cd treated cells; microfilaments, in contrast, accumulated in lamellipodium and adhesion plaques, which suggested that Cd enhanced cellular activity. Second, by using whole-exome sequencing (WES) we detected 4222 unique SNPs in Cd-treated cells, which included 382 unique non-synonymous mutation sites. The corresponding mutated genes, after GO and KEGG enrichments, were involved mainly in cell adhesion, movement, and metabolic pathways. Third, by RNA-seq analysis, we showed that 1250 genes (784 up and 466 down), 1623 mRNAs (1023 up and 591 down), and 679 lncRNAs (375 up and 304 down) were expressed differently. Furthermore, GO enrichment of these RNA-seq results suggested that most differentially expressed genes were related to cell adhesion and organization of the extracellular matrix in biological process terms; KEGG enrichment revealed that the differentially expressed genes took part in 26 pathways, among which the metabolic pathway was the most significant. These findings could be important for unveiling mechanisms of Cd-related cancers and for developing cancer therapies in the future.}, } @article {pmid34880150, year = {2022}, author = {Hussain, M and Liaqat, I and Mubin, M and Nisar, B and Shahzad, K and Durrani, AI and Zafar, U and Afzaal, M and Ehsan, A and Rubab, S}, title = {DNA Barcoding: Molecular Identification and Phylogenetic Analysis of Pheretimoid Earthworm (Metaphire sp. and Amynthas sp.) Based on Mitochondrial Partial COI Gene from Sialkot, Pakistan.}, journal = {Journal of oleo science}, volume = {71}, number = {1}, pages = {83-93}, doi = {10.5650/jos.ess21246}, pmid = {34880150}, issn = {1347-3352}, mesh = {Animals ; DNA Barcoding, Taxonomic/*methods ; Electron Transport Complex IV/*genetics ; Mitochondria/*enzymology/*genetics ; Oligochaeta/anatomy & histology/classification/*genetics ; Pakistan ; *Phylogeny ; Species Specificity ; }, abstract = {The extremely difficult and challenging process is identifying pheretimoid species, genus Metaphire and Amynthas involving increased homoplasy in various morphological characteristics. The molecular identification, phylogenetic relationships, and evolutionary divergence time of earthworms belonging to the pheretimoid complex were investigated in this study using partial mitochondrial COI (cytochrome C oxidase subunit I) gene sequences ranging from 550-680 bp. Results revealed that 86 pheretimoid earthworms were morphologically different from a total of 342 mature worms. Moreover, 11 pheretimoid species were molecularly identified, including Metaphire posthuma (02), M. anomala (01), M. houlleti (02), M. californica (01), M. birmanica (02), Amynthas minimus (01), A. morrisi (01), and M. bununa (01). A phylogenetic tree was constructed with bootstrap values of 95%, which supported a monophyletic lineage of two well-supported clades formed by 12 partial COI sequences and 48 GenBank sequences using Hirudo medicinalis as an outgroup. The monophyly of these obtained genera indicated overall similarity at species level. Today, species like Amynthas, Metaphire and Pheretima have worm diversity in the form of pheretimoid earthworms, which dates to the Late Miocene (11.2-5.3 Mya) and the Pliocene (5.3-2.4 Mya). Compared to all relevant pheretimoid species, genetic p-distance values ranged from 0.0% to 0.57% (less than 1%). These low range values demonstrated that both genera Metaphire and Amynthas, supported the theory, which states that there are shared similarities among the species, despite different morphology. The current study is the first attempt in Pakistan to identify earthworms through DNA barcoding thus providing a genomic stamp. The work explored the significance of COI gene sequences to construct molecular tools that will be useful to overcome the different obstacles in morphologically similar earthworm identification and their phylogenetic study.}, } @article {pmid34887330, year = {2022}, author = {Zandi, M}, title = {ORF8/ORF8a: a difference between SARS-CoV-2 and SARS-CoV.}, journal = {The European respiratory journal}, volume = {59}, number = {2}, pages = {}, pmid = {34887330}, issn = {1399-3003}, mesh = {Biomarkers ; *COVID-19 ; Humans ; Phylogeny ; *SARS-CoV-2 ; }, abstract = {ORF8 as an accessory protein of SARS-CoV-2 https://bit.ly/3Gr3OTK}, } @article {pmid34887560, year = {2021}, author = {Guberovic, I and Hurtado-Bagès, S and Rivera-Casas, C and Knobloch, G and Malinverni, R and Valero, V and Leger, MM and García, J and Basquin, J and Gómez de Cedrón, M and Frigolé-Vivas, M and Cheema, MS and Pérez, A and Ausió, J and Ramírez de Molina, A and Salvatella, X and Ruiz-Trillo, I and Eirin-Lopez, JM and Ladurner, AG and Buschbeck, M}, title = {Evolution of a histone variant involved in compartmental regulation of NAD metabolism.}, journal = {Nature structural & molecular biology}, volume = {28}, number = {12}, pages = {1009-1019}, pmid = {34887560}, issn = {1545-9985}, mesh = {Cell Nucleus/metabolism ; Chromatin/metabolism ; DNA Repair/genetics ; Energy Metabolism/*physiology ; Eukaryota/metabolism ; Histones/*genetics/*metabolism ; Humans ; NAD/*metabolism ; Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors ; }, abstract = {NAD metabolism is essential for all forms of life. Compartmental regulation of NAD[+] consumption, especially between the nucleus and the mitochondria, is required for energy homeostasis. However, how compartmental regulation evolved remains unclear. In the present study, we investigated the evolution of the macrodomain-containing histone variant macroH2A1.1, an integral chromatin component that limits nuclear NAD[+] consumption by inhibiting poly(ADP-ribose) polymerase 1 in vertebrate cells. We found that macroH2A originated in premetazoan protists. The crystal structure of the macroH2A macrodomain from the protist Capsaspora owczarzaki allowed us to identify highly conserved principles of ligand binding and pinpoint key residue substitutions, selected for during the evolution of the vertebrate stem lineage. Metabolic characterization of the Capsaspora lifecycle suggested that the metabolic function of macroH2A was associated with nonproliferative stages. Taken together, we provide insight into the evolution of a chromatin element involved in compartmental NAD regulation, relevant for understanding its metabolism and potential therapeutic applications.}, } @article {pmid34890311, year = {2021}, author = {Zaccaron, AZ and Stergiopoulos, I}, title = {Characterization of the mitochondrial genomes of three powdery mildew pathogens reveals remarkable variation in size and nucleotide composition.}, journal = {Microbial genomics}, volume = {7}, number = {12}, pages = {}, pmid = {34890311}, issn = {2057-5858}, mesh = {Ascomycota/*genetics ; Base Composition ; Cytochromes b/genetics ; Erysiphe/*genetics ; Genome Size ; Genome, Fungal ; *Genome, Mitochondrial ; Introns ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Powdery mildews comprise a large group of economically important phytopathogenic fungi. However, limited information exists on their mitochondrial genomes. Here, we assembled and compared the mitochondrial genomes of the powdery mildew pathogens Blumeria graminis f. sp. tritici, Erysiphe pisi, and Golovinomyces cichoracearum. Included in the comparative analysis was also the mitochondrial genome of Erysiphe necator that was previously analysed. The mitochondrial genomes of the four Erysiphales exhibit a similar gene content and organization but a large variation in size, with sizes ranging from 109800 bp in B. graminis f. sp. tritici to 332165 bp in G. cichoracearum, which is the largest mitochondrial genome of a fungal pathogen reported to date. Further comparative analysis revealed an unusual bimodal GC distribution in the mitochondrial genomes of B. graminis f. sp. tritici and G. cichoracearum that was not previously observed in fungi. The cytochrome b (cob) genes of E. necator, E. pisi, and G. cichoracearum were also exceptionally rich in introns, which in turn harboured rare open reading frames encoding reverse transcriptases that were likely acquired horizontally. Golovinomyces cichoracearum had also the longest cob gene (45 kb) among 703 fungal cob genes analysed. Collectively, these results provide novel insights into the organization of mitochondrial genomes of powdery mildew pathogens and represent valuable resources for population genetics and evolutionary studies.}, } @article {pmid34899176, year = {2021}, author = {Anoar, S and Woodling, NS and Niccoli, T}, title = {Mitochondria Dysfunction in Frontotemporal Dementia/Amyotrophic Lateral Sclerosis: Lessons From Drosophila Models.}, journal = {Frontiers in neuroscience}, volume = {15}, number = {}, pages = {786076}, pmid = {34899176}, issn = {1662-4548}, support = {MR/V003585/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by declining motor and cognitive functions. Even though these diseases present with distinct sets of symptoms, FTD and ALS are two extremes of the same disease spectrum, as they show considerable overlap in genetic, clinical and neuropathological features. Among these overlapping features, mitochondrial dysfunction is associated with both FTD and ALS. Recent studies have shown that cells derived from patients' induced pluripotent stem cells (iPSC)s display mitochondrial abnormalities, and similar abnormalities have been observed in a number of animal disease models. Drosophila models have been widely used to study FTD and ALS because of their rapid generation time and extensive set of genetic tools. A wide array of fly models have been developed to elucidate the molecular mechanisms of toxicity for mutations associated with FTD/ALS. Fly models have been often instrumental in understanding the role of disease associated mutations in mitochondria biology. In this review, we discuss how mutations associated with FTD/ALS disrupt mitochondrial function, and we review how the use of Drosophila models has been pivotal to our current knowledge in this field.}, } @article {pmid34904040, year = {2021}, author = {Gopan, A and Sarma, MS}, title = {Mitochondrial hepatopathy: Respiratory chain disorders- 'breathing in and out of the liver'.}, journal = {World journal of hepatology}, volume = {13}, number = {11}, pages = {1707-1726}, pmid = {34904040}, issn = {1948-5182}, abstract = {Mitochondria, the powerhouse of a cell, are closely linked to the pathophysiology of various common as well as not so uncommon disorders of the liver and beyond. Evolution supports a prokaryotic descent, and, unsurprisingly, the organelle is worthy of being labeled an organism in itself. Since highly metabolically active organs require a continuous feed of energy, any dysfunction in the structure and function of mitochondria can have variable impact, with the worse end of the spectrum producing catastrophic consequences with a multisystem predisposition. Though categorized a hepatopathy, mitochondrial respiratory chain defects are not limited to the liver in time and space. The liver involvement is also variable in clinical presentation as well as in age of onset, from acute liver failure, cholestasis, or chronic liver disease. Other organs like eye, muscle, central and peripheral nervous system, gastrointestinal tract, hematological, endocrine, and renal systems are also variably involved. Diagnosis hinges on recognition of subtle clinical clues, screening metabolic investigations, evaluation of the extra-hepatic involvement, and role of genetics and tissue diagnosis. Treatment is aimed at both circumventing the acute metabolic crisis and long-term management including nutritional rehabilitation. This review lists and discusses the burden of mitochondrial respiratory chain defects, including various settings when to suspect, their evolution with time, including certain specific disorders, their tiered evaluation with diagnostic algorithms, management dilemmas, role of liver transplantation, and the future research tools.}, } @article {pmid34905682, year = {2021}, author = {Niedźwiedzka-Rystwej, P and Bębnowska, D and Kołacz, R and Deptuła, W}, title = {Mitochondria, pattern recognition receptors and autophagy under physiological and pathological conditions, including viral infections.}, journal = {Acta biochimica Polonica}, volume = {69}, number = {1}, pages = {1-10}, doi = {10.18388/abp.2020_5807}, pmid = {34905682}, issn = {1734-154X}, mesh = {Animals ; Autophagy ; DNA, Mitochondrial/genetics ; Mammals/genetics/metabolism ; *Mitochondria/metabolism ; Receptors, Pattern Recognition/metabolism ; *Virus Diseases/metabolism ; }, abstract = {Research on the health of mammals invariably shows how dynamic immunology is and how the role of many elements and immune processes of the macroorganism, developed in the process of evolution in protecting against threats, including infections, is changing. Among these elements conditioning the homeostasis of the macroorganism are mitochondria, PRR receptors (pattern recognition receptors) and the phenomenon of autophagy. In the context of physiological and pathological states in the body, mitochondria perform various functions. The primary function of these organelles is to produce energy in the cell, but on the other hand, they are heavily involved in various cellular processes, including ROS production and calcium homeostasis. They are largely involved in the activation of immune mechanisms during infectious and non-infectious conditions through mtDNA and the mitochondrial MAVS protein. Mitochondrial involvement has been also determined in PRR-related mechanisms as mtDNA has the ability to directly stimulate TLRs. On the other hand, mitochondria are also associated with apoptotic cell death and autophagy.}, } @article {pmid34911545, year = {2021}, author = {Lewis, AJO and Hegde, RS}, title = {A unified evolutionary origin for the ubiquitous protein transporters SecY and YidC.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {266}, pmid = {34911545}, issn = {1741-7007}, support = {MC_UP_A022_1007/MRC_/Medical Research Council/United Kingdom ; MC_ UP_A022_1007/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Bacterial Proteins/metabolism ; Cell Membrane/metabolism ; *Escherichia coli Proteins/metabolism ; Hydrophobic and Hydrophilic Interactions ; Membrane Proteins/genetics/metabolism ; Membrane Transport Proteins/genetics ; }, abstract = {BACKGROUND: Protein transporters translocate hydrophilic segments of polypeptide across hydrophobic cell membranes. Two protein transporters are ubiquitous and date back to the last universal common ancestor: SecY and YidC. SecY consists of two pseudosymmetric halves, which together form a membrane-spanning protein-conducting channel. YidC is an asymmetric molecule with a protein-conducting hydrophilic groove that partially spans the membrane. Although both transporters mediate insertion of membrane proteins with short translocated domains, only SecY transports secretory proteins and membrane proteins with long translocated domains. The evolutionary origins of these ancient and essential transporters are not known.

RESULTS: The features conserved by the two halves of SecY indicate that their common ancestor was an antiparallel homodimeric channel. Structural searches with SecY's halves detect exceptional similarity with YidC homologs. The SecY halves and YidC share a fold comprising a three-helix bundle interrupted by a helical hairpin. In YidC, this hairpin is cytoplasmic and facilitates substrate delivery, whereas in SecY, it is transmembrane and forms the substrate-binding lateral gate helices. In both transporters, the three-helix bundle forms a protein-conducting hydrophilic groove delimited by a conserved hydrophobic residue. Based on these similarities, we propose that SecY originated as a YidC homolog which formed a channel by juxtaposing two hydrophilic grooves in an antiparallel homodimer. We find that archaeal YidC and its eukaryotic descendants use this same dimerisation interface to heterodimerise with a conserved partner. YidC's sufficiency for the function of simple cells is suggested by the results of reductive evolution in mitochondria and plastids, which tend to retain SecY only if they require translocation of large hydrophilic domains.

CONCLUSIONS: SecY and YidC share previously unrecognised similarities in sequence, structure, mechanism, and function. Our delineation of a detailed correspondence between these two essential and ancient transporters enables a deeper mechanistic understanding of how each functions. Furthermore, key differences between them help explain how SecY performs its distinctive function in the recognition and translocation of secretory proteins. The unified theory presented here explains the evolution of these features, and thus reconstructs a key step in the origin of cells.}, } @article {pmid34917101, year = {2021}, author = {Nunes, JPS and Moraes-Vieira, PM and Chevillard, C and Cunha-Neto, E}, title = {Editorial: Mitochondria at the Crossroads of Immunity and Inflammatory Tissue Damage.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {810787}, doi = {10.3389/fimmu.2021.810787}, pmid = {34917101}, issn = {1664-3224}, support = {P50 AI098461/AI/NIAID NIH HHS/United States ; U19 AI098461/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; Immunity/*immunology ; Inflammation/*immunology ; Mitochondria/*immunology ; }, } @article {pmid34919556, year = {2021}, author = {Lima-Cordón, RA and Cahan, SH and McCann, C and Dorn, PL and Justi, SA and Rodas, A and Monroy, MC and Stevens, L}, title = {Insights from a comprehensive study of Trypanosoma cruzi: A new mitochondrial clade restricted to North and Central America and genetic structure of TcI in the region.}, journal = {PLoS neglected tropical diseases}, volume = {15}, number = {12}, pages = {e0010043}, pmid = {34919556}, issn = {1935-2735}, mesh = {Central America ; Chagas Disease/*parasitology ; Electron Transport Complex I/genetics/metabolism ; Electron Transport Complex IV/genetics/metabolism ; Humans ; Mitochondria/*genetics/metabolism ; Phylogeny ; Protozoan Proteins/genetics/metabolism ; South America ; Trypanosoma cruzi/*classification/genetics/*isolation & purification ; }, abstract = {More than 100 years since the first description of Chagas Disease and with over 29,000 new cases annually due to vector transmission (in 2010), American Trypanosomiasis remains a Neglected Tropical Disease (NTD). This study presents the most comprehensive Trypanosoma cruzi sampling in terms of geographic locations and triatomine species analyzed to date and includes both nuclear and mitochondrial genomes. This addresses the gap of information from North and Central America. We incorporate new and previously published DNA sequence data from two mitochondrial genes, Cytochrome oxidase II (COII) and NADH dehydrogenase subunit 1 (ND1). These T. cruzi samples were collected over a broad geographic range including 111 parasite DNA samples extracted from triatomines newly collected across North and Central America, all of which were infected with T. cruzi in their natural environment. In addition, we present parasite reduced representation (Restriction site Associated DNA markers, RAD-tag) genomic nuclear data combined with the mitochondrial gene sequences for a subset of the triatomines (27 specimens) collected from Guatemala and El Salvador. Our mitochondrial phylogenetic reconstruction revealed two of the major mitochondrial lineages circulating across North and Central America, as well as the first ever mitochondrial data for TcBat from a triatomine collected in Central America. Our data also show that within mtTcIII, North and Central America represent an independent, distinct clade from South America, named here as mtTcIIINA-CA, geographically restricted to North and Central America. Lastly, the most frequent lineage detected across North and Central America, mtTcI, was also an independent, distinct clade from South America, noted as mtTcINA-CA. Furthermore, nuclear genome data based on Single Nucleotide Polymorphism (SNP) showed genetic structure of lineage TcI from specimens collected in Guatemala and El Salvador supporting the hypothesis that genetic diversity at a local scale has a geographical component. Our multiscale analysis contributes to the understanding of the independent and distinct evolution of T. cruzi lineages in North and Central America regions.}, } @article {pmid34925295, year = {2021}, author = {Fonseca, PLC and De-Paula, RB and Araújo, DS and Tomé, LMR and Mendes-Pereira, T and Rodrigues, WFC and Del-Bem, LE and Aguiar, ERGR and Góes-Neto, A}, title = {Global Characterization of Fungal Mitogenomes: New Insights on Genomic Diversity and Dynamism of Coding Genes and Accessory Elements.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {787283}, pmid = {34925295}, issn = {1664-302X}, abstract = {Fungi comprise a great diversity of species with distinct ecological functions and lifestyles. Similar to other eukaryotes, fungi rely on interactions with prokaryotes and one of the most important symbiotic events was the acquisition of mitochondria. Mitochondria are organelles found in eukaryotic cells whose main function is to generate energy through aerobic respiration. Mitogenomes (mtDNAs) are double-stranded circular or linear DNA from mitochondria that may contain core genes and accessory elements that can be replicated, transcribed, and independently translated from the nuclear genome. Despite their importance, investigative studies on the diversity of fungal mitogenomes are scarce. Herein, we have evaluated 788 curated fungal mitogenomes available at NCBI database to assess discrepancies and similarities among them and to better understand the mechanisms involved in fungal mtDNAs variability. From a total of 12 fungal phyla, four do not have any representative with available mitogenomes, which highlights the underrepresentation of some groups in the current available data. We selected representative and non-redundant mitogenomes based on the threshold of 90% similarity, eliminating 81 mtDNAs. Comparative analyses revealed considerable size variability of mtDNAs with a difference of up to 260 kb in length. Furthermore, variation in mitogenome length and genomic composition are generally related to the number and length of accessory elements (introns, HEGs, and uORFs). We identified an overall average of 8.0 (0-39) introns, 8.0 (0-100) HEGs, and 8.2 (0-102) uORFs per genome, with high variation among phyla. Even though the length of the core protein-coding genes is considerably conserved, approximately 36.3% of the mitogenomes evaluated have at least one of the 14 core coding genes absent. Also, our results revealed that there is not even a single gene shared among all mitogenomes. Other unusual genes in mitogenomes were also detected in many mitogenomes, such as dpo and rpo, and displayed diverse evolutionary histories. Altogether, the results presented in this study suggest that fungal mitogenomes are diverse, contain accessory elements and are absent of a conserved gene that can be used for the taxonomic classification of the Kingdom Fungi.}, } @article {pmid34930424, year = {2021}, author = {Kelly, S}, title = {The economics of organellar gene loss and endosymbiotic gene transfer.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {345}, pmid = {34930424}, issn = {1474-760X}, mesh = {Arabidopsis/genetics ; Bacteria/*genetics ; Cell Nucleus ; Chloroplasts ; Gene Transfer, Horizontal ; *Genome, Chloroplast ; *Genome, Mitochondrial ; Genome, Plant ; Host Microbial Interactions/genetics ; Mitochondria/genetics ; Proteomics ; Symbiosis/*genetics ; }, abstract = {BACKGROUND: The endosymbiosis of the bacterial progenitors of the mitochondrion and the chloroplast are landmark events in the evolution of life on Earth. While both organelles have retained substantial proteomic and biochemical complexity, this complexity is not reflected in the content of their genomes. Instead, the organellar genomes encode fewer than 5% of the genes found in living relatives of their ancestors. While many of the 95% of missing organellar genes have been discarded, others have been transferred to the host nuclear genome through a process known as endosymbiotic gene transfer.

RESULTS: Here, we demonstrate that the difference in the per-cell copy number of the organellar and nuclear genomes presents an energetic incentive to the cell to either delete organellar genes or transfer them to the nuclear genome. We show that, for the majority of transferred organellar genes, the energy saved by nuclear transfer exceeds the costs incurred from importing the encoded protein into the organelle where it can provide its function. Finally, we show that the net energy saved by endosymbiotic gene transfer can constitute an appreciable proportion of total cellular energy budgets and is therefore sufficient to impart a selectable advantage to the cell.

CONCLUSION: Thus, reduced cellular cost and improved energy efficiency likely played a role in the reductive evolution of mitochondrial and chloroplast genomes and the transfer of organellar genes to the nuclear genome.}, } @article {pmid34934212, year = {2021}, author = {Donoso-Fuentes, A and Arriagada-Santis, D}, title = {[Organ dysfunction syndrome and mitochondrial adaptation in the septic patient].}, journal = {Boletin medico del Hospital Infantil de Mexico}, volume = {78}, number = {6}, pages = {597-611}, doi = {10.24875/BMHIM.20000323}, pmid = {34934212}, issn = {1665-1146}, mesh = {Humans ; Microcirculation ; Mitochondria ; *Multiple Organ Failure ; *Shock, Septic ; }, abstract = {The ability to maintain an adequate energy balance and to respond and adapt to environmental stress at the cellular level are cornerstones for the survival and evolution of organisms. Therefore, in the presence of various factors, a cellular protection response is triggered by activation of mitochondrial function-dependent signaling. However, this essential reaction for individual cell survival can be detrimental to organ function (maladaptation), transforming the close balance between the two into the pathogenetic axis of organ dysfunction and eventual recovery in septic patients. Macrocirculatory and microcirculatory disruption undoubtedly contributes to organ dysfunction in the early stage of septic shock, while intrinsic metabolic-bioenergetic failure (cytopathic hypoxia) perpetuates inadequate cellular function. Therefore, mitochondrial dysfunction is a key process in the induction of multiple organ dysfunction syndrome in the septic patient. This syndrome can be considered as a complex hypometabolic adaptive phenomenon in the face of excessive and prolonged inflammatory stimulus to achieve regulation of energy homeostasis and preservation of organ function. In the future, there should be a transition from the current consensus therapeutic options, which are limited to control of the infectious focus, hemodynamic and life support, to metabolic resuscitation based on the molecular and genetic alterations triggered by the infection.}, } @article {pmid34938509, year = {2021}, author = {Wade, MJ and Fogarty, L}, title = {Adaptive co-evolution of mitochondria and the Y-chromosome: A resolution to conflict between evolutionary opponents.}, journal = {Ecology and evolution}, volume = {11}, number = {23}, pages = {17307-17313}, pmid = {34938509}, issn = {2045-7758}, abstract = {In most species with motile sperm, male fertility depends upon genes located on the Y-chromosome and in the mitochondrial genome. Coordinated adaptive evolution for the function of male fertility between genes on the Y and the mitochondrion is hampered by their uniparental inheritance in opposing sexes: The Y-chromosome is inherited uniparentally, father to son, and the mitochondrion is inherited maternally, mother to offspring. Preserving male fertility is problematic, because maternal inheritance permits mitochondrial mutations advantageous to females, but deleterious to male fertility, to accumulate in a population. Although uniparental inheritance with sex-restricted adaptation also affects genes on the Y-chromosome, females lack a Y-chromosome and escape the potential maladaptive consequences of male-limited selection. Evolutionary models have shown that mitochondrial mutations deleterious to male fertility can be countered by compensatory evolution of Y-linked mutations that restore it. However, direct adaptive coevolution of Y- and mitochondrial gene combinations has not yet been mathematically characterized. We use population genetic models to show that adaptive coevolution of Y and mitochondrial genes are possible when Y-mt gene combinations have positive effects on male fertility and populations are inbred.}, } @article {pmid34941991, year = {2022}, author = {Song, MH and Yan, C and Li, JT}, title = {MEANGS: an efficient seed-free tool for de novo assembling animal mitochondrial genome using whole genome NGS data.}, journal = {Briefings in bioinformatics}, volume = {23}, number = {1}, pages = {}, doi = {10.1093/bib/bbab538}, pmid = {34941991}, issn = {1477-4054}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing/methods ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA ; Software ; Whole Genome Sequencing/*methods ; }, abstract = {Advances in next-generation sequencing (NGS) technologies have led to an exponential increase in the number of whole genome sequences (WGS) in databases. This wealth of WGS data has greatly facilitated the recovery of full mitochondrial genomes (mitogenomes), which are vital for phylogenetic, evolutionary and ecological studies. Unfortunately, most existing software cannot easily assemble mitogenome reference sequences conveniently or efficiently. Therefore, we developed a seed-free de novo assembly tool, MEANGS, which applies the trie-search method to extend contigs from self-discovery seeds and assemble a mitogenome from animal WGS data. We then used data from 16 species with different qualities to compare the performance of MEANGS with three other available programs. MEANGS exhibited the best overall performance since it was the only one that completed all tests, and it assembled full or partial mitogenomes for all of the tested samples while the others failed. Furthermore, MEANGS selects superior assembly sequences and annotates protein-coding genes. Thus, MEANGS can be one of the most efficient software for generating high-quality mitogenomes so far, the further use of it will benefit the study on mitogenome based on whole genome NGS data. MEANGS is available at https://github.com/YanCCscu/meangs.}, } @article {pmid34942301, year = {2022}, author = {Bohálová, N and Dobrovolná, M and Brázda, V and Bidula, S}, title = {Conservation and over-representation of G-quadruplex sequences in regulatory regions of mitochondrial DNA across distinct taxonomic sub-groups.}, journal = {Biochimie}, volume = {194}, number = {}, pages = {28-34}, doi = {10.1016/j.biochi.2021.12.006}, pmid = {34942301}, issn = {1638-6183}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *G-Quadruplexes ; Genome ; Humans ; Mitochondria ; Regulatory Sequences, Nucleic Acid/genetics ; }, abstract = {G-quadruplexes have important regulatory roles in the nuclear genome but their distribution and potential roles in mitochondrial DNA (mtDNA) are poorly understood. We analysed 11883 mtDNA sequences from 18 taxonomic sub-groups and identified their frequency and location within mtDNA. Large differences in both the frequency and number of putative quadruplex-forming sequences (PQS) were observed amongst all the organisms and PQS frequency was negatively correlated with an increase in evolutionary age. PQS were over-represented in the 3'UTRs, D-loops, replication origins, and stem loops, indicating regulatory roles for quadruplexes in mtDNA. Variations of the G-quadruplex-forming sequence in the conserved sequence block II (CSBII) region of the human D-loop were conserved amongst other mammals, amphibians, birds, reptiles, and fishes. This D-loop PQS was conserved in the duplicated control regions of some birds and reptiles, indicating its importance to mitochondrial function. The guanine tracts in these PQS also displayed significant length heterogeneity and the length of these guanine tracts were generally longest in bird mtDNA. This information provides further insights into how G4s may contribute to the regulation and function of mtDNA and acts as a database of information for future studies investigating mitochondrial G4s in organisms other than humans.}, } @article {pmid34943861, year = {2021}, author = {Key, J and Torres-Odio, S and Bach, NC and Gispert, S and Koepf, G and Reichlmeir, M and West, AP and Prokisch, H and Freisinger, P and Newman, WG and Shalev, S and Sieber, SA and Wittig, I and Auburger, G}, title = {Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, pmid = {34943861}, issn = {2073-4409}, support = {W81XWH-20-1-0150//Office of the Assistant Secretary for Health/ ; W81XWH-17-1-0052//Office of the Assistant Secretary for Health/ ; R01 HL148153/HL/NHLBI NIH HHS/United States ; GN2494//Action Medical Research/ ; mitoNET, 01GM1906D//German Network for Mitochondrial Disorders/ ; }, mesh = {Adult ; Amino Acids/metabolism ; Brain/metabolism ; Cell Nucleus/*metabolism ; Computational Biology ; Conserved Sequence ; DNA, Mitochondrial/*metabolism ; Endopeptidase Clp/*metabolism ; Fibroblasts/metabolism ; Humans ; Male ; Mitochondria/*metabolism ; Mitochondrial Proteins/metabolism ; Models, Biological ; Protein Binding ; Protein Interaction Maps ; Proteome/metabolism ; Skin/pathology ; Subcellular Fractions/metabolism ; Transcription, Genetic ; }, abstract = {Biallelic pathogenic variants in CLPP, encoding mitochondrial matrix peptidase ClpP, cause a rare autosomal recessive condition, Perrault syndrome type 3 (PRLTS3). It is characterized by primary ovarian insufficiency and early sensorineural hearing loss, often associated with progressive neurological deficits. Mouse models showed that accumulations of (i) its main protein interactor, the substrate-selecting AAA+ ATPase ClpX, (ii) mitoribosomes, and (iii) mtDNA nucleoids are the main cellular consequences of ClpP absence. However, the sequence of these events and their validity in human remain unclear. Here, we studied global proteome profiles to define ClpP substrates among mitochondrial ClpX interactors, which accumulated consistently in ClpP-null mouse embryonal fibroblasts and brains. Validation work included novel ClpP-mutant patient fibroblast proteomics. ClpX co-accumulated in mitochondria with the nucleoid component POLDIP2, the mitochondrial poly(A) mRNA granule element LRPPRC, and tRNA processing factor GFM1 (in mouse, also GRSF1). Only in mouse did accumulated ClpX, GFM1, and GRSF1 appear in nuclear fractions. Mitoribosomal accumulation was minor. Consistent accumulations in murine and human fibroblasts also affected multimerizing factors not known as ClpX interactors, namely, OAT, ASS1, ACADVL, STOM, PRDX3, PC, MUT, ALDH2, PMPCB, UQCRC2, and ACADSB, but the impact on downstream metabolites was marginal. Our data demonstrate the primary impact of ClpXP on the assembly of proteins with nucleic acids and show nucleoid enlargement in human as a key consequence.}, } @article {pmid34943968, year = {2021}, author = {Singh, LN and Kao, SH and Wallace, DC}, title = {Unlocking the Complexity of Mitochondrial DNA: A Key to Understanding Neurodegenerative Disease Caused by Injury.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, pmid = {34943968}, issn = {2073-4409}, support = {MH108592/NH/NIH HHS/United States ; P50 HD105354/HD/NICHD NIH HHS/United States ; OD010944/NH/NIH HHS/United States ; W81XWH-21-1-0128//United States Department of Defense/ ; NS021328/NH/NIH HHS/United States ; }, mesh = {Brain Injuries, Traumatic/*genetics/pathology ; DNA, Mitochondrial/*genetics ; Genetic Variation/genetics ; Humans ; Mitochondria/*genetics ; Risk Factors ; Stroke/*genetics/pathology ; }, abstract = {Neurodegenerative disorders that are triggered by injury typically have variable and unpredictable outcomes due to the complex and multifactorial cascade of events following the injury and during recovery. Hence, several factors beyond the initial injury likely contribute to the disease progression and pathology, and among these are genetic factors. Genetics is a recognized factor in determining the outcome of common neurodegenerative diseases. The role of mitochondrial genetics and function in traditional neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, is well-established. Much less is known about mitochondrial genetics, however, regarding neurodegenerative diseases that result from injuries such as traumatic brain injury and ischaemic stroke. We discuss the potential role of mitochondrial DNA genetics in the progression and outcome of injury-related neurodegenerative diseases. We present a guide for understanding mitochondrial genetic variation, along with the nuances of quantifying mitochondrial DNA variation. Evidence supporting a role for mitochondrial DNA as a risk factor for neurodegenerative disease is also reviewed and examined. Further research into the impact of mitochondrial DNA on neurodegenerative disease resulting from injury will likely offer key insights into the genetic factors that determine the outcome of these diseases together with potential targets for treatment.}, } @article {pmid34946956, year = {2021}, author = {Tahami, MS and Dincă, V and Lee, KM and Vila, R and Joshi, M and Heikkilä, M and Dapporto, L and Schmid, S and Huemer, P and Mutanen, M}, title = {Genomics Reveal Admixture and Unexpected Patterns of Diversity in a Parapatric Pair of Butterflies.}, journal = {Genes}, volume = {12}, number = {12}, pages = {}, pmid = {34946956}, issn = {2073-4425}, mesh = {Animals ; Balkan Peninsula ; Butterflies/anatomy & histology/*classification/genetics ; Cell Nucleus/*genetics ; DNA, Mitochondrial/*genetics ; Evolution, Molecular ; Gene Flow ; Genetic Speciation ; Genomics/*methods ; Mitochondria/genetics ; Phylogeny ; Sequence Analysis, DNA ; Sympatry ; }, abstract = {We studied the evolutionary relationship of two widely distributed parapatric butterfly species, Melitaea athalia and Melitaea celadussa, using the ddRAD sequencing approach, as well as genital morphology and mtDNA data. M. athalia was retrieved as paraphyletic with respect to M. celadussa. Several cases of mito-nuclear discordance and morpho-genetic mismatch were found in the contact zone. A strongly diverged and marginally sympatric clade of M. athalia from the Balkans was revealed. An in-depth analysis of genomic structure detected high levels of admixture between M. athalia and M. celadussa at the contact zone, though not reaching the Balkan clade. The demographic modelling of populations supported the intermediate genetic make-up of European M. athalia populations with regards to M. celadussa and the Balkan clade. However, the dissimilarity matrix of genotype data (PCoA) suggested the Balkan lineage having a genetic component that is unrelated to the athalia-celadussa group. Although narrowly sympatric, almost no signs of gene flow were found between the main M. athalia group and the Balkan clade. We propose two possible scenarios on the historical evolution of our model taxa and the role of the last glacial maximum in shaping their current distribution. Finally, we discuss the complexities regarding the taxonomic delimitation of parapatric taxa.}, } @article {pmid34946978, year = {2021}, author = {Romanova, EV and Bukin, YS and Mikhailov, KV and Logacheva, MD and Aleoshin, VV and Sherbakov, DY}, title = {The Mitochondrial Genome of a Freshwater Pelagic Amphipod Macrohectopus branickii Is among the Longest in Metazoa.}, journal = {Genes}, volume = {12}, number = {12}, pages = {}, pmid = {34946978}, issn = {2073-4425}, mesh = {Amphipoda/*genetics ; Animals ; Gene Order ; Genes, rRNA ; Genome Size ; Genome, Mitochondrial ; Mitochondria/*genetics ; RNA, Transfer/genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {There are more than 350 species of amphipods (Crustacea) in Lake Baikal, which have emerged predominantly through the course of endemic radiation. This group represents a remarkable model for studying various aspects of evolution, one of which is the evolution of mitochondrial (mt) genome architectures. We sequenced and assembled the mt genome of a pelagic Baikalian amphipod species Macrohectopus branickii. The mt genome is revealed to have an extraordinary length (42,256 bp), deviating significantly from the genomes of other amphipod species and the majority of animals. The mt genome of M. branickii has a unique gene order within amphipods, duplications of the four tRNA genes and Cox2, and a long non-coding region, that makes up about two thirds of the genome's size. The extension of the mt genome was most likely caused by multiple duplications and inversions of regions harboring ribosomal RNA genes. In this study, we analyzed the patterns of mt genome length changes in amphipods and other animal phyla. Through a statistical analysis, we demonstrated that the variability in the mt genome length may be a characteristic of certain phyla and is primarily conferred by expansions of non-coding regions.}, } @article {pmid34964900, year = {2022}, author = {Rand, DM and Mossman, JA and Spierer, AN and Santiago, JA}, title = {Mitochondria as environments for the nuclear genome in Drosophila: mitonuclear G×G×E.}, journal = {The Journal of heredity}, volume = {113}, number = {1}, pages = {37-47}, pmid = {34964900}, issn = {1465-7333}, support = {1R35GM139607/NH/NIH HHS/United States ; R35 GM139607/GM/NIGMS NIH HHS/United States ; R01 GM067862/GM/NIGMS NIH HHS/United States ; T32 AG041688/AG/NIA NIH HHS/United States ; 2R01GM067862/NH/NIH HHS/United States ; }, mesh = {Animals ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; *Drosophila/genetics ; Epistasis, Genetic ; *Genome, Mitochondrial ; Mitochondria/genetics ; }, abstract = {Mitochondria evolved from a union of microbial cells belonging to distinct lineages that were likely anaerobic. The evolution of eukaryotes required a massive reorganization of the 2 genomes and eventual adaptation to aerobic environments. The nutrients and oxygen that sustain eukaryotic metabolism today are processed in mitochondria through coordinated expression of 37 mitochondrial genes and over 1000 nuclear genes. This puts mitochondria at the nexus of gene-by-gene (G×G) and gene-by-environment (G×E) interactions that sustain life. Here we use a Drosophila model of mitonuclear genetic interactions to explore the notion that mitochondria are environments for the nuclear genome, and vice versa. We construct factorial combinations of mtDNA and nuclear chromosomes to test for epistatic interactions (G×G), and expose these mitonuclear genotypes to altered dietary environments to examine G×E interactions. We use development time and genome-wide RNAseq analyses to assess the relative contributions of mtDNA, nuclear chromosomes, and environmental effects on these traits (mitonuclear G×G×E). We show that the nuclear transcriptional response to alternative mitochondrial "environments" (G×G) has significant overlap with the transcriptional response of mitonuclear genotypes to altered dietary environments. These analyses point to specific transcription factors (e.g., giant) that mediated these interactions, and identified coexpressed modules of genes that may account for the overlap in differentially expressed genes. Roughly 20% of the transcriptome includes G×G genes that are concordant with G×E genes, suggesting that mitonuclear interactions are part of an organism's environment.}, } @article {pmid34972821, year = {2022}, author = {Irwin, NAT and Pittis, AA and Richards, TA and Keeling, PJ}, title = {Systematic evaluation of horizontal gene transfer between eukaryotes and viruses.}, journal = {Nature microbiology}, volume = {7}, number = {2}, pages = {327-336}, pmid = {34972821}, issn = {2058-5276}, mesh = {Eukaryota/*genetics ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; *Host Microbial Interactions ; Phylogeny ; Viruses/*genetics ; }, abstract = {Gene exchange between viruses and their hosts acts as a key facilitator of horizontal gene transfer and is hypothesized to be a major driver of evolutionary change. Our understanding of this process comes primarily from bacteria and phage co-evolution, but the mode and functional importance of gene transfers between eukaryotes and their viruses remain anecdotal. Here we systematically characterized viral-eukaryotic gene exchange across eukaryotic and viral diversity, identifying thousands of transfers and revealing their frequency, taxonomic distribution and projected functions. Eukaryote-derived viral genes, abundant in the Nucleocytoviricota, highlighted common strategies for viral host-manipulation, including metabolic reprogramming, proteolytic degradation and extracellular modification. Furthermore, viral-derived eukaryotic genes implicate genetic exchange in the early evolution and diversification of eukaryotes, particularly through viral-derived glycosyltransferases, which have impacted structures as diverse as algal cell walls, trypanosome mitochondria and animal tissues. These findings illuminate the nature of viral-eukaryotic gene exchange and its impact on the evolution of viruses and their eukaryotic hosts.}, } @article {pmid34976854, year = {2021}, author = {Valdés-Aguayo, JJ and Garza-Veloz, I and Vargas-Rodríguez, JR and Martinez-Vazquez, MC and Avila-Carrasco, L and Bernal-Silva, S and González-Fuentes, C and Comas-García, A and Alvarado-Hernández, DE and Centeno-Ramirez, ASH and Rodriguez-Sánchez, IP and Delgado-Enciso, I and Martinez-Fierro, ML}, title = {Peripheral Blood Mitochondrial DNA Levels Were Modulated by SARS-CoV-2 Infection Severity and Its Lessening Was Associated With Mortality Among Hospitalized Patients With COVID-19.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {754708}, pmid = {34976854}, issn = {2235-2988}, mesh = {*COVID-19 ; DNA, Mitochondrial/genetics ; Humans ; Immunity, Innate ; Mitochondria/genetics ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the virus hijacks the mitochondria causing damage of its membrane and release of mt-DNA into the circulation which can trigger innate immunity and generate an inflammatory state. In this study, we explored the importance of peripheral blood mt-DNA as an early predictor of evolution in patients with COVID-19 and to evaluate the association between the concentration of mt-DNA and the severity of the disease and the patient's outcome.

METHODS: A total 102 patients (51 COVID-19 cases and 51 controls) were included in the study. mt-DNA obtained from peripheral blood was quantified by qRT-PCR using the NADH mitochondrial gene.

RESULTS: There were differences in peripheral blood mt-DNA between patients with COVID-19 (4.25 ng/μl ± 0.30) and controls (3.3 ng/μl ± 0.16) (p = 0.007). Lower mt-DNA concentrations were observed in patients with severe COVID-19 when compared with mild (p= 0.005) and moderate (p= 0.011) cases of COVID-19. In comparison with patients with severe COVID-19 who survived (3.74 ± 0.26 ng/μl) decreased levels of mt-DNA in patients with severe COVID-19 who died (2.4 ± 0.65 ng/μl) were also observed (p = 0.037).

CONCLUSION: High levels of mt-DNA were associated with COVID-19 and its decrease could be used as a potential biomarker to establish a prognosis of severity and mortality of patients with COVID-19.}, } @article {pmid34993838, year = {2022}, author = {Jiang, Z and Cai, X and Kong, J and Zhang, R and Ding, Y}, title = {Maternally transmitted diabetes mellitus may be associated with mitochondrial ND5 T12338C and tRNA[Ala] T5587C variants.}, journal = {Irish journal of medical science}, volume = {191}, number = {6}, pages = {2625-2633}, pmid = {34993838}, issn = {1863-4362}, mesh = {Humans ; *RNA, Transfer, Ala ; *Diabetes Mellitus, Type 2/genetics ; Phylogeny ; DNA, Mitochondrial/genetics ; Mitochondria ; Pedigree ; Mutation ; }, abstract = {INTRODUCTION: Mutations/variants in mitochondrial genomes are found to be associated with type 2 diabetes mellitus (T2DM), but the pathophysiology of this disease remains largely unknown.

AIM: The aim of this study is to investigate the relationship between mitochondrial DNA (mtDNA) variants and T2DM.

METHODOLOGY: A maternally inherited T2DM pedigree is underwent clinical, genetic, and molecular assessment. Moreover, the complete mitochondrial genomes of the matrilineal relatives of this family are PCR amplified and sequenced. We also utilize the phylogenetic conservation analysis, haplogroup classification, and the pathogenicity scoring system to determine the T2DM-associated potential pathogenic mtDNA variants.

RESULT: Four of seven matrilineal relatives of this pedigree suffered from T2DM with variable ages of onset. Screening for the entire mtDNA genes of matrilineal members reveals co-existence of ND5 T12338C and tRNA[Ala] T5587C variants, as well as 21 genetic polymorphisms which belong to East Asian haplogroup F2. Interestingly, the T12338C variant causes the alternation of first amino acid Met to Thr, shortened two amino acids of ND5 protein. Furthermore, T5587C variant is located at position 73 in the 3'end of mt-tRNA[Ala] and may have structural and functional consequences.

CONCLUSIONS: The co-occurrence of ND5 T12338C and tRNA[Ala] T5587C variants may impair the mitochondrial function, which are associated with the development of T2DM in this family.}, } @article {pmid34994554, year = {2022}, author = {Liu, Y and Li, Q and Gu, M and Lu, D and Xiong, X and Zhang, Z and Pan, Y and Liao, Y and Ding, Q and Gong, W and Chen, DS and Guan, M and Wu, J and Tian, Z and Deng, H and Gu, L and Hong, X and Xiao, Y}, title = {A Second Near-Infrared Ru(II) Polypyridyl Complex for Synergistic Chemo-Photothermal Therapy.}, journal = {Journal of medicinal chemistry}, volume = {65}, number = {3}, pages = {2225-2237}, doi = {10.1021/acs.jmedchem.1c01736}, pmid = {34994554}, issn = {1520-4804}, mesh = {Apoptosis/drug effects ; Biocompatible Materials/chemistry/pharmacology/therapeutic use ; Cell Line, Tumor ; Coordination Complexes/*chemistry/pharmacology/therapeutic use ; Drug Design ; Fluorescent Dyes/chemistry/pharmacology/therapeutic use ; G2 Phase Cell Cycle Checkpoints/drug effects ; Humans ; Hyperthermia, Induced ; *Infrared Rays ; Neoplasms/diagnostic imaging/drug therapy/therapy ; Phenazines/chemistry ; Photothermal Therapy/methods ; Polyethylene Glycols/chemistry ; Quantum Theory ; Ruthenium/*chemistry ; Spectroscopy, Near-Infrared ; }, abstract = {The clinical success of cisplatin ushered in a new era of the application of metallodrugs. When it comes to practice, however, drug resistance, tumor recurrence, and drug systemic toxicity make it implausible to completely heal the patients. Herein, we successfully transform an electron acceptor [1, 2, 5]thiadiazolo[3,4-g]quinoxaline into a novel second near-infrared (NIR-II) fluorophore H7. After PEGylation and chelation, HL-PEG2k exhibits a wavelength bathochromic shift, enhanced photothermal conversion efficiency (41.77%), and an antineoplastic effect against glioma. Its potential for in vivo tumor tracking and image-guided chemo-photothermal therapy is explored. High levels of uptake and high-resolution NIR-II imaging results are thereafter obtained. The hyperthermia effect could disrupt the lysosomal membranes, which in turn aggravate the mitochondria dysfunction, arrest the cell cycle in the G2 phase, and finally lead to cancer cell apoptosis. HL-PEG2k displays a superior biocompatibility and thus can be a potential theranostic platform to combat the growth and recurrence of tumors.}, } @article {pmid34997986, year = {2022}, author = {Ereskovsky, A and Tokina, D}, title = {Ultrastructural research of spermiogenesis in two sponges, Crellomima imparidens and Hymedesmia irregularis (Demospongiae): New evidence of sperms with acrosome in sponges.}, journal = {Journal of morphology}, volume = {283}, number = {3}, pages = {333-345}, doi = {10.1002/jmor.21446}, pmid = {34997986}, issn = {1097-4687}, mesh = {*Acrosome/ultrastructure ; Animals ; Male ; Phylogeny ; *Porifera ; Spermatids/ultrastructure ; Spermatogenesis ; Spermatozoa ; }, abstract = {Details of spermatogenesis and sperm organization are often useful for reconstructing the phylogeny of closely related taxa of invertebrates. Here, the spermiogenesis and the ultrastructure of sperm were studied in two marine demosponges, Crellomima imparidens and Hymedesmia irregularis (order Poecilosclerida). In C. imparidens and H. irregularis, we found bundles of microtubules arranged along the nucleus during spermiogenesis. These bundles derived from the basal body of axoneme, reaching the apical pole of the cell. In C. imparidens, the microtubules surround the nucleus, forming the manchette. In H. irregularis, the microtubules pass along only one side of the cell periphery. During spermiogenesis, the nucleus stretches and elongates. In both species, the nucleus is twisted into a spiral structure. We suppose that the manchette of microtubules could be responsible for controlling the elongation and shaping of the sperm nucleus to a helical form and for the twisting and/or condensation of chromatin in these sponges. The spermatozoon of both species has an elongated shape. Its apical part has an acrosome, which is dome-shaped in C. imparidens and flattened and lenticular in H. irregularis. The cytoplasm of the spermatozoa contains some small mitochondria, and proximal and distal centrioles arranged at an angle to each other. There is a small volume of residual cytoplasm with dark glycogen-like granules. The axoneme of the spermatid and the flagellum of the sperm of both sponges is located in the deep tunnel-like cytoplasmic depression. The comparison of spermatozoa morphology of different species of the order Poecilosclerida demonstrates that the knowledge of variation within genera and families can give valuable insights into the significance of many characters proposed for phylogenetic studies of this order.}, } @article {pmid35007655, year = {2022}, author = {Liu, T and Lin, S and Du, Y and Gong, Y and Li, S}, title = {SpBAG3 assisted WSSV infection in mud crab (Scylla paramamosain) by inhibiting apoptosis.}, journal = {Developmental and comparative immunology}, volume = {129}, number = {}, pages = {104349}, doi = {10.1016/j.dci.2022.104349}, pmid = {35007655}, issn = {1879-0089}, mesh = {Animals ; Apoptosis ; Apoptosis Regulatory Proteins/genetics ; Arthropod Proteins/genetics ; Brachyura/*immunology ; Gene Expression Profiling ; Hemocytes/immunology ; Immunity, Innate/genetics ; Membrane Potential, Mitochondrial ; Mitochondria/metabolism ; Phylogeny ; White spot syndrome virus 1/physiology ; }, abstract = {The function of B-cell lymphoma-2 (Bcl-2) family proteins can be divided into two categories: anti-apoptotic and pro-apoptotic. As an anti-apoptotic protein, Bcl2-associated athanogene 3 (BAG3) plays a key role in regulating apoptosis, development, cell movement, and autophagy, and mediating the adaptability of cells to stimulation. However, SpBAG3 has not been reported in mud crab (Scylla paramamosain), and the regulatory effect of SpBAG3 on apoptosis in mud crab and its function in antiviral immunity is still unknown. In this study, SpBAG3 was found, and characterized, which encoded a total of 175 amino acid (molecular mass 19.3 kDa), including a specific conserved domain of the BAG family. SpBAG3 was significantly down-regulated at 0-48 h post-infection with WSSV in vivo. The antiviral effect of SpBAG3 was investigated using RNA interference. The results indicated that SpBAG3 might be involved in assisting the replication of WSSV in the host. SpBAG3 could change the mitochondrial membrane potential (△ψm), and affect cell apoptosis through mitochondrial apoptotic pathways. Therefore, the results of this study suggested that SpBAG3 could assist WSSV infection by inhibiting the apoptosis of the hemocytes in mud crab.}, } @article {pmid35017538, year = {2022}, author = {Li, CH and Haider, S and Boutros, PC}, title = {Age influences on the molecular presentation of tumours.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {208}, pmid = {35017538}, issn = {2041-1723}, support = {P30 CA016042/CA/NCI NIH HHS/United States ; U01 CA214194/CA/NCI NIH HHS/United States ; SVB-145586//CIHR/Canada ; }, mesh = {Age Factors ; Aging/*genetics/metabolism ; CREB-Binding Protein/*genetics/metabolism ; Carcinogenesis/genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/*genetics/metabolism ; *DNA Repair ; DNA, Neoplasm/*genetics/metabolism ; Datasets as Topic ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mitochondria/metabolism ; Mutation Rate ; Neoplasm Proteins/*genetics/metabolism ; Neoplasms/classification/*genetics/metabolism/pathology ; Repressor Proteins/deficiency/genetics ; Smoking/genetics/metabolism ; Transcriptome ; X-linked Nuclear Protein/genetics/metabolism ; }, abstract = {Cancer is often called a disease of aging. There are numerous ways in which cancer epidemiology and behaviour change with the age of the patient. The molecular bases for these relationships remain largely underexplored. To characterise them, we analyse age-associations in the nuclear and mitochondrial somatic mutational landscape of 20,033 tumours across 35 tumour-types. Age influences both the number of mutations in a tumour (0.077 mutations per megabase per year) and their evolutionary timing. Specific mutational signatures are associated with age, reflecting differences in exogenous and endogenous oncogenic processes such as a greater influence of tobacco use in the tumours of younger patients, but higher activity of DNA damage repair signatures in those of older patients. We find that known cancer driver genes such as CDKN2A and CREBBP are mutated in age-associated frequencies, and these alter the transcriptome and predict for clinical outcomes. These effects are most striking in brain cancers where alterations like SUFU loss and ATRX mutation are age-dependent prognostic biomarkers. Using three cancer datasets, we show that age shapes the somatic mutational landscape of cancer, with clinical implications.}, } @article {pmid35020439, year = {2022}, author = {Gogoi, J and Bhatnagar, A and Ann, KJ and Pottabathini, S and Singh, R and Mazeed, M and Kuncha, SK and Kruparani, SP and Sankaranarayanan, R}, title = {Switching a conflicted bacterial DTD-tRNA code is essential for the emergence of mitochondria.}, journal = {Science advances}, volume = {8}, number = {2}, pages = {eabj7307}, pmid = {35020439}, issn = {2375-2548}, abstract = {Mitochondria emerged through an endosymbiotic event involving a proteobacterium and an archaeal host. However, the process of optimization of cellular processes required for the successful evolution and survival of mitochondria, which integrates components from two evolutionarily distinct ancestors as well as novel eukaryotic elements, is not well understood. We identify two key switches in the translational machinery—one in the discriminator recognition code of a chiral proofreader DTD [d-aminoacyl–transfer RNA (tRNA) deacylase] and the other in mitochondrial tRNA[Gly]—that enable the compatibility between disparate elements essential for survival. Notably, the mito-tRNA[Gly] discriminator element is the only one to switch from pyrimidine to purine during the bacteria-to-mitochondria transition. We capture this code transition in the Jakobida, an early diverging eukaryotic clade bearing the most bacterial-like mito-genome, wherein both discriminator elements are present. This study underscores the need to explore the fundamental integration strategies critical for mitochondrial and eukaryotic evolution.}, } @article {pmid35022483, year = {2022}, author = {Dash, A and Ghag, SB}, title = {Genome-wide in silico characterization and stress induced expression analysis of BcL-2 associated athanogene (BAG) family in Musa spp.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {625}, pmid = {35022483}, issn = {2045-2322}, mesh = {*Musa/genetics/metabolism ; *Gene Expression Regulation, Plant ; *Plant Proteins/genetics/metabolism ; *Stress, Physiological/genetics ; *Phylogeny ; Multigene Family ; Genome, Plant ; Computer Simulation ; Gene Expression Profiling ; }, abstract = {Programmed cell death (PCD) is a genetically controlled process for the selective removal of damaged cells. Though understanding about plant PCD has improved over years, the mechanisms are yet to be fully deciphered. Among the several molecular players of PCD in plants, B cell lymphoma 2 (Bcl-2)-associated athanogene (BAG) family of co-chaperones are evolutionary conserved and regulate cell death, growth and development. In this study, we performed a genome-wide in silico analysis of the MusaBAG gene family in a globally important fruit crop banana. Thirteen MusaBAG genes were identified, out of which MusaBAG1, 7 and 8 genes were found to have multiple copies. MusaBAG genes were distributed on seven out of 11 chromosomes in banana. Except for one paralog of MusaBAG8 all the other 12 proteins have characteristic BAG domain. MusaBAG1, 2 and 4 have an additional ubiquitin-like domain whereas MusaBAG5-8 have a calmodulin binding motif. Most of the MusaBAG proteins were predicted to be localized in the nucleus and mitochondria or chloroplast. The in silico cis-regulatory element analysis suggested regulation associated with photoperiodic control, abiotic and biotic stress. The phylogenetic analysis revealed 2 major clusters. Digital gene expression analysis and quantitative real-time RT-PCR depicted the differential expression pattern of MusaBAG genes under abiotic and biotic stress conditions. Further studies are warranted to uncover the role of each of these proteins in growth, PCD and stress responses so as to explore them as candidate genes for engineering transgenic banana plants with improved agronomic traits.}, } @article {pmid35025030, year = {2022}, author = {Liu, S and Liu, Y and He, J and Lin, Z and Xue, Q}, title = {The complete mitochondrial genome of Crassostrea hongkongensis from East China Sea indicates species' range may extend northward.}, journal = {Molecular biology reports}, volume = {49}, number = {2}, pages = {1631-1635}, pmid = {35025030}, issn = {1573-4978}, support = {2021S009//Science and Technology Planning Project of Ningbo City/ ; }, mesh = {Animals ; China ; Conservation of Natural Resources/methods ; Crassostrea/*genetics ; Ecosystem ; Genome, Mitochondrial/*genetics ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Crassostrea hongkongensis is an important mariculture shellfish with a relatively narrow distribution range. Recently, larger wild oysters were identified as C. hongkongensis from Sanmen bay in East China Sea. No natural distribution had been reported for this species here, and its origin remains unknown.

METHODS AND RESULTS: We assembled the complete 18,617 bp circular mitochondrial genome of C. hongkongensis from Sanmen bay by next generation sequencing. It included 12 protein-coding genes, 23 tRNAs, and two rRNAs. The A/T content of the mitogenome was higher than its G/C content. Similar values and features were previously found for five other specimens of C. hongkongensis, and were comparable to those of other congeneric species. A phylogenetic analysis based on the 12 protein-coding genes and complete mitochondrial sequence indicated that the six specimens of C. hongkongensis formed a monophyletic group and shared a sister group relationship with C. ariakensis, C. nippona, C. sikamea, C. angulata, C. gigas, and C. iredalei, whereas specimens from the Sanmen bay area clustered later with the five other C. hongkongensis individuals, sharing a sub-clade. The newly sequenced mitogenome had more singleton sites than previously published C. hongkongensis mitogenomes.

CONCLUSIONS: Crassostrea hongkongensis may be a native species, and the species' range extends further to the north than previously known. Our data may therefore contribute to a better understanding of the species diversity and conservation of Crassostrea oysters.}, } @article {pmid35026224, year = {2022}, author = {Uzarska, MA and Grochowina, I and Soldek, J and Jelen, M and Schilke, B and Marszalek, J and Craig, EA and Dutkiewicz, R}, title = {During FeS cluster biogenesis, ferredoxin and frataxin use overlapping binding sites on yeast cysteine desulfurase Nfs1.}, journal = {The Journal of biological chemistry}, volume = {298}, number = {2}, pages = {101570}, pmid = {35026224}, issn = {1083-351X}, support = {R35 GM127009/GM/NIGMS NIH HHS/United States ; }, mesh = {Binding Sites ; Carbon-Sulfur Lyases/genetics/metabolism ; *Ferredoxins/metabolism ; Iron-Binding Proteins/metabolism ; *Iron-Sulfur Proteins/metabolism ; *Mitochondrial Proteins/metabolism ; Saccharomyces cerevisiae/enzymology/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/metabolism ; *Sulfurtransferases/metabolism ; Frataxin ; }, abstract = {In mitochondria, cysteine desulfurase (Nfs1) plays a central role in the biosynthesis of iron-sulfur (FeS) clusters, cofactors critical for activity of many cellular proteins. Nfs1 functions both as a sulfur donor for cluster assembly and as a binding platform for other proteins functioning in the process. These include not only the dedicated scaffold protein (Isu1) on which FeS clusters are synthesized but also accessory FeS cluster biogenesis proteins frataxin (Yfh1) and ferredoxin (Yah1). Yfh1 has been shown to activate cysteine desulfurase enzymatic activity, whereas Yah1 supplies electrons for the persulfide reduction. While Yfh1 interaction with Nfs1 is well understood, the Yah1-Nfs1 interaction is not. Here, based on the results of biochemical experiments involving purified WT and variant proteins, we report that in Saccharomyces cerevisiae, Yah1 and Yfh1 share an evolutionary conserved interaction site on Nfs1. Consistent with this notion, Yah1 and Yfh1 can each displace the other from Nfs1 but are inefficient competitors when a variant with an altered interaction site is used. Thus, the binding mode of Yah1 and Yfh1 interacting with Nfs1 in mitochondria of S. cerevisiae resembles the mutually exclusive binding of ferredoxin and frataxin with cysteine desulfurase reported for the bacterial FeS cluster assembly system. Our findings are consistent with the generally accepted scenario that the mitochondrial FeS cluster assembly system was inherited from bacterial ancestors of mitochondria.}, } @article {pmid35027725, year = {2022}, author = {Muñoz-Gómez, SA and Susko, E and Williamson, K and Eme, L and Slamovits, CH and Moreira, D and López-García, P and Roger, AJ}, title = {Site-and-branch-heterogeneous analyses of an expanded dataset favour mitochondria as sister to known Alphaproteobacteria.}, journal = {Nature ecology & evolution}, volume = {6}, number = {3}, pages = {253-262}, pmid = {35027725}, issn = {2397-334X}, mesh = {*Alphaproteobacteria/genetics/metabolism ; Metagenome ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins ; Phylogeny ; }, abstract = {Determining the phylogenetic origin of mitochondria is key to understanding the ancestral mitochondrial symbiosis and its role in eukaryogenesis. However, the precise evolutionary relationship between mitochondria and their closest bacterial relatives remains hotly debated. The reasons include pervasive phylogenetic artefacts as well as limited protein and taxon sampling. Here we developed a new model of protein evolution that accommodates both across-site and across-branch compositional heterogeneity. We applied this site-and-branch-heterogeneous model (MAM60 + GFmix) to a considerably expanded dataset that comprises 108 mitochondrial proteins of alphaproteobacterial origin, and novel metagenome-assembled genomes from microbial mats, microbialites and sediments. The MAM60 + GFmix model fits the data much better and agrees with analyses of compositionally homogenized datasets with conventional site-heterogenous models. The consilience of evidence thus suggests that mitochondria are sister to the Alphaproteobacteria to the exclusion of MarineProteo1 and Magnetococcia. We also show that the ancestral presence of the crista-developing mitochondrial contact site and cristae organizing system (a mitofilin-domain-containing Mic60 protein) in mitochondria and the Alphaproteobacteria only supports their close relationship.}, } @article {pmid35038074, year = {2022}, author = {Zhang, H and Qin, J and Lan, X and Zeng, W and Zhou, J and Huang, TE and Xiao, WL and Wang, QQ and Sun, S and Su, W and Nie, W and Yang, S and Yang, J and Gao, Q and Xiang, Y}, title = {Handelin extends lifespan and healthspan of Caenorhabditis elegans by reducing ROS generation and improving motor function.}, journal = {Biogerontology}, volume = {23}, number = {1}, pages = {115-128}, pmid = {35038074}, issn = {1573-6768}, mesh = {Animals ; *Caenorhabditis elegans/physiology ; *Caenorhabditis elegans Proteins/genetics/metabolism ; Ethanol/pharmacology ; Longevity/physiology ; Mammals/metabolism ; Plant Extracts/pharmacology ; Reactive Oxygen Species/metabolism ; Terpenes ; }, abstract = {Aging and aging-related disorders contribute to formidable socioeconomic and healthcare challenges. Several promising small molecules have been identified to target conserved genetic pathways delaying aging to extend lifespan and healthspan in many organisms. We previously found that extract from an edible and medicinal plant Chrysanthemum indicum L. (C. indicum L.) protect skin from UVB-induced photoaging, partially by reducing reactive oxygen species (ROS) generation. Thus, we hypothesized that C. indicum L. and its biological active compound may extend lifespan and health span in vivo. We find that both water and ethanol extracts from C. indicum L. extended lifespan of Caenorhabditis elegans, with better biological effect on life extending for ethanol extracts. As one of the major biological active compounds, handelin extended lifespan of C. elegans too. RNA-seq analysis revealed overall gene expression change of C. elegans post stimulation of handelin focus on several antioxidative proteins. Handelin significantly reduced ROS level and maintained the number and morphology of mitochondria. Moreover, handelin improveed many C. elegans behaviors related to healthspan, including increased pharyngeal pumping and body movement. Muscle fiber imaging analyses revealed that handelin maintains muscle architecture by stabilizing myofilaments. In conclusion, our present study finds a novel compound handelin, from C. indicum L., which bring about biologically beneficial effects by mild stress response, termed as hormetin, that can extend both lifespan and healthspan in vivo on C. elegans. Further study on mammal animal model of natural aging or sarcopenia will verify the potential clinical value of handelin.}, } @article {pmid35039544, year = {2022}, author = {Lebedev, VS and Shenbrot, GI and Krystufek, B and Mahmoudi, A and Melnikova, MN and Solovyeva, EN and Lisenkova, AA and Undrakhbayar, E and Rogovin, KA and Surov, AV and Bannikova, AA}, title = {Phylogenetic relations and range history of jerboas of the Allactaginae subfamily (Dipodidae, Rodentia).}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {842}, pmid = {35039544}, issn = {2045-2322}, support = {21-14-00007//Russian Science Foundation/ ; }, mesh = {Animals ; Ecosystem ; European Union ; Genetic Variation ; Mitochondria/genetics ; *Phylogeny ; Rodentia/classification/*genetics ; Species Specificity ; }, abstract = {Five-toed jerboas of the subfamily Allactaginae comprise several complex taxa occurring over a wide distribution range covering a large part of the Eurasian arid belt. In this study, we employed current methods of molecular phylogenetics based on 15 nuclear genes and the mitochondrial gene cytb to revise relations and systematics within Allactaginae. We also applied species distribution modelling projected on paleo-environmental data to reconstruct the geographic patterns of speciation in Allactaginae. We elucidated the intergeneric relationships within this subfamily and clarified interspecies relations within the genus Scarturus. Moreover, our results demonstrate the species status of S. caprimulga; outline the currently understudied diversity within Orientallactaga, Allactaga, and Pygeretmus; and improve the divergence estimates of these taxa. Based on our results from modelling of geographic range fragmentation in allactagines, we suggest the dating and location of speciation events and present hypotheses regarding general habitat niche conservatism in small mammals.}, } @article {pmid35051222, year = {2022}, author = {Tsai, CY and Chiou, SJ and Ko, HJ and Cheng, YF and Lin, SY and Lai, YL and Lin, CY and Wang, C and Cheng, JT and Liu, HF and Kwan, AL and Loh, JK and Hong, YR}, title = {Deciphering the evolution of composite-type GSKIP in mitochondria and Wnt signaling pathways.}, journal = {PloS one}, volume = {17}, number = {1}, pages = {e0262138}, pmid = {35051222}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Armadillo Domain Proteins/chemistry/genetics/*metabolism ; Binding Sites ; Cloning, Molecular ; Conserved Sequence ; Evolution, Molecular ; Glycogen Synthase Kinase 3 beta/*metabolism ; Humans ; Mitochondria/*metabolism ; Models, Molecular ; Mutagenesis, Site-Directed ; Phylogeny ; Protein Binding ; Protein Conformation ; RNA-Binding Proteins/chemistry/genetics/*metabolism ; Repressor Proteins/chemistry/*genetics/*metabolism ; Sequence Analysis, DNA ; Two-Hybrid System Techniques ; Wnt Signaling Pathway ; }, abstract = {We previously revealed the origin of mammalian simple-type glycogen synthase kinase interaction protein (GSKIP), which served as a scavenger and a competitor in the Wnt signaling pathway during evolution. In this study, we investigated the conserved and nonconserved regions of the composite-type GSKIP by utilizing bioinformatics tools, site-directed mutagenesis, and yeast two-hybrid methods. The regions were denoted as the pre-GSK3β binding site, which is located at the front of GSK3β-binding sites. Our data demonstrated that clustered mitochondria protein 1 (CLU1), a type of composite-type GSKIP that exists in the mitochondria of all eukaryotic organisms, possesses the protein known as domain of unknown function 727 (DUF727), with a pre-GSK3β-binding site and a mutant GSK3β-binding flanking region. Another type of composite-type GSKIP, armadillo repeat containing 4 (ARMC4), which is known for cilium movement in vertebrates, contains an unintegrated DUF727 flanking region with a pre-GSK3β-binding site (115SPxF118) only. In addition, the sequence of the GSK3β-binding site in CLU1 revealed that Q126L and V130L were not conserved, differing from the ideal GSK3β-binding sequence of simple-type GSKIP. We further illustrated two exceptions, namely 70 kilodalton heat shock proteins (Hsp70/DnaK) and Mitofilin in nematodes, that presented an unexpected ideal GSK3β-binding region with a pre-GSK3β sequence; this composite-type GSKIP could only occur in vertebrate species. Furthermore, we revealed the importance of the pre-GSK3β-binding site (118F or 118Y) and various mutant GSK3β-binding sites of composite-type GSKIP. Collectively, our data suggest that the new composite-type GSKIP starts with a DUF727 domain followed by a pre-GSK3β-binding site, with the subsequent addition of the GSK3β-binding site, which plays vital roles for CLU1, Mitofilin, and ARMC4 in mitochondria and Wnt signaling pathways during evolution.}, } @article {pmid35052455, year = {2022}, author = {Deng, MX and Xiao, B and Yuan, JX and Hu, JM and Kim, KS and Westbury, MV and Lai, XL and Sheng, GL}, title = {Ancient Mitogenomes Suggest Stable Mitochondrial Clades of the Siberian Roe Deer.}, journal = {Genes}, volume = {13}, number = {1}, pages = {}, pmid = {35052455}, issn = {2073-4425}, mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial/analysis/*genetics ; Deer/*genetics ; *Evolution, Molecular ; Fossils ; *Genetic Variation ; *Genome, Mitochondrial ; Haplotypes ; Mitochondria/*genetics ; *Phylogeny ; }, abstract = {The roe deer (Capreolus spp.) has been present in China since the early Pleistocene. Despite abundant fossils available for detailed morphological analyses, little is known about the phylogenetic relationships of the fossil individuals to contemporary roe deer. We generated near-complete mitochondrial genomes for four roe deer remains from Northeastern China to explore the genetic connection of the ancient roe deer to the extant populations and to investigate the evolutionary history and population dynamics of this species. Phylogenetic analyses indicated the four ancient samples fall into three out of four different haplogroups of the Siberian roe deer. Haplogroup C, distributed throughout Eurasia, have existed in Northeastern China since at least the Late Pleistocene, while haplogroup A and D, found in the east of Lake Baikal, emerged in Northeastern China after the Mid Holocene. The Bayesian estimation suggested that the first split within the Siberian roe deer occurred approximately 0.34 million years ago (Ma). Moreover, Bayesian skyline plot analyses suggested that the Siberian roe deer had a population increase between 325 and 225 thousand years ago (Kya) and suffered a transient decline between 50 and 18 Kya. This study provides novel insights into the evolutionary history and population dynamics of the roe deer.}, } @article {pmid35055190, year = {2022}, author = {Belostotsky, R and Frishberg, Y}, title = {Catabolism of Hydroxyproline in Vertebrates: Physiology, Evolution, Genetic Diseases and New siRNA Approach for Treatment.}, journal = {International journal of molecular sciences}, volume = {23}, number = {2}, pages = {}, pmid = {35055190}, issn = {1422-0067}, support = {not relevant//Oxalosis and Hyperoxaluria Foundation/ ; }, mesh = {Animals ; Evolution, Molecular ; Genetic Predisposition to Disease ; Glyoxylates/metabolism ; Humans ; Hydrogen Peroxide/metabolism ; Hydroxyproline/*metabolism ; Hyperoxaluria, Primary/drug therapy/*genetics/metabolism ; Mitochondria/metabolism ; Peroxisomes/metabolism ; RNA, Small Interfering/*pharmacology/therapeutic use ; }, abstract = {Hydroxyproline is one of the most prevalent amino acids in animal proteins. It is not a genetically encoded amino acid, but, rather, it is produced by the post-translational modification of proline in collagen, and a few other proteins, by prolyl hydroxylase enzymes. Although this post-translational modification occurs in a limited number of proteins, its biological significance cannot be overestimated. Considering that hydroxyproline cannot be re-incorporated into pro-collagen during translation, it should be catabolized following protein degradation. A cascade of reactions leads to production of two deleterious intermediates: glyoxylate and hydrogen peroxide, which need to be immediately converted. As a result, the enzymes involved in hydroxyproline catabolism are located in specific compartments: mitochondria and peroxisomes. The particular distribution of catabolic enzymes in these compartments, in different species, depends on their dietary habits. Disturbances in hydroxyproline catabolism, due to genetic aberrations, may lead to a severe disease (primary hyperoxaluria), which often impairs kidney function. The basis of this condition is accumulation of glyoxylate and its conversion to oxalate. Since calcium oxalate is insoluble, children with this rare inherited disorder suffer from progressive kidney damage. This condition has been nearly incurable until recently, as significant advances in substrate reduction therapy using small interference RNA led to a breakthrough in primary hyperoxaluria type 1 treatment.}, } @article {pmid35058355, year = {2022}, author = {Pei, Y and Forstmeier, W and Ruiz-Ruano, FJ and Mueller, JC and Cabrero, J and Camacho, JPM and Alché, JD and Franke, A and Hoeppner, M and Börno, S and Gessara, I and Hertel, M and Teltscher, K and Knief, U and Suh, A and Kempenaers, B}, title = {Occasional paternal inheritance of the germline-restricted chromosome in songbirds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {4}, pages = {}, pmid = {35058355}, issn = {1091-6490}, mesh = {Animals ; *Chromosomes ; Cytogenetic Analysis ; DNA, Mitochondrial ; Evolution, Molecular ; Female ; *Germ Cells ; Haplotypes ; Male ; *Paternal Inheritance ; Phylogeny ; Songbirds/classification/*genetics ; Spermatozoa ; }, abstract = {Songbirds have one special accessory chromosome, the so-called germline-restricted chromosome (GRC), which is only present in germline cells and absent from all somatic tissues. Earlier work on the zebra finch (Taeniopygia guttata castanotis) showed that the GRC is inherited only through the female line-like the mitochondria-and is eliminated from the sperm during spermatogenesis. Here, we show that the GRC has the potential to be paternally inherited. Confocal microscopy using GRC-specific fluorescent in situ hybridization probes indicated that a considerable fraction of sperm heads (1 to 19%) in zebra finch ejaculates still contained the GRC. In line with these cytogenetic data, sequencing of ejaculates revealed that individual males from two families differed strongly and consistently in the number of GRCs in their ejaculates. Examining a captive-bred male hybrid of the two zebra finch subspecies (T. g. guttata and T. g. castanotis) revealed that the mitochondria originated from a castanotis mother, whereas the GRC came from a guttata father. Moreover, analyzing GRC haplotypes across nine castanotis matrilines, estimated to have diverged for up to 250,000 y, showed surprisingly little variability among GRCs. This suggests that a single GRC haplotype has spread relatively recently across all examined matrilines. A few diagnostic GRC mutations that arose since this inferred spreading suggest that the GRC has continued to jump across matriline boundaries. Our findings raise the possibility that certain GRC haplotypes could selfishly spread through the population via occasional paternal transmission, thereby outcompeting other GRC haplotypes that were limited to strict maternal inheritance, even if this was partly detrimental to organismal fitness.}, } @article {pmid35061308, year = {2022}, author = {Choi, IS and Wojciechowski, MF and Steele, KP and Hunter, SG and Ruhlman, TA and Jansen, RK}, title = {Born in the mitochondrion and raised in the nucleus: evolution of a novel tandem repeat family in Medicago polymorpha (Fabaceae).}, journal = {The Plant journal : for cell and molecular biology}, volume = {110}, number = {2}, pages = {389-406}, doi = {10.1111/tpj.15676}, pmid = {35061308}, issn = {1365-313X}, mesh = {*Genome, Mitochondrial/genetics ; Genome, Plant/genetics ; *Medicago/genetics ; Mitochondria/genetics ; Tandem Repeat Sequences/genetics ; }, abstract = {Plant nuclear genomes harbor sequence elements derived from the organelles (mitochondrion and plastid) through intracellular gene transfer (IGT). Nuclear genomes also show a dramatic range of repeat content, suggesting that any sequence can be readily amplified. These two aspects of plant nuclear genomes are well recognized but have rarely been linked. Through investigation of 31 Medicago taxa we detected exceptionally high post-IGT amplification of mitochondrial (mt) DNA sequences containing rps10 in the nuclear genome of Medicago polymorpha and closely related species. The amplified sequences were characterized as tandem arrays of five distinct repeat motifs (2157, 1064, 987, 971, and 587 bp) that have diverged from the mt genome (mitogenome) in the M. polymorpha nuclear genome. The mt rps10-like arrays were identified in seven loci (six intergenic and one telomeric) of the nuclear chromosome assemblies and were the most abundant tandem repeat family, representing 1.6-3.0% of total genomic DNA, a value approximately three-fold greater than the entire mitogenome in M. polymorpha. Compared to a typical mt gene, the mt rps10-like sequence coverage level was 691.5-7198-fold higher in M. polymorpha and closely related species. In addition to the post-IGT amplification, our analysis identified the canonical telomeric repeat and the species-specific satellite arrays that are likely attributable to an ancestral chromosomal fusion in M. polymorpha. A possible relationship between chromosomal instability and the mt rps10-like tandem repeat family in the M. polymorpha clade is discussed.}, } @article {pmid35063045, year = {2022}, author = {Fan, Y and Zhang, Y and Rui, C and Zhang, H and Xu, N and Wang, J and Han, M and Lu, X and Chen, X and Wang, D and Wang, S and Guo, L and Zhao, L and Huang, H and Wang, J and Sun, L and Chen, C and Ye, W}, title = {Molecular structures and functional exploration of NDA family genes respond tolerant to alkaline stress in Gossypium hirsutum L.}, journal = {Biological research}, volume = {55}, number = {1}, pages = {4}, pmid = {35063045}, issn = {0717-6287}, mesh = {*Gene Expression Regulation, Plant ; Genome, Plant ; *Gossypium/genetics ; Molecular Structure ; Multigene Family/genetics ; Phylogeny ; Plant Proteins/genetics/metabolism ; Stress, Physiological/genetics ; }, abstract = {BACKGROUND: The internal NAD(P)H dehydrogenase (NDA) gene family was a member of the NAD(P)H dehydrogenase (ND) gene family, mainly involved in the non-phosphorylated respiratory pathways in mitochondria and played crucial roles in response to abiotic stress.

METHODS: The whole genome identification, structure analysis and expression pattern of NDA gene family were conducted to analyze the NDA gene family.

RESULTS: There were 51, 52, 26, and 24 NDA genes identified in G. hirsutum, G. barbadense, G. arboreum and G. raimondii, respectively. According to the structural characteristics of genes and traits of phylogenetic tree, we divided the NDA gene family into 8 clades. Gene structure analysis showed that the NDA gene family was relatively conservative. The four Gossypium species had good collinearity, and segmental duplication played an important role in the evolution of the NDA gene family. Analysis of cis-elements showed that most GhNDA genes contained cis-elements related to light response and plant hormones (ABA, MeJA and GA). The analysis of the expression patterns of GhNDA genes under different alkaline stress showed that GhNDA genes were actively involved in the response to alkaline stress, possibly through different molecular mechanisms. By analyzing the existing RNA-Seq data after alkaline stress, it was found that an NDA family gene GhNDA32 was expressed, and then theGhNDA32 was silenced by virus-induced gene silencing (VIGS). By observing the phenotype, we found that the wilting degree of silenced plants was much higher than that of the control plant after alkaline treatment, suggesting that GhNDA32 gene was involved in the response to alkaline stress.

CONCLUSIONS: In this study, GhNDAs participated in response to alkaline stress, especially NaHCO3 stress. It was of great significance for the future research on the molecular mechanism of NDA gene family in responding to abiotic stresses.}, } @article {pmid35066390, year = {2022}, author = {Muthye, V and Mackereth, CD and Stewart, JB and Lavrov, DV}, title = {Large dataset of octocoral mitochondrial genomes provides new insights into mt-mutS evolution and function.}, journal = {DNA repair}, volume = {110}, number = {}, pages = {103273}, doi = {10.1016/j.dnarep.2022.103273}, pmid = {35066390}, issn = {1568-7856}, mesh = {Animals ; *Anthozoa/genetics ; DNA, Mitochondrial/chemistry/genetics ; Escherichia coli Proteins ; Evolution, Molecular ; *Genome, Mitochondrial ; MutS DNA Mismatch-Binding Protein/genetics ; Nucleotides ; Phylogeny ; }, abstract = {All studied octocoral mitochondrial genomes (mt-genomes) contain a homologue of the Escherichia coli mutS gene, a member of a gene family encoding proteins involved in DNA mismatch repair, other types of DNA repair, meiotic recombination, and other functions. Although mutS homologues are found in all domains of life, as well as viruses, octocoral mt-mutS is the only such gene found in an organellar genome. While the function of mtMutS is not known, its domain architecture, conserved sequence, and presence of several characteristic residues suggest its involvement in mitochondrial DNA repair. This inference is supported by exceptionally low rates of mt-sequence evolution observed in octocorals. Previous studies of mt-mutS have been limited by the small number of octocoral mt-genomes available. We utilized sequence-capture data from the recent Quattrini et al. 2020 study [Nature Ecology & Evolution 4:1531-1538] to assemble complete mt-genomes for 94 species of octocorals. Combined with sequences publicly available in GenBank, this resulted in a dataset of 184 complete mt-genomes, which we used to re-analyze the conservation and evolution of mt-mutS. In our analysis, we discovered the first case of mt-mutS loss among octocorals in one of the two Pseudoanthomastus spp. assembled from Quattrini et al. data. This species displayed accelerated rate and changed patterns of nucleotide substitutions in mt-genome, which we argue provide additional evidence for the role of mtMutS in DNA repair. In addition, we found accelerated mt-sequence evolution in the presence of mt-mutS in several octocoral lineages. This accelerated evolution did not appear to be the result of relaxed selection pressure and did not entail changes in patterns of nucleotide substitutions. Overall, our results support previously reported patterns of conservation in mt-mutS and suggest that mtMutS is involved in DNA repair in octocoral mitochondria. They also indicate that the presence of mt-mutS contributes to, but does not fully explain, the low rates of sequence evolution in octocorals.}, } @article {pmid35077696, year = {2022}, author = {Smith, DR}, title = {Genome evolution: Minicircular mtDNA and unusual heteroplasmy in a parasitic plant.}, journal = {Current biology : CB}, volume = {32}, number = {2}, pages = {R86-R89}, doi = {10.1016/j.cub.2021.12.001}, pmid = {35077696}, issn = {1879-0445}, mesh = {*DNA, Mitochondrial/genetics ; *Genome, Mitochondrial/genetics ; Heteroplasmy ; Mitochondria/genetics ; Plants/genetics ; }, abstract = {Minicircular organelle genomes exist in diverse species but have never been observed in plants - that is, until now. The mitochondrial genome of the holoparasite Rhopalocnemis phalloides comprises 21 minicircles, which are extremely heteroplasmic, providing an exceptional example of convergent organelle evolution across disparate lineages.}, } @article {pmid35078356, year = {2022}, author = {Munasinghe, M and Haller, BC and Clark, AG}, title = {Migration restores hybrid incompatibility driven by mitochondrial-nuclear sexual conflict.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1967}, pages = {20212561}, pmid = {35078356}, issn = {1471-2954}, mesh = {Cell Nucleus/genetics ; Female ; *Genome, Mitochondrial ; Humans ; Male ; Mitochondria/genetics ; Mutation ; Reproductive Isolation ; }, abstract = {In the mitochondrial genome, sexual asymmetry in transmission allows the accumulation of male-harming mutations since selection acts only on the effect of the mutation in females. Called the 'Mother's Curse', this phenomenon induces a selective pressure for nuclear variants that compensate for this reduction in male fitness. Previous work has demonstrated the existence of these interactions and their potential to act as Dobzhansky-Muller incompatibilities, contributing to reproductive isolation between populations. However, it is not clear how readily they would give rise to and sustain hybrid incompatibilities. Here, we use computer simulations in SLiM 3 to investigate the consequences of sexually antagonistic mitochondrial-nuclear interactions in a subdivided population. We consider distinct migration schemes and vary the chromosomal location, and consequently the transmission pattern, of nuclear restorers. Disrupting these co-evolved interactions results in less-fit males, skewing the sex ratio toward females. Restoration of male fitness depends on both the chromosomal location of nuclear restorer loci and the migration scheme. Our results show that these interactions may act as Dobzhansky-Muller incompatibilities, but their strength is not enough to drive population isolation. Overall, this model shows the varied ways in which populations can respond to migration's disruption of co-evolved mitochondrial-nuclear interactions.}, } @article {pmid35104579, year = {2022}, author = {Gowri, P and Sathish, P and Mahesh Kumar, S and Sundaresan, P}, title = {Mutation profile of neurodegenerative mitochondriopathy - LHON in Southern India.}, journal = {Gene}, volume = {819}, number = {}, pages = {146202}, doi = {10.1016/j.gene.2022.146202}, pmid = {35104579}, issn = {1879-0038}, mesh = {Adolescent ; Adult ; Asian People/genetics ; Child ; Child, Preschool ; DNA, Mitochondrial/metabolism ; Female ; Genes, Mitochondrial ; Genetic Predisposition to Disease ; Genome, Mitochondrial ; Humans ; India ; Male ; Methylation ; Middle Aged ; Mitochondria/*genetics ; *Mutation ; Neurodegenerative Diseases/*genetics ; Optic Atrophy, Hereditary, Leber/*genetics ; Pedigree ; Phylogeny ; Young Adult ; }, abstract = {BACKGROUND: Leber's Hereditary Optic Neuropathy (LHON) is a rare mitochondriopathy causing retinal ganglion cell degeneration resulting in central vision loss. It is caused by mitochondrial DNA (mtDNA) mutations and thus follows maternal inheritance pattern.

METHODS: We analysed the whole mitochondrial genome in 100 South Indian LHON patients by utilizing Sanger and Next Generation Sequencing approaches. Haplogroup analysis was performed using HaploGrep2 to predict the risk group. Methylation changes in the mtDNA D-loop region were investigated by performing methylation-specific polymerase chain reaction (MSP).

RESULTS: LHON associated mutations were detected in 55% of the patients of which 42% harboured the primary mutations and 13% harboured potentially pathogenic variants that were previously reported to cause LHON. The candidate mutations identified with confirmed pathogenicity are: m.11778G > A (38%), m.14484 T > C (3%), m.4171C > A (1%) and m.11696G > A (1%). MSP results demonstrated that the D-loop region was unmethylated in all the study subjects including mutation-positive patients, mutation-negative patients, asymptomatic carriers, and controls. Haplogroup-M was prevalent (69%) in the study cohort followed by R (14%), U (9%), N (3%), HV (2%), G (2%), and W (1%). The frequency of the predominant mutation m.11778G > A was found lower (̴ 11%) in haplogroup-U.

CONCLUSIONS: South Indian LHON cohort shows a unique profile of mtDNA mutations and haplogroup association presumably with no role of D-loop methylation. MT-ND4, MT-ND5, and MT-ND1 serve as the hotspot genes in this cohort. The presence of LHON associated mutations in patients lacking the common primary mutations insists on the necessity of mitochondrial genome sequencing in individuals suspected with LHON.}, } @article {pmid35107193, year = {2022}, author = {Huisman, TAGM and Kralik, SF and Desai, NK and Serrallach, BL and Orman, G}, title = {Neuroimaging of primary mitochondrial disorders in children: A review.}, journal = {Journal of neuroimaging : official journal of the American Society of Neuroimaging}, volume = {32}, number = {2}, pages = {191-200}, doi = {10.1111/jon.12976}, pmid = {35107193}, issn = {1552-6569}, mesh = {Child ; Diagnosis, Differential ; Humans ; Mitochondria/metabolism ; *Mitochondrial Diseases/diagnostic imaging/genetics ; Neuroimaging/methods ; }, abstract = {Mitochondrial disorders represent a diverse and complex group of entities typified by defective energy metabolism. The mitochondrial oxidative phosphorylation system is typically impaired, which is the predominant source of energy production. Because mitochondria are present in nearly all organs, multiple systems may be affected including the central nervous system, skeletal muscles, kidneys, and liver. In particular, those organs that are metabolically active with high energy demands are explicitly vulnerable. Initial diagnostic work up relies on a detailed evaluation of clinical symptoms including physical examination as well as a comprehensive review of the evolution of symptoms over time, relation to possible "triggering" events (eg, fever, infection), blood workup, and family history. High-end neuroimaging plays a pivotal role in establishing diagnosis, narrowing differential diagnosis, monitoring disease progression, and predicting prognosis. The pattern and characteristics of the neuroimaging findings are often highly suggestive of a mitochondrial disorder; unfortunately, in many cases the wide variability of involved metabolic processes prevents a more specific subclassification. Consequently, additional diagnostic steps including muscle biopsy, metabolic workup, and genetic tests are necessary. In the current manuscript, basic concepts of energy production, genetics, and inheritance patterns are reviewed. In addition, the imaging findings of several illustrative mitochondrial disorders are presented to familiarize the involved physicians with pediatric mitochondrial disorders. In addition, the significance of spinal cord imaging and the value of "reversed image-based discovery" for the recognition and correct (re-)classification of mitochondrial disorders is discussed.}, } @article {pmid35108076, year = {2022}, author = {Giannotti, D and Boscaro, V and Husnik, F and Vannini, C and Keeling, PJ}, title = {The "Other" Rickettsiales: an Overview of the Family "Candidatus Midichloriaceae".}, journal = {Applied and environmental microbiology}, volume = {88}, number = {6}, pages = {e0243221}, pmid = {35108076}, issn = {1098-5336}, mesh = {*Alphaproteobacteria/genetics ; Animals ; Bacteria ; Phylogeny ; *Rickettsiales ; Symbiosis ; }, abstract = {The family "Candidatus Midichloriaceae" constitutes the most diverse but least studied lineage within the important order of intracellular bacteria Rickettsiales. "Candidatus Midichloriaceae" endosymbionts are found in many hosts, including terrestrial arthropods, aquatic invertebrates, and protists. Representatives of the family are not documented to be pathogenic, but some are associated with diseased fish or corals. Different genera display a range of unusual features, such as full sets of flagellar genes without visible flagella or the ability to invade host mitochondria. Since studies on "Ca. Midichloriaceae" tend to focus on the host, the family is rarely addressed as a unit, and we therefore lack a coherent picture of its diversity. Here, we provide four new midichloriaceae genomes, and we survey molecular and ecological data from the entire family. Features like genome size, ecological context, and host transitions vary considerably even among closely related midichloriaceae, suggesting a high frequency of such shifts, incomplete sampling, or both. Important functional traits involved in energy metabolism, flagella, and secretion systems were independently reduced multiple times with no obvious correspondence to host or habitat, corroborating the idea that many features of these "professional symbionts" are largely independent of host identity. Finally, despite "Ca. Midichloriaceae" being predominantly studied in ticks, our analyses show that the clade is mainly aquatic, with a few terrestrial offshoots. This highlights the importance of considering aquatic hosts, and protists in particular, when reconstructing the evolution of these endosymbionts and by extension all Rickettsiales. IMPORTANCE Among endosymbiotic bacterial lineages, few are as intensely studied as Rickettsiales, which include the causative agents of spotted fever, typhus, and anaplasmosis. However, an important subgroup called "Candidatus Midichloriaceae" receives little attention despite accounting for a third of the diversity of Rickettsiales and harboring a wide range of bacteria with unique features, like the ability to infect mitochondria. Midichloriaceae are found in many hosts, from ticks to corals to unicellular protozoa, and studies on them tend to focus on the host groups. Here, for the first time since the establishment of this clade, we address the genomics, evolution, and ecology of "Ca. Midichloriaceae" as a whole, highlighting trends and patterns, the remaining gaps in our knowledge, and its importance for the understanding of symbiotic processes in intracellular bacteria.}, } @article {pmid35111395, year = {2022}, author = {Yuan, Z and Jiang, W and Sha, Z}, title = {A review of the common crab genus Macromedaeus Ward, 1942 (Brachyura, Xanthidae) from China Seas with description of a new species using integrative taxonomy methods.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e12735}, pmid = {35111395}, issn = {2167-8359}, mesh = {Animals ; Male ; *Brachyura/anatomy & histology ; Phylogeny ; Oceans and Seas ; Mitochondria ; China ; }, abstract = {Macromedaeus is one of the most common xanthid genera in shallow waters of the Indo-West Pacific. In this study, we describe a new species, Macromedaeus hainanensis sp. nov., and report on two newly recorded species, M. quinquedentatus (Krauss, 1843) and M. orientalis (Takeda & Miyake, 1969) from Hainan Island, South China Sea. M. hainanensis is most related to M. distinguendus (De Haan, 1833-1850) and M. orientalis on the carapace shape and granular appearance, but can be distinguished by unique morphological characteristics especially its front, pereopods and male first gonopod. Taxonomic identities of the six Macromedaeus species recorded from China seas are discussed, and a phylogenetic analyzation is performed on Macromedaeus and related taxa based on three mitochondrial and two nuclear markers (12S, 16S, COI, H3, 18S). Integrated taxonomic evidence is used to support the taxonomic status of each species.}, } @article {pmid35113355, year = {2022}, author = {Singh, P and Lim, B}, title = {Targeting Apoptosis in Cancer.}, journal = {Current oncology reports}, volume = {24}, number = {3}, pages = {273-284}, pmid = {35113355}, issn = {1534-6269}, mesh = {*Antineoplastic Agents/pharmacology/therapeutic use ; Apoptosis ; Humans ; Mitochondria/metabolism ; *Neoplasms/drug therapy/metabolism ; Proto-Oncogene Proteins c-bcl-2 ; }, abstract = {PURPOSE OF REVIEW: Apoptosis is a major mechanism of cancer cell death. Thus, evasion of apoptosis results in therapy resistance. Here, we review apoptosis modulators in cancer and their recent developments, including MDM2 inhibitors and kinase inhibitors that can induce effective apoptosis.

RECENT FINDINGS: Both extrinsic pathways (external stimuli through cell surface death receptor) and intrinsic pathways (mitochondrial-mediated regulation upon genotoxic stress) regulate the complex process of apoptosis through orchestration of various proteins such as members of the BCL-2 family. Dysregulation within these complex steps can result in evasion of apoptosis. However, via the combined evolution of medicinal chemistry and molecular biology, omics assays have led to innovative inducers of apoptosis and inhibitors of anti-apoptotic regulators. Many of these agents are now being tested in cancer patients in early-phase trials. We believe that despite a sluggish speed of development, apoptosis targeting holds promise as a relevant strategy in cancer therapeutics.}, } @article {pmid35119574, year = {2022}, author = {Munekage, YN and Taniguchi, YY}, title = {A scheme for C4 evolution derived from a comparative analysis of the closely related C3, C3-C4 intermediate, C4-like, and C4 species in the genus Flaveria.}, journal = {Plant molecular biology}, volume = {110}, number = {4-5}, pages = {445-454}, pmid = {35119574}, issn = {1573-5028}, support = {17K07456//Japan Society for the Promotion of Science/ ; 16H06557//Japan Society for the Promotion of Science/ ; 21K05520//Japan Society for the Promotion of Science/ ; }, mesh = {*Flaveria/genetics ; Photosynthesis/physiology ; Mesophyll Cells ; Electron Transport ; Plants ; }, abstract = {A comparative analysis of the genus Flaveria showed a C4 evolutionary process in which the anatomical and metabolic features of C4 photosynthesis were gradually acquired through C3-C4 intermediate stages. C4 photosynthesis has been acquired in multiple lineages of angiosperms during evolution to suppress photorespiration. Crops that perform C4 photosynthesis exhibit high rates of CO2 assimilation and high grain production even under high-temperature in semiarid environments; therefore, engineering C4 photosynthesis in C3 plants is of great importance in the application field. The genus Flaveria contains a large number of C3, C3-C4 intermediate, C4-like, and C4 species, making it a good model genus to study the evolution of C4 photosynthesis, and these studies indicate the direction for C4 engineering. C4 photosynthesis was acquired gradually through the C3-C4 intermediate stage. First, a two-celled C2 cycle called C2 photosynthesis was acquired by localizing glycine decarboxylase activity in the mitochondria of bundle sheath cells. With the development of two-cell metabolism, anatomical features also changed. Next, the replacement of the two-celled C2 cycle by the two-celled C4 cycle was induced by the acquisition of cell-selective expression in addition to the upregulation of enzymes in the C4 cycle during the C3-C4 intermediate stage. This was supported by an increase in cyclic electron transport activity in response to an increase in the ATP/NADPH demand for metabolism. Suppression of the C3 cycle in mesophyll cells was induced after the functional establishment of the C4 cycle, and optimization of electron transport by suppressing the activity of photosystem II also occurred during the final phase of C4 evolution.}, } @article {pmid35122922, year = {2022}, author = {Baratange, C and Paris-Palacios, S and Bonnard, I and Delahaut, L and Grandjean, D and Wortham, L and Sayen, S and Gallorini, A and Michel, J and Renault, D and Breider, F and Loizeau, JL and Cosio, C}, title = {Metabolic, cellular and defense responses to single and co-exposure to carbamazepine and methylmercury in Dreissena polymorpha.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {300}, number = {}, pages = {118933}, doi = {10.1016/j.envpol.2022.118933}, pmid = {35122922}, issn = {1873-6424}, mesh = {Animals ; Carbamazepine/analysis/toxicity ; *Dreissena/metabolism ; Gills/metabolism ; *Methylmercury Compounds/metabolism/toxicity ; *Water Pollutants, Chemical/analysis ; }, abstract = {Carbamazepine (CBZ) and Hg are widespread and persistent micropollutants in aquatic environments. Both pollutants are known to trigger similar toxicity mechanisms, e.g. reactive oxygen species (ROS) production. Here, their effects were assessed in the zebra mussel Dreissena polymorpha, frequently used as a freshwater model in ecotoxicology and biomonitoring. Single and co-exposures to CBZ (3.9 μg L[-1]) and MeHg (280 ng L[-1]) were performed for 1 and 7 days. Metabolomics analyses evidenced that the co-exposure was the most disturbing after 7 days, reducing the amount of 25 metabolites involved in protein synthesis, energy metabolism, antioxidant response and osmoregulation, and significantly altering cells and organelles' structure supporting a reduction of functions of gills and digestive glands. CBZ alone after 7 days decreased the amount of α-aminobutyric acid and had a moderate effect on the structure of mitochondria in digestive glands. MeHg alone had no effect on mussels' metabolome, but caused a significant alteration of cells and organelles' structure in gills and digestive glands. Single exposures and the co-exposure increased antioxidant responses vs control in gills and digestive glands, without resulting in lipid peroxidation, suggesting an increased ROS production caused by both pollutants. Data globally supported that a higher number of hyperactive cells compensated cellular alterations in the digestive gland of mussels exposed to CBZ or MeHg alone, while CBZ + MeHg co-exposure overwhelmed this compensation after 7 days. Those effects were unpredictable based on cellular responses to CBZ and MeHg alone, highlighting the need to consider molecular toxicity pathways for a better anticipation of effects of pollutants in biota in complex environmental conditions.}, } @article {pmid35129136, year = {2022}, author = {Balasubramaniam, S and Soman, M and Katneni, VK and Tomy, S and Gopalapillay, G and Vijayan, KK}, title = {Mitochondrial DNA based diversity studies reveal distinct and substructured populations of pearlspot, Etroplus suratensis (Bloch, 1790) in Indian waters.}, journal = {Journal of genetics}, volume = {101}, number = {}, pages = {}, pmid = {35129136}, issn = {0973-7731}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; Genetic Variation ; Genetics, Population ; Haplotypes/genetics ; India ; *Mitochondria/genetics ; Phylogeny ; }, abstract = {Pearlspot (Etroplus suratensis) is one of the most commercially important brackish water fish species widely found along the coastal regions of peninsular India and Sri Lanka. Pearlspot is known for its tender flesh, delectable taste, culinary tourism and highyielding market value. Information on the genetic makeup of stocks/populations is extremely vital as it forms the basis for future genetic studies. For this, we utilized ATPase6/8 genes of mtDNA of pearlspot populations collected from nine different locations ranging from Ratnagiri in Maharashtra state on the west coast to Chilika in Odisha on the east coast. Sequence analyses of these genes revealed 33 polymorphic sites, which include 17 singleton and 16 parsimony informative sites. Pair-wise genetic differentiation study (FST = 0.75) indicated significant (P<0.001) differences among all the pairs of stocks except those from Chilika and Nagayalanka. The spatial analysis of molecular variance (SAMOVA) significantly delineated the population into four groups (FCT = 0.69, P = 0.0001), namely northwest (Ratnagiri and Goa); southwest (Mangalore and lakes at Vembanad, Ashtamudi and Vellayani in Kerala); southeast (Pulicat in Tamil Nadu) and northeast (Chilika in Odisha and Nagayalanka in Andhra Pradesh). The above delineation is supported by clades of the phylogenetic tree and also the clusters of median joining haplotype network. The high haplotype diversity (0.84), low nucleotide diversity (0.003), and negative values of Tajima's D (-1.47) and Fu's Fs statistic (-14.89) are characteristic of populations having recently undergone demographic expansion. Mantel test revealed significant isolation by distance. The study identifies highly delineated structured populations with restricted gene flow. If such a stock is overfished, it is highly unlikely that it would recover through migration. For any future breeding programme in this species, it would be desirable to form a base population which incorporates the genetic material from all the locations so that we get a wide gene pool to select from.}, } @article {pmid35132109, year = {2022}, author = {Verma, RK and Kalyakulina, A and Mishra, A and Ivanchenko, M and Jalan, S}, title = {Role of mitochondrial genetic interactions in determining adaptation to high altitude human population.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {2046}, pmid = {35132109}, issn = {2045-2322}, mesh = {Adaptation, Physiological/*genetics ; *Altitude ; Epistasis, Genetic/*genetics ; Ethiopia ; Genes, Mitochondrial/*genetics/*physiology ; Humans ; Mitochondria/*genetics/*physiology ; Polymorphism, Genetic ; South America ; Tibet ; }, abstract = {Physiological and haplogroup studies performed to understand high-altitude adaptation in humans are limited to individual genes and polymorphic sites. Due to stochastic evolutionary forces, the frequency of a polymorphism is affected by changes in the frequency of a near-by polymorphism on the same DNA sample making them connected in terms of evolution. Here, first, we provide a method to model these mitochondrial polymorphisms as "co-mutation networks" for three high-altitude populations, Tibetan, Ethiopian and Andean. Then, by transforming these co-mutation networks into weighted and undirected gene-gene interaction (GGI) networks, we were able to identify functionally enriched genetic interactions of CYB and CO3 genes in Tibetan and Andean populations, while NADH dehydrogenase genes in the Ethiopian population playing a significant role in high altitude adaptation. These co-mutation based genetic networks provide insights into the role of different set of genes in high-altitude adaptation in human sub-populations.}, } @article {pmid35133488, year = {2022}, author = {Shumenko, PG and Tatonova, YV}, title = {Assessing the population structure of trematode Metagonimus suifunensis using three mitochondrial markers.}, journal = {Parasitology research}, volume = {121}, number = {3}, pages = {915-923}, pmid = {35133488}, issn = {1432-1955}, mesh = {Animals ; DNA, Mitochondrial/chemistry/genetics ; Asia, Eastern ; Genetic Variation ; *Heterophyidae/genetics ; Mitochondria/genetics ; Phylogeny ; Russia ; }, abstract = {In this work, for the first time, the genetic variability of the Metagonimus suifunensis population in the Russian southern Far East was estimated based on the full-length sequences of the nad1 gene of mitochondrial DNA. In addition, for a sample of the same size, the sequences of cox1 and cytb genes, previously used for population studies for M. suifunensis, were reanalysed. Three markers were combined to a common sequence, and the obtained data were studied. Despite the higher level of variability, nad1 and cox1 mtDNA genes did not reveal subdivisions within the population. The combined dataset made it possible to determine that the sample from the Odyr River was the centre of the species' range formation and clarified the continental migration route of the parasite from south to north. According to the data obtained, it was presumed that piscivorous birds participate in the life cycle of the parasite. The subdivision within population revealed that using all three mitochondrial markers is consistent with the features of differentiation within populations of related species, but the reasons for its formation remain unclear due to the insufficient amount of data and the use of different markers in studies of different species.}, } @article {pmid35135343, year = {2022}, author = {Horrell, HD and Lindeque, A and Farrell, AP and Seymour, RS and White, CR and Kruger, KM and Snelling, EP}, title = {Relationship between capillaries, mitochondria and maximum power of the heart: a meta-study from shrew to elephant.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1968}, pages = {20212461}, pmid = {35135343}, issn = {1471-2954}, mesh = {Animals ; *Capillaries ; *Elephants ; Humans ; Mitochondria ; Oxygen ; Oxygen Consumption ; Phylogeny ; Shrews ; }, abstract = {This meta-study uses phylogenetic scaling models across more than 30 species, spanning five orders of magnitude in body mass, to show that cardiac capillary numerical density and mitochondrial volume density decrease with body mass raised to the -0.07 ± 0.03 and -0.04 ± 0.01 exponents, respectively. Thus, while an average 10 g mammal has a cardiac capillary density of approximately 4150 mm[-2] and a mitochondrial density of 33%, a 1 t mammal has considerably lower corresponding values of 1850 mm[-2] and 21%. These similar scaling trajectories suggest quantitative matching for the primary oxygen supply and oxygen consuming structures of the heart, supporting economic design at the cellular level of the oxygen cascade in this aerobic organ. These scaling trajectories are nonetheless somewhat shallower than the exponent of -0.11 calculated for the maximum external mechanical power of the cardiac tissue, under conditions of heavy exercise, when oxygen flow between capillaries and mitochondria is probably fully exploited. This mismatch, if substantiated, implies a declining external mechanical efficiency of the heart with increasing body mass, whereby larger individuals put more energy in but get less energy out, a scenario with implications for cardiovascular design, aerobic capacity and limits of body size.}, } @article {pmid35143947, year = {2022}, author = {Sai Satyanarayana, D and Ahlawat, S and Sharma, R and Arora, R and Sharma, A and Tantia, MS and Vijh, RK}, title = {Mitochondrial DNA diversity divulges high levels of haplotype diversity and lack of genetic structure in the Indian camels.}, journal = {Gene}, volume = {820}, number = {}, pages = {146279}, doi = {10.1016/j.gene.2022.146279}, pmid = {35143947}, issn = {1879-0038}, mesh = {Animals ; Biodiversity ; Camelus/*genetics ; DNA, Mitochondrial/*genetics ; Female ; *Genetic Variation ; Haplotypes ; India ; Male ; Mitochondria/*genetics ; Phylogeny ; }, abstract = {Camels represent an important genetic resource of the desert ecosystems of India, with the dromedary and Bactrian camels inhabiting the hot and cold deserts, respectively. This study is the first attempt to investigate mitochondrial DNA based genetic diversity in the Indian camel populations and explores their relationship in the context of global genetic diversity of all the three large camel species (Camelus ferus, Camelus bactrianus and Camelus dromedaries). A mitochondrial DNA fragment encompassing part of cytochrome b gene, tRNA[Thr], tRNA[Pro] and the beginning of the control region was amplified and analyzed in 72 dromedary and 8 Bactrian camels of India. Sequence analysis revealed that the haplotype and nucleotide diversity (Hd: 0.937 and π: 0.00431) in the Indian dromedaries was higher than the indices reported so far for the dromedary or Bactrian camels across the globe. The corresponding values in the Indian Bactrian camels were 1.000 and 0.00393, respectively. Signals of population expansion were evident in the dromedaries of India on the basis of mismatch analysis and Fu's Fs values. The analysis of molecular variance attributed most of the genetic variance (92.15%) between the dromedary, wild Bactrian and domestic Bactrian camels indicating separate maternal origins. The existence of three mitochondrial lineages in the old world camels (C. bactrianus: Lineage A; C. ferus: Lineage B and C. dromedarius: Lineage C) was also substantiated by the topology of the Median-Joining network.}, } @article {pmid35145105, year = {2022}, author = {Elsemman, IE and Rodriguez Prado, A and Grigaitis, P and Garcia Albornoz, M and Harman, V and Holman, SW and van Heerden, J and Bruggeman, FJ and Bisschops, MMM and Sonnenschein, N and Hubbard, S and Beynon, R and Daran-Lapujade, P and Nielsen, J and Teusink, B}, title = {Whole-cell modeling in yeast predicts compartment-specific proteome constraints that drive metabolic strategies.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {801}, pmid = {35145105}, issn = {2041-1723}, support = {BB/M025748/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M025756/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Fermentation ; Gene Expression Regulation, Fungal ; Glucose/metabolism ; *Metabolic Networks and Pathways/genetics ; Mitochondria/metabolism ; Proteome/*metabolism ; *Proteomics ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Yeasts/*genetics/growth & development/*metabolism ; }, abstract = {When conditions change, unicellular organisms rewire their metabolism to sustain cell maintenance and cellular growth. Such rewiring may be understood as resource re-allocation under cellular constraints. Eukaryal cells contain metabolically active organelles such as mitochondria, competing for cytosolic space and resources, and the nature of the relevant cellular constraints remain to be determined for such cells. Here, we present a comprehensive metabolic model of the yeast cell, based on its full metabolic reaction network extended with protein synthesis and degradation reactions. The model predicts metabolic fluxes and corresponding protein expression by constraining compartment-specific protein pools and maximising growth rate. Comparing model predictions with quantitative experimental data suggests that under glucose limitation, a mitochondrial constraint limits growth at the onset of ethanol formation-known as the Crabtree effect. Under sugar excess, however, a constraint on total cytosolic volume dictates overflow metabolism. Our comprehensive model thus identifies condition-dependent and compartment-specific constraints that can explain metabolic strategies and protein expression profiles from growth rate optimisation, providing a framework to understand metabolic adaptation in eukaryal cells.}, } @article {pmid35148829, year = {2022}, author = {Loconte, V and Singla, J and Li, A and Chen, JH and Ekman, A and McDermott, G and Sali, A and Le Gros, M and White, KL and Larabell, CA}, title = {Soft X-ray tomography to map and quantify organelle interactions at the mesoscale.}, journal = {Structure (London, England : 1993)}, volume = {30}, number = {4}, pages = {510-521.e3}, pmid = {35148829}, issn = {1878-4186}, support = {P30 GM138441/GM/NIGMS NIH HHS/United States ; P41 GM103445/GM/NIGMS NIH HHS/United States ; P41 GM109824/GM/NIGMS NIH HHS/United States ; R01 GM083960/GM/NIGMS NIH HHS/United States ; }, mesh = {*Imaging, Three-Dimensional/methods ; Insulin ; Mitochondria/ultrastructure ; Organelles ; *Tomography, X-Ray/methods ; }, abstract = {Inter-organelle interactions are a vital part of normal cellular function; however, these have proven difficult to quantify due to the range of scales encountered in cell biology and the throughput limitations of traditional imaging approaches. Here, we demonstrate that soft X-ray tomography (SXT) can be used to rapidly map ultrastructural reorganization and inter-organelle interactions in intact cells. SXT takes advantage of the naturally occurring, differential X-ray absorption of the carbon-rich compounds in each organelle. Specifically, we use SXT to map the spatiotemporal evolution of insulin vesicles and their co-localization and interaction with mitochondria in pancreatic β cells during insulin secretion and in response to different stimuli. We quantify changes in the morphology, biochemical composition, and relative position of mitochondria and insulin vesicles. These findings highlight the importance of a comprehensive and unbiased mapping at the mesoscale to characterize cell reorganization that would be difficult to detect with other existing methodologies.}, } @article {pmid35157851, year = {2022}, author = {Grass, M and McDougal, AD and Blazeski, A and Kamm, RD and García-Cardeña, G and Dewey, CF}, title = {A computational model of cardiomyocyte metabolism predicts unique reperfusion protocols capable of reducing cell damage during ischemia/reperfusion.}, journal = {The Journal of biological chemistry}, volume = {298}, number = {5}, pages = {101693}, pmid = {35157851}, issn = {1083-351X}, support = {T32 HL007627/HL/NHLBI NIH HHS/United States ; }, mesh = {*Computer Simulation ; Humans ; Ischemia/metabolism ; Mitochondria, Heart/metabolism ; *Myocardial Reperfusion Injury/metabolism ; *Myocytes, Cardiac/metabolism/pathology ; Oxygen/metabolism ; Reactive Oxygen Species/metabolism ; Reperfusion/*methods ; }, abstract = {If a coronary blood vessel is occluded and the neighboring cardiomyocytes deprived of oxygen, subsequent reperfusion of the ischemic tissue can lead to oxidative damage due to excessive generation of reactive oxygen species. Cardiomyocytes and their mitochondria are the main energy producers and consumers of the heart, and their metabolic changes during ischemia seem to be a key driver of reperfusion injury. Here, we hypothesized that tracking changes in cardiomyocyte metabolism, such as oxygen and ATP concentrations, would help in identifying points of metabolic failure during ischemia and reperfusion. To track some of these changes continuously from the onset of ischemia through reperfusion, we developed a system of differential equations representing the chemical reactions involved in the production and consumption of 67 molecular species. This model was validated and used to identify conditions present during periods of critical transition in ischemia and reperfusion that could lead to oxidative damage. These simulations identified a range of oxygen concentrations that lead to reverse mitochondrial electron transport at complex I of the respiratory chain and a spike in mitochondrial membrane potential, which are key suspects in the generation of reactive oxygen species at the onset of reperfusion. Our model predicts that a short initial reperfusion treatment with reduced oxygen content (5% of physiological levels) could reduce the cellular damage from both of these mechanisms. This model should serve as an open-source platform to test ideas for treatment of the ischemia reperfusion process by following the temporal evolution of molecular concentrations in the cardiomyocyte.}, } @article {pmid35162994, year = {2022}, author = {Phillips, MA and Arnold, KR and Vue, Z and Beasley, HK and Garza-Lopez, E and Marshall, AG and Morton, DJ and McReynolds, MR and Barter, TT and Hinton, A}, title = {Combining Metabolomics and Experimental Evolution Reveals Key Mechanisms Underlying Longevity Differences in Laboratory Evolved Drosophila melanogaster Populations.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, pmid = {35162994}, issn = {1422-0067}, support = {U54 CA163069/CA/NCI NIH HHS/United States ; T32 HL007121/HL/NHLBI NIH HHS/United States ; R25 HL106365/HL/NHLBI NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; R25 GM059994/GM/NIGMS NIH HHS/United States ; }, mesh = {Aging/*genetics/metabolism ; Animals ; Carbohydrate Metabolism ; Citric Acid Cycle ; Directed Molecular Evolution ; Drosophila melanogaster/genetics/*physiology ; Genomics/*methods ; Longevity ; Metabolomics/*methods ; Mitochondria/metabolism ; Multifactorial Inheritance ; NAD/metabolism ; Polymorphism, Single Nucleotide ; }, abstract = {Experimental evolution with Drosophila melanogaster has been used extensively for decades to study aging and longevity. In recent years, the addition of DNA and RNA sequencing to this framework has allowed researchers to leverage the statistical power inherent to experimental evolution to study the genetic basis of longevity itself. Here, we incorporated metabolomic data into to this framework to generate even deeper insights into the physiological and genetic mechanisms underlying longevity differences in three groups of experimentally evolved D. melanogaster populations with different aging and longevity patterns. Our metabolomic analysis found that aging alters mitochondrial metabolism through increased consumption of NAD[+] and increased usage of the TCA cycle. Combining our genomic and metabolomic data produced a list of biologically relevant candidate genes. Among these candidates, we found significant enrichment for genes and pathways associated with neurological development and function, and carbohydrate metabolism. While we do not explicitly find enrichment for aging canonical genes, neurological dysregulation and carbohydrate metabolism are both known to be associated with accelerated aging and reduced longevity. Taken together, our results provide plausible genetic mechanisms for what might be driving longevity differences in this experimental system. More broadly, our findings demonstrate the value of combining multiple types of omic data with experimental evolution when attempting to dissect mechanisms underlying complex and highly polygenic traits such as aging.}, } @article {pmid35163296, year = {2022}, author = {Amaroli, A and Ravera, S and Zekiy, A and Benedicenti, S and Pasquale, C}, title = {A Narrative Review on Oral and Periodontal Bacteria Microbiota Photobiomodulation, through Visible and Near-Infrared Light: From the Origins to Modern Therapies.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, pmid = {35163296}, issn = {1422-0067}, mesh = {Bacteria ; Humans ; Infrared Rays ; Light ; Low-Level Light Therapy/methods/*trends ; Microbiota/*radiation effects ; Mitochondria ; Periodontal Diseases/*microbiology/radiotherapy ; Phototherapy/methods/trends ; Stomatitis/radiotherapy ; }, abstract = {Photobiomodulation (PBM) consists of a photon energy transfer to the cell, employing non-ionizing light sources belonging to the visible and infrared spectrum. PBM acts on some intrinsic properties of molecules, energizing them through specific light wavelengths. During the evolution of life, semiconducting minerals were energized by sun radiation. The molecules that followed became photoacceptors and were expressed into the first proto-cells and prokaryote membranes. Afterward, the components of the mitochondria electron transport chain influenced the eukaryotic cell physiology. Therefore, although many organisms have not utilized light as an energy source, many of the molecules involved in their physiology have retained their primordial photoacceptive properties. Thus, in this review, we discuss how PBM can affect the oral microbiota through photo-energization and the non-thermal effect of light on photoacceptors (i.e., cytochromes, flavins, and iron-proteins). Sometimes, the interaction of photons with pigments of an endogenous nature is followed by thermal or photodynamic-like effects. However, the preliminary data do not allow determining reliable therapies but stress the need for further knowledge on light-bacteria interactions and microbiota management in the health and illness of patients through PBM.}, } @article {pmid35163574, year = {2022}, author = {Falchi, FA and Pizzoccheri, R and Briani, F}, title = {Activity and Function in Human Cells of the Evolutionary Conserved Exonuclease Polynucleotide Phosphorylase.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, pmid = {35163574}, issn = {1422-0067}, mesh = {*Evolution, Molecular ; *Exoribonucleases/genetics/metabolism ; Humans ; *Mutation ; *RNA/genetics/metabolism ; *RNA Stability ; *RNA-Binding Proteins/genetics/metabolism ; Mitochondrial Proteins ; }, abstract = {Polynucleotide phosphorylase (PNPase) is a phosphorolytic RNA exonuclease highly conserved throughout evolution. Human PNPase (hPNPase) is located in mitochondria and is essential for mitochondrial function and homeostasis. Not surprisingly, mutations in the PNPT1 gene, encoding hPNPase, cause serious diseases. hPNPase has been implicated in a plethora of processes taking place in different cell compartments and involving other proteins, some of which physically interact with hPNPase. This paper reviews hPNPase RNA binding and catalytic activity in relation with the protein structure and in comparison, with the activity of bacterial PNPases. The functions ascribed to hPNPase in different cell compartments are discussed, highlighting the gaps that still need to be filled to understand the physiological role of this ancient protein in human cells.}, } @article {pmid35163579, year = {2022}, author = {Lin, YH and Lim, SN and Chen, CY and Chi, HC and Yeh, CT and Lin, WR}, title = {Functional Role of Mitochondrial DNA in Cancer Progression.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, pmid = {35163579}, issn = {1422-0067}, support = {MOST 109-2314-B-182A-068-//Ministry of Science and Technology of the Republic of China/ ; MOST 110-2314-B-182A-095-//Ministry of Science and Technology of the Republic of China/ ; MOST 110-2311-B-182A-001-MY3//Ministry of Science and Technology of the Republic of China/ ; CMRPG3K2292//Chang Gung Memorial Hospital, Taiwan/ ; CMRPG3J0693//Chang Gung Memorial Hospital, Taiwan/ ; CMRPG3J1681//Chang Gung Memorial Hospital, Taiwan/ ; NRRPG3L6011//Chang Gung Memorial Hospital, Taiwan/ ; }, mesh = {*DNA, Mitochondrial/genetics/metabolism ; *DNA, Neoplasm/genetics/metabolism ; Humans ; *Mitochondria/genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; *Mutation ; Neoplasm Proteins/genetics/metabolism ; *Neoplasms/genetics/metabolism ; *Polymorphism, Single Nucleotide ; }, abstract = {Mitochondrial DNA (mtDNA) has been identified as a significant genetic biomarker in disease, cancer and evolution. Mitochondria function as modulators for regulating cellular metabolism. In the clinic, mtDNA variations (mutations/single nucleotide polymorphisms) and dysregulation of mitochondria-encoded genes are associated with survival outcomes among cancer patients. On the other hand, nuclear-encoded genes have been found to regulate mitochondria-encoded gene expression, in turn regulating mitochondrial homeostasis. These observations suggest that the crosstalk between the nuclear genome and mitochondrial genome is important for cellular function. Therefore, this review summarizes the significant mechanisms and functional roles of mtDNA variations (DNA level) and mtDNA-encoded genes (RNA and protein levels) in cancers and discusses new mechanisms of crosstalk between mtDNA and the nuclear genome.}, } @article {pmid35163839, year = {2022}, author = {Davoudi, M and Chen, J and Lou, Q}, title = {Genome-Wide Identification and Expression Analysis of Heat Shock Protein 70 (HSP70) Gene Family in Pumpkin (Cucurbita moschata) Rootstock under Drought Stress Suggested the Potential Role of these Chaperones in Stress Tolerance.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, pmid = {35163839}, issn = {1422-0067}, support = {BE2021357 and 2021YFD1200201-04//the Key Research and Development Program/ ; }, mesh = {Cucurbita/genetics/*physiology ; *Down-Regulation ; Droughts ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Plant ; Genomics/*methods ; HSP70 Heat-Shock Proteins/*genetics ; Multigene Family ; Phylogeny ; Plant Proteins/genetics ; Promoter Regions, Genetic ; Selection, Genetic ; Stress, Physiological ; }, abstract = {Heat shock protein 70s (HSP70s) are highly conserved proteins that are involved in stress responses. These chaperones play pivotal roles in protein folding, removing the extra amounts of oxidized proteins, preventing protein denaturation, and improving the antioxidant system activities. This conserved family has been characterized in several crops under drought stress conditions. However, there is no study on HSP70s in pumpkin (Cucurbita moschata). Therefore, we performed a comprehensive analysis of this gene family, including phylogenetic relationship, motif and gene structure analysis, gene duplication, collinearity, and promoter analysis. In this research, we found 21 HSP70s that were classified into five groups (from A to E). These genes were mostly localized in the cytoplasm, chloroplast, mitochondria, nucleus, and endoplasmic reticulum (ER). We could observe more similarity in closely linked subfamilies in terms of motifs, the number of introns/exons, and the corresponding cellular compartments. According to the collinearity analysis, gene duplication had occurred as a result of purifying selection. The results showed that the occurrence of gene duplication for all nine gene pairs was due to segmental duplication (SD). Synteny analysis revealed a closer relationship between pumpkin and cucumber than pumpkin and Arabidopsis. Promoter analysis showed the presence of various cis-regulatory elements in the up-stream region of the HSP70 genes, such as hormones and stress-responsive elements, indicating a potential role of this gene family in stress tolerance. We furtherly performed the gene expression analysis of the HSP70s in pumpkin under progressive drought stress. Pumpkin is widely used as a rootstock to improve stress tolerance, as well as fruit quality of cucumber scion. Since stress-responsive mobile molecules translocate through vascular tissue from roots to the whole plant body, we used the xylem of grafted materials to study the expression patterns of the HSP70 (potentially mobile) gene family. The results indicated that all CmoHSP70s had very low expression levels at 4 days after stress (DAS). However, the genes showed different expression patterns by progressing he drought period. For example, the expression of CmoHSP70-4 (in subgroup E) and CmoHSP70-14 (in subgroup C) sharply increased at 6 and 11 DAS, respectively. However, the expression of all genes belonging to subgroup A did not change significantly in response to drought stress. These findings indicated the diverse roles of this gene family under drought stress and provided valuable information for further investigation on the function of this gene family, especially under stressful conditions.}, } @article {pmid35174241, year = {2021}, author = {Ahmad, HI and Afzal, G and Iqbal, MN and Iqbal, MA and Shokrollahi, B and Mansoor, MK and Chen, J}, title = {Positive Selection Drives the Adaptive Evolution of Mitochondrial Antiviral Signaling (MAVS) Proteins-Mediating Innate Immunity in Mammals.}, journal = {Frontiers in veterinary science}, volume = {8}, number = {}, pages = {814765}, pmid = {35174241}, issn = {2297-1769}, abstract = {The regulated production of filamentous protein complexes is essential in many biological processes and provides a new paradigm in signal transmission. The mitochondrial antiviral signaling protein (MAVS) is a critical signaling hub in innate immunity that is activated when a receptor induces a shift in the globular caspase activation and recruitment domain of MAVS into helical superstructures (filaments). It is of interest whether adaptive evolution affects the proteins involved in innate immunity. Here, we explore and confer the role of selection and diversification on mitochondrial antiviral signaling protein in mammalian species. We obtined the MAVS proteins of mammalian species and examined their differences in evolutionary patterns. We discovered evidence for these proteins being subjected to substantial positive selection. We demonstrate that immune system proteins, particularly those encoding recognition proteins, develop under positive selection using codon-based probability methods. Positively chosen regions within recognition proteins cluster in domains involved in microorganism recognition, implying that molecular interactions between hosts and pathogens may promote adaptive evolution in the mammalian immune systems. These significant variations in MAVS development in mammalian species highlights the involvement of MAVS in innate immunity. Our findings highlight the significance of accounting for how non-synonymous alterations affect structure and function when employing sequence-level studies to determine and quantify positive selection.}, } @article {pmid35175958, year = {2023}, author = {Buja, LM}, title = {Pathobiology of Myocardial Ischemia and Reperfusion Injury: Models, Modes, Molecular Mechanisms, Modulation, and Clinical Applications.}, journal = {Cardiology in review}, volume = {31}, number = {5}, pages = {252-264}, pmid = {35175958}, issn = {1538-4683}, abstract = {This review presents an integrated approach to the analysis of myocardial ischemia and reperfusion injury and the modulating influence of myocardial conditioning during the evolution of acute myocardial infarction (AMI) and other clinical settings. Experimental studies have involved a spectrum of in vitro, ex vivo, and in vivo models, and guidelines have been developed for the conduct of rigorous preclinical studies and for the identification of various forms of cell injury and death in evolving AMI. AMI in vivo is dominated by oncosis (cell injury with swelling) leading to necroptosis and final necrosis of ischemic cardiomyocytes (CMCs), without or with contraction band formation. Early after coronary occlusion, reperfusion salvages a significant amount of ischemic myocardium in the subepicardium while reperfusion injury contributes up to 50% of the final subendocardial infarct. AMI progression is mediated by damage (or danger)-associated molecular patterns, also known as alarmins, which activate pattern recognition receptors and initiate the inflammatory response. In preclinical studies, lethal reperfusion injury can largely be prevented with preconditioning or postconditioning by pharmacologic or physical means due to effects on both the CMC and microvasculature. Conditioning involves triggers, cytosolic mediators, and intracellular effectors. Mitochondria have a central role in the maintenance and loss of viability of CMCs. Reperfusion of severely ischemic myocardium leads to sustained opening of the mitochondrial permeability transition pore (MPTP). Once the MPTP is opened, the mitochondrial membrane potential (ΔΨm) is rapidly lost and energy production ceases. Conditioning blocks the sustained opening of the MPTP. Translation of conditioning strategies to the clinical management of patients has been challenging. The status of translation of experimental findings to approaches to modulate and ameliorate ischemic and reperfusion injury is discussed for the clinical settings of acute coronary syndromes treated with percutaneous interventions and cardiac preservation during open heart surgery and cardiac transplantation.}, } @article {pmid35187492, year = {2022}, author = {Juhaszova, M and Kobrinsky, E and Zorov, DB and Nuss, HB and Yaniv, Y and Fishbein, KW and de Cabo, R and Montoliu, L and Gabelli, SB and Aon, MA and Cortassa, S and Sollott, SJ}, title = {ATP Synthase K[+]- and H[+]-fluxes Drive ATP Synthesis and Enable Mitochondrial K[+]-"Uniporter" Function: II. Ion and ATP Synthase Flux Regulation.}, journal = {Function (Oxford, England)}, volume = {3}, number = {2}, pages = {zqac001}, pmid = {35187492}, issn = {2633-8823}, mesh = {Bayes Theorem ; Myeloid Cell Leukemia Sequence 1 Protein/metabolism ; Phylogeny ; *Mitochondrial Proton-Translocating ATPases/genetics ; *Mitochondria/metabolism ; Adenosine Triphosphate/metabolism ; }, abstract = {We demonstrated that ATP synthase serves the functions of a primary mitochondrial K[+] "uniporter," i.e., the primary way for K[+] to enter mitochondria. This K[+] entry is proportional to ATP synthesis, regulating matrix volume and energy supply-vs-demand matching. We show that ATP synthase can be upregulated by endogenous survival-related proteins via IF1. We identified a conserved BH3-like domain of IF1 which overlaps its "minimal inhibitory domain" that binds to the β-subunit of F1. Bcl-xL and Mcl-1 possess a BH3-binding-groove that can engage IF1 and exert effects, requiring this interaction, comparable to diazoxide to augment ATP synthase's H[+] and K[+] flux and ATP synthesis. Bcl-xL and Mcl-1, but not Bcl-2, serve as endogenous regulatory ligands of ATP synthase via interaction with IF1 at this BH3-like domain, to increase its chemo-mechanical efficiency, enabling its function as the recruitable mitochondrial KATP-channel that can limit ischemia-reperfusion injury. Using Bayesian phylogenetic analysis to examine potential bacterial IF1-progenitors, we found that IF1 is likely an ancient (∼2 Gya) Bcl-family member that evolved from primordial bacteria resident in eukaryotes, corresponding to their putative emergence as symbiotic mitochondria, and functioning to prevent their parasitic ATP consumption inside the host cell.}, } @article {pmid35188099, year = {2022}, author = {De La Rossa, A and Laporte, MH and Astori, S and Marissal, T and Montessuit, S and Sheshadri, P and Ramos-Fernández, E and Mendez, P and Khani, A and Quairiaux, C and Taylor, EB and Rutter, J and Nunes, JM and Carleton, A and Duchen, MR and Sandi, C and Martinou, JC}, title = {Paradoxical neuronal hyperexcitability in a mouse model of mitochondrial pyruvate import deficiency.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35188099}, issn = {2050-084X}, mesh = {3-Hydroxybutyric Acid/pharmacology ; Animals ; Anion Transport Proteins/genetics/*metabolism ; Biological Transport ; Calcium/physiology ; Gene Expression Regulation/drug effects ; Homeostasis/drug effects/physiology ; Ketone Bodies ; Mice ; Mice, Knockout ; Mitochondria/*metabolism ; Mitochondrial Membrane Transport Proteins/genetics/*metabolism ; Monocarboxylic Acid Transporters/genetics/*metabolism ; Neurons/drug effects/metabolism ; Oxidation-Reduction ; Pentylenetetrazole/toxicity ; Phosphorylation ; Pyruvic Acid/*metabolism ; Seizures/chemically induced ; Tamoxifen/pharmacology ; }, abstract = {Neuronal excitation imposes a high demand of ATP in neurons. Most of the ATP derives primarily from pyruvate-mediated oxidative phosphorylation, a process that relies on import of pyruvate into mitochondria occuring exclusively via the mitochondrial pyruvate carrier (MPC). To investigate whether deficient oxidative phosphorylation impacts neuron excitability, we generated a mouse strain carrying a conditional deletion of MPC1, an essential subunit of the MPC, specifically in adult glutamatergic neurons. We found that, despite decreased levels of oxidative phosphorylation and decreased mitochondrial membrane potential in these excitatory neurons, mice were normal at rest. Surprisingly, in response to mild inhibition of GABA mediated synaptic activity, they rapidly developed severe seizures and died, whereas under similar conditions the behavior of control mice remained unchanged. We report that neurons with a deficient MPC were intrinsically hyperexcitable as a consequence of impaired calcium homeostasis, which reduced M-type potassium channel activity. Provision of ketone bodies restored energy status, calcium homeostasis and M-channel activity and attenuated seizures in animals fed a ketogenic diet. Our results provide an explanation for the seizures that frequently accompany a large number of neuropathologies, including cerebral ischemia and diverse mitochondriopathies, in which neurons experience an energy deficit.}, } @article {pmid35189365, year = {2022}, author = {Hawlitschek, O and Ortiz, EM and Noori, S and Webster, KC and Husemann, M and Pereira, RJ}, title = {Transcriptomic data reveals nuclear-mitochondrial discordance in Gomphocerinae grasshoppers (Insecta: Orthoptera: Acrididae).}, journal = {Molecular phylogenetics and evolution}, volume = {170}, number = {}, pages = {107439}, doi = {10.1016/j.ympev.2022.107439}, pmid = {35189365}, issn = {1095-9513}, mesh = {Animals ; *Grasshoppers/genetics ; Hybridization, Genetic ; Mitochondria/genetics ; *Orthoptera/genetics ; Phylogeny ; Transcriptome ; }, abstract = {The phylogeny of many groups of Orthoptera remains poorly understood. Previous phylogenetic studies largely restricted to few mitochondrial markers found many species in the grasshopper subfamily Gomphocerinae to be para- or polyphyletic, presumably because of incomplete lineage sorting and ongoing hybridization between putatively young lineages. Resolving the phylogeny of the Chorthippus biguttulus species complex is important because many morphologically cryptic species occupy overlapping ranges across Eurasia and serve important ecological functions. We investigated whether multispecies coalescent analysis of 540 genes generated by transcriptome sequencing could resolve the phylogeny of the C. biguttulus complex and related Gomphocerinae species. Our divergence time estimates confirm that Gomphocerinae is a very young radiation, with an age estimated at 1.38 (2.35-0.77) mya for the C. biguttulus complex. Our estimated topology based on complete mitogenomes recovered some species as para- or polyphyletic. In contrast, the multispecies coalescent based on nuclear genes retrieved all species as monophyletic clusters, corroborating most taxonomic hypotheses. Our results underline the importance of using nuclear multispecies coalescent methods for studying young radiations and highlight the need of further taxonomic revision in Gomphocerinae grasshoppers.}, } @article {pmid35191499, year = {2022}, author = {Zamudio-Ochoa, A and Morozov, YI and Sarfallah, A and Anikin, M and Temiakov, D}, title = {Mechanisms of mitochondrial promoter recognition in humans and other mammalian species.}, journal = {Nucleic acids research}, volume = {50}, number = {5}, pages = {2765-2781}, pmid = {35191499}, issn = {1362-4962}, support = {R35 GM131832/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA, Mitochondrial/genetics ; DNA-Directed RNA Polymerases/metabolism ; Humans ; Mammals/genetics/metabolism ; Mitochondria/enzymology/*genetics ; Mitochondrial Proteins/metabolism ; Transcription Factors/chemistry/genetics ; Transcription Initiation Site ; *Transcription, Genetic ; }, abstract = {Recognition of mammalian mitochondrial promoters requires the concerted action of mitochondrial RNA polymerase (mtRNAP) and transcription initiation factors TFAM and TFB2M. In this work, we found that transcript slippage results in heterogeneity of the human mitochondrial transcripts in vivo and in vitro. This allowed us to correctly interpret the RNAseq data, identify the bona fide transcription start sites (TSS), and assign mitochondrial promoters for > 50% of mammalian species and some other vertebrates. The divergent structure of the mammalian promoters reveals previously unappreciated aspects of mtDNA evolution. The correct assignment of TSS also enabled us to establish the precise register of the DNA in the initiation complex and permitted investigation of the sequence-specific protein-DNA interactions. We determined the molecular basis of promoter recognition by mtRNAP and TFB2M, which cooperatively recognize bases near TSS in a species-specific manner. Our findings reveal a role of mitochondrial transcription machinery in mitonuclear coevolution and speciation.}, } @article {pmid35197365, year = {2022}, author = {Łabędzka-Dmoch, K and Rażew, M and Gapińska, M and Piątkowski, J and Kolondra, A and Salmonowicz, H and Wenda, JM and Nowotny, M and Golik, P}, title = {The Pet127 protein is a mitochondrial 5'-to-3' exoribonuclease from the PD-(D/E)XK superfamily involved in RNA maturation and intron degradation in yeasts.}, journal = {RNA (New York, N.Y.)}, volume = {28}, number = {5}, pages = {711-728}, pmid = {35197365}, issn = {1469-9001}, mesh = {Candida albicans ; *Exoribonucleases/genetics ; Fungal Proteins/genetics/metabolism ; Introns/genetics ; Mitochondrial Proteins/genetics ; Phylogeny ; *RNA ; }, abstract = {Pet127 is a mitochondrial protein found in multiple eukaryotic lineages, but absent from several taxa, including plants and animals. Distant homology suggests that it belongs to the divergent PD-(D/E)XK superfamily which includes various nucleases and related proteins. Earlier yeast genetics experiments suggest that it plays a nonessential role in RNA degradation and 5' end processing. Our phylogenetic analysis suggests that it is a primordial eukaryotic invention that was retained in diverse groups, and independently lost several times in the evolution of other organisms. We demonstrate for the first time that the fungal Pet127 protein in vitro is a processive 5'-to-3' exoribonuclease capable of digesting various substrates in a sequence nonspecific manner. Mutations in conserved residues essential in the PD-(D/E)XK superfamily active site abolish the activity of Pet127. Deletion of the PET127 gene in the pathogenic yeast Candida albicans results in a moderate increase in the steady-state levels of several transcripts and in accumulation of unspliced precursors and intronic sequences of three introns. Mutations in the active site residues result in a phenotype identical to that of the deletant, confirming that the exoribonuclease activity is related to the physiological role of the Pet127 protein. Pet127 activity is, however, not essential for maintaining the mitochondrial respiratory activity in C. albicans.}, } @article {pmid35199143, year = {2022}, author = {Helmstetter, N and Chybowska, AD and Delaney, C and Da Silva Dantas, A and Gifford, H and Wacker, T and Munro, C and Warris, A and Jones, B and Cuomo, CA and Wilson, D and Ramage, G and Farrer, RA}, title = {Population genetics and microevolution of clinical Candida glabrata reveals recombinant sequence types and hyper-variation within mitochondrial genomes, virulence genes, and drug targets.}, journal = {Genetics}, volume = {221}, number = {1}, pages = {}, pmid = {35199143}, issn = {1943-2631}, support = {MR/V033417/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Antifungal Agents/pharmacology ; *Candida glabrata/genetics ; Drug Resistance, Fungal/genetics ; Genetics, Population ; *Genome, Mitochondrial ; Humans ; Virulence/genetics ; }, abstract = {Candida glabrata is the second most common etiological cause of worldwide systemic candidiasis in adult patients. Genome analysis of 68 isolates from 8 hospitals across Scotland, together with 83 global isolates, revealed insights into the population genetics and evolution of C. glabrata. Clinical isolates of C. glabrata from across Scotland are highly genetically diverse, including at least 19 separate sequence types that have been recovered previously in globally diverse locations, and 1 newly discovered sequence type. Several sequence types had evidence for ancestral recombination, suggesting transmission between distinct geographical regions has coincided with genetic exchange arising in new clades. Three isolates were missing MATα1, potentially representing a second mating type. Signatures of positive selection were identified in every sequence type including enrichment for epithelial adhesins thought to facilitate fungal adhesin to human epithelial cells. In patent microevolution was identified from 7 sets of recurrent cases of candidiasis, revealing an enrichment for nonsynonymous and frameshift indels in cell surface proteins. Microevolution within patients also affected epithelial adhesins genes, and several genes involved in drug resistance including the ergosterol synthesis gene ERG4 and the echinocandin target FKS1/2, the latter coinciding with a marked drop in fluconazole minimum inhibitory concentration. In addition to nuclear genome diversity, the C. glabrata mitochondrial genome was particularly diverse, with reduced conserved sequence and conserved protein-encoding genes in all nonreference ST15 isolates. Together, this study highlights the genetic diversity within the C. glabrata population that may impact virulence and drug resistance, and 2 major mechanisms generating this diversity: microevolution and genetic exchange/recombination.}, } @article {pmid35205149, year = {2022}, author = {Zhu, Y}, title = {Gap Junction-Dependent and -Independent Functions of Connexin43 in Biology.}, journal = {Biology}, volume = {11}, number = {2}, pages = {}, pmid = {35205149}, issn = {2079-7737}, abstract = {For the first time in animal evolution, the emergence of gap junctions allowed direct exchanges of cellular substances for communication between two cells. Innexin proteins constituted primordial gap junctions until the connexin protein emerged in deuterostomes and took over the gap junction function. After hundreds of millions of years of gene duplication, the connexin gene family now comprises 21 members in the human genome. Notably, GJA1, which encodes the Connexin43 protein, is one of the most widely expressed and commonly studied connexin genes. The loss of Gja1 in mice leads to swelling and a blockage of the right ventricular outflow tract and death of the embryos at birth, suggesting a vital role of Connexin43 gap junction in heart development. Since then, the importance of Connexin43-mediated gap junction function has been constantly expanded to other types of cells. Other than forming gap junctions, Connexin43 can also form hemichannels to release or uptake small molecules from the environment or even mediate many physiological processes in a gap junction-independent manner on plasma membranes. Surprisingly, Connexin43 also localizes to mitochondria in the cell, playing important roles in mitochondrial potassium import and respiration. At the molecular level, Connexin43 mRNA and protein are processed with very distinct mechanisms to yield carboxyl-terminal fragments with different sizes, which have their unique subcellular localization and distinct biological activities. Due to many exciting advancements in Connexin43 research, this review aims to start with a brief introduction of Connexin43 and then focuses on updating our knowledge of its gap junction-independent functions.}, } @article {pmid35205291, year = {2022}, author = {Zhang, BQ and Song, XP and Zhang, XQ and Huang, YX and Liang, YJ and Zhou, S and Yang, CF and Yang, LT and Huang, X and Li, YR}, title = {Differential Gene Expression Analysis of SoCBL Family Calcineurin B-like Proteins: Potential Involvement in Sugarcane Cold Stress.}, journal = {Genes}, volume = {13}, number = {2}, pages = {}, pmid = {35205291}, issn = {2073-4425}, mesh = {Calcineurin/genetics ; Cold-Shock Response/genetics ; Gene Expression ; Phylogeny ; *Saccharum/genetics ; }, abstract = {Sugarcan e is a major crop for sugar and biofuel production and is cultivated in tropical and subtropical areas worldwide. Sugarcane growth is constrained because of winter's low-temperature stress, and cold resistance is an important limitation in sugarcane growth enhancement. Therefore, in this study, we identified a gene involved in the low-temperature stress response of sugarcane. Calcineurin B-like (CBL) protein is a calcium signal receptor involved in the cold stress response. Five sugarcane CBL genes were cloned, sequenced, and named SoCBL1, SoCBL3, SoCBL5, SoCBL6, and SoCBL9. The protein sequences of these genes were analyzed. The calculated molecular weight of these proteins was 24.5, 25.9, 25.2, 25.6, and 26.3 kD, respectively. Subcellular localization analysis revealed that SoCBL1, SoCBL3, SoCBL6, and SoCBL9 were situated in the cytoplasm, while SoCBL5 was present in mitochondria. Secondary structure analysis showed that these five CBL proteins had similar secondary structures. Conserved domain analysis displayed that each sugarcane CBL protein contained three conserved EF domains. According to the self-expanding values of the phylogenetic tree, the CBL gene family was divided into four groups. The CBL1 and CBL9 genes were classified into one group, illustrating that these two genes might possess a similar function. The expression analysis of the SoCBL gene under low temperatures showed that SoCBL3 and SoCBL5 were affected significantly, while SoCBL1 and SoCBL9 were less affected. These results demonstrate that the CBL genes in sugarcane have similar characteristics and present differences in genetic diversity and gene expression response to low temperatures. Therefore, these genes might be novel candidates for fighting cold stress in sugarcane.}, } @article {pmid35207539, year = {2022}, author = {Lei, L and Burton, ZF}, title = {"Superwobbling" and tRNA-34 Wobble and tRNA-37 Anticodon Loop Modifications in Evolution and Devolution of the Genetic Code.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35207539}, issn = {2075-1729}, abstract = {The genetic code evolved around the reading of the tRNA anticodon on the primitive ribosome, and tRNA-34 wobble and tRNA-37 modifications coevolved with the code. We posit that EF-Tu, the closing mechanism of the 30S ribosomal subunit, methylation of wobble U34 at the 5-carbon and suppression of wobbling at the tRNA-36 position were partly redundant and overlapping functions that coevolved to establish the code. The genetic code devolved in evolution of mitochondria to reduce the size of the tRNAome (all of the tRNAs of an organism or organelle). "Superwobbling" or four-way wobbling describes a major mechanism for shrinking the mitochondrial tRNAome. In superwobbling, unmodified wobble tRNA-U34 can recognize all four codon wobble bases (A, G, C and U), allowing a single unmodified tRNA-U34 to read a 4-codon box. During code evolution, to suppress superwobbling in 2-codon sectors, U34 modification by methylation at the 5-carbon position appears essential. As expected, at the base of code evolution, tRNA-37 modifications mostly related to the identity of the adjacent tRNA-36 base. TRNA-37 modifications help maintain the translation frame during elongation.}, } @article {pmid35208909, year = {2022}, author = {Cevallos, MA and Degli Esposti, M}, title = {New Alphaproteobacteria Thrive in the Depths of the Ocean with Oxygen Gradient.}, journal = {Microorganisms}, volume = {10}, number = {2}, pages = {}, pmid = {35208909}, issn = {2076-2607}, abstract = {We survey here the Alphaproteobacteria, a large class encompassing physiologically diverse bacteria which are divided in several orders established since 2007. Currently, there is considerable uncertainty regarding the classification of an increasing number of marine metagenome-assembled genomes (MAGs) that remain poorly defined in their taxonomic position within Alphaproteobacteria. The traditional classification of NCBI taxonomy is increasingly complemented by the Genome Taxonomy Database (GTDB), but the two taxonomies differ considerably in the classification of several Alphaproteobacteria, especially from ocean metagenomes. We analyzed the classification of Alphaproteobacteria lineages that are most common in marine environments, using integrated approaches of phylogenomics and functional profiling of metabolic features that define their aerobic metabolism. Using protein markers such as NuoL, the largest membrane subunit of complex I, we have identified new clades of Alphaproteobacteria that are specific to marine niches with steep oxygen gradients (oxycline). These bacteria have relatives among MAGs found in anoxic strata of Lake Tanganyika and together define a lineage that is distinct from either Rhodospirillales or Sneathiellales. We characterized in particular the new 'oxycline' clade. Our analysis of Alphaproteobacteria also reveals new clues regarding the ancestry of mitochondria, which likely evolved in oxycline marine environments.}, } @article {pmid35215562, year = {2022}, author = {Levy, D and Giannini, M and Oulehri, W and Riou, M and Marcot, C and Pizzimenti, M and Debrut, L and Charloux, A and Geny, B and Meyer, A}, title = {Long Term Follow-Up of Sarcopenia and Malnutrition after Hospitalization for COVID-19 in Conventional or Intensive Care Units.}, journal = {Nutrients}, volume = {14}, number = {4}, pages = {}, pmid = {35215562}, issn = {2072-6643}, mesh = {Aged ; *COVID-19/complications ; Follow-Up Studies ; Hand Strength ; Hospitalization ; Humans ; Intensive Care Units ; *Malnutrition/diagnosis/epidemiology ; Quality of Life ; SARS-CoV-2 ; *Sarcopenia/diagnosis/epidemiology/etiology ; }, abstract = {BACKGROUND: The post-COVID-19 condition, defined as COVID-19-related signs and symptoms lasting at least 2 months and persisting more than 3 months after infection, appears now as a public health issue in terms of frequency and quality of life alterations. Nevertheless, few data are available concerning long term evolution of malnutrition and sarcopenia, which deserve further attention.

METHOD: Sarcopenia was investigated prospectively, together with weight evolution, at admission and at 3 and 6 months after hospital discharge in 139 COVID-19 patients, using the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, associating both decreased muscle strength and muscle mass, assessed, respectively, with hand dynamometer and dual-energy X-ray absorptiometry.

RESULTS: Of the 139 patients, 22 presented with sarcopenia at 3 months; intensive care units (ICU) length of stay was the sole factor associated with sarcopenia after multivariate analysis. Although the entire group did not demonstrate significant weight change, weight decreased significantly in the sarcopenia group (Five and eight patients, showing, respectively, >5 or >10% weight decrease). Interestingly, at 6 months, 16 of the 22 patients recovered from sarcopenia and their weight returned toward baseline values.

CONCLUSIONS: Sarcopenia and malnutrition are frequently observed in patients hospitalized for COVID-19, even 3 months after infection occurrence, but can largely be reversed at 6 months after discharge. Enhanced patient care is needed in sarcopenic patients, particularly during long stays in an ICU.}, } @article {pmid35219813, year = {2022}, author = {Xia, L and Cheng, C and Zhao, X and He, X and Yu, X and Li, J and Wang, Y and Chen, J}, title = {Characterization of the mitochondrial genome of Cucumis hystrix and comparison with other cucurbit crops.}, journal = {Gene}, volume = {823}, number = {}, pages = {146342}, doi = {10.1016/j.gene.2022.146342}, pmid = {35219813}, issn = {1879-0038}, mesh = {Crops, Agricultural/genetics ; Cucumis/*genetics ; Cucurbitaceae/classification/*genetics ; Evolution, Molecular ; Gene Transfer, Horizontal ; Genome Size ; *Genome, Mitochondrial ; Genomics ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA/*methods ; }, abstract = {The mitochondria ofCucumis genus contain several intriguing features such as paternal inheritance and three-ring genome structure. However, the evolutionary relationships of mitochondria inCucumisremain elusive. Here, we assembled the mitochondrial genome ofC. hystrixand performed a comparative genomic analysis with other crops inthe Cucurbitaceae. The mitochondrial genome ofC. hystrixhas three circular-mapping chromosomes of lengths 1,113,461 bp, 110,683 bp, and 92,288 bp, which contain 73 genes including 38 protein-coding genes, 31tRNAgenes, and 4rRNAgenes. Repeat sequences, RNA editing, and horizontal gene transfer events were identified. The results of phylogenetic analyses, collinearity and gene clusters revealed thatC. hystrixis closer toC. sativus than to C. melo. Meanwhile, wedemonstrated mitochondrial paternal inheritance inC. hystrixbymolecular markers. In comparison with other cucurbitcrops, wefound amarker foridentification of germplasm resources ofCucumis. Collectively, our findings provide a tool to help clarify the paternal lineage within that genus in the evolution of Cucumis.}, } @article {pmid35222958, year = {2022}, author = {Zárate, D and Lima, TG and Poole, JD and Calfee, E and Burton, RS and Kohn, JR}, title = {Admixture in Africanized honey bees (Apis mellifera) from Panamá to San Diego, California (U.S.A.).}, journal = {Ecology and evolution}, volume = {12}, number = {2}, pages = {e8580}, pmid = {35222958}, issn = {2045-7758}, abstract = {The Africanized honey bee (AHB) is a New World amalgamation of several subspecies of the western honey bee (Apis mellifera), a diverse taxon historically grouped into four major biogeographic lineages: A (African), M (Western European), C (Eastern European), and O (Middle Eastern). In 1956, accidental release of experimentally bred "Africanized" hybrids from a research apiary in Sao Paulo, Brazil initiated a hybrid species expansion that now extends from northern Argentina to northern California (U.S.A.). Here, we assess nuclear admixture and mitochondrial ancestry in 60 bees from four countries (Panamá; Costa Rica, Mexico; U.S.A) across this expansive range to assess ancestry of AHB several decades following initial introduction and test the prediction that African ancestry decreases with increasing latitude. We find that AHB nuclear genomes from Central America and Mexico have predominately African genomes (76%-89%) with smaller contributions from Western and Eastern European lineages. Similarly, nearly all honey bees from Central America and Mexico possess mitochondrial ancestry from the African lineage with few individuals having European mitochondria. In contrast, AHB from San Diego (CA) shows markedly lower African ancestry (38%) with substantial genomic contributions from all four major honey bee lineages and mitochondrial ancestry from all four clades as well. Genetic diversity measures from all New World populations equal or exceed those of ancestral populations. Interestingly, the feral honey bee population of San Diego emerges as a reservoir of diverse admixture and high genetic diversity, making it a potentially rich source of genetic material for honey bee breeding.}, } @article {pmid35231030, year = {2022}, author = {Güngör, B and Flohr, T and Garg, SG and Herrmann, JM}, title = {The ER membrane complex (EMC) can functionally replace the Oxa1 insertase in mitochondria.}, journal = {PLoS biology}, volume = {20}, number = {3}, pages = {e3001380}, pmid = {35231030}, issn = {1545-7885}, mesh = {Amino Acid Sequence ; Cell Respiration/genetics ; Electron Transport Complex IV/genetics/*metabolism ; Endoplasmic Reticulum/*metabolism ; Membrane Proteins/genetics/*metabolism ; Mitochondria/genetics/*metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Mitochondrial Proton-Translocating ATPases/genetics/metabolism ; Mutation ; Nuclear Proteins/genetics/*metabolism ; Phylogeny ; Protein Biosynthesis/genetics ; Protein Transport/genetics ; Saccharomyces cerevisiae/genetics/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/classification/genetics/metabolism ; Sequence Homology, Amino Acid ; }, abstract = {Two multisubunit protein complexes for membrane protein insertion were recently identified in the endoplasmic reticulum (ER): the guided entry of tail anchor proteins (GET) complex and ER membrane complex (EMC). The structures of both of their hydrophobic core subunits, which are required for the insertion reaction, revealed an overall similarity to the YidC/Oxa1/Alb3 family members found in bacteria, mitochondria, and chloroplasts. This suggests that these membrane insertion machineries all share a common ancestry. To test whether these ER proteins can functionally replace Oxa1 in yeast mitochondria, we generated strains that express mitochondria-targeted Get2-Get1 and Emc6-Emc3 fusion proteins in Oxa1 deletion mutants. Interestingly, the Emc6-Emc3 fusion was able to complement an Δoxa1 mutant and restored its respiratory competence. The Emc6-Emc3 fusion promoted the insertion of the mitochondrially encoded protein Cox2, as well as of nuclear encoded inner membrane proteins, although was not able to facilitate the assembly of the Atp9 ring. Our observations indicate that protein insertion into the ER is functionally conserved to the insertion mechanism in bacteria and mitochondria and adheres to similar topological principles.}, } @article {pmid35242350, year = {2022}, author = {Pearman, WS and Wells, SJ and Dale, J and Silander, OK and Freed, NE}, title = {Long-read sequencing reveals atypical mitochondrial genome structure in a New Zealand marine isopod.}, journal = {Royal Society open science}, volume = {9}, number = {1}, pages = {211550}, pmid = {35242350}, issn = {2054-5703}, abstract = {Most animal mitochondrial genomes are small, circular and structurally conserved. However, recent work indicates that diverse taxa possess unusual mitochondrial genomes. In Isopoda, species in multiple lineages have atypical and rearranged mitochondrial genomes. However, more species of this speciose taxon need to be evaluated to understand the evolutionary origins of atypical mitochondrial genomes in this group. In this study, we report the presence of an atypical mitochondrial structure in the New Zealand endemic marine isopod, Isocladus armatus. Data from long- and short-read DNA sequencing suggest that I. armatus has two mitochondrial chromosomes. The first chromosome consists of two mitochondrial genomes that have been inverted and fused together in a circular form, and the second chromosome consists of a single mitochondrial genome in a linearized form. This atypical mitochondrial structure has been detected in other isopod lineages, and our data from an additional divergent isopod lineage (Sphaeromatidae) lends support to the hypothesis that atypical structure evolved early in the evolution of Isopoda. Additionally, we find that an asymmetrical site previously observed across many species within Isopoda is absent in I. armatus, but confirm the presence of two asymmetrical sites recently reported in two other isopod species.}, } @article {pmid35243551, year = {2022}, author = {Choi, H and Lee, K and Kim, D and Kim, S and Lee, JH}, title = {The implication of holocytochrome c synthase mutation in Korean familial hypoplastic amelogenesis imperfecta.}, journal = {Clinical oral investigations}, volume = {26}, number = {6}, pages = {4487-4498}, pmid = {35243551}, issn = {1436-3771}, support = {2021R1F1A104718511//National Research Foundation of Korea/ ; 2020R1A6A1A03047902//National Research Foundation of Korea/ ; 2021R1A2B5B01001903//National Research Foundation of Korea/ ; }, mesh = {*Amelogenesis Imperfecta/genetics ; Dentists ; Humans ; Lyases ; Mutation ; Professional Role ; Republic of Korea ; }, abstract = {OBJECTIVES: This study aimed to comprehensively characterise genetic variants of amelogenesis imperfecta in a single Korean family through whole-exome sequencing and bioinformatics analysis.

MATERIAL AND METHODS: Thirty-one individuals of a Korean family, 9 of whom were affected and 22 unaffected by amelogenesis imperfecta, were enrolled. Whole-exome sequencing was performed on 12 saliva samples, including samples from 8 affected and 4 unaffected individuals. The possible candidate genes associated with the disease were screened by segregation analysis and variant filtering. In silico mutation impact analysis was then performed on the filtered variants based on sequence conservation and protein structure.

RESULTS: Whole-exome sequencing data revealed an X-linked dominant, heterozygous genomic missense mutation in the mitochondrial gene holocytochrome c synthase (HCCS). We also found that HCCS is potentially related to the role of mitochondria in amelogenesis. The HCCS variant was expected to be deleterious in both evolution-based and large population-based analyses. Further, the variant was predicted to have a negative effect on catalytic function of HCCS by in silico analysis of protein structure. In addition, HCCS had significant association with amelogenesis in literature mining analysis.

CONCLUSIONS: These findings suggest new evidence for the relationship between amelogenesis and mitochondria function, which could be implicated in the pathogenesis of amelogenesis imperfecta.

CLINICAL RELEVANCE: The discovery of HCCS mutations and a deeper understanding of the pathogenesis of amelogenesis imperfecta could lead to finding solutions for the fundamental treatment of this disease. Furthermore, it enables dental practitioners to establish predictable prosthetic treatment plans at an early stage by early detection of amelogenesis imperfecta through personalised medicine.}, } @article {pmid35247316, year = {2022}, author = {Moorthy, BT and Jiang, C and Patel, DM and Ban, Y and O'Shea, CR and Kumar, A and Yuan, T and Birnbaum, MD and Gomes, AV and Chen, X and Fontanesi, F and Lampidis, TJ and Barrientos, A and Zhang, F}, title = {The evolutionarily conserved arginyltransferase 1 mediates a pVHL-independent oxygen-sensing pathway in mammalian cells.}, journal = {Developmental cell}, volume = {57}, number = {5}, pages = {654-669.e9}, pmid = {35247316}, issn = {1878-1551}, support = {R01 GM138557/GM/NIGMS NIH HHS/United States ; R35 GM118141/GM/NIGMS NIH HHS/United States ; }, mesh = {*Aminoacyltransferases/genetics/metabolism ; Animals ; Humans ; Mammals/metabolism ; *Oxygen ; Phylogeny ; Proteolysis ; }, abstract = {The response to oxygen availability is a fundamental process concerning metabolism and survival/death in all mitochondria-containing eukaryotes. However, the known oxygen-sensing mechanism in mammalian cells depends on pVHL, which is only found among metazoans but not in other species. Here, we present an alternative oxygen-sensing pathway regulated by ATE1, an enzyme ubiquitously conserved in eukaryotes that influences protein degradation by posttranslational arginylation. We report that ATE1 centrally controls the hypoxic response and glycolysis in mammalian cells by preferentially arginylating HIF1α that is hydroxylated by PHD in the presence of oxygen. Furthermore, the degradation of arginylated HIF1α is independent of pVHL E3 ubiquitin ligase but dependent on the UBR family proteins. Bioinformatic analysis of human tumor data reveals that the ATE1/UBR and pVHL pathways jointly regulate oxygen sensing in a transcription-independent manner with different tissue specificities. Phylogenetic analysis suggests that eukaryotic ATE1 likely evolved during mitochondrial domestication, much earlier than pVHL.}, } @article {pmid35248958, year = {2022}, author = {Rodríguez-Martín, D and Murciano, A and Herráiz, M and de Francisco, P and Amaro, F and Gutiérrez, JC and Martín-González, A and Díaz, S}, title = {Arsenate and arsenite differential toxicity in Tetrahymena thermophila.}, journal = {Journal of hazardous materials}, volume = {431}, number = {}, pages = {128532}, doi = {10.1016/j.jhazmat.2022.128532}, pmid = {35248958}, issn = {1873-3336}, mesh = {Animals ; Arsenates/metabolism/toxicity ; *Arsenic/metabolism/toxicity ; *Arsenites/metabolism/toxicity ; Metallothionein ; *Tetrahymena thermophila/genetics ; }, abstract = {A comparative analysis of toxicities of both arsenic forms (arsenite and arsenate) in the model eukaryotic microorganism Tetrahymena thermophila (ciliate protozoa) has shown the presence of various detoxification mechanisms and cellular effects comparable to those of animal cells under arsenic stress. In the wild type strain SB1969 arsenate is almost 2.5 times more toxic than arsenite. According to the concentration addition model used in binary metallic mixtures their toxicities show an additive effect. Using fluorescent assays and flow cytometry, it has been detected that As(V) generates elevated levels of ROS/RNS compared to As(III). Both produce the same levels of superoxide anion, but As(V) also causes greater increases in hydrogen peroxide and peroxynitrite. The mitochondrial membrane potential is affected by both As(V) and As(III), and electron microscopy has also revealed that mitochondria are the main target of both arsenic ionic forms. Fusion/fission and swelling mitochondrial and mitophagy, together with macroautophagy, vacuolization and mucocyst extruction are mainly associated to As(V) toxicity, while As(III) induces an extensive lipid metabolism dysfunction (adipotropic effect). Quantitative RT-PCR analysis of some genes encoding antioxidant proteins or enzymes has shown that glutathione and thioredoxin metabolisms are involved in the response to arsenic stress. Likewise, the function of metallothioneins seems to be crucial in arsenic detoxification processes, after using both metallothionein knockout and knockdown strains and cells overexpressing metallothionein genes from this ciliate. The analysis of the differential toxicity of As(III) and As(V) shown in this study provides cytological and molecular tools to be used as biomarkers for each of the two arsenic ionic forms.}, } @article {pmid35255175, year = {2022}, author = {Treidel, LA and Quintanilla Ramirez, GS and Chung, DJ and Menze, MA and Vázquez-Medina, JP and Williams, CM}, title = {Selection on dispersal drives evolution of metabolic capacities for energy production in female wing-polymorphic sand field crickets, Gryllus firmus.}, journal = {Journal of evolutionary biology}, volume = {35}, number = {4}, pages = {599-609}, pmid = {35255175}, issn = {1420-9101}, support = {//Society for Integrative and Comparative Biology (SICB)/ ; //University of California Berkeley/ ; //Hellman Family Foundation/ ; }, mesh = {Animals ; Energy Metabolism ; Female ; *Gryllidae/physiology ; Phenotype ; Wings, Animal/metabolism ; }, abstract = {Life history and metabolism covary, but the mechanisms and individual traits responsible for these linkages remain unresolved. Dispersal capability is a critical component of life history that is constrained by metabolic capacities for energy production. Conflicting relationships between metabolism and life histories may be explained by accounting for variation in dispersal and maximal metabolic rates. We used female wing-polymorphic sand field crickets, Gryllus firmus, selected either for long wings (LW, flight-capable) or short wings (SW, flightless) to test the hypothesis that selection on dispersal capability drives the evolution of metabolic capacities. While resting metabolic rates were similar, long-winged crickets reached higher maximal metabolic rates than short-winged crickets, resulting in improved running performance. We further provided insight into the mechanisms responsible for covariation between life history and metabolism by comparing mitochondrial content of tissues involved in powering locomotion and assessing the function of mitochondria isolated from long- and short-winged crickets. Our results demonstrated that larger metabolic capacities in long-winged crickets were underpinned by increases in mitochondrial content of dorsoventral flight muscle and enhanced bioenergetic capacities of mitochondria within the fat body, a tissue responsible for fuel storage and mobilization. Thus, selection on flight capability correlates with increases in maximal, but not resting metabolic rates, through modifications of tissues powering locomotion at the cellular and organelle levels. This allows organisms to meet high energetic demands of activity for life history. Dispersal capability should therefore explicitly be considered as a potential factor driving the evolution of metabolic capacities.}, } @article {pmid35258392, year = {2022}, author = {Magalhaes-Novais, S and Blecha, J and Naraine, R and Mikesova, J and Abaffy, P and Pecinova, A and Milosevic, M and Bohuslavova, R and Prochazka, J and Khan, S and Novotna, E and Sindelka, R and Machan, R and Dewerchin, M and Vlcak, E and Kalucka, J and Stemberkova Hubackova, S and Benda, A and Goveia, J and Mracek, T and Barinka, C and Carmeliet, P and Neuzil, J and Rohlenova, K and Rohlena, J}, title = {Mitochondrial respiration supports autophagy to provide stress resistance during quiescence.}, journal = {Autophagy}, volume = {18}, number = {10}, pages = {2409-2426}, pmid = {35258392}, issn = {1554-8635}, mesh = {AMP-Activated Protein Kinases/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; *Autophagy ; Cysteine/metabolism ; DNA, Mitochondrial/metabolism ; Dextrans/metabolism ; Endothelial Cells/metabolism ; Fibroblasts/metabolism ; Formaldehyde/metabolism ; Humans ; *Inflammatory Bowel Diseases/metabolism ; Isothiocyanates ; Lipopolysaccharides/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice ; Microtubule-Associated Proteins/metabolism ; Mitochondria/metabolism ; Phosphatidylethanolamines/metabolism ; Reactive Oxygen Species/metabolism ; Respiration ; Sirolimus ; }, abstract = {Mitochondrial oxidative phosphorylation (OXPHOS) generates ATP, but OXPHOS also supports biosynthesis during proliferation. In contrast, the role of OXPHOS during quiescence, beyond ATP production, is not well understood. Using mouse models of inducible OXPHOS deficiency in all cell types or specifically in the vascular endothelium that negligibly relies on OXPHOS-derived ATP, we show that selectively during quiescence OXPHOS provides oxidative stress resistance by supporting macroautophagy/autophagy. Mechanistically, OXPHOS constitutively generates low levels of endogenous ROS that induce autophagy via attenuation of ATG4B activity, which provides protection from ROS insult. Physiologically, the OXPHOS-autophagy system (i) protects healthy tissue from toxicity of ROS-based anticancer therapy, and (ii) provides ROS resistance in the endothelium, ameliorating systemic LPS-induced inflammation as well as inflammatory bowel disease. Hence, cells acquired mitochondria during evolution to profit from oxidative metabolism, but also built in an autophagy-based ROS-induced protective mechanism to guard against oxidative stress associated with OXPHOS function during quiescence.Abbreviations: AMPK: AMP-activated protein kinase; AOX: alternative oxidase; Baf A: bafilomycin A1; CI, respiratory complexes I; DCF-DA: 2',7'-dichlordihydrofluorescein diacetate; DHE: dihydroethidium; DSS: dextran sodium sulfate; ΔΨmi: mitochondrial inner membrane potential; EdU: 5-ethynyl-2'-deoxyuridine; ETC: electron transport chain; FA: formaldehyde; HUVEC; human umbilical cord endothelial cells; IBD: inflammatory bowel disease; LC3B: microtubule associated protein 1 light chain 3 beta; LPS: lipopolysaccharide; MEFs: mouse embryonic fibroblasts; MTORC1: mechanistic target of rapamycin kinase complex 1; mtDNA: mitochondrial DNA; NAC: N-acetyl cysteine; OXPHOS: oxidative phosphorylation; PCs: proliferating cells; PE: phosphatidylethanolamine; PEITC: phenethyl isothiocyanate; QCs: quiescent cells; ROS: reactive oxygen species; PLA2: phospholipase A2, WB: western blot.}, } @article {pmid35259985, year = {2022}, author = {Perez, M and Breusing, C and Angers, B and Beinart, RA and Won, YJ and Young, CR}, title = {Divergent paths in the evolutionary history of maternally transmitted clam symbionts.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1970}, pages = {20212137}, pmid = {35259985}, issn = {1471-2954}, mesh = {Animals ; Bacteria/genetics ; *Bivalvia/genetics ; *Gammaproteobacteria/genetics ; Genome Size ; Genome, Bacterial ; Phylogeny ; Symbiosis/genetics ; }, abstract = {Vertical transmission of bacterial endosymbionts is accompanied by virtually irreversible gene loss that results in a progressive reduction in genome size. While the evolutionary processes of genome reduction have been well described in some terrestrial symbioses, they are less understood in marine systems where vertical transmission is rarely observed. The association between deep-sea vesicomyid clams and chemosynthetic Gammaproteobacteria is one example of maternally inherited symbioses in the ocean. Here, we assessed the contributions of drift, recombination and selection to genome evolution in two extant vesicomyid symbiont clades by comparing 15 representative symbiont genomes (1.017-1.586 Mb) to those of closely related bacteria and the hosts' mitochondria. Our analyses suggest that drift is a significant force driving genome evolution in vesicomyid symbionts, though selection and interspecific recombination appear to be critical for maintaining symbiont functional integrity and creating divergent patterns of gene conservation. Notably, the two symbiont clades possess putative functional differences in sulfide physiology, anaerobic respiration and dependency on environmental vitamin B12, which probably reflect adaptations to different ecological habitats available to each symbiont group. Overall, these results contribute to our understanding of the eco-evolutionary processes shaping reductive genome evolution in vertically transmitted symbioses.}, } @article {pmid35272287, year = {2022}, author = {Ho, KM and Morgan, DJR}, title = {The Proximal Tubule as the Pathogenic and Therapeutic Target in Acute Kidney Injury.}, journal = {Nephron}, volume = {146}, number = {5}, pages = {494-502}, doi = {10.1159/000522341}, pmid = {35272287}, issn = {2235-3186}, mesh = {*Acute Kidney Injury/drug therapy/pathology ; Humans ; Kidney/pathology ; Kidney Glomerulus/pathology ; *Kidney Tubular Necrosis, Acute ; Kidney Tubules, Proximal/pathology ; }, abstract = {BACKGROUND: In 2004, the term acute kidney injury (AKI) was introduced with the intention of broadening our understanding of rapid declines in renal function and to replace the historical terms of acute renal failure and acute tubular necrosis (ATN). Despite this evolution in terminology, the mechanisms of AKI have stayed largely elusive with the pathophysiological concepts of ATN remaining the mainstay in our understanding of AKI.

SUMMARY: The proximal tubule (PT), having the highest mitochondrial content in the kidney and relying heavily on oxidative phosphorylation to generate ATP, is vulnerable to ischaemic insults and mitochondrial dysfunction. Histologically, pathological changes in the PT are more consistent than changes to the glomeruli or the loop of Henle in AKI. Physiologically, activation of tubuloglomerular feedback due to PT dysfunction leads to an increase in preglomerular afferent arteriole resistance and a reduction in glomerular filtration. Pharmacologically, frusemide - a drug commonly used in the setting of oliguric AKI - is actively secreted by the PT and its diuretic effect is compromised by its failure to be secreted into the urine and thus be delivered to its site of action at the loop of Henle in AKI. Increases in the urinary, but not plasma biomarkers, of PT injury within 1 h of shock suggest that the PT as the initiation pathogenic target of AKI.

KEY MESSAGE: Therapeutic agents targeting specifically the PT epithelial cells, in particular its mitochondria - including amino acid ergothioneine and superoxide scavenger MitoTEMPO - show great promises in ameliorating AKI.}, } @article {pmid35277964, year = {2022}, author = {Lam, SM and Li, J and Sun, H and Mao, W and Lu, Z and Zhao, Q and Han, C and Gong, X and Jiang, B and Chua, GH and Zhao, Z and Meng, F and Shui, G}, title = {Quantitative Lipidomics and Spatial MS-Imaging Uncovered Neurological and Systemic Lipid Metabolic Pathways Underlying Troglomorphic Adaptations in Cave-Dwelling Fish.}, journal = {Molecular biology and evolution}, volume = {39}, number = {4}, pages = {}, pmid = {35277964}, issn = {1537-1719}, mesh = {Animals ; Biological Evolution ; Caves ; *Characidae/genetics ; *Cyprinidae ; *Demyelinating Diseases ; Lipidomics ; Metabolic Networks and Pathways ; Phospholipids ; }, abstract = {Sinocyclocheilus represents a rare, freshwater teleost genus endemic to China that comprises the river-dwelling surface fish and the cave-dwelling cavefish. Using a combinatorial approach of quantitative lipidomics and mass-spectrometry imaging (MSI), we demonstrated that neural compartmentalization of lipid distribution and lipid metabolism is associated with the evolution of troglomorphic traits in Sinocyclocheilus. Attenuated docosahexaenoic acid (DHA) biosynthesis via the Δ4 desaturase pathway led to reductions in DHA-phospholipids in cavefish cerebellum. Instead, cavefish accumulates arachidonic acid-phospholipids that may disfavor retinotectal arbor growth. Importantly, MSI of sulfatides coupled with immunostaining of myelin basic protein and transmission electron microscopy images of hindbrain axons revealed demyelination in cavefish raphe serotonergic neurons. Demyelination in cavefish parallels the loss of neuroplasticity governing social behavior such as aggressive dominance. Outside the brain, quantitative lipidomics and qRT-PCR revealed systemic reductions in membrane esterified DHAs in the liver, attributed to suppression of genes along the Sprecher pathway (elovl2, elovl5, and acox1). Development of fatty livers was observed in cavefish; likely mediated by an impeded mobilization of storage lipids, as evident in the diminished expressions of pnpla2, lipea, lipeb, dagla, and mgll; and suppressed β-oxidation of fatty acyls via both mitochondria and peroxisomes as reflected in the reduced expressions of cpt1ab, hadhaa, cpt2, decr1, and acox1. These neurological and systemic metabolic adaptations serve to reduce energy expenditure, forming the basis of recessive evolution that eliminates nonessential morphological and behavioral traits and giving cavefish a selective advantage to thrive in caves where proper resource allocation becomes a major determinant of survival.}, } @article {pmid35279439, year = {2022}, author = {Zhou, B and Qi, D and Liu, S and Qi, H and Wang, Y and Zhao, K and Tian, F}, title = {Physiological, morphological and transcriptomic responses of Tibetan naked carps (Gymnocypris przewalskii) to salinity variations.}, journal = {Comparative biochemistry and physiology. Part D, Genomics & proteomics}, volume = {42}, number = {}, pages = {100982}, doi = {10.1016/j.cbd.2022.100982}, pmid = {35279439}, issn = {1878-0407}, mesh = {Animals ; *Carps ; *Cyprinidae/genetics ; Gills ; Lakes ; Salinity ; Tibet ; Transcriptome ; }, abstract = {Gymnocypris przewalskii is a native cyprinid fish that dwells in the Lake Qinghai with salinity of 12-13‰. It migrates annually to the freshwater rivers for spawning, experiencing the significant changes in salinity. In the present study, we performed the physiological, morphological and transcriptomic analyses to understand the osmoregulation in G. przewalskii. The physiological assay showed that the osmotic pressure of G. przewalskii was almost isosmotic to the brackish lake water. The low salinity reduced its ionic concentrations and osmotic pressure. The plasticity of gill microstructure was linked to the salinity variations, including the presence of mucus and intact tight junctions in brackish water and the development of the mitochondria-rich cells and the loosened tight junctions in freshwater. RNA-seq analysis identified 1926 differentially expressed genes, including 710 and 1216 down- and up-regulated genes in freshwater, which were enriched in ion transport, cell-cell adhesion, and mucus secretion. Genes in ion uptake were activated in low salinity, and mucus pathways and tight junction showed the higher transcription in brackish water. The isosmoticity between the body fluid and the environment suggested G. przewalskii was in the metabolic-saving condition in the brackish water. The decreased salinity disrupted this balance, which activated the ion uptake in freshwater to maintain osmotic homeostasis. The gill remodeling was involved in this process through the development of the mitochondria-rich cells to enhance ion uptake. The current finding provided insights into the potential mechanisms of G. przewalskii to cope with salinity alteration.}, } @article {pmid35289381, year = {2022}, author = {Drechsel, V and Schneebauer, G and Sandbichler, AM and Fiechtner, B and Pelster, B}, title = {Oxygen consumption and acid secretion in isolated gas gland cells of the European eel Anguilla anguilla.}, journal = {Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology}, volume = {192}, number = {3-4}, pages = {447-457}, pmid = {35289381}, issn = {1432-136X}, support = {I 2984/FWF_/Austrian Science Fund FWF/Austria ; I2984-B25//Österreichische Forschungsförderungsgesellschaft/ ; }, mesh = {Air Sacs/metabolism ; *Anguilla/metabolism ; Animals ; Glucose/metabolism ; Oxygen/metabolism ; Oxygen Consumption ; }, abstract = {Swimbladder gas gland cells are known to produce lactic acid required for the acidification of swimbladder blood and decreasing the oxygen carrying capacity of swimbladder blood, i.e., the onset of the Root effect. Gas gland cells have also been shown to metabolize glucose via the pentose phosphate shunt, but the role of the pentose phosphate shunt for acid secretion has not yet been evaluated. Similarly, aerobic metabolism of gas gland cells has been largely neglected so far. In the present study, we therefore simultaneously assessed the role of glycolysis and of the pentose phosphate shunt for acid secretion and recorded oxygen consumption of isolated swimbladder gas gland cells of the European eel. Presence of glucose was essential for acid secretion, and at glucose concentrations of about 1.5 mmol l[-1] acid secretion of gas gland cells reached a maximum, indicating that glucose concentrations in swimbladder blood should not be limiting acid production and secretion under physiological conditions. The data revealed that most of the acid was produced in the glycolytic pathway, but a significant fraction was also contributed by the pentose phosphate shunt. Addition of glucose to gas gland cells incubated in a glucose-free medium resulted in a reduction of oxygen uptake. Inhibition of mitochondrial respiration significantly reduced oxygen consumption, but a fraction of mitochondria-independent respiration remained in presence of rotenone and antimycin A. In the presence of glucose, application of either iodo-acetate inhibiting glycolysis or 6-AN inhibiting the pentose phosphate shunt did not significantly affect oxygen uptake, indicating an independent regulation of oxidative phosphorylation and of acid production. Inhibition of the muscarinic acetylcholine receptor caused a slight elevation in acid secretion, while forskolin caused a concentration-dependent reduction in acid secretion, indicating muscarinic and c-AMP-dependent control of acid secretion in gas gland cells.}, } @article {pmid35294555, year = {2022}, author = {Karmin, M and Flores, R and Saag, L and Hudjashov, G and Brucato, N and Crenna-Darusallam, C and Larena, M and Endicott, PL and Jakobsson, M and Lansing, JS and Sudoyo, H and Leavesley, M and Metspalu, M and Ricaut, FX and Cox, MP}, title = {Episodes of Diversification and Isolation in Island Southeast Asian and Near Oceanian Male Lineages.}, journal = {Molecular biology and evolution}, volume = {39}, number = {3}, pages = {}, pmid = {35294555}, issn = {1537-1719}, mesh = {Asia, Southeastern ; *Asian People ; *DNA, Mitochondrial/genetics ; Humans ; Male ; Mitochondria/genetics ; Phylogeny ; }, abstract = {Island Southeast Asia (ISEA) and Oceania host one of the world's richest assemblages of human phenotypic, linguistic, and cultural diversity. Despite this, the region's male genetic lineages are globally among the last to remain unresolved. We compiled ∼9.7 Mb of Y chromosome (chrY) sequence from a diverse sample of over 380 men from this region, including 152 first reported here. The granularity of this data set allows us to fully resolve and date the regional chrY phylogeny. This new high-resolution tree confirms two main population bursts: multiple rapid diversifications following the region's initial settlement ∼50 kya, and extensive expansions <6 kya. Notably, ∼40-25 kya the deep rooting local lineages of C-M130, M-P256, and S-B254 show almost no further branching events in ISEA, New Guinea, and Australia, matching a similar pause in diversification seen in maternal mitochondrial DNA lineages. The main local lineages start diversifying ∼25 kya, at the time of the last glacial maximum. This improved chrY topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and ISEA, potential interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape observed today formed. The high-resolution phylogeny of the chrY presented here thus enables a detailed exploration of past isolation, interaction, and change in one of the world's least understood regions.}, } @article {pmid35306886, year = {2022}, author = {Zluvova, J and Kubat, Z and Hobza, R and Janousek, B}, title = {Adaptive changes of the autosomal part of the genome in a dioecious clade of Silene.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {377}, number = {1850}, pages = {20210228}, pmid = {35306886}, issn = {1471-2970}, mesh = {Chromosomes, Plant ; Evolution, Molecular ; *Magnoliopsida ; Sex Chromosomes ; *Silene/genetics ; }, abstract = {The genus Silene brings many opportunities for the study of various processes involved in the evolution of dioecy and young sex chromosomes. Here we focus on a dioecious clade in Silene subgenus Silene and closely related species. This study provides improved support for monophyly of this clade (based on inclusion of further dioecious species) and a new estimate of its age (ca 2.3 million years). We observed a rise in adaptive evolution in the autosomal and pseudoautosomal parts of the genome on the branch where dioecy originated. This increase is not a result of the accumulation of sexually antagonistic genes in the pseudoautosomal region. It is also not caused by the coevolution of genes acting in mitochondria (despite the possibility that dioecy along this branch could have evolved from a nucleo-cytoplasmic male sterility-based system). After considering other possibilities, the most parsimonious explanation for the increase seen in the number of positively selected codons is the adaptive evolution of genes involved in the adaptation of the autosomal part of the genome to dioecy, as described in Charnov's sex-allocation theory. As the observed coincidence cannot prove causality, studies in other dioecious clades are necessary to allow the formation of general conclusions. This article is part of the theme issue 'Sex determination and sex chromosome evolution in land plants'.}, } @article {pmid35307029, year = {2022}, author = {Smith, AJ and Advani, J and Brock, DC and Nellissery, J and Gumerson, J and Dong, L and Aravind, L and Kennedy, B and Swaroop, A}, title = {GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {68}, pmid = {35307029}, issn = {1741-7007}, support = {ZIA EY000546/ImNIH/Intramural NIH HHS/United States ; ZIAEY000546/EY/NEI NIH HHS/United States ; ZIAEY000450/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Gammaproteobacteria/metabolism ; *Glycation End Products, Advanced/metabolism ; Mammals ; Mice ; Mitochondrial Proteins/genetics ; Protein Deglycase DJ-1/metabolism ; }, abstract = {BACKGROUND: Functional complexity of the eukaryotic mitochondrial proteome is augmented by independent gene acquisition from bacteria since its endosymbiotic origins. Mammalian homologs of many ancestral mitochondrial proteins have uncharacterized catalytic activities. Recent forward genetic approaches attributed functions to proteins in established metabolic pathways, thereby limiting the possibility of identifying novel biology relevant to human disease. We undertook a bottom-up biochemistry approach to discern evolutionarily conserved mitochondrial proteins with catalytic potential.

RESULTS: Here, we identify a Parkinson-associated DJ-1/PARK7-like protein-glutamine amidotransferase-like class 1 domain-containing 3A (GATD3A), with bacterial evolutionary affinities although not from alphaproteobacteria. We demonstrate that GATD3A localizes to the mitochondrial matrix and functions as a deglycase. Through its amidolysis domain, GATD3A removes non-enzymatic chemical modifications produced during the Maillard reaction between dicarbonyls and amines of nucleotides and amino acids. GATD3A interacts with factors involved in mitochondrial mRNA processing and translation, suggestive of a role in maintaining integrity of important biomolecules through its deglycase activity. The loss of GATD3A in mice is associated with accumulation of advanced glycation end products (AGEs) and altered mitochondrial dynamics.

CONCLUSIONS: An evolutionary perspective helped us prioritize a previously uncharacterized but predicted mitochondrial protein GATD3A, which mediates the removal of early glycation intermediates. GATD3A restricts the formation of AGEs in mitochondria and is a relevant target for diseases where AGE deposition is a pathological hallmark.}, } @article {pmid35318703, year = {2022}, author = {Hammond, M and Dorrell, RG and Speijer, D and Lukeš, J}, title = {Eukaryotic cellular intricacies shape mitochondrial proteomic complexity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {44}, number = {5}, pages = {e2100258}, doi = {10.1002/bies.202100258}, pmid = {35318703}, issn = {1521-1878}, mesh = {Biological Evolution ; Eukaryota/physiology ; *Eukaryotic Cells/metabolism ; Mitochondria/metabolism ; Organelles/metabolism ; Phylogeny ; *Proteomics ; }, abstract = {Mitochondria have been fundamental to the eco-physiological success of eukaryotes since the last eukaryotic common ancestor (LECA). They contribute essential functions to eukaryotic cells, above and beyond classical respiration. Mitochondria interact with, and complement, metabolic pathways occurring in other organelles, notably diversifying the chloroplast metabolism of photosynthetic organisms. Here, we integrate existing literature to investigate how mitochondrial metabolism varies across the landscape of eukaryotic evolution. We illustrate the mitochondrial remodelling and proteomic changes undergone in conjunction with major evolutionary transitions. We explore how the mitochondrial complexity of the LECA has been remodelled in specific groups to support subsequent evolutionary transitions, such as the acquisition of chloroplasts in photosynthetic species and the emergence of multicellularity. We highlight the versatile and crucial roles played by mitochondria during eukaryotic evolution, extending from its huge contribution to the development of the LECA itself to the dynamic evolution of individual eukaryote groups, reflecting both their current ecologies and evolutionary histories.}, } @article {pmid35322502, year = {2022}, author = {Cantoni, D and Osborne, A and Taib, N and Thompson, G and Martín-Escolano, R and Kazana, E and Edrich, E and Brown, IR and Gribaldo, S and Gourlay, CW and Tsaousis, AD}, title = {Localization and functional characterization of the alternative oxidase in Naegleria.}, journal = {The Journal of eukaryotic microbiology}, volume = {69}, number = {4}, pages = {e12908}, pmid = {35322502}, issn = {1550-7408}, support = {BB/M009971/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Eukaryota ; Mitochondrial Proteins ; *Naegleria ; *Naegleria fowleri ; Oxidoreductases/metabolism ; Plant Proteins ; Alternative Oxidase ; }, abstract = {The alternative oxidase (AOX) is a protein involved in supporting enzymatic reactions of the Krebs cycle in instances when the canonical (cytochrome-mediated) respiratory chain has been inhibited, while allowing for the maintenance of cell growth and necessary metabolic processes for survival. Among eukaryotes, alternative oxidases have dispersed distribution and are found in plants, fungi, and protists, including Naegleria ssp. Naegleria species are free-living unicellular amoeboflagellates and include the pathogenic species of N. fowleri, the so-called "brain-eating amoeba." Using a multidisciplinary approach, we aimed to understand the evolution, localization, and function of AOX and the role that plays in Naegleria's biology. Our analyses suggest that AOX was present in last common ancestor of the genus and structure prediction showed that all functional residues are also present in Naegleria species. Using cellular and biochemical techniques, we also functionally characterize N. gruberi's AOX in its mitochondria, and we demonstrate that its inactivation affects its proliferation. Consequently, we discuss the benefits of the presence of this protein in Naegleria species, along with its potential pathogenicity role in N. fowleri. We predict that our findings will spearhead new explorations to understand the cell biology, metabolism, and evolution of Naegleria and other free-living relatives.}, } @article {pmid35325186, year = {2022}, author = {Ye, Z and Zhao, C and Raborn, RT and Lin, M and Wei, W and Hao, Y and Lynch, M}, title = {Genetic Diversity, Heteroplasmy, and Recombination in Mitochondrial Genomes of Daphnia pulex, Daphnia pulicaria, and Daphnia obtusa.}, journal = {Molecular biology and evolution}, volume = {39}, number = {4}, pages = {}, pmid = {35325186}, issn = {1537-1719}, support = {R35 GM122566/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA, Mitochondrial/genetics ; Daphnia/genetics ; *Genome, Mitochondrial ; Heteroplasmy ; *Pulicaria/genetics ; Recombination, Genetic ; }, abstract = {Genetic variants of mitochondrial DNA at the individual (heteroplasmy) and population (polymorphism) levels provide insight into their roles in multiple cellular and evolutionary processes. However, owing to the paucity of genome-wide data at the within-individual and population levels, the broad patterns of these two forms of variation remain poorly understood. Here, we analyze 1,804 complete mitochondrial genome sequences from Daphnia pulex, Daphnia pulicaria, and Daphnia obtusa. Extensive heteroplasmy is observed in D. obtusa, where the high level of intraclonal divergence must have resulted from a biparental-inheritance event, and recombination in the mitochondrial genome is apparent, although perhaps not widespread. Global samples of D. pulex reveal remarkably low mitochondrial effective population sizes, <3% of those for the nuclear genome. In addition, levels of population diversity in mitochondrial and nuclear genomes are uncorrelated across populations, suggesting an idiosyncratic evolutionary history of mitochondria in D. pulex. These population-genetic features appear to be a consequence of background selection associated with highly deleterious mutations arising in the strongly linked mitochondrial genome, which is consistent with polymorphism and divergence data suggesting a predominance of strong purifying selection. Nonetheless, the fixation of mildly deleterious mutations in the mitochondrial genome also appears to be driving positive selection on genes encoded in the nuclear genome whose products are deployed in the mitochondrion.}, } @article {pmid35333655, year = {2022}, author = {Jackson, TD and Crameri, JJ and Muellner-Wong, L and Frazier, AE and Palmer, CS and Formosa, LE and Hock, DH and Fujihara, KM and Stait, T and Sharpe, AJ and Thorburn, DR and Ryan, MT and Stroud, DA and Stojanovski, D}, title = {Sideroflexin 4 is a complex I assembly factor that interacts with the MCIA complex and is required for the assembly of the ND2 module.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {13}, pages = {e2115566119}, pmid = {35333655}, issn = {1091-6490}, mesh = {Adenosine Triphosphate/metabolism ; *Electron Transport Complex I/metabolism ; Humans ; Membrane Proteins ; Mitochondria/genetics/metabolism ; *Mitochondrial Diseases/genetics ; Mitochondrial Proteins/genetics/metabolism ; Mutation ; }, abstract = {SignificanceMitochondria are double-membraned eukaryotic organelles that house the proteins required for generation of ATP, the energy currency of cells. ATP generation within mitochondria is performed by five multisubunit complexes (complexes I to V), the assembly of which is an intricate process. Mutations in subunits of these complexes, or the suite of proteins that help them assemble, lead to a severe multisystem condition called mitochondrial disease. We show that SFXN4, a protein that causes mitochondrial disease when mutated, assists with the assembly of complex I. This finding explains why mutations in SFXN4 cause mitochondrial disease and is surprising because SFXN4 belongs to a family of amino acid transporter proteins, suggesting that it has undergone a dramatic shift in function through evolution.}, } @article {pmid35340599, year = {2022}, author = {Hickey, T and Devaux, J and Rajagopal, V and Power, A and Crossman, D}, title = {Paradoxes of Hymenoptera flight muscles, extreme machines.}, journal = {Biophysical reviews}, volume = {14}, number = {1}, pages = {403-412}, pmid = {35340599}, issn = {1867-2450}, abstract = {In the Carboniferous, insects evolved flight. Intense selection drove for high performance and approximately 100 million years later, Hymenoptera (bees, wasps and ants) emerged. Some species had proportionately small wings, with apparently impossible aerodynamic challenges including a need for high frequency flight muscles (FMs), powered exclusively off aerobic pathways and resulting in extreme aerobic capacities. Modern insect FMs are the most refined and form large dense blocks that occupy 90% of the thorax. These can beat wings at 200 to 230 Hz, more than double that achieved by standard neuromuscular systems. To do so, rapid repolarisation was circumvented through evolution of asynchronous stimulation, stretch activation, elastic recoil and a paradoxically slow Ca[2+] reuptake. While the latter conserves ATP, considerable ATP is demanded at the myofibrils. FMs have diminished sarcoplasmic volumes, and ATP is produced solely by mitochondria, which pack myocytes to maximal limits and have very dense cristae. Gaseous oxygen is supplied directly to mitochondria. While FMs appear to be optimised for function, several unusual paradoxes remain. FMs lack any significant equivalent to the creatine kinase shuttle, and myofibrils are twice as wide as those of within cardiomyocytes. The mitochondrial electron transport systems also release large amounts of reactive oxygen species (ROS) and respiratory complexes do not appear to be present at any exceptional level. Given that the loss of the creatine kinase shuttle and elevated ROS impairs heart function, we question how do FM shuttle adenylates at high rates and tolerate oxidative stress conditions that occur in diseased hearts?}, } @article {pmid35342946, year = {2022}, author = {Senarat, S and Kettratad, J and Pairohakul, S and Ampawong, S and Huggins, BP and Coleman, MM and Kaneko, G}, title = {An update on the evolutionary origin of aglomerular kidney with structural and ultrastructural descriptions of the kidney in three fish species.}, journal = {Journal of fish biology}, volume = {100}, number = {5}, pages = {1283-1298}, doi = {10.1111/jfb.15045}, pmid = {35342946}, issn = {1095-8649}, support = {//Johnson Foundation/ ; //Chulalongkorn University/ ; }, mesh = {Animals ; *Batrachoidiformes ; Kidney/ultrastructure ; Kidney Glomerulus/ultrastructure ; Kidney Tubules ; Nephrons/ultrastructure ; *Smegmamorpha ; }, abstract = {The kidney of fish contains numerous nephrons, each of which is divided into the renal corpuscle and renal tubules. This glomerular structure is the filtration unit of the nephron and is important for the kidney function, but it has been reported that the renal corpuscle was lost in at least four independent linages of fish (i.e., aglomerular kidney). In this study, the authors newly described renal structures for three species by histological and ultrastructural observations: two aglomerular kidneys from a seahorse Hippocampus barbouri and a toadfish Allenbatrachus grunniens and a glomerular kidney from a snake eel Pisodonophis boro. The renal development of H. barbouri was also described during 1-35 days after birth. In all species tested, the anterior kidney was comprised of haematopoietic tissues and a few renal tubules, whereas the posterior kidney contained more renal tubules. Although the glomerular structure was present in P. boro, light microscopic observations identified no glomeruli in the kidney of H. barbouri and A. grunniens. Ultrastructurally, abundant deep basal infoldings with mitochondria in the renal tubules were observed in A. grunniens compared to H. barbouri and P. boro, suggesting the possible role of basal infoldings in maintaining the osmotic balance. By integrating the results from the three species and comprehensive literature search, the authors further showed that 56 species have been reported to be aglomerular, and that the aglomerular kidney has evolved at least eight times in bony fishes.}, } @article {pmid35348760, year = {2022}, author = {Azuma, T and Pánek, T and Tice, AK and Kayama, M and Kobayashi, M and Miyashita, H and Suzaki, T and Yabuki, A and Brown, MW and Kamikawa, R}, title = {An Enigmatic Stramenopile Sheds Light on Early Evolution in Ochrophyta Plastid Organellogenesis.}, journal = {Molecular biology and evolution}, volume = {39}, number = {4}, pages = {}, pmid = {35348760}, issn = {1537-1719}, mesh = {Ecosystem ; Evolution, Molecular ; *Genome, Plastid ; Phylogeny ; Plants/genetics ; Plastids/genetics ; *Stramenopiles/genetics ; }, abstract = {Ochrophyta is an algal group belonging to the Stramenopiles and comprises diverse lineages of algae which contribute significantly to the oceanic ecosystems as primary producers. However, early evolution of the plastid organelle in Ochrophyta is not fully understood. In this study, we provide a well-supported tree of the Stramenopiles inferred by the large-scale phylogenomic analysis that unveils the eukaryvorous (nonphotosynthetic) protist Actinophrys sol (Actinophryidae) is closely related to Ochrophyta. We used genomic and transcriptomic data generated from A. sol to detect molecular traits of its plastid and we found no evidence of plastid genome and plastid-mediated biosynthesis, consistent with previous ultrastructural studies that did not identify any plastids in Actinophryidae. Moreover, our phylogenetic analyses of particular biosynthetic pathways provide no evidence of a current and past plastid in A. sol. However, we found more than a dozen organellar aminoacyl-tRNA synthases (aaRSs) that are of algal origin. Close relationships between aaRS from A. sol and their ochrophyte homologs document gene transfer of algal genes that happened before the divergence of Actinophryidae and Ochrophyta lineages. We further showed experimentally that organellar aaRSs of A. sol are targeted exclusively to mitochondria, although organellar aaRSs in Ochrophyta are dually targeted to mitochondria and plastids. Together, our findings suggested that the last common ancestor of Actinophryidae and Ochrophyta had not yet completed the establishment of host-plastid partnership as seen in the current Ochrophyta species, but acquired at least certain nuclear-encoded genes for the plastid functions.}, } @article {pmid35351912, year = {2022}, author = {Lessios, HA and Hendler, G}, title = {Mitochondrial phylogeny of the brittle star genus Ophioderma.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {5304}, pmid = {35351912}, issn = {2045-2322}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *Echinodermata/genetics ; *Evolution, Molecular ; Mitochondria/genetics ; Phylogeny ; }, abstract = {We reconstructed the mitochondrial phylogeny of the species of the brittle star genus Ophioderma, using sequences of the Cytochrome Oxidase I gene (COI) to address four questions: (i) Are the species of Ophioderma described on morphological evidence reflected in mitochondrial genealogy? (ii) Which species separated from which? (iii) When did speciation events occur? (iv) What is the rate of COI evolution in ophiuroids? We found that most of the 22 described species we sampled coincide with monophyletic clusters of COI sequences, but there are exceptions, most notably in the eastern Pacific, in which three undescribed species were indicated. The COI phylogeny lacks resolution in the deeper nodes, but it does show that there are four species pairs, the members of which are found on either side of the central American Isthmus. Two pairs with a genetic distance of ~ 4% between Atlantic and Pacific members were probably split during the final stages of Isthmus completion roughly 3 million years ago. The rate of divergence provided by these pairs allowed the calibration of a relaxed molecular clock. Estimated dates of divergence indicate that the lineages leading to extant species coalesce at times much older than congeneric species in other classes of echinoderms, suggesting that low extinction rates may be one of the reasons that ophiuroids are species-rich. The mean rate of COI substitution in Ophioderma is three times slower than that of echinoids. Conclusions of previous mitochondrial DNA studies of ophiuroids that relied on echinoid calibrations to determine divergence times need to be revised.}, } @article {pmid35353639, year = {2022}, author = {Lipko, NB}, title = {Photobiomodulation: Evolution and Adaptation.}, journal = {Photobiomodulation, photomedicine, and laser surgery}, volume = {40}, number = {4}, pages = {213-233}, doi = {10.1089/photob.2021.0145}, pmid = {35353639}, issn = {2578-5478}, mesh = {Humans ; Lasers ; *Low-Level Light Therapy/methods ; Mitochondria ; }, abstract = {Photobiomodulation (PBM) can be described as the intentional use of low-power laser or light-emitting diode light in the visible and near-infrared light spectra as a medical treatment to living biological tissues. This article describes the evolution of photochemical reactions on Earth, the mitochondria, and their implications in PBM; the science of light and energy (necessary to understand the mechanisms of PBM); and the clinical science of light as therapeutic medicine. Finally, selected reviews of current treatment protocols and ongoing research regarding the possibilities for the use of PBM in the human body are examined.}, } @article {pmid35358979, year = {2022}, author = {Risser, C and Tran Ba Loc, P and Binder-Foucard, F and Fabacher, T and Lefèvre, H and Sauvage, C and Sauleau, EA and Wolff, V}, title = {COVID-19 Impact on Stroke Admissions during France's First Epidemic Peak: An Exhaustive, Nationwide, Observational Study.}, journal = {Cerebrovascular diseases (Basel, Switzerland)}, volume = {51}, number = {5}, pages = {663-669}, pmid = {35358979}, issn = {1421-9786}, mesh = {Bayes Theorem ; *COVID-19/epidemiology ; Cohort Studies ; Communicable Disease Control ; Hospitalization ; Humans ; Pandemics ; *Stroke/diagnosis/epidemiology/therapy ; }, abstract = {INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic continues to have great impacts on the care of non-COVID-19 patients. This was especially true during the first epidemic peak in France, which coincided with the national lockdown. The aim of this study was to identify whether a decrease in stroke admissions occurred in spring 2020, by analyzing the evolution of all stroke admissions in France from January 2019 to June 2020.

METHODS: We conducted a nationwide cohort study using the French national database of hospital admissions (Information Systems Medicalization Program) to extract exhaustive data on all hospitalizations in France with at least one stroke diagnosis between January 1, 2019, and June 30, 2020. The primary endpoint was the difference in the slope gradients of stroke hospitalizations between pre-epidemic, epidemic peak, and post-epidemic peak phases. Modeling was carried out using Bayesian techniques.

RESULTS: Stroke hospitalizations dropped from March 10, 2020 (slope gradient: -11.70), and began to rise again from March 22 (slope gradient: 2.090) to May 7. In total, there were 23,873 stroke admissions during the period March-April 2020, compared to 29,263 at the same period in 2019, representing a decrease of 18.42%. The percentage change was -15.63%, -25.19%, -18.62% for ischemic strokes, transient ischemic attacks, and hemorrhagic strokes, respectively.

DISCUSSION/CONCLUSION: Stroke hospitalizations in France experienced a decline during the first lockdown period, which cannot be explained by a sudden change in stroke incidence. This decline is therefore likely to be a direct, or indirect, result of the COVID-19 pandemic.}, } @article {pmid35359176, year = {2022}, author = {Ceriotti, LF and Gatica-Soria, L and Sanchez-Puerta, MV}, title = {Cytonuclear coevolution in a holoparasitic plant with highly disparate organellar genomes.}, journal = {Plant molecular biology}, volume = {109}, number = {6}, pages = {673-688}, pmid = {35359176}, issn = {1573-5028}, support = {PICT-2017-0691//Agencia Nacional de Promoción Científica y Tecnológica/ ; 06/A724//Universidad Nacional de Cuyo/ ; }, mesh = {*Balanophoraceae/genetics ; Cell Nucleus/genetics ; Chloroplast Proteins/genetics ; Evolution, Molecular ; Gene Transfer, Horizontal ; Genome, Plant/genetics ; Phylogeny ; Plants/genetics ; *Plastids/genetics ; }, abstract = {Contrasting substitution rates in the organellar genomes of Lophophytum agree with the DNA repair, replication, and recombination gene content. Plastid and nuclear genes whose products form multisubunit complexes co-evolve. The organellar genomes of the holoparasitic plant Lophophytum (Balanophoraceae) show disparate evolution. In the plastid, the genome has been severely reduced and presents a > 85% AT content, while in the mitochondria most protein-coding genes have been replaced by homologs acquired by horizontal gene transfer (HGT) from their hosts (Fabaceae). Both genomes carry genes whose products form multisubunit complexes with those of nuclear genes, creating a possible hotspot of cytonuclear coevolution. In this study, we assessed the evolutionary rates of plastid, mitochondrial and nuclear genes, and their impact on cytonuclear evolution of genes involved in multisubunit complexes related to lipid biosynthesis and proteolysis in the plastid and those in charge of the oxidative phosphorylation in the mitochondria. Genes from the plastid and the mitochondria (both native and foreign) of Lophophytum showed extremely high and ordinary substitution rates, respectively. These results agree with the biased loss of plastid-targeted proteins involved in angiosperm organellar repair, replication, and recombination machinery. Consistent with the high rate of evolution of plastid genes, nuclear-encoded subunits of plastid complexes showed disproportionate increases in non-synonymous substitution rates, while those of the mitochondrial complexes did not show different rates than the control (i.e. non-organellar nuclear genes). Moreover, the increases in the nuclear-encoded subunits of plastid complexes were positively correlated with the level of physical interaction they possess with the plastid-encoded ones. Overall, these results suggest that a structurally-mediated compensatory factor may be driving plastid-nuclear coevolution in Lophophytum, and that mito-nuclear coevolution was not altered by HGT.}, } @article {pmid35360860, year = {2022}, author = {Bever, BW and Dietz, ZP and Sullins, JA and Montoya, AM and Bergthorsson, U and Katju, V and Estes, S}, title = {Mitonuclear Mismatch is Associated With Increased Male Frequency, Outcrossing, and Male Sperm Size in Experimentally-Evolved C. elegans.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {742272}, pmid = {35360860}, issn = {1664-8021}, abstract = {We provide a partial test of the mitonuclear sex hypothesis with the first controlled study of how male frequencies and rates of outcrossing evolve in response to mitonuclear mismatch by allowing replicate lineages of C. elegans nematodes containing either mitochondrial or nuclear mutations of electron transport chain (ETC) genes to evolve under three sexual systems: facultatively outcrossing (wildtype), obligately selfing, and obligately outcrossing. Among facultatively outcrossing lines, we found evolution of increased male frequency in at least one replicate line of all four ETC mutant backgrounds tested-nuclear isp-1, mitochondrial cox-1 and ctb-1, and an isp-1 IV; ctb-1M mitonuclear double mutant-and confirmed for a single line set (cox-1) that increased male frequency also resulted in successful outcrossing. We previously found the same result for lines evolved from another nuclear ETC mutant, gas-1. For several lines in the current experiment, however, male frequency declined to wildtype levels (near 0%) in later generations. Male frequency did not change in lines evolved from a wildtype control strain. Additional phenotypic assays of lines evolved from the mitochondrial cox-1 mutant indicated that evolution of high male frequency was accompanied by evolution of increased male sperm size and mating success with tester females, but that it did not translate into increased mating success with coevolved hermaphrodites. Rather, hermaphrodites' self-crossed reproductive fitness increased, consistent with sexually antagonistic coevolution. In accordance with evolutionary theory, males and sexual outcrossing may be most beneficial to populations evolving from a state of low ancestral fitness (gas-1, as previously reported) and less beneficial or deleterious to those evolving from a state of higher ancestral fitness (cox-1). In support of this idea, the obligately outcrossing fog-2 V; cox-1 M lines exhibited no fitness evolution compared to their ancestor, while facultatively outcrossing lines showed slight upward evolution of fitness, and all but one of the obligately selfing xol-1 X; cox-1 M lines evolved substantially increased fitness-even beyond wildtype levels. This work provides a foundation to directly test the effect of reproductive mode on the evolutionary dynamics of mitonuclear genomes, as well as whether compensatory mutations (nuclear or mitochondrial) can rescue populations from mitochondrial dysfunction.}, } @article {pmid35372951, year = {2020}, author = {Chevalier, RL}, title = {Bioenergetic Evolution Explains Prevalence of Low Nephron Number at Birth: Risk Factor for CKD.}, journal = {Kidney360}, volume = {1}, number = {8}, pages = {863-879}, pmid = {35372951}, issn = {2641-7650}, mesh = {Adult ; Energy Metabolism/genetics ; Female ; Humans ; Infant, Newborn ; Male ; *Nephrons ; Placenta/metabolism ; Pregnancy ; *Premature Birth/metabolism ; Prevalence ; *Renal Insufficiency, Chronic/epidemiology ; Risk Factors ; }, abstract = {There is greater than tenfold variation in nephron number of the human kidney at birth. Although low nephron number is a recognized risk factor for CKD, its determinants are poorly understood. Evolutionary medicine represents a new discipline that seeks evolutionary explanations for disease, broadening perspectives on research and public health initiatives. Evolution of the kidney, an organ rich in mitochondria, has been driven by natural selection for reproductive fitness constrained by energy availability. Over the past 2 million years, rapid growth of an energy-demanding brain in Homo sapiens enabled hominid adaptation to environmental extremes through selection for mutations in mitochondrial and nuclear DNA epigenetically regulated by allocation of energy to developing organs. Maternal undernutrition or hypoxia results in intrauterine growth restriction or preterm birth, resulting in low birth weight and low nephron number. Regulated through placental transfer, environmental oxygen and nutrients signal nephron progenitor cells to reprogram metabolism from glycolysis to oxidative phosphorylation. These processes are modulated by counterbalancing anabolic and catabolic metabolic pathways that evolved from prokaryote homologs and by hypoxia-driven and autophagy pathways that evolved in eukaryotes. Regulation of nephron differentiation by histone modifications and DNA methyltransferases provide epigenetic control of nephron number in response to energy available to the fetus. Developmental plasticity of nephrogenesis represents an evolved life history strategy that prioritizes energy to early brain growth with adequate kidney function through reproductive years, the trade-off being increasing prevalence of CKD delayed until later adulthood. The research implications of this evolutionary analysis are to identify regulatory pathways of energy allocation directing nephrogenesis while accounting for the different life history strategies of animal models such as the mouse. The clinical implications are to optimize nutrition and minimize hypoxic/toxic stressors in childbearing women and children in early postnatal development.}, } @article {pmid35377454, year = {2022}, author = {Monteiro, LB and Prodonoff, JS and Favero de Aguiar, C and Correa-da-Silva, F and Castoldi, A and Bakker, NVT and Davanzo, GG and Castelucci, B and Pereira, JADS and Curtis, J and Büscher, J and Reis, LMD and Castro, G and Ribeiro, G and Virgílio-da-Silva, JV and Adamoski, D and Dias, SMG and Consonni, SR and Donato, J and Pearce, EJ and Câmara, NOS and Moraes-Vieira, PM}, title = {Leptin Signaling Suppression in Macrophages Improves Immunometabolic Outcomes in Obesity.}, journal = {Diabetes}, volume = {71}, number = {7}, pages = {1546-1561}, doi = {10.2337/db21-0842}, pmid = {35377454}, issn = {1939-327X}, mesh = {Adipose Tissue/metabolism ; Animals ; Inflammation/metabolism ; *Insulin Resistance ; *Leptin/metabolism ; Macrophages/metabolism ; Mice ; Mice, Inbred C57BL ; Obesity/metabolism ; }, abstract = {Obesity is a major concern for global health care systems. Systemic low-grade inflammation in obesity is a major risk factor for insulin resistance. Leptin is an adipokine secreted by the adipose tissue that functions by controlling food intake, leading to satiety. Leptin levels are increased in obesity. Here, we show that leptin enhances the effects of LPS in macrophages, intensifying the production of cytokines, glycolytic rates, and morphological and functional changes in the mitochondria through an mTORC2-dependent, mTORC1-independent mechanism. Leptin also boosts the effects of IL-4 in macrophages, leading to increased oxygen consumption, expression of macrophage markers associated with a tissue repair phenotype, and wound healing. In vivo, hyperleptinemia caused by diet-induced obesity increases the inflammatory response by macrophages. Deletion of leptin receptor and subsequently of leptin signaling in myeloid cells (ObR-/-) is sufficient to improve insulin resistance in obese mice and decrease systemic inflammation. Our results indicate that leptin acts as a systemic nutritional checkpoint to regulate macrophage fitness and contributes to obesity-induced inflammation and insulin resistance. Thus, specific interventions aimed at downstream modulators of leptin signaling may represent new therapeutic targets to treat obesity-induced systemic inflammation.}, } @article {pmid35379961, year = {2022}, author = {Mok, BY and Kotrys, AV and Raguram, A and Huang, TP and Mootha, VK and Liu, DR}, title = {CRISPR-free base editors with enhanced activity and expanded targeting scope in mitochondrial and nuclear DNA.}, journal = {Nature biotechnology}, volume = {40}, number = {9}, pages = {1378-1387}, pmid = {35379961}, issn = {1546-1696}, support = {RM1 HG009490/HG/NHGRI NIH HHS/United States ; R35 GM118062/GM/NIGMS NIH HHS/United States ; R01 EB027793/EB/NIBIB NIH HHS/United States ; R35 GM122455/GM/NIGMS NIH HHS/United States ; T32 GM095450/GM/NIGMS NIH HHS/United States ; U01 AI142756/AI/NIAID NIH HHS/United States ; R01 EB031172/EB/NIBIB NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*CRISPR-Cas Systems ; Cytidine Deaminase/genetics ; DNA, Mitochondrial/genetics ; *Gene Editing ; Humans ; Mitochondria/genetics/metabolism ; }, abstract = {The all-protein cytosine base editor DdCBE uses TALE proteins and a double-stranded DNA-specific cytidine deaminase (DddA) to mediate targeted C•G-to-T•A editing. To improve editing efficiency and overcome the strict TC sequence-context constraint of DddA, we used phage-assisted non-continuous and continuous evolution to evolve DddA variants with improved activity and expanded targeting scope. Compared to canonical DdCBEs, base editors with evolved DddA6 improved mitochondrial DNA (mtDNA) editing efficiencies at TC by 3.3-fold on average. DdCBEs containing evolved DddA11 offered a broadened HC (H = A, C or T) sequence compatibility for both mitochondrial and nuclear base editing, increasing average editing efficiencies at AC and CC targets from less than 10% for canonical DdCBE to 15-30% and up to 50% in cell populations sorted to express both halves of DdCBE. We used these evolved DdCBEs to efficiently install disease-associated mtDNA mutations in human cells at non-TC target sites. DddA6 and DddA11 substantially increase the effectiveness and applicability of all-protein base editing.}, } @article {pmid35383845, year = {2022}, author = {Sharbrough, J and Conover, JL and Fernandes Gyorfy, M and Grover, CE and Miller, ER and Wendel, JF and Sloan, DB}, title = {Global Patterns of Subgenome Evolution in Organelle-Targeted Genes of Six Allotetraploid Angiosperms.}, journal = {Molecular biology and evolution}, volume = {39}, number = {4}, pages = {}, pmid = {35383845}, issn = {1537-1719}, mesh = {Cell Nucleus/genetics ; Evolution, Molecular ; Genome, Plant ; *Magnoliopsida/genetics ; Plastids/genetics ; Polyploidy ; Ribulose-Bisphosphate Carboxylase/genetics ; }, abstract = {Whole-genome duplications (WGDs) are a prominent process of diversification in eukaryotes. The genetic and evolutionary forces that WGD imposes on cytoplasmic genomes are not well understood, despite the central role that cytonuclear interactions play in eukaryotic function and fitness. Cellular respiration and photosynthesis depend on successful interaction between the 3,000+ nuclear-encoded proteins destined for the mitochondria or plastids and the gene products of cytoplasmic genomes in multi-subunit complexes such as OXPHOS, organellar ribosomes, Photosystems I and II, and Rubisco. Allopolyploids are thus faced with the critical task of coordinating interactions between the nuclear and cytoplasmic genes that were inherited from different species. Because the cytoplasmic genomes share a more recent history of common descent with the maternal nuclear subgenome than the paternal subgenome, evolutionary "mismatches" between the paternal subgenome and the cytoplasmic genomes in allopolyploids might lead to the accelerated rates of evolution in the paternal homoeologs of allopolyploids, either through relaxed purifying selection or strong directional selection to rectify these mismatches. We report evidence from six independently formed allotetraploids that the subgenomes exhibit unequal rates of protein-sequence evolution, but we found no evidence that cytonuclear incompatibilities result in altered evolutionary trajectories of the paternal homoeologs of organelle-targeted genes. The analyses of gene content revealed mixed evidence for whether the organelle-targeted genes are lost more rapidly than the non-organelle-targeted genes. Together, these global analyses provide insights into the complex evolutionary dynamics of allopolyploids, showing that the allopolyploid subgenomes have separate evolutionary trajectories despite sharing the same nucleus, generation time, and ecological context.}, } @article {pmid35390639, year = {2022}, author = {Schneider, A}, title = {Evolution and diversification of mitochondrial protein import systems.}, journal = {Current opinion in cell biology}, volume = {75}, number = {}, pages = {102077}, doi = {10.1016/j.ceb.2022.102077}, pmid = {35390639}, issn = {1879-0410}, mesh = {Animals ; Carrier Proteins/metabolism ; Mammals/metabolism ; Membrane Proteins/metabolism ; Mitochondria/metabolism ; *Mitochondrial Membranes/metabolism ; *Mitochondrial Proteins/genetics/metabolism ; Protein Transport/physiology ; Saccharomyces cerevisiae/metabolism ; }, abstract = {More than 95% of mitochondrial proteins are encoded in the nucleus, synthesised in the cytosol and imported into the organelle. The evolution of mitochondrial protein import systems was therefore a prerequisite for the conversion of the α-proteobacterial mitochondrial ancestor into an organelle. Here, I review that the origin of the mitochondrial outer membrane import receptors can best be understood by convergent evolution. Subsequently, I discuss an evolutionary scenario that was proposed to explain the diversification of the inner membrane carrier protein translocases between yeast and mammals. Finally, I illustrate a scenario that can explain how the two specialised inner membrane protein translocase complexes found in most eukaryotes were reduced to a single multifunctional one in trypanosomes.}, } @article {pmid35390830, year = {2021}, author = {Takano, KT and Gao, JJ and Hu, YG and Li, NN and Yafuso, M and Suwito, A and Repin, R and Pungga, RAS and Meleng, PA and Kaliang, CH and Chong, L and Toda, MJ}, title = {Phylogeny, taxonomy and flower-breeding ecology of the Colocasiomyia cristata species group (Diptera: Drosophilidae), with descriptions of ten new species.}, journal = {Zootaxa}, volume = {5079}, number = {1}, pages = {170}, doi = {10.11646/zootaxa.5079.1.1}, pmid = {35390830}, issn = {1175-5334}, mesh = {Animals ; *Diptera ; *Drosophilidae ; Flowers ; Mitochondria ; Phylogeny ; Plant Breeding ; }, abstract = {The phylogeny of the Colocasiomyia cristata species group is reconstructed as a hypothesis, based on DNA sequences of two mitochondrial and six nuclear genes and 51 morphological characters. The resulting tree splits this species group into two clades, one of which corresponds to the colocasiae subgroup. Therefore, a new species subgroup named as the cristata subgroup is established for the other clade. Within the cristata subgroup, three subclades are recognized and each of them is defined as a species complex: the cristata complex composed of five species (including three new ones: C. kinabaluana sp. nov., C. kotana sp. nov. and C. matthewsi sp. nov.), the sabahana complex of two species (C. sabahana sp. nov. and C. sarawakana sp. nov.), and the xenalocasiae complex of five species (including C. sumatrana sp. nov. and C. leucocasiae sp. nov.). There are, however, three new species (C. ecornuta sp. nov., C. grandis sp. nov. and C. vieti sp. nov.) not assigned to any species complex. In addition, breeding habits are described for four cristata-subgroup species, each of which monopolizes its specific host plant. And, data of host-plant use are compiled for all species of the cristata group from records at various localities in the Oriental and Papuan regions. The evolution of host-plant selection and sharing modes is considered by mapping host-plant genera of each species on the phylogenetic tree resulting from the present study.}, } @article {pmid35391113, year = {2022}, author = {Lobon-Rovira, J and Conradie, W and Pinto, PV and Keates, C and Edwards, S and Plessis, AD and Branch, WR}, title = {Systematic revision of Afrogecko ansorgii (Boulenger, 1907) (Sauria: Gekkonidae) from western Angola.}, journal = {Zootaxa}, volume = {5124}, number = {4}, pages = {401-430}, doi = {10.11646/zootaxa.5124.4.1}, pmid = {35391113}, issn = {1175-5334}, mesh = {Angola ; Animals ; Cell Nucleus/genetics ; *Lizards/genetics ; Male ; Mitochondria ; Phylogeny ; }, abstract = {Here we provide the first phylogenetic analysis that include Afrogecko ansorgii and a detailed morphological comparison with other species of leaf-toed geckos. For this purpose, we used two mitochondrial (16S, ND2) and four nuclear (RAG1, RAG2, CMOS, PDC) genes to produce a robust phylogenetic reconstruction. This allowed us to show that A. ansorgii is not related as previously believed to circum-Indian Ocean leaf-toed geckos and is rather more closely related to other Malagasy leaf-toed geckos. Additionally, we explore and compare osteological variation in A. ansorgii skulls through High Resolution X-ray Computed Tomography with previously published material. This allowed us to describe herein a new genus, Bauerius gen. nov., and additionally provide a detailed redescription of the species (including the first description of male material), supplementing the limited original description and type series, which consisted of only two females.}, } @article {pmid35391231, year = {2022}, author = {Chen, Z and Liu, F and Li, D and Xu, X}, title = {Four new species of the primitively segmented spider genus Songthela (Mesothelae, Liphistiidae) from Chongqing Municipality, China.}, journal = {Zootaxa}, volume = {5091}, number = {4}, pages = {546-558}, doi = {10.11646/zootaxa.5091.4.2}, pmid = {35391231}, issn = {1175-5334}, mesh = {Animals ; China ; DNA Barcoding, Taxonomic ; DNA, Mitochondrial/genetics ; Female ; Male ; Mitochondria/genetics ; *Spiders/genetics ; }, abstract = {This paper reports four new species of the primitively segmented spider genus Songthela from Chongqing Municipality, China, based on morphological characters of both males and females: S. jinyun sp. nov., S. longbao sp. nov., S. serriformis sp. nov. and S. wangerbao sp. nov. We also provide the GenBank accession codes of mitochondrial DNA barcode gene, cytochrome c oxidase subunit I (COI), for the holotype of four new species for future identification.}, } @article {pmid35397926, year = {2022}, author = {Zhu, D and Li, X and Tian, Y}, title = {Mitochondrial-to-nuclear communication in aging: an epigenetic perspective.}, journal = {Trends in biochemical sciences}, volume = {47}, number = {8}, pages = {645-659}, doi = {10.1016/j.tibs.2022.03.008}, pmid = {35397926}, issn = {0968-0004}, mesh = {Cell Nucleus/metabolism ; Epigenesis, Genetic ; *Longevity/physiology ; *Mitochondria/metabolism ; }, abstract = {Age-associated changes in mitochondria are closely involved in aging. Apart from the established roles in bioenergetics and biosynthesis, mitochondria are signaling organelles that communicate their fitness to the nucleus, triggering transcriptional programs to adapt homeostasis stress that is essential for organismal health and aging. Emerging studies revealed that mitochondrial-to-nuclear (mito-nuclear) communication via altered levels of mitochondrial metabolites or stress signals causes various epigenetic changes, facilitating efforts to maintain homeostasis and affect aging. Here, we summarize recent studies on the mechanisms by which mito-nuclear communication modulates epigenomes and their effects on regulating the aging process. Insights into understanding how mitochondrial metabolites serve as prolongevity signals and how aging affects this communication will help us develop interventions to promote longevity and health.}, } @article {pmid35406135, year = {2022}, author = {Snell, TW and Carberry, J}, title = {Astaxanthin Bioactivity Is Determined by Stereoisomer Composition and Extraction Method.}, journal = {Nutrients}, volume = {14}, number = {7}, pages = {}, pmid = {35406135}, issn = {2072-6643}, mesh = {Animals ; *Antioxidants/pharmacology ; Reactive Oxygen Species/metabolism ; Stereoisomerism ; *Xanthophylls/chemistry/pharmacology ; }, abstract = {Astaxanthin (ASX) is a natural product and one of the most powerful antioxidants known. It has significant effects on the metabolism of many animals, increasing fecundity, egg yolk volume, growth rates, immune responses, and disease resistance. A large part of the bioactivity of ASX is due to its targeting of mitochondria, where it inserts itself into cell membranes. Here, ASX stabilizes membranes and acts as a powerful antioxidant, protecting mitochondria from damage by reactive oxygen species (ROS). ROS are ubiquitous by-products of energy metabolism that must be tightly regulated by cells, lest they bind to and inactivate proteins, DNA and RNA, lipids, and signaling molecules. Most animals cannot synthesize ASX, so they need to acquire it in their diet. ASX is easily thermally denatured during extraction, and its high hydrophobicity limits its bioavailability. Our focus in this review is to contrast the bioactivity of different ASX stereoisomers and how extraction methods can denature ASX, compromising its bioavailability and bioactivity. We discuss the commercial sources of astaxanthin, structure of stereoisomers, relative bioavailability and bioactivity of ASX stereoisomers, mechanisms of ASX bioactivity, evolution of carotenoids, and why mitochondrial targeting makes ASX such an effective antioxidant.}, } @article {pmid35408834, year = {2022}, author = {Scaltsoyiannes, V and Corre, N and Waltz, F and Giegé, P}, title = {Types and Functions of Mitoribosome-Specific Ribosomal Proteins across Eukaryotes.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35408834}, issn = {1422-0067}, support = {ANR 16 CE11-0024; ANR 20 CE11-0021//Agence Nationale de la Recherche/ ; }, mesh = {Cryoelectron Microscopy ; Eukaryota/genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; *Mitochondrial Ribosomes/metabolism ; RNA, Ribosomal/metabolism ; *Ribosomal Proteins/metabolism ; }, abstract = {Mitochondria are key organelles that combine features inherited from their bacterial endosymbiotic ancestor with traits that arose during eukaryote evolution. These energy producing organelles have retained a genome and fully functional gene expression machineries including specific ribosomes. Recent advances in cryo-electron microscopy have enabled the characterization of a fast-growing number of the low abundant membrane-bound mitochondrial ribosomes. Surprisingly, mitoribosomes were found to be extremely diverse both in terms of structure and composition. Still, all of them drastically increased their number of ribosomal proteins. Interestingly, among the more than 130 novel ribosomal proteins identified to date in mitochondria, most of them are composed of a-helices. Many of them belong to the nuclear encoded super family of helical repeat proteins. Here we review the diversity of functions and the mode of action held by the novel mitoribosome proteins and discuss why these proteins that share similar helical folds were independently recruited by mitoribosomes during evolution in independent eukaryote clades.}, } @article {pmid35409376, year = {2022}, author = {Kasperski, A}, title = {Life Entrapped in a Network of Atavistic Attractors: How to Find a Rescue.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35409376}, issn = {1422-0067}, mesh = {Cell Physiological Phenomena ; Cell Transformation, Neoplastic/metabolism ; *Energy Metabolism ; Humans ; Mitochondria/metabolism ; *Neoplasms/metabolism ; }, abstract = {In view of unified cell bioenergetics, cell bioenergetic problems related to cell overenergization can cause excessive disturbances in current cell fate and, as a result, lead to a change of cell-fate. At the onset of the problem, cell overenergization of multicellular organisms (especially overenergization of mitochondria) is solved inter alia by activation and then stimulation of the reversible Crabtree effect by cells. Unfortunately, this apparently good solution can also lead to a much bigger problem when, despite the activation of the Crabtree effect, cell overenergization persists for a long time. In such a case, cancer transformation, along with the Warburg effect, may occur to further reduce or stop the charging of mitochondria by high-energy molecules. Understanding the phenomena of cancer transformation and cancer development has become a real challenge for humanity. To date, many models have been developed to understand cancer-related mechanisms. Nowadays, combining all these models into one coherent universal model of cancer transformation and development can be considered a new challenge. In this light, the aim of this article is to present such a potentially universal model supported by a proposed new model of cellular functionality evolution. The methods of fighting cancer resulting from unified cell bioenergetics and the two presented models are also considered.}, } @article {pmid35409414, year = {2022}, author = {Tsai, HC and Hsieh, CH and Hsu, CW and Hsu, YH and Chien, LF}, title = {Cloning and Organelle Expression of Bamboo Mitochondrial Complex I Subunits Nad1, Nad2, Nad4, and Nad5 in the Yeast Saccharomyces cerevisiae.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35409414}, issn = {1422-0067}, support = {NSC96-2313-B-005-030-MY2, NSC96-2752-B-005-013-PAE, MOST110-2221-E-005-078//Ministry of Science and Technology of Taiwan/ ; }, mesh = {Cloning, Molecular ; DNA, Mitochondrial/genetics ; *Electron Transport Complex I/genetics ; Mitochondria/genetics ; Phylogeny ; *Saccharomyces cerevisiae/genetics ; }, abstract = {Mitochondrial respiratory complex I catalyzes electron transfer from NADH to ubiquinone and pumps protons from the matrix into the intermembrane space. In particular, the complex I subunits Nad1, Nad2, Nad4, and Nad5, which are encoded by the nad1, nad2, nad4, and nad5 genes, reside at the mitochondrial inner membrane and possibly function as proton (H[+]) and ion translocators. To understand the individual functional roles of the Nad1, Nad2, Nad4, and Nad5 subunits in bamboo, each cDNA of these four genes was cloned into the pYES2 vector and expressed in the mitochondria of the yeast Saccharomyces cerevisiae. The mitochondrial targeting peptide mt gene (encoding MT) and the egfp marker gene (encoding enhanced green fluorescent protein, EGFP) were fused at the 5'-terminal and 3'-terminal ends, respectively. The constructed plasmids were then transformed into yeast. RNA transcripts and fusion protein expression were observed in the yeast transformants. Mitochondrial localizations of the MT-Nad1-EGFP, MT-Nad2-EGFP, MT-Nad4-EGFP, and MT-Nad5-EGFP fusion proteins were confirmed by fluorescence microscopy. The ectopically expressed bamboo subunits Nad1, Nad2, Nad4, and Nad5 may function in ion translocation, which was confirmed by growth phenotype assays with the addition of different concentrations of K[+], Na[+], or H[+].}, } @article {pmid35418016, year = {2022}, author = {Yuan, F and Lan, X}, title = {Sequencing the organelle genomes of Bougainvillea spectabilis and Mirabilis jalapa (Nyctaginaceae).}, journal = {BMC genomic data}, volume = {23}, number = {1}, pages = {28}, pmid = {35418016}, issn = {2730-6844}, mesh = {*Genome, Chloroplast/genetics ; *Genome, Mitochondrial/genetics ; *Mirabilis/genetics ; Mitochondria/genetics ; *Nyctaginaceae/genetics ; }, abstract = {OBJECTIVES: Mirabilis jalapa L. and Bougainvillea spectabilis are two Mirabilis species known for their ornamental and pharmaceutical values. The organelle genomes are highly conserved with a rapid evolution rate making them suitable for evolutionary studies. Therefore, mitochondrial and chloroplast genomes of B. spectabilis and M. jalapa were sequenced to understand their evolutionary relationship with other angiosperms.

DATA DESCRIPTION: Here, we report the complete mitochondrial genomes of B. spectabilis and M. jalapa (343,746 bp and 267,334 bp, respectively) and chloroplast genomes of B. spectabilis (154,520 bp) and M. jalapa (154,532 bp) obtained from Illumina NovaSeq. The mitochondrial genomes of B. spectabilis and M. jalapa consisted of 70 and 72 genes, respectively. Likewise, the chloroplast genomes of B. spectabilis and M. jalapa contained 131 and 132 genes, respectively. The generated genomic data will be useful for molecular characterization and evolutionary studies.}, } @article {pmid35435757, year = {2022}, author = {Nakabachi, A and Moran, NA}, title = {Extreme Polyploidy of Carsonella, an Organelle-Like Bacterium with a Drastically Reduced Genome.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0035022}, pmid = {35435757}, issn = {2165-0497}, mesh = {Animals ; Bacteria/genetics ; *Gammaproteobacteria ; Genome, Bacterial ; *Hemiptera/genetics/microbiology ; Organelles ; Phylogeny ; Polyploidy ; Symbiosis ; }, abstract = {Polyploidy is the state of having multiple copies of the genome within a nucleus or a cell, which has repeatedly evolved across the domains of life. Whereas most bacteria are monoploid, some bacterial species and endosymbiotic organelles that are derived from bacteria are stably polyploid. In the present study, using absolute quantitative PCR, we assessed the ploidy of Candidatus Carsonella ruddii (Gammaproteobacteria, Oceanospirillales), the obligate symbiont of the hackberry petiole gall psyllid, Pachypsylla venusta (Hemiptera, Psylloidea). The genome of this symbiont is one of the smallest known for cellular organisms, at 160 kb. The analysis revealed that Carsonella within a single bacteriocyte has ∼6 × 10[4] copies of the genome, indicating that some Carsonella cells can contain thousands or even tens of thousands of genomic copies per cell. The basis of polyploidy of Carsonella is unknown, but it potentially plays a role in the repair of DNA damage through homologous recombination. IMPORTANCE Mitochondria and plastids are endosymbiotic organelles in eukaryotic cells and are derived from free-living bacteria. They have many highly reduced genomes from which numerous genes have been transferred to the host nucleus. Similar, but more recently established, symbiotic systems are observed in some insect lineages. Although the genomic sequence data of such bacterial symbionts are rapidly accumulating, little is known about their ploidy. The present study revealed that a bacterium with a drastically reduced genome is an extreme polyploid, which is reminiscent of the case of organelles.}, } @article {pmid35441886, year = {2022}, author = {Egusquiza-Alvarez, CA and Robles-Flores, M}, title = {An approach to p32/gC1qR/HABP1: a multifunctional protein with an essential role in cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {148}, number = {8}, pages = {1831-1854}, pmid = {35441886}, issn = {1432-1335}, support = {IV200220//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; IN229420//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; FOSSIS 2017-289600//Consejo Nacional de Ciencia y Tecnología/ ; }, mesh = {Carrier Proteins ; Humans ; Ligands ; Mitochondria/metabolism ; *Mitochondrial Proteins/metabolism ; *Neoplasms/pathology ; }, abstract = {P32/gC1qR/HABP1 is a doughnut-shaped acidic protein, highly conserved in eukaryote evolution and ubiquitous in the organism. Although its canonical subcellular localization is the mitochondria, p32 can also be found in the cytosol, nucleus, cytoplasmic membrane, and it can be secreted. Therefore, it is considered a multicompartmental protein. P32 can interact with many physiologically divergent ligands in each subcellular location and modulate their functions. The main ligands are C1q, hyaluronic acid, calreticulin, CD44, integrins, PKC, splicing factor ASF/SF2, and several microbial proteins. Among the functions in which p32 participates are mitochondrial metabolism and dynamics, apoptosis, splicing, immune response, inflammation, and modulates several cell signaling pathways. Notably, p32 is overexpressed in a significant number of epithelial tumors, where its expression level negatively correlates with patient survival. Several studies of gain and/or loss of function in cancer cells have demonstrated that p32 is a promoter of malignant hallmarks such as proliferation, cell survival, chemoresistance, angiogenesis, immunoregulation, migration, invasion, and metastasis. All of this strongly suggests that p32 is a potential diagnostic molecule and therapeutic target in cancer. Indeed, preclinical advances have been made in developing therapeutic strategies using p32 as a target. They include tumor homing peptides, monoclonal antibodies, an intracellular inhibitor, a p32 peptide vaccine, and p32 CAR T cells. These advances are promising and will allow soon to include p32 as part of targeted cancer therapies.}, } @article {pmid35444563, year = {2022}, author = {Mendez-Romero, O and Ricardez-García, C and Castañeda-Tamez, P and Chiquete-Félix, N and Uribe-Carvajal, S}, title = {Thriving in Oxygen While Preventing ROS Overproduction: No Two Systems Are Created Equal.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {874321}, pmid = {35444563}, issn = {1664-042X}, abstract = {From 2.5 to 2.0 billion years ago, atmospheric oxygen concentration [O2] rose thousands of times, leading to the first mass extinction. Reactive Oxygen Species (ROS) produced by the non-catalyzed partial reduction of O2 were highly toxic eliminating many species. Survivors developed different strategies to cope with ROS toxicity. At the same time, using O2 as the final acceptor in respiratory chains increased ATP production manifold. Thus, both O2 and ROS were strong drivers of evolution, as species optimized aerobic metabolism while developing ROS-neutralizing mechanisms. The first line of defense is preventing ROS overproduction and two mechanisms were developed in parallel: 1) Physiological uncoupling systems (PUS), which increase the rate of electron fluxes in respiratory systems. 2) Avoidance of excess [O2]. However, it seems that as avoidance efficiency improved, PUSs became less efficient. PUS includes branched respiratory chains and proton sinks, which may be proton specific, the mitochondrial uncoupling proteins (UCPs) or unspecific, the mitochondrial permeability transition pore (PTP). High [O2] avoidance also involved different strategies: 1) Cell association, as in biofilms or in multi-cellularity allowed gas-permeable organisms (oxyconformers) from bacterial to arthropods to exclude O2. 2) Motility, to migrate from hypoxic niches. 3) Oxyregulator organisms: as early as in fish, and O2-impermeable epithelium excluded all gases and only exact amounts entered through specialized respiratory systems. Here we follow the parallel evolution of PUS and O2-avoidance, PUS became less critical and lost efficiency. In regard, to proton sinks, there is fewer evidence on their evolution, although UCPs have indeed drifted in function while in some species it is not clear whether PTPs exist.}, } @article {pmid35446419, year = {2022}, author = {Fields, PD and Waneka, G and Naish, M and Schatz, MC and Henderson, IR and Sloan, DB}, title = {Complete Sequence of a 641-kb Insertion of Mitochondrial DNA in the Arabidopsis thaliana Nuclear Genome.}, journal = {Genome biology and evolution}, volume = {14}, number = {5}, pages = {}, pmid = {35446419}, issn = {1759-6653}, support = {R01 GM118046/GM/NIGMS NIH HHS/United States ; BB/V003984/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Arabidopsis/genetics ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial ; In Situ Hybridization, Fluorescence ; Mitochondria/genetics ; Sequence Analysis, DNA ; }, abstract = {Intracellular transfers of mitochondrial DNA continue to shape nuclear genomes. Chromosome 2 of the model plant Arabidopsis thaliana contains one of the largest known nuclear insertions of mitochondrial DNA (numts). Estimated at over 600 kb in size, this numt is larger than the entire Arabidopsis mitochondrial genome. The primary Arabidopsis nuclear reference genome contains less than half of the numt because of its structural complexity and repetitiveness. Recent data sets generated with improved long-read sequencing technologies (PacBio HiFi) provide an opportunity to finally determine the accurate sequence and structure of this numt. We performed a de novo assembly using sequencing data from recent initiatives to span the Arabidopsis centromeres, producing a gap-free sequence of the Chromosome 2 numt, which is 641 kb in length and has 99.933% nucleotide sequence identity with the actual mitochondrial genome. The numt assembly is consistent with the repetitive structure previously predicted from fiber-based fluorescent in situ hybridization. Nanopore sequencing data indicate that the numt has high levels of cytosine methylation, helping to explain its biased spectrum of nucleotide sequence divergence and supporting previous inferences that it is transcriptionally inactive. The original numt insertion appears to have involved multiple mitochondrial DNA copies with alternative structures that subsequently underwent an additional duplication event within the nuclear genome. This work provides insights into numt evolution, addresses one of the last unresolved regions of the Arabidopsis reference genome, and represents a resource for distinguishing between highly similar numt and mitochondrial sequences in studies of transcription, epigenetic modifications, and de novo mutations.}, } @article {pmid35446942, year = {2022}, author = {Gil Del Alcazar, CR and Trinh, A and Alečković, M and Rojas Jimenez, E and Harper, NW and Oliphant, MUJ and Xie, S and Krop, ED and Lulseged, B and Murphy, KC and Keenan, TE and Van Allen, EM and Tolaney, SM and Freeman, GJ and Dillon, DA and Muthuswamy, SK and Polyak, K}, title = {Insights into Immune Escape During Tumor Evolution and Response to Immunotherapy Using a Rat Model of Breast Cancer.}, journal = {Cancer immunology research}, volume = {10}, number = {6}, pages = {680-697}, pmid = {35446942}, issn = {2326-6074}, support = {P50 CA168504/CA/NCI NIH HHS/United States ; R35 CA197623/CA/NCI NIH HHS/United States ; R35 CA232128/CA/NCI NIH HHS/United States ; T32 CA009172/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Breast Neoplasms/genetics/immunology/therapy ; Female ; Hormones ; Humans ; Immunologic Factors ; Immunotherapy ; Mice ; Rats ; Rats, Sprague-Dawley ; Receptors, Antigen, T-Cell ; }, abstract = {Animal models are critical for the preclinical validation of cancer immunotherapies. Unfortunately, mouse breast cancer models do not faithfully reproduce the molecular subtypes and immune environment of the human disease. In particular, there are no good murine models of estrogen receptor-positive (ER+) breast cancer, the predominant subtype in patients. Here, we show that Nitroso-N-methylurea-induced mammary tumors in outbred Sprague-Dawley rats recapitulate the heterogeneity for mutational profiles, ER expression, and immune evasive mechanisms observed in human breast cancer. We demonstrate the utility of this model for preclinical studies by dissecting mechanisms of response to immunotherapy using combination TGFBR inhibition and PD-L1 blockade. Short-term treatment of early-stage tumors induced durable responses. Gene expression profiling and spatial mapping classified tumors as inflammatory and noninflammatory, and identified IFNγ, T-cell receptor (TCR), and B-cell receptor (BCR) signaling, CD74/MHC II, and epithelium-interacting CD8+ T cells as markers of response, whereas the complement system, M2 macrophage phenotype, and translation in mitochondria were associated with resistance. We found that the expression of CD74 correlated with leukocyte fraction and TCR diversity in human breast cancer. We identified a subset of rat ER+ tumors marked by expression of antigen-processing genes that had an active immune environment and responded to treatment. A gene signature characteristic of these tumors predicted disease-free survival in patients with ER+ Luminal A breast cancer and overall survival in patients with metastatic breast cancer receiving anti-PD-L1 therapy. We demonstrate the usefulness of this preclinical model for immunotherapy and suggest examination to expand immunotherapy to a subset of patients with ER+ disease. See related Spotlight by Roussos Torres, p. 672.}, } @article {pmid35451706, year = {2022}, author = {Vella, A and Vella, N and Acosta-Díaz, C}, title = {The first complete mitochondrial genomes for Serranus papilionaceus and Serranus scriba, and their phylogenetic position within Serranidae.}, journal = {Molecular biology reports}, volume = {49}, number = {7}, pages = {6295-6302}, pmid = {35451706}, issn = {1573-4978}, support = {BioCon_Innovate Research Excellence Grant//University of Malta/ ; FINS//Ministry of Education/ ; }, mesh = {Animals ; *Bass/genetics ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial/genetics ; Phylogeny ; RNA, Ribosomal/genetics ; }, abstract = {BACKGROUND: Butterfly-winged comber, Serranus papilionaceus Valenciennes, 1832, was recently resurrected and so it is no longer considered as a junior synonym of the Painted comber, Serranus scriba (Linneus, 1758). This calls for a more comprehensive phylogenetic assessment using mitochondria DNA genomes to better understand the relationship and delineate these two species.

METHODS AND RESULTS: Next-generation Sequencing was applied to sequence the genome of these two Serranus species. The data generated was then used to construct the mitochondrial genome of these two species. This produced the first complete mitochondrial genomes for the genus Serranus here represented by Serranus papilionaceus and Serranus scriba. These two mitochondrial genomes are 16,514 bp and 16,512 bp respectively, and both contained the typical 37 genes found in vertebrates (13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs), together with the OL and the control region.

CONCLUSIONS: These mitochondrial genomes provide a new insight into the phylogenetic and evolutionary connections between the various subfamilies within Serranidae, while providing new molecular data that can be applied to discriminate between the studied species.}, } @article {pmid35452707, year = {2022}, author = {Chen, Q and Chen, L and Liao, CQ and Wang, X and Wang, M and Huang, GH}, title = {Comparative mitochondrial genome analysis and phylogenetic relationship among lepidopteran species.}, journal = {Gene}, volume = {830}, number = {}, pages = {146516}, doi = {10.1016/j.gene.2022.146516}, pmid = {35452707}, issn = {1879-0038}, mesh = {Animals ; *Butterflies/genetics ; *Genome, Mitochondrial ; *Lepidoptera/genetics ; Mitochondria/genetics ; *Moths/genetics ; Phylogeny ; RNA, Transfer/genetics ; }, abstract = {Lepidoptera has rich species including many agricultural pests and economical insects around the world. The mitochondrial genomes (mitogenomes) were utilized to explore the phylogenetic relationships between difference taxonomic levels in Lepidoptera. However, the knowledge of mitogenomic characteristics and phylogenetic position about superfamily-level in this order is unresolved. In this study, we integrated 794 mitogenomes consisting of 37 genes and a noncoding control region, which covered 26 lepidopteran superfamilies from newly sequenced and publicly available genomes for comparative genomic and phylogenetic analysis. In primitive taxon, putative start codon of cox1 gene was ATA or ATT instead of CGA, but stop codon of that showed four types, namely TAA, TAG, TA and T. The 7-bp overlap between atp8 and atp6 presented as "ATGATAA". Moreover, the most frequently utilized amino acids were leucine (UUA) in 13 PCGs. Phylogenetic analysis showed that the main backbone relationship in Lepidoptera was (Hepialoidea + (Nepticuloidea + (Adeloidea + (Tischerioidea + (Tineoidea + (Yponomeutoidea + (Gracillarioidea + (Papilionoidea + ((Zygaenoidea + Tortricoidea) + (Gelechioidea + (Pyraloidea + ((Geometroidea + Noctuoidea) + (Lasiocampoidea + Bombycoidea))))))))))))).}, } @article {pmid35453058, year = {2022}, author = {Coleman, PS and Parlo, RA}, title = {Cancer's camouflage: Microvesicle shedding from cholesterol-rich tumor plasma membranes might blindfold first-responder immunosurveillance strategies.}, journal = {European journal of cell biology}, volume = {101}, number = {2}, pages = {151219}, doi = {10.1016/j.ejcb.2022.151219}, pmid = {35453058}, issn = {1618-1298}, mesh = {Animals ; Cell Membrane/metabolism ; Cholesterol/metabolism ; *Lipid Bilayers ; Mammals/metabolism ; Membrane Lipids/metabolism ; Monitoring, Immunologic ; *Neoplasms ; }, abstract = {Intermediary metabolism of tumors is characterized, in part, by a dysregulation of the cholesterol biosynthesis pathway at its rate-controlling enzyme providing the molecular basis for tumor membranes (mitochondria, plasma membrane) to become enriched with cholesterol (Bloch, 1965; Feo et al., 1975; Brown and Goldstein, 1980; Goldstein and Brown, 1990). Cholesterol enriched tumor mitochondria manifest preferential citrate export, thereby providing a continuous supply of substrate precursor for the tumor's dysregulated cholesterogenesis via a "truncated" Krebs/TCA cycle (Kaplan et al., 1986; Coleman et al., 1997). Proliferating tumors shed elevated amounts of plasma membrane-derived extracellular vesicles (pmEV) compared with normal tissues (van Blitterswijk et al., 1979; Black, 1980). Coordination of these metabolic phenomena in tumors supports the enhanced intercalation of cholesterol within the plasma membrane lipid bilayer's cytoplasmic face, the promotion of outward protrusions from the plasma membrane, and the evolution of cholesterol enriched pmEV. The pmEV shed by tumors possess elevated cholesterol and concentrated cell surface antigen clusters found on the tumor cells themselves (Kim et al., 2002). Upon exfoliation, saturation of the extracellular milieu with tumor-derived pmEV could allow early onset mammalian immune surveillance mechanisms to become "blind" to an evolving cancer and lose their ability to detect and initiate strategies to destroy the cancer. However, a molecular mechanism is lacking that would help explain how cholesterol enrichment of the pmEV inner lipid bilayer might allow the tumor cell to evade the host immune system. We offer a hypothesis, endorsed by published mathematical modeling of biomembrane structure as well as by decades of in vivo data with diverse cancers, that a cholesterol enriched inner bilayer leaflet, coupled with a logarithmic expansion in surface area of shed tumor pmEV load relative to its derivative cancer cell, conspire to force exposure of otherwise unfamiliar membrane integral protein domains as antigenic epitopes to the host's circulating immune surveillance system, allowing the tumor cells to evade destruction. We provide elementary numerical estimations comparing the amount of pmEV shed from tumor versus normal cells.}, } @article {pmid35453370, year = {2022}, author = {Hambardikar, V and Guitart-Mampel, M and Scoma, ER and Urquiza, P and Nagana, GGA and Raftery, D and Collins, JA and Solesio, ME}, title = {Enzymatic Depletion of Mitochondrial Inorganic Polyphosphate (polyP) Increases the Generation of Reactive Oxygen Species (ROS) and the Activity of the Pentose Phosphate Pathway (PPP) in Mammalian Cells.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {}, pmid = {35453370}, issn = {2076-3921}, support = {K99 AG055701/AG/NIA NIH HHS/United States ; R00 AG055701/AG/NIA NIH HHS/United States ; }, abstract = {Inorganic polyphosphate (polyP) is an ancient biopolymer that is well preserved throughout evolution and present in all studied organisms. In mammals, it shows a high co-localization with mitochondria, and it has been demonstrated to be involved in the homeostasis of key processes within the organelle, including mitochondrial bioenergetics. However, the exact extent of the effects of polyP on the regulation of cellular bioenergetics, as well as the mechanisms explaining these effects, still remain poorly understood. Here, using HEK293 mammalian cells under Wild-type (Wt) and MitoPPX (cells enzymatically depleted of mitochondrial polyP) conditions, we show that depletion of polyP within mitochondria increased oxidative stress conditions. This is characterized by enhanced mitochondrial O2[-] and intracellular H2O2 levels, which may be a consequence of the dysregulation of oxidative phosphorylation (OXPHOS) that we have demonstrated in MitoPPX cells in our previous work. These findings were associated with an increase in basal peroxiredoxin-1 (Prx1), superoxide dismutase-2 (SOD2), and thioredoxin (Trx) antioxidant protein levels. Using [13]C-NMR and immunoblotting, we assayed the status of glycolysis and the pentose phosphate pathway (PPP) in Wt and MitoPPX cells. Our results show that MitoPPX cells display a significant increase in the activity of the PPP and an increase in the protein levels of transaldolase (TAL), which is a crucial component of the non-oxidative phase of the PPP and is involved in the regulation of oxidative stress. In addition, we observed a trend towards increased glycolysis in MitoPPX cells, which corroborates our prior work. Here, for the first time, we show the crucial role played by mitochondrial polyP in the regulation of mammalian redox homeostasis. Moreover, we demonstrate a significant effect of mitochondrial polyP on the regulation of global cellular bioenergetics in these cells.}, } @article {pmid35453648, year = {2022}, author = {Russo, C and Valle, MS and Casabona, A and Spicuzza, L and Sambataro, G and Malaguarnera, L}, title = {Vitamin D Impacts on Skeletal Muscle Dysfunction in Patients with COPD Promoting Mitochondrial Health.}, journal = {Biomedicines}, volume = {10}, number = {4}, pages = {}, pmid = {35453648}, issn = {2227-9059}, abstract = {Skeletal muscle dysfunction is frequently associated with chronic obstructive pulmonary disease (COPD), which is characterized by a permanent airflow limitation, with a worsening respiratory disorder during disease evolution. In COPD, the pathophysiological changes related to the chronic inflammatory state affect oxidant-antioxidant balance, which is one of the main mechanisms accompanying extra-pulmonary comorbidity such as muscle wasting. Muscle impairment is characterized by alterations on muscle fiber architecture, contractile protein integrity, and mitochondrial dysfunction. Exogenous and endogenous sources of reactive oxygen species (ROS) are present in COPD pathology. One of the endogenous sources of ROS is represented by mitochondria. Evidence demonstrated that vitamin D plays a crucial role for the maintenance of skeletal muscle health. Vitamin D deficiency affects oxidative stress and mitochondrial function influencing disease course through an effect on muscle function in COPD patients. This review will focus on vitamin-D-linked mechanisms that could modulate and ameliorate the damage response to free radicals in muscle fibers, evaluating vitamin D supplementation with enough potent effect to contrast mitochondrial impairment, but which avoids potential severe side effects.}, } @article {pmid35457201, year = {2022}, author = {Juskeviciene, R and Fritz, AK and Brilkova, M and Akbergenov, R and Schmitt, K and Rehrauer, H and Laczko, E and Isnard-Petit, P and Thiam, K and Eckert, A and Schacht, J and Wolfer, DP and Böttger, EC and Shcherbakov, D}, title = {Phenotype of Mrps5-Associated Phylogenetic Polymorphisms Is Intimately Linked to Mitoribosomal Misreading.}, journal = {International journal of molecular sciences}, volume = {23}, number = {8}, pages = {}, pmid = {35457201}, issn = {1422-0067}, mesh = {Animals ; Mice ; *Mitochondrial Proteins/genetics ; Mutation ; Phenotype ; Phylogeny ; Protein Biosynthesis ; *Ribosomal Proteins/genetics ; }, abstract = {We have recently identified point mutation V336Y in mitoribosomal protein Mrps5 (uS5m) as a mitoribosomal ram (ribosomal ambiguity) mutation conferring error-prone mitochondrial protein synthesis. In vivo in transgenic knock-in animals, homologous mutation V338Y was associated with a discrete phenotype including impaired mitochondrial function, anxiety-related behavioral alterations, enhanced susceptibility to noise-induced hearing damage, and accelerated metabolic aging in muscle. To challenge the postulated link between Mrps5 V338Y-mediated misreading and the in vivo phenotype, we introduced mutation G315R into the mouse Mrps5 gene as Mrps5 G315R is homologous to the established bacterial ram mutation RpsE (uS5) G104R. However, in contrast to bacterial translation, the homologous G → R mutation in mitoribosomal Mrps5 did not affect the accuracy of mitochondrial protein synthesis. Importantly, in the absence of mitochondrial misreading, homozygous mutant MrpS5[G315R/G315R] mice did not show a phenotype distinct from wild-type animals.}, } @article {pmid35460575, year = {2022}, author = {Liu, Q and Iqbal, MF and Yaqub, T and Firyal, S and Zhao, Y and Stoneking, M and Li, M}, title = {The transmission of human mitochondrial DNA in four-generation pedigrees.}, journal = {Human mutation}, volume = {43}, number = {9}, pages = {1259-1267}, doi = {10.1002/humu.24390}, pmid = {35460575}, issn = {1098-1004}, mesh = {*DNA, Mitochondrial/genetics ; Humans ; Mitochondria/genetics ; *Mitochondrial Diseases/genetics ; Pedigree ; Selection, Genetic ; }, abstract = {Most of the pathogenic variants in mitochondrial DNA (mtDNA) exist in a heteroplasmic state (coexistence of mutant and wild-type mtDNA). Understanding how mtDNA is transmitted is crucial for predicting mitochondrial disease risk. Previous studies were based mainly on two-generation pedigree data, which are limited by the randomness in a single transmission. In this study, we analyzed the transmission of heteroplasmies in 16 four-generation families. First, we found that 57.8% of the variants in the great grandmother were transmitted to the fourth generation. The direction and magnitude of the frequency change during transmission appeared to be random. Moreover, no consistent correlation was identified between the frequency changes among the continuous transmissions, suggesting that most variants were functionally neutral or mildly deleterious and thus not subject to strong natural selection. Additionally, we found that the frequency of one nonsynonymous variant (m.15773G>A) showed a consistent increase in one family, suggesting that this variant may confer a fitness advantage to the mitochondrion/cell. We also estimated the effective bottleneck size during transmission to be 21-71. In summary, our study demonstrates the advantages of multigeneration data for studying the transmission of mtDNA for shedding new light on the dynamics of the mutation frequency in successive generations.}, } @article {pmid35460877, year = {2022}, author = {Kodagoda, YK and Liyanage, DS and Omeka, WKM and Kwon, H and Hwang, SD and Lee, J}, title = {Molecular characterization, expression, and functional analysis of cystatin B in the big-belly seahorse (Hippocampus abdominalis).}, journal = {Fish & shellfish immunology}, volume = {124}, number = {}, pages = {442-453}, doi = {10.1016/j.fsi.2022.04.020}, pmid = {35460877}, issn = {1095-9947}, mesh = {Animals ; *Cyprinidae/genetics ; Cystatin B/genetics ; *Cystatins/genetics ; *Fish Diseases ; Fish Proteins/chemistry ; Male ; Phylogeny ; Poly I-C/pharmacology ; Sequence Alignment ; *Smegmamorpha ; }, abstract = {Cystatins are a diverse group of cysteine protease inhibitors widely present among various organisms. Beyond their protease inhibitor function, cystatins play a crucial role in diverse pathophysiological conditions in animals, including neurodegenerative disorders, tumor progression, inflammatory diseases, and immune response. However, the role of cystatins in immunity against viral and bacterial infections in fish remains to be elucidated. In this study, the cystatin B from big-belly seahorse, Hippocampus abdominalis, designated as HaCSTB, was identified and characterized. HaCSTB shared the highest homology with type 1 cystatin family members of teleosts and had three cystatin catalytic domains with no signal peptides or disulfide bonds. HaCSTB transcripts were mainly expressed in peripheral blood cells (PBCs), followed by the testis and pouch of healthy big-belly seahorses. Immune challenge with lipopolysaccharides (LPS), polyinosinic:polycytidylic acid (Poly I:C), and Streptococcus iniae induced upregulation of relative HaCSTB mRNA expression in PBCs. Subcellular localization analysis revealed the distribution of HaCSTB in the cytosol, mitochondria, and nuclei of fathead minnow cells (FHM). Recombinant HaCSTB (rHaCSTB) exhibited potent in vitro inhibitory activity against papain, a cysteine protease, in a concentration-, pH-, and temperature-dependent manner. Overexpression of HaCSTB in viral hemorrhagic septicemia virus (VHSV)-susceptible FHM cells increased cell viability and reduced VHSV-induced apoptosis. Collectively, these results suggest that HaCSTB might engage in the teleostean immune protection against bacteria and viruses.}, } @article {pmid35463435, year = {2022}, author = {Yi, L and Liu, B and Nixon, PJ and Yu, J and Chen, F}, title = {Recent Advances in Understanding the Structural and Functional Evolution of FtsH Proteases.}, journal = {Frontiers in plant science}, volume = {13}, number = {}, pages = {837528}, pmid = {35463435}, issn = {1664-462X}, abstract = {The FtsH family of proteases are membrane-anchored, ATP-dependent, zinc metalloproteases. They are universally present in prokaryotes and the mitochondria and chloroplasts of eukaryotic cells. Most bacteria bear a single ftsH gene that produces hexameric homocomplexes with diverse house-keeping roles. However, in mitochondria, chloroplasts and cyanobacteria, multiple FtsH homologs form homo- and heterocomplexes with specialized functions in maintaining photosynthesis and respiration. The diversification of FtsH homologs combined with selective pairing of FtsH isomers is a versatile strategy to enable functional adaptation. In this article we summarize recent progress in understanding the evolution, structure and function of FtsH proteases with a focus on the role of FtsH in photosynthesis and respiration.}, } @article {pmid35480047, year = {2022}, author = {De Pinto, V and Mahalakshmi, R and Messina, A}, title = {Editorial: VDAC Structure and Function: An Up-to-Date View.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {871586}, pmid = {35480047}, issn = {1664-042X}, support = {IA/S/20/2/505182/WTDBT_/DBT-Wellcome Trust India Alliance/India ; }, } @article {pmid35480563, year = {2022}, author = {Di-Nizo, CB and Suárez-Villota, EY and Silva, MJJ}, title = {Species limits and recent diversification of Cerradomys (Sigmodontinae: Oryzomyini) during the Pleistocene.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e13011}, pmid = {35480563}, issn = {2167-8359}, mesh = {Animals ; *Sigmodontinae ; Phylogeny ; *Biological Evolution ; Mitochondria ; South America ; }, abstract = {Cerradomys is a genus of the tribe Oryzomyini with eight species currently recognized, and a controversial taxonomy. These species are mainly distributed in the South America dry diagonal, but some species extend into Atlantic Forest, reaching the coastal sandy plains known as Restingas. This study aimed to address species limits and patterns of diversification of Cerradomys species. For this purpose, we performed cytogenetic and molecular analyses (phylogeny, coalescent species delimitation, barcoding, and divergence times estimation) using multiple mitochondrial and nuclear markers on a comprehensive sampling, representing all nominal taxa reported so far. Chromosomal information was a robust marker recognizing eight Cerradomys species. Reciprocal monophyly was recovered for all the species, except for C. subflavus. These results together with coalescent analyses recovered eight species as the most congruent species delimitation scenario for the genus (mean C tax : 0.72). Divergence time estimates revealed that Cerradomys' diversification occurred about 1.32 million years ago (Mya) during the Pleistocene. Although our results conservatively support the eight Cerradomys species described so far, different lines of evidence suggest that C. langguthi and C. subflavus could potentially be species-complexes. We discussed this scenario in the light of multiple evolutionary processes within and between species and populations, since Cerradomys comprises a species group with recent diversification affected by Pleistocene climatic changes and by the complex biogeographic history of South America dry diagonal. This work supports that the diversity of Cerradomys is underestimated and reiterates that interdisciplinary approaches are mandatory to identify small rodent species properly, and to unhide cryptic species.}, } @article {pmid35483362, year = {2022}, author = {David, P and Degletagne, C and Saclier, N and Jennan, A and Jarne, P and Plénet, S and Konecny, L and François, C and Guéguen, L and Garcia, N and Lefébure, T and Luquet, E}, title = {Extreme mitochondrial DNA divergence underlies genetic conflict over sex determination.}, journal = {Current biology : CB}, volume = {32}, number = {10}, pages = {2325-2333.e6}, doi = {10.1016/j.cub.2022.04.014}, pmid = {35483362}, issn = {1879-0445}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; Evolution, Molecular ; Female ; *Genome, Mitochondrial ; Haplotypes ; Mitochondria/genetics ; }, abstract = {Cytoplasmic male sterility (CMS) is a form of genetic conflict over sex determination that results from differences in modes of inheritance between genomic compartments.[1-3] Indeed, maternally transmitted (usually mitochondrial) genes sometimes enhance their transmission by suppressing the male function in a hermaphroditic organism to the detriment of biparentally inherited nuclear genes. Therefore, these hermaphrodites become functionally female and may coexist with regular hermaphrodites in so-called gynodioecious populations.[3] CMS has been known in plants since Darwin's times[4] but is previously unknown in the animal kingdom.[5-8] We relate the first observation of CMS in animals. It occurs in a freshwater snail population, where some individuals appear unable to sire offspring in controlled crosses and show anatomical, physiological, and behavioral characters consistent with a suppression of the male function. Male sterility is associated with a mitochondrial lineage that underwent a spectacular acceleration of DNA substitution rates, affecting the entire mitochondrial genome-this acceleration concerns both synonymous and non-synonymous substitutions and therefore results from increased mitogenome mutation rates. Consequently, mitochondrial haplotype divergence within the population is exceptionally high, matching that observed between snail taxa that diverged 475 million years ago. This result is reminiscent of similar accelerations in mitogenome evolution observed in plant clades where gynodioecy is frequent,[9][,][10] both being consistent with arms-race evolution of genome regions implicated in CMS.[11][,][12] Our study shows that genomic conflicts can trigger independent evolution of similar sex-determination systems in plants and animals and dramatically accelerate molecular evolution.}, } @article {pmid35490656, year = {2022}, author = {Das, R and Kumar, A and Dalai, R and Goswami, C}, title = {Cytochrome C interacts with the pathogenic mutational hotspot region of TRPV4 and forms complexes that differ in mutation and metal ion-sensitive manner.}, journal = {Biochemical and biophysical research communications}, volume = {611}, number = {}, pages = {172-178}, doi = {10.1016/j.bbrc.2022.04.066}, pmid = {35490656}, issn = {1090-2104}, mesh = {*Cytochromes c/genetics/metabolism ; Ions/metabolism ; Mutation ; *TRPV Cation Channels/metabolism ; }, abstract = {The importance of TRPV4 in physiology and disease has been reported by several groups. Recently we have reported that TRPV4 localizes in the mitochondria in different cellular systems, regulates mitochondrial metabolism and electron transport chain functions. Here, we show that TRPV4 colocalizes with Cytochrome C (Cyt C), both in resting as well as in activated conditions. Amino acid region 592-630 of TRPV4 (termed as Fr592-630) that also covers TM4-Loop-TM5 region (which is also a hotspot of several pathogenic mutations) interacts with Cyt C, in a Ca[2+]-sensitive manner. This interaction is also variable and sensitive to other divalent and trivalent cations (i.e., Cu[2+], Mn[2+], Ni[2+], Zn[2+], Fe[3+]). Key residues of TRPV4 involved in these interactions remain conserved throughout the vertebrate evolution. Accordingly, this interaction is variable in the case of different pathogenic mutations (R616Q, F617L, L618P, V620I). Our data suggest that the TRPV4-Cyt C complex differs due to different mutations and is sensitive to the presence of different metal ions. We propose that TRPV4-Cyt C complex formation is important for physiological functions and relevant for TRPV4-induced channelopathies.}, } @article {pmid35497189, year = {2022}, author = {Chen, Z and Schrödl, M}, title = {How many single-copy orthologous genes from whole genomes reveal deep gastropod relationships?.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e13285}, pmid = {35497189}, issn = {2167-8359}, mesh = {Animals ; *Gastropoda/genetics ; Phylogeny ; Mollusca ; Genome/genetics ; Transcriptome ; }, abstract = {The Gastropoda contains 80% of existing mollusks and is the most diverse animal class second only to the Insecta. However, the deep phylogeny of gastropods has been controversial for a long time. Especially the position of Patellogastropoda is a major uncertainty. Morphology and some mitochondria studies concluded that Patellogastropoda is likely to be sister to all other gastropods (Orthogastropoda hypothesis), while transcriptomic and other mitogenomic studies indicated that Patellogastropoda and Vetigastropoda are sister taxa (Psilogastropoda). With the release of high-quality genomes, orthologous genes can be better identified and serve as powerful candidates for phylogenetic analysis. The question is, given the current limitations on the taxon sampling side, how many markers are needed to provide robust results. Here, we identified single-copy orthologous genes (SOGs) from 14 gastropods species with whole genomes available which cover five main gastropod subclasses. We generated different datasets from 395 to 1610 SOGs by allowing species missing in different levels. We constructed gene trees of each SOG, and inferred species trees from different collections of gene trees. We found as the number of SOGs increased, the inferred topology changed from Patellogastropoda being sister to all other gastropods to Patellogastropoda being sister to Vetigastropoda + Neomphalina (Psilogastropoda s.l.), with considerable support. Our study thus rejects the Orthogastropoda concept showing that the selection of the representative species and use of sufficient informative sites greatly influence the analysis of deep gastropod phylogeny.}, } @article {pmid35501686, year = {2022}, author = {Liu, H and Zhao, W and Hua, W and Liu, J}, title = {A large-scale population based organelle pan-genomes construction and phylogeny analysis reveal the genetic diversity and the evolutionary origins of chloroplast and mitochondrion in Brassica napus L.}, journal = {BMC genomics}, volume = {23}, number = {1}, pages = {339}, pmid = {35501686}, issn = {1471-2164}, support = {31871664//National Natural Science Foundation of China/ ; CAAS-ZDRW2019003//Agricultural Science and Technology Innovation Program/ ; }, mesh = {Brassica/genetics ; *Brassica napus/genetics ; Brassica rapa/genetics ; Chloroplasts/genetics ; Genetic Variation ; *Genome, Chloroplast ; *Genome, Mitochondrial ; Genome, Plant ; Mitochondria/genetics ; Phylogeny ; }, abstract = {BACKGROUND: Allotetraploid oilseed rape (Brassica napus L.) is an important worldwide oil-producing crop. The origin of rapeseed is still undetermined due to the lack of wild resources. Despite certain genetic architecture and phylogenetic studies have been done focus on large group of Brassica nuclear genomes, the organelle genomes information under global pattern is largely unknown, which provide unique material for phylogenetic studies of B. napus. Here, based on de novo assemblies of 1,579 B. napus accessions collected globally, we constructed the chloroplast and mitochondrial pan-genomes of B. napus, and investigated the genetic diversity, phylogenetic relationships of B. napus, B. rapa and B. oleracea.

RESULTS: Based on mitotype-specific markers and mitotype-variant ORFs, four main cytoplasmic haplotypes were identified in our groups corresponding the nap, pol, ole, and cam mitotypes, among which the structure of chloroplast genomes was more conserved without any rearrangement than mitochondrial genomes. A total of 2,092 variants were detected in chloroplast genomes, whereas only 326 in mitochondrial genomes, indicating that chloroplast genomes exhibited a higher level of single-base polymorphism than mitochondrial genomes. Based on whole-genome variants diversity analysis, eleven genetic difference regions among different cytoplasmic haplotypes were identified on chloroplast genomes. The phylogenetic tree incorporating accessions of the B. rapa, B. oleracea, natural and synthetic populations of B. napus revealed multiple origins of B. napus cytoplasm. The cam-type and pol-type were both derived from B. rapa, while the ole-type was originated from B. oleracea. Notably, the nap-type cytoplasm was identified in both the B. rapa population and the synthetic B. napus, suggesting that B. rapa might be the maternal ancestor of nap-type B. napus.

CONCLUSIONS: The phylogenetic results provide novel insights into the organelle genomic evolution of Brassica species. The natural rapeseeds contained at least four cytoplastic haplotypes, of which the predominant nap-type might be originated from B. rapa. Besides, the organelle pan-genomes and the overall variation data offered useful resources for analysis of cytoplasmic inheritance related agronomical important traits of rapeseed, which can substantially facilitate the cultivation and improvement of rapeseed varieties.}, } @article {pmid35503755, year = {2022}, author = {Niu, Y and Lu, Y and Song, W and He, X and Liu, Z and Zheng, C and Wang, S and Shi, C and Liu, J}, title = {Assembly and comparative analysis of the complete mitochondrial genome of three Macadamia species (M. integrifolia, M. ternifolia and M. tetraphylla).}, journal = {PloS one}, volume = {17}, number = {5}, pages = {e0263545}, pmid = {35503755}, issn = {1932-6203}, mesh = {Genome Size ; *Genome, Chloroplast ; *Genome, Mitochondrial/genetics ; Genome, Plant ; Macadamia/genetics ; Phylogeny ; }, abstract = {BACKGROUND: Macadamia is a true dicotyledonous plant that thrives in a mild, humid, low wind environment. It is cultivated and traded internationally due to its high-quality nuts thus, has significant development prospects and scientific research value. However, information on the genetic resources of Macadamia spp. remains scanty.

RESULTS: The mitochondria (mt) genomes of three economically important Macadamia species, Macadamia integrifolia, M. ternifolia and M. tetraphylla, were assembled through the Illumina sequencing platform. The results showed that each species has 71 genes, including 42 protein-coding genes, 26 tRNAs, and 3 rRNAs. Repeated sequence analysis, RNA editing site prediction, and analysis of genes migrating from chloroplast (cp) to mt were performed in the mt genomes of the three Macadamia species. Phylogenetic analysis based on the mt genome of the three Macadamia species and 35 other species was conducted to reveal the evolution and taxonomic status of Macadamia. Furthermore, the characteristics of the plant mt genome, including genome size and GC content, were studied through comparison with 36 other plant species. The final non-synonymous (Ka) and synonymous (Ks) substitution analysis showed that most of the protein-coding genes in the mt genome underwent negative selections, indicating their importance in the mt genome.

CONCLUSION: The findings of this study provide a better understanding of the Macadamia genome and will inform future research on the genus.}, } @article {pmid35504558, year = {2022}, author = {Zhou, W and Zhao, Z and Yu, Z and Hou, Y and Keerthiga, R and Fu, A}, title = {Mitochondrial transplantation therapy inhibits the proliferation of malignant hepatocellular carcinoma and its mechanism.}, journal = {Mitochondrion}, volume = {65}, number = {}, pages = {11-22}, doi = {10.1016/j.mito.2022.04.004}, pmid = {35504558}, issn = {1872-8278}, mesh = {Animals ; Apoptosis ; *Carcinoma, Hepatocellular/metabolism/pathology/therapy ; Cell Line, Tumor ; Cell Proliferation ; Female ; *Liver Neoplasms/metabolism/pathology/therapy ; Male ; Mice ; Mitochondria/metabolism ; }, abstract = {Mitochondrial dysfunction plays a vital role in growth and malignancy of tumors. In recent scenarios, mitochondrial transplantation therapy is considered as an effective method to remodel mitochondrial function in mitochondria-related diseases. However, the mechanism by which mitochondrial transplantation blocks tumor cell proliferation is still not determined. In addition, mitochondria are maternal inheritance in evolution, and mitochondria obtained from genders exhibit differences in mitochondrial activity. Therefore, the study indicates the inhibitory effect of mitochondria from different genders on hepatocellular carcinoma and explores the molecular mechanism. The results reveal that the healthy mitochondria can retard the proliferation of the hepatocellular carcinoma cells in vitro and in vivo through arresting cell cycle and inducing apoptosis. The molecular mechanism suggests that mitochondrial transplantation therapy can decrease aerobic glycolysis, and down-regulate the expression of cycle-related proteins while up-regulate apoptosis-related proteins in tumor cells. In addition, the antitumor activity of mitochondria from female mice (F-Mito) is relatively higher than that of mitochondria from male mice (M-Mito), which would be related to the evidence that the F-Mito process higher activity than the M-Mito. This study clarifies the mechanism of exogenous mitochondria inhibiting the proliferation of hepatocellular carcinoma and contributes a new biotechnology for therapy of mitochondria-related diseases from different genders.}, } @article {pmid35508562, year = {2022}, author = {Kidd, KK and Evsanaa, B and Togtokh, A and Brissenden, JE and Roscoe, JM and Dogan, M and Neophytou, PI and Gurkan, C and Bulbul, O and Cherni, L and Speed, WC and Murtha, M and Kidd, JR and Pakstis, AJ}, title = {North Asian population relationships in a global context.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {7214}, pmid = {35508562}, issn = {2045-2322}, mesh = {*Asian People/genetics ; Ethnicity/genetics ; Genetic Variation ; *Genetics, Population ; Haplotypes ; Humans ; Phylogeny ; Principal Component Analysis ; }, abstract = {Population genetic studies of North Asian ethnic groups have focused on genetic variation of sex chromosomes and mitochondria. Studies of the extensive variation available from autosomal variation have appeared infrequently. We focus on relationships among population samples using new North Asia microhaplotype data. We combined genotypes from our laboratory on 58 microhaplotypes, distributed across 18 autosomes, on 3945 individuals from 75 populations with corresponding data extracted for 26 populations from the Thousand Genomes consortium and for 22 populations from the GenomeAsia 100 K project. A total of 7107 individuals in 122 total populations are analyzed using STRUCTURE, Principal Component Analysis, and phylogenetic tree analyses. North Asia populations sampled in Mongolia include: Buryats, Mongolians, Altai Kazakhs, and Tsaatans. Available Siberians include samples of Yakut, Khanty, and Komi Zyriane. Analyses of all 122 populations confirm many known relationships and show that most populations from North Asia form a cluster distinct from all other groups. Refinement of analyses on smaller subsets of populations reinforces the distinctiveness of North Asia and shows that the North Asia cluster identifies a region that is ancestral to Native Americans.}, } @article {pmid35543999, year = {2022}, author = {Corsaro, D}, title = {Insights into Microsporidia Evolution from Early Diverging Microsporidia.}, journal = {Experientia supplementum (2012)}, volume = {114}, number = {}, pages = {71-90}, pmid = {35543999}, issn = {1664-431X}, mesh = {Animals ; Fungi ; *Microsporidia/genetics ; *Parasites ; Phylogeny ; }, abstract = {Microsporidia have drastically modified genomes and cytology resulting from their high level of adaptation to intracytoplasmic parasitism. Their origins, which had long remained enigmatic, were placed within the line of Rozella, a primitive endoparasitic chytrid. These origins became more and more refined with the discovery of various parasites morphologically similar to the primitive lines of microsporidia (Metchnikovellids and Chytridiopsids) but which possess fungal-like genomes and functional mitochondria. These various parasites turn out to be distinct missing links between a large assemblage of chytrid-like rozellids and the true microsporidians, which are actually a very evolved branch of the rozellids themselves. The question of how to consider the historically known Microsporidia and the various microsporidia-like organisms within paraphyletic rozellids is discussed.}, } @article {pmid35547863, year = {2021}, author = {Benz, R}, title = {Historical Perspective of Pore-Forming Activity Studies of Voltage-Dependent Anion Channel (Eukaryotic or Mitochondrial Porin) Since Its Discovery in the 70th of the Last Century.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {734226}, pmid = {35547863}, issn = {1664-042X}, abstract = {Eukaryotic porin, also known as Voltage-Dependent Anion Channel (VDAC), is the most frequent protein in the outer membrane of mitochondria that are responsible for cellular respiration. Mitochondria are most likely descendants of strictly aerobic Gram-negative bacteria from the α-proteobacterial lineage. In accordance with the presumed ancestor, mitochondria are surrounded by two membranes. The mitochondrial outer membrane contains besides the eukaryotic porins responsible for its major permeability properties a variety of other not fully identified channels. It encloses also the TOM apparatus together with the sorting mechanism SAM, responsible for the uptake and assembly of many mitochondrial proteins that are encoded in the nucleus and synthesized in the cytoplasm at free ribosomes. The recognition and the study of electrophysiological properties of eukaryotic porin or VDAC started in the late seventies of the last century by a study of Schein et al., who reconstituted the pore from crude extracts of Paramecium mitochondria into planar lipid bilayer membranes. Whereas the literature about structure and function of eukaryotic porins was comparatively rare during the first 10years after the first study, the number of publications started to explode with the first sequencing of human Porin 31HL and the recognition of the important function of eukaryotic porins in mitochondrial metabolism. Many genomes contain more than one gene coding for homologs of eukaryotic porins. More than 100 sequences of eukaryotic porins are known to date. Although the sequence identity between them is relatively low, the polypeptide length and in particular, the electrophysiological characteristics are highly preserved. This means that all eukaryotic porins studied to date are anion selective in the open state. They are voltage-dependent and switch into cation-selective substates at voltages in the physiological relevant range. A major breakthrough was also the elucidation of the 3D structure of the eukaryotic pore, which is formed by 19 β-strands similar to those of bacterial porin channels. The function of the presumed gate an α-helical stretch of 20 amino acids allowed further studies with respect to voltage dependence and function, but its exact role in channel gating is still not fully understood.}, } @article {pmid35563133, year = {2022}, author = {Bonturi, CR and Silva Teixeira, AB and Rocha, VM and Valente, PF and Oliveira, JR and Filho, CMB and Fátima Correia Batista, I and Oliva, MLV}, title = {Plant Kunitz Inhibitors and Their Interaction with Proteases: Current and Potential Pharmacological Targets.}, journal = {International journal of molecular sciences}, volume = {23}, number = {9}, pages = {}, pmid = {35563133}, issn = {1422-0067}, support = {2017/06630-7 and 2019/22243-9//São Paulo Research Foundation/ ; Finance Code 001//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 301721/2016-5//National Council for Scientific and Technological Development/ ; }, mesh = {Endopeptidases ; Fungi/metabolism ; Humans ; *Plants/metabolism ; *Protease Inhibitors/chemistry/pharmacology/therapeutic use ; Serine Proteases/metabolism ; }, abstract = {The action of proteases can be controlled by several mechanisms, including regulation through gene expression; post-translational modifications, such as glycosylation; zymogen activation; targeting specific compartments, such as lysosomes and mitochondria; and blocking proteolysis using endogenous inhibitors. Protease inhibitors are important molecules to be explored for the control of proteolytic processes in organisms because of their ability to act on several proteases. In this context, plants synthesize numerous proteins that contribute to protection against attacks by microorganisms (fungi and bacteria) and/or invertebrates (insects and nematodes) through the inhibition of proteases in these organisms. These proteins are widely distributed in the plant kingdom, and are present in higher concentrations in legume seeds (compared to other organs and other botanical families), motivating studies on their inhibitory effects in various organisms, including humans. In most cases, the biological roles of these proteins have been assigned based mostly on their in vitro action, as is the case with enzyme inhibitors. This review highlights the structural evolution, function, and wide variety of effects of plant Kunitz protease inhibitors, and their potential for pharmaceutical application based on their interactions with different proteases.}, } @article {pmid35575078, year = {2022}, author = {Lee, J and Willett, CS}, title = {Frequent Paternal Mitochondrial Inheritance and Rapid Haplotype Frequency Shifts in Copepod Hybrids.}, journal = {The Journal of heredity}, volume = {113}, number = {2}, pages = {171-183}, doi = {10.1093/jhered/esab068}, pmid = {35575078}, issn = {1465-7333}, support = {IOS-1155325//National Science Foundation/ ; //University of North Carolina at Chapel Hill/ ; }, mesh = {Animals ; *Copepoda/genetics ; DNA, Mitochondrial/genetics ; Genes, Mitochondrial ; Haplotypes ; Mitochondria/genetics ; Phylogeny ; }, abstract = {Mitochondria are assumed to be maternally inherited in most animal species, and this foundational concept has fostered advances in phylogenetics, conservation, and population genetics. Like other animals, mitochondria were thought to be solely maternally inherited in the marine copepod Tigriopus californicus, which has served as a useful model for studying mitonuclear interactions, hybrid breakdown, and environmental tolerance. However, we present PCR, Sanger sequencing, and Illumina Nextera sequencing evidence that extensive paternal mitochondrial DNA (mtDNA) transmission is occurring in inter-population hybrids of T. californicus. PCR on four types of crosses between three populations (total sample size of 376 F1 individuals) with 20% genome-wide mitochondrial divergence showed 2% to 59% of F1 hybrids with both paternal and maternal mtDNA, where low and high paternal leakage values were found in different cross directions of the same population pairs. Sequencing methods further verified nucleotide similarities between F1 mtDNA and paternal mtDNA sequences. Interestingly, the paternal mtDNA in F1s from some crosses inherited haplotypes that were uncommon in the paternal population. Compared to some previous research on paternal leakage, we employed more rigorous methods to rule out contamination and false detection of paternal mtDNA due to non-functional nuclear mitochondrial DNA fragments. Our results raise the potential that other animal systems thought to only inherit maternal mitochondria may also have paternal leakage, which would then affect the interpretation of past and future population genetics or phylogenetic studies that rely on mitochondria as uniparental markers.}, } @article {pmid35577294, year = {2022}, author = {Xu, X and Yu, L and Li, F and Wang, B and Liu, F and Li, D}, title = {Phylogenetic placement and species delimitation of the crab spider genus Phrynarachne (Araneae: Thomisidae) from China.}, journal = {Molecular phylogenetics and evolution}, volume = {173}, number = {}, pages = {107521}, doi = {10.1016/j.ympev.2022.107521}, pmid = {35577294}, issn = {1095-9513}, mesh = {Animals ; China ; Mitochondria/genetics ; Phylogeny ; *Spiders/genetics ; }, abstract = {Evolutionary biologists have long been fascinated by the striking resemblance to bird droppings of the sit-and-wait crab spiders of the genus Phrynarachne. In doing so, species of Phrynarachne have evolved not to avoid detection, but rather, to cause predators to misidentify them as inedible and/or inanimate bird droppings. However, the lack of a phylogeny for Phrynarachne impedes our understanding of the evolution of this trait in the genus. Here we explore species boundaries in species of Phrynarachne from China using single- and multi-locus species delimitation approaches based on 30 Phrynarachne samples. All species delimitation approaches supported six species of Phrynarachne in China. We further present the first phylogenetic analysis of the genus Phrynarachne and estimate divergence times using two mitochondrial and three nuclear genes. All of our phylogenetic analyses supported the monophyly of Phrynarachne in China, with the genus still included within the higher 'Thomisus group' based on our results. Our dating analyses place the crown age of Phrynarachne in China to the middle Miocene. Taken together, our study provides a time-calibrated phylogeny of the genus Phrynarachne in China for testing hypotheses regarding the evolution of the lineage and bird dropping masquerade.}, } @article {pmid35577958, year = {2022}, author = {Bates, M and Keller-Findeisen, J and Przybylski, A and Hüper, A and Stephan, T and Ilgen, P and Cereceda Delgado, AR and D'Este, E and Egner, A and Jakobs, S and Sahl, SJ and Hell, SW}, title = {Optimal precision and accuracy in 4Pi-STORM using dynamic spline PSF models.}, journal = {Nature methods}, volume = {19}, number = {5}, pages = {603-612}, pmid = {35577958}, issn = {1548-7105}, mesh = {Animals ; Artifacts ; *Lenses ; Mammals ; Microscopy ; Optical Imaging ; *Single Molecule Imaging ; }, abstract = {Coherent fluorescence imaging with two objective lenses (4Pi detection) enables single-molecule localization microscopy with sub-10 nm spatial resolution in three dimensions. Despite its outstanding sensitivity, wider application of this technique has been hindered by complex instrumentation and the challenging nature of the data analysis. Here we report the development of a 4Pi-STORM microscope, which obtains optimal resolution and accuracy by modeling the 4Pi point spread function (PSF) dynamically while also using a simpler optical design. Dynamic spline PSF models incorporate fluctuations in the modulation phase of the experimentally determined PSF, capturing the temporal evolution of the optical system. Our method reaches the theoretical limits for precision and minimizes phase-wrapping artifacts by making full use of the information content of the data. 4Pi-STORM achieves a near-isotropic three-dimensional localization precision of 2-3 nm, and we demonstrate its capabilities by investigating protein and nucleic acid organization in primary neurons and mammalian mitochondria.}, } @article {pmid35580797, year = {2022}, author = {Sandamalika, WMG and Udayantha, HMV and Liyanage, DS and Lim, C and Kim, G and Kwon, H and Lee, J}, title = {Identification of reactive oxygen species modulator 1 (Romo 1) from black rockfish (Sebastes schlegelii) and deciphering its molecular characteristics, immune responses, oxidative stress modulation, and wound healing properties.}, journal = {Fish & shellfish immunology}, volume = {125}, number = {}, pages = {266-275}, doi = {10.1016/j.fsi.2022.05.026}, pmid = {35580797}, issn = {1095-9947}, mesh = {Amino Acid Sequence ; Animals ; *Bass ; DNA, Complementary/genetics ; Female ; Fish Proteins/chemistry ; Immunity, Innate/genetics ; Lipopolysaccharides/metabolism/pharmacology ; Male ; Mammals/genetics/metabolism ; Oxidative Stress ; *Perciformes ; Phylogeny ; Reactive Oxygen Species ; Sequence Alignment ; Wound Healing ; }, abstract = {Reactive oxygen species modulator 1 (Romo1) is a mitochondrial inner membrane protein that induces mitochondrial reactive oxygen species (ROS) generation. In this study, we identified the Romo1 homolog from the black rockfish (Sebastes schlegelii), named it as SsRomo1, and characterized it at the molecular as well as functional levels. An open reading frame consisting of 240 bp was identified in the SsRomo1 complementary DNA (cDNA) sequence that encodes a 79 amino acid-long polypeptide with a molecular weight of 8,293 Da and a theoretical isoelectric point (pI) of 9.89. The in silico analysis revealed the characteristic features of SsRomo1, namely the presence of a transmembrane domain and the lack of a signal peptide. Homology analysis revealed that SsRomo1 exhibits the highest sequence identity with its fish counterparts (>93%) and shares a similar percentage of sequence identity with mammals (>92%). Additionally, it is closely clustered together with the fish clade in the constructed phylogenetic tree. The subcellular localization analysis confirmed its mitochondrial localization within the fathead minnow (FHM) cells. Under normal physiological conditions, the SsRomo1 mRNA is highly expressed in the rockfish ovary, followed by the blood and testis, indicating the abundance of mitochondria in these tissues. Furthermore, the significant upregulation of SsRomo1 in cells treated with lipopolysachharide (LPS), polyinosinic:polycytidylic acid, and Streptococcus iniae suggest that the increased ROS production is induced by SsRomo1 to eliminate pathogens during infections. Incidentally, we believe that this study is the first to determine the involvement of SsRomo1 in LPS-mediated nitric oxide (NO) production in RAW267.4 cells, based on their higher NO production as compared to that in the control. Moreover, overexpression of SsRomo1 enhanced the wound healing ability of FHM cells, indicating its high invasion and migration properties. We also determined the hydrogen peroxide-mediated cell viability of SsRomo1-overexpressed FHM cells and observed a significant reduction in viability, which is possibly due to increased ROS production. Collectively, our observations suggest that SsRomo1 plays an important role in oxidative stress modulation upon immune stimulation and in maintenance of tissue homeostasis in black rockfish.}, } @article {pmid35580923, year = {2022}, author = {Maldonado, JA and Firneno, TJ and Hall, AS and Fujita, MK}, title = {Parthenogenesis doubles the rate of amino acid substitution in whiptail mitochondria.}, journal = {Evolution; international journal of organic evolution}, volume = {76}, number = {7}, pages = {1434-1442}, doi = {10.1111/evo.14509}, pmid = {35580923}, issn = {1558-5646}, mesh = {Amino Acid Substitution ; *Genome, Mitochondrial ; Humans ; Male ; Mitochondria/genetics ; Mutation ; Parthenogenesis/genetics ; Phylogeny ; *Reproduction, Asexual/genetics ; }, abstract = {Sexual reproduction is ubiquitous in the natural world, suggesting that sex must have extensive benefits to overcome the cost of males compared to asexual reproduction. One hypothesized advantage of sex with strong theoretical support is that sex plays a role in removing deleterious mutations from the genome. Theory predicts that transitions to asexuality should lead to the suppression of recombination and segregation and, in turn, weakened natural selection, allowing for the accumulation of slightly deleterious mutations. We tested this prediction by estimating the dN/dS ratios in asexual vertebrate lineages in the genus Aspidoscelis using whole mitochondrial genomes from seven asexual and five sexual species. We found higher dN/dS ratios in asexual Aspidoscelis species, indicating that asexual whiptails accumulate nonsynonymous substitutions due to weaker purifying selection. Additionally, we estimated nucleotide diversity and found that asexuals harbor significantly less diversity. Thus, despite their recent origins, slightly deleterious mutations accumulated rapidly enough in asexual lineages to be detected. We provide empirical evidence to corroborate the connection between asexuality and increased amino acid substitutions in asexual vertebrate lineages.}, } @article {pmid35584780, year = {2022}, author = {da Silva E Silva, LH and da Silva, FS and Medeiros, DBA and Cruz, ACR and da Silva, SP and Aragão, AO and Dias, DD and Sena do Nascimento, BL and Júnior, JWR and Vieira, DBR and Monteiro, HAO and Neto, JPN}, title = {Description of the mitogenome and phylogeny of Aedes spp. (Diptera: Culicidae) from the Amazon region.}, journal = {Acta tropica}, volume = {232}, number = {}, pages = {106500}, doi = {10.1016/j.actatropica.2022.106500}, pmid = {35584780}, issn = {1873-6254}, mesh = {*Aedes ; Animals ; *Culicidae/genetics ; *Genome, Mitochondrial/genetics ; Mosquito Vectors/genetics ; Phylogeny ; *Zika Virus/genetics ; *Zika Virus Infection ; }, abstract = {The genus Aedes (Diptera: Culicidae) includes species of great epidemiological relevance, particularly involved in transmission cycles of leading arboviruses in the Brazilian Amazon region, such as the Zika virus (ZIKV), Dengue virus (DENV), Yellow fever virus (YFV), and Chikungunya virus (CHIKV). We report here the first putatively complete sequencing of the mitochondrial genomes of Brazilian populations of the species Aedes albopictus, Aedes scapularis and Aedes serratus. The sequences obtained showed an average length of 14,947 bp, comprising 37 functional subunits, typical in animal mitochondria (13 PCGs, 22 tRNA, and 2 rRNA). The phylogeny reconstructed by Maximum likelihood method, based on the concatenated sequences of all 13 PCGs produced at least two non-directly related groupings, composed of representatives of the subgenus Ochlerotatus and Stegomyia of the genus Aedes. The data and information produced here may be useful for future taxonomic and evolutionary studies of the genus Aedes, as well as the Culicidae family.}, } @article {pmid35585601, year = {2022}, author = {Vujovic, F and Hunter, N and Farahani, RM}, title = {Notch ankyrin domain: evolutionary rise of a thermodynamic sensor.}, journal = {Cell communication and signaling : CCS}, volume = {20}, number = {1}, pages = {66}, pmid = {35585601}, issn = {1478-811X}, mesh = {Animals ; *Ankyrins/chemistry/metabolism ; Mice ; *Neural Stem Cells/chemistry/metabolism ; Phylogeny ; Protein Domains ; *Receptors, Notch/chemistry/metabolism ; Signal Transduction ; Thermodynamics ; }, abstract = {Notch signalling pathway plays a key role in metazoan biology by contributing to resolution of binary decisions in the life cycle of cells during development. Outcomes such as proliferation/differentiation dichotomy are resolved by transcriptional remodelling that follows a switch from Notch[on] to Notch[off] state, characterised by dissociation of Notch intracellular domain (NICD) from DNA-bound RBPJ. Here we provide evidence that transitioning to the Notch[off] state is regulated by heat flux, a phenomenon that aligns resolution of fate dichotomies to mitochondrial activity. A combination of phylogenetic analysis and computational biochemistry was utilised to disclose structural adaptations of Notch1 ankyrin domain that enabled function as a sensor of heat flux. We then employed DNA-based micro-thermography to measure heat flux during brain development, followed by analysis in vitro of the temperature-dependent behaviour of Notch1 in mouse neural progenitor cells. The structural capacity of NICD to operate as a thermodynamic sensor in metazoans stems from characteristic enrichment of charged acidic amino acids in β-hairpins of the ankyrin domain that amplify destabilising inter-residue electrostatic interactions and render the domain thermolabile. The instability emerges upon mitochondrial activity which raises the perinuclear and nuclear temperatures to 50 °C and 39 °C, respectively, leading to destabilization of Notch1 transcriptional complex and transitioning to the Notch[off] state. Notch1 functions a metazoan thermodynamic sensor that is switched on by intercellular contacts, inputs heat flux as a proxy for mitochondrial activity in the Notch[on] state via the ankyrin domain and is eventually switched off in a temperature-dependent manner. Video abstract.}, } @article {pmid35587988, year = {2022}, author = {Huynen, MA and Elurbe, DM}, title = {Mitochondrial complex complexification.}, journal = {Science (New York, N.Y.)}, volume = {376}, number = {6595}, pages = {794-795}, doi = {10.1126/science.abq0368}, pmid = {35587988}, issn = {1095-9203}, mesh = {*Electron Transport Complex I/chemistry/genetics ; *Electron Transport Complex IV/chemistry/genetics ; Evolution, Molecular ; *Mitochondria/enzymology ; Oxidative Phosphorylation ; Protein Subunits/chemistry/genetics ; *Tetrahymena thermophila/enzymology ; }, abstract = {Variation in complex composition provides clues about the function of individual subunits.}, } @article {pmid35588086, year = {2022}, author = {Santos, HJ and Nozaki, T}, title = {The mitosome of the anaerobic parasitic protist Entamoeba histolytica: A peculiar and minimalist mitochondrion-related organelle.}, journal = {The Journal of eukaryotic microbiology}, volume = {69}, number = {6}, pages = {e12923}, pmid = {35588086}, issn = {1550-7408}, support = {JP20fk0108138//Japan Agency for Medical Research and Development/ ; JP18H02650//Japan Society for the Promotion of Science/ ; JP20K16233//Japan Society for the Promotion of Science/ ; JP21H02723//Japan Society for the Promotion of Science/ ; JPJSCCB20190010//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; Anaerobiosis ; *Entamoeba histolytica/metabolism ; Membrane Proteins/metabolism ; *Mitochondria/metabolism ; *Organelles/metabolism ; }, abstract = {The simplest class of mitochondrion-related organelles (MROs) is the mitosome, an organelle present in a few anaerobic protozoan parasites such as Entamoeba histolytica, Giardia intestinalis, and Cryptosporidium parvum. E. histolytica causes amoebiasis in humans, deemed as one of the important, yet neglected tropical infections in the world. Much of the enigma of the E. histolytica mitosome circles around the obvious lack of a majority of known mitochondrial components and functions exhibited in other organisms. The identification of enzymes responsible for sulfate activation (AS, IPP, and APSK) and a number of lineage-specific proteins such as the outer membrane beta-barrel protein (MBOMP30), and transmembrane domain-containing proteins that bind to various organellar proteins (ETMP1, ETMP30, EHI_170120, and EHI_099350) showcased the remarkable divergence of this organelle compared to the other MROs of anaerobic protozoa. Here, we summarize the findings regarding the biology of the mitosomes in E. histolytica, from their discovery up to the present understanding of its roles and interactions. We also include current advances and future perspectives on the biology, biochemistry, and evolution of the mitosomes of E. histolytica.}, } @article {pmid35596716, year = {2022}, author = {Yu, G and Nakajima, K and Gruber, A and Rio Bartulos, C and Schober, AF and Lepetit, B and Yohannes, E and Matsuda, Y and Kroth, PG}, title = {Mitochondrial phosphoenolpyruvate carboxylase contributes to carbon fixation in the diatom Phaeodactylum tricornutum at low inorganic carbon concentrations.}, journal = {The New phytologist}, volume = {235}, number = {4}, pages = {1379-1393}, doi = {10.1111/nph.18268}, pmid = {35596716}, issn = {1469-8137}, mesh = {Bicarbonates/metabolism ; Carbon/metabolism ; Carbon Cycle ; Carbon Dioxide/metabolism/pharmacology ; *Diatoms/metabolism ; Mitochondria/metabolism ; Phosphoenolpyruvate Carboxylase/genetics/metabolism ; Photosynthesis ; }, abstract = {Photosynthetic carbon fixation is often limited by CO2 availability, which led to the evolution of CO2 concentrating mechanisms (CCMs). Some diatoms possess CCMs that employ biochemical fixation of bicarbonate, similar to C4 plants, but whether biochemical CCMs are commonly found in diatoms is a subject of debate. In the diatom Phaeodactylum tricornutum, phosphoenolpyruvate carboxylase (PEPC) is present in two isoforms, PEPC1 in the plastids and PEPC2 in the mitochondria. We used real-time quantitative polymerase chain reaction, Western blots, and enzymatic assays to examine PEPC expression and PEPC activity, under low and high concentrations of dissolved inorganic carbon (DIC). We generated and analyzed individual knockout cell lines of PEPC1 and PEPC2, as well as a PEPC1/2 double-knockout strain. While we could not detect an altered phenotype in the PEPC1 knockout strains at ambient, low or high DIC concentrations, PEPC2 and the double-knockout strains grown under ambient air or lower DIC availability conditions showed reduced growth and photosynthetic affinity for DIC while behaving similarly to wild-type (WT) cells at high DIC concentrations. These mutants furthermore exhibited significantly lower [13] C/[12] C ratios compared to the WT. Our data imply that in P. tricornutum at least parts of the CCM rely on biochemical bicarbonate fixation catalyzed by the mitochondrial PEPC2.}, } @article {pmid35609548, year = {2022}, author = {Schärer, L}, title = {Evolution: Mitochondrial lodgers can take over in hermaphroditic snails.}, journal = {Current biology : CB}, volume = {32}, number = {10}, pages = {R477-R479}, doi = {10.1016/j.cub.2022.04.039}, pmid = {35609548}, issn = {1879-0445}, mesh = {Animals ; Cytoplasm ; *Hermaphroditic Organisms ; *Mitochondria ; *Snails ; }, abstract = {Mitochondria - the cell's power stations - are inherited uniparentally via eggs, not sperm. In hermaphroditic plants, they sometimes prevent their hosts from making pollen (and sperm), causing cytoplasmic male sterility. New evidence from a hermaphroditic freshwater snail now documents cytoplasmic male sterility in animals.}, } @article {pmid35614856, year = {2022}, author = {Xu, JJ and Hu, M and Yang, L and Chen, XY}, title = {How plants synthesize coenzyme Q.}, journal = {Plant communications}, volume = {3}, number = {5}, pages = {100341}, pmid = {35614856}, issn = {2590-3462}, mesh = {Mitochondria/metabolism ; Oxidation-Reduction ; *Plants/genetics/metabolism ; *Ubiquinone/metabolism ; }, abstract = {Coenzyme Q (CoQ) is a conserved redox-active lipid that has a wide distribution across the domains of life. CoQ plays a key role in the oxidative electron transfer chain and serves as a crucial antioxidant in cellular membranes. Our understanding of CoQ biosynthesis in eukaryotes has come mostly from studies of yeast. Recently, significant advances have been made in understanding CoQ biosynthesis in plants. Unique mitochondrial flavin-dependent monooxygenase and benzenoid ring precursor biosynthetic pathways have been discovered, providing new insights into the diversity of CoQ biosynthetic pathways and the evolution of phototrophic eukaryotes. We summarize research progress on CoQ biosynthesis and regulation in plants and recent efforts to increase the CoQ content in plant foods.}, } @article {pmid35626633, year = {2022}, author = {Eyenga, P and Rey, B and Eyenga, L and Sheu, SS}, title = {Regulation of Oxidative Phosphorylation of Liver Mitochondria in Sepsis.}, journal = {Cells}, volume = {11}, number = {10}, pages = {}, pmid = {35626633}, issn = {2073-4409}, mesh = {Adenosine Triphosphate/metabolism ; Electron Transport Complex IV/metabolism ; Humans ; Mitochondria, Liver/metabolism ; *Oxidative Phosphorylation ; *Sepsis/metabolism ; }, abstract = {The link between liver dysfunction and decreased mitochondrial oxidative phosphorylation in sepsis has been clearly established in experimental models. Energy transduction is plastic: the efficiency of mitochondrial coupling collapses in the early stage of sepsis but is expected to increase during the recovery phases of sepsis. Among the mechanisms regulating the coupling efficiency of hepatic mitochondria, the slipping reactions at the cytochrome oxidase and ATP synthase seem to be a determining element, whereas other regulatory mechanisms such as those involving proton leakage across the mitochondrial membrane have not yet been formally proven in the context of sepsis. If the dysfunction of hepatic mitochondria is related to impaired cytochrome c oxidase and ATP synthase functions, we need to consider therapeutic avenues to restore their activities for recovery from sepsis. In this review, we discussed previous findings regarding the regulatory mechanism involved in changes in the oxidative phosphorylation of liver mitochondria in sepsis, and propose therapeutic avenues to improve the functions of cytochrome c oxidase and ATP synthase in sepsis.}, } @article {pmid35627195, year = {2022}, author = {Popadin, K and Gunbin, K and Peshkin, L and Annis, S and Fleischmann, Z and Franco, M and Kraytsberg, Y and Markuzon, N and Ackermann, RR and Khrapko, K}, title = {Mitochondrial Pseudogenes Suggest Repeated Inter-Species Hybridization among Direct Human Ancestors.}, journal = {Genes}, volume = {13}, number = {5}, pages = {}, pmid = {35627195}, issn = {2073-4425}, support = {R01 HD073104/HD/NICHD NIH HHS/United States ; R01 HD091439/HD/NICHD NIH HHS/United States ; R01-HD091439/NH/NIH HHS/United States ; }, mesh = {Animals ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; *Hominidae/genetics ; Humans ; Hybridization, Genetic ; Mitochondria/genetics ; *Pseudogenes/genetics ; }, abstract = {The hypothesis that the evolution of humans involves hybridization between diverged species has been actively debated in recent years. We present the following novel evidence in support of this hypothesis: the analysis of nuclear pseudogenes of mtDNA ("NUMTs"). NUMTs are considered "mtDNA fossils" as they preserve sequences of ancient mtDNA and thus carry unique information about ancestral populations. Our comparison of a NUMT sequence shared by humans, chimpanzees, and gorillas with their mtDNAs implies that, around the time of divergence between humans and chimpanzees, our evolutionary history involved the interbreeding of individuals whose mtDNA had diverged as much as ~4.5 Myr prior. This large divergence suggests a distant interspecies hybridization. Additionally, analysis of two other NUMTs suggests that such events occur repeatedly. Our findings suggest a complex pattern of speciation in primate/human ancestors and provide one potential explanation for the mosaic nature of fossil morphology found at the emergence of the hominin lineage. A preliminary version of this manuscript was uploaded to the preprint server BioRxiv in 2017 (10.1101/134502).}, } @article {pmid35630799, year = {2022}, author = {Xie, DM and Zhang, Q and Xin, LK and Wang, GK and Liu, CB and Qin, MJ}, title = {Cloning and Functional Characterization of Two Germacrene A Oxidases Isolated from Xanthium sibiricum.}, journal = {Molecules (Basel, Switzerland)}, volume = {27}, number = {10}, pages = {}, pmid = {35630799}, issn = {1420-3049}, support = {81503190//Dongmei Xie/ ; 2021hxts22//Dongmei Xie/ ; }, mesh = {Cloning, Molecular ; Oxidoreductases/metabolism ; Phylogeny ; Plant Proteins/metabolism ; Sesquiterpenes, Germacrane ; *Xanthium/genetics ; }, abstract = {Sesquiterpene lactones (STLs) from the cocklebur Xanthium sibiricum exhibit significant anti-tumor activity. Although germacrene A oxidase (GAO), which catalyzes the production of Germacrene A acid (GAA) from germacrene A, an important precursor of germacrene-type STLs, has been reported, the remaining GAOs corresponding to various STLs' biosynthesis pathways remain unidentified. In this study, 68,199 unigenes were studied in a de novo transcriptome assembly of X. sibiricum fruits. By comparison with previously published GAO sequences, two candidate X. sibiricum GAO gene sequences, XsGAO1 (1467 bp) and XsGAO2 (1527 bp), were identified, cloned, and predicted to encode 488 and 508 amino acids, respectively. Their protein structure, motifs, sequence similarity, and phylogenetic position were similar to those of other GAO proteins. They were most strongly expressed in fruits, according to a quantitative real-time polymerase chain reaction (qRT-PCR), and both XsGAO proteins were localized in the mitochondria of tobacco leaf epidermal cells. The two XsGAO genes were cloned into the expression vector for eukaryotic expression in Saccharomyces cerevisiae, and the enzyme reaction products were detected by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) methods. The results indicated that both XsGAO1 and XsGAO2 catalyzed the two-step conversion of germacrene A (GA) to GAA, meaning they are unlike classical GAO enzymes, which catalyze a three-step conversion of GA to GAA. This cloning and functional study of two GAO genes from X. sibiricum provides a useful basis for further elucidation of the STL biosynthesis pathway in X. sibiricum.}, } @article {pmid35633884, year = {2022}, author = {Zhang, L and Liu, K and Zhuan, Q and Liu, Z and Meng, L and Fu, X and Jia, G and Hou, Y}, title = {Mitochondrial Calcium Disorder Affects Early Embryonic Development in Mice through Regulating the ERK/MAPK Pathway.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {8221361}, pmid = {35633884}, issn = {1942-0994}, mesh = {Animals ; *Calcium/metabolism ; *Embryonic Development ; *MAP Kinase Signaling System ; Mice ; Mitochondria/metabolism ; *Mitogen-Activated Protein Kinases/metabolism ; Oocytes/metabolism ; }, abstract = {The homeostasis of mitochondrial calcium ([Ca[2+]]mt) in oocytes plays a critical role in maintaining normal reproductive cellular progress such as meiosis. However, little is known about the association between [Ca[2+]]mt homeostasis and early embryonic development. Two in vitro mouse MII oocyte models were established by using a specific agonist or inhibitor targeting mitochondrial calcium uniporters (MCU) to upregulate or downregulate [Ca[2+]]mt concentrations. The imbalance of [Ca[2+]]mt in MII oocytes causes mitochondrial dysfunction and morphological abnormity, leading to an abnormal spindle/chromosome structure. Oocytes in drug-treated groups are less likely to develop into blastocyst during in vitro culture. Abnormal [Ca[2+]]mt concentrations in oocytes hindered epigenetic modification and regulated mitogen-activated protein kinase (MAPK) signaling that is associated with gene expression. We also found that MAPK/ERK signaling is regulating DNA methylation in MII oocytes to modulate epigenetic modification. These data provide a new insight into the protective role of [Ca[2+]]mt homeostasis in early embryonic development and also demonstrate a new mechanism of MAPK signaling regulated by [Ca[2+]]mt that influences epigenetic modification.}, } @article {pmid35636077, year = {2022}, author = {Jiang, YJ and Jin, J and Nan, QY and Ding, J and Cui, S and Xuan, MY and Piao, MH and Piao, SG and Zheng, HL and Jin, JZ and Chung, BH and Yang, CW and Li, C}, title = {Coenzyme Q10 attenuates renal fibrosis by inhibiting RIP1-RIP3-MLKL-mediated necroinflammation via Wnt3α/β-catenin/GSK-3β signaling in unilateral ureteral obstruction.}, journal = {International immunopharmacology}, volume = {108}, number = {}, pages = {108868}, doi = {10.1016/j.intimp.2022.108868}, pmid = {35636077}, issn = {1878-1705}, mesh = {Animals ; Fibrosis ; Glycogen Synthase Kinase 3 beta ; Hydrogen Peroxide/pharmacology ; Intracellular Signaling Peptides and Proteins/metabolism ; Kidney/pathology ; *Kidney Diseases/drug therapy/pathology ; Protein Kinases/metabolism ; Rats ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Ubiquinone/analogs & derivatives ; *Ureteral Obstruction/drug therapy ; beta Catenin ; }, abstract = {OBJECTIVE: Coenzyme Q10 (CoQ10) protects against various types of injury, but its role in preventing renal scarring in chronic kidney disease remains an open question. Herein, we evaluated whether CoQ10 attenuates renal fibrosis by interfering with necroinflammation in a rat model of unilateral ureteral obstruction (UUO) and in vitro.

METHODS: Rats with UUO were treated daily with CoQ10 or an RIP inhibitor (necrostatin-1 or GSK872) for 7 days. The influence of CoQ10 on renal injury caused by UUO was evaluated by histopathology and analysis of gene expression, oxidative stress, intracellular organelles, apoptosis, and Wnt3α/β-catenin/GSK-3β signaling·H2O2-exposed human kidney (HK-2) cells were also examined after treatment with CoQ10 or an RIP inhibitor.

RESULTS: UUO induced marked renal tubular necrosis, upregulation of RIP1-RIP3-MLKL axis proteins, activation of the NLRP3 inflammasome, and evolution of renal fibrosis. UUO-induced oxidative stress evoked excessive endoplasmic reticulum stress and mitochondrial dysfunction, which triggered apoptotic cell death through Wnt3α/β-catenin/GSK-3β signaling. All of these effects were mitigated by CoQ10 or an RIP inhibitor. In H2O2-treated HK-2 cells, CoQ10 or an RIP inhibitor suppressed the expression of RIP1-RIP3-MLKL proteins and pyroptosis-related cytokines, and hindered the production of intracellular reactive oxygen species as shown by MitoSOX Red staining and apoptotic cell death but increased cell viability. The CoQ10 or Wnt/β-catenin inhibitor ICG-001 deactivated H2O2-stimulated activation of Wnt3α/β-catenin/GSK-3β signaling.

CONCLUSION: These findings suggest that CoQ10 attenuates renal fibrosis by inhibiting RIP1-RIP3-MLKL-mediated necroinflammation via Wnt3α/β-catenin/GSK-3β signaling in UUO.}, } @article {pmid35637201, year = {2022}, author = {Kodama, Y and Fujishima, M}, title = {Endosymbiotic Chlorella variabilis reduces mitochondrial number in the ciliate Paramecium bursaria.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {8216}, pmid = {35637201}, issn = {2045-2322}, mesh = {Antibodies, Monoclonal/metabolism ; *Chlorella/metabolism ; Mitochondria ; *Paramecium/metabolism ; Symbiosis ; }, abstract = {Extant symbioses illustrate endosymbiosis is a driving force for evolution and diversification. In the ciliate Paramecium bursaria, the endosymbiotic alga Chlorella variabilis in perialgal vacuole localizes beneath the host cell cortex by adhesion between the perialgal vacuole membrane and host mitochondria. We investigated whether host mitochondria are also affected by algal endosymbiosis. Transmission electron microscopy of host cells showed fewer mitochondria beneath the algae-bearing host cell cortex than that of alga-free cells. To compare the density and distribution of host mitochondria with or without symbiotic algae, we developed a monoclonal antibody against Paramecium mitochondria. Immunofluorescence microscopy with the monoclonal antibody showed that the mitochondrial density of the algae-bearing P. bursaria was significantly lower than that of the alga-free cells. The total cell protein concentration of alga-free P. bursaria cells was approximately 1.8-fold higher than that of algae-bearing cells, and the protein content of mitochondria was significantly higher in alga-free cells than that in the algae-bearing cells. These results corresponded with those obtained by transmission electron and immunofluorescence microscopies. This paper shows that endosymbiotic algae affect reduced mitochondrial number in the host P. bursaria significantly.}, } @article {pmid35638362, year = {2022}, author = {Li, M and Chen, WT and Zhang, QL and Liu, M and Xing, CW and Cao, Y and Luo, FZ and Yuan, ML}, title = {Mitochondrial phylogenomics provides insights into the phylogeny and evolution of spiders (Arthropoda: Araneae).}, journal = {Zoological research}, volume = {43}, number = {4}, pages = {566-584}, pmid = {35638362}, issn = {2095-8137}, mesh = {Animals ; *Arthropods ; *Genome, Mitochondrial/genetics ; Mitochondria/genetics ; Phylogeny ; RNA, Transfer/genetics ; *Spiders/genetics ; }, abstract = {Spiders are among the most varied terrestrial predators, with highly diverse morphology, ecology, and behavior. Morphological and molecular data have greatly contributed to advances in the phylogeny and evolutionary dynamics of spiders. Here, we performed comprehensive mitochondrial phylogenomics analysis on 78 mitochondrial genomes (mitogenomes) representing 29 families; of these, 23 species from eight families were newly generated. Mesothelae retained the same gene arrangement as the arthropod ancestor (Limulus polyphemus), while Opisthothelae showed extensive rearrangement, with 12 rearrangement types in transfer RNAs (tRNAs) and control region. Most spider tRNAs were extremely truncated and lacked typical dihydrouridine or TΨC arms, showing high tRNA structural diversity; in particular, trnS1 exhibited anticodon diversity across the phylogeny. The evolutionary rates of mitochondrial genes were potentially associated with gene rearrangement or truncated tRNAs. Both mitogenomic sequences and rearrangements possessed phylogenetic characteristics, providing a robust backbone for spider phylogeny, as previously reported. The monophyly of suborder, infraorder, retrolateral tibial apophysis clade, and families (except for Pisauridae) was separately supported, and high-level relationships were resolved as (Mesothelae, (Mygalomorphae, (Entelegynae, (Synspermiata, Hypochilidae)))). The phylogenetic positions of several families were also resolved (e.g., Eresidae, Oecobiidae and Titanoecidae). Two reconstructions of ancestral web type obtained almost identical results, indicating that the common ancestor of spiders likely foraged using a silk-lined burrow. This study, the largest mitochondrial phylogenomics analysis of spiders to date, highlights the usefulness of mitogenomic data not only for providing efficient phylogenetic signals for spider phylogeny, but also for characterizing trait diversification in spider evolution.}, } @article {pmid35639693, year = {2022}, author = {Calatrava, V and Stephens, TG and Gabr, A and Bhaya, D and Bhattacharya, D and Grossman, AR}, title = {Retrotransposition facilitated the establishment of a primary plastid in the thecate amoeba Paulinella.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {23}, pages = {e2121241119}, pmid = {35639693}, issn = {1091-6490}, mesh = {*Amoeba/genetics ; *Biological Evolution ; Eukaryota/genetics ; Plastids/genetics ; *Rhizaria ; *Symbiosis/genetics ; }, abstract = {The evolution of eukaryotic life was predicated on the development of organelles such as mitochondria and plastids. During this complex process of organellogenesis, the host cell and the engulfed prokaryote became genetically codependent, with the integration of genes from the endosymbiont into the host nuclear genome and subsequent gene loss from the endosymbiont. This process required that horizontally transferred genes become active and properly regulated despite inherent differences in genetic features between donor (endosymbiont) and recipient (host). Although this genetic reorganization is considered critical for early stages of organellogenesis, we have little knowledge about the mechanisms governing this process. The photosynthetic amoeba Paulinella micropora offers a unique opportunity to study early evolutionary events associated with organellogenesis and primary endosymbiosis. This amoeba harbors a “chromatophore,” a nascent photosynthetic organelle derived from a relatively recent cyanobacterial association (∼120 million years ago) that is independent of the evolution of primary plastids in plants (initiated ∼1.5 billion years ago). Analysis of the genome and transcriptome of Paulinella revealed that retrotransposition of endosymbiont-derived nuclear genes was critical for their domestication in the host. These retrocopied genes involved in photoprotection in cyanobacteria became expanded gene families and were “rewired,” acquiring light-responsive regulatory elements that function in the host. The establishment of host control of endosymbiont-derived genes likely enabled the cell to withstand photo-oxidative stress generated by oxygenic photosynthesis in the nascent organelle. These results provide insights into the genetic mechanisms and evolutionary pressures that facilitated the metabolic integration of the host–endosymbiont association and sustained the evolution of a photosynthetic organelle.}, } @article {pmid35642316, year = {2022}, author = {Bremer, N and Tria, FDK and Skejo, J and Garg, SG and Martin, WF}, title = {Ancestral State Reconstructions Trace Mitochondria But Not Phagocytosis to the Last Eukaryotic Common Ancestor.}, journal = {Genome biology and evolution}, volume = {14}, number = {6}, pages = {}, pmid = {35642316}, issn = {1759-6653}, support = {101018894/ERC_/European Research Council/International ; }, mesh = {Animals ; *Biological Evolution ; *Eukaryota/genetics ; Eukaryotic Cells/physiology ; Mitochondria/genetics ; Phagocytosis/physiology ; Phylogeny ; Symbiosis/genetics ; }, abstract = {Two main theories have been put forward to explain the origin of mitochondria in eukaryotes: phagotrophic engulfment (undigested food) and microbial symbiosis (physiological interactions). The two theories generate mutually exclusive predictions about the order in which mitochondria and phagocytosis arose. To discriminate the alternatives, we have employed ancestral state reconstructions (ASR) for phagocytosis as a trait, phagotrophy as a feeding habit, the presence of mitochondria, the presence of plastids, and the multinucleated organization across major eukaryotic lineages. To mitigate the bias introduced by assuming a particular eukaryotic phylogeny, we reconstructed the appearance of these traits across 1789 different rooted gene trees, each having species from opisthokonts, mycetozoa, hacrobia, excavate, archeplastida, and Stramenopiles, Alveolates and Rhizaria. The trees reflect conflicting relationships and different positions of the root. We employed a novel phylogenomic test that summarizes ASR across trees which reconstructs a last eukaryotic common ancestor that possessed mitochondria, was multinucleated, lacked plastids, and was non-phagotrophic as well as non-phagocytic. This indicates that both phagocytosis and phagotrophy arose subsequent to the origin of mitochondria, consistent with findings from comparative physiology. Furthermore, our ASRs uncovered multiple origins of phagocytosis and of phagotrophy across eukaryotes, indicating that, like wings in animals, these traits are useful but neither ancestral nor homologous across groups. The data indicate that mitochondria preceded the origin of phagocytosis, such that phagocytosis cannot have been the mechanism by which mitochondria were acquired.}, } @article {pmid35654156, year = {2022}, author = {Hautekiet, P and Saenen, ND and Aerts, R and Martens, DS and Roels, HA and Bijnens, EM and Nawrot, TS}, title = {Higher buccal mtDNA content is associated with residential surrounding green in a panel study of primary school children.}, journal = {Environmental research}, volume = {213}, number = {}, pages = {113551}, doi = {10.1016/j.envres.2022.113551}, pmid = {35654156}, issn = {1096-0953}, mesh = {Child ; *DNA, Mitochondrial/genetics ; Ethnicity ; Humans ; Mitochondria ; *Parks, Recreational ; Residence Characteristics ; Schools ; }, abstract = {BACKGROUND: Mitochondria are known to respond to environmental stressors but whether green space is associated with mitochondrial abundance is unexplored. Furthermore, as exposures may affect health from early life onwards, we here evaluate if residential green space is associated with mitochondria DNA content (mtDNAc) in children.

METHODS: In primary schoolchildren (COGNAC study), between 2012 and 2014, buccal mtDNAc was repeatedly (three times) assessed using qPCR. Surrounding low (<3m), high (≥3m) and total (sum of low and high) green space within different radii (100m-1000m) from the residence and distance to the nearest large green space (>0.5ha) were estimated using a remote sensing derived map. Given the repeated measures design, we applied a mixed-effects model with school and subject as random effect while adjusting for a priori chosen fixed covariates.

RESULTS: mtDNAc was assessed in 246 children with a total of 436 measurements (mean age 10.3 years). Within a 1000m radius around the residential address, an IQR increment in low (11.0%), high (9.5%), and total (13.9%) green space was associated with a respectively 15.2% (95% CI: 7.2%-23.7%), 10.8% (95% CI: 4.5%-17.5%), and 13.4% (95% CI: 7.4%-19.7%) higher mtDNAc. Conversely, an IQR increment (11.6%) in agricultural area in the same radius was associated with a -3.4% (95% CI: 6.7% to -0.1%) lower mtDNAc. Finally, a doubling in distance to large green space was associated with a -5.2% (95% CI: 7.9 to -2.4%) lower mtDNAc.

CONCLUSION: To our knowledge, this is the first study evaluating associations between residential surrounding green space and mtDNAc in children. Our results showed that green space was associated with a higher mtDNAc in children, which indicates the importance of the early life environment. To what extent these findings contribute to later life health effects should be further examined.}, } @article {pmid35661419, year = {2022}, author = {Dawson, NJ and Scott, GR}, title = {Adaptive increases in respiratory capacity and O2 affinity of subsarcolemmal mitochondria from skeletal muscle of high-altitude deer mice.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {36}, number = {7}, pages = {e22391}, doi = {10.1096/fj.202200219R}, pmid = {35661419}, issn = {1530-6860}, mesh = {*Altitude ; Animals ; Hypoxia ; Mitochondria ; Mitochondria, Muscle ; Muscle, Skeletal ; *Peromyscus/physiology ; }, abstract = {Aerobic energy demands have led to the evolution of complex mitochondrial reticula in highly oxidative muscles, but the extent to which metabolic challenges can be met with adaptive changes in physiology of specific mitochondrial fractions remains unresolved. We examined mitochondrial mechanisms supporting adaptive increases in aerobic performance in deer mice (Peromyscus maniculatus) adapted to the hypoxic environment at high altitude. High-altitude and low-altitude mice were born and raised in captivity, and exposed as adults to normoxia or hypobaric hypoxia (12 kPa O2 for 6-8 weeks). Subsarcolemmal and intermyofibrillar mitochondria were isolated from the gastrocnemius, and a comprehensive substrate titration protocol was used to examine mitochondrial physiology and O2 kinetics by high-resolution respirometry and fluorometry. High-altitude mice had greater yield, respiratory capacity for oxidative phosphorylation, and O2 affinity (lower P50) of subsarcolemmal mitochondria compared to low-altitude mice across environments, but there were no species difference in these traits in intermyofibrillar mitochondria. High-altitude mice also had greater capacities of complex II relative to complexes I + II and higher succinate dehydrogenase activities in both mitochondrial fractions. Exposure to chronic hypoxia reduced reactive oxygen species (ROS) emission in high-altitude mice but not in low-altitude mice. Our findings suggest that functional changes in subsarcolemmal mitochondria contribute to improving aerobic performance in hypoxia in high-altitude deer mice. Therefore, physiological variation in specific mitochondrial fractions can help overcome the metabolic challenges of life at high altitude.}, } @article {pmid35666201, year = {2022}, author = {Simon, M and Durand, S and Ricou, A and Vrielynck, N and Mayjonade, B and Gouzy, J and Boyer, R and Roux, F and Camilleri, C and Budar, F}, title = {APOK3, a pollen killer antidote in Arabidopsis thaliana.}, journal = {Genetics}, volume = {221}, number = {4}, pages = {}, pmid = {35666201}, issn = {1943-2631}, mesh = {Alleles ; Antidotes/metabolism ; *Arabidopsis/genetics/metabolism ; *Poisons/metabolism ; Pollen/genetics ; }, abstract = {The principles of heredity state that the two alleles carried by a heterozygote are equally transmitted to the progeny. However, genomic regions that escape this rule have been reported in many organisms. It is notably the case of genetic loci referred to as gamete killers, where one allele enhances its transmission by causing the death of the gametes that do not carry it. Gamete killers are of great interest, particularly to understand mechanisms of evolution and speciation. Although being common in plants, only a few, all in rice, have so far been deciphered to the causal genes. Here, we studied a pollen killer found in hybrids between two accessions of Arabidopsis thaliana. Exploring natural variation, we observed this pollen killer in many crosses within the species. Genetic analyses revealed that three genetically linked elements are necessary for pollen killer activity. Using mutants, we showed that this pollen killer works according to a poison-antidote model, where the poison kills pollen grains not producing the antidote. We identified the gene encoding the antidote, a chimeric protein addressed to mitochondria. De novo genomic sequencing in 12 natural variants with different behaviors regarding the pollen killer revealed a hyper variable locus, with important structural variations particularly in killer genotypes, where the antidote gene recently underwent duplications. Our results strongly suggest that the gene has newly evolved within A. thaliana. Finally, we identified in the protein sequence polymorphisms related to its antidote activity.}, } @article {pmid35670055, year = {2022}, author = {Choudhury, S and Ananthanarayanan, V and Ayappa, KG}, title = {Coupling of mitochondrial population evolution to microtubule dynamics in fission yeast cells: a kinetic Monte Carlo study.}, journal = {Soft matter}, volume = {18}, number = {23}, pages = {4483-4492}, doi = {10.1039/d2sm00155a}, pmid = {35670055}, issn = {1744-6848}, mesh = {Kinetics ; Microtubules/metabolism ; Mitochondria ; Monte Carlo Method ; *Schizosaccharomyces/genetics ; }, abstract = {Mitochondrial populations in cells are maintained by cycles of fission and fusion events. Perturbation of this balance has been observed in several diseases such as cancer and neurodegeneration. In fission yeast cells, the association of mitochondria with microtubules inhibits mitochondrial fission [Mehta et al., J. Biol. Chem., 2019, 294, 3385], illustrating the intricate coupling between mitochondria and the dynamic population of microtubules within the cell. In order to understand this coupling, we carried out kinetic Monte Carlo (KMC) simulations to predict the evolution of mitochondrial size distributions for different cases; wild-type cells, cells with short and long microtubules, and cells without microtubules. Comparisons are made with mitochondrial distributions reported in experiments with fission yeast cells. Using experimentally determined mitochondrial fission and fusion frequencies, simulations implemented without the coupling of microtubule dynamics predicted an increase in the mean number of mitochondria, equilibrating within 50 s. The mitochondrial length distribution in these models also showed a higher occurrence of shorter mitochondria, implying a greater tendency for fission, similar to the scenario observed in the absence of microtubules and cells with short microtubules. Interestingly, this resulted in overestimating the mean number of mitochondria and underestimating mitochondrial lengths in cells with wild-type and long microtubules. However, coupling mitochondria's fission and fusion events to the microtubule dynamics effectively captured the mitochondrial number and size distributions in wild-type and cells with long microtubules. Thus, the model provides greater physical insight into the temporal evolution of mitochondrial populations in different microtubule environments, allowing one to study both the short-time evolution as observed in the experiments (<5 minutes) as well as their transition towards a steady-state (>15 minutes). Our study illustrates the critical role of microtubules in mitochondrial dynamics and coupling microtubule growth and shrinkage dynamics is critical to predicting the evolution of mitochondrial populations within the cell.}, } @article {pmid35673874, year = {2022}, author = {Tassé, M and Choquette, T and Angers, A and Stewart, DT and Pante, E and Breton, S}, title = {The longest mitochondrial protein in metazoans is encoded by the male-transmitted mitogenome of the bivalve Scrobicularia plana.}, journal = {Biology letters}, volume = {18}, number = {6}, pages = {20220122}, pmid = {35673874}, issn = {1744-957X}, mesh = {Amino Acids/genetics/metabolism ; Animals ; *Bivalvia/genetics/metabolism ; Cyclooxygenase 2/genetics/metabolism ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial ; Male ; Mitochondrial Proteins/genetics ; }, abstract = {Cytochrome c oxidase subunit II (COX2) is one of the three mitochondrially encoded proteins of the complex IV of the respiratory chain that catalyses the reduction of oxygen to water. The cox2 gene spans about 690 base pairs in most animal species and produces a protein composed of approximately 230 amino acids. We discovered an extreme departure from this pattern in the male-transmitted mitogenome of the bivalve Scrobicularia plana with doubly uniparental inheritance (DUI) of mitochondrial DNA (mtDNA), which possesses an important in-frame insertion of approximately 4.8 kb in its cox2 gene. This feature-an enlarged male cox2 gene-is found in many species with DUI; the COX2 protein can be up to 420 amino acids long. Through RT-PCRs, immunoassays and comparative genetics, the evolution and functionality of this insertion in S. plana were characterized. The in-frame insertion is conserved among individuals from different populations and bears the signature of purifying selection seemingly indicating maintenance of functionality. Its transcription and translation were confirmed: this gene produces a polypeptide of 1892 amino acids, making it the largest metazoan COX2 protein known to date. We hypothesize that these extreme modifications in the COX2 protein affect the metabolism of mitochondria containing the male-transmitted mtDNA in Scrobicularia plana.}, } @article {pmid35682809, year = {2022}, author = {Eugenin, E and Camporesi, E and Peracchia, C}, title = {Direct Cell-Cell Communication via Membrane Pores, Gap Junction Channels, and Tunneling Nanotubes: Medical Relevance of Mitochondrial Exchange.}, journal = {International journal of molecular sciences}, volume = {23}, number = {11}, pages = {}, pmid = {35682809}, issn = {1422-0067}, support = {R01 MH128082/MH/NIMH NIH HHS/United States ; R01 NS105584/NS/NINDS NIH HHS/United States ; NS105584/NS/NINDS NIH HHS/United States ; MH128082/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Cell Communication/physiology ; Cell Membrane Structures ; *Gap Junctions/metabolism ; Ion Channels/metabolism ; Mitochondria ; *Nanotubes/chemistry ; }, abstract = {The history of direct cell-cell communication has evolved in several small steps. First discovered in the 1930s in invertebrate nervous systems, it was thought at first to be an exception to the "cell theory", restricted to invertebrates. Surprisingly, however, in the 1950s, electrical cell-cell communication was also reported in vertebrates. Once more, it was thought to be an exception restricted to excitable cells. In contrast, in the mid-1960s, two startling publications proved that virtually all cells freely exchange small neutral and charged molecules. Soon after, cell-cell communication by gap junction channels was reported. While gap junctions are the major means of cell-cell communication, in the early 1980s, evidence surfaced that some cells might also communicate via membrane pores. Questions were raised about the possible artifactual nature of the pores. However, early in this century, we learned that communication via membrane pores exists and plays a major role in medicine, as the structures involved, "tunneling nanotubes", can rescue diseased cells by directly transferring healthy mitochondria into compromised cells and tissues. On the other hand, pathogens/cancer could also use these communication systems to amplify pathogenesis. Here, we describe the evolution of the discovery of these new communication systems and the potential therapeutic impact on several uncurable diseases.}, } @article {pmid35682820, year = {2022}, author = {Cartalas, J and Coudray, L and Gobert, A}, title = {How RNases Shape Mitochondrial Transcriptomes.}, journal = {International journal of molecular sciences}, volume = {23}, number = {11}, pages = {}, pmid = {35682820}, issn = {1422-0067}, mesh = {Endoribonucleases/metabolism ; Eukaryota/genetics/metabolism ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/metabolism ; RNA/metabolism ; *Ribonucleases/metabolism ; *Transcriptome ; }, abstract = {Mitochondria are the power houses of eukaryote cells. These endosymbiotic organelles of prokaryote origin are considered as semi-autonomous since they have retained a genome and fully functional gene expression mechanisms. These pathways are particularly interesting because they combine features inherited from the bacterial ancestor of mitochondria with characteristics that appeared during eukaryote evolution. RNA biology is thus particularly diverse in mitochondria. It involves an unexpectedly vast array of factors, some of which being universal to all mitochondria and others being specific from specific eukaryote clades. Among them, ribonucleases are particularly prominent. They play pivotal functions such as the maturation of transcript ends, RNA degradation and surveillance functions that are required to attain the pool of mature RNAs required to synthesize essential mitochondrial proteins such as respiratory chain proteins. Beyond these functions, mitochondrial ribonucleases are also involved in the maintenance and replication of mitochondrial DNA, and even possibly in the biogenesis of mitochondrial ribosomes. The diversity of mitochondrial RNases is reviewed here, showing for instance how in some cases a bacterial-type enzyme was kept in some eukaryotes, while in other clades, eukaryote specific enzymes were recruited for the same function.}, } @article {pmid35683389, year = {2022}, author = {Ruiz, D and Santibañez, M and Lavín, BA and Berja, A and Montalban, C and Vazquez, LA}, title = {Evolution of Mitochondrially Derived Peptides Humanin and MOTSc, and Changes in Insulin Sensitivity during Early Gestation in Women with and without Gestational Diabetes.}, journal = {Journal of clinical medicine}, volume = {11}, number = {11}, pages = {}, pmid = {35683389}, issn = {2077-0383}, abstract = {Our purpose is to study the evolution of mitochondrially derived peptides (MDPs) and their relationship with changes in insulin sensitivity from the early stages of pregnancy in a cohort of pregnant women with and without gestational diabetes (GDM). MDPs (humanin and MOTSc) were assessed in the first and second trimesters of gestation in 28 pregnant women with gestational diabetes mellitus (GDM) and a subgroup of 45 pregnant women without GDM matched by BMI, age, previous gestations, and time of sampling. Insulin resistance (IR) was defined as a HOMA-IR index ≥70th percentile. We observed a significant reduction in both humanin and MOTSc levels from the first to the second trimesters of pregnancy. After adjusting for predefined variables, including BMI, statistically nonsignificant associations between lower levels of humanin and the occurrence of a high HOMA-IR index were obtained (adjusted OR = 2.63 and 3.14 for the first and second trimesters, linear p-trend 0.260 and 0.175, respectively). Regarding MOTSc, an association was found only for the second trimester: adjusted OR = 7.68 (95% CI 1.49-39.67), linear p-trend = 0.012. No significant associations were observed in humanin change with insulin resistance throughout pregnancy, but changes in MOTSc levels were significantly associated with HOMA-IR index: adjusted OR 3.73 (95% CI 1.03-13.50). In conclusion, MOTSc levels, especially a strong decrease from the first to second trimester of gestation, may be involved in increasing insulin resistance during early gestation.}, } @article {pmid35688936, year = {2022}, author = {Groux, K and Verschueren, A and Nanteau, C and Clémençon, M and Fink, M and Sahel, JA and Boccara, C and Paques, M and Reichman, S and Grieve, K}, title = {Dynamic full-field optical coherence tomography allows live imaging of retinal pigment epithelium stress model.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {575}, pmid = {35688936}, issn = {2399-3642}, mesh = {Animals ; Fluorescein Angiography ; Humans ; *Macular Degeneration/metabolism ; Mitochondria ; *Retinal Pigment Epithelium/metabolism ; Swine ; Tomography, Optical Coherence/methods ; }, abstract = {Retinal degenerative diseases lead to the blindness of millions of people around the world. In case of age-related macular degeneration (AMD), the atrophy of retinal pigment epithelium (RPE) precedes neural dystrophy. But as crucial as understanding both healthy and pathological RPE cell physiology is for those diseases, no current technique allows subcellular in vivo or in vitro live observation of this critical cell layer. To fill this gap, we propose dynamic full-field OCT (D-FFOCT) as a candidate for live observation of in vitro RPE phenotype. In this way, we monitored primary porcine and human stem cell-derived RPE cells in stress model conditions by performing scratch assays. In this study, we quantified wound healing parameters on the stressed RPE, and observed different cell phenotypes, displayed by the D-FFOCT signal. In order to decipher the subcellular contributions to these dynamic profiles, we performed immunohistochemistry to identify which organelles generate the signal and found mitochondria to be the main contributor to D-FFOCT contrast. Altogether, D-FFOCT appears to be an innovative method to follow degenerative disease evolution and could be an appreciated method in the future for live patient diagnostics and to direct treatment choice.}, } @article {pmid35695456, year = {2022}, author = {Jiang, X and Coroian, D and Barahona, E and Echavarri-Erasun, C and Castellanos-Rueda, R and Eseverri, Á and Aznar-Moreno, JA and Burén, S and Rubio, LM}, title = {Functional Nitrogenase Cofactor Maturase NifB in Mitochondria and Chloroplasts of Nicotiana benthamiana.}, journal = {mBio}, volume = {13}, number = {3}, pages = {e0026822}, pmid = {35695456}, issn = {2150-7511}, mesh = {*Archaeal Proteins/genetics ; *Azotobacter vinelandii/genetics ; Bacterial Proteins/metabolism ; Chloroplasts/genetics/metabolism ; Fertilizers ; Iron Compounds/*metabolism ; Mitochondria/metabolism ; Nitrogen/metabolism ; Nitrogen Fixation/genetics ; Nitrogenase/genetics/metabolism ; Phylogeny ; Nicotiana/genetics/metabolism ; }, abstract = {Engineering plants to synthesize nitrogenase and assimilate atmospheric N2 will reduce crop dependency on industrial N fertilizers. This technology can be achieved by expressing prokaryotic nitrogen fixation gene products for the assembly of a functional nitrogenase in plants. NifB is a critical nitrogenase component since it catalyzes the first committed step in the biosynthesis of all types of nitrogenase active-site cofactors. Here, we used a library of 30 distinct nifB sequences originating from different phyla and ecological niches to restore diazotrophic growth of an Azotobacter vinelandii nifB mutant. Twenty of these variants rescued the nifB mutant phenotype despite their phylogenetic distance to A. vinelandii. Because multiple protein interactions are required in the iron-molybdenum cofactor (FeMo-co) biosynthetic pathway, the maturation of nitrogenase in a heterologous host can be divided in independent modules containing interacting proteins that function together to produce a specific intermediate. Therefore, nifB functional modules composed of a nifB variant, together with the A. vinelandii NifS and NifU proteins (for biosynthesis of NifB [Fe4S4] clusters) and the FdxN ferredoxin (for NifB function), were expressed in Nicotiana benthamiana chloroplasts and mitochondria. Three archaeal NifB proteins accumulated at high levels in soluble fractions of chloroplasts (Methanosarcina acetivorans and Methanocaldococcus infernus) or mitochondria (M. infernus and Methanothermobacter thermautotrophicus). These NifB proteins were shown to accept [Fe4S4] clusters from NifU and were functional in FeMo-co synthesis in vitro. The accumulation of significant levels of soluble and functional NifB proteins in chloroplasts and mitochondria is critical to engineering biological nitrogen fixation in plants. IMPORTANCE Biological nitrogen fixation is the conversion of inert atmospheric dinitrogen gas into nitrogen-reactive ammonia, a reaction catalyzed by the nitrogenase enzyme of diazotrophic bacteria and archaea. Because plants cannot fix their own nitrogen, introducing functional nitrogenase in cereals and other crop plants would reduce our strong dependency on N fertilizers. NifB is required for the biosynthesis of the active site cofactors of all nitrogenases, which arguably makes it the most important protein in global nitrogen fixation. NifB functionality is therefore a requisite to engineer a plant nitrogenase. The expression of nifB genes from a wide range of prokaryotes into the model diazotroph Azotobacter vinelandii shows a surprising level of genetic complementation suggestive of plasticity in the nitrogenase biosynthetic pathway. In addition, we obtained NifB proteins from both mitochondria and chloroplasts of tobacco that are functional in vitro after reconstitution by providing [Fe4S4] clusters from NifU, paving the way to nitrogenase cofactor biosynthesis in plants.}, } @article {pmid35697683, year = {2022}, author = {Paredes, GF and Viehboeck, T and Markert, S and Mausz, MA and Sato, Y and Liebeke, M and König, L and Bulgheresi, S}, title = {Differential regulation of degradation and immune pathways underlies adaptation of the ectosymbiotic nematode Laxus oneistus to oxic-anoxic interfaces.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {9725}, pmid = {35697683}, issn = {2045-2322}, support = {DOC 69/FWF_/Austrian Science Fund FWF/Austria ; P 28743/FWF_/Austrian Science Fund FWF/Austria ; P28743-B22/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; Chromadorea ; *Chromatiaceae ; Hypoxia ; *Nematoda/microbiology ; Oxygen/metabolism ; Sand ; Sulfides ; Sulfur/metabolism ; }, abstract = {Eukaryotes may experience oxygen deprivation under both physiological and pathological conditions. Because oxygen shortage leads to a reduction in cellular energy production, all eukaryotes studied so far conserve energy by suppressing their metabolism. However, the molecular physiology of animals that naturally and repeatedly experience anoxia is underexplored. One such animal is the marine nematode Laxus oneistus. It thrives, invariably coated by its sulfur-oxidizing symbiont Candidatus Thiosymbion oneisti, in anoxic sulfidic or hypoxic sand. Here, transcriptomics and proteomics showed that, whether in anoxia or not, L. oneistus mostly expressed genes involved in ubiquitination, energy generation, oxidative stress response, immune response, development, and translation. Importantly, ubiquitination genes were also highly expressed when the nematode was subjected to anoxic sulfidic conditions, together with genes involved in autophagy, detoxification and ribosome biogenesis. We hypothesize that these degradation pathways were induced to recycle damaged cellular components (mitochondria) and misfolded proteins into nutrients. Remarkably, when L. oneistus was subjected to anoxic sulfidic conditions, lectin and mucin genes were also upregulated, potentially to promote the attachment of its thiotrophic symbiont. Furthermore, the nematode appeared to survive oxygen deprivation by using an alternative electron carrier (rhodoquinone) and acceptor (fumarate), to rewire the electron transfer chain. On the other hand, under hypoxia, genes involved in costly processes (e.g., amino acid biosynthesis, development, feeding, mating) were upregulated, together with the worm's Toll-like innate immunity pathway and several immune effectors (e.g., bactericidal/permeability-increasing proteins, fungicides). In conclusion, we hypothesize that, in anoxic sulfidic sand, L. oneistus upregulates degradation processes, rewires the oxidative phosphorylation and reinforces its coat of bacterial sulfur-oxidizers. In upper sand layers, instead, it appears to produce broad-range antimicrobials and to exploit oxygen for biosynthesis and development.}, } @article {pmid35699132, year = {2022}, author = {Brischigliaro, M and Cabrera-Orefice, A and Sturlese, M and Elurbe, DM and Frigo, E and Fernandez-Vizarra, E and Moro, S and Huynen, MA and Arnold, S and Viscomi, C and Zeviani, M}, title = {CG7630 is the Drosophila melanogaster homolog of the cytochrome c oxidase subunit COX7B.}, journal = {EMBO reports}, volume = {23}, number = {8}, pages = {e54825}, pmid = {35699132}, issn = {1469-3178}, mesh = {Amino Acid Sequence ; Animals ; *Drosophila melanogaster/genetics/metabolism ; *Electron Transport Complex IV/genetics/metabolism ; Mammals/metabolism ; Mitochondria/genetics/metabolism ; Proteomics ; }, abstract = {The mitochondrial respiratory chain (MRC) is composed of four multiheteromeric enzyme complexes. According to the endosymbiotic origin of mitochondria, eukaryotic MRC derives from ancestral proteobacterial respiratory structures consisting of a minimal set of complexes formed by a few subunits associated with redox prosthetic groups. These enzymes, which are the "core" redox centers of respiration, acquired additional subunits, and increased their complexity throughout evolution. Cytochrome c oxidase (COX), the terminal component of MRC, has a highly interspecific heterogeneous composition. Mammalian COX consists of 14 different polypeptides, of which COX7B is considered the evolutionarily youngest subunit. We applied proteomic, biochemical, and genetic approaches to investigate the COX composition in the invertebrate model Drosophila melanogaster. We identified and characterized a novel subunit which is widely different in amino acid sequence, but similar in secondary and tertiary structures to COX7B, and provided evidence that this object is in fact replacing the latter subunit in virtually all protostome invertebrates. These results demonstrate that although individual structures may differ the composition of COX is functionally conserved between vertebrate and invertebrate species.}, } @article {pmid35701688, year = {2022}, author = {Zheng, J and Zhao, L and Zhao, X and Gao, T and Song, N}, title = {High Genetic Connectivity Inferred from Whole-Genome Resequencing Provides Insight into the Phylogeographic Pattern of Larimichthys polyactis.}, journal = {Marine biotechnology (New York, N.Y.)}, volume = {24}, number = {4}, pages = {671-680}, pmid = {35701688}, issn = {1436-2236}, support = {2018YFD0900905//Key Technologies Research and Development Program/ ; 41806180//Innovative Research Group Project of the National Natural Science Foundation of China/ ; }, mesh = {Animals ; Fishes/genetics ; Gene Flow ; Microsatellite Repeats ; *Perciformes/genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Compared with terrestrial biota, marine fishes usually present lower genetic differentiation among different geographical populations because of high-level gene flow and lack of physical barriers. Understanding the genetic structure of marine fishes is essential for dividing management unit and making reasonable protection measures. The small yellow croaker (Larimichthys polyactis) belongs to the family Sciaenidae, which is an economic fish and widely distributed in the Western Pacific. To delineate genetic diversity and phylogeographic pattern, whole-genome resequencing was used to evaluate genetic connectivity, genetic diversity, and spatial pattern of L. polyactis for the first time. We obtained 6,645,711 high-quality single nucleotide polymorphisms (SNPs) markers from 40 L. polyactis individuals. The phylogenetic analysis, STRUCTURE, principal component analysis, and Fst results all indicated that no genetic structure consistent with the distribution pattern was found. This result revealed high genetic connectivity of L. polyactis in different sampling sites. High genetic diversity was also detected, indicating that there was sufficient evolutionary potential to maintain its effective population size. Besides, a similar result of high genetic connectivity and genetic diversity was also detected by mitochondria DNA marker. Our study demonstrated the persistence of high levels of genetic connectivity and a lack of population structure across L. polyactis in different sea areas. This study aimed to analyze the division of population structure and the reason for the decline and not exhaustion of L. polyactis resource on a genetic level.}, } @article {pmid35706021, year = {2022}, author = {Wu, B and Hao, W and Cox, MP}, title = {Reconstruction of gene innovation associated with major evolutionary transitions in the kingdom Fungi.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {144}, pmid = {35706021}, issn = {1741-7007}, mesh = {Animals ; *Evolution, Molecular ; *Fungi/genetics ; Gene Transfer, Horizontal ; Phylogeny ; Plants/genetics ; }, abstract = {BACKGROUND: Fungi exhibit astonishing diversity with multiple major phenotypic transitions over the kingdom's evolutionary history. As part of this process, fungi developed hyphae, adapted to land environments (terrestrialization), and innovated their sexual structures. These changes also helped fungi establish ecological relationships with other organisms (animals and plants), but the genomic basis of these changes remains largely unknown.

RESULTS: By systematically analyzing 304 genomes from all major fungal groups, together with a broad range of eukaryotic outgroups, we have identified 188 novel orthogroups associated with major changes during the evolution of fungi. Functional annotations suggest that many of these orthogroups were involved in the formation of key trait innovations in extant fungi and are functionally connected. These innovations include components for cell wall formation, functioning of the spindle pole body, polarisome formation, hyphal growth, and mating group signaling. Innovation of mitochondria-localized proteins occurred widely during fungal transitions, indicating their previously unrecognized importance. We also find that prokaryote-derived horizontal gene transfer provided a small source of evolutionary novelty with such genes involved in key metabolic pathways.

CONCLUSIONS: The overall picture is one of a relatively small number of novel genes appearing at major evolutionary transitions in the phylogeny of fungi, with most arising de novo and horizontal gene transfer providing only a small additional source of evolutionary novelty. Our findings contribute to an increasingly detailed portrait of the gene families that define fungal phyla and underpin core features of extant fungi.}, } @article {pmid35711783, year = {2022}, author = {Della Rocca, G and Papini, A and Posarelli, I and Barberini, S and Tani, C and Danti, R and Moricca, S}, title = {Ultrastructure of Terpene and Polyphenol Synthesis in the Bark of Cupressus sempervirens After Seiridium cardinale Infection.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {886331}, pmid = {35711783}, issn = {1664-302X}, abstract = {Cypress Canker Disease (CCD) pandemic caused by Seiridium cardinale is the major constraint of many Cupressaceae worldwide. One of the main symptoms of the disease is the flow of resin from the cankered barks. While inducible phloem axial resin duct-like structures (PARDs) have recently been characterized from an anatomical point of view, their actual resin production is still being debated and has never been demonstrated. Although the involvement of polyphenolic parenchyma cells (PP cells) in the bark of Cupressus sempervirens after S. cardinale infection was revealed in one of our previous studies using light microscopy, their evolution from the phloem parenchyma cells is yet to be clarified. This study investigated functional and ultrastructural aspects of both PARD-like structures and PP cells by means of more in-depth light (LM) and fluorescence microscopy (FM) combined with histochemical staining (using Sudan red, Fluorol Yellow, NADI Aniline blue black, and Toluidine blue staining), in addition to Transmission Electron Microscope (TEM). Two-year-old stem sections of a C. sempervirens canker-resistant clone (var. "Bolgheri"), artificially inoculated with S. cardinale, were sampled 5, 7, 14, 21, and 45 days after inoculation, for time-course observations. FM observation using Fluorol yellow dye clearly showed the presence of lipid material in PARD-like structures lining cells of the cavity and during their secretion into the duct space/cavity. The same tissues were also positive for NADI staining, revealing the presence of terpenoids. The cytoplasm of the ducts' lining cells was also positive for Sudan red. TEM observation highlighted the involvement of plastids and endoplasmic reticulum in the production of terpenoids and the consequent secretion of terpenoids directly through the plasma membrane, without exhibiting vesicle formation. The presence of a high number of mitochondria around the area of terpenoid production suggests that this process is active and consumes ATP. The LM observations showed that PP cells originated from the phloem parenchyma cells (and possibly albuminous cells) through the accumulation of phenolic substances in the vacuole. Here, plastids were again involved in their production. Thus, the findings of this work suggest that the PARD-like structures can actually be considered PARDs or even bark traumatic resin ducts (BTRD).}, } @article {pmid35730682, year = {2022}, author = {P, K and Chakraborty, B and Rani, V and Koner, AL}, title = {Rationally designed far-red emitting styryl chromones and a magnetic nanoconjugate for strip-based 'on-site' detection of metabolic markers.}, journal = {Journal of materials chemistry. B}, volume = {10}, number = {26}, pages = {5071-5085}, doi = {10.1039/d2tb00879c}, pmid = {35730682}, issn = {2050-7518}, mesh = {*Chromones ; Fluorescent Dyes/chemistry ; Molecular Docking Simulation ; *Nanoconjugates ; Serum Albumin ; Spectrometry, Fluorescence ; }, abstract = {The global burden of liver damage and renal failure necessitates technology-aided evolution towards point-of-care (POC) testing of metabolic markers. Hence in the prevalence of current health conditions, achieving on-site detection and quantifying serum albumin (SA) can contribute significantly to halting the increased mortality and morbidity rate. Herein, we have rationally designed and synthesized far-red emitting, solvatofluorochromic styryl chromone (SC) derivatives SC1 and SC2, and SC2-conjugated fluorescent magnetic nanoparticles (SCNPs) for sensing SA with a fluorogenic response via interacting at an atypical drug binding site. In solution, the highly sensitive and selective fluorogenic response was evaluated by the prominent amplification and blue-shift in the emission maxima of the probes from deep red to dark yellow through an intermediate orange emission. The transformation of the fluorogen into a fluorophore was manifested through spectroscopic measurements. The stabilization of the probes at protein pockets was ascribed to the non-covalent interactions, such as H-bonding, cation-π, and hydrophobic interactions, as unveiled by docking studies. The practical applications revealed the novelty of SC derivatives through (a) the capability to detect SA isolated from real blood samples via a turn-on fluorescence response; (b) the design of a simple, cheap, and portable test-strip using a glass-slide loaded with solid-state emissive SC2, which provided differential emission color of the SC2-HSA complex in solution and the solid-state with increasing concentration of HSA. Moreover, a smartphone-based color analysis application was employed to obtain the ratio of green and red (G/R) channels, which was utilized for quantitative detection of HSA; (c) the biocompatibility of the SC1 was ascertained through confocal laser scanning microscopic imaging (CLSM). Detailed investigation showed that SC1 could entirely localize in the mitochondria and evolve as a promising biomarker for distinguishing cancer cells from normal cells. Additionally, the validation of uncommon binding of SC1 and SC2 between domains I and III was determined using competition experiments with a known site-specific binder and molecular docking studies. This unique property of the probes can be further exploited to understand the cellular intake of HSA-drug complexes in the multifaceted biological system. These results find the utility of SC derivatives as small molecule-based chemosensors for at-home SA detection and as a biomarker for cancer.}, } @article {pmid35739999, year = {2022}, author = {Martínez-González, JJ and Guevara-Flores, A and Del Arenal Mena, IP}, title = {Evolutionary Adaptations of Parasitic Flatworms to Different Oxygen Tensions.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {6}, pages = {}, pmid = {35739999}, issn = {2076-3921}, support = {IN217920//Dirección General de Asuntos del Personal Académico (DGAPA),UNAM/ ; }, abstract = {During the evolution of the Earth, the increase in the atmospheric concentration of oxygen gave rise to the development of organisms with aerobic metabolism, which utilized this molecule as the ultimate electron acceptor, whereas other organisms maintained an anaerobic metabolism. Platyhelminthes exhibit both aerobic and anaerobic metabolism depending on the availability of oxygen in their environment and/or due to differential oxygen tensions during certain stages of their life cycle. As these organisms do not have a circulatory system, gas exchange occurs by the passive diffusion through their body wall. Consequently, the flatworms developed several adaptations related to the oxygen gradient that is established between the aerobic tegument and the cellular parenchyma that is mostly anaerobic. Because of the aerobic metabolism, hydrogen peroxide (H2O2) is produced in abundance. Catalase usually scavenges H2O2 in mammals; however, this enzyme is absent in parasitic platyhelminths. Thus, the architecture of the antioxidant systems is different, depending primarily on the superoxide dismutase, glutathione peroxidase, and peroxiredoxin enzymes represented mainly in the tegument. Here, we discuss the adaptations that parasitic flatworms have developed to be able to transit from the different metabolic conditions to those they are exposed to during their life cycle.}, } @article {pmid35741703, year = {2022}, author = {Orlova, VF and Solovyeva, EN and Dunayev, EA and Ananjeva, NB}, title = {Integrative Taxonomy within Eremias multiocellata Complex (Sauria, Lacertidae) from the Western Part of Range: Evidence from Historical DNA.}, journal = {Genes}, volume = {13}, number = {6}, pages = {}, pmid = {35741703}, issn = {2073-4425}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *Lizards/genetics ; Mitochondria/genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {The Kokshaal racerunner, Eremias kokshaaliensis Eremchenko et Panfilov, 1999, together with other central Asian racerunner species, is included in the Eremias multiocellata complex. In the present work, for the first time, the results of the analysis of historical mitochondrial DNA (barcode) are presented and the taxonomic status and preliminary phylogenetic relationships within the complex are specified. We present, for the first time, the results of the molecular analysis using historical DNA recovered from specimens of several species of this complex (paratypes of the Kokshaal racerunner and historical collections of the Kashgar racerunner E. buechneri from Kashgaria) using DNA barcoding.}, } @article {pmid35741788, year = {2022}, author = {Hawkins, MTR and Bailey, CA and Brown, AM and Tinsman, J and Hagenson, RA and Culligan, RR and Barela, AG and Randriamanana, JC and Ranaivoarisoa, JF and Zaonarivelo, JR and Louis, EE}, title = {Nuclear and Mitochondrial Phylogenomics of the Sifakas Reveal Cryptic Variation in the Diademed Sifaka.}, journal = {Genes}, volume = {13}, number = {6}, pages = {}, pmid = {35741788}, issn = {2073-4425}, mesh = {Animals ; Ecosystem ; Humans ; *Indriidae/classification ; Mitochondria ; Phylogeny ; Sea Urchins ; }, abstract = {The most comprehensive phylogenomic reconstruction to date was generated on all nominal taxa within the lemur genus Propithecus. Over 200 wild-caught individuals were included in this study to evaluate the intra and interspecific relationships across this genus. Ultraconserved Elements (UCEs) resulted in well-supported phylogenomic trees. Complete mitochondrial genomes (CMGs) largely agreed with the UCEs, except where a mitochondrial introgression was detected between one clade of the diademed sifaka (Propithecus diadema) and the Milne-Edwards sifaka (P. edwardsi). Additionally, the crowned (P. coronatus) and Von der Decken’s (P. deckeni) sifakas belonged to a single admixed lineage from UCEs. Further sampling across these two species is warranted to determine if our sampling represents a hybrid zone. P. diadema recovered two well-supported clades, which were dated and estimated as being ancient as the split between the Perrier’s (P. perrierii) and silky (P. candidus) sifakas. The reconstructed demographic history of the two clades also varied over time. We then modeled the modern ecological niches of the two cryptic P. diadema clades and found that they were significantly diverged (p < 0.01). These ecological differences result in a very limited zone of geographic overlap for the P. diadema clades (<60 km2). Niche models also revealed that the Onive River acts as a potential barrier to dispersal between P. diadema and P. edwardsi. Further taxonomic work is required on P. diadema to determine if its taxonomic status should be revised. This first genomic evaluation of the genus resolved the relationships between the taxa and the recovered cryptic diversity within one species.}, } @article {pmid35741832, year = {2022}, author = {Solana, JC and Chicharro, C and García, E and Aguado, B and Moreno, J and Requena, JM}, title = {Assembly of a Large Collection of Maxicircle Sequences and Their Usefulness for Leishmania Taxonomy and Strain Typing.}, journal = {Genes}, volume = {13}, number = {6}, pages = {}, pmid = {35741832}, issn = {2073-4425}, mesh = {*Genome, Mitochondrial ; Humans ; *Leishmania infantum/genetics ; *Leishmaniasis ; Phylogeny ; *Trypanosoma ; }, abstract = {Parasites of medical importance, such as Leishmania and Trypanosoma, are characterized by the presence of thousands of circular DNA molecules forming a structure known as kinetoplast, within the mitochondria. The maxicircles, which are equivalent to the mitochondrial genome in other eukaryotes, have been proposed as a promising phylogenetic marker. Using whole-DNA sequencing data, it is also possible to assemble maxicircle sequences as shown here and in previous works. In this study, based on data available in public databases and using a bioinformatics workflow previously reported by our group, we assembled the complete coding region of the maxicircles for 26 prototypical strains of trypanosomatid species. Phylogenetic analysis based on this dataset resulted in a robust tree showing an accurate taxonomy of kinetoplastids, which was also able to discern between closely related Leishmania species that are usually difficult to discriminate by classical methodologies. In addition, we provide a dataset of the maxicircle sequences of 60 Leishmania infantum field isolates from America, Western Europe, North Africa, and Eastern Europe. In agreement with previous studies, our data indicate that L. infantum parasites from Brazil are highly homogeneous and closely related to European strains, which were transferred there during the discovery of America. However, this study showed the existence of different L. infantum populations/clades within the Mediterranean region. A maxicircle signature for each clade has been established. Interestingly, two L. infantum clades were found coexisting in the same region of Spain, one similar to the American strains, represented by the Spanish JPCM5 reference strain, and the other, named "non-JPC like", may be related to an important leishmaniasis outbreak that occurred in Madrid a few years ago. In conclusion, the maxicircle sequence emerges as a robust molecular marker for phylogenetic analysis and species typing within the kinetoplastids, which also has the potential to discriminate intraspecific variability.}, } @article {pmid35743096, year = {2022}, author = {Ždralević, M and Giannattasio, S}, title = {Mitochondrial Research: Yeast and Human Cells as Models.}, journal = {International journal of molecular sciences}, volume = {23}, number = {12}, pages = {}, pmid = {35743096}, issn = {1422-0067}, mesh = {Humans ; *Mitochondria/metabolism ; Organelles/metabolism ; *Saccharomyces cerevisiae/metabolism ; }, abstract = {The evolution of complex eukaryotes would have been impossible without mitochondria, key cell organelles responsible for the oxidative metabolism of sugars and the bulk of ATP production [...].}, } @article {pmid35758251, year = {2022}, author = {Garrido, C and Wollman, FA and Lafontaine, I}, title = {The Evolutionary History of Peptidases Involved in the Processing of Organelle-Targeting Peptides.}, journal = {Genome biology and evolution}, volume = {14}, number = {7}, pages = {}, pmid = {35758251}, issn = {1759-6653}, mesh = {*Chloroplasts/genetics/metabolism ; Mitochondria/genetics/metabolism ; *Peptide Hydrolases/genetics/metabolism ; Peptides/genetics/metabolism ; Proteolysis ; }, abstract = {Most of the proteins present in mitochondria and chloroplasts, the organelles acquired via endosymbiotic events, are encoded in the nucleus and translated into the cytosol. Most of such nuclear-encoded proteins are specifically recognized via an N-terminal-encoded targeting peptide (TP) and imported into the organelles via a translocon machinery. Once imported, the TP is degraded by a succession of cleavage steps ensured by dedicated peptidases. Here, we retrace the evolution of the families of the mitochondrial processing peptidase (MPP), stromal processing peptidase (SPP), presequence protease (PreP), and organellar oligo-peptidase (OOP) that play a central role in TP processing and degradation across the tree of life. Their bacterial distributions are widespread but patchy, revealing unsurprisingly complex history of lateral transfers among bacteria. We provide evidence for the eukaryotic acquisition of MPP, OOP, and PreP by lateral gene transfers from bacteria at the time of the mitochondrial endosymbiosis. We show that the acquisition of SPP and of a second copy of OOP and PreP at the time of the chloroplast endosymbiosis was followed by a differential loss of one PreP paralog in photosynthetic eukaryotes. We identified some contrasting sequence conservations between bacterial and eukaryotic homologs that could reflect differences in the functional context of their peptidase activity. The close vicinity of the eukaryotic peptidases MPP and OOP to those of several bacterial pathogens, showing antimicrobial resistance, supports a scenario where such bacteria were instrumental in the establishment of the proteolytic pathway for TP degradation in organelles. The evidence for their role in the acquisition of PreP is weaker, and none is observed for SPP, although it cannot be excluded by the present study.}, } @article {pmid35764672, year = {2022}, author = {Jenkins, HL and Graham, R and Porter, JS and Vieira, LM and de Almeida, ACS and Hall, A and O'Dea, A and Coppard, SE and Waeschenbach, A}, title = {Unprecedented frequency of mitochondrial introns in colonial bilaterians.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {10889}, pmid = {35764672}, issn = {2045-2322}, mesh = {Animals ; *Gene Transfer, Horizontal ; Introns/genetics ; *Mitochondria/genetics ; Phylogeny ; RNA-Directed DNA Polymerase/genetics ; }, abstract = {Animal mitogenomes are typically devoid of introns. Here, we report the largest number of mitochondrial introns ever recorded from bilaterian animals. Mitochondrial introns were identified for the first time from the phylum Bryozoa. They were found in four species from three families (Order Cheilostomatida). A total of eight introns were found in the complete mitogenome of Exechonella vieirai, and five, 17 and 18 introns were found in the partial mitogenomes of Parantropora penelope, Discoporella cookae and Cupuladria biporosa, respectively. Intron-encoded protein domains reverse transcriptase and intron maturase (RVT-IM) were identified in all species. Introns in E. vieirai and P. penelope had conserved Group II intron ribozyme domains V and VI. Conserved domains were lacking from introns in D. cookae and C. biporosa, preventing their further categorization. Putative origins of metazoan introns were explored in a phylogenetic context, using an up-to-date alignment of mitochondrial RVT-IM domains. Results confirmed previous findings of multiple origins of annelid, placozoan and sponge RVT-IM domains and provided evidence for common intron donor sources across metazoan phyla. Our results corroborate growing evidence that some metazoans with regenerative abilities (i.e. placozoans, sponges, annelids and bryozoans) are susceptible to intron integration, most likely via horizontal gene transfer.}, } @article {pmid35764697, year = {2022}, author = {Anderson, L and Camus, MF and Monteith, KM and Salminen, TS and Vale, PF}, title = {Variation in mitochondrial DNA affects locomotor activity and sleep in Drosophila melanogaster.}, journal = {Heredity}, volume = {129}, number = {4}, pages = {225-232}, pmid = {35764697}, issn = {1365-2540}, mesh = {Adenosine Triphosphate/metabolism ; Animals ; *DNA, Mitochondrial/genetics ; Drosophila/genetics ; *Drosophila melanogaster/genetics ; Female ; Locomotion/genetics ; Male ; Mitochondria/genetics ; Sleep/genetics ; }, abstract = {Mitochondria are organelles that produce cellular energy in the form of ATP through oxidative phosphorylation, and this primary function is conserved among many taxa. Locomotion is a trait that is highly reliant on metabolic function and expected to be greatly affected by disruptions to mitochondrial performance. To this end, we aimed to examine how activity and sleep vary between Drosophila melanogaster strains with different geographic origins, how these patterns are affected by mitochondrial DNA (mtDNA) variation, and how breaking up co-evolved mito-nuclear gene combinations affect the studied activity traits. Our results demonstrate that Drosophila strains from different locations differ in sleep and activity, and that females are generally more active than males. By comparing activity and sleep of mtDNA variants introgressed onto a common nuclear background in cytoplasmic hybrid (cybrid) strains, we were able to quantify the among-line variance attributable to mitochondrial DNA, and we establish that mtDNA variation affects both activity and sleep, in a sex-specific manner. Altogether our study highlights the important role that mitochondrial genome variation plays on organismal physiology and behaviour.}, } @article {pmid35764832, year = {2022}, author = {Kurt, F and Kurt, B and Filiz, E and Yildiz, K and Akbudak, MA}, title = {Mitochondrial iron transporter (MIT) gene in potato (Solanum tuberosum): comparative bioinformatics, physiological and expression analyses in response to drought and salinity.}, journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine}, volume = {35}, number = {5}, pages = {875-887}, pmid = {35764832}, issn = {1572-8773}, mesh = {*Arabidopsis/genetics ; Computational Biology ; Droughts ; Gene Expression Regulation, Plant ; Iron/metabolism ; Membrane Transport Proteins/genetics ; Phylogeny ; Plant Proteins/genetics/metabolism ; Plants/metabolism ; Salinity ; *Solanum tuberosum/genetics/metabolism ; Stress, Physiological/genetics ; }, abstract = {Mitochondrial iron transporter (MIT) genes are essential for mitochondrial acquisition/import of iron and vital to proper functioning of mitochondria. Unlike other organisms, research on the MITs in plants is limited. The present study provides comparative bioinformatics assays for the potato MIT gene (StMIT) as well as gene expression analyses. The phylogenetic analyses revealed monocots-dicot divergence in MIT proteins and it was also found clade specific motif diversity. In addition, docking analyses indicated that Asp172 and Gly100 residues to be identified as the closest residues binding to ferrous iron. The percentage of structure overlap of the StMIT 3D protein model with Arabidopsis, maize and rice MIT proteins was found between 80.18% and 85.71%. The transcript analyses exhibited that the expression of StMIT was triggered under drought and salinity stresses. The findings of the present study would provide valuable leads for further studies targeting specifically the MIT gene and generally the plant iron metabolism.}, } @article {pmid35766356, year = {2022}, author = {Mondal, S and Kinatukara, P and Singh, S and Shambhavi, S and Patil, GS and Dubey, N and Singh, SH and Pal, B and Shekar, PC and Kamat, SS and Sankaranarayanan, R}, title = {DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35766356}, issn = {2050-084X}, support = {/WT_/Wellcome Trust/United Kingdom ; IA/I/15/2/502058/WTDBT_/DBT-Wellcome Trust India Alliance/India ; }, mesh = {Animals ; *Diglycerides/metabolism ; Homeostasis ; Lipid Metabolism ; Mice ; *Saccharomyces cerevisiae/genetics/metabolism ; Triglycerides/metabolism ; }, abstract = {Chain-length-specific subsets of diacylglycerol (DAG) lipids are proposed to regulate differential physiological responses ranging from signal transduction to modulation of the membrane properties. However, the mechanism or molecular players regulating the subsets of DAG species remain unknown. Here, we uncover the role of a conserved eukaryotic protein family, DISCO-interacting protein 2 (DIP2) as a homeostatic regulator of a chemically distinct subset of DAGs using yeast, fly, and mouse models. Genetic and chemical screens along with lipidomics analysis in yeast reveal that DIP2 prevents the toxic accumulation of specific DAGs in the logarithmic growth phase, which otherwise leads to endoplasmic reticulum stress. We also show that the fatty acyl-AMP ligase-like domains of DIP2 are essential for the redirection of the flux of DAG subspecies to storage lipid, triacylglycerols. DIP2 is associated with vacuoles through mitochondria-vacuole contact sites and such modulation of selective DAG abundance by DIP2 is found to be crucial for optimal vacuole membrane fusion and consequently osmoadaptation in yeast. Thus, the study illuminates an unprecedented DAG metabolism route and provides new insights on how cell fine-tunes DAG subspecies for cellular homeostasis and environmental adaptation.}, } @article {pmid35776057, year = {2022}, author = {Jardim-Messeder, D and Zamocky, M and Sachetto-Martins, G and Margis-Pinheiro, M}, title = {Chloroplastic ascorbate peroxidases targeted to stroma or thylakoid membrane: The chicken or egg dilemma.}, journal = {FEBS letters}, volume = {596}, number = {23}, pages = {2989-3004}, doi = {10.1002/1873-3468.14438}, pmid = {35776057}, issn = {1873-3468}, support = {304583/2018-9//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 421551/2018-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; E26/111.234/2014//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; VEGA 2/0012/22//Slovak Grant Agency/ ; APVV-20-0284//Slovak Research and Development Agency/ ; }, mesh = {Ascorbate Peroxidases/genetics/metabolism ; *Thylakoids/metabolism ; Phylogeny ; *Peroxidases/genetics/metabolism ; Chloroplasts/metabolism ; Hydrogen Peroxide/metabolism ; Antioxidants ; Gene Expression Regulation, Plant ; }, abstract = {Ascorbate peroxidases (APXs) are heme peroxidases that remove hydrogen peroxide in different subcellular compartments with concomitant ascorbate cycling. Here, we analysed and discussed phylogenetic and molecular features of the APX family. Ancient APX originated as a soluble stromal enzyme, and early during plant evolution, acquired both chloroplast-targeting and mitochondrion-targeting sequences and an alternative splicing mechanism whereby it could be expressed as a soluble or thylakoid membrane-bound enzyme. Later, independent duplication and neofunctionalization events in some angiosperm groups resulted in individual genes encoding stromal, thylakoidal and mitochondrial isoforms. These data reaffirm the complexity of plant antioxidant defenses that allow diverse plant species to acquire new means to adapt to changing environmental conditions.}, } @article {pmid35780856, year = {2022}, author = {Savu, DI and Moisoi, N}, title = {Mitochondria - Nucleus communication in neurodegenerative disease. Who talks first, who talks louder?.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1863}, number = {7}, pages = {148588}, doi = {10.1016/j.bbabio.2022.148588}, pmid = {35780856}, issn = {1879-2650}, mesh = {*Cell Communication ; Cell Nucleus/genetics ; DNA Damage ; Humans ; Mitochondria/metabolism ; *Neurodegenerative Diseases/metabolism ; }, abstract = {Mitochondria - nuclear coadaptation has been central to eukaryotic evolution. The dynamic dialogue between the two compartments within the context of multiorganellar interactions is critical for maintaining cellular homeostasis and directing the balance survival-death in case of cellular stress. The conceptualisation of mitochondria - nucleus communication has so far been focused on the communication from the mitochondria under stress to the nucleus and the consequent signalling responses, as well as from the nucleus to mitochondria in the context of DNA damage and repair. During ageing processes this dialogue may be better viewed as an integrated bidirectional 'talk' with feedback loops that expand beyond these two organelles depending on physiological cues. Here we explore the current views on mitochondria - nucleus dialogue and its role in maintaining cellular health with a focus on brain cells and neurodegenerative disease. Thus, we detail the transcriptional responses initiated by mitochondrial dysfunction in order to protect itself and the general cellular homeostasis. Additionally, we are reviewing the knowledge of the stress pathways initiated by DNA damage which affect mitochondria homeostasis and we add the information provided by the study of combined mitochondrial and genotoxic damage. Finally, we reflect on how each organelle may take the lead in this dialogue in an ageing context where both compartments undergo accumulation of stress and damage and where, perhaps, even the communications' mechanisms may suffer interruptions.}, } @article {pmid35792646, year = {2022}, author = {Gumińska, N and Milanowski, R}, title = {[Types of circular DNA in Eukarya].}, journal = {Postepy biochemii}, volume = {68}, number = {2}, pages = {129-141}, doi = {10.18388/pb.2021_423}, pmid = {35792646}, issn = {0032-5422}, mesh = {Cell Division ; Cytoplasm ; *DNA, Circular/genetics ; *Eukaryota/genetics ; Mitochondria ; }, abstract = {In eukaryotic cells, DNA occurs mainly in a linear chromosomes. In addition, it can also take the form of circular molecules. Mitochondrial and chloroplast genomes are the most thoroughly studied circular DNAs. However, the repertoire of circular DNA in Eukarya is much broader. It also includes extrachromosomal circular DNA (eccDNA): circular forms of rDNA, telomeric circles, small polydisperse DNA, microDNA, and other types of eccDNA of nuclear origin. The occurrence of eccDNA has been confirmed in all organisms tested so far. Previous studies have shown that some eccDNAs are present at every stage of the cell cycle, while others appear and/or accumulate under specific circumstances. It has been proven that eccDNA accumulation accompanies severe genome destabilization caused by malignancies or stress conditions. Despite growing interest in eccDNA, they remain a poorly understood component of eukaryotic genomes. Still little is known about the mechanisms of their formation, evolution and biological functions.}, } @article {pmid35808858, year = {2023}, author = {Cassidy-Hanley, DM and Doerder, FP and Hossain, M and Devine, C and Clark, T}, title = {Molecular identification of Tetrahymena species.}, journal = {The Journal of eukaryotic microbiology}, volume = {70}, number = {1}, pages = {e12936}, pmid = {35808858}, issn = {1550-7408}, support = {P40 OD010964/OD/NIH HHS/United States ; P40 RR019688/RR/NCRR NIH HHS/United States ; }, mesh = {*Tetrahymena/genetics ; Mitochondria/genetics ; DNA, Intergenic/genetics ; Phylogeny ; }, abstract = {Mitochondrial cox1 689 bp barcodes are routinely used for identification of Tetrahymena species. Here, we examine whether two shorter nuclear sequences, the 5.8S rRNA gene region and the intergenic region between H3 and H4 histone genes, might also be useful either singly or in combination with each other or cox1. We obtained sequences from ~300 wild isolates deposited at the Tetrahymena Stock Center and analyzed additional sequences obtained from GenBank. The 5.8S rRNA gene and portions of its transcribed flanks identify isolates as to their major clade and uniquely identify some, but not all, species. The ~330 bp H3/H4 intergenic region possesses low intraspecific variability and is unique for most species. However, it fails to distinguish between two pairs of common species and their rarer counterparts, and its use is complicated by the presence of duplicate genes in some species. The results show that while the cox1 sequence is the best single marker for Tetrahymena species identification, 5.8S rRNA, and the H3/H4 intergenic regions sequences are useful, singly or in combination, to confirm cox1 species assignments or as part of a preliminary survey of newly collected Tetrahymena. From our newly collected isolates, the results extend the biogeographical range of T. shanghaiensis and T. malaccensis and identify a new species, Tetrahymena arleneae n. sp. herein described.}, } @article {pmid35809880, year = {2022}, author = {Bononi, G and Masoni, S and Di Bussolo, V and Tuccinardi, T and Granchi, C and Minutolo, F}, title = {Historical perspective of tumor glycolysis: A century with Otto Warburg.}, journal = {Seminars in cancer biology}, volume = {86}, number = {Pt 2}, pages = {325-333}, doi = {10.1016/j.semcancer.2022.07.003}, pmid = {35809880}, issn = {1096-3650}, mesh = {Humans ; *Glycolysis ; *Neoplasms/pathology ; Mitochondria/metabolism ; Oxygen/metabolism ; Lactic Acid/metabolism ; }, abstract = {Tumors have long been known to rewire their metabolism to endorse their proliferation, growth, survival, and invasiveness. One of the common characteristics of these alterations is the enhanced glucose uptake and its subsequent transformation into lactic acid by means of glycolysis, regardless the availability of oxygen or the mitochondria effectiveness. This phenomenon is called the "Warburg effect", which has turned into a century of age now, since its first disclosure by German physiologist Otto Heinrich Warburg. Since then, this peculiar metabolic switch in tumors has been addressed by extensive studies covering several areas of research. In this historical perspective, we aim at illustrating the evolution of these studies over time and their implication in various fields of science.}, } @article {pmid35836411, year = {2022}, author = {Shen, LL and Waheed, A and Wang, YP and Nkurikiyimfura, O and Wang, ZH and Yang, LN and Zhan, J}, title = {Mitochondrial Genome Contributes to the Thermal Adaptation of the Oomycete Phytophthora infestans.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {928464}, pmid = {35836411}, issn = {1664-302X}, abstract = {As a vital element of climate change, elevated temperatures resulting from global warming present new challenges to natural and agricultural sustainability, such as ecological disease management. Mitochondria regulate the energy production of cells in responding to environmental fluctuation, but studying their contribution to the thermal adaptation of species is limited. This knowledge is needed to predict future disease epidemiology for ecology conservation and food security. Spatial distributions of the mitochondrial genome (mtDNA) in 405 Phytophthora infestans isolates originating from 15 locations were characterized. The contribution of MtDNA to thermal adaptation was evaluated by comparative analysis of mtDNA frequency and intrinsic growth rate, relative population differentiation in nuclear and mtDNA, and associations of mtDNA distribution with local geography climate conditions. Significant variation in frequency, intrinsic growth rate, and spatial distribution was detected in mtDNA. Population differentiation in mtDNA was significantly higher than that in the nuclear genome, and spatial distribution of mtDNA was strongly associated with local climatic conditions and geographic parameters, particularly air temperature, suggesting natural selection caused by a local temperature is the main driver of the adaptation. Dominant mtDNA grew faster than the less frequent mtDNA. Our results provide useful insights into the evolution of pathogens under global warming. Given its important role in biological functions and adaptation to local air temperature, mtDNA intervention has become an increasing necessity for future disease management. To secure ecological integrity and food production under global warming, a synergistic study on the interactive effect of changing temperature on various components of biological and ecological functions of mitochondria in an evolutionary frame is urgently needed.}, } @article {pmid35842180, year = {2022}, author = {Biró, B and Gál, Z and Schiavo, G and Ribari, A and Joe Utzeri, V and Brookman, M and Fontanesi, L and Hoffmann, OI}, title = {Nuclear mitochondrial DNA sequences in the rabbit genome.}, journal = {Mitochondrion}, volume = {66}, number = {}, pages = {1-6}, doi = {10.1016/j.mito.2022.07.003}, pmid = {35842180}, issn = {1872-8278}, mesh = {Animals ; Cell Nucleus/genetics ; *DNA, Mitochondrial/chemistry/genetics ; Genome ; *Genome, Mitochondrial ; Mammals/genetics ; Mitochondria/genetics ; Phylogeny ; Rabbits ; Sequence Analysis, DNA ; }, abstract = {Numtogenesis is observable in the mammalian genomes resulting in the integration of mitochondrial segments into the nuclear genomes (numts). To identify numts in rabbit, we aligned mitochondrial and nuclear genomes. Alignment significance threshold was calculated and individual characteristics of numts were analysed. We found 153 numts in the nuclear genome. The GC content of numts were significantly lower than the GC content of their genomic flanking regions or the genome itself. The frequency of three mammalian-wide interspersed repeats were increased in the proximity of numts. The decreased GC content around numts strengthen the theory which supposes a link between DNA structural instability and numt integration.}, } @article {pmid35850262, year = {2022}, author = {Rottenberg, H}, title = {The accelerated evolution of human cytochrome c oxidase - Selection for reduced rate and proton pumping efficiency?.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1863}, number = {8}, pages = {148595}, doi = {10.1016/j.bbabio.2022.148595}, pmid = {35850262}, issn = {1879-2650}, mesh = {Adenosine Triphosphate ; Animals ; Cattle ; Cytochromes c ; DNA, Mitochondrial ; *Electron Transport Complex IV/genetics/metabolism ; Haplorhini/metabolism ; Humans ; Mammals/metabolism ; Mice ; Oxidoreductases ; Oxygen ; Primates/genetics/metabolism ; *Proton Pumps/genetics ; Protons ; Superoxides ; }, abstract = {The cytochrome c oxidase complex, complex VI (CIV), catalyzes the terminal step of the mitochondrial electron transport chain where the reduction of oxygen to water by cytochrome c is coupled to the generation of a protonmotive force that drive the synthesis of ATP. CIV evolution was greatly accelerated in humans and other anthropoid primates and appears to be driven by adaptive selection. However, it is not known if there are significant functional differences between the anthropoid primates CIV, and other mammals. Comparison of the high-resolution structures of bovine CIV, mouse CIV and human CIV shows structural differences that are associated with anthropoid-specific substitutions. Here I examine the possible effects of these substitutions in four CIV peptides that are known to affect proton pumping: the mtDNA-coded subunits I, II and III, and the nuclear-encoded subunit VIa2. I conclude that many of the anthropoid-specific substitutions could be expected to modulate the rate and/or the efficiency of proton pumping. These results are compatible with the previously proposed hypothesis that the accelerated evolution of CIV in anthropoid primates is driven by selection pressure to lower the mitochondrial protonmotive force and thus decrease the rate of superoxide generation by mitochondria.}, } @article {pmid35856299, year = {2022}, author = {Carter, CS and Kingsbury, MA}, title = {Oxytocin and oxygen: the evolution of a solution to the 'stress of life'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {377}, number = {1858}, pages = {20210054}, pmid = {35856299}, issn = {1471-2970}, support = {R01 HD098117/HD/NICHD NIH HHS/United States ; R21 HD098603/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Hypothalamo-Hypophyseal System ; Inflammation ; Mammals/metabolism ; Oxygen ; *Oxytocin ; Pituitary-Adrenal System ; Receptors, Oxytocin/metabolism ; }, abstract = {Oxytocin (OT) and the OT receptor occupy essential roles in our current understanding of mammalian evolution, survival, sociality and reproduction. This narrative review examines the hypothesis that many functions attributed to OT can be traced back to conditions on early Earth, including challenges associated with managing life in the presence of oxygen and other basic elements, including sulfur. OT regulates oxidative stress and inflammation especially through effects on the mitochondria. A related nonapeptide, vasopressin, as well as molecules in the hypothalamic-pituitary-adrenal axis, including the corticotropin-releasing hormone family of molecules, have a broad set of functions that interact with OT. Interactions among these molecules have roles in the causes and consequence of social behaviour and the management of threat, fear and stress. Here, we discuss emerging evidence suggesting that unique properties of the OT system allowed vertebrates, and especially mammals, to manage over-reactivity to the 'side effects' of oxygen, including inflammation, oxidation and free radicals, while also supporting high levels of sociality and a perception of safety. This article is part of the theme issue 'Interplays between oxytocin and other neuromodulators in shaping complex social behaviours'.}, } @article {pmid35858057, year = {2022}, author = {Brzęk, P and Roussel, D and Konarzewski, M}, title = {Mice selected for a high basal metabolic rate evolved larger guts but not more efficient mitochondria.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1978}, pages = {20220719}, pmid = {35858057}, issn = {1471-2954}, mesh = {Animals ; *Basal Metabolism ; Mice ; *Mitochondria ; Organ Size ; }, abstract = {Intra-specific variation in both the basal metabolic rate (BMR) and mitochondrial efficiency (the amount of ATP produced per unit of oxygen consumed) has profound evolutionary and ecological consequences. However, the functional mechanisms responsible for this variation are not fully understood. Mitochondrial efficiency is negatively correlated with BMR at the interspecific level but it is positively correlated with performance capacity at the intra-specific level. This discrepancy is surprising, as theories explaining the evolution of endothermy assume a positive correlation between BMR and performance capacity. Here, we quantified mitochondrial oxidative phosphorylation activity and efficiency in two lines of laboratory mice divergently selected for either high (H-BMR) or low (L-BMR) levels of BMR. H-BMR mice had larger livers and kidneys (organs that are important predictors of BMR). H-BMR mice also showed higher oxidative phosphorylation activity in liver mitochondria but this difference can be hypothesized to be a direct effect of selection only if the heritability of this trait is low. However, mitochondrial efficiency in all studied organs did not differ between the two lines. We conclude that the rapid evolution of BMR can reflect changes in organ size rather than mitochondrial properties, and does not need to be accompanied obligatorily by changes in mitochondrial efficiency.}, } @article {pmid35860045, year = {2022}, author = {Jamaludin, NA and Jamaluddin, JAF and Rahim, MA and Mohammed Akib, NA and Ratmuangkhwang, S and Mohd Arshaad, W and Mohd Nor, SA}, title = {Mitochondrial marker implies fishery separate management units for spotted sardinella, Amblygaster sirm (Walbaum, 1792) populations in the South China Sea and the Andaman Sea.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e13706}, pmid = {35860045}, issn = {2167-8359}, mesh = {Animals ; Phylogeny ; *Fisheries ; *Conservation of Natural Resources ; Mitochondria/genetics ; Fishes/genetics ; China ; }, abstract = {The spotted sardinella, Amblygaster sirm (Walbaum, 1792), is a commercial sardine commonly caught in Malaysia. Lack of management of these marine species in Malaysian waters could lead to overfishing and potentially declining fish stock populations. Therefore, sustainable management of this species is of paramount importance to ensure its longevity. As such, molecular information is vital in determining the A. sirm population structure and management strategy. In the present study, mitochondrial DNA Cytochrome b was sequenced from 10 A. sirm populations: the Andaman Sea (AS) (two), South China Sea (SCS) (six), Sulu Sea (SS) (one), and Celebes Sea (CS) (one). Accordingly, the intra-population haplotype diversity (Hd) was high (0.91-1.00), and nucleotide diversity (π) was low (0.002-0.009), which suggests a population bottleneck followed by rapid population growth. Based on the phylogenetic trees, minimum spanning network (MSN), population pairwise comparison, and F ST,and supported by analysis of molecular variance (AMOVA) and spatial analysis of molecular variance (SAMOVA) tests, distinct genetic structures were observed (7.2% to 7.6% genetic divergence) between populations in the SCS and its neighboring waters, versus those in the AS. Furthermore, the results defined A. sirm stock boundaries and evolutionary between the west and east coast (which shares the same waters as western Borneo) of Peninsular Malaysia. In addition, genetic homogeneity was revealed throughout the SCS, SS, and CS based on the non-significant F STpairwise comparisons. Based on the molecular evidence, separate management strategies may be required for A. sirm of the AS and the SCS, including its neighboring waters.}, } @article {pmid35862496, year = {2022}, author = {Cadart, C and Heald, R}, title = {Scaling of biosynthesis and metabolism with cell size.}, journal = {Molecular biology of the cell}, volume = {33}, number = {9}, pages = {}, pmid = {35862496}, issn = {1939-4586}, support = {R35 GM118183/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Cell Size ; Humans ; Mitochondria ; *Ploidies ; *Polyploidy ; }, abstract = {Cells adopt a size that is optimal for their function, and pushing them beyond this limit can cause cell aging and death by senescence or reduce proliferative potential. However, by increasing their genome copy number (ploidy), cells can increase their size dramatically and homeostatically maintain physiological properties such as biosynthesis rate. Recent studies investigating the relationship between cell size and rates of biosynthesis and metabolism under normal, polyploid, and pathological conditions are revealing new insights into how cells attain the best function or fitness for their size by tuning processes including transcription, translation, and mitochondrial respiration. A new frontier is to connect single-cell scaling relationships with tissue and whole-organism physiology, which promises to reveal molecular and evolutionary principles underlying the astonishing diversity of size observed across the tree of life.}, } @article {pmid35866365, year = {2022}, author = {McCall, CE and Zhu, X and Zabalawi, M and Long, D and Quinn, MA and Yoza, BK and Stacpoole, PW and Vachharajani, V}, title = {Sepsis, pyruvate, and mitochondria energy supply chain shortage.}, journal = {Journal of leukocyte biology}, volume = {112}, number = {6}, pages = {1509-1514}, pmid = {35866365}, issn = {1938-3673}, mesh = {Mice ; Humans ; Animals ; *Pyruvic Acid/metabolism ; Pyruvate Dehydrogenase Complex/metabolism ; *Sepsis ; Mitochondria/metabolism ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase ; Acetates/pharmacology ; }, abstract = {Balancing high energy-consuming danger resistance and low energy supply of disease tolerance is a universal survival principle that often fails during sepsis. Our research supports the concept that sepsis phosphorylates and deactivates mitochondrial pyruvate dehydrogenase complex control over the tricarboxylic cycle and the electron transport chain. StimulatIng mitochondrial energetics in septic mice and human sepsis cell models can be achieved by inhibiting pyruvate dehydrogenase kinases with the pyruvate structural analog dichloroacetate. Stimulating the pyruvate dehydrogenase complex by dichloroacetate reverses a disruption in the tricarboxylic cycle that induces itaconate, a key mediator of the disease tolerance pathway. Dichloroacetate treatment increases mitochondrial respiration and ATP synthesis, decreases oxidant stress, overcomes metabolic paralysis, regenerates tissue, organ, and innate and adaptive immune cells, and doubles the survival rate in a murine model of sepsis.}, } @article {pmid35870233, year = {2022}, author = {Visinoni, F and Delneri, D}, title = {Mitonuclear interplay in yeast: from speciation to phenotypic adaptation.}, journal = {Current opinion in genetics & development}, volume = {76}, number = {}, pages = {101957}, doi = {10.1016/j.gde.2022.101957}, pmid = {35870233}, issn = {1879-0380}, support = {BB/L021471/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adaptation, Physiological/genetics ; *Hybridization, Genetic ; Mitochondria/genetics/metabolism ; Phenotype ; *Proteome/genetics ; }, abstract = {Saccharomyces yeasts have evolved into an important model system to study mitonuclear incompatibilities, thanks to recent advances in the field of sequencing, yeast hybridisation and multigenerational breeding. Yeast hybrids contain two homologous proteomes but retain only one type of mitochondria allowing studies on the effect of mitochondria on phenotype and gene expression. Here, we discuss the recent developments in the growing field of yeast mitogenomics spanning from the impact that this organelle has in shaping yeast fitness and genome evolution to the dissection of molecular determinants of mitonuclear incompatibilities. Applying the state-of-the-art genetic tools to a broader range of natural yeast species from different environments will help progress the field and untap the mitochondrial potential in strain development.}, } @article {pmid35875852, year = {2022}, author = {Ebner, JN and Wyss, MK and Ritz, D and von Fumetti, S}, title = {Effects of thermal acclimation on the proteome of the planarian Crenobia alpina from an alpine freshwater spring.}, journal = {The Journal of experimental biology}, volume = {225}, number = {15}, pages = {}, pmid = {35875852}, issn = {1477-9145}, support = {31003A_176234//Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung/ ; 31003A_176234//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; //Universitat Basel/ ; }, mesh = {Acclimatization/physiology ; Animals ; Climate Change ; Fresh Water ; Humans ; *Planarians ; *Proteome ; Temperature ; }, abstract = {Species' acclimation capacity and their ability to maintain molecular homeostasis outside ideal temperature ranges will partly predict their success following climate change-induced thermal regime shifts. Theory predicts that ectothermic organisms from thermally stable environments have muted plasticity, and that these species may be particularly vulnerable to temperature increases. Whether such species retained or lost acclimation capacity remains largely unknown. We studied proteome changes in the planarian Crenobia alpina, a prominent member of cold-stable alpine habitats that is considered to be a cold-adapted stenotherm. We found that the species' critical thermal maximum (CTmax) is above its experienced habitat temperatures and that different populations exhibit differential CTmax acclimation capacity, whereby an alpine population showed reduced plasticity. In a separate experiment, we acclimated C. alpina individuals from the alpine population to 8, 11, 14 or 17°C over the course of 168 h and compared their comprehensively annotated proteomes. Network analyses of 3399 proteins and protein set enrichment showed that while the species' proteome is overall stable across these temperatures, protein sets functioning in oxidative stress response, mitochondria, protein synthesis and turnover are lower in abundance following warm acclimation. Proteins associated with an unfolded protein response, ciliogenesis, tissue damage repair, development and the innate immune system were higher in abundance following warm acclimation. Our findings suggest that this species has not suffered DNA decay (e.g. loss of heat-shock proteins) during evolution in a cold-stable environment and has retained plasticity in response to elevated temperatures, challenging the notion that stable environments necessarily result in muted plasticity.}, } @article {pmid35877596, year = {2022}, author = {Wu, CS and Chaw, SM}, title = {Evolution of mitochondrial RNA editing in extant gymnosperms.}, journal = {The Plant journal : for cell and molecular biology}, volume = {111}, number = {6}, pages = {1676-1687}, pmid = {35877596}, issn = {1365-313X}, mesh = {Amino Acids ; Cycadopsida/genetics ; *Magnoliopsida/genetics ; Mitochondrial Proteins/genetics ; RNA Editing/genetics ; RNA, Mitochondrial ; *Tracheophyta/genetics ; }, abstract = {To unveil the evolution of mitochondrial RNA editing in gymnosperms, we characterized mitochondrial genomes (mitogenomes), plastid genomes, RNA editing sites, and pentatricopeptide repeat (PPR) proteins from 10 key taxa representing four of the five extant gymnosperm clades. The assembled mitogenomes vary in gene content due to massive gene losses in Gnetum and Conifer II clades. Mitochondrial gene expression levels also vary according to protein function, with the most highly expressed genes involved in the respiratory complex. We identified 9132 mitochondrial C-to-U editing sites, as well as 2846 P-class and 8530 PLS-class PPR proteins. Regains of editing sites were demonstrated in Conifer II rps3 transcripts whose corresponding mitogenomic sequences lack introns due to retroprocessing. Our analyses reveal that non-synonymous editing is efficient and results in more codons encoding hydrophobic amino acids. In contrast, synonymous editing, although performed with variable efficiency, can increase the number of U-ending codons that are preferentially utilized in gymnosperm mitochondria. The inferred loss-to-gain ratio of mitochondrial editing sites in gymnosperms is 2.1:1, of which losses of non-synonymous editing are mainly due to genomic C-to-T substitutions. However, such substitutions only explain a small fraction of synonymous editing site losses, indicating distinct evolutionary mechanisms. We show that gymnosperms have experienced multiple lineage-specific duplications in PLS-class PPR proteins. These duplications likely contribute to accumulated RNA editing sites, as a mechanistic correlation between RNA editing and PLS-class PPR proteins is statistically supported.}, } @article {pmid35879672, year = {2022}, author = {Ge, H and Xu, J and Hua, M and An, W and Wu, J and Wang, B and Li, P and Fang, H}, title = {Genome-wide identification and analysis of ACP gene family in Sorghum bicolor (L.) Moench.}, journal = {BMC genomics}, volume = {23}, number = {1}, pages = {538}, pmid = {35879672}, issn = {1471-2164}, support = {32101730//National Natural Science Foundation of China/ ; MS22020033//the Social Livelihood Science and Technology Project of Nantong City,china/ ; 135420609055//Nantong University Scientific Research Start-up project for Introducing Talents/ ; 202110304081Y//the Practice Innovation Training Program Projects for College Students in 2021/ ; }, mesh = {Acyl Carrier Protein/genetics/metabolism ; Droughts ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/genetics/metabolism ; *Sorghum/metabolism ; Stress, Physiological/genetics ; Zea mays/genetics/metabolism ; }, abstract = {BACKGROUND: Acyl carrier proteins (ACP) constitute a very conserved carrier protein family. Previous studies have found that ACP not only takes part in the fatty acid synthesis process of almost all organisms, but also participates in the regulation of plant growth, development, and metabolism, and makes plants adaptable to stresses. However, this gene family has not been systematically studied in sorghum.

RESULTS: Nine ACP family members were identified in the sorghum genome, which were located on chromosomes 1, 2, 5, 7, 8 and 9, respectively. Evolutionary analysis among different species divided the ACP family into four subfamilies, showing that the SbACPs were more closely related to maize. The prediction results of subcellular localization showed that SbACPs were mainly distributed in chloroplasts and mitochondria, while fluorescence localization showed that SbACPs were mainly localized in chloroplasts in tobacco leaf. The analysis of gene structure revealed a relatively simple genetic structure, that there were 1-3 introns in the sorghum ACP family, and the gene structure within the same subfamily had high similarity. The amplification method of SbACPs was mainly large fragment replication, and SbACPs were more closely related to ACPs in maize and rice. In addition, three-dimensional structure analysis showed that all ACP genes in sorghum contained four α helices, and the second helix structure was more conserved, implying a key role in function. Cis-acting element analysis indicated that the SbACPs might be involved in light response, plant growth and development regulation, biotic and abiotic stress response, plant hormone regulation, and other physiological processes. What's more, qRT-PCR analysis uncovered that some of SbACPs might be involved in the adaptive regulation of drought and salt stresses, indicating the close relationship between fatty acids and the resistance to abiotic stresses in sorghum.

CONCLUSIONS: In summary, these results showed a comprehensive overview of the SbACPs and provided a theoretical basis for further studies on the biological functions of SbACPs in sorghum growth, development and abiotic stress responses.}, } @article {pmid35883288, year = {2022}, author = {Shang, Y and Wang, X and Liu, G and Wu, X and Wei, Q and Sun, G and Mei, X and Dong, Y and Sha, W and Zhang, H}, title = {Adaptability and Evolution of Gobiidae: A Genetic Exploration.}, journal = {Animals : an open access journal from MDPI}, volume = {12}, number = {14}, pages = {}, pmid = {35883288}, issn = {2076-2615}, support = {31872242//National Natural Science Foundation of China/ ; 32070405//National Natural Science Foundation of China/ ; 32001228//National Natural Science Foundation of China/ ; 32170530//National Natural Science Foundation of China/ ; }, abstract = {The Gobiidae family occupy one of the most diverse habitat ranges of all fishes. One key reason for their successful colonization of different habitats is their ability to adapt to different energy demands. This energy requirement is related to the ability of mitochondria in cells to generate energy via oxidative phosphorylation (OXPHOS). Here, we assembled three complete mitochondrial genomes of Rhinogobius shennongensis, Rhinogobius wuyanlingensis, and Chaenogobius annularis. These mitogenomes are circular and include 13 protein-coding genes (PCGs), two rRNAs, 22 tRNAs, and one non-coding control region (CR). We used comparative mitochondrial DNA (mtDNA) genome and selection pressure analyses to explore the structure and evolutionary rates of Gobiidae mitogenomics in different environments. The CmC model showed that the ω ratios of all mtDNA PCGs were <1, and that the evolutionary rate of adenosine triphosphate 8 (atp8) was faster in Gobiidae than in other mitochondrial DNA PCGs. We also found evidence of positive selection for several sites of NADH dehydrogenase (nd) 6 and atp8 genes. Thus, divergent mechanisms appear to underlie the evolution of mtDNA PCGs, which might explain the ability of Gobiidae to adapt to diverse environments. Our study provides new insights on the adaptive evolution of Gobiidae mtDNA genome and molecular mechanisms of OXPHOS.}, } @article {pmid35889091, year = {2022}, author = {Mendoza-Hoffmann, F and Zarco-Zavala, M and Ortega, R and Celis-Sandoval, H and Torres-Larios, A and García-Trejo, JJ}, title = {Evolution of the Inhibitory and Non-Inhibitory ε, ζ, and IF1 Subunits of the F1FO-ATPase as Related to the Endosymbiotic Origin of Mitochondria.}, journal = {Microorganisms}, volume = {10}, number = {7}, pages = {}, pmid = {35889091}, issn = {2076-2607}, support = {DGAPA-PAPIIT IN217520//National Autonomous University of Mexico/ ; }, abstract = {The F1FO-ATP synthase nanomotor synthesizes >90% of the cellular ATP of almost all living beings by rotating in the “forward” direction, but it can also consume the same ATP pools by rotating in “reverse.” To prevent futile F1FO-ATPase activity, several different inhibitory proteins or domains in bacteria (ε and ζ subunits), mitochondria (IF1), and chloroplasts (ε and γ disulfide) emerged to block the F1FO-ATPase activity selectively. In this study, we analyze how these F1FO-ATPase inhibitory proteins have evolved. The phylogeny of the α-proteobacterial ε showed that it diverged in its C-terminal side, thus losing both the inhibitory function and the ATP-binding/sensor motif that controls this inhibition. The losses of inhibitory function and the ATP-binding site correlate with an evolutionary divergence of non-inhibitory α-proteobacterial ε and mitochondrial δ subunits from inhibitory bacterial and chloroplastidic ε subunits. Here, we confirm the lack of inhibitory function of wild-type and C-terminal truncated ε subunits of P. denitrificans. Taken together, the data show that ζ evolved to replace ε as the primary inhibitor of the F1FO-ATPase of free-living α-proteobacteria. However, the ζ inhibitory function was also partially lost in some symbiotic α-proteobacteria and totally lost in some strictly parasitic α-proteobacteria such as the Rickettsiales order. Finally, we found that ζ and IF1 likely evolved independently via convergent evolution before and after the endosymbiotic origin mitochondria, respectively. This led us to propose the ε and ζ subunits as tracer genes of the pre-endosymbiont that evolved into the actual mitochondria.}, } @article {pmid35891364, year = {2022}, author = {Tao, J and Li, B and Cheng, J and Shi, Y and Qiao, C and Lin, Z and Liu, H}, title = {Genomic Divergence Characterization and Quantitative Proteomics Exploration of Type 4 Porcine Astrovirus.}, journal = {Viruses}, volume = {14}, number = {7}, pages = {}, pmid = {35891364}, issn = {1999-4915}, mesh = {Animals ; Antiviral Agents ; *Astroviridae Infections/veterinary ; China ; Genomics ; Humans ; Mamastrovirus ; Mitochondrial Proteins ; Phylogeny ; Proteomics ; Swine ; *Swine Diseases ; }, abstract = {Porcine astrovirus (PAstV) has been identified as an important diarrheic pathogen with a broad global distribution. The PAstV is a potential pathogen to human beings and plays a role in public health. Until now, the divergence characteristics and pathogenesis of the PAstV are still not well known. In this study, the PAstV-4 strain PAstV/CH/2022/CM1 was isolated from the diarrheal feces of a piglet in Shanghai, which was identified to be a recombination of PAstV4/JPN (LC201612) and PAstV4/CHN (JX060808). A time tree based on the ORF2 protein of the astrovirus demonstrated that type 2-5 PAstV (PAstV-2 to 5) diverged from type 1 PAstV (PAstV-1) at a point from 1992 to 2000. To better understand the molecular basis of the virus, we sought to explore the host cell response to the PAstV/CH/2022/CM1 infection using proteomics. The results demonstrate that viral infection elicits global protein changes, and that the mitochondria seems to be a primary and an important target in viral infection. Importantly, there was crosstalk between autophagy and apoptosis, in which ATG7 might be the key mediator. In addition, the NOD-like receptor X1 (NLRX1) in the mitochondria was activated and participated in several important antiviral signaling pathways after the PAstV/CH/2022/CM1 infection, which was closely related to mitophagy. The NLRX1 may be a crucial protein for antagonizing a viral infection through autophagy, but this has yet to be validated. In conclusion, the data in this study provides more information for understanding the virus genomic characterization and the potential antiviral targets in a PAstV infection.}, } @article {pmid35893881, year = {2022}, author = {Ghanem, J and Passadori, A and Severac, F and Dieterlen, A and Geny, B and Andrès, E}, title = {Effects of Rehabilitation on Long-COVID-19 Patient's Autonomy, Symptoms and Nutritional Observance.}, journal = {Nutrients}, volume = {14}, number = {15}, pages = {}, pmid = {35893881}, issn = {2072-6643}, mesh = {*COVID-19/complications ; Fatigue/complications ; Humans ; *Malnutrition/diagnosis ; Nutrition Assessment ; Nutritional Status ; Post-Acute COVID-19 Syndrome ; }, abstract = {Background: Despite significant improvements in COVID-19 therapy, many patients still present with persistent symptoms and quality-of-life alterations. The aim of this study was to simultaneously investigate the long-term evolution of autonomy, malnutrition and long-lasting symptoms in people infected with COVID-19 and hospitalized in the ICU. Method: Patients’ clinical characteristics; extent of their loss of autonomy based on “Autonomie Gérontologie Groupes Iso-Ressources” (AG-GIR) classification; nutritional status while following the French and Global Leadership Initiative on Malnutrition (GLIM) recommendations; and symptom evolutions before infection, during hospitalization and rehabilitation, and up to 6 months after returning home were determined in thirty-seven patients. Results: Prior to a COVID-19 infection, all patients were autonomous, but upon admission to the rehabilitation center (CRM), 39% of them became highly dependent. After discharge from the center and 6 months after returning home, only 6 and 3%, respectively, still required considerable assistance. Of these thirty-seven patients, 11% were moderately malnourished and 81% presented with severe malnutrition, with a significant correlation being observed between malnutrition and autonomy (p < 0.05). Except for fatigue, which persisted in 70% of the patients 6 months after discharge from rehabilitation, all other symptoms decreased significantly. Conclusions: This study shows a striking decrease in autonomy associated with malnutrition after hospitalization for a COVID-19 infection and a clear beneficial effect from personalized rehabilitation. However, although almost all patients regained autonomy 6 months after returning home, they often still suffer from fatigue. Patient compliance with their nutritional recommendations deserves further improvement, preferably through personalized and persistent follow-up with the patient.}, } @article {pmid35895186, year = {2022}, author = {Atayik, MC and Çakatay, U}, title = {Melatonin-related signaling pathways and their regulatory effects in aging organisms.}, journal = {Biogerontology}, volume = {23}, number = {5}, pages = {529-539}, pmid = {35895186}, issn = {1573-6768}, mesh = {Aging/metabolism ; Antioxidants/metabolism ; Free Radicals/metabolism ; Humans ; *Melatonin ; Signal Transduction ; }, abstract = {Melatonin is a tryptophan-derived ancestral molecule evolved in bacteria. According to the endosymbiotic theory, eukaryotic cells received mitochondria, plastids, and other organelles from bacteria by internalization. After the endosymbiosis, bacteria evolved into organelles and retained their ability of producing melatonin. Melatonin is a small, evolutionarily conserved indole with multiple receptor-mediated, receptor-dependent, and independent actions. Melatonin's initial function was likely a radical scavenger in bacteria that's why there was high intensity of free radicals on primitive atmosphere in the ancient times, and hormetic functions of melatonin, which are effecting through the level of gene expression via prooxidant and antioxidant redox pathways, are developed in throughout the eukaryotic evolution. In the earlier stages of life, endosymbiotic events between mitochondria and other downstream organelles continue with mutual benefits. However, this interaction gradually deteriorates as a result of the imperfection of both mitochondrial and extramitochondrial endosymbiotic crosstalk with the advancing age of eukaryotic organisms. Throughout the aging process melatonin levels tend to reduce and as a manifestation of this, many symptoms in organisms' homeostasis, such as deterioration in adjustment of cellular clocks, are commonly seen. In addition, due to deterioration in mitochondrial integrity and functions, immunity decreases, and lower levels of melatonin renders older individuals to be more susceptible to impaired redox modulation and age-related diseases. Our aim in this paper is to focus on the several redox modulation mechanisms in which melatonin signaling has a central role, to discuss melatonin's gerontological aspects and to provide new research ideas with researchers.}, } @article {pmid35899483, year = {2022}, author = {Pani, P and Bal, NC}, title = {Avian adjustments to cold and non-shivering thermogenesis: whats, wheres and hows.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {97}, number = {6}, pages = {2106-2126}, doi = {10.1111/brv.12885}, pmid = {35899483}, issn = {1469-185X}, mesh = {Animals ; *Thermogenesis/physiology ; *Cold Temperature ; Adipose Tissue, Brown/physiology ; Birds ; Muscle, Skeletal/physiology ; Mammals ; Acclimatization/physiology ; }, abstract = {Avian cold adaptation is hallmarked by innovative strategies of both heat conservation and thermogenesis. While minimizing heat loss can reduce the thermogenic demands of body temperature maintenance, it cannot eliminate the requirement for thermogenesis. Shivering and non-shivering thermogenesis (NST) are the two synergistic mechanisms contributing to endothermy. Birds are of particular interest in studies of NST as they lack brown adipose tissue (BAT), the major organ of NST in mammals. Critical analysis of the existing literature on avian strategies of cold adaptation suggests that skeletal muscle is the principal site of NST. Despite recent progress, isolating the mechanisms involved in avian muscle NST has been difficult as shivering and NST co-exist with its primary locomotory function. Herein, we re-evaluate various proposed molecular bases of avian skeletal muscle NST. Experimental evidence suggests that sarco(endo)plasmic reticulum Ca[2+] -ATPase (SERCA) and ryanodine receptor 1 (RyR1) are key in avian muscle NST, through their mediation of futile Ca[2+] cycling and thermogenesis. More recent studies have shown that SERCA regulation by sarcolipin (SLN) facilitates muscle NST in mammals; however, its role in birds is unclear. Ca[2+] signalling in the muscle seems to be common to contraction, shivering and NST, but elucidating its roles will require more precise measurement of local Ca[2+] levels inside avian myofibres. The endocrine control of avian muscle NST is still poorly defined. A better understanding of the mechanistic details of avian muscle NST will provide insights into the roles of these processes in regulatory thermogenesis, which could further inform our understanding of the evolution of endothermy among vertebrates.}, } @article {pmid35910652, year = {2022}, author = {Yu, J and Ran, Z and Zhang, J and Wei, L and Ma, W}, title = {Genome-Wide Insights Into the Organelle Translocation of Photosynthetic NDH-1 Genes During Evolution.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {956578}, pmid = {35910652}, issn = {1664-302X}, abstract = {Translocation of chloroplast-located genes to mitochondria or nucleus is considered to be a safety strategy that impedes mutation of photosynthetic genes and maintains their household function during evolution. The organelle translocation strategy is also developed in photosynthetic NDH-1 (pNDH-1) genes but its understanding is still far from complete. Here, we found that the mutation rate of the conserved pNDH-1 genes was gradually reduced but their selection pressure was maintained at a high level during evolution from cyanobacteria to angiosperm. By contrast, oxygenic photosynthesis-specific (OPS) pNDH-1 genes had an opposite trend, explaining the reason why they were transferred from the reactive oxygen species (ROS)-enriched chloroplast to the ROS-barren nucleus. Further, genome-wide sequence analysis supported the possibility that all conserved pNDH-1 genes lost in chloroplast genomes of Chlorophyceae and Pinaceae were transferred to the ROS-less mitochondrial genome as deduced from their truncated pNDH-1 gene fragments. Collectively, we propose that the organelle translocation strategy of pNDH-1 genes during evolution is necessary to maintain the function of the pNDH-1 complex as an important antioxidant mechanism for efficient photosynthesis.}, } @article {pmid35915152, year = {2022}, author = {Schavemaker, PE and Muñoz-Gómez, SA}, title = {The role of mitochondrial energetics in the origin and diversification of eukaryotes.}, journal = {Nature ecology & evolution}, volume = {6}, number = {9}, pages = {1307-1317}, pmid = {35915152}, issn = {2397-334X}, support = {R35 GM122566/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; DNA ; *Eukaryota/genetics ; Mitochondria/genetics/metabolism ; Prokaryotic Cells/metabolism ; }, abstract = {The origin of eukaryotic cell size and complexity is often thought to have required an energy excess supplied by mitochondria. Recent observations show energy demands to scale continuously with cell volume, suggesting that eukaryotes do not have higher energetic capacity. However, respiratory membrane area scales superlinearly with the cell surface area. Furthermore, the consequences of the contrasting genomic architectures between prokaryotes and eukaryotes have not been precisely quantified. Here, we investigated (1) the factors that affect the volumes at which prokaryotes become surface area-constrained, (2) the amount of energy divested to DNA due to contrasting genomic architectures and (3) the costs and benefits of respiring symbionts. Our analyses suggest that prokaryotes are not surface area-constrained at volumes of 10[0]‒10[3] µm[3], the genomic architecture of extant eukaryotes is only slightly advantageous at genomes sizes of 10[6]‒10[7] base pairs and a larger host cell may have derived a greater advantage (lower cost) from harbouring ATP-producing symbionts. This suggests that eukaryotes first evolved without the need for mitochondria since these ranges hypothetically encompass the last eukaryotic common ancestor and its relatives. Our analyses also show that larger and faster-dividing prokaryotes would have a shortage of respiratory membrane area and divest more energy into DNA. Thus, we argue that although mitochondria may not have been required by the first eukaryotes, eukaryote diversification was ultimately dependent on mitochondria.}, } @article {pmid35920046, year = {2022}, author = {Paulino, MG and Rossi, PA and Venturini, FP and Tavares, D and Sakuragui, MM and Moraes, G and Terezan, AP and Fernandes, JB and Giani, A and Fernandes, MN}, title = {Liver dysfunction and energy storage mobilization in traíra, Hoplias malabaricus (Teleostei, Erythrinidae) induced by subchronic exposure to toxic cyanobacterial crude extract.}, journal = {Environmental toxicology}, volume = {37}, number = {11}, pages = {2683-2691}, doi = {10.1002/tox.23628}, pmid = {35920046}, issn = {1522-7278}, support = {Proc GT 346//Companhia Energética de Minas Gerais/ ; Proc. 306818/2020-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; Proc. 2276/2011//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; Proc. 2012/00728-1//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; //Programa Nacional de Pós-Doutorado/ ; }, mesh = {Acid Phosphatase/metabolism ; Alanine Transaminase/metabolism ; Alkaline Phosphatase/metabolism ; Ammonia ; Animals ; Aspartate Aminotransferases/metabolism ; Bilirubin/metabolism ; *Characiformes ; Complex Mixtures/metabolism/toxicity ; *Cyanobacteria/metabolism ; Glucose/metabolism ; Glycogen/metabolism ; Lactates ; Lipids ; Liver/metabolism ; *Liver Diseases/metabolism ; Microcystins/metabolism/toxicity ; Pyruvates/metabolism ; }, abstract = {Microcystins (MC) are hepatotoxic for organisms. Liver MC accumulation and structural change are intensely studied, but the functional hepatic enzymes and energy metabolism have received little attention. This study investigated the liver and hepatocyte structures and the activity of key hepatic functional enzymes with emphasis on energetic metabolism changes after subchronic fish exposure to cyanobacterial crude extract (CE) containing MC. The Neotropical erythrinid fish, Hoplias malabaricus, were exposed intraperitoneally to CE containing 100 μg MC-LR eq kg[-1] for 30 days and, thereafter, the plasma, liver, and white muscle was sampled for analyses. Liver tissue lost cellular structure organization showing round hepatocytes, hyperemia, and biliary duct obstruction. At the ultrastructural level, the mitochondria and the endoplasmic reticulum exhibited disorganization. Direct and total bilirubin increased in plasma. In the liver, the activity of acid phosphatase (ACP) increased, and the aspartate aminotransferase (AST) decreased; AST increased in plasma. Alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were unchanged in the liver, muscle, and plasma. Glycogen stores and the energetic metabolites as glucose, lactate, and pyruvate decrease in the liver; pyruvate decreased in plasma and lactate decreased in muscle. Ammonia levels increased and protein concentration decreased in plasma. CE alters liver morphology by causing hepatocyte intracellular disorder, obstructive cholestasis, and dysfunction in the activity of key liver enzymes. The increasing energy demand implies glucose mobilization and metabolic adjustments maintaining protein preservation and lipid recruitment to supply the needs for detoxification allowing fish survival.}, } @article {pmid35920138, year = {2022}, author = {Liao, T and Wang, S and Stüeken, EE and Luo, H}, title = {Phylogenomic Evidence for the Origin of Obligate Anaerobic Anammox Bacteria Around the Great Oxidation Event.}, journal = {Molecular biology and evolution}, volume = {39}, number = {8}, pages = {}, pmid = {35920138}, issn = {1537-1719}, mesh = {*Ammonium Compounds ; Anaerobic Ammonia Oxidation ; Anaerobiosis ; Bacteria/genetics ; *Bacteria, Anaerobic/genetics ; Nitrites ; Nitrogen ; Oxidation-Reduction ; Phylogeny ; Quaternary Ammonium Compounds ; }, abstract = {The anaerobic ammonium oxidation (anammox) bacteria can transform ammonium and nitrite to dinitrogen gas, and this obligate anaerobic process accounts for up to half of the global nitrogen loss in surface environments. Yet its origin and evolution, which may give important insights into the biogeochemistry of early Earth, remain enigmatic. Here, we performed a comprehensive phylogenomic and molecular clock analysis of anammox bacteria within the phylum Planctomycetes. After accommodating the uncertainties and factors influencing time estimates, which include implementing both a traditional cyanobacteria-based and a recently developed mitochondria-based molecular dating approach, we estimated a consistent origin of anammox bacteria at early Proterozoic and most likely around the so-called Great Oxidation Event (GOE; 2.32-2.5 Ga) which fundamentally changed global biogeochemical cycles. We further showed that during the origin of anammox bacteria, genes involved in oxidative stress adaptation, bioenergetics, and anammox granules formation were recruited, which might have contributed to their survival on an increasingly oxic Earth. Our findings suggest the rising levels of atmospheric oxygen, which made nitrite increasingly available, was a potential driving force for the emergence of anammox bacteria. This is one of the first studies that link the GOE to the evolution of obligate anaerobic bacteria.}, } @article {pmid35931723, year = {2022}, author = {Silva, NM and Kreutzer, S and Souleles, A and Triantaphyllou, S and Kotsakis, K and Urem-Kotsou, D and Halstead, P and Efstratiou, N and Kotsos, S and Karamitrou-Mentessidi, G and Adaktylou, F and Chondroyianni-Metoki, A and Pappa, M and Ziota, C and Sampson, A and Papathanasiou, A and Vitelli, K and Cullen, T and Kyparissi-Apostolika, N and Lanz, AZ and Peters, J and Rio, J and Wegmann, D and Burger, J and Currat, M and Papageorgopoulou, C}, title = {Ancient mitochondrial diversity reveals population homogeneity in Neolithic Greece and identifies population dynamics along the Danubian expansion axis.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {13474}, pmid = {35931723}, issn = {2045-2322}, support = {31003A_156853/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {Bayes Theorem ; DNA, Ancient ; *DNA, Mitochondrial/genetics ; Europe ; Genetics, Population ; Greece ; History, Ancient ; Humans ; *Mitochondria/genetics ; Population Dynamics ; }, abstract = {The aim of the study is to investigate mitochondrial diversity in Neolithic Greece and its relation to hunter-gatherers and farmers who populated the Danubian Neolithic expansion axis. We sequenced 42 mitochondrial palaeogenomes from Greece and analysed them together with European set of 328 mtDNA sequences dating from the Early to the Final Neolithic and 319 modern sequences. To test for population continuity through time in Greece, we use an original structured population continuity test that simulates DNA from different periods by explicitly considering the spatial and temporal dynamics of populations. We explore specific scenarios of the mode and tempo of the European Neolithic expansion along the Danubian axis applying spatially explicit simulations coupled with Approximate Bayesian Computation. We observe a striking genetic homogeneity for the maternal line throughout the Neolithic in Greece whereas population continuity is rejected between the Neolithic and present-day Greeks. Along the Danubian expansion axis, our best-fitting scenario supports a substantial decrease in mobility and an increasing local hunter-gatherer contribution to the gene-pool of farmers following the initial rapid Neolithic expansion. Οur original simulation approach models key demographic parameters rather than inferring them from fragmentary data leading to a better understanding of this important process in European prehistory.}, } @article {pmid35955668, year = {2022}, author = {Manousaki, A and Bagnall, J and Spiller, D and Balarezo-Cisneros, LN and White, M and Delneri, D}, title = {Quantitative Characterisation of Low Abundant Yeast Mitochondrial Proteins Reveals Compensation for Haplo-Insufficiency in Different Environments.}, journal = {International journal of molecular sciences}, volume = {23}, number = {15}, pages = {}, pmid = {35955668}, issn = {1422-0067}, support = {BB/K003097/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/T002123/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M011208/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adaptor Proteins, Signal Transducing/metabolism ; GTP Phosphohydrolases/metabolism ; Membrane Proteins/metabolism ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; *Saccharomyces cerevisiae/metabolism ; *Saccharomyces cerevisiae Proteins/metabolism ; }, abstract = {The quantification of low abundant membrane-binding proteins such as transcriptional factors and chaperones has proven difficult, even with the most sophisticated analytical technologies. Here, we exploit and optimise the non-invasive Fluorescence Correlation Spectroscopy (FCS) for the quantitation of low abundance proteins, and as proof of principle, we choose two interacting proteins involved in the fission of mitochondria in yeast, Fis1p and Mdv1p. In Saccharomyces cerevisiae, the recruitment of Fis1p and Mdv1p to mitochondria is essential for the scission of the organelles and the retention of functional mitochondrial structures in the cell. We use FCS in single GFP-labelled live yeast cells to quantify the protein abundance in homozygote and heterozygote cells and to investigate the impact of the environments on protein copy number, bound/unbound protein state and mobility kinetics. Both proteins were observed to localise predominantly at mitochondrial structures, with the Mdv1p bound state increasing significantly in a strictly respiratory environment. Moreover, a compensatory mechanism that controls Fis1p abundance upon deletion of one allele was observed in Fis1p but not in Mdv1p, suggesting differential regulation of Fis1p and Mdv1p protein expression.}, } @article {pmid35957532, year = {2022}, author = {Wang, G and Wang, Y and Ni, J and Li, R and Zhu, F and Wang, R and Tian, Q and Shen, Q and Yang, Q and Tang, J and Murcha, MW and Wang, G}, title = {An MCIA-like complex is required for mitochondrial complex I assembly and seed development in maize.}, journal = {Molecular plant}, volume = {15}, number = {9}, pages = {1470-1487}, doi = {10.1016/j.molp.2022.08.001}, pmid = {35957532}, issn = {1752-9867}, mesh = {Cell Nucleus/metabolism ; *Electron Transport Complex I/genetics/metabolism ; Humans ; Mitochondria/metabolism ; Mitochondrial Proteins/genetics/metabolism ; Seeds/metabolism ; *Zea mays/metabolism ; }, abstract = {During adaptive radiation, mitochondria have co-evolved with their hosts, leading to gain or loss of subunits and assembly factors of respiratory complexes. Plant mitochondrial complex I harbors ∼40 nuclear- and 9 mitochondrial-encoded subunits, and is formed by stepwise assembly during which different intermediates are integrated via various assembly factors. In mammals, the mitochondrial complex I intermediate assembly (MCIA) complex is required for building the membrane arm module. However, plants have lost almost all of the MCIA complex components, giving rise to the hypothesis that plants follow an ancestral pathway to assemble the membrane arm subunits. Here, we characterize a maize crumpled seed mutant, crk1, and reveal by map-based cloning that CRK1 encodes an ortholog of human complex I assembly factor 1, zNDUFAF1, the only evolutionarily conserved MCIA subunit in plants. zNDUFAF1 is localized in the mitochondria and accumulates in two intermediate complexes that contain complex I membrane arm subunits. Disruption of zNDUFAF1 results in severe defects in complex I assembly and activity, a cellular bioenergetic shift to aerobic glycolysis, and mitochondrial vacuolation. Moreover, we found that zNDUFAF1, the putative mitochondrial import inner membrane translocase ZmTIM17-1, and the isovaleryl-coenzyme A dehydrogenase ZmIVD1 interact each other, and could be co-precipitated from the mitochondria and co-migrate in the same assembly intermediates. Knockout of either ZmTIM17-1 or ZmIVD1 could lead to the significantly reduced complex I stability and activity as well as defective seeds. These results suggest that zNDUFAF1, ZmTIM17-1 and ZmIVD1 probably form an MCIA-like complex that is essential for the biogenesis of mitochondrial complex I and seed development in maize. Our findings also imply that plants and mammals recruit MCIA subunits independently for mitochondrial complex I assembly, highlighting the importance of parallel evolution in mitochondria adaptation to their hosts.}, } @article {pmid35973607, year = {2022}, author = {Holt, AG and Davies, AM}, title = {A comparison of mtDNA deletion mutant proliferation mechanisms.}, journal = {Journal of theoretical biology}, volume = {551-552}, number = {}, pages = {111244}, doi = {10.1016/j.jtbi.2022.111244}, pmid = {35973607}, issn = {1095-8541}, mesh = {Cell Proliferation/genetics ; Clone Cells ; *DNA, Mitochondrial/genetics ; Humans ; *Mitochondria/genetics ; Mutation ; Mutation Rate ; }, abstract = {In this paper we use simulation methods to investigate the proliferation of deletion mutations of mitochondrial DNA in neurons. We simulate three mtDNA proliferation mechanisms, namely, random drift, replicative advantage and vicious cycle. For each mechanism, we investigated the effect mutation rates have on neuron loss within a human host. We also compare heteroplasmy of each mechanism at mutation rates that yield the levels neuron loss that would be associated with dementia. Both random drift and vicious cycle predicted high levels of heteroplasmy, while replicative advantage showed a small number of dominant clones with a low background of heteroplasmy.}, } @article {pmid35978085, year = {2022}, author = {Yue, J and Lu, Q and Ni, Y and Chen, P and Liu, C}, title = {Comparative analysis of the plastid and mitochondrial genomes of Artemisia giraldii Pamp.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {13931}, pmid = {35978085}, issn = {2045-2322}, mesh = {*Artemisia/genetics ; Evolution, Molecular ; *Genome, Mitochondrial ; *Genome, Plastid ; Phylogeny ; Plastids/genetics ; }, abstract = {Artemisia giraldii Pamp. is an herbaceous plant distributed only in some areas in China. To understand the evolutionary relationship between plastid and mitochondria in A. giraldii, we sequenced and analysed the plastome and mitogenome of A. giraldii on the basis of Illumina and Nanopore DNA sequencing data. The mitogenome was 194,298 bp long, and the plastome was 151,072 bp long. The mitogenome encoded 56 genes, and the overall GC content was 45.66%. Phylogenetic analysis of the two organelle genomes revealed that A. giraldii is located in the same branching position. We found 13 pairs of homologous sequences between the plastome and mitogenome, and only one of them might have transferred from the plastid to the mitochondria. Gene selection pressure analysis in the mitogenome showed that ccmFc, nad1, nad6, atp9, atp1 and rps12 may undergo positive selection. According to the 18 available plastome sequences, we found 17 variant sites in two hypervariable regions that can be used in completely distinguishing 18 Artemisia species. The most interesting discovery was that the mitogenome of A. giraldii was only 43,226 bp larger than the plastome. To the best of our knowledge, this study represented one of the smallest differences between all sequenced mitogenomes and plastomes from vascular plants. The above results can provide a reference for future taxonomic and molecular evolution studies of Asteraceae species.}, } @article {pmid35997667, year = {2022}, author = {Hirakawa, Y and Hanawa, Y and Yoneda, K and Suzuki, I}, title = {Evolution of a chimeric mitochondrial carbonic anhydrase through gene fusion in a haptophyte alga.}, journal = {FEBS letters}, volume = {596}, number = {23}, pages = {3051-3059}, doi = {10.1002/1873-3468.14475}, pmid = {35997667}, issn = {1873-3468}, support = {LA-2022-011//Institute for Fermentation, Osaka/ ; KAKENHI 18K06358//Japan Society for the Promotion of Science/ ; KAKENHI 19H03280//Japan Society for the Promotion of Science/ ; }, mesh = {*Haptophyta/genetics/metabolism ; *Carbonic Anhydrases/genetics/metabolism ; Plants/metabolism ; Carbon Dioxide/metabolism ; Recombinant Proteins/genetics ; Gene Fusion ; }, abstract = {Carbonic anhydrases (CAs) are a universal enzyme family that catalyses the interconversion of carbon dioxide and bicarbonate, and they are localized in most compartments including mitochondria and plastids. Thus far, eight classes of CAs (α-, β-, γ-, δ-, ζ-, η-, θ- and ι-CA) have been characterized. This study reports an interesting gene encoding a fusion protein of β-CA and ι-CA found in the haptophyte Isochrysis galbana. Recombinant protein assays demonstrated that the C-terminal ι-CA region catalyses CO2 hydration, whereas the N-terminal β-CA region no longer exhibits enzymatic activity. Considering that haptophytes generally have mitochondrion-localized β-CAs and plastid-localized ι-CAs, the fusion CA would show an intermediate stage in which mitochondrial β-CA is replaced by ι-CA in a haptophyte species.}, } @article {pmid35998817, year = {2022}, author = {Franzolin, GN and Araújo, BL and Zatti, SA and Naldoni, J and Adriano, EA}, title = {Occurrence of the host-parasite system Rhaphiodon vulpinus and Ceratomyxa barbata n. sp. in the two largest watersheds in South America.}, journal = {Parasitology international}, volume = {91}, number = {}, pages = {102651}, doi = {10.1016/j.parint.2022.102651}, pmid = {35998817}, issn = {1873-0329}, mesh = {Animals ; DNA, Ribosomal/genetics ; *Fish Diseases/epidemiology/parasitology ; Fishes ; Gallbladder/parasitology ; *Myxozoa ; *Parasites/genetics ; *Parasitic Diseases, Animal/parasitology ; Phylogeny ; }, abstract = {While around world, species of the genus Ceratomyxa parasite majority marine hosts, growing diversity has been reported in South American freshwater fish. The present study reports Ceratomyxa barbata n. sp. parasitizing the gallbladder of the Rhaphiodon vulpinus fish from the Amazon and La Plata basins. Morphological (light and transmission electron microscopy), molecular (sequencing of small subunit ribosomal DNA - SSU rDNA), and phylogenetic analyses were used to characterize the new species. Worm-like plasmodia endowed with motility were found swimming freely in the bile. The myxospores were elongated, lightly arcuate, with rounded ends and had polar tubules with 3 coils in the polar capsules. Ultrastructural analysis revealed plasmodia composed of an outer cytoplasmic region, where elongated tubular mitochondria, a rough endoplasmic reticulum, sporogonic stages, and a large vacuole occupying the internal area were observed. Phylogenetic analysis, based on SSU rDNA, found that among all South America freshwater Ceratomyxa species, C. barbata n. sp. arises as an earlier divergent species. The present study reveals the occurrence of this host-parasite system (R. vulpinus/C. barbata n. sp.) in the two largest watersheds on the continent.}, } @article {pmid36009607, year = {2022}, author = {Wu, L and Tong, Y and Ayivi, SPG and Storey, KB and Zhang, JY and Yu, DN}, title = {The Complete Mitochondrial Genomes of Three Sphenomorphinae Species (Squamata: Scincidae) and the Selective Pressure Analysis on Mitochondrial Genomes of Limbless Isopachys gyldenstolpei.}, journal = {Animals : an open access journal from MDPI}, volume = {12}, number = {16}, pages = {}, pmid = {36009607}, issn = {2076-2615}, support = {31801963//the National Natural Science Foundation of China/ ; }, abstract = {In order to adapt to diverse habitats, organisms often evolve corresponding adaptive mechanisms to cope with their survival needs. The species-rich family of Scincidae contains both limbed and limbless species, which differ fundamentally in their locomotor demands, such as relying on the movement of limbs or only body swing to move. Locomotion requires energy, and different types of locomotion have their own energy requirements. Mitochondria are the energy factories of living things, which provide a lot of energy for various physiological activities of organisms. Therefore, mitochondrial genomes could be tools to explore whether the limb loss of skinks are selected by adaptive evolution. Isopachys gyldenstolpei is a typical limbless skink. Here, we report the complete mitochondrial genomes of I. gyldenstolpei, Sphenomorphus indicus, and Tropidophorus hainanus. The latter two species were included as limbed comparator species to the limbless I. gyldenstolpei. The results showed that the full lengths of the mitochondrial genomes of I. gyldenstolpei, S. indicus, and T. hainanus were 17,210, 16,944, and 17,001 bp, respectively. Three mitochondrial genomes have typical circular double-stranded structures similar to other reptiles, including 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs, and the control region. Three mitochondrial genomes obtained in this study were combined with fifteen mitochondrially complete genomes of Scincidae in the NCBI database; the phylogenetic relationship between limbless I. gyldenstolpei and limbed skinks (S. indicus and T. hainanus) is discussed. Through BI and ML trees, Sphenomorphinae and Mabuyinae were monophyletic, while the paraphyly of Scincinae was also recovered. The limbless skink I. gyldenstolpei is closer to the species of Tropidophorus, which has formed a sister group with (T. hainanus + T. hangman). In the mitochondrial genome adaptations between limbless I. gyldenstolpei and limbed skinks, one positively selected site was found in the branch-site model analysis, which was located in ND2 (at position 28, BEB value = 0.907). Through analyzing the protein structure and function of the selected site, we found it was distributed in mitochondrial protein complex I. Positive selection of some mitochondrial genes in limbless skinks may be related to the requirement of energy to fit in their locomotion. Further research is still needed to confirm this conclusion though.}, } @article {pmid36010594, year = {2022}, author = {Liu, Y and Chen, C and Wang, X and Sun, Y and Zhang, J and Chen, J and Shi, Y}, title = {An Epigenetic Role of Mitochondria in Cancer.}, journal = {Cells}, volume = {11}, number = {16}, pages = {}, pmid = {36010594}, issn = {2073-4409}, mesh = {Carcinogenesis/genetics/metabolism ; *Epigenesis, Genetic ; Histones/metabolism ; Humans ; Mitochondria/genetics/metabolism ; *Neoplasms/genetics/metabolism ; Tumor Microenvironment ; }, abstract = {Mitochondria are not only the main energy supplier but are also the cell metabolic center regulating multiple key metaborates that play pivotal roles in epigenetics regulation. These metabolites include acetyl-CoA, α-ketoglutarate (α-KG), S-adenosyl methionine (SAM), NAD[+], and O-linked beta-N-acetylglucosamine (O-GlcNAc), which are the main substrates for DNA methylation and histone post-translation modifications, essential for gene transcriptional regulation and cell fate determination. Tumorigenesis is attributed to many factors, including gene mutations and tumor microenvironment. Mitochondria and epigenetics play essential roles in tumor initiation, evolution, metastasis, and recurrence. Targeting mitochondrial metabolism and epigenetics are promising therapeutic strategies for tumor treatment. In this review, we summarize the roles of mitochondria in key metabolites required for epigenetics modification and in cell fate regulation and discuss the current strategy in cancer therapies via targeting epigenetic modifiers and related enzymes in metabolic regulation. This review is an important contribution to the understanding of the current metabolic-epigenetic-tumorigenesis concept.}, } @article {pmid36042193, year = {2022}, author = {Kuhle, B and Hirschi, M and Doerfel, LK and Lander, GC and Schimmel, P}, title = {Structural basis for shape-selective recognition and aminoacylation of a D-armless human mitochondrial tRNA.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {5100}, pmid = {36042193}, issn = {2041-1723}, support = {S10 OD032467/OD/NIH HHS/United States ; R01 NS095892/NS/NINDS NIH HHS/United States ; R21 AG061697/AG/NIA NIH HHS/United States ; S10 OD021634/OD/NIH HHS/United States ; R01 GM125908/GM/NIGMS NIH HHS/United States ; R21 AG067594/AG/NIA NIH HHS/United States ; }, mesh = {*Amino Acyl-tRNA Synthetases/metabolism ; Aminoacylation/genetics ; Animals ; Humans ; Mammals/genetics ; Mitochondria/metabolism ; RNA, Mitochondrial/metabolism ; *RNA, Transfer/genetics/metabolism ; }, abstract = {Human mitochondrial gene expression relies on the specific recognition and aminoacylation of mitochondrial tRNAs (mtRNAs) by nuclear-encoded mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs). Despite their essential role in cellular energy homeostasis, strong mutation pressure and genetic drift have led to an unparalleled sequence erosion of animal mtRNAs. The structural and functional consequences of this erosion are not understood. Here, we present cryo-EM structures of the human mitochondrial seryl-tRNA synthetase (mSerRS) in complex with mtRNA[Ser(GCU)]. These structures reveal a unique mechanism of substrate recognition and aminoacylation. The mtRNA[Ser(GCU)] is highly degenerated, having lost the entire D-arm, tertiary core, and stable L-shaped fold that define canonical tRNAs. Instead, mtRNA[Ser(GCU)] evolved unique structural innovations, including a radically altered T-arm topology that serves as critical identity determinant in an unusual shape-selective readout mechanism by mSerRS. Our results provide a molecular framework to understand the principles of mito-nuclear co-evolution and specialized mechanisms of tRNA recognition in mammalian mitochondrial gene expression.}, } @article {pmid36045215, year = {2022}, author = {Monsanto, DM and Main, DC and Janion-Scheepers, C and Emami-Khoyi, A and Deharveng, L and Bedos, A and Potapov, M and Parbhu, SP and Le Roux, JJ and Teske, PR and van Vuuren, BJ}, title = {Mitogenome selection in the evolution of key ecological strategies in the ancient hexapod class Collembola.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {14810}, pmid = {36045215}, issn = {2045-2322}, mesh = {Animals ; *Arthropods/genetics/metabolism ; Evolution, Molecular ; Fossils ; Genes, Mitochondrial ; *Genome, Mitochondrial ; Insecta/genetics ; Phylogeny ; }, abstract = {A longstanding question in evolutionary biology is how natural selection and environmental pressures shape the mitochondrial genomic architectures of organisms. Mitochondria play a pivotal role in cellular respiration and aerobic metabolism, making their genomes functionally highly constrained. Evaluating selective pressures on mitochondrial genes can provide functional and ecological insights into the evolution of organisms. Collembola (springtails) are an ancient hexapod group that includes the oldest terrestrial arthropods in the fossil record, and that are closely associated with soil environments. Of interest is the diversity of habitat stratification preferences (life forms) exhibited by different species within the group. To understand whether signals of positive selection are linked to the evolution of life forms, we analysed 32 published Collembola mitogenomes in a phylomitogenomic framework. We found no evidence that signatures of selection are correlated with the evolution of novel life forms, but rather that mutations have accumulated as a function of time. Our results highlight the importance of nuclear-mitochondrial interactions in the evolution of collembolan life forms and that mitochondrial genomic data should be interpreted with caution, as complex selection signals may complicate evolutionary inferences.}, } @article {pmid36055768, year = {2022}, author = {Khan, K and Van Aken, O}, title = {The colonization of land was a likely driving force for the evolution of mitochondrial retrograde signalling in plants.}, journal = {Journal of experimental botany}, volume = {73}, number = {21}, pages = {7182-7197}, pmid = {36055768}, issn = {1460-2431}, support = {2017-03854//Swedish Research Council/ ; NNF18OC0034822//Novo Nordisk Fonden/ ; UPD2019-0211//Wenner-Gren Foundation/ ; }, mesh = {*Signal Transduction ; Seeds ; Mitochondria ; Eukaryota ; Cyclin-Dependent Kinases ; *Arabidopsis/genetics ; Transcription Factors/genetics ; }, abstract = {Most retrograde signalling research in plants was performed using Arabidopsis, so an evolutionary perspective on mitochondrial retrograde regulation (MRR) is largely missing. Here, we used phylogenetics to track the evolutionary origins of factors involved in plant MRR. In all cases, the gene families can be traced to ancestral green algae or earlier. However, the specific subfamilies containing factors involved in plant MRR in many cases arose during the transition to land. NAC transcription factors with C-terminal transmembrane domains, as observed in the key regulator ANAC017, can first be observed in non-vascular mosses, and close homologs to ANAC017 can be found in seed plants. Cyclin-dependent kinases (CDKs) are common to eukaryotes, but E-type CDKs that control MRR also diverged in conjunction with plant colonization of land. AtWRKY15 can be traced to the earliest land plants, while AtWRKY40 only arose in angiosperms and AtWRKY63 even more recently in Brassicaceae. Apetala 2 (AP2) transcription factors are traceable to algae, but the ABI4 type again only appeared in seed plants. This strongly suggests that the transition to land was a major driver for developing plant MRR pathways, while additional fine-tuning events have appeared in seed plants or later. Finally, we discuss how MRR may have contributed to meeting the specific challenges that early land plants faced during terrestrialization.}, } @article {pmid36071602, year = {2022}, author = {Zhang, M and Zhang, C and Hu, P and Shi, L and Ju, M and Zhang, B and Li, X and Han, X and Wang, K and Li, X and Qiao, R}, title = {Comprehensive analysis of mitogenome of native Henan pig breeds with 58 worldwide pig breeds.}, journal = {Animal genetics}, volume = {53}, number = {6}, pages = {803-813}, doi = {10.1111/age.13261}, pmid = {36071602}, issn = {1365-2052}, support = {U1904115//National Natural Science Foundation of China/ ; 202300410195//Outstanding Youth Foundation of Henan Province/ ; }, mesh = {Animals ; DNA, Mitochondrial/genetics ; Genetic Variation ; *Genome, Mitochondrial ; Haplotypes ; Phylogeny ; Swine/genetics ; }, abstract = {Mitochondria follow non-Mendelian maternal inheritance, and thus can be used to compare genetic diversity and infer the expansion and migration between animal populations. Based on the mitochondrial DNA sequences of 58 pig breeds from Asia, Europe, Oceania, and America, we observed a distinct division of Eurasian pig species into two main Haplogroups (A and B), with the exception of the Berkshire and Yorkshire breeds. Oceanian pigs were much more similar to European and American pigs in Haplogroup A. Additionally, native Chinese pigs exhibited the most abundant genetic polymorphisms and occupied the centre of Haplogroup B. Miyazaki (Japan) and Siberia (Russia) are two distant and disconnected regions; however, most pigs from these regions were clustered into a subcluster, while native pigs from Korea clustered into a second subcluster. This study is the first to report that pigs from Thailand and Vietnam had haplotypes similar to those of Henan, where the earliest evidence of domestic pigs was found from the Yellow River Basin of North China. Local Henan pig breeds are related to many Asian breeds while still having their own mutation identity, such as g.314 delins T>AC/AT/C of the 12S rRNA gene in Yuxi. Some pigs from Palawan, Itbayat, and Batan Islands of the Philippines and Lanyu Island of China were distinct from other Asian pigs and clustered together into Haplogroup C. These findings show that the complexity of domestication of worldwide pig breeds and mitochondria could reflect genetic communication between pig breeds due to geographical proximity and human activities.}, } @article {pmid36083445, year = {2022}, author = {Wang, S and Luo, H}, title = {Estimating the Divergence Times of Alphaproteobacteria Based on Mitochondrial Endosymbiosis and Eukaryotic Fossils.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2569}, number = {}, pages = {95-116}, pmid = {36083445}, issn = {1940-6029}, mesh = {*Alphaproteobacteria/genetics ; Eukaryota ; Evolution, Molecular ; Fossils ; Mitochondria/genetics ; Phylogeny ; Symbiosis/genetics ; }, abstract = {Alphaproteobacteria is one of the most abundant bacterial lineages that successfully colonize diverse marine and terrestrial environments on Earth. In addition, many alphaproteobacterial lineages have established close association with eukaryotes. This makes Alphaproteobacteria a promising system to test the link between the emergence of ecologically important bacteria and related geological events and the co-evolution between symbiotic bacteria and their hosts. Understanding the timescale of evolution of Alphaproteobacteria is key to testing these hypotheses, which is limited by the scarcity of bacterial fossils, however. Based on the mitochondrial endosymbiosis which posits that the mitochondrion originated from an alphaproteobacterial lineage, we propose a new strategy to estimate the divergence times of lineages within the Alphaproteobacteria by leveraging the fossil records of eukaryotes. In this chapter, we describe the workflow of the mitochondria-based method to date Alphaproteobacteria evolution by detailing the software, methods, and commands used for each step. Visualization of data and results is also described. We also provide related notes with background information and alternative options. All codes used to build this protocol are made available to the public, and we strive to make this protocol user-friendly in particular to microbiologists with limited practical skills in bioinformatics.}, } @article {pmid36083897, year = {2022}, author = {Ba, Q and Hei, Y and Dighe, A and Li, W and Maziarz, J and Pak, I and Wang, S and Wagner, GP and Liu, Y}, title = {Proteotype coevolution and quantitative diversity across 11 mammalian species.}, journal = {Science advances}, volume = {8}, number = {36}, pages = {eabn0756}, pmid = {36083897}, issn = {2375-2548}, support = {P50 CA196530/CA/NCI NIH HHS/United States ; R01 GM137031/GM/NIGMS NIH HHS/United States ; U54 CA209992/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Gene Expression Profiling ; *Mammals/genetics/metabolism ; Proteome/metabolism ; *Proteomics ; Transcriptome ; }, abstract = {Evolutionary profiling has been largely limited to the nucleotide level. Using consistent proteomic methods, we quantified proteomic and phosphoproteomic layers in fibroblasts from 11 common mammalian species, with transcriptomes as reference. Covariation analysis indicates that transcript and protein expression levels and variabilities across mammals remarkably follow functional role, with extracellular matrix-associated expression being the most variable, demonstrating strong transcriptome-proteome coevolution. The biological variability of gene expression is universal at both interindividual and interspecies scales but to a different extent. RNA metabolic processes particularly show higher interspecies versus interindividual variation. Our results further indicate that while the ubiquitin-proteasome system is strongly conserved in mammals, lysosome-mediated protein degradation exhibits remarkable variation between mammalian lineages. In addition, the phosphosite profiles reveal a phosphorylation coevolution network independent of protein abundance.}, } @article {pmid36085554, year = {2022}, author = {Jacquat, AG and Ulla, SB and Debat, HJ and Muñoz-Adalia, EJ and Theumer, MG and Pedrajas, MDG and Dambolena, JS}, title = {An in silico analysis revealed a novel evolutionary lineage of putative mitoviruses.}, journal = {Environmental microbiology}, volume = {24}, number = {12}, pages = {6463-6475}, doi = {10.1111/1462-2920.16202}, pmid = {36085554}, issn = {1462-2920}, mesh = {Genome, Viral ; Mitochondria/genetics ; Phylogeny ; Plant Diseases/microbiology ; *RNA Viruses/genetics ; RNA, Viral ; }, abstract = {Mitoviruses (family Mitoviridae) are small capsid-less RNA viruses that replicate in the mitochondria of fungi and plants. However, to date, the only authentic animal mitovirus infecting an insect was identified as Lutzomyia longipalpis mitovirus 1 (LulMV1). Public databases of transcriptomic studies from several animals may be a good source for identifying the often missed mitoviruses. Consequently, a search of mitovirus-like transcripts at the NCBI transcriptome shotgun assembly (TSA) library, and a search for the mitoviruses previously recorded at the NCBI non-redundant (nr) protein sequences library, were performed in order to identify new mitovirus-like sequences associated with animals. In total, 10 new putative mitoviruses were identified in the TSA database and 8 putative mitoviruses in the nr protein database. To our knowledge, these results represent the first evidence of putative mitoviruses associated with poriferan, cnidarians, echinoderms, crustaceans, myriapods and arachnids. According to different phylogenetic inferences using the maximum likelihood method, these 18 putative mitoviruses form a robust monophyletic lineage with LulMV1, the only known animal-infecting mitovirus. These findings based on in silico procedures provide strong evidence for the existence of a clade of putative mitoviruses associated with animals, which has been provisionally named 'kvinmitovirus'.}, } @article {pmid36097126, year = {2022}, author = {Joshi, BD and Kumar, V and De, R and Sharma, R and Bhattacharya, A and Dolker, S and Pal, R and Kumar, VP and Sathyakumar, S and Adhikari, BS and Habib, B and Goyal, SP}, title = {Mitochondrial cytochrome b indicates the presence of two paraphyletic diverged lineages of the blue sheep Pseudois nayaur across the Indian Himalaya: conservation implications.}, journal = {Molecular biology reports}, volume = {49}, number = {11}, pages = {11177-11186}, pmid = {36097126}, issn = {1573-4978}, mesh = {Animals ; *Cytochromes b/genetics ; *Genetics, Population ; Haplotypes/genetics ; Phylogeny ; Phylogeography ; Sheep/genetics ; *Mitochondria/metabolism ; }, abstract = {BACKGROUND: Populations exhibit signatures of local adaptive traits due to spatial and environmental heterogeneity resulting in microevolution. The blue sheep is widely distributed across the high Asian mountains and are the snow leopard's principal prey species. These mountains differ in their evolutionary history due to differential glaciation and deglaciation periods, orography, and rainfall patterns, and such factors causes diversification in species.

METHODS AND RESULTS: Therefore, we assess the phylogeographic status of blue sheep using the mitochondrial cytochrome b gene (220 bp) across the Indian Himalayan region (IHR) and its relationship with other populations. Of the observed five haplotypes, two and three were from the western Himalayas (WH) and eastern Himalayas (EH) respectively. One of the haplotypes from WH was shared with the population of Pamir plateau, suggesting historical maternal connectivity between these areas. The phylogenetic analyses split the blue sheep into two paraphyletic clades, and western and eastern populations of IHR were within the Pamir and Tibetan plateau clades, respectively. We observed a relatively higher mean sequence divergence in the EH population than in the WH.

CONCLUSION: We propose five 'Evolutionary Significant Units' across the blue sheep distribution range based on observed variation in the species' ecological requirements, orography, climatic conditions, and maternal lineages, viz.; Western Himalaya-Pamir plateau (WHPP); Eastern Himalaya-Tibetan plateau (EHTP); Qilian mountains; Helan mountains and Hengduan mountains population. Despite the small sample size, population divergence was observed across the IHR, therefore, we suggest a transboundary, collaborative study on comparative morphology, anatomy, ecology, behaviour, and population genetics using harmonized different genetic markers for identifying the overall taxonomic status of the blue sheep across its range for planning effective conservation strategies.}, } @article {pmid36101314, year = {2022}, author = {Zhou, S and He, LI and Ma, S and Xu, S and Zhai, Q and Guan, P and Wang, H and Shi, J}, title = {Taxonomic status of Rana nigromaculata mongolia and the validity of Pelophylax tenggerensis (Anura, Ranidae).}, journal = {Zootaxa}, volume = {5165}, number = {4}, pages = {486-500}, doi = {10.11646/zootaxa.5165.4.2}, pmid = {36101314}, issn = {1175-5334}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Mongolia ; Phylogeny ; *Ranidae/genetics ; }, abstract = {The Black-spotted Pond Frog, Pelophylax nigromaculatus, is widely distributed across mainland China, Korean Peninsula, and Japan. The taxonomic relationships among P. n. nigromaculatus, Rana nigromaculata mongolia (sensu P. n. mongolicus), and P. tenggerensis have long been ambiguous. Here we examine the topotype specimens of P. tenggerensis and R. n. mongolia, and provide phylogenic analyses based on four mitochondrial DNA sequences. The combined evidences from morphology and molecular phylogeny have shown the distinct specific-level of P. n. mongolicus that distant from P. nigromaculatus, while indicating the homogeneity between P. n. mongolicus and P. tenggerensis. Thus, we suggest elevating P. n. mongolicus as a full species Pelophylax mongolicus comb. nov., and place P. tenggerensis to be a secondary synonym of P. mongolicus comb. nov.}, } @article {pmid36107771, year = {2022}, author = {Lesch, E and Schilling, MT and Brenner, S and Yang, Y and Gruss, OJ and Knoop, V and Schallenberg-Rüdinger, M}, title = {Plant mitochondrial RNA editing factors can perform targeted C-to-U editing of nuclear transcripts in human cells.}, journal = {Nucleic acids research}, volume = {50}, number = {17}, pages = {9966-9983}, pmid = {36107771}, issn = {1362-4962}, mesh = {Amino Acids ; Cytidine ; Humans ; *Plant Proteins/genetics ; RNA/genetics ; RNA, Mitochondrial/genetics ; RNA, Plant/genetics ; *RNA-Binding Proteins/genetics/metabolism ; Uridine/genetics ; }, abstract = {RNA editing processes are strikingly different in animals and plants. Up to thousands of specific cytidines are converted into uridines in plant chloroplasts and mitochondria whereas up to millions of adenosines are converted into inosines in animal nucleo-cytosolic RNAs. It is unknown whether these two different RNA editing machineries are mutually incompatible. RNA-binding pentatricopeptide repeat (PPR) proteins are the key factors of plant organelle cytidine-to-uridine RNA editing. The complete absence of PPR mediated editing of cytosolic RNAs might be due to a yet unknown barrier that prevents its activity in the cytosol. Here, we transferred two plant mitochondrial PPR-type editing factors into human cell lines to explore whether they could operate in the nucleo-cytosolic environment. PPR56 and PPR65 not only faithfully edited their native, co-transcribed targets but also different sets of off-targets in the human background transcriptome. More than 900 of such off-targets with editing efficiencies up to 91%, largely explained by known PPR-RNA binding properties, were identified for PPR56. Engineering two crucial amino acid positions in its PPR array led to predictable shifts in target recognition. We conclude that plant PPR editing factors can operate in the entirely different genetic environment of the human nucleo-cytosol and can be intentionally re-engineered towards new targets.}, } @article {pmid36115336, year = {2022}, author = {Giannakis, K and Arrowsmith, SJ and Richards, L and Gasparini, S and Chustecki, JM and Røyrvik, EC and Johnston, IG}, title = {Evolutionary inference across eukaryotes identifies universal features shaping organelle gene retention.}, journal = {Cell systems}, volume = {13}, number = {11}, pages = {874-884.e5}, doi = {10.1016/j.cels.2022.08.007}, pmid = {36115336}, issn = {2405-4720}, mesh = {*Eukaryota/genetics ; Bayes Theorem ; *Biological Evolution ; Plastids/genetics/metabolism ; Mitochondria/metabolism ; }, abstract = {Mitochondria and plastids power complex life. Why some genes and not others are retained in their organelle DNA (oDNA) genomes remains a debated question. Here, we attempt to identify the properties of genes and associated underlying mechanisms that determine oDNA retention. We harness over 15k oDNA sequences and over 300 whole genome sequences across eukaryotes with tools from structural biology, bioinformatics, machine learning, and Bayesian model selection. Previously hypothesized features, including the hydrophobicity of a protein product, and less well-known features, including binding energy centrality within a protein complex, predict oDNA retention across eukaryotes, with additional influences of nucleic acid and amino acid biochemistry. Notably, the same features predict retention in both organelles, and retention models learned from one organelle type quantitatively predict retention in the other, supporting the universality of these features-which also distinguish gene profiles in more recent, independent endosymbiotic relationships. A record of this paper's transparent peer review process is included in the supplemental information.}, } @article {pmid36143326, year = {2022}, author = {Govindharaj, GP and Babu, SB and Choudhary, JS and Asad, M and Chidambaranathan, P and Gadratagi, BG and Rath, PC and Naaz, N and Jaremko, M and Qureshi, KA and Kumar, U}, title = {Genome Organization and Comparative Evolutionary Mitochondriomics of Brown Planthopper, Nilaparvata lugens Biotype 4 Using Next Generation Sequencing (NGS).}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {9}, pages = {}, pmid = {36143326}, issn = {2075-1729}, abstract = {Nilaparvata lugens is the main rice pest in India. Until now, the Indian N. lugens mitochondrial genome has not been sequenced, which is a very important basis for population genetics and phylogenetic evolution studies. An attempt was made to sequence two examples of the whole mitochondrial genome of N. lugens biotype 4 from the Indian population for the first time. The mitogenomes of N. lugens are 16,072 and 16,081 bp long with 77.50% and 77.45% A + T contents, respectively, for both of the samples. The mitochondrial genome of N. lugens contains 37 genes, including 13 protein-coding genes (PCGs) (cox1-3, atp6, atp8, nad1-6, nad4l, and cob), 22 transfer RNA genes, and two ribosomal RNA (rrnS and rrnL) subunits genes, which are typical of metazoan mitogenomes. However, both samples of N. lugens mitogenome in the present study retained one extra copy of the trnC gene. Additionally, we also found 93 bp lengths for the atp8 gene in both of the samples, which were 60-70 bp less than that of the other sequenced mitogenomes of hemipteran insects. The phylogenetic analysis of the 19 delphacids mitogenome dataset yielded two identical topologies when rooted with Ugyops sp. in one clade, and the remaining species formed another clade with P. maidis and M. muiri being sisters to the remaining species. Further, the genus Nilaparvata formed a separate subclade with the other genera (Sogatella, Laodelphax, Changeondelphax, and Unkanodes) of Delphacidae. Additionally, the relationship among the biotypes of N. lugens was recovered as the present study samples (biotype-4) were separated from the three biotypes reported earlier. The present study provides the reference mitogenome for N. lugens biotype 4 that may be utilized for biotype differentiation and molecular-aspect-based future studies of N. lugens.}, } @article {pmid36146890, year = {2023}, author = {Pierszalowski, SP and Steel, DJ and Gabriele, CM and Neilson, JL and Vanselow, PBS and Cedarleaf, JA and Straley, JM and Baker, CS}, title = {mtDNA heteroplasmy gives rise to a new maternal lineage in North Pacific humpback whales (Megaptera novaeangliae).}, journal = {The Journal of heredity}, volume = {114}, number = {1}, pages = {14-21}, pmid = {36146890}, issn = {1465-7333}, mesh = {Animals ; Female ; Cattle ; *Humpback Whale/genetics ; DNA, Mitochondrial/genetics ; Heteroplasmy ; Mitochondria/genetics ; Cetacea/genetics ; }, abstract = {Heteroplasmy in the mitochondrial genome offers a rare opportunity to track the evolution of a newly arising maternal lineage in populations of non-model species. Here, we identified a previously unreported mitochondrial DNA haplotype while assembling an integrated database of DNA profiles and photo-identification records from humpback whales in southeastern Alaska (SEAK). The haplotype, referred to as A8, was shared by only 2 individuals, a mature female with her female calf, and differed by only a single base pair from a common haplotype in the North Pacific, referred to as A-. To investigate the origins of the A8 haplotype, we reviewed n = 1,089 electropherograms (including replicate samples) of n = 710 individuals with A- haplotypes from an existing collection. From this review, we found 20 individuals with clear evidence of heteroplasmy for A-/A8 (parental/derived) haplotypes. Of these, 15 were encountered in SEAK, 4 were encountered on the Hawaiian breeding ground (the primary migratory destination for whales in SEAK), and 1 was encountered in the northern Gulf of Alaska. We used genotype exclusion and likelihood to identify one of the heteroplasmic females as the likely mother of the A8 cow and grandmother of the A8 calf, establishing the inheritance and germ-line fixation of the new haplotype from the parental heteroplasmy. The mutation leading to this heteroplasmy and the fixation of the A8 haplotype provide an opportunity to document the population dynamics and regional fidelity of a newly arising maternal lineage in a population recovering from exploitation.}, } @article {pmid36158221, year = {2022}, author = {Ikeda, A and Imai, Y and Hattori, N}, title = {Neurodegeneration-associated mitochondrial proteins, CHCHD2 and CHCHD10-what distinguishes the two?.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {996061}, pmid = {36158221}, issn = {2296-634X}, abstract = {Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) and Coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) are mitochondrial proteins that are thought to be genes which duplicated during evolution and are the causative genes for Parkinson's disease and amyotrophic lateral sclerosis/frontotemporal lobe dementia, respectively. CHCHD2 forms a heterodimer with CHCHD10 and a homodimer with itself, both of which work together within the mitochondria. Various pathogenic and disease-risk variants have been identified; however, how these mutations cause neurodegeneration in specific diseases remains a mystery. This review focuses on important new findings published since 2019 and discusses avenues to solve this mystery.}, } @article {pmid36180833, year = {2022}, author = {Xiao, S and Xing, J and Nie, T and Su, A and Zhang, R and Zhao, Y and Song, W and Zhao, J}, title = {Comparative analysis of mitochondrial genomes of maize CMS-S subtypes provides new insights into male sterility stability.}, journal = {BMC plant biology}, volume = {22}, number = {1}, pages = {469}, pmid = {36180833}, issn = {1471-2229}, mesh = {*Genome, Mitochondrial/genetics ; Humans ; *Infertility, Male/genetics ; Male ; NADH Dehydrogenase/genetics ; Phylogeny ; Plant Infertility/genetics ; Zea mays/genetics ; }, abstract = {BACKGROUND: Cytoplasmic male sterility (CMS) is a trait of economic importance in the production of hybrid seeds. In CMS-S maize, exerted anthers appear frequently in florets of field-grown female populations where only complete male-sterile plants were expected. It has been reported that these reversions are associated with the loss of sterility-conferring regions or other rearrangements in the mitochondrial genome. However, the relationship between mitochondrial function and sterility stability is largely unknown.

RESULTS: In this study, we determined the ratio of plants carrying exerted anthers in the population of two CMS-S subtypes. The subtype with a high ratio of exerted anthers was designated as CMS-Sa, and the other with low ratio was designated as CMS-Sb. Through next-generation sequencing, we assembled and compared mitochondrial genomes of two CMS-S subtypes. Phylogenetic analyses revealed strong similarities between the two mitochondrial genomes. The sterility-associated regions, S plasmids, and terminal inverted repeats (TIRs) were intact in both genomes. The two subtypes maintained high transcript levels of the sterility gene orf355 in anther tissue. Most of the functional genes/proteins were identical at the nucleotide sequence and amino acid sequence levels in the two subtypes, except for NADH dehydrogenase subunit 1 (nad1). In the mitochondrial genome of CMS-Sb, a 3.3-kilobase sequence containing nad1-exon1 was absent from the second copy of the 17-kb repeat region. Consequently, we detected two copies of nad1-exon1 in CMS-Sa, but only one copy in CMS-Sb. During pollen development, nad1 transcription and mitochondrial biogenesis were induced in anthers of CMS-Sa, but not in those of CMS-Sb. We suggest that the impaired mitochondrial function in the anthers of CMS-Sb is associated with its more stable sterility.

CONCLUSIONS: Comprehensive analyses revealed diversity in terms of the copy number of the mitochondrial gene nad1-exon1 between two subtypes of CMS-S maize. This difference in copy number affected the transcript levels of nad1 and mitochondrial biogenesis in anther tissue, and affected the reversion rate of CMS-S maize. The results of this study suggest the involvement of mitochondrial robustness in modulation of sterility stability in CMS-S maize.}, } @article {pmid36183779, year = {2022}, author = {Moreno, ACR and Olean-Oliveira, A and Olean-Oliveira, T and Nunes, MT and Teixeira, MFS and Seraphim, PM}, title = {Resistance training prevents damage to the mitochondrial function of the skeletal muscle of rats exposed to secondary cigarette smoke.}, journal = {Life sciences}, volume = {309}, number = {}, pages = {121017}, doi = {10.1016/j.lfs.2022.121017}, pmid = {36183779}, issn = {1879-0631}, mesh = {Humans ; Rats ; Animals ; *Resistance Training ; *Cigarette Smoking ; Rats, Wistar ; Muscle, Skeletal/metabolism ; Mitochondria ; Nicotiana/adverse effects ; Oxygen/metabolism ; Adenosine Triphosphate/metabolism ; }, abstract = {AIM: To analyze the consumption of oxygen and to quantify the mitochondrial respiratory chain proteins (OXPHOS) in the gastrocnemius muscle of rats exposed to cigarette smoke and/or RT practitioners.

MAIN METHODS: Wistar rats were divided into groups: Control (C), Smoker (S), Exercise (E) and Exercise Smoker (ES). Groups F and ES were exposed to the smoke of 4 cigarettes for 30 min, 2× a day, 5× a week, for 16 weeks. Groups E and ES performed four climbs with progressive load, 1× per day, 5× per week, for 16 weeks. The gastrocnemius muscle was collected for analysis of OXPHOS content and oxygen consumption. Groups S (vs. C) and ES (vs. C and E) showed lower body weight gain when observing the evolution curve.

KEY FINDINGS: The S rats showed a reduction in the NDUFB8 proteins of complex 1, SDHB of complex 2, MTC01 of complex 4 and ATP5A of complex 5 (ATP Synthase) compared to Group C. Additionally, S rats also showed increased consumption of O2 in Basal, Leak, Complex I and I/II combined measures compared to the other groups, suggesting that the activity of the mitochondria of these animals increased in terms of coupling and uncoupling parameters.

SIGNIFICANCE: Our data suggest that exposure to cigarette smoke for 16 weeks is capable of causing impairment of mitochondrial function with reduced expression of respiratory chain proteins in skeletal muscle. However, the RT was effective in preventing impairment of mitochondrial function in the skeletal muscle of rats exposed to secondary cigarette smoke.}, } @article {pmid36198798, year = {2022}, author = {Wei, W and Schon, KR and Elgar, G and Orioli, A and Tanguy, M and Giess, A and Tischkowitz, M and Caulfield, MJ and Chinnery, PF}, title = {Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes.}, journal = {Nature}, volume = {611}, number = {7934}, pages = {105-114}, pmid = {36198798}, issn = {1476-4687}, support = {212219/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; //Medical Research Council UK/ ; MR/S005021/1/MRC_/Medical Research Council/United Kingdom ; RPG-2018-408/WT_/Wellcome Trust/United Kingdom ; MC_UP_1501/2/MRC_/Medical Research Council/United Kingdom ; MC_UU_00015/9/MRC_/Medical Research Council/United Kingdom ; MC_UU_00028/7/MRC_/Medical Research Council/United Kingdom ; MR/M008886/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_13047/MRC_/Medical Research Council/United Kingdom ; MR/S035699/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Cell Nucleus/genetics/metabolism ; *DNA, Mitochondrial/genetics/metabolism ; *Genome, Human/genetics ; Mitochondria/genetics ; Phylogeny ; Sequence Analysis, DNA ; Mutation ; Liposarcoma, Myxoid/genetics ; Neoplasms/genetics ; Germ-Line Mutation ; DNA Breaks, Double-Stranded ; DNA Repair ; Histone-Lysine N-Methyltransferase ; }, abstract = {DNA transfer from cytoplasmic organelles to the cell nucleus is a legacy of the endosymbiotic event-the majority of nuclear-mitochondrial segments (NUMTs) are thought to be ancient, preceding human speciation[1-3]. Here we analyse whole-genome sequences from 66,083 people-including 12,509 people with cancer-and demonstrate the ongoing transfer of mitochondrial DNA into the nucleus, contributing to a complex NUMT landscape. More than 99% of individuals had at least one of 1,637 different NUMTs, with 1 in 8 individuals having an ultra-rare NUMT that is present in less than 0.1% of the population. More than 90% of the extant NUMTs that we evaluated inserted into the nuclear genome after humans diverged from apes. Once embedded, the sequences were no longer under the evolutionary constraint seen within the mitochondrion, and NUMT-specific mutations had a different mutational signature to mitochondrial DNA. De novo NUMTs were observed in the germline once in every 10[4] births and once in every 10[3] cancers. NUMTs preferentially involved non-coding mitochondrial DNA, linking transcription and replication to their origin, with nuclear insertion involving multiple mechanisms including double-strand break repair associated with PR domain zinc-finger protein 9 (PRDM9) binding. The frequency of tumour-specific NUMTs differed between cancers, including a probably causal insertion in a myxoid liposarcoma. We found evidence of selection against NUMTs on the basis of size and genomic location, shaping a highly heterogenous and dynamic human NUMT landscape.}, } @article {pmid36203893, year = {2022}, author = {Mondal, S and Singh, SP}, title = {New insights on thioredoxins (Trxs) and glutaredoxins (Grxs) by in silico amino acid sequence, phylogenetic and comparative structural analyses in organisms of three domains of life.}, journal = {Heliyon}, volume = {8}, number = {10}, pages = {e10776}, pmid = {36203893}, issn = {2405-8440}, abstract = {Thioredoxins (Trxs) and Glutaredoxins (Grxs) regulate several cellular processes by controlling the redox state of their target proteins. Trxs and Grxs belong to thioredoxin superfamily and possess characteristic Trx/Grx fold. Several phylogenetic, biochemical and structural studies have contributed to our overall understanding of Trxs and Grxs. However, comparative study of closely related Trxs and Grxs in organisms of all domains of life was missing. Here, we conducted in silico comparative structural analysis combined with amino acid sequence and phylogenetic analyses of 65 Trxs and 88 Grxs from 12 organisms of three domains of life to get insights into evolutionary and structural relationship of two proteins. Outcomes suggested that despite diversity in their amino acids composition in distantly related organisms, both Trxs and Grxs strictly conserved functionally and structurally important residues. Also, position of these residues was highly conserved in all studied Trxs and Grxs. Notably, if any substitution occurred during evolution, preference was given to amino acids having similar chemical properties. Trxs and Grxs were found more different in eukaryotes than prokaryotes due to altered helical conformation. The surface of Trxs was negatively charged, while Grxs surface was positively charged, however, the active site was constituted by uncharged amino acids in both proteins. Also, phylogenetic analysis of Trxs and Grxs in three domains of life supported endosymbiotic origins of chloroplast and mitochondria, and suggested their usefulness in molecular systematics. We also report previously unknown catalytic motifs of two proteins, and discuss in detail about effect of abovementioned parameters on overall structural and functional diversity of Trxs and Grxs.}, } @article {pmid36205366, year = {2022}, author = {Nofrianto, AB and Lawelle, SA and Mokodongan, DF and Masengi, KWA and Inomata, N and Hashiguchi, Y and Kitano, J and Sumarto, BKA and Kakioka, R and Yamahira, K}, title = {Ancient Admixture in Freshwater Halfbeaks of the Genus Nomorhamphus in Southeast Sulawesi.}, journal = {Zoological science}, volume = {39}, number = {5}, pages = {453-458}, doi = {10.2108/zs220023}, pmid = {36205366}, issn = {0289-0003}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *Fresh Water ; Indonesia ; *Mitochondria/genetics ; Phylogeny ; Water ; }, abstract = {Freshwater halfbeaks of the genus Nomorhamphus (Zenarchopteridae) uniquely diversified on Sulawesi Island, where tectonic movements have been very active since the Pliocene. Most species of this genus have quite limited distributions, which indicates that geographic isolations have contributed to their diversification. In this study, we demonstrated that secondary contacts and resultant admixtures between long-isolated species/populations may have also been important. We found that the mitochondrial phylogeny of a group of Nomorhamphus in Southeast Sulawesi was discordant with the nuclear phylogeny. Most notably, individuals in the upper and lower streams of the Moramo River, a small river in this region, clustered with each other in the mitochondrial phylogeny but not in the nuclear phylogeny; in the latter, the lower-stream individuals formed a clade with individuals in the Anduna River, a different river with no present water connection to the Moramo River. Phylogenetic network and population structure analyses using genomic data obtained from RNA-seq revealed that the lower-stream Moramo population admixed with the upper-stream Moramo lineage in ancient times. These findings indicate that the observed mito-nuclear discordance was caused by mitochondrial introgression and not incomplete lineage sorting. The phylogenetic network also revealed several other admixtures between ancient lineages. Repeated admixtures were also evidenced by topological incongruence in population trees estimated using the RNA-seq data. We propose that activities of many fault systems dissecting Southeast Sulawesi caused repeated secondary contact.}, } @article {pmid36212359, year = {2022}, author = {Liu, S and Storti, M and Finazzi, G and Bowler, C and Dorrell, RG}, title = {A metabolic, phylogenomic and environmental atlas of diatom plastid transporters from the model species Phaeodactylum.}, journal = {Frontiers in plant science}, volume = {13}, number = {}, pages = {950467}, pmid = {36212359}, issn = {1664-462X}, abstract = {Diatoms are an important group of algae, contributing nearly 40% of total marine photosynthetic activity. However, the specific molecular agents and transporters underpinning the metabolic efficiency of the diatom plastid remain to be revealed. We performed in silico analyses of 70 predicted plastid transporters identified by genome-wide searches of Phaeodactylum tricornutum. We considered similarity with Arabidopsis thaliana plastid transporters, transcriptional co-regulation with genes encoding core plastid metabolic pathways and with genes encoded in the mitochondrial genomes, inferred evolutionary histories using single-gene phylogeny, and environmental expression trends using Tara Oceans meta-transcriptomics and meta-genomes data. Our data reveal diatoms conserve some of the ion, nucleotide and sugar plastid transporters associated with plants, such as non-specific triose phosphate transporters implicated in the transport of phosphorylated sugars, NTP/NDP and cation exchange transporters. However, our data also highlight the presence of diatom-specific transporter functions, such as carbon and amino acid transporters implicated in intricate plastid-mitochondria crosstalk events. These confirm previous observations that substrate non-specific triose phosphate transporters (TPT) may exist as principal transporters of phosphorylated sugars into and out of the diatom plastid, alongside suggesting probable agents of NTP exchange. Carbon and amino acid transport may be related to intricate metabolic plastid-mitochondria crosstalk. We additionally provide evidence from environmental meta-transcriptomic/meta- genomic data that plastid transporters may underpin diatom sensitivity to ocean warming, and identify a diatom plastid transporter (J43171) whose expression may be positively correlated with temperature.}, } @article {pmid36213509, year = {2022}, author = {Kotov, AA and Taylor, DJ}, title = {Daphnia japonica sp. nov. (Crustacea: Cladocera) an eastern Palearctic montane species with mitochondrial discordance.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e14113}, pmid = {36213509}, issn = {2167-8359}, mesh = {Animals ; *Cladocera/genetics ; Daphnia/genetics ; Phylogeny ; Mitochondria/genetics ; Genes, Mitochondrial ; DNA ; }, abstract = {The Daphnia longispina complex (Crustacea: Cladocera) contains several keystone freshwater species such as D. longispina O.F. Müller (D. rosea Sars is a junior synonym), D. galeata Sars, D. cucullata Sars, and D. dentifera Forbes. The complex is common throughout the Holarctic, but there are several geographic regions where local forms have been assigned to European species names based on a superficial morphological resemblance. Here we examine the species status of a form that was previously assigned to D. rosea from a montane bog pond on Honshu, Japan. We used two nuclear non-coding loci (nDNA), mitochondrial sequences (the ND2 protein-coding region) and morphology for evidence. The mitochondrial gene evidence supported the existence of a divergent lineage that is more closely related to D. galeata than to D. dentifera. However, morphology and the nuclear DNA data indicated a lineage that is most closely related to D. dentifera. As our evidence supported the existence of a cohesive divergent lineage, we described a new species, Daphnia japonica sp. nov. Recognition of local and subalpine diversity in this group is critical as ongoing anthropogenic disturbance has been associated with introductions, local extirpations, and hybridization.}, } @article {pmid36225907, year = {2022}, author = {Zhang, A and Xu, J and Xu, X and Wu, J and Li, P and Wang, B and Fang, H}, title = {Genome-wide identification and characterization of the KCS gene family in sorghum (Sorghum bicolor (L.) Moench).}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e14156}, pmid = {36225907}, issn = {2167-8359}, mesh = {*Sorghum/genetics ; Plant Proteins/genetics ; Phylogeny ; Regulatory Sequences, Nucleic Acid ; Promoter Regions, Genetic ; }, abstract = {The aboveground parts of plants are covered with cuticle, a hydrophobic layer composed of cutin polyester and cuticular wax that can protect plants from various environmental stresses. β-Ketoacyl-CoA synthase (KCS) is the key rate-limiting enzyme in plant wax synthesis. Although the properties of KCS family genes have been investigated in many plant species, the understanding of this gene family in sorghum is still limited. Here, a total of 25 SbKCS genes were identified in the sorghum genome, which were named from SbKCS1 to SbKCS25. Evolutionary analysis among different species divided the KCS family into five subfamilies and the SbKCSs were more closely related to maize, implying a closer evolutionary relationship between sorghum and maize. All SbKCS genes were located on chromosomes 1, 2, 3, 4, 5, 6, 9 and 10, respectively, while Chr 1 and Chr 10 contained more KCS genes than other chromosomes. The prediction results of subcellular localization showed that SbKCSs were mainly expressed in the plasma membrane and mitochondria. Gene structure analysis revealed that there was 0-1 intron in the sorghum KCS family and SbKCSs within the same subgroup were similar. Multiple cis-acting elements related to abiotic stress, light and hormone response were enriched in the promoters of SbKCS genes, which indicated the functional diversity among these genes. The three-dimensional structure analysis showed that a compact spherical space structure was formed by various secondary bonds to maintain the stability of SbKCS proteins, which was necessary for their biological activity. qRT-PCR results revealed that nine randomly selected SbKCS genes expressed differently under drought and salt treatments, among which SbKCS8 showed the greatest fold of expression difference at 12 h after drought and salt stresses, which suggested that the SbKCS genes played a potential role in abiotic stress responses. Taken together, these results provided an insight into investigating the functions of KCS family in sorghum and in response to abiotic stress.}, } @article {pmid36226970, year = {2022}, author = {Chen, L and Kashina, A}, title = {Arginylation Regulates Cytoskeleton Organization and Cell Division and Affects Mitochondria in Fission Yeast.}, journal = {Molecular and cellular biology}, volume = {42}, number = {11}, pages = {e0026122}, pmid = {36226970}, issn = {1098-5549}, support = {R01 NS102435/NS/NINDS NIH HHS/United States ; R35 GM122505/GM/NIGMS NIH HHS/United States ; GM122505//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; NS102435//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; }, mesh = {Animals ; Mice ; *Schizosaccharomyces/genetics/metabolism ; Arginine/metabolism ; Cytoskeleton/metabolism ; Cell Division ; Mitochondria/metabolism ; *Biological Phenomena ; Mammals/metabolism ; }, abstract = {Protein arginylation mediated by arginyltransferase Ate1 is a posttranslational modification of emerging importance implicated in the regulation of mammalian embryogenesis, the cardiovascular system, tissue morphogenesis, cell migration, neurodegeneration, cancer, and aging. Ate1 deletion results in embryonic lethality in mice but does not affect yeast viability, making yeast an ideal system to study the molecular pathways regulated by arginylation. Here, we conducted a global analysis of cytoskeleton-related arginylation-dependent phenotypes in Schizosaccharomyces pombe, a fission yeast species that shares many fundamental features of higher eukaryotic cells. Our studies revealed roles of Ate1 in cell division, cell polarization, organelle transport, and interphase cytoskeleton organization and dynamics. We also found a role of Ate1 in mitochondria morphology and maintenance. Furthermore, targeted mass spectrometry analysis of the total Sc. pombe arginylome identified a number of arginylated proteins, including those that play direct roles in these processes; lack of their arginylation may be responsible for ate1-knockout phenotypes. Our work outlines global biological processes potentially regulated by arginylation and paves the way to unraveling the functions of protein arginylation that are conserved at multiple levels of evolution and potentially constitute the primary role of this modification in vivo.}, } @article {pmid36227729, year = {2022}, author = {Loiacono, FV and Walther, D and Seeger, S and Thiele, W and Gerlach, I and Karcher, D and Schöttler, MA and Zoschke, R and Bock, R}, title = {Emergence of Novel RNA-Editing Sites by Changes in the Binding Affinity of a Conserved PPR Protein.}, journal = {Molecular biology and evolution}, volume = {39}, number = {12}, pages = {}, pmid = {36227729}, issn = {1537-1719}, mesh = {RNA Editing ; *Arabidopsis Proteins/genetics/metabolism ; *Arabidopsis/genetics/metabolism ; Chloroplasts/metabolism ; RNA ; Plant Proteins/genetics/metabolism ; }, abstract = {RNA editing converts cytidines to uridines in plant organellar transcripts. Editing typically restores codons for conserved amino acids. During evolution, specific C-to-U editing sites can be lost from some plant lineages by genomic C-to-T mutations. By contrast, the emergence of novel editing sites is less well documented. Editing sites are recognized by pentatricopeptide repeat (PPR) proteins with high specificity. RNA recognition by PPR proteins is partially predictable, but prediction is often inadequate for PPRs involved in RNA editing. Here we have characterized evolution and recognition of a recently gained editing site. We demonstrate that changes in the RNA recognition motifs that are not explainable with the current PPR code allow an ancient PPR protein, QED1, to uniquely target the ndhB-291 site in Brassicaceae. When expressed in tobacco, the Arabidopsis QED1 edits 33 high-confident off-target sites in chloroplasts and mitochondria causing a spectrum of mutant phenotypes. By manipulating the relative expression levels of QED1 and ndhB-291, we show that the target specificity of the PPR protein depends on the RNA:protein ratio. Finally, our data suggest that the low expression levels of PPR proteins are necessary to ensure the specificity of editing site selection and prevent deleterious off-target editing.}, } @article {pmid36251232, year = {2023}, author = {Giuditta, A and Zucconi, GG and Sadile, A}, title = {Brain Metabolic DNA: A Long Story and Some Conclusions.}, journal = {Molecular neurobiology}, volume = {60}, number = {1}, pages = {228-234}, pmid = {36251232}, issn = {1559-1182}, mesh = {Animals ; Humans ; Mice ; *DNA/metabolism ; *Mitochondria/metabolism ; Brain/metabolism ; Cytoplasm/metabolism ; RNA/metabolism ; DNA, Mitochondrial/metabolism ; }, abstract = {We have previously outlined the main properties of brain metabolic DNA (BMD) and its involvement in circadian oscillations, learning, and post-trial sleep. The presence of BMD in certain subcellular fractions and their behavior in cesium gradients have suggested that BMD originates from cytoplasmic reverse transcription and subsequently acquires a double-stranded configuration. More recently, it has been reported that some DNA sequences of cytoplasmic BMD in learning mice are different from that of the control animals. Furthermore, BMD is located in vicinity of the genes involved in different modifications of synaptic activity, suggesting that BMD may contribute to the brain's response to the changing environment. The present review outlines recent data with a special emphasis on reverse transcription of BMD that may recapitulate the molecular events at the time of the "RNA world" by activating mitochondrial telomerase and generating RNA templates from mitochondrial transcripts. The latter unexpected role of mitochondria is likely to promote a better understanding of mitochondrial contribution to cellular interactions and eukaryotic evolution. An initial step regards the role of human mitochondria in embryonic BMD synthesis, which is exclusively of maternal origin. In addition, mitochondrial transcripts involved in reverse transcription of BMD might possibly reveal unexpected features elucidating mitochondrial involvement in cancer events and neurodegenerative disorders.}, } @article {pmid36253367, year = {2022}, author = {Tobiasson, V and Berzina, I and Amunts, A}, title = {Structure of a mitochondrial ribosome with fragmented rRNA in complex with membrane-targeting elements.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6132}, pmid = {36253367}, issn = {2041-1723}, mesh = {*Chlorophyta/metabolism ; Mitochondria/metabolism ; *Mitochondrial Ribosomes/metabolism ; RNA, Ribosomal/metabolism ; RNA, Ribosomal, 5S/metabolism ; Ribosomes/metabolism ; }, abstract = {Mitoribosomes of green algae display a great structural divergence from their tracheophyte relatives, with fragmentation of both rRNA and proteins as a defining feature. Here, we report a 2.9 Å resolution structure of the mitoribosome from the alga Polytomella magna harbouring a reduced rRNA split into 13 fragments. We found that the rRNA contains a non-canonical reduced form of the 5S, as well as a permutation of the LSU domain I. The mt-5S rRNA is stabilised by mL40 that is also found in mitoribosomes lacking the 5S, which suggests an evolutionary pathway. Through comparison to other ribosomes with fragmented rRNAs, we observe that the pattern is shared across large evolutionary distances, and between cellular compartments, indicating an evolutionary convergence and supporting the concept of a primordial fragmented ribosome. On the protein level, eleven peripherally associated HEAT-repeat proteins are involved in the binding of 3' rRNA termini, and the structure features a prominent pseudo-trimer of one of them (mL116). Finally, in the exit tunnel, mL128 constricts the tunnel width of the vestibular area, and mL105, a homolog of a membrane targeting component mediates contacts with an inner membrane bound insertase. Together, the structural analysis provides insight into the evolution of the ribosomal machinery in mitochondria.}, } @article {pmid36255631, year = {2023}, author = {Marx, C and Marx-Blümel, L and Sonnemann, J and Wang, ZQ}, title = {Assessment of Mitochondrial Dysfunctions After Sirtuin Inhibition.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2589}, number = {}, pages = {269-291}, pmid = {36255631}, issn = {1940-6029}, mesh = {*Sirtuins/metabolism ; Lysine/metabolism ; Phylogeny ; Acetylation ; Histone Deacetylases/metabolism ; Histone Acetyltransferases/metabolism ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; Histone Deacetylase Inhibitors/pharmacology ; }, abstract = {Posttranslational modifications are important for protein functions and cellular signaling pathways. The acetylation of lysine residues is catalyzed by histone acetyltransferases (HATs) and removed by histone deacetylases (HDACs), with the latter being grouped into four phylogenetic classes. The class III of the HDAC family, the sirtuins (SIRTs), contributes to gene expression, genomic stability, cell metabolism, and tumorigenesis. Thus, several specific SIRT inhibitors (SIRTi) have been developed to target cancer cell proliferation. Here we provide an overview of methods to study SIRT-dependent cell metabolism and mitochondrial functionality. The chapter describes metabolic flux analysis using Seahorse analyzers, methods for normalization of Seahorse data, flow cytometry and fluorescence microscopy to determine the mitochondrial membrane potential, mitochondrial content per cell and mitochondrial network structures, and Western blot analysis to measure mitochondrial proteins.}, } @article {pmid36260528, year = {2022}, author = {Zhang, K and Li, J and Li, G and Zhao, Y and Dong, Y and Zhang, Y and Sun, W and Wang, J and Yao, J and Ma, Y and Wang, H and Zhang, Z and Wang, T and Xie, K and Wendel, JF and Liu, B and Gong, L}, title = {Compensatory Genetic and Transcriptional Cytonuclear Coordination in Allopolyploid Lager Yeast (Saccharomyces pastorianus).}, journal = {Molecular biology and evolution}, volume = {39}, number = {11}, pages = {}, pmid = {36260528}, issn = {1537-1719}, mesh = {*Beer ; *Gene Conversion ; Genome ; Cell Nucleus/genetics ; Saccharomyces ; }, abstract = {Cytonuclear coordination between biparental-nuclear genomes and uniparental-cytoplasmic organellar genomes in plants is often resolved by genetic and transcriptional cytonuclear responses. Whether this mechanism also acts in allopolyploid members of other kingdoms is not clear. Additionally, cytonuclear coordination of interleaved allopolyploid cells/individuals within the same population is underexplored. The yeast Saccharomyces pastorianus provides the opportunity to explore cytonuclear coevolution during different growth stages and from novel dimensions. Using S. pastorianus cells from multiple growth stages in the same environment, we show that nuclear mitochondria-targeted genes have undergone both asymmetric gene conversion and growth stage-specific biased expression favoring genes from the mitochondrial genome donor (Saccharomyces eubayanus). Our results suggest that cytonuclear coordination in allopolyploid lager yeast species entails an orchestrated and compensatory genetic and transcriptional evolutionary regulatory shift. The common as well as unique properties of cytonuclear coordination underlying allopolyploidy between unicellular yeasts and higher plants offers novel insights into mechanisms of cytonuclear evolution associated with allopolyploid speciation.}, } @article {pmid36271979, year = {2022}, author = {Hajibarat, Z and Saidi, A and Gorji, AM and Zeinalabedini, M and Ghaffari, MR and Hajibarat, Z and Nasrollahi, A}, title = {Identification of myosin genes and their expression in response to biotic (PVY, PVX, PVS, and PVA) and abiotic (Drought, Heat, Cold, and High-light) stress conditions in potato.}, journal = {Molecular biology reports}, volume = {49}, number = {12}, pages = {11983-11996}, pmid = {36271979}, issn = {1573-4978}, mesh = {*Solanum tuberosum/genetics/metabolism ; Droughts ; Phylogeny ; Plant Proteins/metabolism ; Hot Temperature ; Plant Breeding ; Stress, Physiological/genetics ; Plants/metabolism ; Myosins/genetics/metabolism ; Gene Expression Regulation, Plant/genetics ; }, abstract = {BACKGROUND: Plant organelles are highly motile where their movement is significant for fast distribution of material around the cell, facilitation of the plant's ability to respond to abiotic and biotic signals, and for appropriate growth. Abiotic and biotic stresses are among the major factors limiting crop yields, and biological membranes are the first target of these stresses. Plants utilize adaptive mechanisms namely myosin to repair injured membranes following exposure to abiotic and biotic stresses.

OBJECTIVE: Due to the economic importance and cultivation of potato grown under abiotic and biotic stress prone areas, identification and characterization of myosin family members in potato were performed in the present research.

METHODS: To identify the myosin genes in potato, we performed genome-wide analysis of myosin genes in the S. tuberosum genome using the phytozome. All putative sequences were approved with the interproscan. Bioinformatics analysis was conducted using phylogenetic tree, gene structure, cis-regulatory elements, protein-protein interaction, and gene expression.

RESULT: The majority of the cell machinery contain actin cytoskeleton and myosins, where motility of organelles are dependent on them. Homology-based analysis was applied to determine seven myosin genes in the potato genome. The members of myosin could be categorized into two groups (XI and VIII). Some of myosin proteins were sub-cellularly located in the nucleus containing 71.5% of myosin proteins and other myosin proteins were localized in the mitochondria, plasma-membrane, and cytoplasm. Determination of co-expressed network, promoter analysis, and gene structure were also performed and gene expression pattern of each gene was surveyed. Number of introns in the gene family members varied from 1 to 39. Gene expression analysis demonstrated that StMyoXI-B and StMyoVIII-2 had the highest transcripts, induced by biotic and abiotic stresses in all three tissues of stem, root, and leaves, respectively. Overall, different cis-elements including abiotic and biotic responsive, hormonal responsive, light responsive, defense responsive elements were found in the myosin promoter sequences. Among the cis-elements, the MYB, G-box, ABRE, JA, and SA contributed the most in the plant growth and development, and in response to abiotic and biotic stress conditions.

CONCLUSION: Our results showed that myosin genes can be utilized in breeding programs and genetic engineering of plants with the aim of increasing tolerance to abiotic and biotic stresses, especially to viral stresses such as PVY, PVX, PVA, PVS, high light, drought, cold and heat.}, } @article {pmid36275864, year = {2022}, author = {Bi, R and Li, Y and Xu, M and Zheng, Q and Zhang, DF and Li, X and Ma, G and Xiang, B and Zhu, X and Zhao, H and Huang, X and Zheng, P and Yao, YG}, title = {Direct evidence of CRISPR-Cas9-mediated mitochondrial genome editing.}, journal = {Innovation (Cambridge (Mass.))}, volume = {3}, number = {6}, pages = {100329}, pmid = {36275864}, issn = {2666-6758}, abstract = {Pathogenic mitochondrial DNA (mtDNA) mutations can cause a variety of human diseases. The recent development of genome-editing technologies to manipulate mtDNA, such as mitochondria-targeted DNA nucleases and base editors, offer a promising way for curing mitochondrial diseases caused by mtDNA mutations. The CRISPR-Cas9 system is a widely used tool for genome editing; however, its application in mtDNA editing is still under debate. In this study, we developed a mito-Cas9 system by adding the mitochondria-targeted sequences and 3' untranslated region of nuclear-encoded mitochondrial genes upstream and downstream of the Cas9 gene, respectively. We confirmed that the mito-Cas9 system was transported into mitochondria and enabled knockin of exogenous single-stranded DNA oligonucleotides (ssODNs) into mtDNA based on proteinase and DNase protection assays. Successful knockin of exogenous ssODNs into mtDNA was further validated using polymerase chain reaction-free third-generation sequencing technology. We also demonstrated that RS-1, an agonist of RAD51, significantly increased knockin efficiency of the mito-Cas9 system. Collectively, we provide direct evidence that mtDNA can be edited using the CRISPR-Cas9 system. The mito-Cas9 system could be optimized as a promising approach for the treatment of mitochondrial diseases caused by pathogenic mtDNA mutations, especially those with homoplasmic mtDNA mutations.}, } @article {pmid36280779, year = {2022}, author = {Fan, L and Wu, D and Goremykin, V and Trost, K and Knopp, M and Zhang, C and Martin, WF and Zhu, R}, title = {Reply to: Phylogenetic affiliation of mitochondria with Alpha-II and Rickettsiales is an artefact.}, journal = {Nature ecology & evolution}, volume = {6}, number = {12}, pages = {1832-1835}, pmid = {36280779}, issn = {2397-334X}, mesh = {*Rickettsiales ; Phylogeny ; *Artifacts ; Mitochondria ; }, } @article {pmid36280780, year = {2022}, author = {Martijn, J and Vosseberg, J and Guy, L and Offre, P and Ettema, TJG}, title = {Phylogenetic affiliation of mitochondria with Alpha-II and Rickettsiales is an artefact.}, journal = {Nature ecology & evolution}, volume = {6}, number = {12}, pages = {1829-1831}, pmid = {36280780}, issn = {2397-334X}, mesh = {*Rickettsiales ; Phylogeny ; *Artifacts ; Mitochondria ; }, } @article {pmid36281555, year = {2023}, author = {Guo, C and Wang, A and Cheng, H and Chen, L}, title = {New imaging instrument in animal models: Two-photon miniature microscope and large field of view miniature microscope for freely behaving animals.}, journal = {Journal of neurochemistry}, volume = {164}, number = {3}, pages = {270-283}, doi = {10.1111/jnc.15711}, pmid = {36281555}, issn = {1471-4159}, mesh = {Animals ; *Microscopy ; *Optical Imaging/methods ; Mammals ; Neurons/metabolism ; Behavior, Animal/physiology ; }, abstract = {Over the past decade, novel optical imaging tools have been developed for imaging neuronal activities along with the evolution of fluorescence indicators with brighter expression and higher sensitivity. Miniature microscopes, as revolutionary approaches, enable the imaging of large populations of neuron ensembles in freely behaving rodents and mammals, which allows exploring the neural basis of behaviors. Recent progress in two-photon miniature microscopes and mesoscale single-photon miniature microscopes further expand those affordable methods to navigate neural activities during naturalistic behaviors. In this review article, two-photon miniature microscopy techniques are summarized historically from the first documented attempt to the latest ones, and comparisons are made. The driving force behind and their potential for neuroscientific inquiries are also discussed. Current progress in terms of the mesoscale, i.e., the large field-of-view miniature microscopy technique, is addressed as well. Then, pipelines for registering single cells from the data of two-photon and large field-of-view miniature microscopes are discussed. Finally, we present the potential evolution of the techniques.}, } @article {pmid36282276, year = {2023}, author = {Wang, D and Teng, J and Ning, C and Wang, W and Liu, S and Zhang, Q and Tang, H}, title = {Mitogenome-wide association study on body measurement traits of Wenshang Barred chickens.}, journal = {Animal biotechnology}, volume = {34}, number = {7}, pages = {3154-3161}, doi = {10.1080/10495398.2022.2137035}, pmid = {36282276}, issn = {1532-2378}, mesh = {Animals ; *Chickens/genetics ; *Genome, Mitochondrial/genetics ; Phylogeny ; Phenotype ; Haplotypes/genetics ; Polymorphism, Single Nucleotide/genetics ; DNA, Mitochondrial/genetics ; }, abstract = {Mitochondria are best known for synthesizing ATP through the tricarboxylic acid cycle and oxidative phosphorylation. The cytoplasmic mitochondrial DNA (mtDNA) is important for maintaining the function. This study was designed to reveal the effect of mtDNA on chicken body measurement traits (BMTs). A population of 605 Wenshang Barred chickens were recorded BMTs, including body slope length, keel length, chest width, etc. The single-nucleotide polymorphisms (SNPs) of their mitogenomes were detected by PCR amplification and DNA sequencing. Totally 69 mutations in mitogenome were discovered, including 18 in noncoding region and 51 in coding region. By multi-sequence alignment and haplotype construction, the chickens were clustered into eight haplotypes and further three haplogroups. The association between BMTs and mtDNA SNPs, haplotypes and haplogroups were analyzed in the linear model by ASReml, respectively. Among them, the SNP mt11086 T/C in ND3 was found to significantly affect chest dept (p < .05) and was highly conservative by phylogenetic conservation analyses, which reflected the genetic effect on body size and growth of chickens. No significant association between the mitochondrial haplotypes or haplogroups and BMTs was found. The polymorphic site reflecting body size could be put into chicken breeding programs as the genetic marker.}, } @article {pmid36288802, year = {2022}, author = {Weaver, RJ and Rabinowitz, S and Thueson, K and Havird, JC}, title = {Genomic Signatures of Mitonuclear Coevolution in Mammals.}, journal = {Molecular biology and evolution}, volume = {39}, number = {11}, pages = {}, pmid = {36288802}, issn = {1537-1719}, support = {R35 GM142836/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *DNA, Mitochondrial/genetics ; *Genes, Mitochondrial ; Mammals/genetics ; Cell Nucleus/genetics ; Mitochondrial Proteins/genetics ; Genomics ; }, abstract = {Mitochondrial (mt) and nuclear-encoded proteins are integrated in aerobic respiration, requiring co-functionality among gene products from fundamentally different genomes. Different evolutionary rates, inheritance mechanisms, and selection pressures set the stage for incompatibilities between interacting products of the two genomes. The mitonuclear coevolution hypothesis posits that incompatibilities may be avoided if evolution in one genome selects for complementary changes in interacting genes encoded by the other genome. Nuclear compensation, in which deleterious mtDNA changes are offset by compensatory nuclear changes, is often invoked as the primary mechanism for mitonuclear coevolution. Yet, direct evidence supporting nuclear compensation is rare. Here, we used data from 58 mammalian species representing eight orders to show strong correlations between evolutionary rates of mt and nuclear-encoded mt-targeted (N-mt) proteins, but not between mt and non-mt-targeted nuclear proteins, providing strong support for mitonuclear coevolution across mammals. N-mt genes with direct mt interactions also showed the strongest correlations. Although most N-mt genes had elevated dN/dS ratios compared to mt genes (as predicted under nuclear compensation), N-mt sites in close contact with mt proteins were not overrepresented for signs of positive selection compared to noncontact N-mt sites (contrary to predictions of nuclear compensation). Furthermore, temporal patterns of N-mt and mt amino acid substitutions did not support predictions of nuclear compensation, even in positively selected, functionally important residues with direct mitonuclear contacts. Overall, our results strongly support mitonuclear coevolution across ∼170 million years of mammalian evolution but fail to support nuclear compensation as the major mode of mitonuclear coevolution.}, } @article {pmid36293209, year = {2022}, author = {Liu, Q and Zhang, L and Zou, Y and Tao, Y and Wang, B and Li, B and Liu, R and Wang, B and Ding, L and Cui, Q and Lin, J and Mao, B and Xiong, W and Yu, M}, title = {Modulating p-AMPK/mTOR Pathway of Mitochondrial Dysfunction Caused by MTERF1 Abnormal Expression in Colorectal Cancer Cells.}, journal = {International journal of molecular sciences}, volume = {23}, number = {20}, pages = {}, pmid = {36293209}, issn = {1422-0067}, support = {32160167, 31760331, 31260276, 31601155, 81860531, 81760507, 82160516//National Nature Science Foundation of China/ ; 202001BB0500080, 202001BB050041//the Key Project of Science and Technology Department of Yunnan Province/ ; 202101AT070006//the Applied Basic Research Programs of Science and Technology Department of Yunnan Province/ ; No. 2017HB077//the Reserve Talents of Young and Middle-aged Academic and Technical Leaders of Yunnan Province/ ; 2020267, 2021Y314//d Yunnan University's Research In-novation Fund for Graduate Students/ ; }, mesh = {Humans ; AMP-Activated Protein Kinases/metabolism ; Reactive Oxygen Species/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Cell Proliferation/genetics ; DNA, Mitochondrial/genetics ; Mitochondria/metabolism ; HCT116 Cells ; Cell Line, Tumor ; *Colonic Neoplasms/metabolism ; Adenosine Triphosphate/metabolism ; *Colorectal Neoplasms/pathology ; Gene Expression Regulation, Neoplastic ; }, abstract = {Human mitochondrial transcription termination factor 1 (MTERF1) has been demonstrated to play an important role in mitochondrial gene expression regulation. However, the molecular mechanism of MTERF1 in colorectal cancer (CRC) remains largely unknown. Here, we found that MTERF1 expression was significantly increased in colon cancer tissues compared with normal colorectal tissue by Western blotting, immunohistochemistry, and tissue microarrays (TMA). Overexpression of MTERF1 in the HT29 cell promoted cell proliferation, migration, invasion, and xenograft tumor formation, whereas knockdown of MTERF1 in HCT116 cells appeared to be the opposite phenotype to HT29 cells. Furthermore, MTERF1 can increase mitochondrial DNA (mtDNA) replication, transcription, and protein synthesis in colorectal cancer cells; increase ATP levels, the mitochondrial crista density, mitochondrial membrane potential, and oxygen consumption rate (OCR); and reduce the ROS production in colorectal cancer cells, thereby enhancing mitochondrial oxidative phosphorylation (OXPHOS) activity. Mechanistically, we revealed that MTERF1 regulates the AMPK/mTOR signaling pathway in cancerous cell lines, and we also confirmed the involvement of the AMPK/mTOR signaling pathway in both xenograft tumor tissues and colorectal cancer tissues. In summary, our data reveal an oncogenic role of MTERF1 in CRC progression, indicating that MTERF1 may represent a new therapeutic target in the future.}, } @article {pmid36309009, year = {2022}, author = {Liu, Y and Zhou, J and Zhang, N and Wu, X and Zhang, Q and Zhang, W and Li, X and Tian, Y}, title = {Two sensory neurons coordinate the systemic mitochondrial stress response via GPCR signaling in C. elegans.}, journal = {Developmental cell}, volume = {57}, number = {21}, pages = {2469-2482.e5}, doi = {10.1016/j.devcel.2022.10.001}, pmid = {36309009}, issn = {1878-1551}, mesh = {Animals ; *Caenorhabditis elegans/metabolism ; *Caenorhabditis elegans Proteins/genetics/metabolism ; Mitochondria/metabolism ; Unfolded Protein Response ; Sensory Receptor Cells/metabolism ; Receptors, G-Protein-Coupled/genetics/metabolism ; }, abstract = {Mitochondrial perturbations within neurons communicate stress signals to peripheral tissues, coordinating organismal-wide mitochondrial homeostasis for optimal fitness. However, the neuronal control of the systemic stress regulation remains poorly understood. Here, we identified a G-protein-coupled receptor (GPCR), SRZ-75, that couples with Gαq signaling in a pair of chemosensory ADL neurons to drive the mitochondrial unfolded protein response (UPR[mt]) activation in the intestine via the release of neuropeptides in Caenorhabditis elegans. Constitutive activation of Gαq signaling in the ADL neurons is sufficient to induce the intestinal UPR[mt], leading to increased stress resistance and metabolic adaptations. Ablation of ADL neurons attenuates the intestinal UPR[mt] activation in response to various forms of neuronal mitochondrial dysfunction. Thus, GPCR and its Gαq downstream signaling in two sensory neurons coordinate the systemic UPR[mt] activation, representing a previously uncharacterized, but potentially conserved, neuronal signaling for organismal-wide mitochondrial stress regulation.}, } @article {pmid36321837, year = {2022}, author = {McGlynn, SE and Perkins, G and Sim, MS and Mackey, M and Deerinck, TJ and Thor, A and Phan, S and Ballard, D and Ellisman, MH and Orphan, VJ}, title = {A Cristae-Like Microcompartment in Desulfobacterota.}, journal = {mBio}, volume = {13}, number = {6}, pages = {e0161322}, pmid = {36321837}, issn = {2150-7511}, support = {P41 GM103412/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anaerobiosis ; *Bacteria/metabolism ; *Archaea/metabolism ; Methane/metabolism ; Sulfates/metabolism ; Oxidation-Reduction ; Geologic Sediments/microbiology ; Phylogeny ; }, abstract = {Some Alphaproteobacteria contain intracytoplasmic membranes (ICMs) and proteins homologous to those responsible for the mitochondrial cristae, an observation which has given rise to the hypothesis that the Alphaproteobacteria endosymbiont had already evolved cristae-like structures and functions. However, our knowledge of microbial fine structure is still limited, leaving open the possibility of structurally homologous ICMs outside the Alphaproteobacteria. Here, we report on the detailed characterization of lamellar cristae-like ICMs in environmental sulfate-reducing Desulfobacterota that form syntrophic partnerships with anaerobic methane-oxidizing (ANME) archaea. These structures are junction-bound to the cytoplasmic membrane and resemble the form seen in the lamellar cristae of opisthokont mitochondria. Extending these observations, we also characterized similar structures in Desulfovibrio carbinolicus, a close relative of the magnetotactic D. magneticus, which does not contain magnetosomes. Despite a remarkable structural similarity, the key proteins involved in cristae formation have not yet been identified in Desulfobacterota, suggesting that an analogous, but not a homologous, protein organization system developed during the evolution of some members of Desulfobacterota. IMPORTANCE Working with anaerobic consortia of methane oxidizing ANME archaea and their sulfate-reducing bacterial partners recovered from deep sea sediments and with the related sulfate-reducing bacterial isolate D. carbinolicus, we discovered that their intracytoplasmic membranes (ICMs) appear remarkably similar to lamellar cristae. Three-dimensional electron microscopy allowed for the novel analysis of the nanoscale attachment of ICMs to the cytoplasmic membrane, and these ICMs are structurally nearly identical to the crista junction architecture seen in metazoan mitochondria. However, the core junction-forming proteins must be different. The outer membrane vesicles were observed to bud from syntrophic Desulfobacterota, and darkly stained granules were prominent in both Desulfobacterota and D. carbinolicus. These findings expand the taxonomic breadth of ICM-producing microorganisms and add to our understanding of three-dimensional microbial fine structure in environmental microorganisms.}, } @article {pmid36323233, year = {2022}, author = {Picard, M and Shirihai, OS}, title = {Mitochondrial signal transduction.}, journal = {Cell metabolism}, volume = {34}, number = {11}, pages = {1620-1653}, pmid = {36323233}, issn = {1932-7420}, support = {R01 AG066828/AG/NIA NIH HHS/United States ; R21 MH123927/MH/NIMH NIH HHS/United States ; R35 GM119793/GM/NIGMS NIH HHS/United States ; R01 MH119336/MH/NIMH NIH HHS/United States ; R01 MH122706/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Mitochondria/metabolism ; *Signal Transduction ; Cell Communication ; Cell Nucleus/metabolism ; }, abstract = {The analogy of mitochondria as powerhouses has expired. Mitochondria are living, dynamic, maternally inherited, energy-transforming, biosynthetic, and signaling organelles that actively transduce biological information. We argue that mitochondria are the processor of the cell, and together with the nucleus and other organelles they constitute the mitochondrial information processing system (MIPS). In a three-step process, mitochondria (1) sense and respond to both endogenous and environmental inputs through morphological and functional remodeling; (2) integrate information through dynamic, network-based physical interactions and diffusion mechanisms; and (3) produce output signals that tune the functions of other organelles and systemically regulate physiology. This input-to-output transformation allows mitochondria to transduce metabolic, biochemical, neuroendocrine, and other local or systemic signals that enhance organismal adaptation. An explicit focus on mitochondrial signal transduction emphasizes the role of communication in mitochondrial biology. This framework also opens new avenues to understand how mitochondria mediate inter-organ processes underlying human health.}, } @article {pmid36324074, year = {2022}, author = {Zhao, B and Gao, S and Zhao, M and Lv, H and Song, J and Wang, H and Zeng, Q and Liu, J}, title = {Mitochondrial genomic analyses provide new insights into the "missing" atp8 and adaptive evolution of Mytilidae.}, journal = {BMC genomics}, volume = {23}, number = {1}, pages = {738}, pmid = {36324074}, issn = {1471-2164}, mesh = {Animals ; *Genome, Mitochondrial ; *Mytilidae/genetics ; Phylogeny ; Genes, Mitochondrial ; Mitochondrial Proton-Translocating ATPases/genetics ; Genomics/methods ; }, abstract = {BACKGROUND: Mytilidae, also known as marine mussels, are widely distributed in the oceans worldwide. Members of Mytilidae show a tremendous range of ecological adaptions, from the species distributed in freshwater to those that inhabit in deep-sea. Mitochondria play an important role in energy metabolism, which might contribute to the adaptation of Mytilidae to different environments. In addition, some bivalve species are thought to lack the mitochondrial protein-coding gene ATP synthase F0 subunit 8. Increasing studies indicated that the absence of atp8 may be caused by annotation difficulties for atp8 gene is characterized by highly divergent, variable length.

RESULTS: In this study, the complete mitochondrial genomes of three marine mussels (Xenostrobus securis, Bathymodiolus puteoserpentis, Gigantidas vrijenhoeki) were newly assembled, with the lengths of 14,972 bp, 20,482, and 17,786 bp, respectively. We annotated atp8 in the sequences that we assembled and the sequences lacking atp8. The newly annotated atp8 sequences all have one predicted transmembrane domain, a similar hydropathy profile, as well as the C-terminal region with positively charged amino acids. Furthermore, we reconstructed the phylogenetic trees and performed positive selection analysis. The results showed that the deep-sea bathymodiolines experienced more relaxed evolutionary constraints. And signatures of positive selection were detected in nad4 of Limnoperna fortunei, which may contribute to the survival and/or thriving of this species in freshwater.

CONCLUSIONS: Our analysis supported that atp8 may not be missing in the Mytilidae. And our results provided evidence that the mitochondrial genes may contribute to the adaptation of Mytilidae to different environments.}, } @article {pmid36326769, year = {2023}, author = {Kierepka, EM and Preckler-Quisquater, S and Reding, DM and Piaggio, AJ and Riley, SPD and Sacks, BN}, title = {Genomic analyses of gray fox lineages suggest ancient divergence and secondary contact in the southern Great Plains.}, journal = {The Journal of heredity}, volume = {114}, number = {2}, pages = {110-119}, doi = {10.1093/jhered/esac060}, pmid = {36326769}, issn = {1465-7333}, mesh = {Humans ; Animals ; *Foxes/genetics ; Phylogeny ; *DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Genomics ; }, abstract = {The gray fox (Urocyon cinereoargenteus) lineage diverged from all other extant canids at their most basal node and is restricted to the Americas. Previous mitochondrial analysis from coastal populations identified deeply divergent (up to 1 Mya) eastern and western lineages that predate most intraspecific splits in carnivores. We conducted genotyping by sequencing and mitochondrial analysis on gray foxes sampled across North America to determine geographic concordance between nuclear and mitochondrial contact zones and divergence times. We also estimated the admixture within the contact zone between eastern and western gray foxes based on nuclear DNA. Both datasets confirmed that eastern and western lineages met in the southern Great Plains (i.e. Texas and Oklahoma), where they maintained high differentiation. Admixture was generally low, with the majority of admixed individuals carrying <10% ancestry from the other lineage. Divergence times confirmed a mid-Pleistocene split, similar to the mitochondrial estimates. Taken together, findings suggest gray fox lineages represent an ancient divergence event, far older than most intraspecific divergences in North American carnivores. Low admixture may reflect a relatively recent time since secondary contact (e.g. post-Pleistocene) or, alternatively, ecological or reproductive barriers between lineages. Though further research is needed to disentangle these factors, our genomic investigation suggests species-level divergence exists between eastern and western gray fox lineages.}, } @article {pmid36327950, year = {2023}, author = {Filimonova, S}, title = {Fine structure of the posterior midgut in the mite Anystis baccarum (L.).}, journal = {Arthropod structure & development}, volume = {72}, number = {}, pages = {101218}, doi = {10.1016/j.asd.2022.101218}, pmid = {36327950}, issn = {1873-5495}, mesh = {Animals ; *Mites/ultrastructure ; Phylogeny ; Digestive System/ultrastructure ; *Arachnida ; Epithelial Cells ; }, abstract = {Homology of the posterior midgut regions (PMG) in different phylogenetic lineages of acariform mites (superorder Acariformes) remains unresolved. In the order Trombidiformes, the ultrastructure of the PMG is known primarily in derived groups; thus this study focuses on species belonging to a relatively basal trombidiform family. PMG of Anystis baccarum consists of the colon and postcolon separated by a small intercolon. The fine structure of the colon and postcolon is close to that of the corresponding organs of sarcoptiform mites with the epithelium showing absorptive and endocytotic activity. The epithelial cells produce a variety of excretory vacuoles and a peritrophic matrix around the feces. Morover, the epithelium of the postcolon is characterized by the highest apical brush border and especially numerous mitochondria suggesting involvement in water and ion absorption. The intercolon functions as a sphincter lined with an epithelium capable of producing excretory granules. A pair of short blind extensions arises assimmetrically from the intercolon into the body cavity. Ultrastructurally, these extensions are similar to the arachnid Malpighian tubules and may be their reduced version. Rare endocrine-like cells have been observed in the colon and postcolon.}, } @article {pmid36330786, year = {2022}, author = {De, AK and Bhattacharya, D and Sawhney, S and Bala, P and Sunder, J and Sujatha, T and Ponraj, P and Chakurkar, EB}, title = {Molecular characterization of Rhipicephalus microplus in Andaman and Nicobar Islands, India: an insight into genetic assemblages.}, journal = {Journal of genetics}, volume = {101}, number = {}, pages = {}, pmid = {36330786}, issn = {0973-7731}, mesh = {Animals ; *Rhipicephalus/genetics ; Phylogeny ; Haplotypes ; Geography ; Mitochondria/genetics ; India ; Islands ; }, abstract = {The tick, Rhipicephalus microplus is considered as the most notorious ectoparasite of veterinary importance in tropical and sub-tropical regions of the world. The present study deals with the molecular characterization of R. microplus in different regions of Andaman and Nicobar Islands using sequence information of mitochondrial cytochrome C oxidase subunit I (COX1) and their phylogenetic relationship with other Indian R. microplus genotypes. DNA polymorphism study identified a total of eight haplotypes with haplotype diversity of 0.909 ± 0.065 and nucleotide diversity of 0.01911 ± 0.00493. Currently, R. microplus complex consists of five taxa; R. microplus clade A sensu Burger et al. (2014), R. microplus clade B sensu Burger et al. (2014), R. microplus clade C sensu Low et al. (2015), R. australis and R. annulatus. Phylogenetic analysis revealed the presence of two clades (clade A and clade C) of R. microplus in Andaman and Nicobar isolates; Nicobar isolates belonged to clade A whereas Andaman isolates belonged to clade C of R. microplus complex. All the other Indian sequences retrieved from GenBank belonged to clade C of R. microplus complex. Andaman isolates under clade C of R. microplus were phylogenetically distinct from Indian isolates, which indicates independent speciation under isolated island milieu. In Indian isolates, no host-specific or geographical location-specific sub-clustering was observed which indicates the species jumping potential of the R. microplus tick. Therefore, this study indicated the presence of two different genetic makeup of R. microplus complex in two areas of the Andaman and Nicobar archipelago separated by a natural geographical barrier. This indicates presence of two different founding populations of ticks, one in the south and north-middle Andaman and the other in Nicobar Island.}, } @article {pmid36331499, year = {2023}, author = {Lestari, SM and Khatun, MF and Acharya, R and Sharma, SR and Shrestha, YK and Jahan, SMH and Aye, TT and Lynn, OM and Win, NKK and Hoat, TX and Thi Dao, H and Tsai, CW and Lee, J and Hwang, HS and Kil, EJ and Lee, S and Kim, SM and Lee, KY}, title = {Genetic diversity of cryptic species of Bemisia tabaci in Asia.}, journal = {Archives of insect biochemistry and physiology}, volume = {112}, number = {2}, pages = {e21981}, doi = {10.1002/arch.21981}, pmid = {36331499}, issn = {1520-6327}, support = {I-1543086-2017-21-01//Exportation Support of Agricultural Products at Animal and Plant Quarantine Agency/ ; Z-1543086-2017-21-01//Exportation Support of Agricultural Products at Animal and Plant Quarantine Agency/ ; }, mesh = {Animals ; Phylogeny ; Asia ; China ; *Mitochondria ; *Hemiptera/genetics ; Genetic Variation ; }, abstract = {Bemisia tabaci is a species complex consisting of various genetically different cryptic species worldwide. To understand the genetic characteristics and geographic distribution of cryptic species of B. tabaci in Asia, we conducted an extensive collection of B. tabaci samples in ten Asian countries (Bangladesh, Indonesia, Japan, Korea, Myanmar, Nepal, Philippines, Singapore, Taiwan, and Vietnam) from 2013 to 2020 and determined 56 different partial sequences of mitochondrial cytochrome oxidase subunit I (COI) DNA. In addition, information on 129 COI sequences of B. tabaci identified from 16 Asian countries was downloaded from the GenBank database. Among the total 185 COI sequences of B. tabaci, the sequence variation reached to 19.68%. In addition, there were 31 cryptic species updated from 16 countries in Asia, that is, Asia I, Asia I India, Asia II (1-13), Asia III, Asia IV, Asia V, China 1-6, MEAM (1, 2, K), MED, Australia/Indonesia, Japan (1 and 2). Further, MED cryptic species consisted of 2 clades, Q1 and Q2. This study provides updated information to understand the genetic variation and geographic diversity of B. tabaci in Asia.}, } @article {pmid36336814, year = {2023}, author = {Vilaça, ST and Maroso, F and Lara, P and de Thoisy, B and Chevallier, D and Arantes, LS and Santos, FR and Bertorelle, G and Mazzoni, CJ}, title = {Evidence of backcross inviability and mitochondrial DNA paternal leakage in sea turtle hybrids.}, journal = {Molecular ecology}, volume = {32}, number = {3}, pages = {628-643}, doi = {10.1111/mec.16773}, pmid = {36336814}, issn = {1365-294X}, support = {//Alexander von Humboldt-Stiftung/ ; //Centre National de la Recherche Scientifique/ ; 491292795//Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)/ ; }, mesh = {Animals ; *DNA, Mitochondrial/genetics ; *Turtles/genetics ; Mitochondria/genetics ; Biological Evolution ; Polymerase Chain Reaction ; }, abstract = {Hybridization is known to be part of many species' evolutionary history. Sea turtles have a fascinating hybridization system in which species separated by as much as 43 million years are still capable of hybridizing. Indeed, the largest nesting populations in Brazil of loggerheads (Caretta caretta) and hawksbills (Eretmochelys imbricata) have a high incidence of hybrids between these two species. A third species, olive ridleys (Lepidochelys olivacea), is also known to hybridize although at a smaller scale. Here, we used restriction site-associated DNA sequencing (RAD-Seq) markers, mitogenomes, and satellite-telemetry to investigate the patterns of hybridization and introgression in the Brazilian sea turtle population and their relationship with the migratory behaviours between feeding and nesting aggregations. We also explicitly test if the mixing of two divergent genomes in sea turtle hybrids causes mitochondrial paternal leakage. We developed a new species-specific PCR-assay capable of detecting mitochondrial DNA (mtDNA) inheritance from both parental species and performed ultra-deep sequencing to estimate the abundance of each mtDNA type. Our results show that all adult hybrids are first generation (F1) and most display a loggerhead migratory behaviour. We detected paternal leakage in F1 hybrids and different proportions of mitochondria from maternal and paternal species. Although previous studies showed no significant fitness decrease in hatchlings, our results support genetically-related hybrid breakdown possibly caused by cytonuclear incompatibility. Further research on hybrids from other populations in addition to Brazil and between different species will show if backcross inviability and mitochondrial paternal leakage is observed across sea turtle species.}, } @article {pmid36351770, year = {2022}, author = {Hénault, M and Marsit, S and Charron, G and Landry, CR}, title = {Hybridization drives mitochondrial DNA degeneration and metabolic shift in a species with biparental mitochondrial inheritance.}, journal = {Genome research}, volume = {32}, number = {11-12}, pages = {2043-2056}, pmid = {36351770}, issn = {1549-5469}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; *Genes, Mitochondrial ; Mitochondria/genetics ; Hybridization, Genetic ; Genotype ; Saccharomyces cerevisiae/genetics ; }, abstract = {Mitochondrial DNA (mtDNA) is a cytoplasmic genome that is essential for respiratory metabolism. Although uniparental mtDNA inheritance is most common in animals and plants, distinct mtDNA haplotypes can coexist in a state of heteroplasmy, either because of paternal leakage or de novo mutations. mtDNA integrity and the resolution of heteroplasmy have important implications, notably for mitochondrial genetic disorders, speciation, and genome evolution in hybrids. However, the impact of genetic variation on the transition to homoplasmy from initially heteroplasmic backgrounds remains largely unknown. Here, we use Saccharomyces yeasts, fungi with constitutive biparental mtDNA inheritance, to investigate the resolution of mtDNA heteroplasmy in a variety of hybrid genotypes. We previously designed 11 crosses along a gradient of parental evolutionary divergence using undomesticated isolates of Saccharomyces paradoxus and Saccharomyces cerevisiae Each cross was independently replicated 48 to 96 times, and the resulting 864 hybrids were evolved under relaxed selection for mitochondrial function. Genome sequencing of 446 MA lines revealed extensive mtDNA recombination, but the recombination rate was not predicted by parental divergence level. We found a strong positive relationship between parental divergence and the rate of large-scale mtDNA deletions, which led to the loss of respiratory metabolism. We also uncovered associations between mtDNA recombination, mtDNA deletion, and genome instability that were genotype specific. Our results show that hybridization in yeast induces mtDNA degeneration through large-scale deletion and loss of function, with deep consequences for mtDNA evolution, metabolism, and the emergence of reproductive isolation.}, } @article {pmid36353057, year = {2022}, author = {Liang, P and Wang, S and Lin, Y and Wang, L and Zhao, L and Liu, S}, title = {The complete mitochondrial genome of Cepola schlegelii from the East China Sea.}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {7}, number = {11}, pages = {1925-1927}, pmid = {36353057}, issn = {2380-2359}, abstract = {Cepola schlegelii (Bleeker 1854) belongs to the genus Cepola in the family Cepolidae and order Priacanthiformes. The complete mitochondrial genome of C. schlegelii was sequenced and analyzed by a high-throughput sequencing approach. The full length of the genome is 17,020 bp, including 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and a non-coding control region (D-loop). Phylogenetic analysis based on complete mitochondrial genomes revealed that C. schlegelii was most closely related to Acanthocepola krusensternii. The complete mitochondrial sequence of C. schlegelii will enrich the mitochondrial genome database and provide useful resources for population genetics and evolution analyses.}, } @article {pmid36355038, year = {2022}, author = {Raval, PK and Garg, SG and Gould, SB}, title = {Endosymbiotic selective pressure at the origin of eukaryotic cell biology.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36355038}, issn = {2050-084X}, mesh = {*Eukaryotic Cells/physiology ; *Symbiosis/genetics ; Biological Evolution ; Eukaryota/genetics ; Archaea/genetics ; Cell Nucleus ; Meiosis ; Biology ; Phylogeny ; }, abstract = {The dichotomy that separates prokaryotic from eukaryotic cells runs deep. The transition from pro- to eukaryote evolution is poorly understood due to a lack of reliable intermediate forms and definitions regarding the nature of the first host that could no longer be considered a prokaryote, the first eukaryotic common ancestor, FECA. The last eukaryotic common ancestor, LECA, was a complex cell that united all traits characterising eukaryotic biology including a mitochondrion. The role of the endosymbiotic organelle in this radical transition towards complex life forms is, however, sometimes questioned. In particular the discovery of the asgard archaea has stimulated discussions regarding the pre-endosymbiotic complexity of FECA. Here we review differences and similarities among models that view eukaryotic traits as isolated coincidental events in asgard archaeal evolution or, on the contrary, as a result of and in response to endosymbiosis. Inspecting eukaryotic traits from the perspective of the endosymbiont uncovers that eukaryotic cell biology can be explained as having evolved as a solution to housing a semi-autonomous organelle and why the addition of another endosymbiont, the plastid, added no extra compartments. Mitochondria provided the selective pressures for the origin (and continued maintenance) of eukaryotic cell complexity. Moreover, they also provided the energetic benefit throughout eukaryogenesis for evolving thousands of gene families unique to eukaryotes. Hence, a synthesis of the current data lets us conclude that traits such as the Golgi apparatus, the nucleus, autophagosomes, and meiosis and sex evolved as a response to the selective pressures an endosymbiont imposes.}, } @article {pmid36355348, year = {2023}, author = {Klucnika, A and Mu, P and Jezek, J and McCormack, M and Di, Y and Bradshaw, CR and Ma, H}, title = {REC drives recombination to repair double-strand breaks in animal mtDNA.}, journal = {The Journal of cell biology}, volume = {222}, number = {1}, pages = {}, pmid = {36355348}, issn = {1540-8140}, support = {203144/WT_/Wellcome Trust/United Kingdom ; 203767/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 202269/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; C6946/A24843/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Humans ; *DNA Repair/genetics ; *DNA, Mitochondrial/genetics ; Drosophila/genetics ; *Drosophila Proteins/genetics ; Homologous Recombination ; Meiosis ; Mitochondria/genetics ; Minichromosome Maintenance Proteins ; }, abstract = {Mechanisms that safeguard mitochondrial DNA (mtDNA) limit the accumulation of mutations linked to mitochondrial and age-related diseases. Yet, pathways that repair double-strand breaks (DSBs) in animal mitochondria are poorly understood. By performing a candidate screen for mtDNA repair proteins, we identify that REC-an MCM helicase that drives meiotic recombination in the nucleus-also localizes to mitochondria in Drosophila. We show that REC repairs mtDNA DSBs by homologous recombination in somatic and germline tissues. Moreover, REC prevents age-associated mtDNA mutations. We further show that MCM8, the human ortholog of REC, also localizes to mitochondria and limits the accumulation of mtDNA mutations. This study provides mechanistic insight into animal mtDNA recombination and demonstrates its importance in safeguarding mtDNA during ageing and evolution.}, } @article {pmid36360182, year = {2022}, author = {Wang, Y and Hua, X and Shi, X and Wang, C}, title = {Origin, Evolution, and Research Development of Donkeys.}, journal = {Genes}, volume = {13}, number = {11}, pages = {}, pmid = {36360182}, issn = {2073-4425}, mesh = {Animals ; *Equidae/genetics ; *Microsatellite Repeats ; Genome/genetics ; Genomics ; Mitochondria/genetics ; }, abstract = {Lack of archaeological and whole-genome diversity data has restricted current knowledge of the evolutionary history of donkeys. With the advancement of science and technology, the discovery of archaeological evidence, the development of molecular genetics, and the improvement of whole-genome sequencing technology, the in-depth understanding of the origin and domestication of donkeys has been enhanced, however. Given the lack of systematic research, the present study carefully screened and collected multiple academic papers and books, journals, and literature on donkeys over the past 15 years. The origin and domestication of donkeys are reviewed in this paper from the aspects of basic information, cultural origin, bioarcheology, mitochondrial and chromosomal microsatellite sequences, and whole-genome sequence comparison. It also highlights and reviews genome assembly technology, by assembling the genome of an individual organism and comparing it with related sample genomes, which can be used to produce more accurate results through big data statistics, analysis, and computational correlation models. Background: The donkey industry in the world and especially in China is developing rapidly, and donkey farming is transforming gradually from the family farming model to large-scale, intensive, and integrated industrial operations, which could ensure the stability of product quality and quantity. However, theoretical research on donkey breeding and its technical development lags far behind that of other livestock, thereby limiting its industrial development. This review provides holistic information for the donkey industry and researchers, that could promote theoretical research, genomic selection (GS), and reproductive management of the donkey population.}, } @article {pmid36360198, year = {2022}, author = {Boulygina, E and Sharko, F and Cheprasov, M and Gladysheva-Azgari, M and Slobodova, N and Tsygankova, S and Rastorguev, S and Grigorieva, L and Kopp, M and Fernandes, JMO and Novgorodov, G and Boeskorov, G and Protopopov, A and Hwang, WS and Tikhonov, A and Nedoluzhko, A}, title = {Ancient DNA Reveals Maternal Philopatry of the Northeast Eurasian Brown Bear (Ursus arctos) Population during the Holocene.}, journal = {Genes}, volume = {13}, number = {11}, pages = {}, pmid = {36360198}, issn = {2073-4425}, mesh = {Animals ; *Ursidae/genetics ; DNA, Ancient ; Phylogeny ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; }, abstract = {Significant palaeoecological and paleoclimatic changes that took place during Late Pleistocene-Early Holocene transition are considered important factors that led to megafauna extinctions. Unlike many other species, the brown bear (Ursus arctos) has survived this geological time. Despite the fact that several mitochondrial DNA clades of brown bears became extinct at the end of the Pleistocene, this species is still widely distributed in Northeast Eurasia. Here, using the ancient DNA analysis of a brown bear individual that inhabited Northeast Asia in the Middle Holocene (3460 ± 40 years BP) and comparative phylogenetic analysis, we show a significant mitochondrial DNA similarity of the studied specimen with modern brown bears inhabiting Yakutia and Chukotka. In this study, we clearly demonstrate the maternal philopatry of the Northeastern Eurasian U. arctos population during the several thousand years of the Holocene.}, } @article {pmid36361939, year = {2022}, author = {Alves, R and Pazos-Gil, M and Medina-Carbonero, M and Sanz-Alcázar, A and Delaspre, F and Tamarit, J}, title = {Evolution of an Iron-Detoxifying Protein: Eukaryotic and Rickettsia Frataxins Contain a Conserved Site Which Is Not Present in Their Bacterial Homologues.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36361939}, issn = {1422-0067}, support = {PID2020-118296RB-I00//Ministerio de Ciencia e Innovación (Spain)/ ; }, mesh = {Humans ; Bacterial Proteins/chemistry/metabolism ; Escherichia coli/metabolism ; Escherichia coli Proteins/genetics ; Eukaryota/metabolism ; Friedreich Ataxia/genetics/metabolism ; Iron/metabolism ; *Iron-Binding Proteins/chemistry/metabolism ; *Neurodegenerative Diseases ; *Rickettsia/metabolism ; Tyrosine/metabolism ; Mitochondria/metabolism/microbiology ; Frataxin ; }, abstract = {Friedreich's ataxia is a neurodegenerative disease caused by mutations in the frataxin gene. Frataxin homologues, including bacterial CyaY proteins, can be found in most species and play a fundamental role in mitochondrial iron homeostasis, either promoting iron assembly into metaloproteins or contributing to iron detoxification. While several lines of evidence suggest that eukaryotic frataxins are more effective than bacterial ones in iron detoxification, the residues involved in this gain of function are unknown. In this work, we analyze conservation of amino acid sequence and protein structure among frataxins and CyaY proteins to identify four highly conserved residue clusters and group them into potential functional clusters. Clusters 1, 2, and 4 are present in eukaryotic frataxins and bacterial CyaY proteins. Cluster 3, containing two serines, a tyrosine, and a glutamate, is only present in eukaryotic frataxins and on CyaY proteins from the Rickettsia genus. Residues from cluster 3 are blocking a small cavity of about 40 Å present in E. coli's CyaY. The function of this cluster is unknown, but we hypothesize that its tyrosine may contribute to prevent formation of reactive oxygen species during iron detoxification. This cluster provides an example of gain of function during evolution in a protein involved in iron homeostasis, as our results suggests that Cluster 3 was present in the endosymbiont ancestor of mitochondria and was conserved in eukaryotic frataxins.}, } @article {pmid36362255, year = {2022}, author = {Zhao, W and Bu, X and Zou, H and Li, W and Wu, S and Li, M and Wang, G}, title = {The Genome of the Mitochondrion-Related Organelle in Cepedea longa, a Large Endosymbiotic Opalinid Inhabiting the Recta of Frogs.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362255}, issn = {1422-0067}, support = {32170437//National Natural Science Foundation of China/ ; 2021M703435//China Postdoctoral Science Foundation/ ; 2019QZKK0304//Second Tibetan Plateau Scientific Expedition and Research Program/ ; CARS-45//earmarked fund for CARS/ ; }, mesh = {Animals ; Phylogeny ; *Anura/genetics ; *Stramenopiles/genetics ; Organelles/metabolism ; Mitochondria/genetics ; }, abstract = {Mitochondrion-related organelles (MROs) are loosely defined as degenerated mitochondria in anaerobic and microaerophilic lineages. Opalinids are commonly regarded as commensals in the guts of cold-blooded amphibians. It may represent an intermediate adaptation stage between the conventional aerobic mitochondria and derived anaerobic MROs. In the present study, we sequenced and analyzed the MRO genome of Cepedea longa. It has a linear MRO genome with large inverted repeat gene regions at both ends. Compared to Blastocystis and Proteromonas lacertae, the MRO genome of C. longa has a higher G + C content and repeat sequences near the central region. Although three Opalinata species have different morphological characteristics, phylogenetic analyses based on eight concatenated nad genes indicate that they are close relatives. The phylogenetic analysis showed that C. longa clustered with P. lacertae with strong support. The 18S rRNA gene-based phylogeny resolved the Opalinea clade as a sister clade to Karotomorpha, which then further grouped with Proteromonas. The paraphyly of Proteromonadea needs to be verified due to the lack of MRO genomes for key species, such as Karotomorpha, Opalina and Protoopalina. Besides, our dataset and analyses offered slight support for the paraphyly of Bigyra.}, } @article {pmid36373631, year = {2023}, author = {Mencía, M}, title = {Acid digestion and symbiont: Proton sharing at the origin of mitochondriogenesis?: Proton production by a symbiotic bacterium may have been the origin of two hallmark eukaryotic features, acid digestion and mitochondria: Proton production by a symbiotic bacterium may have been the origin of two hallmark eukaryotic features, acid digestion and mitochondria.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {45}, number = {1}, pages = {e2200136}, doi = {10.1002/bies.202200136}, pmid = {36373631}, issn = {1521-1878}, mesh = {*Protons ; Phylogeny ; *Eukaryota ; Symbiosis ; Bacteria ; Mitochondria ; Digestion ; Biological Evolution ; }, abstract = {The initial relationships between organisms leading to endosymbiosis and the first eukaryote are currently a topic of hot debate. Here, I present a theory that offers a gradual scenario in which the origins of phagocytosis and mitochondria are intertwined in such a way that the evolution of one would not be possible without the other. In this scenario, the premitochondrial bacterial symbiont became initially associated with a protophagocytic host on the basis of cooperation to kill prey with symbiont-produced toxins and reactive oxygen species (ROS). Subsequently, the cooperation was focused on the digestion stage, through the acidification of the protophagocytic cavities via exportation of protons produced by the aerobic respiration of the symbiont. The host gained an improved phagocytic capacity and the symbiont received organic compounds from prey. As the host gradually lost its membrane energetics to develop lysosomal digestion, respiration was centralized in the premitochondrial symbiont for energy production for the consortium.}, } @article {pmid36382523, year = {2022}, author = {Watson, ET and Flanagan, BA and Pascar, JA and Edmands, S}, title = {Mitochondrial effects on fertility and longevity in Tigriopus californicus contradict predictions of the mother's curse hypothesis.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1987}, pages = {20221211}, pmid = {36382523}, issn = {1471-2954}, mesh = {Female ; Animals ; *Longevity ; Mitochondria/genetics ; Maternal Inheritance ; Fertility ; *Genome, Mitochondrial ; DNA, Mitochondrial/genetics ; }, abstract = {Strict maternal inheritance of mitochondria favours the evolutionary accumulation of sex-biased fitness effects, as mitochondrial evolution occurs exclusively in female lineages. The 'mother's curse' hypothesis proposes that male-harming mutations should accumulate in mitochondrial genomes when they have neutral or beneficial effects on female fitness. Rigorous empirical tests have largely focused on Drosophila, where support for the predictions of mother's curse has been mixed. We investigated the impact of mother's curse mutations in Tigriopus californicus, a minute crustacean. Using non-recombinant backcrosses, we introgressed four divergent mitochondrial haplotypes into two nuclear backgrounds and recorded measures of fertility and longevity. We found that the phenotypic effects of mitochondrial mutations were context dependent, being influenced by the nuclear background in which they were expressed, as well as the sex of the individual and rearing temperature. Mitochondrial haplotype effects were greater for fertility than longevity, and temperature effects were greater for longevity. However, in opposition to mother's curse expectations, females had higher mitochondrial genetic variance than males for fertility and longevity, little evidence of sexual antagonism favouring females was found, and the impacts of mitonuclear mismatch harmed females but not males. Together, this indicates that selection on mitochondrial variation has not resulted in the accumulation of male mutation load in Tigriopus californicus.}, } @article {pmid36386853, year = {2022}, author = {Radzvilavicius, AL and Johnston, IG}, title = {Organelle bottlenecks facilitate evolvability by traversing heteroplasmic fitness valleys.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {974472}, pmid = {36386853}, issn = {1664-8021}, abstract = {Bioenergetic organelles-mitochondria and plastids-retain their own genomes (mtDNA and ptDNA), and these organelle DNA (oDNA) molecules are vital for eukaryotic life. Like all genomes, oDNA must be able to evolve to suit new environmental challenges. However, mixed oDNA populations in cells can challenge cellular bioenergetics, providing a penalty to the appearance and adaptation of new mutations. Here we show that organelle "bottlenecks," mechanisms increasing cell-to-cell oDNA variability during development, can overcome this mixture penalty and facilitate the adaptation of beneficial mutations. We show that oDNA heteroplasmy and bottlenecks naturally emerge in evolutionary simulations subjected to fluctuating environments, demonstrating that this evolvability is itself evolvable. Usually thought of as a mechanism to clear damaging mutations, organelle bottlenecks therefore also resolve the tension between intracellular selection for pure cellular oDNA populations and the "bet-hedging" need for evolvability and adaptation to new environments. This general theory suggests a reason for the maintenance of organelle heteroplasmy in cells, and may explain some of the observed diversity in organelle maintenance and inheritance across taxa.}, } @article {pmid36397290, year = {2023}, author = {Mallard, J and Hucteau, E and Schott, R and Trensz, P and Pflumio, C and Kalish-Weindling, M and Favret, F and Pivot, X and Hureau, TJ and Pagano, AF}, title = {Early skeletal muscle deconditioning and reduced exercise capacity during (neo)adjuvant chemotherapy in patients with breast cancer.}, journal = {Cancer}, volume = {129}, number = {2}, pages = {215-225}, pmid = {36397290}, issn = {1097-0142}, mesh = {Humans ; Female ; *Hand Strength/physiology ; Exercise Tolerance ; *Breast Neoplasms/drug therapy ; Quality of Life ; Muscle, Skeletal ; Chemotherapy, Adjuvant/adverse effects ; }, abstract = {BACKGROUND: Fatigue is a hallmark of breast cancer and is associated with skeletal muscle deconditioning. If cancer-related fatigue occurs early during chemotherapy (CT), the development of skeletal muscle deconditioning and its effect on exercise capacity remain unclear. The aim of this study was to investigate the evolution of skeletal muscle deconditioning and exercise capacity in patients with early-stage breast cancer during CT.

METHODS: Patients with breast cancer had a visit before undergoing CT, at 8 weeks, and at the end of chemotherapy (post-CT). Body composition was determined through bioelectrical impedance analysis. Knee extensor, handgrip muscle force and fatigue was quantified by performing maximal voluntary isometric contractions and exercise capacity using the 6-min walking test. Questionnaires were also administered to evaluate quality of life, cancer-related fatigue, and physical activity level.

RESULTS: Among the 100 patients, reductions were found in muscle mass (-2.3%, p = .002), exercise capacity (-6.7%, p < .001), and knee extensor force (-4.9%, p < .001) post-CT, which occurred within the first 8 weeks of treatment with no further decrease thereafter. If muscle fatigue did not change, handgrip muscle force decreased post-CT only (-2.5%, p = .001), and exercise capacity continued to decrease between 8 weeks and post-CT (-4.6%, p < .001). Quality of life and cancer-related fatigue were impaired after 8 weeks (p < .001) and remained stable thereafter, whereas the physical activity level remained stable during chemotherapy.

CONCLUSIONS: Similar to cancer-related fatigue, skeletal muscle deconditioning and reduced exercise capacity occurred early during breast cancer CT. Thus, it appears essential to prevent these alterations through exercise training implemented during CT.}, } @article {pmid36403761, year = {2023}, author = {Shi, F and Yu, T and Xu, Y and Zhang, S and Niu, Y and Ge, S and Tao, J and Zong, S}, title = {Comparative mitochondrial genomic analysis provides new insights into the evolution of the subfamily Lamiinae (Coleoptera: Cerambycidae).}, journal = {International journal of biological macromolecules}, volume = {225}, number = {}, pages = {634-647}, doi = {10.1016/j.ijbiomac.2022.11.125}, pmid = {36403761}, issn = {1879-0003}, mesh = {Animals ; *Coleoptera/genetics ; Phylogeny ; Mitochondria/genetics ; RNA, Transfer/genetics ; Genomics ; }, abstract = {The genus Monochamus within the subfamily Lamiinae is the main vector of Bursaphelenchus xylophilus, which causes pine wilt disease and induces substantial economic and ecological losses. Only three complete mitochondrial genomes of the genus Monochamus have been sequenced to date, and no comparative mitochondrial genomic studies of Lamiinae have been conducted. Here, the mitochondrial genomes of two Monochamus species, M. saltuarius and M. urussovi, were newly sequenced and annotated. The composition and order of genes in the mitochondrial genomes of Monochamus species are conserved. All transfer RNAs exhibit the typical clover-leaf secondary structure, with the exception of trnS1. Similar to other longhorn beetles, Lamiinae mitochondrial genomes have an A + T bias. All 13 protein-coding genes have experienced purifying selection, and tandem repeat sequences are abundant in the A + T-rich region. Phylogenetic analyses revealed congruent topologies among trees inferred from the five datasets, with the monophyly of Acanthocinini, Agapanthiini, Batocerini, Dorcaschematini, Pteropliini, and Saperdini receiving high support. The findings of this study enhance our understanding of mitochondrial genome evolution and will provide a basis for future studies of population genetics and phylogenetic investigations in this group.}, } @article {pmid36403966, year = {2022}, author = {Maciszewski, K and Fells, A and Karnkowska, A}, title = {Challenging the Importance of Plastid Genome Structure Conservation: New Insights From Euglenophytes.}, journal = {Molecular biology and evolution}, volume = {39}, number = {12}, pages = {}, pmid = {36403966}, issn = {1537-1719}, mesh = {*Genome, Plastid ; }, abstract = {Plastids, similar to mitochondria, are organelles of endosymbiotic origin, which retained their vestigial genomes (ptDNA). Their unique architecture, commonly referred to as the quadripartite (four-part) structure, is considered to be strictly conserved; however, the bulk of our knowledge on their variability and evolutionary transformations comes from studies of the primary plastids of green algae and land plants. To broaden our perspective, we obtained seven new ptDNA sequences from freshwater species of photosynthetic euglenids-a group that obtained secondary plastids, known to have dynamically evolving genome structure, via endosymbiosis with a green alga. Our analyses have demonstrated that the evolutionary history of euglenid plastid genome structure is exceptionally convoluted, with a patchy distribution of inverted ribosomal operon (rDNA) repeats, as well as several independent acquisitions of tandemly repeated rDNA copies. Moreover, we have shown that inverted repeats in euglenid ptDNA do not share their genome-stabilizing property documented in chlorophytes. We hypothesize that the degeneration of the quadripartite structure of euglenid plastid genomes is connected to the group II intron expansion. These findings challenge the current global paradigms of plastid genome architecture evolution and underscore the often-underestimated divergence between the functionality of shared traits in primary and complex plastid organelles.}, } @article {pmid36412071, year = {2023}, author = {Shimpi, GG and Bentlage, B}, title = {Ancient endosymbiont-mediated transmission of a selfish gene provides a model for overcoming barriers to gene transfer into animal mitochondrial genomes.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {45}, number = {2}, pages = {e2200190}, doi = {10.1002/bies.202200190}, pmid = {36412071}, issn = {1521-1878}, mesh = {Animals ; *Genome, Mitochondrial/genetics ; Gene Transfer, Horizontal/genetics ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Repetitive Sequences, Nucleic Acid/genetics ; Phylogeny ; Evolution, Molecular ; }, abstract = {In contrast to bilaterian animals, non-bilaterian mitochondrial genomes contain atypical genes, often attributed to horizontal gene transfer (HGT) as an ad hoc explanation. Although prevalent in plants, HGT into animal mitochondrial genomes is rare, lacking suitable explanatory models for their occurrence. HGT of the mismatch DNA repair gene (mtMutS) from giant viruses to octocoral (soft corals and their kin) mitochondrial genomes provides a model for how barriers to HGT to animal mitochondria may be overcome. A review of the available literature suggests that this HGT was mediated by an alveolate endosymbiont infected with a lysogenic phycodnavirus that enabled insertion of the homing endonuclease containing mtMutS into octocoral mitochondrial genomes. We posit that homing endonuclease domains and similar selfish elements play a crucial role in such inter-domain gene transfers. Understanding the role of selfish genetic elements in HGT has the potential to aid development of tools for manipulating animal mitochondrial DNA.}, } @article {pmid36413915, year = {2023}, author = {Guette-Marquet, S and Roques, C and Bergel, A}, title = {Direct electrochemical detection of trans-plasma membrane electron transfer: A possible alternative pathway for cell respiration.}, journal = {Biosensors & bioelectronics}, volume = {220}, number = {}, pages = {114896}, doi = {10.1016/j.bios.2022.114896}, pmid = {36413915}, issn = {1873-4235}, mesh = {Chlorocebus aethiops ; Animals ; *Electrons ; Vero Cells ; *Biosensing Techniques ; Cell Respiration ; Cell Membrane ; Carbon ; }, abstract = {An electrochemical protocol was designed to enable Vero cells to transfer electrons to an electrode without any added redox mediator. The cells were cultured on the surface of electrodes polarized at the optimal potential of 400 mV/silver pseudo-reference. Gold, carbon, and CNT-coated carbon electrodes displayed similar current record patterns. Extracellular electron transfer was sustained for several days. Its intensity, up to 1.5 pA.cell[-1], was in the range of the electron flows implemented by cell respiration. A large fraction of the current vanished as soon as anoxic conditions were established, which suggests a mitochondrial origin for a large proportion of the electrons. The current records always showed a two-phase pattern. The occurrence of the two phases was not due to an evolution of the cell mat structure, which was fully established during the first day of polarization and did not change significantly thereafter. Increasing the cell seeding density decreased the maximum current reached during the first phase and the duration of the phase. These observations put together lead us to propose a model, in which only the cells adhered on the electrode surface produced current by metabolizing glutamine during the first phase. The possible role of this extracellular electron transfer as an alternative cell respiration pathway is discussed. The key roles it could play in regulating pH and pO2 gradients are considered, specifically to explain the pH gradient reversal observed in cancer cells. These pioneering results pave the way for electrochemical sensors to directly address cellular metabolic pathways.}, } @article {pmid36414480, year = {2023}, author = {Sahayasheela, VJ and Yu, Z and Hidaka, T and Pandian, GN and Sugiyama, H}, title = {Mitochondria and G-quadruplex evolution: an intertwined relationship.}, journal = {Trends in genetics : TIG}, volume = {39}, number = {1}, pages = {15-30}, pmid = {36414480}, issn = {0168-9525}, support = {R01 CA236350/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *G-Quadruplexes ; Mitochondria/genetics ; }, abstract = {G-quadruplexes (G4s) are non-canonical structures formed in guanine (G)-rich sequences through stacked G tetrads by Hoogsteen hydrogen bonding. Several studies have demonstrated the existence of G4s in the genome of various organisms, including humans, and have proposed that G4s have a regulatory role in various cellular functions. However, little is known regarding the dissemination of G4s in mitochondria. In this review, we report the observation that the number of potential G4-forming sequences in the mitochondrial genome increases with the evolutionary complexity of different species, suggesting that G4s have a beneficial role in higher-order organisms. We also discuss the possible function of G4s in mitochondrial (mt)DNA and long noncoding (lnc)RNA and their role in various biological processes.}, } @article {pmid36417880, year = {2022}, author = {Aman, Y and Erinjeri, AP and Tataridas-Pallas, N and Williams, R and Wellman, R and Chapman, H and Labbadia, J}, title = {Loss of MTCH-1 suppresses age-related proteostasis collapse through the inhibition of programmed cell death factors.}, journal = {Cell reports}, volume = {41}, number = {8}, pages = {111690}, doi = {10.1016/j.celrep.2022.111690}, pmid = {36417880}, issn = {2211-1247}, support = {BB/P005535/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Proteostasis/physiology ; *Proteome/metabolism ; Protein Folding ; Caenorhabditis elegans/metabolism ; Apoptosis ; }, abstract = {The age-related loss of protein homeostasis (proteostasis) is at the heart of numerous neurodegenerative diseases. Therefore, finding ways to preserve proteome integrity in aged cells may be a powerful way to promote long-term health. Here, we show that reducing the activity of a highly conserved mitochondrial outer membrane protein, MTCH-1/MTCH2, suppresses age-related proteostasis collapse in Caenorhabditis elegans without disrupting development, growth, or reproduction. Loss of MTCH-1 does not influence proteostasis capacity in aged tissues through previously described pathways but instead operates by reducing CED-4 levels. This results in the sequestration of HSP-90 by inactive CED-3, which in turn leads to an increase in HSF-1 activity, transcriptional remodeling of the proteostasis network, and maintenance of proteostasis capacity with age. Together, our findings reveal a role for programmed cell death factors in determining proteome health and suggest that inhibiting MTCH-1 activity in adulthood may safeguard the aging proteome and suppress age-related diseases.}, } @article {pmid36421375, year = {2022}, author = {Ding, H and Bi, D and Zhang, S and Han, S and Ye, Y and Yi, R and Yang, J and Liu, B and Wu, L and Zhuo, R and Kan, X}, title = {The Mitogenome of Sedum plumbizincicola (Crassulaceae): Insights into RNA Editing, Lateral Gene Transfer, and Phylogenetic Implications.}, journal = {Biology}, volume = {11}, number = {11}, pages = {}, pmid = {36421375}, issn = {2079-7737}, support = {NEL&MARA-003//the Opening Foundation of National Engineering Laboratory of Soil Pollution Control and Remediation Technologies, and Key Laboratory of Heavy Metal Pollution Prevention & Control, Ministry of Agriculture and Rural Affairs/ ; BK20211078//the Basic Research Program (Natural Science Foundation) of Jiangsu Province/ ; YJS20210136//the Scientific Research Project Foundation of Postgraduate of the Anhui Higher Education Institutions of China/ ; }, abstract = {As the largest family within the order Saxifragales, Crassulaceae contains about 34 genera with 1400 species. Mitochondria play a critical role in cellular energy production. Since the first land plant mitogenome was reported in Arabidopsis, more than 400 mitogenomic sequences have been deposited in a public database. However, no entire mitogenome data have been available for species of Crassulaceae to date. To better understand the evolutionary history of the organelles of Crassulaceae, we sequenced and performed comprehensive analyses on the mitogenome of Sedum plumbizincicola. The master mitogenomic circle is 212,159 bp in length, including 31 protein-coding genes (PCGs), 14 tRNA genes, and 3 rRNA genes. We further identified totally 508 RNA editing sites in PCGs, and demonstrated that the second codon positions of mitochondrial genes are most prone to RNA editing events. Notably, by neutrality plot analyses, we observed that the mitochondrial RNA editing events have large effects on the driving forces of plant evolution. Additionally, 4 MTPTs and 686 NUMTs were detected in the mitochondrial and nuclear genomes of S. plumbizincicola, respectively. Additionally, we conducted further analyses on gene transfer, secondary structures of mitochondrial RNAs, and phylogenetic implications. Therefore, the findings presented here will be helpful for future investigations on plant mitogenomes.}, } @article {pmid36421825, year = {2022}, author = {Kyrgiafini, MA and Giannoulis, T and Moutou, KA and Mamuris, Z}, title = {Investigating the Impact of a Curse: Diseases, Population Isolation, Evolution and the Mother's Curse.}, journal = {Genes}, volume = {13}, number = {11}, pages = {}, pmid = {36421825}, issn = {2073-4425}, mesh = {Male ; Female ; Humans ; *Mothers ; DNA, Mitochondrial/genetics ; Maternal Inheritance/genetics ; *Genome, Mitochondrial/genetics ; Mitochondria/genetics ; }, abstract = {The mitochondrion was characterized for years as the energy factory of the cell, but now its role in many more cellular processes is recognized. The mitochondrion and mitochondrial DNA (mtDNA) also possess a set of distinct properties, including maternal inheritance, that creates the Mother's Curse phenomenon. As mtDNA is inherited from females to all offspring, mutations that are harmful to males tend to accumulate more easily. The Mother's Curse is associated with various diseases, and has a significant effect on males, in many cases even affecting their reproductive ability. Sometimes, it even leads to reproductive isolation, as in crosses between different populations, the mitochondrial genome cannot cooperate effectively with the nuclear one resulting in a mito-nuclear incompatibility and reduce the fitness of the hybrids. This phenomenon is observed both in the laboratory and in natural populations, and have the potential to influence their evolution and speciation. Therefore, it turns out that the study of mitochondria is an exciting field that finds many applications, including pest control, and it can shed light on the molecular mechanism of several diseases, improving successful diagnosis and therapeutics. Finally, mito-nuclear co-adaptation, paternal leakage, and kin selection are some mechanisms that can mitigate the impact of the Mother's Curse.}, } @article {pmid36421831, year = {2022}, author = {Tang, Y and Huo, Z and Liu, Y and Wang, Y and Zuo, L and Fang, L and Zhao, W and Tan, Y and Yan, X}, title = {Full Mitochondrial Genomes Reveal Species Differences between the Venerid Clams Ruditapes philippinarum and R. variegatus.}, journal = {Genes}, volume = {13}, number = {11}, pages = {}, pmid = {36421831}, issn = {2073-4425}, mesh = {Animals ; *Genome, Mitochondrial/genetics ; Phylogeny ; Species Specificity ; NADH Dehydrogenase ; *Bivalvia/genetics ; }, abstract = {In natural sea areas along the coast of China, venerid clams Ruditapes philippinarum and R. variegatus exhibit similar adult shell forms and are especially difficult to distinguish as spat and juveniles. This study used comparative mitochondrial genome analysis to reveal differences between these species. The results showed that: (1) the mitochondrial genomes of R. philippinarum and R. variegatus share a large number of similar gene clusters arranged in consistent order, yet they also display noncommon genes, with both gene rearrangements and random losses found; (2) the 13 protein-coding genes in R. philippinarum as well as two-fold and four-fold degenerate sites in R. variegatus have an evident AT bias; (3) the Ka/Ks ratio of the mitochondrial ATP8 gene was significantly higher in R. philippinarum than in R. variegatus, and an analysis of selection pressure revealed that the mitochondrial NADH dehydrogenase subunit 2 gene and NADH dehydrogenase subunit 6 gene of R. variegatus were under great selective pressure during its evolution; and finally, (4) the two species clustered into one branch on a phylogenetic tree, further affirming their phylogenetic closeness. Based on these results, we speculate that the species differences between R. variegatus and R. philippinarum are largely attributable to adaptive evolution to the environment. The present findings provide a reference for the development of germplasm identification.}, } @article {pmid36427759, year = {2023}, author = {Munro, D and Rodríguez, E and Blier, PU}, title = {The longest-lived metazoan, Arctica islandica, exhibits high mitochondrial H2O2 removal capacities.}, journal = {Mitochondrion}, volume = {68}, number = {}, pages = {81-86}, doi = {10.1016/j.mito.2022.11.005}, pmid = {36427759}, issn = {1872-8278}, mesh = {Mice ; Animals ; *Hydrogen Peroxide ; Longevity ; Reactive Oxygen Species ; *Bivalvia/physiology ; Mitochondria ; Antioxidants ; }, abstract = {A greater capacity of endogenous matrix antioxidants has recently been hypothesized to characterize mitochondria of long-lived species, curbing bursts of reactive oxygen species (ROS) generated in this organelle. Evidence for this has been obtained from studies comparing the long-lived naked mole rat to laboratory mice. We tested this hypothesis by comparing the longest-lived metazoan, the marine bivalve Arctica islandica (MLSP = 507 y), with shorter-lived and evolutionarily related species. We used a recently developed fluorescent technique to assess mantle and gill tissue mitochondria's capacity to consume hydrogen peroxide (H2O2) in multiple physiological states ex vivo. Depending on the type of respiratory substrate provided, mitochondria of Arctica islandica could consume between 3 and 14 times more H2O2 than shorter-lived species. These findings support the contention that a greater capacity for the elimination of ROS characterizes long-lived species, a novel property of mitochondria thus far demonstrated in two key biogerontological models from distant evolutionary lineages.}, } @article {pmid36430970, year = {2022}, author = {Pożoga, M and Armbruster, L and Wirtz, M}, title = {From Nucleus to Membrane: A Subcellular Map of the N-Acetylation Machinery in Plants.}, journal = {International journal of molecular sciences}, volume = {23}, number = {22}, pages = {}, pmid = {36430970}, issn = {1422-0067}, support = {Wi 3560/4-1//Deutsche Forschungsgemeinschaft/ ; Wi 3560/7-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; Acetylation ; *Saccharomyces cerevisiae ; *Protein Processing, Post-Translational ; Plants/metabolism ; }, abstract = {N-terminal acetylation (NTA) is an ancient protein modification conserved throughout all domains of life. N-terminally acetylated proteins are present in the cytosol, the nucleus, the plastids, mitochondria and the plasma membrane of plants. The frequency of NTA differs greatly between these subcellular compartments. While up to 80% of cytosolic and 20-30% of plastidic proteins are subject to NTA, NTA of mitochondrial proteins is rare. NTA alters key characteristics of proteins such as their three-dimensional structure, binding properties and lifetime. Since the majority of proteins is acetylated by five ribosome-bound N-terminal acetyltransferases (Nats) in yeast and humans, NTA was long perceived as an exclusively co-translational process in eukaryotes. The recent characterization of post-translationally acting plant Nats, which localize to the plasma membrane and the plastids, has challenged this view. Moreover, findings in humans, yeast, green algae and higher plants uncover differences in the cytosolic Nat machinery of photosynthetic and non-photosynthetic eukaryotes. These distinctive features of the plant Nat machinery might constitute adaptations to the sessile lifestyle of plants. This review sheds light on the unique role of plant N-acetyltransferases in development and stress responses as well as their evolution-driven adaptation to function in different cellular compartments.}, } @article {pmid36442091, year = {2022}, author = {Insalata, F and Hoitzing, H and Aryaman, J and Jones, NS}, title = {Stochastic survival of the densest and mitochondrial DNA clonal expansion in aging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {49}, pages = {e2122073119}, pmid = {36442091}, issn = {1091-6490}, mesh = {*DNA, Mitochondrial/genetics ; *Mitochondria ; Cellular Senescence/genetics ; Muscle Fibers, Skeletal ; }, abstract = {The expansion of mitochondrial DNA molecules with deletions has been associated with aging, particularly in skeletal muscle fibers; its mechanism has remained unclear for three decades. Previous accounts have assigned a replicative advantage (RA) to mitochondrial DNA containing deletion mutations, but there is also evidence that cells can selectively remove defective mitochondrial DNA. Here we present a spatial model that, without an RA, but instead through a combination of enhanced density for mutants and noise, produces a wave of expanding mutations with speeds consistent with experimental data. A standard model based on RA yields waves that are too fast. We provide a formula that predicts that wave speed drops with copy number, consonant with experimental data. Crucially, our model yields traveling waves of mutants even if mutants are preferentially eliminated. Additionally, we predict that mutant loads observed in single-cell experiments can be produced by de novo mutation rates that are drastically lower than previously thought for neutral models. Given this exemplar of how spatial structure (multiple linked mtDNA populations), noise, and density affect muscle cell aging, we introduce the mechanism of stochastic survival of the densest (SSD), an alternative to RA, that may underpin other evolutionary phenomena.}, } @article {pmid36446749, year = {2023}, author = {Li, SP and Jiang, H and Liu, ZB and Yu, WJ and Cai, XS and Liu, C and Xie, WY and Quan, FS and Gao, W and Kim, NH and Yuan, B and Chen, CZ and Zhang, JB}, title = {TBX2 affects proliferation, apoptosis and cholesterol generation by regulating mitochondrial function and autophagy in bovine cumulus cell.}, journal = {Veterinary medicine and science}, volume = {9}, number = {1}, pages = {326-335}, pmid = {36446749}, issn = {2053-1095}, mesh = {Female ; Animals ; Cattle ; *Cumulus Cells/metabolism ; Cell Proliferation ; *Autophagy ; Apoptosis/genetics ; Mitochondria ; Cholesterol/metabolism/pharmacology ; Adenosine Triphosphate/metabolism/pharmacology ; }, abstract = {BACKGROUND: T-box transcription factor 2 (TBX2) is a member of T-box gene family whose members are highly conserved in evolution and encoding genes and are involved in the regulation of developmental processes. The encoding genes play an important role in growth and development. Although TBX2 has been widely studied in cancer cell growth and development, its biological functions in bovine cumulus cells remain unclear.

OBJECTIVES: This study aimed to investigate the regulatory effects of TBX2 in bovine cumulus cells.

METHODS: TBX2 gene was knockdown with siRNA to clarify the function in cellular physiological processes. Cell proliferation and cycle changes were determined by xCELLigence cell function analyzer and flow cytometry. Mitochondrial membrane potential and autophagy were detected by fluorescent dye staining and immunofluorescence techniques. Western blot and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression changes of proliferation and autophagy-related proteins. Aadenosine triphosphate (ATP) production, glucose metabolism, and cholesterol synthesis of cumulus cells were measured by optical density and chemiluminescence analysis.

RESULTS: After inhibition of TBX2, the cell cycle was disrupted. The levels of apoptosis, ratio of light chain 3 beta II/I, and reactive oxygen species were increased. The proliferation, expansion ability, ATP production, and the amount of cholesterol secreted by cumulus cells were significantly decreased.

CONCLUSIONS: TBX2 plays important roles in regulating the cells' proliferation, expansion, apoptosis, and autophagy; maintaining the mitochondrial function and cholesterol generation of bovine cumulus cells.}, } @article {pmid36450825, year = {2023}, author = {Missiroli, S and Perrone, M and Gafà, R and Nicoli, F and Bonora, M and Morciano, G and Boncompagni, C and Marchi, S and Lebiedzinska-Arciszewska, M and Vezzani, B and Lanza, G and Kricek, F and Borghi, A and Fiorica, F and Ito, K and Wieckowski, MR and Di Virgilio, F and Abelli, L and Pinton, P and Giorgi, C}, title = {PML at mitochondria-associated membranes governs a trimeric complex with NLRP3 and P2X7R that modulates the tumor immune microenvironment.}, journal = {Cell death and differentiation}, volume = {30}, number = {2}, pages = {429-441}, pmid = {36450825}, issn = {1476-5403}, support = {R01 DK098263/DK/NIDDK NIH HHS/United States ; R01 DK115577/DK/NIDDK NIH HHS/United States ; R01 HL148852/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Cytokines ; Inflammasomes ; Mitochondria ; *NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; *Tumor Microenvironment ; *Receptors, Purinergic P2X7/metabolism ; *Promyelocytic Leukemia Protein/metabolism ; }, abstract = {Uncontrolled inflammatory response arising from the tumor microenvironment (TME) significantly contributes to cancer progression, prompting an investigation and careful evaluation of counter-regulatory mechanisms. We identified a trimeric complex at the mitochondria-associated membranes (MAMs), in which the purinergic P2X7 receptor - NLRP3 inflammasome liaison is fine-tuned by the tumor suppressor PML. PML downregulation drives an exacerbated immune response due to a loss of P2X7R-NLRP3 restraint that boosts tumor growth. PML mislocalization from MAMs elicits an uncontrolled NLRP3 activation, and consequent cytokines blast fueling cancer and worsening the tumor prognosis in different human cancers. New mechanistic insights are provided for the PML-P2X7R-NLRP3 axis to govern the TME in human carcinogenesis, fostering new targeted therapeutic approaches.}, } @article {pmid36463372, year = {2023}, author = {Nikelski, E and Rubtsov, AS and Irwin, D}, title = {High heterogeneity in genomic differentiation between phenotypically divergent songbirds: a test of mitonuclear co-introgression.}, journal = {Heredity}, volume = {130}, number = {1}, pages = {1-13}, pmid = {36463372}, issn = {1365-2540}, mesh = {Animals ; *Songbirds/genetics ; Genome ; Genomics ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Phylogeny ; }, abstract = {Comparisons of genomic variation among closely related species often show more differentiation in mitochondrial DNA (mtDNA) and sex chromosomes than in autosomes, a pattern expected due to the differing effective population sizes and evolutionary dynamics of these genomic components. Yet, introgression can cause species pairs to deviate dramatically from general differentiation trends. The yellowhammer (Emberiza citrinella) and pine bunting (E. leucocephalos) are hybridizing avian sister species that differ greatly in appearance and moderately in nuclear DNA, but that show no mtDNA differentiation. This discordance is best explained by adaptive mtDNA introgression-a process that can select for co-introgression at nuclear genes with mitochondrial functions (mitonuclear genes). To better understand these discordant differentiation patterns and characterize nuclear differentiation in this system, we investigated genome-wide differentiation between allopatric yellowhammers and pine buntings and compared it to what was seen previously in mtDNA. We found significant nuclear differentiation that was highly heterogeneous across the genome, with a particularly wide differentiation peak on the sex chromosome Z. We further investigated mitonuclear gene co-introgression between yellowhammers and pine buntings and found support for this process in the direction of pine buntings into yellowhammers. Genomic signals indicative of co-introgression were common in mitonuclear genes coding for subunits of the mitoribosome and electron transport chain complexes. Such introgression of mitochondrial DNA and mitonuclear genes provides a possible explanation for the patterns of high genomic heterogeneity in genomic differentiation seen among some species groups.}, } @article {pmid36463410, year = {2023}, author = {Krynická, V and Skotnicová, P and Jackson, PJ and Barnett, S and Yu, J and Wysocka, A and Kaňa, R and Dickman, MJ and Nixon, PJ and Hunter, CN and Komenda, J}, title = {FtsH4 protease controls biogenesis of the PSII complex by dual regulation of high light-inducible proteins.}, journal = {Plant communications}, volume = {4}, number = {1}, pages = {100502}, pmid = {36463410}, issn = {2590-3462}, support = {BB/M000265/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M012166/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Peptide Hydrolases ; Photosystem II Protein Complex/genetics/metabolism ; Phylogeny ; Thylakoids/metabolism ; Chloroplasts/metabolism ; *Arabidopsis/genetics/metabolism ; *Synechocystis/genetics/metabolism ; *Arabidopsis Proteins/genetics/metabolism ; Metalloproteases/genetics/metabolism ; }, abstract = {FtsH proteases are membrane-embedded proteolytic complexes important for protein quality control and regulation of various physiological processes in bacteria, mitochondria, and chloroplasts. Like most cyanobacteria, the model species Synechocystis sp. PCC 6803 contains four FtsH homologs, FtsH1-FtsH4. FtsH1-FtsH3 form two hetero-oligomeric complexes, FtsH1/3 and FtsH2/3, which play a pivotal role in acclimation to nutrient deficiency and photosystem II quality control, respectively. FtsH4 differs from the other three homologs by the formation of a homo-oligomeric complex, and together with Arabidopsis thaliana AtFtsH7/9 orthologs, it has been assigned to another phylogenetic group of unknown function. Our results exclude the possibility that Synechocystis FtsH4 structurally or functionally substitutes for the missing or non-functional FtsH2 subunit in the FtsH2/3 complex. Instead, we demonstrate that FtsH4 is involved in the biogenesis of photosystem II by dual regulation of high light-inducible proteins (Hlips). FtsH4 positively regulates expression of Hlips shortly after high light exposure but is also responsible for Hlip removal under conditions when their elevated levels are no longer needed. We provide experimental support for Hlips as proteolytic substrates of FtsH4. Fluorescent labeling of FtsH4 enabled us to assess its localization using advanced microscopic techniques. Results show that FtsH4 complexes are concentrated in well-defined membrane regions at the inner and outer periphery of the thylakoid system. Based on the identification of proteins that co-purified with the tagged FtsH4, we speculate that FtsH4 concentrates in special compartments in which the biogenesis of photosynthetic complexes takes place.}, } @article {pmid36469010, year = {2023}, author = {Penter, L and Ten Hacken, E and Southard, J and Lareau, CA and Ludwig, LS and Li, S and Neuberg, DS and Livak, KJ and Wu, CJ}, title = {Mitochondrial DNA Mutations as Natural Barcodes for Lineage Tracing of Murine Tumor Models.}, journal = {Cancer research}, volume = {83}, number = {5}, pages = {667-672}, pmid = {36469010}, issn = {1538-7445}, support = {R01 CA216273/CA/NCI NIH HHS/United States ; P01 CA206978/CA/NCI NIH HHS/United States ; R01 CA155010/CA/NCI NIH HHS/United States ; R50 CA251956/CA/NCI NIH HHS/United States ; R21 CA267527/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Mice ; *DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Chromatin ; Mutation ; *Neoplasms/genetics ; }, abstract = {UNLABELLED: Murine models are indispensable tools for functional genomic studies and preclinical testing of novel therapeutic approaches. Mitochondrial single-cell assay for transposase-accessible chromatin using sequencing (mtscATAC-seq) enables the dissection of cellular heterogeneity and clonal dynamics by capturing chromatin accessibility, copy-number variations (CNV), and mitochondrial DNA (mtDNA) mutations, yet its applicability to murine studies remains unexplored. By leveraging mtscATAC-seq in novel chronic lymphocytic leukemia and Richter syndrome mouse models, we report the detection of mtDNA mutations, particularly in highly proliferative murine cells, alongside CNV and chromatin state changes indicative of clonal evolution upon secondary transplant. This study thus demonstrates the feasibility and utility of multi-modal single-cell and natural barcoding approaches to characterize murine cancer models.

SIGNIFICANCE: mtDNA mutations can serve as natural barcodes to enable lineage tracing in murine cancer models, which can be used to provide new insights into disease biology and to identify therapeutic vulnerabilities.}, } @article {pmid36470482, year = {2023}, author = {Liu, J and Ni, Y and Liu, C}, title = {Polymeric structure of the Cannabis sativa L. mitochondrial genome identified with an assembly graph model.}, journal = {Gene}, volume = {853}, number = {}, pages = {147081}, doi = {10.1016/j.gene.2022.147081}, pmid = {36470482}, issn = {1879-0038}, mesh = {*Genome, Mitochondrial/genetics ; *Cannabis/genetics ; Plant Breeding ; *Genome, Chloroplast ; Repetitive Sequences, Nucleic Acid ; DNA, Mitochondrial/genetics ; Phylogeny ; Evolution, Molecular ; }, abstract = {Cannabis sativa L. belongs to the family Cannabaceae in Rosales. It has been widely used as medicines, building materials, and textiles. Elucidating its genome is critical for molecular breeding and synthetic biology study. Many studies have shown that the mitochondrial genomes (mitogenomes) and even chloroplast genomes (plastomes) had complex polymeric structures. Using the Nanopore sequencing platform, we sequenced, assembled, and analyzed its mitogenome and plastome. The resulting unitig graph suggested that the mitogenome had a complex polymeric structure. However, a gap-free, circular sequence was further assembled from the unitig graph. In contrast, a circular sequence representing the plastome was obtained. The mitogenome major conformation was 415,837 bp long, and the plastome was 153,927 bp long. To test if the repeat sequences promote recombination, which corresponds to the branch points in the structure, we tested the sequences around repeats by long-read mapping. Among 208 pairs of predicted repeats, the mapping results supported the presence of cross-over around 25 pairs of repeats. Subsequent PCR amplification confirmed the presence of cross-over around 15 of the 25 repeats. By comparing the mitogenome and plastome sequences, we identified 19 mitochondria plastid DNAs, including seven complete genes (trnW-CCA, trnP-UGG, psbJ, trnN-GUU, trnD-GUC, trnH-GUG, trnM-CAU) and nine gene fragments. Furthermore, the selective pressure analysis results showed that five genes (atp1, ccmB, ccmC, cox1, nad7) had 19 positively selected sites. Lastly, we predicted 28 RNA editing sites. A total of 8 RNA editing sites located in the coding regions were successfully validated by PCR amplification and Sanger sequencing, of which four were synonymous, and four were nonsynonymous. In particular, the RNA editing events appeared to be tissue-specific in C. sativa mitogenome. In summary, we have confirmed the major confirmation of C. sativa mitogenome and characterized its structural features in detail. These results provide critical information for future variety breeding and resource development for C. sativa.}, } @article {pmid36472108, year = {2022}, author = {Cahill, MA}, title = {Unde venisti PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {27}, number = {11}, pages = {317}, doi = {10.31083/j.fbl2711317}, pmid = {36472108}, issn = {2768-6698}, mesh = {Animals ; Humans ; *Eukaryota ; *Proteomics ; Epigenesis, Genetic ; Receptors, Progesterone/metabolism ; Glycolysis ; Heme/metabolism ; Mammals/metabolism ; Membrane Proteins/genetics/metabolism ; }, abstract = {The title usage of Unde venisti 'from where have you come' is from a now dead language (Latin) that foundationally influenced modern English (not the major influence, but an essential formative one). This is an apt analogy for how both the ancient eukaryotic and eumetazoan functions of PGRMC proteins (PGRMC1 and PGRMC2 in mammals) probably influence modern human biology: via a formative trajectory from an evolutionarily foundational fulcrum. There is an arguable probability, although not a certainty, that PGRMC-like proteins were involved in eukaryogenesis. If so, then the proto-eukaryotic ancestral protein is modelled as having initiated the oxygen-induced and CYP450 (Cytochrome P450)-mediated synthesis of sterols in the endoplasmic reticulum to regulate proto-mitochondrial activity and heme homeostasis, as well as having enabled sterol transport between endoplasmic reticulum (ER) and mitochondria membranes involving the actin cytoskeleton, transport of heme from mitochondria, and possibly the regulation/origins of mitosis/meiosis. Later, during animal evolution, the last eumetazoan common ancestor (LEUMCA) acquired PGRMC phosphorylated tyrosines coincidentally with the gastrulation organizer, Netrin/deleted in colorectal carcinoma (DCC) signaling, muscle fibers, synapsed neurons, and neural recovery via a sleep-like process. Modern PGRMC proteins regulate multiple functions, including CYP450-mediated steroidogenesis, membrane trafficking, heme homeostasis, glycolysis/Warburg effect, fatty acid metabolism, mitochondrial regulation, and genomic CpG epigenetic regulation of gene expression. The latter imposes the system of differentiation status-sensitive cell-type specific proteomic complements in multi-tissued descendants of the LEUMCA. This paper attempts to trace PGRMC functions through time, proposing that key functions were involved in early eukaryotes, and were later added upon in the LEUMCA. An accompanying paper considers the implications of this awareness for human health and disease.}, } @article {pmid36473440, year = {2022}, author = {Leger, MM and Stairs, C}, title = {Eukaryotic evolution: Spatial proteomics sheds light on mitochondrial reduction.}, journal = {Current biology : CB}, volume = {32}, number = {23}, pages = {R1308-R1311}, doi = {10.1016/j.cub.2022.10.039}, pmid = {36473440}, issn = {1879-0445}, mesh = {*Eukaryota ; *Proteomics ; }, abstract = {Multi-organelle spatial proteomics has revolutionized animal cell biology, but its use in protists has so far been limited. A new study delivers the first such proteome of a free-living protist, uncovering a previously overlooked function of highly reduced mitochondria.}, } @article {pmid36497015, year = {2022}, author = {Kozhukhar, N and Alexeyev, MF}, title = {TFAM's Contributions to mtDNA Replication and OXPHOS Biogenesis Are Genetically Separable.}, journal = {Cells}, volume = {11}, number = {23}, pages = {}, pmid = {36497015}, issn = {2073-4409}, support = {S10 OD025089/OD/NIH HHS/United States ; R01 OD010944/OD/NIH HHS/United States ; P01 HL066299/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Humans ; Chickens/genetics ; *DNA Replication ; DNA, Mitochondrial/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; Mitochondria/genetics/metabolism ; *Mitochondrial Proteins/genetics/metabolism ; Phylogeny ; *Transcription Factors/genetics/metabolism ; }, abstract = {The ability of animal orthologs of human mitochondrial transcription factor A (hTFAM) to support the replication of human mitochondrial DNA (hmtDNA) does not follow a simple pattern of phylogenetic closeness or sequence similarity. In particular, TFAM from chickens (Gallus gallus, chTFAM), unlike TFAM from the "living fossil" fish coelacanth (Latimeria chalumnae), cannot support hmtDNA replication. Here, we implemented the recently developed GeneSwap approach for reverse genetic analysis of chTFAM to obtain insights into this apparent contradiction. By implementing limited "humanization" of chTFAM focused either on amino acid residues that make DNA contacts, or the ones with significant variances in side chains, we isolated two variants, Ch13 and Ch22. The former has a low mtDNA copy number (mtCN) but robust respiration. The converse is true of Ch22. Ch13 and Ch22 complement each other's deficiencies. Opposite directionalities of changes in mtCN and respiration were also observed in cells expressing frog TFAM. This led us to conclude that TFAM's contributions to mtDNA replication and respiratory chain biogenesis are genetically separable. We also present evidence that TFAM residues that make DNA contacts play the leading role in mtDNA replication. Finally, we present evidence for a novel mode of regulation of the respiratory chain biogenesis by regulating the supply of rRNA subunits.}, } @article {pmid36498828, year = {2022}, author = {Ge, Q and Peng, P and Cheng, M and Meng, Y and Cao, Y and Zhang, S and Long, Y and Li, G and Kang, G}, title = {Genome-Wide Identification and Analysis of FKBP Gene Family in Wheat (Triticum asetivum).}, journal = {International journal of molecular sciences}, volume = {23}, number = {23}, pages = {}, pmid = {36498828}, issn = {1422-0067}, mesh = {*Triticum/metabolism ; Genome, Plant ; Phylogeny ; Gene Expression Regulation, Plant ; Tacrolimus Binding Proteins/genetics/metabolism ; Plant Proteins/genetics/metabolism ; Stress, Physiological/genetics ; *Arabidopsis/genetics ; Multigene Family ; }, abstract = {FK506-binding protein (FKBP) genes have been found to play vital roles in plant development and abiotic stress responses. However, limited information is available about this gene family in wheat (Triticum aestivum L.). In this study, a total of 64 FKBP genes were identified in wheat via a genome-wide analysis involving a homologous search of the latest wheat genome data, which was unevenly distributed in 21 chromosomes, encoded 152 to 649 amino acids with molecular weights ranging from 16 kDa to 72 kDa, and was localized in the chloroplast, cytoplasm, nucleus, mitochondria, peroxisome and endoplasmic reticulum. Based on sequence alignment and phylogenetic analysis, 64 TaFKBPs were divided into four different groups or subfamilies, providing evidence of an evolutionary relationship with Aegilops tauschii, Brachypodium distachyon, Triticum dicoccoides, Arabidopsis thaliana and Oryza sativa. Hormone-related, abiotic stress-related and development-related cis-elements were preferentially presented in promoters of TaFKBPs. The expression levels of TaFKBP genes were investigated using transcriptome data from the WheatExp database, which exhibited tissue-specific expression patterns. Moreover, TaFKBPs responded to drought and heat stress, and nine of them were randomly selected for validation by qRT-PCR. Yeast cells expressing TaFKBP19-2B-2 or TaFKBP18-6B showed increased influence on drought stress, indicating their negative roles in drought tolerance. Collectively, our results provide valuable information about the FKBP gene family in wheat and contribute to further characterization of FKBPs during plant development and abiotic stress responses, especially in drought stress.}, } @article {pmid36501134, year = {2022}, author = {Żmijewski, MA}, title = {Nongenomic Activities of Vitamin D.}, journal = {Nutrients}, volume = {14}, number = {23}, pages = {}, pmid = {36501134}, issn = {2072-6643}, support = {2017/25/B/NZ3/00431//National Science Center/ ; }, mesh = {*Receptors, Calcitriol/genetics ; *Vitamin D/pharmacology/metabolism ; Calcium/metabolism ; Ultraviolet Rays ; Hedgehog Proteins ; Calcitriol/metabolism ; Vitamins ; }, abstract = {Vitamin D shows a variety of pleiotropic activities which cannot be fully explained by the stimulation of classic pathway- and vitamin D receptor (VDR)-dependent transcriptional modulation. Thus, existence of rapid and nongenomic responses to vitamin D was suggested. An active form of vitamin D (calcitriol, 1,25(OH)2D3) is an essential regulator of calcium-phosphate homeostasis, and this process is tightly regulated by VDR genomic activity. However, it seems that early in evolution, the production of secosteroids (vitamin-D-like steroids) and their subsequent photodegradation served as a protective mechanism against ultraviolet radiation and oxidative stress. Consequently, direct cell-protective activities of vitamin D were proven. Furthermore, calcitriol triggers rapid calcium influx through epithelia and its uptake by a variety of cells. Subsequently, protein disulfide-isomerase A3 (PDIA3) was described as a membrane vitamin D receptor responsible for rapid nongenomic responses. Vitamin D was also found to stimulate a release of secondary massagers and modulate several intracellular processes-including cell cycle, proliferation, or immune responses-through wingless (WNT), sonic hedgehog (SSH), STAT1-3, or NF-kappaB pathways. Megalin and its coreceptor, cubilin, facilitate the import of vitamin D complex with vitamin-D-binding protein (DBP), and its involvement in rapid membrane responses was suggested. Vitamin D also directly and indirectly influences mitochondrial function, including fusion-fission, energy production, mitochondrial membrane potential, activity of ion channels, and apoptosis. Although mechanisms of the nongenomic responses to vitamin D are still not fully understood, in this review, their impact on physiology, pathology, and potential clinical applications will be discussed.}, } @article {pmid36502540, year = {2022}, author = {Alsaad, RKA}, title = {Past, present and future of Trichomonas vaginalis: a review study.}, journal = {Annals of parasitology}, volume = {68}, number = {3}, pages = {409-419}, doi = {10.17420/ap6803.447}, pmid = {36502540}, issn = {2299-0631}, mesh = {Male ; Female ; Humans ; *Trichomonas vaginalis/genetics ; *Trichomonas Vaginitis/diagnosis/epidemiology/parasitology ; *Trichomonas Infections/epidemiology ; Metronidazole ; Prevalence ; }, abstract = {Trichomonas vaginalis (TV) is the most common non-viral sexually transmitted infection (STI) microaerophilic protist parasite, which is the causative agent of trichomonosis. Globally, the estimated annual incidence is more than 270 million cases. It is correlated for several health problems including pelvic inflammatory disease (PID), pregnancy miscarriages, cervical carcinoma, prostatitis, prostatic adenocarcinomas, infertility, and the acquisition of human immunodeficiency virus (HIV). Most individuals infected with TV are asymptomatic. Metronidazole (MTZ) has been the treatment of choice for women. Currently, there is no effective vaccine against this pathogen despite efforts at vaccine development. Different socio-economic, demographic, behavioral, and biological factors are associated with the disease. Apart from its role as a pathogenic agent of diseases, it is also a fascinating organism with a surprisingly large genome for a parasite, i.e. larger than 160 Mb, and physiology adapted to its microaerophilic lifestyle. Particularly, the hydrogenosome, a mitochondria-derived organelle that releases hydrogen, attracted much interest in the last decades and rendered TV a model organism for eukaryotic evolution. According to the high prevalence and health consequences associated with TV, there is a requirement for improved screening programs in Iraq. The early diagnosis of asymptomatic diseases and effective treatment regimens are mandatory. Despite being highly prevalent of trichomonosis in the world, there is no review research published that solely focuses on T. vaginalis infections in Iraq.}, } @article {pmid36508337, year = {2022}, author = {Xu, R and Martelossi, J and Smits, M and Iannello, M and Peruzza, L and Babbucci, M and Milan, M and Dunham, JP and Breton, S and Milani, L and Nuzhdin, SV and Bargelloni, L and Passamonti, M and Ghiselli, F}, title = {Multi-tissue RNA-Seq Analysis and Long-read-based Genome Assembly Reveal Complex Sex-specific Gene Regulation and Molecular Evolution in the Manila Clam.}, journal = {Genome biology and evolution}, volume = {14}, number = {12}, pages = {}, pmid = {36508337}, issn = {1759-6653}, support = {S10 RR025496/RR/NCRR NIH HHS/United States ; S10 OD010794/OD/NIH HHS/United States ; }, mesh = {Animals ; Female ; Male ; *DNA, Mitochondrial/genetics ; RNA-Seq ; *Bivalvia/genetics ; Mitochondria/genetics ; Evolution, Molecular ; }, abstract = {The molecular factors and gene regulation involved in sex determination and gonad differentiation in bivalve molluscs are unknown. It has been suggested that doubly uniparental inheritance (DUI) of mitochondria may be involved in these processes in species such as the ubiquitous and commercially relevant Manila clam, Ruditapes philippinarum. We present the first long-read-based de novo genome assembly of a Manila clam, and a RNA-Seq multi-tissue analysis of 15 females and 15 males. The highly contiguous genome assembly was used as reference to investigate gene expression, alternative splicing, sequence evolution, tissue-specific co-expression networks, and sexual contrasting SNPs. Differential expression (DE) and differential splicing (DS) analyses revealed sex-specific transcriptional regulation in gonads, but not in somatic tissues. Co-expression networks revealed complex gene regulation in gonads, and genes in gonad-associated modules showed high tissue specificity. However, male gonad-associated modules showed contrasting patterns of sequence evolution and tissue specificity. One gene set was related to the structural organization of male gametes and presented slow sequence evolution but high pleiotropy, whereas another gene set was enriched in reproduction-related processes and characterized by fast sequence evolution and tissue specificity. Sexual contrasting SNPs were found in genes overrepresented in mitochondrial-related functions, providing new candidates for investigating the relationship between mitochondria and sex in DUI species. Together, these results increase our understanding of the role of DE, DS, and sequence evolution of sex-specific genes in an understudied taxon. We also provide resourceful genomic data for studies regarding sex diagnosis and breeding in bivalves.}, } @article {pmid36512580, year = {2022}, author = {Guo, S and Lin, X and Song, N}, title = {Mitochondrial phylogenomics reveals deep relationships of scarab beetles (Coleoptera, Scarabaeidae).}, journal = {PloS one}, volume = {17}, number = {12}, pages = {e0278820}, pmid = {36512580}, issn = {1932-6203}, mesh = {Animals ; Phylogeny ; *Coleoptera/genetics ; *Genome, Mitochondrial ; Mitochondria/genetics ; Base Sequence ; }, abstract = {In this study, we newly sequenced the complete mitochondrial genomes (mitogenomes) of two phytophagous scarab beetles, and investigated the deep level relationships within Scarabaeidae combined with other published beetle mitogenome sequences. The complete mitogenomes of Dicronocephalus adamsi Pascoe (Cetoniinae) and Amphimallon sp. (Melolonthinae) are 15,563 bp and 17,433 bp in size, respectively. Both mitogenomes have the typical set of 37 genes (13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes) and an A+T-rich region, with the same gene arrangement found in the majority of beetles. The secondary structures for ribosomal RNA genes (rrnL and rrnS) were inferred by comparative analysis method. Results from phylogenetic analyses provide support for major lineages and current classification of Scarabaeidae. Amino acid data recovered Scarabaeidae as monophyletic. The Scarabaeidae was split into two clades. One clade contained the subfamilies Scarabaeinae and Aphodiinae. The other major clade contained the subfamilies Dynastinae, Rutelinae, Cetoniinae, Melolonthinae and Sericini. The monophyly of Scarabaeinae, Aphodiinae, Dynastinae, Cetoniinae and Sericini were strongly supported. The Scarabaeinae was the sister group of Aphodiinae. The Cetoniinae was sister to the Dynastinae + Rutelinae clade. The Melolonthinae was a non-monophyletic group. The removal of fast-evolving sites from nucleotide dataset using a pattern sorting method (OV-sorting) supported the family Scarabaeidae as a monophyletic group. At the tribe level, the Onthophagini was non-monophyletic with respect to Oniticellini. Ateuchini was sister to a large clade comprising the tribes Onthophagini, Oniticellini and Onitini. Eurysternini was a sister group of the Phanaeini + Ateuchini clade.}, } @article {pmid36519158, year = {2022}, author = {Kim, S and Eom, H and Nandre, R and Choi, YJ and Lee, H and Ryu, H and Ro, HS}, title = {Comparative structural analysis on the mitochondrial DNAs from various strains of Lentinula edodes.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1034387}, pmid = {36519158}, issn = {1664-302X}, abstract = {The evolution of mitochondria through variations in mitochondrial DNA (mtDNA) is one of the intriguing questions in eukaryotic cells. In order to assess the causes of the variations in mitochondria, the mtDNAs of the 21 strains of Lentinula edodes were assembled for this study, and analyzed together with four published mtDNA sequences. The mtDNAs were within the sizes of 117 kb ~ 122 kb. The gene number was observed consistent except for two mtDNAs, which carry a duplicated trnG1-trnG2 unit or a putative gene deletion. The size variation was largely attributed to the number of introns, repeated sequences, transposable elements (TEs), and plasmid-related sequences. Intron loss and gain were found from cox1, rnl, and rns of three mtDNAs. Loss of two introns in cox1 of KY217797.1 reduced its size by 2.7 kb, making it the smallest cox1 gene (8.4 kb) among the cox1s of the 25 mtDNAs, whereas gain of a Group II intron (2.65 kb) and loss of a Group I intron (1.7 kb) in cox1 of MF774813.1 resulted in the longest cox1 (12 kb). In rnl of L. edodes, we discovered four intron insertion consensus sequences which were unique to basidiomycetes but not ascomycetes. Differential incorporation of introns was the primary cause of the rnl size polymorphism. Homing endonucleases (HEGs) were suggestively involved in the mobilization of the introns because all of the introns have HEG genes of the LAGRIDADG or GIY-YIG families with the conserved HEG cleavage sites. TEs contributed to 11.04% of the mtDNA size in average, of which 7.08% was LTR-retrotransposon and 3.96% was DNA transposon, whereas the repeated sequences covered 4.6% of the mtDNA. The repeat numbers were variable in a strain-dependent manner. Both the TEs and repeated sequences were mostly found in the intronic and intergenic regions. Lastly, two major deletions were found in the plasmid-related sequence regions (pol2-pol3 and pol1-atp8) in the five mtDNAs. Particularly, the 6.8 kb-long deletion at pol2-pol3 region made MF774813.1 the shortest mtDNA of all. Our results demonstrate that mtDNA is a dynamic molecule that persistently evolves over a short period of time by insertion/deletion and repetition of DNA segments at the strain level.}, } @article {pmid36520311, year = {2023}, author = {Marszalek, J and Craig, EA and Tomiczek, B}, title = {J-Domain Proteins Orchestrate the Multifunctionality of Hsp70s in Mitochondria: Insights from Mechanistic and Evolutionary Analyses.}, journal = {Sub-cellular biochemistry}, volume = {101}, number = {}, pages = {293-318}, pmid = {36520311}, issn = {0306-0225}, mesh = {*Saccharomyces cerevisiae Proteins/metabolism ; HSP70 Heat-Shock Proteins/genetics/metabolism ; Mitochondria/genetics/metabolism ; Molecular Chaperones/genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; }, abstract = {Mitochondrial J-domain protein (JDP) co-chaperones orchestrate the function of their Hsp70 chaperone partner(s) in critical organellar processes that are essential for cell function. These include folding, refolding, and import of mitochondrial proteins, maintenance of mitochondrial DNA, and biogenesis of iron-sulfur cluster(s) (FeS), prosthetic groups needed for function of mitochondrial and cytosolic proteins. Consistent with the organelle's endosymbiotic origin, mitochondrial Hsp70 and the JDPs' functioning in protein folding and FeS biogenesis clearly descended from bacteria, while the origin of the JDP involved in protein import is less evident. Regardless of their origin, all mitochondrial JDP/Hsp70 systems evolved unique features that allowed them to perform mitochondria-specific functions. Their modes of functional diversification and specialization illustrate the versatility of JDP/Hsp70 systems and inform our understanding of system functioning in other cellular compartments.}, } @article {pmid36523555, year = {2022}, author = {Hogg, DW and Reid, AL and Dodsworth, TL and Chen, Y and Reid, RM and Xu, M and Husic, M and Biga, PR and Slee, A and Buck, LT and Barsyte-Lovejoy, D and Locke, M and Lovejoy, DA}, title = {Skeletal muscle metabolism and contraction performance regulation by teneurin C-terminal-associated peptide-1.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {1031264}, pmid = {36523555}, issn = {1664-042X}, abstract = {Skeletal muscle regulation is responsible for voluntary muscular movement in vertebrates. The genes of two essential proteins, teneurins and latrophilins (LPHN), evolving in ancestors of multicellular animals form a ligand-receptor pair, and are now shown to be required for skeletal muscle function. Teneurins possess a bioactive peptide, termed the teneurin C-terminal associated peptide (TCAP) that interacts with the LPHNs to regulate skeletal muscle contractility strength and fatigue by an insulin-independent glucose importation mechanism in rats. CRISPR-based knockouts and siRNA-associated knockdowns of LPHN-1 and-3 in the C2C12 mouse skeletal cell line shows that TCAP stimulates an LPHN-dependent cytosolic Ca[2+] signal transduction cascade to increase energy metabolism and enhance skeletal muscle function via increases in type-1 oxidative fiber formation and reduce the fatigue response. Thus, the teneurin/TCAP-LPHN system is presented as a novel mechanism that regulates the energy requirements and performance of skeletal muscle.}, } @article {pmid36527364, year = {2023}, author = {Knoop, V}, title = {C-to-U and U-to-C: RNA editing in plant organelles and beyond.}, journal = {Journal of experimental botany}, volume = {74}, number = {7}, pages = {2273-2294}, doi = {10.1093/jxb/erac488}, pmid = {36527364}, issn = {1460-2431}, mesh = {*RNA Editing ; Uridine/genetics/metabolism ; *Organelles/genetics/metabolism ; Plants/genetics/metabolism ; Chloroplasts/metabolism ; RNA, Plant/genetics/metabolism ; Plant Proteins/metabolism ; }, abstract = {The genomes in the two energy-converting organelles of plant cells, chloroplasts and mitochondria, contain numerous 'errors' that are corrected at the level of RNA transcript copies. The genes encoded in the two endosymbiotic organelles would not function properly if their transcripts were not altered by site-specific cytidine-to-uridine (C-to-U) exchanges and by additional reverse U-to-C exchanges in hornworts, lycophytes, and ferns. These peculiar processes of plant RNA editing, re-establishing genetic information that could alternatively be present at the organelle genome level, has spurred much research over >30 years. Lately new studies have revealed numerous interesting insights, notably on the biochemical machinery identifying specific pyrimidine nucleobases for conversion from C to U and vice versa. Here, I will summarize prominent research findings that lately have contributed to our better understanding of these phenomena introducing an added layer of information processing in plant cells. Some of this recent progress is based on the successful functional expression of plant RNA editing factors in bacteria and mammalian cells. These research approaches have recapitulated natural processes of horizontal gene transfer through which some protist lineages seem to have acquired plant RNA editing factors and adapted them functionally for their own purposes.}, } @article {pmid36543798, year = {2022}, author = {Zawal, A and Skuza, L and Michoński, G and Bańkowska, A and Szućko-Kociuba, I and Gastineau, R}, title = {Complete mitochondrial genome of Hygrobates turcicus Pešić, Esen & Dabert, 2017 (Acari, Hydrachnidia, Hygrobatoidea).}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {22063}, pmid = {36543798}, issn = {2045-2322}, mesh = {Animals ; Female ; Male ; *Acari/genetics ; *Genome, Mitochondrial ; Mitochondria/genetics ; Codon, Initiator ; RNA, Ribosomal/genetics ; Phylogeny ; Sequence Analysis, DNA ; RNA, Transfer/genetics ; DNA, Mitochondrial/genetics ; }, abstract = {The aim of the study was sequencing of the mitogenome of Hygrobates turcicus Pešić, Esen & Dabert, 2017 to expand knowledge of the polymorphism and cryptic or pseudocryptic diversity within Hydrachnidia. The samples originated from Bulgaria, Vidima River near Debnewo, 42°56'41.4''N, 24°48'44.6''E, depth 0.4 m, stones on the bottom, water flow 0.71 m/s, temperature 10 °C, pH 8.53, oxygen 110%, conductivity 279 µS/cm, hardness 121 CaO mg/l; 11 males, 27 females, 2 deutonymphs 12.x.2019 leg. Zawal, Michoński & Bańkowska; one male and one female dissected and slides mounted. The study was carried out using the following methods: DNA extraction, sequencing, assembly and annotation, comparison with other populations of H. turcicus, and multigene phylogeny. As a result of the study, it was determined that the mitogenome is 15,006 bp long and encodes for 13 proteins, 2 rRNAs, and 22 tRNAs. The genome is colinear with those of H. longiporus and H. taniguchii, the difference in size originating from a non-coding region located between protein-coding genes ND4L and ND3. Five genes have alternative start-codon, and four display premature termination. The multigene phylogeny obtained using all mitochondrial protein-coding genes unambiguously associates H. turcicus with the cluster formed by H. longiporus and H. taniguchii.}, } @article {pmid36543927, year = {2022}, author = {Cunha, RL and Faleh, AB and Francisco, S and Šanda, R and Vukić, J and Corona, L and Dia, M and Glavičić, I and Kassar, A and Castilho, R and Robalo, JI}, title = {Three mitochondrial lineages and no Atlantic-Mediterranean barrier for the bogue Boops boops across its widespread distribution.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {22124}, pmid = {36543927}, issn = {2045-2322}, mesh = {Humans ; Animals ; Phylogeny ; Phylogeography ; Azores ; Portugal ; *Mitochondria ; *Perciformes/genetics ; Atlantic Ocean ; Genetic Variation ; Mediterranean Sea ; }, abstract = {Marine species exhibiting wide distributional ranges are frequently subdivided into discrete genetic units over limited spatial scales. This is often due to specific life-history traits or oceanographic barriers that prevent gene flow. Fine-scale sampling studies revealed distinct phylogeographic patterns in the northeastern Atlantic and the Mediterranean, ranging from panmixia to noticeable population genetic structure. Here, we used mitochondrial sequence data to analyse connectivity in the bogue Boops boops throughout most of its widespread distribution. Our results identified the existence of three clades, one comprising specimens from the Azores and eastern Atlantic/Mediterranean, another with individuals from the Canary Islands, Madeira and Cape Verde archipelagos, and the third with samples from Mauritania only. One of the branches of the northern subtropical gyre (Azores Current) that drifts towards the Gulf of Cádiz promotes a closer connection between the Azores, southern Portugal and the Mediterranean B. boops populations. The Almería-Oran Front, widely recognised as an oceanographic barrier for many organisms to cross the Atlantic-Mediterranean divide, does not seem to affect the dispersal of this benthopelagic species. The southward movement of the Cape Verde Frontal Zone during the winter, combined with the relatively short duration of the pelagic larval stage of B. boops, may be potential factors for preventing the connectivity between the Atlantic oceanic archipelagos and Mauritania shaping the genetic signature of this species.}, } @article {pmid36543969, year = {2023}, author = {Zhu, X and Zhao, Y and Zheng, X and Sun, X}, title = {Genetic Diversity of Four Populations of Silver Carp (Hypophthalmichthys molitrix) Based on Mitochondrial Sequences.}, journal = {Biochemical genetics}, volume = {61}, number = {4}, pages = {1231-1241}, pmid = {36543969}, issn = {1573-4927}, support = {HSY2020K1//Open Project of the National and Local Joint Engineering Laboratory for Freshwater Fish Breeding/ ; }, mesh = {Animals ; *Carps/genetics ; Phylogeny ; Genetic Variation ; Mitochondria/genetics ; DNA, Mitochondrial/genetics ; Haplotypes ; China ; }, abstract = {Three mitochondrial DNA sequences (COI, ATP 8&6, and D-loop) were employed to assess the genetic diversity of four populations of silver carp from three main drainages in China, including the Yangtze River, the Amur River, and the Pearl River. As a result, 98 haplotypes were identified in combined sequences of COI, ATP8&6, and D-loop. A total of 196 variable sites and 116 parsimony-informative sites were observed. AMOVA based on assembled sequences indicated that 12.12% of the variation was among populations, while 87.88% of the variation was within populations. Additionally, the phylogenetic relationships of populations were depicted in a phylogenetic tree based on assembled sequences. Mismatch distribution analysis and the negative significant Fu's Fs values supported population expansion in all populations. Despite the high level of genetic diversity, the establishment of a state-level original breeding farm in the Amur River basin and the Pearl River basin may be an effective conservation strategy for the protection of local unique haplotypes.}, } @article {pmid36545736, year = {2023}, author = {He, L and Maheshwari, A}, title = {Mitochondria in Early Life.}, journal = {Current pediatric reviews}, volume = {19}, number = {4}, pages = {395-416}, doi = {10.2174/1573396319666221221110728}, pmid = {36545736}, issn = {1875-6336}, support = {R01 DK120309/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Epigenesis, Genetic ; *Mitochondria/genetics/metabolism ; Signal Transduction ; }, abstract = {Mitochondria are highly-dynamic, membrane-bound organelles that generate most of the chemical energy needed to power the biochemical reactions in eukaryotic cells. These organelles also communicate with the nucleus and other cellular structures to help maintain somatic homeostasis, allow cellular adaptation to stress, and help maintain the developmental trajectory. Mitochondria also perform numerous other functions to support metabolic, energetic, and epigenetic regulation in our cells. There is increasing information on various disorders caused by defects in intrinsic mitochondrial or supporting nuclear genes, on different organ systems. In this review, we have summarized the ultrastructural morphology, structural components, our current understanding of the evolution, biogenesis, dynamics, function, clinical manifestations of mitochondrial dysfunction, and future possibilities. The implications of deficits in mitochondrial dynamics and signaling for embryo viability and offspring health are also explored. We present information from our own clinical and laboratory research in conjunction with information collected from an extensive search in the databases PubMed, EMBASE, and Scopus.}, } @article {pmid36553495, year = {2022}, author = {Kunerth, HD and Tapisso, JT and Valente, R and Mathias, MDL and Alves, PC and Searle, JB and Vega, R and Paupério, J}, title = {Characterising Mitochondrial Capture in an Iberian Shrew.}, journal = {Genes}, volume = {13}, number = {12}, pages = {}, pmid = {36553495}, issn = {2073-4425}, mesh = {Animals ; Phylogeny ; *Shrews/genetics ; *Chromosomes ; Mitochondria/genetics ; Spain ; }, abstract = {Mitochondrial introgression raises questions of biogeography and of the extent of reproductive isolation and natural selection. Previous phylogenetic work on the Sorex araneus complex revealed apparent mitonuclear discordance in Iberian shrews, indicating past hybridisation of Sorex granarius and the Carlit chromosomal race of S. araneus, enabling introgression of the S. araneus mitochondrial genome into S. granarius. To further study this, we genetically typed 61 Sorex araneus/coronatus/granarius from localities in Portugal, Spain, France, and Andorra at mitochondrial, autosomal, and sex-linked loci and combined our data with the previously published sequences. Our data are consistent with earlier data indicating that S. coronatus and S. granarius are the most closely related of the three species, confirming that S. granarius from the Central System mountain range in Spain captured the mitochondrial genome from a population of S. araneus. This mitochondrial capture event can be explained by invoking a biogeographical scenario whereby S. araneus was in contact with S. granarius during the Younger Dryas in central Iberia, despite the two species currently having disjunct distributions. We discuss whether selection favoured S. granarius with an introgressed mitochondrial genome. Our data also suggest recent hybridisation and introgression between S. coronatus and S. granarius, as well as between S. araneus and S. coronatus.}, } @article {pmid36555867, year = {2022}, author = {Malnick, SDH and Alin, P and Somin, M and Neuman, MG}, title = {Fatty Liver Disease-Alcoholic and Non-Alcoholic: Similar but Different.}, journal = {International journal of molecular sciences}, volume = {23}, number = {24}, pages = {}, pmid = {36555867}, issn = {1422-0067}, mesh = {Humans ; *Non-alcoholic Fatty Liver Disease/metabolism ; *Carcinoma, Hepatocellular/metabolism ; *Metabolic Syndrome/metabolism ; *Liver Neoplasms/metabolism ; Liver/metabolism ; *Liver Diseases, Alcoholic/metabolism ; Liver Cirrhosis/metabolism ; Ethanol/metabolism ; }, abstract = {In alcohol-induced liver disease (ALD) and in non-alcoholic fatty liver disease (NAFLD), there are abnormal accumulations of fat in the liver. This phenomenon may be related to excessive alcohol consumption, as well as the combination of alcohol consumption and medications. There is an evolution from simple steatosis to steatohepatitis, fibrosis and cirrhosis leading to hepatocellular carcinoma (HCC). Hepatic pathology is very similar regarding non-alcoholic fatty liver disease (NAFLD) and ALD. Initially, there is lipid accumulation in parenchyma and progression to lobular inflammation. The morphological changes in the liver mitochondria, perivenular and perisinusoidal fibrosis, and hepatocellular ballooning, apoptosis and necrosis and accumulation of fibrosis may lead to the development of cirrhosis and HCC. Medical history of ethanol consumption, laboratory markers of chronic ethanol intake, AST/ALT ratio on the one hand and features of the metabolic syndrome on the other hand, may help in estimating the contribution of alcohol intake and the metabolic syndrome, respectively, to liver steatosis.}, } @article {pmid36563715, year = {2023}, author = {Shukla, P and Mukherjee, S and Patil, A and Joshi, B}, title = {Molecular characterization of variants in mitochondrial DNA encoded genes using next generation sequencing analysis and mitochondrial dysfunction in women with PCOS.}, journal = {Gene}, volume = {855}, number = {}, pages = {147126}, doi = {10.1016/j.gene.2022.147126}, pmid = {36563715}, issn = {1879-0038}, mesh = {Humans ; Female ; DNA, Mitochondrial/genetics ; High-Throughput Nucleotide Sequencing/methods ; *Polycystic Ovary Syndrome/genetics ; Mitochondria/genetics ; RNA, Transfer ; *Genome, Mitochondrial ; }, abstract = {Emerging studies indicates mitochondrial dysfunction and involvement of mitochondrial DNA (mtDNA) variants in the pathogenesis of polycystic ovary syndrome (PCOS). Cumulative effect of mtDNA rare variants are now gaining considerable interest apart from common variants in the pathogenesis of complex diseases. Rare variants may modify the effect of polymorphism or in combination with the common variants may affect the risk of disease. With the evolution of high throughput sequencing techniques, which can be utilized to identify common as well as rare variants along with heteroplasmy levels, comprehensive characterization of the mtDNA variants is possible. Till date, few studies reported common mtDNA variants using traditional sequencing techniques but rare variants in mtDNA encoding genes remain unexplored in women with PCOS. These mtDNA variants may be responsible for mitochondrial dysfunction and may contribute in PCOS pathogenesis. In this study we determined mtDNA copy number, a biomarker of mitochondrial dysfunction and first time analysed variants in mtDNA encoded genes in women with PCOS using mitochondrial Next Generation sequencing (NGS) approach and compared allele frequency from mitochondrial 1000 genome dataset. Variant annotation and prioritization was done using highly automated pipeline, MToolBox that excludes reads mapped from nuclear mitochondrial DNA sequences (NumtS) to identify unique mtDNA reads. The present study identified significant reduction in mtDNA copy number in women with PCOS compared to non-PCOS women. A total of unique 214 prioritized common to rare variants were identified in mtDNA encoded genes, 183 variants in OXPHOS complexes, 14 variants in MT-tRNA and 17 variants in MT-rRNA genes that may be involved in mitochondrial dysfunction in PCOS. Numerous variants were heteroplasmic, pathogenic in nature and occurred in evolutionary conserved region. Heteroplasmic variants were more frequently occurred in MT-CO3 gene. Non-synonymous variants were more than synonymous variants and mainly occurred in OXPHOS complex I and IV. Few variants were found to be associated with diseases in MITOMAP database. The study provides a better understanding towards pathogenesis of PCOS from novel aspects focusing on mitochondrial genetic defects as underlying cause for contributing mitochondrial dysfunction in women with PCOS.}, } @article {pmid36574824, year = {2023}, author = {Baião, GC and Schneider, DI and Miller, WJ and Klasson, L}, title = {Multiple introgressions shape mitochondrial evolutionary history in Drosophila paulistorum and the Drosophila willistoni group.}, journal = {Molecular phylogenetics and evolution}, volume = {180}, number = {}, pages = {107683}, doi = {10.1016/j.ympev.2022.107683}, pmid = {36574824}, issn = {1095-9513}, support = {P 28255/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; *Drosophila/genetics ; Phylogeny ; Nucleic Acid Hybridization ; *Hybridization, Genetic ; }, abstract = {Hybridization and the consequent introgression of genomic elements is an important source of genetic diversity for biological lineages. This is particularly evident in young clades in which hybrid incompatibilities are still incomplete and mixing between species is more likely to occur. Drosophila paulistorum, a representative of the Neotropical Drosophila willistoni subgroup, is a classic model of incipient speciation. The species is divided into six semispecies that show varying degrees of pre- and post-mating incompatibility with each other. In the present study, we investigate the mitochondrial evolutionary history of D. paulistorum and the willistoni subgroup. For that, we perform phylogenetic and comparative analyses of the complete mitochondrial genomes and draft nuclear assemblies of 25 Drosophila lines of the willistoni and saltans species groups. Our results show that the mitochondria of D. paulistorum are polyphyletic and form two non-sister clades that we name α and β. Identification and analyses of nuclear mitochondrial insertions further reveal that the willistoni subgroup has an α-like mitochondrial ancestor and strongly suggest that both the α and β mitochondria of D. paulistorum were acquired through introgression from unknown fly lineages of the willistoni subgroup. We also uncover multiple mitochondrial introgressions across D. paulistorum semispecies and generate novel insight into the evolution of the species.}, } @article {pmid36601706, year = {2023}, author = {Kashinina, NV and Lushchekina, AA and Sorokin, PA and Tarasyan, KK and Kholodova, MV}, title = {The modern state of the European saiga population (Saiga tatarica tatarica): mtDNA, DRB3 MHC gene, and microsatellite diversity.}, journal = {Integrative zoology}, volume = {18}, number = {4}, pages = {661-676}, doi = {10.1111/1749-4877.12704}, pmid = {36601706}, issn = {1749-4877}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; *Antelopes/genetics ; Mitochondria/genetics ; Alleles ; }, } @article {pmid36602189, year = {2023}, author = {Delling, B and Thörn, F and Norén, M and Irestedt, M}, title = {Museomics reveals the phylogenetic position of the extinct Moroccan trout Salmo pallaryi.}, journal = {Journal of fish biology}, volume = {102}, number = {3}, pages = {619-627}, doi = {10.1111/jfb.15299}, pmid = {36602189}, issn = {1095-8649}, mesh = {Animals ; Phylogeny ; *Trout/genetics ; *DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Sequence Analysis, DNA ; }, abstract = {The authors used museomics to reconstruct the mitochondrial genome from two individuals of the Moroccan, endemic and extinct trout, Salmo pallaryi. They further obtained partial data from 21 nuclear genes previously used for trout phylogenetic analyses. Phylogenetic analyses, including publicly available data from the mitochondrial control region and the cytochrome b gene, and the 21 nuclear genes, place S. pallaryi among other North African trouts. mtDNA places S. pallaryi close to Salmo macrostigma within a single North African clade. Although the nuclear coverage of the genome was low, both specimens were independently positioned as sisters to one of two distantly related North African clades, viz. the Atlas clade with the Dades trout, Salmo multipunctatus. Phylogenetic discordance between mtDNA and nuclear DNA phylogenies is briefly discussed. As several specimens that were extracted failed to produce DNA of sufficient quality, the authors discuss potential reasons for the failure. They suggest that museum specimens in poor physical condition may be better for DNA extraction compared to better-preserved ones, possibly related to the innovation of formalin as a fixative before ethanol storage in the early 20th century.}, } @article {pmid36605941, year = {2022}, author = {Locatelli, AG and Cenci, S}, title = {Autophagy and longevity: Evolutionary hints from hyper-longevous mammals.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {1085522}, pmid = {36605941}, issn = {1664-2392}, mesh = {Animals ; Mice ; *Longevity/genetics ; *Aging/genetics/metabolism ; Autophagy/physiology ; Saccharomyces cerevisiae ; Mammals ; }, abstract = {Autophagy is a fundamental multi-tasking adaptive cellular degradation and recycling strategy. Following its causal implication in age-related decline, autophagy is currently among the most broadly studied and challenged mechanisms within aging research. Thanks to these efforts, new cellular nodes interconnected with this phylogenetically ancestral pathway and unexpected roles of autophagy-associated genetic products are unveiled daily, yet the history of functional adaptations of autophagy along its evolutive trail is poorly understood and documented. Autophagy is traditionally studied in canonical and research-wise convenient model organisms such as yeast and mice. However, unconventional animal models endowed with extended longevity and exemption from age-related diseases offer a privileged perspective to inquire into the role of autophagy in the evolution of longevity. In this mini review we retrace the appearance and functions evolved by autophagy in eukaryotic cells and its protective contribution in the pathophysiology of aging.}, } @article {pmid36605953, year = {2022}, author = {Wu, CS and Chen, CI and Chaw, SM}, title = {Plastid phylogenomics and plastome evolution in the morning glory family (Convolvulaceae).}, journal = {Frontiers in plant science}, volume = {13}, number = {}, pages = {1061174}, pmid = {36605953}, issn = {1664-462X}, abstract = {Convolvulaceae, the morning glories or bindweeds, is a large family containing species of economic value, including crops, traditional medicines, ornamentals, and vegetables. However, not only are the phylogenetic relationships within this group still debated at the intertribal and intergeneric levels, but also plastid genome (plastome) complexity within Convolvulaceae is not well surveyed. We gathered 78 plastomes representing 17 genera across nine of the 12 Convolvulaceae tribes. Our plastid phylogenomic trees confirm the monophyly of Convolvulaceae, place the genus Jacquemontia within the subfamily Dicranostyloideae, and suggest that the tribe Merremieae is paraphyletic. In contrast, positions of the two genera Cuscuta and Erycibe are uncertain as the bootstrap support of the branches leading to them is moderate to weak. We show that nucleotide substitution rates are extremely variable among Convolvulaceae taxa and likely responsible for the topological uncertainty. Numerous plastomic rearrangements are detected in Convolvulaceae, including inversions, duplications, contraction and expansion of inverted repeats (IRs), and losses of genes and introns. Moreover, integrated foreign DNA of mitochondrial origin was found in the Jacquemontia plastome, adding a rare example of gene transfer from mitochondria to plastids in angiosperms. In the IR of Dichondra, we discovered an extra copy of rpl16 containing a direct repeat of ca. 200 bp long. This repeat was experimentally demonstrated to trigger effective homologous recombination, resulting in the coexistence of intron-containing and -lacking rpl16 duplicates. Therefore, we propose a hypothetical model to interpret intron loss accompanied by invasion of direct repeats at appropriate positions. Our model complements the intron loss model driven by retroprocessing when genes have lost introns but contain abundant RNA editing sites adjacent to former splicing sites.}, } @article {pmid36610569, year = {2023}, author = {Ji, X and Tian, Y and Liu, W and Lin, C and He, F and Yang, J and Miao, W and Li, Z}, title = {Mitochondrial characteristics of the powdery mildew genus Erysiphe revealed an extraordinary evolution in protein-coding genes.}, journal = {International journal of biological macromolecules}, volume = {230}, number = {}, pages = {123153}, doi = {10.1016/j.ijbiomac.2023.123153}, pmid = {36610569}, issn = {1879-0003}, mesh = {*Erysiphe ; Phylogeny ; *Ascomycota/genetics ; Plants/microbiology ; Plant Diseases/genetics/microbiology ; }, abstract = {The genus Erysiphe was an obligate parasite causing powdery mildew disease on a wide range of higher plants. However, the knowledge of their mitogenome architecture for lifestyle adaptability was scarce. Here, we assembled the first complete mitogenome (190,559 bp in size) for rubber tree powdery mildew pathogen Erysiphe quercicola. Comparable analysis of the Erysiphe mitogenomes exhibited conserved gene content, genome organization and codon usage bias, but extensive dynamic intron gain/loss events were presented between Erysiphe species. The phylogeny of the Ascomycota species constructed in the phylogenetic analysis showed genetic divergences of the Erysiphe species. Compared with other distant saprophytic and plant pathogenic fungi, Erysiphe had a flat distribution of evolutionary pressures on fungal standard protein-coding genes (PCGs). The Erysiphe PCGs had the highest mean selection pressure. In particular, Erysiphe's cox1, nad1, cob and rps3 genes had the most elevated selection pressures among corresponding PCGs across fungal genera. Altogether, the investigations provided a novel insight into the potential evolutionary pattern of the genus Erysiphe to adapt obligate biotrophic lifestyle and promoted the understanding of the high plasticity and population evolution of fungal mitogenomes.}, } @article {pmid36613565, year = {2022}, author = {Bottoni, P and Gionta, G and Scatena, R}, title = {Remarks on Mitochondrial Myopathies.}, journal = {International journal of molecular sciences}, volume = {24}, number = {1}, pages = {}, pmid = {36613565}, issn = {1422-0067}, mesh = {Humans ; *Mitochondria/genetics/metabolism ; *Mitochondrial Myopathies/genetics ; Cell Respiration ; Oxidative Phosphorylation ; NAD/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Mitochondrial myopathies represent a heterogeneous group of diseases caused mainly by genetic mutations to proteins that are related to mitochondrial oxidative metabolism. Meanwhile, a similar etiopathogenetic mechanism (i.e., a deranged oxidative phosphorylation and a dramatic reduction of ATP synthesis) reveals that the evolution of these myopathies show significant differences. However, some physiological and pathophysiological aspects of mitochondria often reveal other potential molecular mechanisms that could have a significant pathogenetic role in the clinical evolution of these disorders, such as: i. a deranged ROS production both in term of signaling and in terms of damaging molecules; ii. the severe modifications of nicotinamide adenine dinucleotide (NAD)+/NADH, pyruvate/lactate, and α-ketoglutarate (α-KG)/2- hydroxyglutarate (2-HG) ratios. A better definition of the molecular mechanisms at the basis of their pathogenesis could improve not only the clinical approach in terms of diagnosis, prognosis, and therapy of these myopathies but also deepen the knowledge of mitochondrial medicine in general.}, } @article {pmid36629021, year = {2023}, author = {Fang, YK and Vaitová, Z and Hampl, V}, title = {A mitochondrion-free eukaryote contains proteins capable of import into an exogenous mitochondrion-related organelle.}, journal = {Open biology}, volume = {13}, number = {1}, pages = {220238}, pmid = {36629021}, issn = {2046-2441}, mesh = {*Eukaryota/metabolism ; *Protozoan Proteins/metabolism ; Organelles/chemistry/metabolism ; Mitochondria/metabolism ; Protein Transport ; }, abstract = {The endobiotic flagellate Monocercomonoides exilis is the only known eukaryote to have lost mitochondria and all its associated proteins in its evolutionary past. This final stage of the mitochondrial evolutionary pathway may serve as a model to explain events at their very beginning such as the initiation of protein import. We have assessed the capability of proteins from this eukaryote to enter emerging mitochondria using a specifically designed in vitro assay. Hydrogenosomes (reduced mitochondria) of Trichomonas vaginalis were incubated with a soluble protein pool derived from a cytosolic fraction of M. exilis, and proteins entering hydrogenosomes were subsequently detected by mass spectrometry. The assay detected 19 specifically and reproducibly imported proteins, and in 14 cases the import was confirmed by the overexpression of their tagged version in T. vaginalis. In most cases, only a small portion of the signal reached the hydrogenosomes, suggesting specific but inefficient transport. Most of these proteins represent enzymes of carbon metabolism, and none exhibited clear signatures of proteins targeted to hydrogenosomes or mitochondria, which is consistent with their inefficient import. The observed phenomenon may resemble a primaeval type of protein import which might play a role in the establishment of the organelle and shaping of its proteome in the initial stages of endosymbiosis.}, } @article {pmid36632145, year = {2023}, author = {Borges, DGF and Carvalho, DS and Bomfim, GC and Ramos, PIP and Brzozowski, J and Góes-Neto, A and Andrade, R and El-Hani, C}, title = {On the origin of mitochondria: a multilayer network approach.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e14571}, pmid = {36632145}, issn = {2167-8359}, mesh = {Phylogeny ; *Mitochondria/genetics ; Biological Evolution ; *Alphaproteobacteria/genetics ; Genes, Mitochondrial ; }, abstract = {BACKGOUND: The endosymbiotic theory is widely accepted to explain the origin of mitochondria from a bacterial ancestor. While ample evidence supports the intimate connection of Alphaproteobacteria to the mitochondrial ancestor, pinpointing its closest relative within sampled Alphaproteobacteria is still an open evolutionary debate. Many different phylogenetic methods and approaches have been used to answer this challenging question, further compounded by the heterogeneity of sampled taxa, varying evolutionary rates of mitochondrial proteins, and the inherent biases in each method, all factors that can produce phylogenetic artifacts. By harnessing the simplicity and interpretability of protein similarity networks, herein we re-evaluated the origin of mitochondria within an enhanced multilayer framework, which is an extension and improvement of a previously developed method.

METHODS: We used a dataset of eight proteins found in mitochondria (N = 6 organisms) and bacteria (N = 80 organisms). The sequences were aligned and resulting identity matrices were combined to generate an eight-layer multiplex network. Each layer corresponded to a protein network, where nodes represented organisms and edges were placed following mutual sequence identity. The Multi-Newman-Girvan algorithm was applied to evaluate community structure, and bifurcation events linked to network partition allowed to trace patterns of divergence between studied taxa.

RESULTS: In our network-based analysis, we first examined the topology of the 8-layer multiplex when mitochondrial sequences disconnected from the main alphaproteobacterial cluster. The resulting topology lent firm support toward an Alphaproteobacteria-sister placement for mitochondria, reinforcing the hypothesis that mitochondria diverged from the common ancestor of all Alphaproteobacteria. Additionally, we observed that the divergence of Rickettsiales was an early event in the evolutionary history of alphaproteobacterial clades.

CONCLUSION: By leveraging complex networks methods to the challenging question of circumscribing mitochondrial origin, we suggest that the entire Alphaproteobacteria clade is the closest relative to mitochondria (Alphaproteobacterial-sister hypothesis), echoing recent findings based on different datasets and methodologies.}, } @article {pmid36634115, year = {2023}, author = {Rossitto De Marchi, B and Gama, AB and Smith, HA}, title = {Evidence of the association between the Q2 mitochondrial group of Bemisia tabaci MED species (Hemiptera: Aleyrodidae) and low competitive displacement capability.}, journal = {PloS one}, volume = {18}, number = {1}, pages = {e0280002}, pmid = {36634115}, issn = {1932-6203}, mesh = {Animals ; Phylogeny ; *Hemiptera/genetics ; Mitochondria/genetics ; Food ; Florida ; }, abstract = {The whitefly, Bemisia tabaci (Gennadius), is one of the most serious agricultural pests worldwide. Bemisia tabaci is a cryptic species complex of more than 40 species among which the invasive MEAM1 and MED species are the most widespread and economically important. Both MEAM1 and MED present intraspecific genetic variability and some haplotypes are reported to be more invasive than others. MED can be further deconstructed into different genetic groups, including MED-Q1 and MED-Q2. However, distinct biological phenotypes discerning the different MED mitochondrial haplotypes are yet to be characterized. Competitive displacement and life-history trials were carried out between MED-Q2 and MEAM1 populations collected in Florida, USA. In addition, a phylogenetic analysis was carried out including populations from previous whitefly competitive displacement studies for identification and comparison of the MED mitochondrial groups. In contrast to other studies with MED-Q1, the MED-Q2 population from Florida is less likely to displace MEAM1 on pepper. In addition, both pepper and watermelon were a more favorable host to MEAM1 compared to MED-Q2 according to the life history trials.}, } @article {pmid36634192, year = {2023}, author = {Osipova, E and Barsacchi, R and Brown, T and Sadanandan, K and Gaede, AH and Monte, A and Jarrells, J and Moebius, C and Pippel, M and Altshuler, DL and Winkler, S and Bickle, M and Baldwin, MW and Hiller, M}, title = {Loss of a gluconeogenic muscle enzyme contributed to adaptive metabolic traits in hummingbirds.}, journal = {Science (New York, N.Y.)}, volume = {379}, number = {6628}, pages = {185-190}, doi = {10.1126/science.abn7050}, pmid = {36634192}, issn = {1095-9203}, mesh = {Animals ; *Birds/genetics/metabolism ; Energy Metabolism/genetics ; *Flight, Animal/physiology ; *Gluconeogenesis/genetics ; *Adaptation, Physiological/genetics ; *Fructose-Bisphosphatase/genetics ; *Muscle, Skeletal/enzymology ; }, abstract = {Hummingbirds possess distinct metabolic adaptations to fuel their energy-demanding hovering flight, but the underlying genomic changes are largely unknown. Here, we generated a chromosome-level genome assembly of the long-tailed hermit and screened for genes that have been specifically inactivated in the ancestral hummingbird lineage. We discovered that FBP2 (fructose-bisphosphatase 2), which encodes a gluconeogenic muscle enzyme, was lost during a time period when hovering flight evolved. We show that FBP2 knockdown in an avian muscle cell line up-regulates glycolysis and enhances mitochondrial respiration, coincident with an increased mitochondria number. Furthermore, genes involved in mitochondrial respiration and organization have up-regulated expression in hummingbird flight muscle. Together, these results suggest that FBP2 loss was likely a key step in the evolution of metabolic muscle adaptations required for true hovering flight.}, } @article {pmid36636864, year = {2023}, author = {Achatz, TJ and Von Holten, ZS and Kipp, JW and Fecchio, A and LaFond, LR and Greiman, SE and Martens, JR and Tkach, VV}, title = {Phylogenetic relationships and further unknown diversity of diplostomids (Diplostomida: Diplostomidae) parasitic in kingfishers.}, journal = {Journal of helminthology}, volume = {97}, number = {}, pages = {e8}, doi = {10.1017/S0022149X22000852}, pmid = {36636864}, issn = {1475-2697}, support = {P20GM103442/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Phylogeny ; *Trematoda ; Fishes/parasitology ; Mitochondria ; Brazil ; }, abstract = {Kingfishers (Alcedinidae Rafinesque) are common inhabitants of wetlands and are known to be definitive hosts to a wide range of digeneans that parasitize fish as second intermediate hosts. Among these digeneans, members of the Diplostomidae Poirier, 1886 (diplostomids) are particularly common. Recent studies of diplostomids collected from kingfishers have revealed that they are probably more diverse than currently known. This particularly concerns the genera Crassiphiala Van Haitsma, 1925 and Uvulifer Yamaguti, 1934. In the present work, we studied seven diplostomid taxa from kingfishers in Brazil, the USA and the Philippines. Partial DNA sequences of the nuclear large ribosomal subunit (28S) and mitochondrial cytochrome c oxidase I (cox1) genes were obtained, and 28S sequences were used to study the phylogenetic interrelationships of these diplostomids. We provide the first DNA sequences from Uvulifer semicircumcisus Dubois et Rausch, 1950 and a member of Subuvulifer Dubois, 1952. Pseudocrassiphiala n. gen. is erected for a previously recognized species-level lineage of Crassiphiala and a new generic diagnosis of Crassiphiala is provided. Crassiphiala jeffreybelli n. sp., Crassiphiala wecksteini n. sp. and Pseudocrassiphiala tulipifera n. sp. are described, and a description of newly collected, high-quality specimens of Crassiphiala bulboglossa Van Haitsma, 1925 (the type-species of the genus) is provided.}, } @article {pmid36638953, year = {2023}, author = {Gnocchi, D and Sabbà, C and Mazzocca, A}, title = {Lactic acid fermentation: A maladaptive mechanism and an evolutionary throwback boosting cancer drug resistance.}, journal = {Biochimie}, volume = {208}, number = {}, pages = {180-185}, doi = {10.1016/j.biochi.2023.01.005}, pmid = {36638953}, issn = {1638-6183}, mesh = {Humans ; *Lactic Acid/metabolism ; Fermentation ; Glycolysis ; Mitochondria/metabolism ; *Neoplasms/drug therapy/genetics/metabolism ; Drug Resistance, Neoplasm/genetics ; }, abstract = {After four decades of research primarily focused on tumour genetics, the importance of metabolism in tumour biology is receiving renewed attention. Cancer cells undergo energy, biosynthetic and metabolic rewiring, which involves several pathways with a prevalent change from oxidative phosphorylation (OXPHOS) to lactic acid fermentation, known as the Warburg effect. During carcinogenesis, microenvironmental changes can trigger the transition from OXPHOS to lactic acid fermentation, an ancient form of energy supply, mimicking the behaviour of certain anaerobic unicellular organisms according to "atavistic" models of cancer. However, the role of this transition as a mechanism of cancer drug resistance is unclear. Here, we hypothesise that the metabolic rewiring of cancer cells to fermentation can be triggered, enhanced, and sustained by exposure to chronic or high-dose chemotherapy, thereby conferring resistance to drug therapy. We try to expand on the idea that metabolic reprogramming from OXPHOS to lactate fermentation in drug-resistant tumour cells occurs as a general phenotypic mechanism in any type of cancer, regardless of tumour cell heterogeneity, biodiversity, and genetic characteristics. This metabolic response may therefore represent a common feature in cancer biology that could be exploited for therapeutic purposes to overcome chemotherapy resistance, which is currently a major challenge in cancer treatment.}, } @article {pmid36642905, year = {2022}, author = {Zhou, XQ and Ma, J and Wang, RY and Wang, RH and Wu, YQ and Yang, XY and Chen, YJ and Tang, XN and Sun, ET}, title = {[Bacterial community diversity in Dermatophagoides farinae using high-throughput sequencing].}, journal = {Zhongguo xue xi chong bing fang zhi za zhi = Chinese journal of schistosomiasis control}, volume = {34}, number = {6}, pages = {630-634}, doi = {10.16250/j.32.1374.2022105}, pmid = {36642905}, issn = {1005-6661}, support = {31870352//National Natural Science Foundation of China/ ; S202110368010//Anhui Provincial University Students' Innovation and Entrepreneurship Training Program/ ; }, mesh = {Humans ; Animals ; *Dermatophagoides farinae/genetics ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; High-Throughput Nucleotide Sequencing ; *Microbiota ; Phylogeny ; }, abstract = {OBJECTIVE: To investigate the bacterial community diversity in Dermatophagoides farinae.

METHODS: Laboratory-cultured D. farinae was collected, and the composition of microbial communities was determined by sequence analyses of the V4 region in the bacterial 16S ribosomal RNA (16S rRNA) gene on an Illumina PE250 high-throughput sequencing platform. Following quality control and filtering of the raw sequence files, valid reads were obtained and subjected to operational taxonomic units (OTU) clustering and analysis of the composition of microbial communities and alpha diversity index using the Usearch software, Silva database, and Mothur software.

RESULTS: A total of 187 616 valid reads were obtained, and 469 OTUs were clustered based on a sequence similarity of more than 97%. OTU annotation showed that the bacteria in D. farinae belonged to 26 phyla, 43 classes, 100 orders, 167 families and 284 genera. The bacteria in D. farinae were mainly annotated to five phyla of Proteobacteria, Firmicutes, Bacteroidota, Actinobacteriota, and Acidobacteriota, with Proteobacteria as the dominant phylum, and mainly annotated to five dominant genera of Ralstonia, norank-f-Mitochondria, Staphylococcus and Sphingomonas, with Wolbachia identified in the non-dominant genus.

CONCLUSIONS: A high diversity is identified in the composition of the bacterial community in D. farinae, and there are differences in bacterial community diversity and abundance among D. farinae.}, } @article {pmid36644898, year = {2023}, author = {He, W and Xiang, K and Chen, C and Wang, J and Wu, Z}, title = {Master graph: an essential integrated assembly model for the plant mitogenome based on a graph-based framework.}, journal = {Briefings in bioinformatics}, volume = {24}, number = {1}, pages = {}, doi = {10.1093/bib/bbac522}, pmid = {36644898}, issn = {1477-4054}, mesh = {Animals ; *Genome, Mitochondrial ; DNA, Mitochondrial/genetics ; Biological Evolution ; Mitochondria/genetics ; Plants/genetics ; Phylogeny ; }, abstract = {Unlike the typical single circular structure of most animal mitochondrial genomes (mitogenome), the drastic structural variation of plant mitogenomes is a result of a mixture of molecules of various sizes and structures. Obtaining the full panoramic plant mitogenome is still considered a roadblock in evolutionary biology. In this study, we developed a graph-based sequence assembly toolkit (GSAT) to construct the pan-structural landscape of plant mitogenome with high-quality mitochondrial master graphs (MMGs) for model species including rice (Oryza sativa) and thale cress (Arabidopsis thaliana). The rice and thale cress MMGs have total lengths of 346 562 and 358 041 bp, including 9 and 6 contigs and 12 and 8 links, respectively, and could be further divided into 6 and 3 minimum master circles and 4 and 2 minimum secondary circles separately. The nuclear mitochondrial DNA segments (NUMTs) in thale cress strongly affected the frequency evaluation of the homologous structures in the mitogenome, while the effects of NUMTs in rice were relatively weak. The mitochondrial plastid DNA segments (MTPTs) in both species had no effects on the assessment of the MMGs. All potential recombinant structures were evaluated, and the findings revealed that all, except for nuclear-homologous structures, MMG structures are present at a much higher frequency than non-MMG structures are. Investigations of potential circular and linear molecules further supported multiple dominant structures in the mitogenomes and could be completely summarized in the MMG. Our study provided an efficient and accurate model for assembling and applying graph-based plant mitogenomes to assess their pan-structural variations.}, } @article {pmid36646908, year = {2023}, author = {Muñoz-Gómez, SA}, title = {Energetics and evolution of anaerobic microbial eukaryotes.}, journal = {Nature microbiology}, volume = {8}, number = {2}, pages = {197-203}, pmid = {36646908}, issn = {2058-5276}, mesh = {*Eukaryota ; Anaerobiosis ; *Mitochondria/metabolism ; Eukaryotic Cells/metabolism ; Fermentation ; }, abstract = {Mitochondria and aerobic respiration have been suggested to be required for the evolution of eukaryotic cell complexity. Aerobic respiration is several times more energetically efficient than fermentation. Moreover, aerobic respiration occurs at internalized mitochondrial membranes that are not constrained by a sublinear scaling with cell volume. However, diverse and complex anaerobic eukaryotes (for example, free-living and parasitic unicellular, and even small multicellular, eukaryotes) that exclusively rely on fermentation for energy generation have evolved repeatedly from aerobic ancestors. How do fermenting eukaryotes maintain their cell volumes and complexity while relying on such a low energy-yielding process? Here I propose that reduced rates of ATP generation in fermenting versus respiring eukaryotes are compensated for by longer cell cycles that satisfy lifetime energy demands. A literature survey and growth efficiency calculations show that fermenting eukaryotes divide approximately four to six times slower than aerobically respiring counterparts with similar cell volumes. Although ecological advantages such as competition avoidance offset lower growth rates and yields in the short term, fermenting eukaryotes inevitably have fewer physiological and ecological possibilities, which ultimately constrain their long-term evolutionary trajectories.}, } @article {pmid36648250, year = {2023}, author = {Graham, AM and Barreto, FS}, title = {Myxozoans (Cnidaria) do not Retain Key Oxygen-Sensing and Homeostasis Toolkit Genes.}, journal = {Genome biology and evolution}, volume = {15}, number = {1}, pages = {}, pmid = {36648250}, issn = {1759-6653}, mesh = {Animals ; *Cnidaria/metabolism ; Oxygen/metabolism ; *Myxozoa/genetics ; Hypoxia/genetics ; Homeostasis ; Hypoxia-Inducible Factor 1, alpha Subunit ; }, abstract = {For aerobic organisms, both the hypoxia-inducible factor pathway and the mitochondrial genomes are key players in regulating oxygen homeostasis. Recent work has suggested that these mechanisms are not as highly conserved as previously thought, prompting more surveys across animal taxonomic levels, which would permit testing of hypotheses about the ecological conditions facilitating evolutionary loss of such genes. The Phylum Cnidaria is known to harbor wide variation in mitochondrial chromosome morphology, including an extreme example, in the Myxozoa, of mitochondrial genome loss. Because myxozoans are obligate endoparasites, frequently encountering hypoxic environments, we hypothesize that variation in environmental oxygen availability could be a key determinant in the evolution of metabolic gene networks associated with oxygen-sensing, hypoxia-response, and energy production. Here, we surveyed genomes and transcriptomes across 46 cnidarian species for the presence of HIF pathway members, as well as for an assortment of hypoxia, mitochondrial, and stress-response toolkit genes. We find that presence of the HIF pathway, as well as number of genes associated with mitochondria, hypoxia, and stress response, do not vary in parallel to mitochondrial genome morphology. More interestingly, we uncover evidence that myxozoans have lost the canonical HIF pathway repression machinery, potentially altering HIF pathway functionality to work under the specific conditions of their parasitic lifestyles. In addition, relative to other cnidarians, myxozoans show loss of large proportions of genes associated with the mitochondrion and involved in response to hypoxia and general stress. Our results provide additional evidence that the HIF regulatory machinery is evolutionarily labile and that variations in the canonical system have evolved in many animal groups.}, } @article {pmid36651963, year = {2023}, author = {Moreira, F and Arenas, M and Videira, A and Pereira, F}, title = {Evolution of TOP1 and TOP1MT Topoisomerases in Chordata.}, journal = {Journal of molecular evolution}, volume = {91}, number = {2}, pages = {192-203}, pmid = {36651963}, issn = {1432-1432}, mesh = {Animals ; *DNA, Mitochondrial/genetics ; *Chordata/genetics ; DNA Topoisomerases, Type I/genetics/chemistry/metabolism ; Mitochondria/genetics ; Cell Nucleus/genetics ; }, abstract = {Type IB topoisomerases relax the torsional stress associated with DNA metabolism in the nucleus and mitochondria and constitute important molecular targets of anticancer drugs. Vertebrates stand out among eukaryotes by having two Type IB topoisomerases acting specifically in the nucleus (TOP1) and mitochondria (TOP1MT). Despite their major importance, the origin and evolution of these paralogues remain unknown. Here, we examine the molecular evolutionary processes acting on both TOP1 and TOP1MT in Chordata, taking advantage of the increasing number of available genome sequences. We found that both TOP1 and TOP1MT evolved under strong purifying selection, as expected considering their essential biological functions. Critical active sites, including those associated with resistance to anticancer agents, were found particularly conserved. However, TOP1MT presented a higher rate of molecular evolution than TOP1, possibly related with its specialized activity on the mitochondrial genome and a less critical role in cells. We could place the duplication event that originated the TOP1 and TOP1MT paralogues early in the radiation of vertebrates, most likely associated with the first round of vertebrate tetraploidization (1R). Moreover, our data suggest that cyclostomes present a specialized mitochondrial Type IB topoisomerase. Interestingly, we identified two missense mutations replacing amino acids in the Linker region of TOP1MT in Neanderthals, which appears as a rare event when comparing the genome of both species. In conclusion, TOP1 and TOP1MT differ in their rates of evolution, and their evolutionary histories allowed us to better understand the evolution of chordates.}, } @article {pmid36656997, year = {2023}, author = {Opazo, JC and Vandewege, MW and Hoffmann, FG and Zavala, K and Meléndez, C and Luchsinger, C and Cavieres, VA and Vargas-Chacoff, L and Morera, FJ and Burgos, PV and Tapia-Rojas, C and Mardones, GA}, title = {How Many Sirtuin Genes Are Out There? Evolution of Sirtuin Genes in Vertebrates With a Description of a New Family Member.}, journal = {Molecular biology and evolution}, volume = {40}, number = {2}, pages = {}, pmid = {36656997}, issn = {1537-1719}, mesh = {Animals ; *Sirtuins/genetics ; *Sirtuin 3/genetics ; Evolution, Molecular ; Vertebrates/genetics ; Phylogeny ; Mammals ; }, abstract = {Studying the evolutionary history of gene families is a challenging and exciting task with a wide range of implications. In addition to exploring fundamental questions about the origin and evolution of genes, disentangling their evolution is also critical to those who do functional/structural studies to allow a deeper and more precise interpretation of their results in an evolutionary context. The sirtuin gene family is a group of genes that are involved in a variety of biological functions mostly related to aging. Their duplicative history is an open question, as well as the definition of the repertoire of sirtuin genes among vertebrates. Our results show a well-resolved phylogeny that represents an improvement in our understanding of the duplicative history of the sirtuin gene family. We identified a new sirtuin gene family member (SIRT3.2) that was apparently lost in the last common ancestor of amniotes but retained in all other groups of jawed vertebrates. According to our experimental analyses, elephant shark SIRT3.2 protein is located in mitochondria, the overexpression of which leads to an increase in cellular levels of ATP. Moreover, in vitro analysis demonstrated that it has deacetylase activity being modulated in a similar way to mammalian SIRT3. Our results indicate that there are at least eight sirtuin paralogs among vertebrates and that all of them can be traced back to the last common ancestor of the group that existed between 676 and 615 millions of years ago.}, } @article {pmid36657651, year = {2023}, author = {Moreno-Carmona, M and Montaña-Lozano, P and Prada Quiroga, CF and Baeza, JA}, title = {Comparative analysis of mitochondrial genomes reveals family-specific architectures and molecular features in scorpions (Arthropoda: Arachnida: Scorpiones).}, journal = {Gene}, volume = {859}, number = {}, pages = {147189}, doi = {10.1016/j.gene.2023.147189}, pmid = {36657651}, issn = {1879-0038}, mesh = {Humans ; Animals ; Scorpions/genetics ; *Arachnida/genetics ; *Genome, Mitochondrial/genetics ; Phylogeny ; Mitochondria/genetics ; RNA, Transfer/genetics ; }, abstract = {Scorpions are a group of arachnids with great evolutionary success that comprise more than 2,000 described species. Mitochondrial genomes have been little studied in this clade. We describe and compare different scorpion mitochondrial genomes and analyze their architecture and molecular characteristics. We assembled eight new scorpion mitochondrial genomes from transcriptomic datasets, annotated them, predicted the secondary structures of tRNAs, and compared the nucleotide composition, codon usage, and relative synonymous codon usage of 16 complete scorpion mitochondrial genomes. Lastly, we provided a phylogeny based on all mitochondrial protein coding genes. We characterized the mitogenomes in detail and reported particularities such as dissimilar synteny in the family Buthidae compared to other scorpions, unusual tRNA secondary structures, and unconventional start and stop codons in all scorpions. Our comparative analysis revealed that scorpion mitochondrial genomes exhibit different architectures and features depending on taxonomic identity. We highlight the parvorder Buthida, particularly the family Buthidae, as it invariably exhibited different mitogenome features such as synteny, codon usage, and AT-skew compared to the parvorder Iurida that included the rest of the scorpion families we analyzed in this study. Our results provide a better understanding of the evolution of mitogenome features and phylogenetic relationships in scorpions.}, } @article {pmid36659315, year = {2017}, author = {Ye, LQ and Zhao, H and Zhou, HJ and Ren, XD and Liu, LL and Otecko, NO and Wang, ZB and Yang, MM and Zeng, L and Hu, XT and Yao, YG and Zhang, YP and Wu, DD}, title = {The RNA editome of Macaca mulatta and functional characterization of RNA editing in mitochondria.}, journal = {Science bulletin}, volume = {62}, number = {12}, pages = {820-830}, doi = {10.1016/j.scib.2017.05.021}, pmid = {36659315}, issn = {2095-9281}, abstract = {RNA editing was first discovered in mitochondrial RNA molecular. However, whether adenosine-to-inosine (A-to-I) RNA editing has functions in nuclear genes involved in mitochondria remains elusive. Here, we retrieved 707,246 A-to-I RNA editing sites in Macaca mulatta leveraging massive transcriptomes of 30 different tissues and genomes of nine tissues, together with the reported data, and found that A-to-I RNA editing occurred frequently in nuclear genes that have functions in mitochondria. The mitochondrial structure, the level of ATP production, and the expression of some key genes involved in mitochondrial function were dysregulated after knocking down the expression of ADAR1 and ADAR2, the key genes encoding the enzyme responsible for RNA editing. When investigating dynamic changes of RNA editing during brain development, an amino-acid-changing RNA editing site (I234/V) in MFN1, a mediator of mitochondrial fusion, was identified to be significantly correlated with age, and could influence the function of MFN1. When studying transcriptomes of brain disorder, we found that dysregulated RNA editing sites in autism were also enriched within genes having mitochondrial functions. These data indicated that RNA editing had a significant function in mitochondria via their influence on nuclear genes.}, } @article {pmid36670920, year = {2022}, author = {Cruz-Gregorio, A and Aranda-Rivera, AK and Aparicio-Trejo, OE and Medina-Campos, ON and Sciutto, E and Fragoso, G and Pedraza-Chaverri, J}, title = {GK-1 Induces Oxidative Stress, Mitochondrial Dysfunction, Decreased Membrane Potential, and Impaired Autophagy Flux in a Mouse Model of Breast Cancer.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {36670920}, issn = {2076-3921}, support = {IN218822//National Autonomous University of Mexico/ ; IN200922//National Autonomous University of Mexico/ ; 302961//Consejo Nacional de Ciencia y Tecnología/ ; A1-S-7495//Consejo Nacional de Ciencia y Tecnología/ ; 5000-9105//Programa de Apoyo a la Investigación y el Posgrado (PAIP), Facultd de Química, UNAM/ ; }, abstract = {Breast cancer (BC) is the second most common cancer worldwide in women. During the last decades, the mortality due to breast cancer has progressively decreased due to early diagnosis and the emergence of more effective new treatments. However, human epidermal growth factor receptor 2 (HER2) and triple-negative breast cancer (TNBC) remain with poor prognoses. In our research group, we are proposing the GK-1 immunomodulatory peptide as a new alternative for immunotherapy of these aggressive tumors. GK-1 reduced the growth rate of established tumors and effectively reduced lung metastasis in the 4T1 experimental murine model of breast cancer. Herein, the effect of GK-1 on the redox state, mitochondrial metabolism, and autophagy of triple-negative tumors that can be linked to cancer evolution was studied. GK-1 decreased catalase activity, reduced glutathione (GSH) content and GSH/oxidized glutathione (GSSG) ratio while increased hydrogen peroxide (H2O2) production, GSSG, and protein carbonyl content, inducing oxidative stress (OS) in tumoral tissues. This imbalance between reactive oxygen species (ROS) and antioxidants was related to mitochondrial dysfunction and uncoupling, characterized by reduced mitochondrial respiratory parameters and dissipation of mitochondrial membrane potential (ΔΨm), respectively. Furthermore, GK-1 likely affected autophagy flux, confirmed by elevated levels of p62, a marker of autophagy flux. Overall, the induction of OS, dysfunction, and uncoupling of the mitochondria and the reduction of autophagy could be molecular mechanisms that underlie the reduction of the 4T1 breast cancer induced by GK-1.}, } @article {pmid36671555, year = {2023}, author = {Righetto, I and Gasparotto, M and Casalino, L and Vacca, M and Filippini, F}, title = {Exogenous Players in Mitochondria-Related CNS Disorders: Viral Pathogens and Unbalanced Microbiota in the Gut-Brain Axis.}, journal = {Biomolecules}, volume = {13}, number = {1}, pages = {}, pmid = {36671555}, issn = {2218-273X}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Brain-Gut Axis ; *Central Nervous System Diseases ; *Gastrointestinal Microbiome ; Mitochondria ; }, abstract = {Billions of years of co-evolution has made mitochondria central to the eukaryotic cell and organism life playing the role of cellular power plants, as indeed they are involved in most, if not all, important regulatory pathways. Neurological disorders depending on impaired mitochondrial function or homeostasis can be caused by the misregulation of "endogenous players", such as nuclear or cytoplasmic regulators, which have been treated elsewhere. In this review, we focus on how exogenous agents, i.e., viral pathogens, or unbalanced microbiota in the gut-brain axis can also endanger mitochondrial dynamics in the central nervous system (CNS). Neurotropic viruses such as Herpes, Rabies, West-Nile, and Polioviruses seem to hijack neuronal transport networks, commandeering the proteins that mitochondria typically use to move along neurites. However, several neurological complications are also associated to infections by pandemic viruses, such as Influenza A virus and SARS-CoV-2 coronavirus, representing a relevant risk associated to seasonal flu, coronavirus disease-19 (COVID-19) and "Long-COVID". Emerging evidence is depicting the gut microbiota as a source of signals, transmitted via sensory neurons innervating the gut, able to influence brain structure and function, including cognitive functions. Therefore, the direct connection between intestinal microbiota and mitochondrial functions might concur with the onset, progression, and severity of CNS diseases.}, } @article {pmid36672951, year = {2023}, author = {Zhang, T and Wang, Y and Song, H}, title = {The Complete Mitochondrial Genome and Gene Arrangement of the Enigmatic Scaphopod Pictodentalium vernedei.}, journal = {Genes}, volume = {14}, number = {1}, pages = {}, pmid = {36672951}, issn = {2073-4425}, mesh = {Animals ; *Genome, Mitochondrial ; Phylogeny ; Gene Order ; Mollusca/genetics ; Mitochondria/genetics ; }, abstract = {The enigmatic scaphopods, or tusk shells, are a small and rare group of molluscs whose phylogenomic position among the Conchifera is undetermined, and the taxonomy within this class also needs revision. Such work is hindered by there only being a very few mitochondrial genomes in this group that are currently available. Here, we present the assembly and annotation of the complete mitochondrial genome from Dentaliida Pictodentalium vernedei, whose mitochondrial genome is 14,519 bp in size, containing 13 protein-coding genes, 22 tRNA genes and two rRNA genes. The nucleotide composition was skewed toward A-T, with a 71.91% proportion of AT content. Due to the mitogenome-based phylogenetic analysis, we defined P. vernedei as a sister to Graptacme eborea in Dentaliida. Although a few re-arrangements occurred, the mitochondrial gene order showed deep conservation within Dentaliida. Yet, such a gene order in Dentaliida largely diverges from Gadilida and other molluscan classes, suggesting that scaphopods have the highest degree of mitogenome arrangement compared to other molluscs.}, } @article {pmid36695030, year = {2023}, author = {Röhricht, H and Przybyla-Toscano, J and Forner, J and Boussardon, C and Keech, O and Rouhier, N and Meyer, EH}, title = {Mitochondrial ferredoxin-like is essential for forming complex I-containing supercomplexes in Arabidopsis.}, journal = {Plant physiology}, volume = {191}, number = {4}, pages = {2170-2184}, pmid = {36695030}, issn = {1532-2548}, mesh = {*Ferredoxins/genetics/metabolism ; *Arabidopsis/genetics/metabolism ; Phylogeny ; Electron Transport Complex I/genetics/metabolism ; Mitochondria/metabolism ; }, abstract = {In eukaryotes, mitochondrial ATP is mainly produced by the oxidative phosphorylation (OXPHOS) system, which is composed of 5 multiprotein complexes (complexes I-V). Analyses of the OXPHOS system by native gel electrophoresis have revealed an organization of OXPHOS complexes into supercomplexes, but their roles and assembly pathways remain unclear. In this study, we characterized an atypical mitochondrial ferredoxin (mitochondrial ferredoxin-like, mFDX-like). This protein was previously found to be part of the bridge domain linking the matrix and membrane arms of the complex I. Phylogenetic analysis suggested that the Arabidopsis (Arabidopsis thaliana) mFDX-like evolved from classical mitochondrial ferredoxins (mFDXs) but lost one of the cysteines required for the coordination of the iron-sulfur (Fe-S) cluster, supposedly essential for the electron transfer function of FDXs. Accordingly, our biochemical study showed that AtmFDX-like does not bind an Fe-S cluster and is therefore unlikely to be involved in electron transfer reactions. To study the function of mFDX-like, we created deletion lines in Arabidopsis using a CRISPR/Cas9-based strategy. These lines did not show any abnormal phenotype under standard growth conditions. However, the characterization of the OXPHOS system demonstrated that mFDX-like is important for the assembly of complex I and essential for the formation of complex I-containing supercomplexes. We propose that mFDX-like and the bridge domain are required for the correct conformation of the membrane arm of complex I that is essential for the association of complex I with complex III2 to form supercomplexes.}, } @article {pmid36702320, year = {2023}, author = {Buonvicino, D and Ranieri, G and Guasti, D and Pistolesi, A and La Rocca, AI and Rapizzi, E and Chiarugi, A}, title = {Early derangement of axonal mitochondria occurs in a mouse model of progressive but not relapsing-remitting multiple sclerosis.}, journal = {Neurobiology of disease}, volume = {178}, number = {}, pages = {106015}, doi = {10.1016/j.nbd.2023.106015}, pmid = {36702320}, issn = {1095-953X}, mesh = {Mice ; Female ; Animals ; *Multiple Sclerosis/pathology ; Hydrogen Peroxide/metabolism ; Mice, Inbred NOD ; *Encephalomyelitis, Autoimmune, Experimental/pathology ; Spinal Cord/pathology ; *Multiple Sclerosis, Relapsing-Remitting/metabolism ; Axons/pathology ; Mitochondria/metabolism ; DNA, Mitochondrial/metabolism ; }, abstract = {INTRODUCTION: Derangement of axonal mitochondrial bioenergetics occurs during progressive multiple sclerosis (PMS). However, whether this is a delayed epiphenomenon or an early causative event of disease progression waits to be understood. Answering this question might further our knowledge of mechanisms underlying neurobiology of PMS and related therapy.

METHODS: MOG35-55-immunized NOD and PLP139-151-immunized SJL female mice were adopted as models of progressive or relapsing-remitting experimental autoimmune encephalomyelitis (EAE), respectively. Multiple parameters of mitochondrial homeostasis were analyzed in the mouse spinal cord during the early asymptomatic stage, also evaluating the effects of scavenging mitochondrial reactive oxygen species with Mito-TEMPO.

RESULTS: Almost identical lumbar spinal cord immune infiltrates consisting of Th1 cells and neutrophils without B and Th17 lymphocytes occurred early upon immunization in both mouse strains. Still, only NOD mice showed axon-restricted dysregulation of mitochondrial homeostasis, with reduced mtDNA contents and increased cristae area. Increased expression of mitochondrial respiratory complex subunits Nd2, Cox1, Atp5d, Sdha also exclusively occurred in lumbar spinal cord of NOD and not SJL mice. Accordingly, in this region genes regulating mitochondrial morphology (Opa1, Mfn1, Mfn2 and Atp5j2) and mitochondriogenesis (Pgc1α, Foxo, Hif-1α and Nrf2) were induced early upon immunization. A reduced extent of mitochondrial derangement occurred in the thoracic spinal cord. Notably, the mitochondrial radical scavenger Mito-TEMPO reduced H2O2 content and prevented both mtDNA depletion and cristae remodeling, having no effects on dysregulation of mitochondrial transcriptome.

DISCUSSION: We provide here the first evidence that axonal-restricted derangement of mitochondrial homeostasis already occurs during the asymptomatic state exclusively in a mouse model of PMS. Data further our understanding of mechanisms related to EAE progression, and point to very early axonal mitochondrial dysfunction as central to the neuropathogenesis of MS evolution.}, } @article {pmid36717086, year = {2023}, author = {Nishita, Y and Amaike, Y and Spassov, N and Hristova, L and Kostov, D and Vladova, D and Peeva, S and Raichev, E and Vlaeva, R and Masuda, R}, title = {Diversity of mitochondrial D-loop haplotypes from ancient Thracian horses in Bulgaria.}, journal = {Animal science journal = Nihon chikusan Gakkaiho}, volume = {94}, number = {1}, pages = {e13810}, doi = {10.1111/asj.13810}, pmid = {36717086}, issn = {1740-0929}, support = {Joint Research Project Grant//Japan Society for the Promotion of Science/ ; The Thracians: Genesis and Development of the Ethn//Bulgarian Academy of Sciences/ ; }, mesh = {Horses/genetics ; Animals ; Bulgaria ; Haplotypes/genetics ; Phylogeny ; *Mitochondria/genetics ; *DNA, Mitochondrial/genetics ; Genetic Variation ; }, abstract = {The domestication of the horse began possibly more than 5000 years ago in the western part of the Eurasian steppe, and according to the leading hypothesis, horses first spread from the Steppe toward the region of the Thracian culture, starting in the second half of the 2nd millennium BCE and flourished from the fifth to first centuries BCE, mainly located in present-day Bulgaria. We analyzed 17 horse bone remains excavated from Thracian archaeological sites (fourth to first centuries BCE) in Bulgaria and successfully identified 17 sequences representing 14 different haplotypes of the mitochondrial D-loop. Compared with the mtDNA haplotypes of modern horses around the world, ancient Thracian horses in Bulgaria are thought to be more closely related to modern horses of Southern Europe and less related to those of Central Asia. In addition, the haplotypes we obtained represented 11 previously reported modern horse mtDNA haplogroups: A, B, D, E, G, H, I, L, N, P, and Q. All the haplogroups contain modern and regionally predominant haplotypes occurring in Europe, the Middle East, and Central Asia. Our results indicate that Thracian horses in Bulgaria have had relatively high genetic diversity and are closely related to modern horse breeds.}, } @article {pmid36717448, year = {2022}, author = {Shilovsky, GA and Putyatina, TS and Markov, AV}, title = {Evolution of Longevity as a Species-Specific Trait in Mammals.}, journal = {Biochemistry. Biokhimiia}, volume = {87}, number = {12}, pages = {1579-1599}, doi = {10.1134/S0006297922120148}, pmid = {36717448}, issn = {1608-3040}, mesh = {Animals ; *Longevity ; *Antioxidants ; Reproducibility of Results ; Aging/metabolism ; Mammals ; }, abstract = {From the evolutionary point of view, the priority problem for an individual is not longevity, but adaptation to the environment associated with the need for survival, food supply, and reproduction. We see two main vectors in the evolution of mammals. One is a short lifespan and numerous offspring ensuring reproductive success (r-strategy). The other one is development of valuable skills in order compete successfully (K-strategy). Species with the K-strategy should develop and enhance specific systems (anti-aging programs) aimed at increasing the reliability and adaptability, including lifespan. These systems are signaling cascades that provide cell repair and antioxidant defense. Hence, any arbitrarily selected long-living species should be characterized by manifestation to a different extent of the longevity-favoring traits (e.g., body size, brain development, sociality, activity of body repair and antioxidant defense systems, resistance to xenobiotics and tumor formation, presence of neotenic traits). Hereafter, we will call a set of such traits as the gerontological success of a species. Longevity is not equivalent to the evolutionary or reproductive success. This difference between these phenomena reaches its peak in mammals due to the development of endothermy and cephalization associated with the cerebral cortex expansion, which leads to the upregulated production of oxidative radicals by the mitochondria (and, consequently, accelerated aging), increase in the number of non-dividing differentiated cells, accumulation of the age-related damage in these cells, and development of neurodegenerative diseases. The article presents mathematical indicators used to assess the predisposition to longevity in different species (including the standard mortality rate and basal metabolic rate, as well as their derivatives). The properties of the evolution of mammals (including the differences between modern mammals and their ancestral forms) are also discussed.}, } @article {pmid36720422, year = {2023}, author = {Baltazar-Soares, M and Karell, P and Wright, D and Nilsson, JÅ and Brommer, JE}, title = {Bringing to light nuclear-mitochondrial insertions in the genomes of nocturnal predatory birds.}, journal = {Molecular phylogenetics and evolution}, volume = {181}, number = {}, pages = {107722}, doi = {10.1016/j.ympev.2023.107722}, pmid = {36720422}, issn = {1095-9513}, mesh = {Animals ; Phylogeny ; *Mitochondria/genetics ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial ; Birds/genetics ; Sequence Analysis, DNA ; Cell Nucleus/genetics ; }, abstract = {Mito-nuclear insertions, or NUMTs, relate to genetic material of mitochondrial origin that have been transferred to the nuclear DNA molecule. The increasing amounts of genomic data currently being produced presents an opportunity to investigate this type of patterns in genome evolution of non-model organisms. Identifying NUMTs across a range of closely related taxa allows one to generalize patterns of insertion and maintenance in autosomes, which is ultimately relevant to the understanding of genome biology and evolution. Here we collected existing pairwise genome-mitogenome data of the order Strigiformes, a group that includes all the nocturnal bird predators. We identified NUMTs by applying percent similarity thresholds after blasting mitochondrial genomes against nuclear genome assemblies. We identified NUMTsin all genomes with numbers ranging from 4 in Bubo bubo to 24 in Ciccaba nigrolineata. Statistical analyses revealed NUMT size to negatively correlate with NUMT's sequence similarity to with original mtDNA region. Lastly, characterizing these nuclear insertions of mitochondrial origin in a comparative genomics framework produced variable phylogenetic patterns, suggesting in some cases that insertions might pre-date speciation events within Strigiformes.}, } @article {pmid36722300, year = {2023}, author = {Russo, MT and Santin, A and Zuccarotto, A and Leone, S and Palumbo, A and Ferrante, MI and Castellano, I}, title = {The first genetic engineered system for ovothiol biosynthesis in diatoms reveals a mitochondrial localization for the sulfoxide synthase OvoA.}, journal = {Open biology}, volume = {13}, number = {2}, pages = {220309}, pmid = {36722300}, issn = {2046-2441}, mesh = {*Diatoms/genetics ; Genetic Engineering ; Methylhistidines ; Biological Evolution ; }, abstract = {Diatoms represent one of the most abundant groups of microalgae in the ocean and are responsible for approximately 20% of photosynthetically fixed CO2 on Earth. Due to their complex evolutionary history and ability to adapt to different environments, diatoms are endowed with striking molecular biodiversity and unique metabolic activities. Their high growth rate and the possibility to optimize their biomass make them very promising 'biofactories' for biotechnological applications. Among bioactive compounds, diatoms can produce ovothiols, histidine-derivatives, endowed with unique antioxidant and anti-inflammatory properties, and occurring in many marine invertebrates, bacteria and pathogenic protozoa. However, the functional role of ovothiols biosynthesis in organisms remains almost unexplored. In this work, we have characterized the thiol fraction of Phaeodactylum tricornutum, providing the first evidence of the presence of ovothiol B in pennate diatoms. We have used P. tricornutum to overexpress the 5-histidylcysteine sulfoxide synthase ovoA, the gene encoding the key enzyme involved in ovothiol biosynthesis and we have discovered that OvoA localizes in the mitochondria, a finding that uncovers new concepts in cellular redox biochemistry. We have also obtained engineered biolistic clones that can produce higher amount of ovothiol B compared to wild-type cells, suggesting a new strategy for the eco-sustainable production of these molecules.}, } @article {pmid36724679, year = {2023}, author = {Rivero, J and Cutillas, C and Callejón, R}, title = {New genetic lineage of whipworm present in Bactrian camel (Camelus bactrianus).}, journal = {Veterinary parasitology}, volume = {315}, number = {}, pages = {109886}, doi = {10.1016/j.vetpar.2023.109886}, pmid = {36724679}, issn = {1873-2550}, mesh = {Animals ; *Camelus/parasitology ; Trichuris/genetics ; Bayes Theorem ; Phylogeny ; Mitochondria ; *Parasites ; }, abstract = {With a global population of around 35 million in 47 countries, camels play a crucial role in the economy of many marginal and desert areas of the world where they survive in harsh conditions. Nonetheless, there is insufficient knowledge regarding camels' parasite fauna which can reduce their milk and meat production. A molecular study for the Trichuris population of Camelus bactrianus from Spain is presented based on sequences of mitochondrial (cox1, cob, rrnL) and ribosomal (ITS1 and ITS2) DNA regions. Bayesian Inference and Maximum Likelihood methods were used to infer phylogenies for (i) each gene separately, (ii) the combined mitochondrial data, and (iii) the combined mitochondrial and ribosomal dataset. Molecular analyses revealed the existence of two different genetic lineages in the Trichuris parasites populations of C. bactrianus. Future studies should focus on whether there is a coevolution process corresponding to the wild or domestic character of C. bactrianus and Camelus dromedarius. Furthermore, it is necessary to increase integrative taxonomic studies on Trichuris spp. based on morphological, biometric, and molecular data, which will inevitably contribute to our knowledge of the etiology of trichuriasis.}, } @article {pmid36726084, year = {2023}, author = {Li, Y and Gu, M and Liu, X and Lin, J and Jiang, H and Song, H and Xiao, X and Zhou, W}, title = {Sequencing and analysis of the complete mitochondrial genomes of Toona sinensis and Toona ciliata reveal evolutionary features of Toona.}, journal = {BMC genomics}, volume = {24}, number = {1}, pages = {58}, pmid = {36726084}, issn = {1471-2164}, support = {2011KJCX002,2012KJCX002,2013KJCX002//Guangdong Forestry Science and Technology Innovation Special Project/ ; 2011KJCX002,2012KJCX002,2013KJCX002//Guangdong Forestry Science and Technology Innovation Special Project/ ; 2011KJCX002,2012KJCX002,2013KJCX002//Guangdong Forestry Science and Technology Innovation Special Project/ ; 2011KJCX002,2012KJCX002,2013KJCX002//Guangdong Forestry Science and Technology Innovation Special Project/ ; 2011KJCX002,2012KJCX002,2013KJCX002//Guangdong Forestry Science and Technology Innovation Special Project/ ; 2011KJCX002,2012KJCX002,2013KJCX002//Guangdong Forestry Science and Technology Innovation Special Project/ ; 2011KJCX002,2012KJCX002,2013KJCX002//Guangdong Forestry Science and Technology Innovation Special Project/ ; 2011KJCX002,2012KJCX002,2013KJCX002//Guangdong Forestry Science and Technology Innovation Special Project/ ; }, mesh = {Toona/genetics ; Phylogeny ; *Genome, Mitochondrial ; Plant Breeding ; *Meliaceae/genetics ; }, abstract = {BACKGROUND: Toona is a critical genus in the Meliaceae, and the plants of this group are an asset for both restorative and restorative purposes, the most flexible of which are Toona sinensis and Toona ciliata. To concentrate on the advancement of mitochondrial(Mt) genome variety in T.sinensis and T.ciliata, the Mt genomes of the two species were sequenced in high throughput independently, after de novo assembly and annotation to construct a Mt genome map for comparison in genome structure. Find their repetitive sequences and analyze them in comparison with the chloroplast genome, along with Maximum-likelihood(ML) phylogenetic analysis with 16 other relatives.

RESULTS: (1) T. sinensis and T.ciliata are both circular structures with lengths of 683482 bp and 68300 bp, respectively. They share a high degree of similarity in encoding genes and have AT preferences. All of them have the largest Phe concentration and are the most frequently used codons. (2) Both of their Mt genome are highly preserved in terms of structural and functional genes, while the main variability is reflected in the length of tRNA, the number of genes, and the value of RSCU. (3) T. siniensis and T. ciliata were detected to have 94 and 87 SSRs, respectively, of which mononucleotides accounted for the absolute proportion. Besides, the vast majority of their SSRs were found to be poly-A or poly-T. (4)10 and 11 migrating fragments were identified in the comparison with the chloroplast genome, respectively. (5) In the ML evolutionary tree, T.sinensis and T.ciliata clustered individually into a small branch with 100% support, reflecting two species of Toona are very similarly related to each other.

CONCLUSIONS: This research provides a basis for the exploitation of T.sinensis and T.ciliata in terms of medicinal, edible, and timber resources to avoid confusion; at the same time, it can explore the evolutionary relationship between the Toona and related species, which does not only have an important practical value, but also provides a theoretical basis for future hybrid breeding of forest trees, molecular markers, and evolutionary aspects of plants, which has great scientific significance.}, } @article {pmid36727263, year = {2023}, author = {Blair, C}, title = {Organellar DNA continues to provide a rich source of information in the genomics era.}, journal = {Molecular ecology}, volume = {32}, number = {9}, pages = {2144-2150}, doi = {10.1111/mec.16872}, pmid = {36727263}, issn = {1365-294X}, mesh = {Phylogeny ; *Information Sources ; *DNA, Mitochondrial/genetics ; Genomics ; Mitochondria/genetics ; DNA, Chloroplast/genetics ; Sequence Analysis, DNA ; }, abstract = {The genomics revolution continues to change how ecologists and evolutionary biologists study the evolution and maintenance of biodiversity. It is now easier than ever to generate large molecular data sets consisting of hundreds to thousands of independently evolving nuclear loci to estimate a suite of evolutionary and demographic parameters. However, any inferences will be incomplete or inaccurate if incorrect taxonomic identities and perpetuated throughout the analytical pipeline. Due to decades of research and comprehensive online databases, sequencing and analysis of mitochondrial DNA (mtDNA), chloroplast DNA (cpDNA) and select nuclear genes can provide researchers with a cost effective and simple means to verify the species identity of samples prior to subsequent phylogeographic and population genomic analysis. The addition of these sequences to genomic studies can also shed light on other important evolutionary questions such as explanations for gene tree-species tree discordance, species limits, sex-biased dispersal patterns, adaptation, and mtDNA introgression. Although the mtDNA and cpDNA genomes often should not be used exclusively to make historical inferences given their well-known limitations, the addition of these data to modern genomic studies adds little cost and effort while simultaneously providing a wealth of useful data that can have significant implications for both basic and applied research.}, } @article {pmid36732530, year = {2023}, author = {Silva, MC and Catry, P and Bried, J and Kawakami, K and Flint, E and Granadeiro, JP}, title = {Contrasting patterns of population structure of Bulwer's petrel (Bulweria bulwerii) between oceans revealed by statistical phylogeography.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {1939}, pmid = {36732530}, issn = {2045-2322}, mesh = {Animals ; Phylogeography ; Oceans and Seas ; *Birds/genetics ; Pacific Ocean ; *Mitochondria/genetics ; DNA, Mitochondrial/genetics ; Phylogeny ; Genetic Variation ; }, abstract = {The patterns of population divergence of mid-latitude marine birds are impacted by only a few biogeographic barriers to dispersal and the effect of intrinsic factors, such as fidelity to natal colonies or wintering grounds, may become more conspicuous. Here we describe, for the first time, the phylogeographic patterns and historical demography of Bulwer's petrel Bulweria bulwerii and provide new insights regarding the drivers of species diversification in the marine environment. We sampled Bulwer's petrels from the main breeding colonies and used a statistical phylogeography approach based on surveying nuclear and mitochondrial loci (~ 9100 bp) to study its mechanisms of global diversification. We uncovered three highly differentiated groups including the Western Pacific, the Central Pacific and the Atlantic. The older divergence occurred within the Pacific Ocean, ca. 850,000 ya, and since then the W Pacific group has been evolving in isolation. Conversely, divergence between the Central Pacific and Atlantic populations occurred within the last 200,000 years. While the Isthmus of Panama is important in restricting gene flow between oceans in Bulwer's petrels, the deepest phylogeographic break is within the Pacific Ocean, where oceanographic barriers are key in driving and maintaining the remarkable structure found in this highly mobile seabird. This is in contrast with the Atlantic, where no structure was detected. Further data will provide insights regarding the extent of lineage divergence of Bulwer's petrels in the Western Pacific.}, } @article {pmid36734850, year = {2023}, author = {Nord, A and Chamkha, I and Elmér, E}, title = {A whole blood approach improves speed and accuracy when measuring mitochondrial respiration in intact avian blood cells.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {37}, number = {3}, pages = {e22766}, doi = {10.1096/fj.202201749R}, pmid = {36734850}, issn = {1530-6860}, mesh = {Animals ; *Mitochondria/metabolism ; *Cell Respiration ; Respiration ; Birds ; Blood Cells ; }, abstract = {Understanding mitochondrial biology and pathology is key to understanding the evolution of animal form and function. However, mitochondrial measurement often involves invasive, or even terminal, sampling, which can be difficult to reconcile in wild models or longitudinal studies. Non-mammal vertebrates contain mitochondria in their red blood cells, which can be exploited for minimally invasive mitochondrial measurement. Several recent bird studies have measured mitochondrial function using isolated blood cells. Isolation adds time in the laboratory and might be associated with physiological complications. We developed and validated a protocol to measure mitochondrial respiration in bird whole blood. Endogenous respiration was comparable between isolated blood cells and whole blood. However, respiration towards oxidative phosphorylation was higher in whole blood, and whole blood mitochondria were better coupled and had higher maximum working capacity. Whole blood measurement was also more reproducible than measurement on isolated cells for all traits considered. Measurements were feasible over a 10-fold range of sample volumes, although both small and large volumes were associated with changes to respiratory traits. The protocol was compatible with long-term storage: after 24 h at 5°C without agitation, all respiration traits but maximum working capacity remained unchanged, the latter decreasing by 14%. Our study suggests that whole blood measurement provides faster, more reproducible, and more biologically and physiologically relevant (mitochondrial integrity) assessment of mitochondrial respiration. We recommend future studies to take a whole blood approach unless specific circumstances require the use of isolated blood cells.}, } @article {pmid36736695, year = {2023}, author = {Fähnrich, A and Stephan, I and Hirose, M and Haarich, F and Awadelkareem, MA and Ibrahim, S and Busch, H and Wohlers, I}, title = {North and East African mitochondrial genetic variation needs further characterization towards precision medicine.}, journal = {Journal of advanced research}, volume = {54}, number = {}, pages = {59-76}, pmid = {36736695}, issn = {2090-1224}, mesh = {Humans ; *DNA, Mitochondrial/genetics ; *East African People/genetics ; Genetic Variation/genetics ; Haplotypes ; Phylogeny ; Precision Medicine ; Sequence Analysis, DNA ; *North African People/genetics ; }, abstract = {INTRODUCTION: Mitochondria are maternally inherited cell organelles with their own genome, and perform various functions in eukaryotic cells such as energy production and cellular homeostasis. Due to their inheritance and manifold biological roles in health and disease, mitochondrial genetics serves a dual purpose of tracing the history as well as disease susceptibility of human populations across the globe. This work requires a comprehensive catalogue of commonly observed genetic variations in the mitochondrial DNAs for all regions throughout the world. So far, however, certain regions, such as North and East Africa have been understudied.

OBJECTIVES: To address this shortcoming, we have created the most comprehensive quality-controlled North and East African mitochondrial data set to date and use it for characterizing mitochondrial genetic variation in this region.

METHODS: We compiled 11 published cohorts with novel data for mitochondrial genomes from 159 Sudanese individuals. We combined these 641 mitochondrial sequences with sequences from the 1000 Genomes (n = 2504) and the Human Genome Diversity Project (n = 828) and used the tool haplocheck for extensive quality control and detection of in-sample contamination, as well as Nanopore long read sequencing for haplogroup validation of 18 samples.

RESULTS: Using a subset of high-coverage mitochondrial sequences, we predict 15 potentially novel haplogroups in North and East African subjects and observe likely phylogenetic deviations from the established PhyloTree reference for haplogroups L0a1 and L2a1.

CONCLUSION: Our findings demonstrate common hitherto unexplored variants in mitochondrial genomes of North and East Africa that lead to novel phylogenetic relationships between haplogroups present in these regions. These observations call for further in-depth population genetic studies in that region to enable the prospective use of mitochondrial genetic variation for precision medicine.}, } @article {pmid36737563, year = {2023}, author = {Rottenberg, H}, title = {The evolution of the human mitochondrial bc1 complex- adaptation for reduced rate of superoxide production?.}, journal = {Journal of bioenergetics and biomembranes}, volume = {55}, number = {1}, pages = {15-31}, pmid = {36737563}, issn = {1573-6881}, mesh = {Humans ; Cattle ; Animals ; Mice ; Sheep ; *Ubiquinone/chemistry/metabolism ; *Superoxides/metabolism ; Cytochromes b/metabolism ; Cytochromes c1/metabolism ; Oxidation-Reduction ; Primates/metabolism ; Electron Transport Complex III/metabolism ; Electron Transport ; }, abstract = {The mitochondrial bc1 complex is a major source of mitochondrial superoxide. While bc1-generated superoxide plays a beneficial signaling role, excess production of superoxide lead to aging and degenerative diseases. The catalytic core of bc1 comprises three peptides -cytochrome b, Fe-S protein, and cytochrome c1. All three core peptides exhibit accelerated evolution in anthropoid primates. It has been suggested that the evolution of cytochrome b in anthropoids was driven by a pressure to reduce the production of superoxide. In humans, the bc1 core peptides exhibit anthropoid-specific substitutions that are clustered near functionally critical sites that may affect the production of superoxide. Here we compare the high-resolution structures of bovine, mouse, sheep and human bc1 to identify structural changes that are associated with human-specific substitutions. Several cytochrome b substitutions in humans alter its interactions with other subunits. Most significantly, there is a cluster of seven substitutions, in cytochrome b, the Fe-S protein, and cytochrome c1 that affect the interactions between these proteins at the tether arm of the Fe-S protein and may alter the rate of ubiquinone oxidation and the rate of superoxide production. Another cluster of substitutions near heme bH and the ubiquinone reduction site, Qi, may affect the rate of ubiquinone reduction and thus alter the rate of superoxide production. These results are compatible with the hypothesis that cytochrome b in humans (and other anthropoid primates) evolve to reduce the rate of production of superoxide thus enabling the exceptional longevity and exceptional cognitive ability of humans.}, } @article {pmid36738170, year = {2023}, author = {Rogers, RL and Grizzard, SL and Garner, JT}, title = {Strong, Recent Selective Sweeps Reshape Genetic Diversity in Freshwater Bivalve Megalonaias nervosa.}, journal = {Molecular biology and evolution}, volume = {40}, number = {2}, pages = {}, pmid = {36738170}, issn = {1537-1719}, support = {R35 GM133376/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Selection, Genetic ; Fresh Water ; Genetic Variation ; *Bivalvia ; *Unionidae ; }, abstract = {Freshwater Unionid bivalves have recently faced ecological upheaval through pollution, barriers to dispersal, harvesting, and changes in fish-host prevalence. Currently, over 70% of species in North America are threatened, endangered or extinct. To characterize the genetic response to recent selective pressures, we collected population genetic data for one successful bivalve species, Megalonaias nervosa. We identify megabase-sized regions that are nearly monomorphic across the population, signals of strong, recent selection reshaping diversity across 73 Mb total. These signatures of selection are greater than is commonly seen in population genetic models. We observe 102 duplicate genes with high dN/dS on terminal branches among regions with sweeps, suggesting that gene duplication is a causative mechanism of recent adaptation in M. nervosa. Genes in sweeps reflect functional classes important for Unionid survival, including anticoagulation genes important for fish host parasitization, detox genes, mitochondria management, and shell formation. We identify sweeps in regions with no known functional impacts, suggesting mechanisms of adaptation that deserve greater attention in future work on species survival. In contrast, polymorphic transposable elements (TEs) appear to be detrimental and underrepresented among regions with sweeps. TE site frequency spectra are skewed toward singleton variants, and TEs among regions with sweeps are present at low frequency. Our work suggests that duplicate genes are an essential source of genetic novelty that has helped this species succeed in environments where others have struggled. These results suggest that gene duplications deserve greater attention in non-model population genomics, especially in species that have recently faced sudden environmental challenges.}, } @article {pmid36739562, year = {2023}, author = {Fang, JM and Basu, S and Phu, J and Nieh, MP and LoTurco, JJ}, title = {Cellular Localization, Aggregation, and Cytotoxicity of Bicelle-Quantum Dot Nanocomposites.}, journal = {ACS applied bio materials}, volume = {6}, number = {2}, pages = {566-577}, doi = {10.1021/acsabm.2c00827}, pmid = {36739562}, issn = {2576-6422}, mesh = {Humans ; HeLa Cells ; *Quantum Dots/toxicity/chemistry ; HEK293 Cells ; *Nanocomposites/toxicity ; Sulfides ; Zinc Compounds ; }, abstract = {Bicelles are discoidal lipid nanoparticles (LNPs) in which the planar bilayer and curved rim are, respectively, composed of long- and short-chain lipids. Bicellar LNPs have a hydrophobic core, allowing hydrophobic molecules and large molecular complexes such as quantum dots (QDs) to be encapsulated. In this study, CdSe/ZnS QDs were encapsulated in bicelles made of dipalmitoyl phosphatidylcholine, dihexanoyl phosphatidylcholine, dipalmitoyl phosphatidylglycerol, and distearoyl phosphatidylethanolamine conjugated with polyethylene glycerol amine 2000 to form a well-defined bicelle-QD nanocomplex (known as NANO[2]-QD or bicelle-QD). The bicelle-QD was then incubated with Hek293t cells and HeLa cells for different periods of time to determine changes in their cellular localization. Bicelle-QDs readily penetrated Hek293t cell membranes within 15 min of incubation, localized to the cytoplasm, and associated with mitochondria and intracellular vesicles. After 1 h, the bicelle-QDs enter the cell nucleus. Large aggregates form throughout the cell after 2 h and QDs are nearly absent from the nucleus by 4 h. Previous reports have demonstrated that CdSe/ZnS QDs can be toxic to cells, and we have found that encapsulating QDs in bicelles can attenuate but did not eliminate cytotoxicity. The present research outcome demonstrates the time-resolved pathway of bicelle-encapsulated QDs in Hek293t cells, morphological evolution in cells over time, and cytotoxicity of the bicelle-QDs, providing important insight into the potential application of the nanocomplex for cellular imaging.}, } @article {pmid36739946, year = {2023}, author = {Schmitz, JM and Wolters, JF and Murray, NH and Guerra, RM and Bingman, CA and Hittinger, CT and Pagliarini, DJ}, title = {Aim18p and Aim46p are chalcone isomerase domain-containing mitochondrial hemoproteins in Saccharomyces cerevisiae.}, journal = {The Journal of biological chemistry}, volume = {299}, number = {3}, pages = {102981}, pmid = {36739946}, issn = {1083-351X}, support = {R35 GM131795/GM/NIGMS NIH HHS/United States ; T32 GM008505/GM/NIGMS NIH HHS/United States ; P30 GM138396/GM/NIGMS NIH HHS/United States ; T32 HG002760/HG/NHGRI NIH HHS/United States ; P41 GM108538/GM/NIGMS NIH HHS/United States ; }, mesh = {Flavonoids/metabolism ; *Intramolecular Lyases/chemistry/metabolism ; *Saccharomyces cerevisiae/enzymology/genetics ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; }, abstract = {Chalcone isomerases (CHIs) have well-established roles in the biosynthesis of plant flavonoid metabolites. Saccharomyces cerevisiae possesses two predicted CHI-like proteins, Aim18p (encoded by YHR198C) and Aim46p (YHR199C), but it lacks other enzymes of the flavonoid pathway, suggesting that Aim18p and Aim46p employ the CHI fold for distinct purposes. Here, we demonstrate using proteinase K protection assays, sodium carbonate extractions, and crystallography that Aim18p and Aim46p reside on the mitochondrial inner membrane and adopt CHI folds, but they lack select active site residues and possess an extra fungal-specific loop. Consistent with these differences, Aim18p and Aim46p lack CHI activity and also the fatty acid-binding capabilities of other CHI-like proteins, but instead bind heme. We further show that diverse fungal homologs also bind heme and that Aim18p and Aim46p possess structural homology to a bacterial hemoprotein. Collectively, our work reveals a distinct function and cellular localization for two CHI-like proteins, introduces a new variation of a hemoprotein fold, and suggests that ancestral CHI-like proteins were hemoproteins.}, } @article {pmid36740932, year = {2023}, author = {Becher, H and Nichols, RA}, title = {Assembly-free quantification of vagrant DNA inserts.}, journal = {Molecular ecology resources}, volume = {23}, number = {5}, pages = {1002-1013}, pmid = {36740932}, issn = {1755-0998}, support = {MC_UU_00007/16/MRC_/Medical Research Council/United Kingdom ; PhD studentship awarded to HB//Queen Mary University of London, School of Biological and Chemical Sciences/ ; }, mesh = {Humans ; *DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Eukaryota/genetics ; *Genome, Mitochondrial ; Cell Nucleus/genetics ; Sequence Analysis, DNA ; Phylogeny ; }, abstract = {Inserts of DNA from extranuclear sources, such as organelles and microbes, are common in eukaryote nuclear genomes. However, sequence similarity between the nuclear and extranuclear DNA, and a history of multiple insertions, make the assembly of these regions challenging. Consequently, the number, sequence and location of these vagrant DNAs cannot be reliably inferred from the genome assemblies of most organisms. We introduce two statistical methods to estimate the abundance of nuclear inserts even in the absence of a nuclear genome assembly. The first (intercept method) only requires low-coverage (<1×) sequencing data, as commonly generated for population studies of organellar and ribosomal DNAs. The second method additionally requires that a subset of the individuals carry extranuclear DNA with diverged genotypes. We validated our intercept method using simulations and by re-estimating the frequency of human NUMTs (nuclear mitochondrial inserts). We then applied it to the grasshopper Podisma pedestris, exceptional for both its large genome size and reports of numerous NUMT inserts, estimating that NUMTs make up 0.056% of the nuclear genome, equivalent to >500 times the mitochondrial genome size. We also re-analysed a museomics data set of the parrot Psephotellus varius, obtaining an estimate of only 0.0043%, in line with reports from other species of bird. Our study demonstrates the utility of low-coverage high-throughput sequencing data for the quantification of nuclear vagrant DNAs. Beyond quantifying organellar inserts, these methods could also be used on endosymbiont-derived sequences. We provide an R implementation of our methods called "vagrantDNA" and code to simulate test data sets.}, } @article {pmid36746982, year = {2023}, author = {de Jong, MJ and Niamir, A and Wolf, M and Kitchener, AC and Lecomte, N and Seryodkin, IV and Fain, SR and Hagen, SB and Saarma, U and Janke, A}, title = {Range-wide whole-genome resequencing of the brown bear reveals drivers of intraspecies divergence.}, journal = {Communications biology}, volume = {6}, number = {1}, pages = {153}, pmid = {36746982}, issn = {2399-3642}, mesh = {Animals ; Male ; *Ursidae/genetics ; DNA, Mitochondrial/genetics ; Phylogeography ; Population Dynamics ; Mitochondria/genetics ; }, abstract = {Population-genomic studies can shed new light on the effect of past demographic processes on contemporary population structure. We reassessed phylogeographical patterns of a classic model species of postglacial recolonisation, the brown bear (Ursus arctos), using a range-wide resequencing dataset of 128 nuclear genomes. In sharp contrast to the erratic geographical distribution of mtDNA and Y-chromosomal haplotypes, autosomal and X-chromosomal multi-locus datasets indicate that brown bear population structure is largely explained by recent population connectivity. Multispecies coalescent based analyses reveal cases where mtDNA haplotype sharing between distant populations, such as between Iberian and southern Scandinavian bears, likely results from incomplete lineage sorting, not from ancestral population structure (i.e., postglacial recolonisation). However, we also argue, using forward-in-time simulations, that gene flow and recombination can rapidly erase genomic evidence of former population structure (such as an ancestral population in Beringia), while this signal is retained by Y-chromosomal and mtDNA, albeit likely distorted. We further suggest that if gene flow is male-mediated, the information loss proceeds faster in autosomes than in X chromosomes. Our findings emphasise that contemporary autosomal genetic structure may reflect recent population dynamics rather than postglacial recolonisation routes, which could contribute to mtDNA and Y-chromosomal discordances.}, } @article {pmid36747727, year = {2023}, author = {Espino-Sanchez, TJ and Wienkers, H and Marvin, RG and Nalder, SA and García-Guerrero, AE and VanNatta, PE and Jami-Alahmadi, Y and Blackwell, AM and Whitby, FG and Wohlschlegel, JA and Kieber-Emmons, MT and Hill, CP and Sigala, PA}, title = {Direct Tests of Cytochrome Function in the Electron Transport Chain of Malaria Parasites.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36747727}, issn = {2692-8205}, support = {P30 GM133894/GM/NIGMS NIH HHS/United States ; T32 DK007115/DK/NIDDK NIH HHS/United States ; R25 HL108828/HL/NHLBI NIH HHS/United States ; R01 GM089778/GM/NIGMS NIH HHS/United States ; U54 DK110858/DK/NIDDK NIH HHS/United States ; R35 GM133764/GM/NIGMS NIH HHS/United States ; }, abstract = {UNLABELLED: The mitochondrial electron transport chain (ETC) of Plasmodium malaria parasites is a major antimalarial drug target, but critical cytochrome functions remain unstudied and enigmatic. Parasites express two distinct cyt c homologs (c and c -2) with unusually sparse sequence identity and uncertain fitness contributions. P. falciparum cyt c -2 is the most divergent eukaryotic cyt c homolog currently known and has sequence features predicted to be incompatible with canonical ETC function. We tagged both cyt c homologs and the related cyt c 1 for inducible knockdown. Translational repression of cyt c and cyt c 1 was lethal to parasites, which died from ETC dysfunction and impaired ubiquinone recycling. In contrast, cyt c -2 knockdown or knock-out had little impact on blood-stage growth, indicating that parasites rely fully on the more conserved cyt c for ETC function. Biochemical and structural studies revealed that both cyt c and c -2 are hemylated by holocytochrome c synthase, but UV-vis absorbance and EPR spectra strongly suggest that cyt c -2 has an unusually open active site in which heme is stably coordinated by only a single axial amino-acid ligand and can bind exogenous small molecules. These studies provide a direct dissection of cytochrome functions in the ETC of malaria parasites and identify a highly divergent Plasmodium cytochrome c with molecular adaptations that defy a conserved role in eukaryotic evolution.

SIGNIFICANCE STATEMENT: Mitochondria are critical organelles in eukaryotic cells that drive oxidative metabolism. The mitochondrion of Plasmodium malaria parasites is a major drug target that has many differences from human cells and remains poorly studied. One key difference from humans is that malaria parasites express two cytochrome c proteins that differ significantly from each other and play untested and uncertain roles in the mitochondrial electron transport chain (ETC). Our study revealed that one cyt c is essential for ETC function and parasite viability while the second, more divergent protein has unusual structural and biochemical properties and is not required for growth of blood-stage parasites. This work elucidates key biochemical properties and evolutionary differences in the mitochondrial ETC of malaria parasites.}, } @article {pmid36748090, year = {2023}, author = {Zhang, Y and Li, W and Bian, Y and Li, Y and Cong, L}, title = {Multifaceted roles of aerobic glycolysis and oxidative phosphorylation in hepatocellular carcinoma.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e14797}, pmid = {36748090}, issn = {2167-8359}, mesh = {Humans ; *Carcinoma, Hepatocellular/metabolism ; Oxidative Phosphorylation ; *Liver Neoplasms/metabolism ; Energy Metabolism ; Glycolysis ; }, abstract = {Liver cancer is a common malignancy with high morbidity and mortality rates. Changes in liver metabolism are key factors in the development of primary hepatic carcinoma, and mitochondrial dysfunction is closely related to the occurrence and development of tumours. Accordingly, the study of the metabolic mechanism of mitochondria in primary hepatic carcinomas has gained increasing attention. A growing body of research suggests that defects in mitochondrial respiration are not generally responsible for aerobic glycolysis, nor are they typically selected during tumour evolution. Conversely, the dysfunction of mitochondrial oxidative phosphorylation (OXPHOS) may promote the proliferation, metastasis, and invasion of primary hepatic carcinoma. This review presents the current paradigm of the roles of aerobic glycolysis and OXPHOS in the occurrence and development of hepatocellular carcinoma (HCC). Mitochondrial OXPHOS and cytoplasmic glycolysis cooperate to maintain the energy balance in HCC cells. Our study provides evidence for the targeting of mitochondrial metabolism as a potential therapy for HCC.}, } @article {pmid36750641, year = {2023}, author = {Kayastha, P and Stec, D and Sługocki, Ł and Gawlak, M and Mioduchowska, M and Kaczmarek, Ł}, title = {Integrative taxonomy reveals new, widely distributed tardigrade species of the genus Paramacrobiotus (Eutardigrada: Macrobiotidae).}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {2196}, pmid = {36750641}, issn = {2045-2322}, mesh = {Animals ; *Tardigrada/genetics ; Phylogeny ; Mitochondria/genetics ; Microscopy, Electron, Scanning ; RNA, Ribosomal, 18S/genetics ; }, abstract = {In a moss sample collected in Ribeiro Frio, Madeira, Paramacrobiotus gadabouti sp. nov. was found and described using the integrative taxonomy approach. The new species is described based on morphological and morphometric data from both phase-contrast light microscopy (PCM), as well as scanning electron microscopy (SEM). Moreover, four DNA markers, three nuclear (18S rRNA, 28S rRNA, ITS-2) and one mitochondrial (COI) markers, were used to elucidate the phylogenetic position of the new species within the family Macrobiotidae. The new species has a microplacoid that placed it within Parmacrobiotus richtersi group and exhibit richtersi-type eggs having processes terminated with cap-like structures. Paramacrobiotus gadabouti sp. nov. is most similar to Pam. alekseevi, Pam. filipi and Pam. garynahi, but differs from them mainly in details of egg morphology and morphometrics. Unlike other species from this group, which were confirmed as bisexual and showed limited distribution, Paramacrobiotus gadabouti sp. nov. is yet another parthenogenetic species with a wide distribution, demonstrating that at least some tardigrades confirm to the hypothesis of 'everything is everywhere'.}, } @article {pmid36759539, year = {2023}, author = {Kise, H and Iguchi, A and Ikegami, T and Onishi, Y and Goto, K and Tanaka, Y and Washburn, TW and Nishijima, M and Kunishima, T and Okamoto, N and Suzuki, A}, title = {Genetic population structures of common scavenging species near hydrothermal vents in the Okinawa Trough.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {2348}, pmid = {36759539}, issn = {2045-2322}, mesh = {Animals ; *Hydrothermal Vents ; Phylogeny ; Genetics, Population ; *Decapoda ; Mitochondria/genetics ; Ecosystem ; }, abstract = {Deep-sea mining of hydrothermal deposits off the coast of Japan is currently under consideration, and environmental baseline studies of the area are required to understand possible impacts. The aim of this study is to clarify population structures of dominant benthic megafaunal species near hydrothermal vent fields in the Okinawa Trough, using a population genetics approach. We examined dominant deep-sea scavenging species including eels, several amphipods, and a decapod and performed population genetic analyses based on the mitochondrial cytochrome c oxidase subunit I region. Several sites were sampled within Okinawa Trough to examine intra-population diversity while two other locations 1400-2400 km away were chosen for inter-population comparisons. For synaphobranchid eels Simenchelys parasitica and Synaphobranchus kaupii, our results showed significant intra-population diversity but no inter-population genetic differentiation, suggesting strong genetic connectivity and/or large population sizes. In addition, single nucleotide polymorphism analysis also confirmed strong genetic connectivity for Simenchelys parasitica. Among scavenging amphipods, we detected seven putative species using molecular phylogenetic analysis. We evaluated population structures of the most abundant species of amphipods and a decapod species (Nematocarcinus lanceopes). Our results provide basic information on the genetic population structures of benthic megafaunal species near hydrothermal vent fields, which can be used to select candidate species for future connectivity analysis with high-resolution genetic markers and aid understanding of the potential population impacts of environmental disturbances.}, } @article {pmid36773750, year = {2023}, author = {Taite, M and Fernández-Álvarez, FÁ and Braid, HE and Bush, SL and Bolstad, K and Drewery, J and Mills, S and Strugnell, JM and Vecchione, M and Villanueva, R and Voight, JR and Allcock, AL}, title = {Genome skimming elucidates the evolutionary history of Octopoda.}, journal = {Molecular phylogenetics and evolution}, volume = {182}, number = {}, pages = {107729}, doi = {10.1016/j.ympev.2023.107729}, pmid = {36773750}, issn = {1095-9513}, mesh = {Animals ; *Octopodiformes/genetics ; Phylogeny ; Bayes Theorem ; Mitochondria/genetics ; *Genome, Mitochondrial ; RNA, Transfer ; }, abstract = {Phylogenies for Octopoda have, until now, been based on morphological characters or a few genes. Here we provide the complete mitogenomes and the nuclear 18S and 28S ribosomal genes of twenty Octopoda specimens, comprising 18 species of Cirrata and Incirrata, representing 13 genera and all five putative families of Cirrata (Cirroctopodidae, Cirroteuthidae, Grimpoteuthidae, Opisthoteuthidae and Stauroteuthidae) and six families of Incirrata (Amphitretidae, Argonautidae, Bathypolypodidae, Eledonidae, Enteroctopodidae, and Megaleledonidae) which were assembled using genome skimming. Phylogenetic trees were built using Maximum Likelihood and Bayesian Inference with several alignment matrices. All mitochondrial genomes had the 'typical' genome composition and gene order previously reported for octopodiforms, except Bathypolypus ergasticus, which appears to lack ND5, two tRNA genes that flank ND5 and two other tRNA genes. Argonautoidea was revealed as sister to Octopodidae by the mitochondrial protein-coding gene dataset, however, it was recovered as sister to all other incirrate octopods with strong support in an analysis using nuclear rRNA genes. Within Cirrata, our study supports two existing classifications suggesting neither is likely in conflict with the true evolutionary history of the suborder. Genome skimming is useful in the analysis of phylogenetic relationships within Octopoda; inclusion of both mitochondrial and nuclear data may be key.}, } @article {pmid36782130, year = {2023}, author = {Zhang, S and Wang, J and He, W and Kan, S and Liao, X and Jordan, DR and Mace, ES and Tao, Y and Cruickshank, AW and Klein, R and Yuan, D and Tembrock, LR and Wu, Z}, title = {Variation in mitogenome structural conformation in wild and cultivated lineages of sorghum corresponds with domestication history and plastome evolution.}, journal = {BMC plant biology}, volume = {23}, number = {1}, pages = {91}, pmid = {36782130}, issn = {1471-2229}, support = {RCYX20200714114538196//Science, Technology, and Innovation Commission of Shenzhen Municipality/ ; 31970244//National Natural Science Foundation of China/ ; 110243160001007//Chinese Academy of Agricultural Sciences Elite Youth Program/ ; }, mesh = {*Genome, Mitochondrial/genetics ; *Sorghum/genetics ; Phylogeny ; Domestication ; Plants/genetics ; Cell Nucleus ; Evolution, Molecular ; Genome, Plant/genetics ; }, abstract = {BACKGROUND: Mitochondria are organelles within eukaryotic cells that are central to the metabolic processes of cellular respiration and ATP production. However, the evolution of mitochondrial genomes (mitogenomes) in plants is virtually unknown compared to animal mitogenomes or plant plastids, due to complex structural variation and long stretches of repetitive DNA making accurate genome assembly more challenging. Comparing the structural and sequence differences of organellar genomes within and between sorghum species is an essential step in understanding evolutionary processes such as organellar sequence transfer to the nuclear genome as well as improving agronomic traits in sorghum related to cellular metabolism.

RESULTS: Here, we assembled seven sorghum mitochondrial and plastid genomes and resolved reticulated mitogenome structures with multilinked relationships that could be grouped into three structural conformations that differ in the content of repeats and genes by contig. The grouping of these mitogenome structural types reflects the two domestication events for sorghum in east and west Africa.

CONCLUSIONS: We report seven mitogenomes of sorghum from different cultivars and wild sources. The assembly method used here will be helpful in resolving complex genomic structures in other plant species. Our findings give new insights into the structure of sorghum mitogenomes that provides an important foundation for future research into the improvement of sorghum traits related to cellular respiration, cytonuclear incompatibly, and disease resistance.}, } @article {pmid36787420, year = {2023}, author = {Zheng, Y and Ye, Z and Xiao, Y}, title = {Subtle Structural Translation Magically Modulates the Super-Resolution Imaging of Self-Blinking Rhodamines.}, journal = {Analytical chemistry}, volume = {95}, number = {8}, pages = {4172-4179}, doi = {10.1021/acs.analchem.2c05298}, pmid = {36787420}, issn = {1520-6882}, mesh = {Rhodamines/chemistry ; *Blinking ; *Fluorescent Dyes/chemistry ; Microscopy, Fluorescence/methods ; Nanotechnology ; }, abstract = {The evolution of super-resolution imaging techniques is benefited from the ongoing competition for optimal rhodamine fluorophores. Yet, it seems blind to construct the desired rhodamine molecule matching the imaging need without the knowledge on imaging impact of even the minimum structural translation. Herein, we have designed a pair of self-blinking sulforhodamines (STMR and SRhB) with the bare distinction of methyl or ethyl substituents and engineered them with Halo protein ligands. Although the two possess similar spectral properties (λab, λfl, ϕ, etc.), they demonstrated unique single-molecule characteristics preferring to individual imaging applications. Experimentally, STMR with high emissive rates was qualified for imaging structures with rapid dynamics (endoplasmic reticulum, and mitochondria), and SRhB with prolonged on-times and photostability was suited for relatively "static" nuclei and microtubules. Using this new knowledge, the mitochondrial morphology during apoptosis and ferroptosis was first super-resolved by STMR. Our study highlights the significance of even the smallest structural modification to the modulation of super-resolution imaging performance and would provide insights for future fluorophore design.}, } @article {pmid36787792, year = {2022}, author = {Broccard, N and Silva, NM and Currat, M}, title = {Simulated patterns of mitochondrial diversity are consistent with partial population turnover in Bronze Age Central Europe.}, journal = {American journal of biological anthropology}, volume = {177}, number = {1}, pages = {134-146}, pmid = {36787792}, issn = {2692-7691}, mesh = {*Mitochondria/genetics ; Europe ; *DNA, Mitochondrial/genetics ; Emigration and Immigration ; Biological Evolution ; DNA, Ancient ; }, abstract = {OBJECTIVES: The analysis of ancient mitochondrial DNA from osteological remains has challenged previous conclusions drawn from the analysis of mitochondrial DNA from present populations, notably by revealing an absence of genetic continuity between the Neolithic and modern populations in Central Europe. Our study investigates how to reconcile these contradictions at the mitochondrial level using a modeling approach.

MATERIALS AND METHODS: We used a spatially explicit computational framework to simulate ancient and modern DNA sequences under various evolutionary scenarios of post Neolithic demographic events and compared the genetic diversity of the simulated and observed mitochondrial sequences. We investigated which-if any-scenarios were able to reproduce statistics of genetic diversity similar to those observed, with a focus on the haplogroup N1a, associated with the spread of early Neolithic farmers.

RESULTS: Demographic fluctuations during the Neolithic transition or subsequent demographic collapses after this period, that is, due to epidemics such as plague, are not sufficient to explain the signal of population discontinuity detected on the mitochondrial DNA in Central Europe. Only a scenario involving a substantial genetic input due to the arrival of migrants after the Neolithic transition, possibly during the Bronze Age, is compatible with observed patterns of genetic diversity.

DISCUSSION: Our results corroborate paleogenomic studies, since out of the alternative hypotheses tested, the best one that was able to recover observed patterns of mitochondrial diversity in modern and ancient Central European populations was one were immigration of populations from the Pontic steppes during the Bronze Age was explicitly simulated.}, } @article {pmid36789533, year = {2023}, author = {Nagarajan-Radha, V and Beekman, M}, title = {G × G × E effect on phenotype expression in a non-conventional model organism, the unicellular slime mould Physarum polycephalum.}, journal = {Biology letters}, volume = {19}, number = {2}, pages = {20220494}, pmid = {36789533}, issn = {1744-957X}, mesh = {*Physarum polycephalum/genetics ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Plasmids ; Phenotype ; }, abstract = {In metazoans, the expression of key phenotypic traits is sensitive to two- and three-way interactions between variation in mitochondrial DNA, nuclear DNA and the external environment. Whether gene-by-environment interactions affect phenotypes in single-celled eukaryotes is poorly studied, except in a few species of yeast and fungi. We developed a genetic panel of the unicellular slime mould, Physarum polycephalum containing strains differing in mitochondrial and nuclear DNA haplotypes. The panel also included two strains harbouring a selfishly replicating mitochondrial-fusion (mF) plasmid that could affect phenotype expression. We assayed movement and growth rate differences among the strains across two temperature regimes: 24° and 28°C. We found that the slime mould's growth rate, but not movement, is affected by G × G × E interactions. Predictably, mtDNA × nDNA interactions significantly affected both traits. The inter-trait correlation across the strains in each temperature regime was positive. Surprisingly, the mF plasmid had no negative effects on our chosen traits. Our study is the first to demonstrate genetic regulation of phenotype expression in a unicellular slime mould. The genetic effect on phenotypes manifests via epistatic interactions with the thermal environment, thus shedding new light on the role of G × G × E interactions in trait evolution in protists.}, } @article {pmid36790104, year = {2023}, author = {Onuț-Brännström, I and Stairs, CW and Campos, KIA and Thorén, MH and Ettema, TJG and Keeling, PJ and Bass, D and Burki, F}, title = {A Mitosome With Distinct Metabolism in the Uncultured Protist Parasite Paramikrocytos canceri (Rhizaria, Ascetosporea).}, journal = {Genome biology and evolution}, volume = {15}, number = {3}, pages = {}, pmid = {36790104}, issn = {1759-6653}, support = {MOP-42517//CIHR/Canada ; }, mesh = {Animals ; *Parasites ; *Rhizaria/genetics ; Organelles ; Mitochondria/genetics/metabolism ; Saccharomyces cerevisiae/metabolism ; }, abstract = {Ascetosporea are endoparasites of marine invertebrates that include economically important pathogens of aquaculture species. Owing to their often-minuscule cell sizes, strict intracellular lifestyle, lack of cultured representatives and minimal availability of molecular data, these unicellular parasites remain poorly studied. Here, we sequenced and assembled the genome and transcriptome of Paramikrocytos canceri, an endoparasite isolated from the European edible crab Cancer pagurus. Using bioinformatic predictions, we show that P. canceri likely possesses a mitochondrion-related organelle (MRO) with highly reduced metabolism, resembling the mitosomes of other parasites but with key differences. Like other mitosomes, this MRO is predicted to have reduced metabolic capacity and lack an organellar genome and function in iron-sulfur cluster (ISC) pathway-mediated Fe-S cluster biosynthesis. However, the MRO in P. canceri is uniquely predicted to produce ATP via a partial glycolytic pathway and synthesize phospholipids de novo through the CDP-DAG pathway. Heterologous gene expression confirmed that proteins from the ISC and CDP-DAG pathways retain mitochondrial targeting sequences that are recognized by yeast mitochondria. This represents a unique combination of metabolic pathways in an MRO, including the first reported case of a mitosome-like organelle able to synthesize phospholipids de novo. Some of these phospholipids, such as phosphatidylserine, are vital in other protist endoparasites that invade their host through apoptotic mimicry.}, } @article {pmid36790303, year = {2023}, author = {Sokolova, IM}, title = {Ectotherm mitochondrial economy and responses to global warming.}, journal = {Acta physiologica (Oxford, England)}, volume = {237}, number = {4}, pages = {e13950}, doi = {10.1111/apha.13950}, pmid = {36790303}, issn = {1748-1716}, mesh = {Reactive Oxygen Species/metabolism ; *Global Warming ; *Mitochondria/metabolism ; Energy Metabolism/physiology ; Adenosine Triphosphate/metabolism ; }, abstract = {Temperature is a key abiotic factor affecting ecology, biogeography, and evolution of species. Alterations of energy metabolism play an important role in adaptations and plastic responses to temperature shifts on different time scales. Mitochondrial metabolism affects cellular bioenergetics and redox balance making these organelles an important determinant of organismal performances such as growth, locomotion, or development. Here I analyze the impacts of environmental temperature on the mitochondrial functions (including oxidative phosphorylation, proton leak, production of reactive oxygen species(ROS), and ATP synthesis) of ectotherms and discuss the mechanisms underlying negative shifts in the mitochondrial energy economy caused by supraoptimal temperatures. Owing to the differences in the thermal sensitivity of different mitochondrial processes, elevated temperatures (beyond the species- and population-specific optimal range) cause reallocation of the electron flux and the protonmotive force (Δp) in a way that decreases ATP synthesis efficiency, elevates the relative cost of the mitochondrial maintenance, causes excessive production of ROS and raises energy cost for antioxidant defense. These shifts in the mitochondrial energy economy might have negative consequences for the organismal fitness traits such as the thermal tolerance or growth. Correlation between the thermal sensitivity indices of the mitochondria and the whole organism indicate that these traits experience similar selective pressures but further investigations are needed to establish whether there is a cause-effect relationship between the mitochondrial failure and loss of organismal performance during temperature change.}, } @article {pmid36795453, year = {2023}, author = {Dong, LF and Rohlena, J and Zobalova, R and Nahacka, Z and Rodriguez, AM and Berridge, MV and Neuzil, J}, title = {Mitochondria on the move: Horizontal mitochondrial transfer in disease and health.}, journal = {The Journal of cell biology}, volume = {222}, number = {3}, pages = {}, pmid = {36795453}, issn = {1540-8140}, mesh = {Animals ; Phylogeny ; *Mitochondria/metabolism ; *Neoplasms/genetics/metabolism ; Energy Metabolism ; Mammals ; }, abstract = {Mammalian genes were long thought to be constrained within somatic cells in most cell types. This concept was challenged recently when cellular organelles including mitochondria were shown to move between mammalian cells in culture via cytoplasmic bridges. Recent research in animals indicates transfer of mitochondria in cancer and during lung injury in vivo, with considerable functional consequences. Since these pioneering discoveries, many studies have confirmed horizontal mitochondrial transfer (HMT) in vivo, and its functional characteristics and consequences have been described. Additional support for this phenomenon has come from phylogenetic studies. Apparently, mitochondrial trafficking between cells occurs more frequently than previously thought and contributes to diverse processes including bioenergetic crosstalk and homeostasis, disease treatment and recovery, and development of resistance to cancer therapy. Here we highlight current knowledge of HMT between cells, focusing primarily on in vivo systems, and contend that this process is not only (patho)physiologically relevant, but also can be exploited for the design of novel therapeutic approaches.}, } @article {pmid36797268, year = {2023}, author = {Preston, AJ and Rogers, A and Sharp, M and Mitchell, G and Toruno, C and Barney, BB and Donovan, LN and Bly, J and Kennington, R and Payne, E and Iovino, A and Furukawa, G and Robinson, R and Shamloo, B and Buccilli, M and Anders, R and Eckstein, S and Fedak, EA and Wright, T and Maley, CC and Kiso, WK and Schmitt, D and Malkin, D and Schiffman, JD and Abegglen, LM}, title = {Elephant TP53-RETROGENE 9 induces transcription-independent apoptosis at the mitochondria.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {66}, pmid = {36797268}, issn = {2058-7716}, support = {S10 OD026959/OD/NIH HHS/United States ; U54 CA217376/CA/NCI NIH HHS/United States ; }, abstract = {Approximately 20 TP53 retrogenes exist in the African and Asian elephant genomes (Loxodonta Africana, Elephas Maximus) in addition to a conserved TP53 gene that encodes a full-length protein. Elephant TP53-RETROGENE 9 (TP53-R9) encodes a p53 protein (p53-R9) that is truncated in the middle of the canonical DNA binding domain. This C-terminally truncated p53 retrogene protein lacks the nuclear localization signals and oligomerization domain of its full-length counterpart. When expressed in human osteosarcoma cells (U2OS), p53-R9 binds to Tid1, the chaperone protein responsible for mitochondrial translocation of human p53 in response to cellular stress. Tid1 expression is required for p53-R9-induced apoptosis. At the mitochondria, p53-R9 binds to the pro-apoptotic BCL-2 family member Bax, which leads to caspase activation, cytochrome c release, and cell death. Our data show, for the first time, that expression of this truncated elephant p53 retrogene protein induces apoptosis in human cancer cells. Understanding the molecular mechanism by which the additional elephant TP53 retrogenes function may provide evolutionary insight that can be utilized for the development of therapeutics to treat human cancers.}, } @article {pmid36806940, year = {2023}, author = {Rivera-Colón, AG and Rayamajhi, N and Minhas, BF and Madrigal, G and Bilyk, KT and Yoon, V and Hüne, M and Gregory, S and Cheng, CHC and Catchen, JM}, title = {Genomics of Secondarily Temperate Adaptation in the Only Non-Antarctic Icefish.}, journal = {Molecular biology and evolution}, volume = {40}, number = {3}, pages = {}, pmid = {36806940}, issn = {1537-1719}, support = {//National Science Foundation/ ; }, mesh = {Animals ; Antarctic Regions ; *Adaptation, Physiological ; Fishes/genetics ; *Perciformes/genetics ; Genomics ; Antifreeze Proteins ; }, abstract = {White-blooded Antarctic icefishes, a family within the adaptive radiation of Antarctic notothenioid fishes, are an example of extreme biological specialization to both the chronic cold of the Southern Ocean and life without hemoglobin. As a result, icefishes display derived physiology that limits them to the cold and highly oxygenated Antarctic waters. Against these constraints, remarkably one species, the pike icefish Champsocephalus esox, successfully colonized temperate South American waters. To study the genetic mechanisms underlying secondarily temperate adaptation in icefishes, we generated chromosome-level genome assemblies of both C. esox and its Antarctic sister species, Champsocephalus gunnari. The C. esox genome is similar in structure and organization to that of its Antarctic congener; however, we observe evidence of chromosomal rearrangements coinciding with regions of elevated genetic divergence in pike icefish populations. We also find several key biological pathways under selection, including genes related to mitochondria and vision, highlighting candidates behind temperate adaptation in C. esox. Substantial antifreeze glycoprotein (AFGP) pseudogenization has occurred in the pike icefish, likely due to relaxed selection following ancestral escape from Antarctica. The canonical AFGP locus organization is conserved in C. esox and C. gunnari, but both show a translocation of two AFGP copies to a separate locus, previously unobserved in cryonotothenioids. Altogether, the study of this secondarily temperate species provides an insight into the mechanisms underlying adaptation to ecologically disparate environments in this otherwise highly specialized group.}, } @article {pmid36810648, year = {2023}, author = {Li, Y and Chen, L and Si, L and Yang, Y and Zhou, C and Yu, F and Xia, G and Wang, H}, title = {Triphenylamine-equipped 1,8-naphthaolactam: a versatile scaffold for the custom design of efficient subcellular imaging agents.}, journal = {Journal of materials chemistry. B}, volume = {11}, number = {11}, pages = {2431-2439}, doi = {10.1039/d2tb02528k}, pmid = {36810648}, issn = {2050-7518}, mesh = {*Optical Imaging ; *Mitochondria ; Amines ; }, abstract = {Fluorescence imaging has enabled much progress in biological fields, while the evolution of commercially available dyes has lagged behind their advanced applications. Herein, we launch triphenylamine-equipped 1,8-naphthaolactam (NP-TPA) as a versatile scaffold for the custom design of an efficient subcellular imaging agent (NP-TPA-Tar), given its bright and constant emissions in various states, significant Stokes shifts, and facile modifiability. The resultant four NP-TPA-Tars maintain excellent emission behavior with targeted modifications and can map the spatial distribution of lysosomes, mitochondria, endoplasmic reticulum, and plasma membrane in Hep G2 cells. Compared to its commercial counterpart, NP-TPA-Tar has a 2.8-25.2 fold increase in Stokes shift, a 1.2-1.9 fold increase in photostability, enhanced targeting capability, and comparable imaging efficiency even at low concentrations of 50 nM. This work will help to accelerate the update of current imaging agents and super-resolution and real-time imaging in biological applications.}, } @article {pmid36822346, year = {2023}, author = {Cheng, A and Zhang, Y and Sun, J and Huang, D and Sulaiman, JE and Huang, X and Wu, L and Ye, W and Wu, C and Lam, H and Shi, Y and Qian, PY}, title = {Pterosin sesquiterpenoids from Pteris laeta Wall. ex Ettingsh. protect cells from glutamate excitotoxicity by modulating mitochondrial signals.}, journal = {Journal of ethnopharmacology}, volume = {308}, number = {}, pages = {116308}, doi = {10.1016/j.jep.2023.116308}, pmid = {36822346}, issn = {1872-7573}, mesh = {Reactive Oxygen Species/metabolism ; Kelch-Like ECH-Associated Protein 1/metabolism ; Glutamic Acid/metabolism ; *Pteris/metabolism ; NF-E2-Related Factor 2/metabolism ; *Sesquiterpenes/pharmacology ; Mitochondria ; Oxidative Stress ; Indans ; }, abstract = {The genus Pteris (Pteridaceae) has been used as a traditional herb for a long time. In particular, Pteris laeta Wall. ex Ettingsh. has been widely used in traditional Chinese medicine to treat nervous system diseases and some pterosin sesquiterpenes from Pteris show neuroprotective activity, but their underlying molecular mechanisms remain elusive. Therefore, to investigate the neuroprotective activity and working mechanism of pterosin sesquiterpenes from P. laeta Wall. ex Ettingsh. will provide a better understanding and guidance in using P. laeta Wall. ex Ettingsh. as a traditional Chinese medicine.

AIM OF THE STUDY: We aim to develop effective treatments for neurodegenerative diseases from pterosin sesquiterpenes by evaluating their neuroprotective activity and investigating their working mechanisms.

MATERIALS AND METHODS: Primary screening on the glutamate-induced excitotoxicity cell model was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Fluorescent-activated cell sorting (FACS) was used to analyze the activation level of glutamate receptors and mitochondria membrane potential after treatment. Transcriptomics and proteomics analysis was performed to identify possible targets of pterosin B. The key pathways were enriched by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis through the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The core targets were visualized by a protein-protein interaction network using STRING. The mRNA and protein expressions were evaluated using real-time quantitative polymerase chain reaction (Q-PCR) and western blot, respectively. Immunocytochemistry was performed to monitor mitochondrial and apoptotic proteins. Cellular reactive oxygen species (ROS) were measured by ROS assay, and Ca[2+] was stained with Fluo-4 AM to quantify intracellular Ca[2+] levels.

RESULTS: We found pterosin B from Pteris laeta Wall. ex Ettingsh. showed significant neuroprotective activity against glutamate excitotoxicity, enhancing cell viability from 43.8% to 105% (p-value: <0.0001). We demonstrated that pterosin B worked on the downstream signaling pathways of glutamate excitotoxicity rather than directly blocking the activation of glutamate receptors. Pterosin B restored mitochondria membrane potentials, alleviated intracellular calcium overload from 107.4% to 95.47% (p-value: 0.0006), eliminated cellular ROS by 36.55% (p-value: 0.0143), and partially secured cells from LPS-induced inflammation by increasing cell survival from 46.75% to 58.5% (p-value: 0.0114). Notably, pterosin B enhanced the expression of nuclear factor-erythroid factor 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) by 2.86-fold (p-value: 0.0006) and 4.24-fold (p-value: 0.0012), and down-regulated Kelch-like ECH-associated protein 1 (KEAP1) expression by 2.5-fold (p-value: 0.0107), indicating that it possibly promotes mitochondrial biogenesis and mitophagy to maintain mitochondria quality control and homeostasis, and ultimately inhibits apoptotic cell death.

CONCLUSIONS: Our work revealed that pterosin B protected cells from glutamate excitotoxicity by targeting the downstream mitochondrial signals, making it a valuable candidate for developing potential therapeutic agents in treating neurodegenerative diseases.}, } @article {pmid36831240, year = {2023}, author = {Fang, Y and Zhang, F and Zhan, Y and Lu, M and Xu, D and Wang, J and Li, Q and Zhao, L and Su, Y}, title = {RpS3 Is Required for Spermatogenesis of Drosophila melanogaster.}, journal = {Cells}, volume = {12}, number = {4}, pages = {}, pmid = {36831240}, issn = {2073-4409}, mesh = {Animals ; Male ; *Drosophila melanogaster/metabolism ; *Drosophila Proteins/metabolism ; *Ribosomal Proteins/metabolism ; Semen/metabolism ; Spermatogenesis ; }, abstract = {Ribosomal proteins (RPs) constitute the ribosome, thus participating in the protein biosynthesis process. Emerging studies have suggested that many RPs exhibit different expression levels across various tissues and function in a context-dependent manner for animal development. Drosophila melanogaster RpS3 encodes the ribosomal protein S3, one component of the 40S subunit of ribosomes. We found that RpS3 is highly expressed in the reproductive organs of adult flies and its depletion in male germline cells led to severe defects in sperm production and male fertility. Immunofluorescence staining showed that RpS3 knockdown had little effect on early germ cell differentiation, but strongly disrupted the spermatid elongation and individualization processes. Furthermore, we observed abnormal morphology and activity of mitochondrial derivatives in the elongating spermatids of RpS3-knockdown testes, which could cause the failure of axoneme elongation. We also found that RpS3 RNAi inhibited the formation of the individualization complex that takes charge of disassociating the spermatid bundle. In addition, excessive apoptotic cells were detected in the RpS3-knockdown testes, possibly to clean the defective spermatids. Together, our data demonstrated that RpS3 plays an important role in regulating spermatid elongation and individualization processes and, therefore, is required for normal Drosophila spermatogenesis.}, } @article {pmid36835385, year = {2023}, author = {Yang, JX and Dierckxsens, N and Bai, MZ and Guo, YY}, title = {Multichromosomal Mitochondrial Genome of Paphiopedilum micranthum: Compact and Fragmented Genome, and Rampant Intracellular Gene Transfer.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36835385}, issn = {1422-0067}, support = {U1804117//National Natural Science Foundation of China/ ; }, mesh = {*Genome, Mitochondrial ; DNA, Mitochondrial ; Mitochondria/genetics ; *Magnoliopsida/genetics ; *Orchidaceae/genetics ; Phylogeny ; }, abstract = {Orchidaceae is one of the largest families of angiosperms. Considering the large number of species in this family and its symbiotic relationship with fungi, Orchidaceae provide an ideal model to study the evolution of plant mitogenomes. However, to date, there is only one draft mitochondrial genome of this family available. Here, we present a fully assembled and annotated sequence of the mitochondrial genome (mitogenome) of Paphiopedilum micranthum, a species with high economic and ornamental value. The mitogenome of P. micranthum was 447,368 bp in length and comprised 26 circular subgenomes ranging in size from 5973 bp to 32,281 bp. The genome encoded for 39 mitochondrial-origin, protein-coding genes; 16 tRNAs (three of plastome origin); three rRNAs; and 16 ORFs, while rpl10 and sdh3 were lost from the mitogenome. Moreover, interorganellar DNA transfer was identified in 14 of the 26 chromosomes. These plastid-derived DNA fragments represented 28.32% (46,273 bp) of the P. micranthum plastome, including 12 intact plastome origin genes. Remarkably, the mitogenome of P. micranthum and Gastrodia elata shared 18% (about 81 kb) of their mitochondrial DNA sequences. Additionally, we found a positive correlation between repeat length and recombination frequency. The mitogenome of P. micranthum had more compact and fragmented chromosomes compared to other species with multichromosomal structures. We suggest that repeat-mediated homologous recombination enables the dynamic structure of mitochondrial genomes in Orchidaceae.}, } @article {pmid36838260, year = {2023}, author = {Fuerst, PA}, title = {The Status of Molecular Analyses of Isolates of Acanthamoeba Maintained by International Culture Collections.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, pmid = {36838260}, issn = {2076-2607}, abstract = {Acanthamoeba is among the most ubiquitous protistan groups in nature. Knowledge of the biological diversity of Acanthamoeba comes in part from the use of strains maintained by the major microbial culture collections, ATCC and CCAP. Standard strains are vital to ensure the comparability of research. The diversity of standard strains of Acanthamoeba in the culture collections is reviewed, emphasizing the extent of genotypic studies based on DNA sequencing of the small subunit ribosomal RNA from the nucleus (18S rRNA gene; Rns) or the mitochondria (16S-like rRNA gene; rns). Over 170 different strains have been maintained at some time by culture centers. DNA sequence information is available for more than 70% of these strains. Determination of the genotypic classification of standard strains within the genus indicates that frequencies of types within culture collections only roughly mirror that from clinical or environmental studies, with significant differences in the frequency of some genotypes. Culture collections include the type of isolate from almost all named species of Acanthamoeba, allowing an evaluation of the validity of species designations. Multiple species are found to share the same Sequence Type, while multiple Sequence Types have been identified for different strains that share the same species name. Issues of sequence reliability and the possibility that a small number of standard strains have been mislabeled when studied are also examined, leading to potential problems for comparative analyses. It is important that all species have reliable genotype designations. The culture collections should be encouraged to assist in completing the molecular inventory of standard strains, while workers in the Acanthamoeba research community should endeavor to ensure that strains representative of genotypes that are missing from the culture collection are provided to the culture centers for preservation.}, } @article {pmid36841519, year = {2023}, author = {Tomita, K and Indo, HP and Sato, T and Tangpong, J and Majima, HJ}, title = {Development of a sensitive double TaqMan Probe-based qPCR Angle-Degree method to detect mutation frequencies.}, journal = {Mitochondrion}, volume = {70}, number = {}, pages = {1-7}, doi = {10.1016/j.mito.2023.02.010}, pmid = {36841519}, issn = {1872-8278}, mesh = {Humans ; Mutation Rate ; *MELAS Syndrome/genetics ; Mutation ; DNA, Mitochondrial/genetics ; *Stroke ; }, abstract = {We designed a method to examine the mutation frequencies of the A3243G mutation of mitochondrial DNA (mtDNA) in patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. We performed a qPCR assay using the FAM and VIC TaqMan probes, which detect the 3243G (mutated) and 3243A (wild-type) sequences of mtDNA, respectively. The results obtained by "degree" in a series of differential mutation frequencies were used to plot a standard curve of the mutation frequency. The standard curve was then applied for qPCR assays of the desired samples. The standard deviation (%) of the samples calculated using the standard curve for the TaqMan probe was 2.4 ± 1.5%. This method could be used to examine mutation frequencies in the context of diabetes, aging, cancer, and neurodegenerative diseases.}, } @article {pmid36858653, year = {2023}, author = {Degli Esposti, M}, title = {The bacterial origin of mitochondria: Incorrect phylogenies and the importance of metabolic traits.}, journal = {International review of cell and molecular biology}, volume = {374}, number = {}, pages = {1-35}, doi = {10.1016/bs.ircmb.2022.11.001}, pmid = {36858653}, issn = {1937-6448}, mesh = {Animals ; Phylogeny ; *Mitochondria ; *Eukaryota ; Oxygen ; Phenotype ; }, abstract = {This article provides an updated review on the evolution of mitochondria from bacteria, which were likely related to extant alphaproteobacteria. Particular attention is given to the timeline of oxygen history on Earth and the entwined phases of eukaryotic evolution that produced the animals that still populate our planet. Mitochondria of early-branching unicellular eukaryotes and plants appear to retain partial or vestigial traits that were directly inherited from the alphaproteobacterial ancestors of the organelles. Most of such traits define the current aerobic physiology of mitochondria. Conversely, the anaerobic traits that would be essential in the syntrophic associations postulated for the evolution of eukaryotic cells are scantly present in extant alphaproteobacteria, and therefore cannot help defining from which bacterial lineage the ancestors of mitochondria originated. This question has recently been addressed quantitatively, reaching the novel conclusion that marine bacteria related to Iodidimonas may be the living relatives of protomitochondria. Additional evidence is presented that either support or does not contrast this novel view of the bacterial origin of mitochondria.}, } @article {pmid36858654, year = {2023}, author = {Rubio-Tomás, T and Sotiriou, A and Tavernarakis, N}, title = {The interplay between selective types of (macro)autophagy: Mitophagy and xenophagy.}, journal = {International review of cell and molecular biology}, volume = {374}, number = {}, pages = {129-157}, doi = {10.1016/bs.ircmb.2022.10.003}, pmid = {36858654}, issn = {1937-6448}, mesh = {*Macroautophagy ; *Mitophagy ; Autophagy ; DNA Damage ; Exercise ; }, abstract = {Autophagy is a physiological response, activated by a myriad of endogenous and exogenous cues, including DNA damage, perturbation of proteostasis, depletion of nutrients or oxygen and pathogen infection. Upon sensing those stimuli, cells employ multiple non-selective and selective autophagy pathways to promote fitness and survival. Importantly, there are a variety of selective types of autophagy. In this review we will focus on autophagy of bacteria (xenophagy) and autophagy of mitochondria (mitophagy). We provide a brief introduction to bulk autophagy, as well as xenophagy and mitophagy, highlighting their common molecular factors. We also describe the role of xenophagy and mitophagy in the detection and elimination of pathogens by the immune system and the adaptive mechanisms that some pathogens have developed through evolution to escape the host autophagic response. Finally, we summarize the recent articles (from the last five years) linking bulk autophagy with xenophagy and/or mitophagy in the context on developmental biology, cancer and metabolism.}, } @article {pmid36860172, year = {2023}, author = {Cantó-Santos, J and Valls-Roca, L and Tobías, E and García-García, FJ and Guitart-Mampel, M and Esteve-Codina, A and Martín-Mur, B and Casado, M and Artuch, R and Solsona-Vilarrasa, E and Fernandez-Checa, JC and García-Ruiz, C and Rentero, C and Enrich, C and Moreno-Lozano, PJ and Milisenda, JC and Cardellach, F and Grau-Junyent, JM and Garrabou, G}, title = {Unravelling inclusion body myositis using a patient-derived fibroblast model.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {14}, number = {2}, pages = {964-977}, pmid = {36860172}, issn = {2190-6009}, support = {PI21/00935//Instituto de Salud Carlos III/ ; PI18/00451//Instituto de Salud Carlos III/ ; PI18/00498//Instituto de Salud Carlos III/ ; //APIF Programme (University of Barcelona)/ ; //CIBERER (ISCIII-FEDER)/ ; //CD21/00019 (ISCIII- FSE+)/ ; //Serra Húnter Programme (Generalitat de Catalunya)/ ; //Torrons Vicens/ ; //PID2019-111669RB-I00/ ; //PID2020-115055RB-I00/ ; //PT17/0009/0019 (ISCIII-MINECO-FEDER)/ ; }, mesh = {Humans ; *Myositis, Inclusion Body/diagnosis/genetics/metabolism ; *Myositis ; Muscles/metabolism ; Inflammation/pathology ; Biomarkers/metabolism ; }, abstract = {BACKGROUND: Inclusion body myositis (IBM) is an inflammatory myopathy clinically characterized by proximal and distal muscle weakness, with inflammatory infiltrates, rimmed vacuoles and mitochondrial changes in muscle histopathology. There is scarce knowledge on IBM aetiology, and non-established biomarkers or effective treatments are available, partly due to the lack of validated disease models.

METHODS: We have performed transcriptomics and functional validation of IBM muscle pathological hallmarks in fibroblasts from IBM patients (n = 14) and healthy controls (n = 12), paired by age and sex. The results comprise an mRNA-seq, together with functional inflammatory, autophagy, mitochondrial and metabolic changes between patients and controls.

RESULTS: Gene expression profile of IBM vs control fibroblasts revealed 778 differentially expressed genes (P-value adj < 0.05) related to inflammation, mitochondria, cell cycle regulation and metabolism. Functionally, an increased inflammatory profile was observed in IBM fibroblasts with higher supernatant cytokine secretion (three-fold increase). Autophagy was reduced considering basal protein mediators (18.4% reduced), time-course autophagosome formation (LC3BII 39% reduced, P-value < 0.05), and autophagosome microscopic evaluation. Mitochondria displayed reduced genetic content (by 33.9%, P-value < 0.05) and function (30.2%-decrease in respiration, 45.6%-decline in enzymatic activity (P-value < 0.001), 14.3%-higher oxidative stress, 135.2%-increased antioxidant defence (P-value < 0.05), 11.6%-reduced mitochondrial membrane potential (P-value < 0.05) and 42.8%-reduced mitochondrial elongation (P-value < 0.05)). In accordance, at the metabolite level, organic acid showed a 1.8-fold change increase, with conserved amino acid profile. Correlating to disease evolution, oxidative stress and inflammation emerge as potential markers of prognosis.

CONCLUSIONS: These findings confirm the presence of molecular disturbances in peripheral tissues from IBM patients and prompt patients' derived fibroblasts as a promising disease model, which may eventually be exported to other neuromuscular disorders. We additionally identify new molecular players in IBM associated with disease progression, setting the path to deepen in disease aetiology, in the identification of novel biomarkers or in the standardization of biomimetic platforms to assay new therapeutic strategies for preclinical studies.}, } @article {pmid36877343, year = {2023}, author = {Palacios-Barreto, P and Mar-Silva, AF and Bayona-Vasquez, NJ and Adams, DH and Díaz-Jaimes, P}, title = {Characterization of the complete mitochondrial genome of the brazilian cownose ray Rhinoptera brasiliensis (Myliobatiformes, Rhinopteridae) in the western Atlantic and its phylogenetic implications.}, journal = {Molecular biology reports}, volume = {50}, number = {5}, pages = {4083-4095}, pmid = {36877343}, issn = {1573-4978}, support = {IN207621//Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT)/ ; 341//LANCAD UNAM-DGTIC/ ; }, mesh = {Animals ; Phylogeny ; *Genome, Mitochondrial/genetics ; Brazil ; DNA, Mitochondrial/genetics ; *Skates, Fish/genetics ; Codon, Terminator ; RNA, Transfer/genetics ; }, abstract = {BACKGROUND: The Brazilian cownose ray, Rhinoptera brasiliensis has undergone a global population reduction and is currently classified by IUCN as Vulnerable. This species is sometimes confused with Rhinoptera bonasus, the only external diagnostic characteristic to distinguish between both species is the number of rows of tooth plates. Both cownose rays overlap geographically from Rio de Janeiro to the western North Atlantic. This calls for a more comprehensive phylogenetic assessment using mitochondria DNA genomes to better understand the relationships and delimitation of these two species.

METHODS AND RESULTS: The mitochondrial genome sequences of R. brasiliensis was obtained by next-generation sequencing. The length of the mitochondrial genome was 17,759 bp containing 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a non-coding control region (D-loop). Each PCG was initiated by an authoritative ATG codon, except for COX1 initiated by a GTG codon. Most of the PCGs were terminated by a complete codon (TAA/TAG), while an incomplete termination codon (TA/T) was found in five out of the 13 PCGs. The phylogenetic analysis showed that R. brasiliensis was closely related to R. steindachneri whereas the reported mitogenome as R. steindachneri (GenBank accession number KM364982), differs from multiple mitocondrial DNA sequences of R. steindachneri and is nearly identical to that of R. javanica.

CONCLUSION: The new mitogenome determined in this study provides new insight into the phylogenetic relationships in Rhinoptera, while providing new molecular data that can be applied to population genetic studies.}, } @article {pmid36882771, year = {2023}, author = {Bu, XL and Zhao, WS and Li, WX and Zou, H and Wu, SG and Li, M and Wang, GT}, title = {Mitochondrial metabolism of the facultative parasite Chilodonella uncinata (Alveolata, Ciliophora).}, journal = {Parasites & vectors}, volume = {16}, number = {1}, pages = {92}, pmid = {36882771}, issn = {1756-3305}, support = {No. 32170437//National Natural Science Foundation of China/ ; No. 2019QZKK0304//the Second Tibetan Plateau Scientific Expedition and Research Program (STEP)/ ; No. CARS-45//the earmarked fund for CARS/ ; }, mesh = {Animals ; *Alveolata ; *Parasites ; Phylogeny ; *Ciliophora/genetics ; Mitochondria ; }, abstract = {BACKGROUND: Chilodonella uncinata is an aerobic ciliate capable of switching between being free-living and parasitic on fish fins and gills, causing tissue damage and host mortality. It is widely used as a model organism for genetic studies, but its mitochondrial metabolism has never been studied. Therefore, we aimed to describe the morphological features and metabolic characteristics of its mitochondria.

METHODS: Fluorescence staining and transmission electron microscopy (TEM) were used to observe the morphology of mitochondria. Single-cell transcriptome data of C. uncinata were annotated by the Clusters of Orthologous Genes (COG) database. Meanwhile, the metabolic pathways were constructed based on the transcriptomes. The phylogenetic analysis was also made based on the sequenced cytochrome c oxidase subunit 1 (COX1) gene.

RESULTS: Mitochondria were stained red using Mito-tracker Red staining and were stained slightly blue by DAPI dye. The cristae and double membrane structures of the mitochondria were observed by TEM. Besides, many lipid droplets were evenly distributed around the macronucleus. A total of 2594 unigenes were assigned to 23 functional classifications of COG. Mitochondrial metabolic pathways were depicted. The mitochondria contained enzymes for the complete tricarboxylic acid (TCA) cycle, fatty acid metabolism, amino acid metabolism, and cytochrome-based electron transport chain (ETC), but only partial enzymes involved in the iron-sulfur clusters (ISCs).

CONCLUSIONS: Our results showed that C. uncinata possess typical mitochondria. Stored lipid droplets inside mitochondria may be the energy storage of C. uncinata that helps its transmission from a free-living to a parasitic lifestyle. These findings also have improved our knowledge of the mitochondrial metabolism of C. uncinata and increased the volume of molecular data for future studies of this facultative parasite.}, } @article {pmid36883279, year = {2023}, author = {García Pascual, B and Nordbotten, JM and Johnston, IG}, title = {Cellular and environmental dynamics influence species-specific extents of organelle gene retention.}, journal = {Proceedings. Biological sciences}, volume = {290}, number = {1994}, pages = {20222140}, pmid = {36883279}, issn = {1471-2954}, mesh = {Species Specificity ; *Mitochondria ; *Eukaryotic Cells ; Eukaryota ; }, abstract = {Mitochondria and plastids rely on many nuclear-encoded genes, but retain small subsets of the genes they need to function in their own organelle DNA (oDNA). Different species retain different numbers of oDNA genes, and the reasons for these differences are not completely understood. Here, we use a mathematical model to explore the hypothesis that the energetic demands imposed by an organism's changing environment influence how many oDNA genes it retains. The model couples the physical biology of cell processes of gene expression and transport to a supply-and-demand model for the environmental dynamics to which an organism is exposed. The trade-off between fulfilling metabolic and bioenergetic environmental demands, and retaining genetic integrity, is quantified for a generic gene encoded either in oDNA or in nuclear DNA. Species in environments with high-amplitude, intermediate-frequency oscillations are predicted to retain the most organelle genes, whereas those in less dynamic or noisy environments the fewest. We discuss support for, and insight from, these predictions with oDNA data across eukaryotic taxa, including high oDNA gene counts in sessile organisms exposed to day-night and intertidal oscillations (including plants and algae) and low counts in parasites and fungi.}, } @article {pmid36883292, year = {2023}, author = {Gaugel, SM and Hawlitschek, O and Dey, LS and Husemann, M}, title = {Evolution of mitogenomic gene order in Orthoptera.}, journal = {Insect molecular biology}, volume = {32}, number = {4}, pages = {387-399}, doi = {10.1111/imb.12838}, pmid = {36883292}, issn = {1365-2583}, mesh = {Animals ; Phylogeny ; Gene Order ; *Mitochondria/genetics ; Genomics ; *Gryllidae ; Evolution, Molecular ; }, abstract = {Mitochondrial gene order has contributed to the elucidation of evolutionary relationships in several animal groups. It generally has found its application as a phylogenetic marker for deep nodes. Yet, in Orthoptera limited research has been performed on the gene order, although the group represents one of the oldest insect orders. We performed a comprehensive study on mitochondrial genome rearrangements (MTRs) within Orthoptera in the context of mitogenomic sequence-based phylogeny. We used 280 published mitogenome sequences from 256 species, including three outgroup species, to reconstruct a molecular phylogeny. Using a heuristic approach, we assigned MTR scenarios to the edges of the phylogenetic tree and reconstructed ancestral gene orders to identify possible synapomorphies in Orthoptera. We found all types of MTRs in our dataset: inversions, transpositions, inverse transpositions, and tandem-duplication/random loss events (TDRL). Most of the suggested MTRs were in single and unrelated species. Out of five MTRs which were unique in subgroups of Orthoptera, we suggest four of them to be synapomorphies; those were in the infraorder Acrididea, in the tribe Holochlorini, in the subfamily Pseudophyllinae, and in the two families Phalangopsidae and Gryllidae or their common ancestor (leading to the relationship ((Phalangopsidae + Gryllidae) + Trigonidiidae)). However, similar MTRs have been found in distant insect lineages. Our findings suggest convergent evolution of specific mitochondrial gene orders in several species, deviant from the evolution of the mitogenome DNA sequence. As most MTRs were detected at terminal nodes, a phylogenetic inference of deeper nodes based on MTRs is not supported. Hence, the marker does not seem to aid resolving the phylogeny of Orthoptera, but adds further evidence for the complex evolution of the whole group, especially at the genetic and genomic levels. The results indicate a high demand for more research on patterns and underlying mechanisms of MTR events in Orthoptera.}, } @article {pmid36889655, year = {2023}, author = {Zhu, X and Liu, T and He, A and Zhang, L and Li, J and Li, T and Miao, X and You, M and You, S}, title = {Diversity of Wolbachia infection and its influence on mitochondrial DNA variation in the diamondback moth, Plutella xylostella.}, journal = {Molecular phylogenetics and evolution}, volume = {182}, number = {}, pages = {107751}, doi = {10.1016/j.ympev.2023.107751}, pmid = {36889655}, issn = {1095-9513}, mesh = {Animals ; *Moths/genetics ; *Wolbachia/genetics ; Phylogeny ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; }, abstract = {Plutella xylostella is a pest that severely damages cruciferous vegetables worldwide and has been shown to be infected with the maternally inherited bacteria Wolbachia, with the main infected strain was plutWB1. In this study, we performed a large-scale global sampling of P. xylostella and amplified 3 mtDNA genes of P. xylostella and 6 Wolbachia genes to analyze the infection status, diversity of Wolbachia in P. xylostella, and its effect on mtDNA variation in P. xylostella. This study provides a conservative estimate of Wolbachia infection rates in P. xylostella, which was found to be 7% (104/1440). The ST 108 (plutWB1) was shared among butterfly species and the moth species P. xylostella, revealing that Wolbachia strain plutWB1 acquisition in P. xylostella may be through horizontal transmission. The Parafit analyses indicated a significant association between Wolbachia and Wolbachia-infected P. xylostella individuals, and individuals infected with plutWB1 tended to cluster in the basal positions of the phylogenetic tree based on the mtDNA data. Additionally, Wolbachia infections were associated with increased mtDNA polymorphism in the infected P. xylostella population. These data suggest that Wolbachia endosymbionts may have a potential effect on mtDNA variation of P. xylostella.}, } @article {pmid36893930, year = {2023}, author = {Jesus, PB and Lyra, GM and Zhang, H and Fujii, MT and Nauer, F and Nunes, JMC and Davis, CC and Oliveira, MC}, title = {Phylogenomics and taxon-rich phylogenies of new and historical specimens shed light on the systematics of Hypnea (Cystocloniaceae, Rhodophyta).}, journal = {Molecular phylogenetics and evolution}, volume = {183}, number = {}, pages = {107752}, doi = {10.1016/j.ympev.2023.107752}, pmid = {36893930}, issn = {1095-9513}, mesh = {Phylogeny ; *Rhodophyta/genetics ; Organelles ; Mitochondria ; Chloroplasts ; }, abstract = {Cystocloniacae is a highly diverse family of Rhodophyta, including species of ecological and economic importance, whose phylogeny remains largely unresolved. Species delimitation is unclear, particularly in the most speciose genus, Hypnea, and cryptic diversity has been revealed by recent molecular assessments, especially in the tropics. Here, we carried out the first phylogenomic investigation of Cystocloniaceae, focused on the genus Hypnea, inferred from chloroplast and mitochondrial genomes including taxa sampled from new and historical collections. In this work, molecular synapomorphies (gene losses, InDels and gene inversions) were identified to better characterize clades in our congruent organellar phylogenies. We also present taxon-rich phylogenies based on plastid and mitochondrial markers. Molecular and morphological comparisons of historic collections with contemporary specimens revealed the need for taxonomic updates in Hypnea, the synonymization of H. marchantiae to a later heterotypic synonym of H. cervicornis and the description of three new species: H. davisiana sp. nov., H. djamilae sp. nov. and H. evaristoae sp. nov.}, } @article {pmid36897956, year = {2023}, author = {Smith, CH and Pinto, BJ and Kirkpatrick, M and Hillis, DM and Pfeiffer, JM and Havird, JC}, title = {A tale of two paths: The evolution of mitochondrial recombination in bivalves with doubly uniparental inheritance.}, journal = {The Journal of heredity}, volume = {114}, number = {3}, pages = {199-206}, pmid = {36897956}, issn = {1465-7333}, support = {R01 GM116853/GM/NIGMS NIH HHS/United States ; R35 GM142836/GM/NIGMS NIH HHS/United States ; R35-GM142836/NH/NIH HHS/United States ; }, mesh = {Animals ; Female ; Male ; Phylogeny ; Mitochondria/genetics ; *Bivalvia/genetics ; DNA, Mitochondrial/genetics ; Inheritance Patterns ; *Genome, Mitochondrial ; Recombination, Genetic ; }, abstract = {In most animals, mitochondrial DNA is strictly maternally inherited and non-recombining. One exception to this pattern is called doubly uniparental inheritance (DUI), a phenomenon involving the independent transmission of female and male mitochondrial genomes. DUI is known only from the molluskan class Bivalvia. The phylogenetic distribution of male-transmitted mitochondrial DNA (M mtDNA) in bivalves is consistent with several evolutionary scenarios, including multiple independent gains, losses, and varying degrees of recombination with female-transmitted mitochondrial DNA (F mtDNA). In this study, we use phylogenetic methods to test M mtDNA origination hypotheses and infer the prevalence of mitochondrial recombination in bivalves with DUI. Phylogenetic modeling using site concordance factors supported a single origin of M mtDNA in bivalves coupled with recombination acting over long evolutionary timescales. Ongoing mitochondrial recombination is present in Mytilida and Venerida, which results in a pattern of concerted evolution of F mtDNA and M mtDNA. Mitochondrial recombination could be favored to offset the deleterious effects of asexual inheritance and maintain mitonuclear compatibility across tissues. Cardiida and Unionida have gone without recent recombination, possibly due to an extension of the COX2 gene in male mitochondrial DNA. The loss of recombination could be connected to the role of M mtDNA in sex determination or sexual development. Our results support that recombination events may occur throughout the mitochondrial genomes of DUI species. Future investigations may reveal more complex patterns of inheritance of recombinants, which could explain the retention of signal for a single origination of M mtDNA in protein-coding genes.}, } @article {pmid36913593, year = {2023}, author = {Swainsbury, DJK and Hawkings, FR and Martin, EC and Musiał, S and Salisbury, JH and Jackson, PJ and Farmer, DA and Johnson, MP and Siebert, CA and Hitchcock, A and Hunter, CN}, title = {Cryo-EM structure of the four-subunit Rhodobacter sphaeroides cytochrome bc1 complex in styrene maleic acid nanodiscs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {12}, pages = {e2217922120}, pmid = {36913593}, issn = {1091-6490}, support = {BB/M000265/1//UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; BB/V006630/1//UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; }, mesh = {*Rhodobacter sphaeroides/chemistry ; Cytochromes c ; Cytochromes b ; Styrene ; Cryoelectron Microscopy ; Quinones ; Lipids ; Electron Transport Complex III ; Oxidation-Reduction ; Benzoquinones ; Maleates ; }, abstract = {Cytochrome bc1 complexes are ubiquinol:cytochrome c oxidoreductases, and as such, they are centrally important components of respiratory and photosynthetic electron transfer chains in many species of bacteria and in mitochondria. The minimal complex has three catalytic components, which are cytochrome b, cytochrome c1, and the Rieske iron-sulfur subunit, but the function of mitochondrial cytochrome bc1 complexes is modified by up to eight supernumerary subunits. The cytochrome bc1 complex from the purple phototrophic bacterium Rhodobacter sphaeroides has a single supernumerary subunit called subunit IV, which is absent from current structures of the complex. In this work we use the styrene-maleic acid copolymer to purify the R. sphaeroides cytochrome bc1 complex in native lipid nanodiscs, which retains the labile subunit IV, annular lipids, and natively bound quinones. The catalytic activity of the four-subunit cytochrome bc1 complex is threefold higher than that of the complex lacking subunit IV. To understand the role of subunit IV, we determined the structure of the four-subunit complex at 2.9 Å using single particle cryogenic electron microscopy. The structure shows the position of the transmembrane domain of subunit IV, which lies across the transmembrane helices of the Rieske and cytochrome c1 subunits. We observe a quinone at the Qo quinone-binding site and show that occupancy of this site is linked to conformational changes in the Rieske head domain during catalysis. Twelve lipids were structurally resolved, making contacts with the Rieske and cytochrome b subunits, with some spanning both of the two monomers that make up the dimeric complex.}, } @article {pmid36915058, year = {2023}, author = {Zumkeller, S and Knoop, V}, title = {Categorizing 161 plant (streptophyte) mitochondrial group II introns into 29 families of related paralogues finds only limited links between intron mobility and intron-borne maturases.}, journal = {BMC ecology and evolution}, volume = {23}, number = {1}, pages = {5}, pmid = {36915058}, issn = {2730-7182}, mesh = {Introns/genetics ; *Evolution, Molecular ; *Mitochondria/genetics ; Plants/genetics ; Cell Nucleus ; }, abstract = {Group II introns are common in the two endosymbiotic organelle genomes of the plant lineage. Chloroplasts harbor 22 positionally conserved group II introns whereas their occurrence in land plant (embryophyte) mitogenomes is highly variable and specific for the seven major clades: liverworts, mosses, hornworts, lycophytes, ferns, gymnosperms and flowering plants. Each plant group features "signature selections" of ca. 20-30 paralogues from a superset of altogether 105 group II introns meantime identified in embryophyte mtDNAs, suggesting massive intron gains and losses along the backbone of plant phylogeny. We report on systematically categorizing plant mitochondrial group II introns into "families", comprising evidently related paralogues at different insertion sites, which may even be more similar than their respective orthologues in phylogenetically distant taxa. Including streptophyte (charophyte) algae extends our sampling to 161 and we sort 104 streptophyte mitochondrial group II introns into 25 core families of related paralogues evidently arising from retrotransposition events. Adding to discoveries of only recently created intron paralogues, hypermobile introns and twintrons, our survey led to further discoveries including previously overlooked "fossil" introns in spacer regions or e.g., in the rps8 pseudogene of lycophytes. Initially excluding intron-borne maturase sequences for family categorization, we added an independent analysis of maturase phylogenies and find a surprising incongruence between intron mobility and the presence of intron-borne maturases. Intriguingly, however, we find that several examples of nuclear splicing factors meantime characterized simultaneously facilitate splicing of independent paralogues now placed into the same intron families. Altogether this suggests that plant group II intron mobility, in contrast to their bacterial counterparts, is not intimately linked to intron-encoded maturases.}, } @article {pmid36916992, year = {2023}, author = {Monné, M and Cianciulli, A and Panaro, MA and Calvello, R and De Grassi, A and Palmieri, L and Mitolo, V and Palmieri, F}, title = {New Insights into the Evolution and Gene Structure of the Mitochondrial Carrier Family Unveiled by Analyzing the Frequent and Conserved Intron Positions.}, journal = {Molecular biology and evolution}, volume = {40}, number = {3}, pages = {}, pmid = {36916992}, issn = {1537-1719}, mesh = {Humans ; Introns ; Phylogeny ; *Mitochondria/genetics/metabolism ; *Membrane Transport Proteins/genetics ; Eukaryota/genetics ; Evolution, Molecular ; Conserved Sequence ; }, abstract = {Mitochondrial carriers (MCs) belong to a eukaryotic protein family of transporters that in higher organisms is called the solute carrier family 25 (SLC25). All MCs have characteristic triplicated sequence repeats forming a 3-fold symmetrical structure of a six-transmembrane α-helix bundle with a centrally located substrate-binding site. Biochemical characterization has shown that MCs altogether transport a wide variety of substrates but can be divided into subfamilies, each transporting a few specific substrates. We have investigated the intron positions in the human MC genes and their orthologs of highly diversified organisms. The results demonstrate that several intron positions are present in numerous MC sequences at the same specific points, of which some are 3-fold symmetry related. Many of these frequent intron positions are also conserved in subfamilies or in groups of subfamilies transporting similar substrates. The analyses of the frequent and conserved intron positions in MCs suggest phylogenetic relationships not only between close but also distant homologs as well as a possible involvement of the intron positions in the evolution of the substrate specificity diversification of the MC family members.}, } @article {pmid36921565, year = {2023}, author = {Huang, L and Zhang, L and Shi, S and Zhou, X and Yuan, H and Song, X and Hu, Y and Pang, W and Yang, G and Gao, L and Chu, G}, title = {Mitochondrial function and E2 synthesis are impaired following alteration of CLOCK gene expression in porcine ovarian granulosa cells.}, journal = {Theriogenology}, volume = {202}, number = {}, pages = {51-60}, doi = {10.1016/j.theriogenology.2023.03.004}, pmid = {36921565}, issn = {1879-3231}, mesh = {Female ; Swine ; Animals ; *Gene Expression Regulation ; Phylogeny ; *Granulosa Cells/physiology ; Estradiol/metabolism ; Mitochondria/metabolism ; Gene Expression ; Mammals ; }, abstract = {Circadian locomotor output cycles kaput (CLOCK) is a critical component of the mammalian circadian clock system and regulates ovarian physiology. However, the functions and mechanisms of CLOCK in porcine granulosa cells (GCs) are poorly understood. The present study focused on CLOCK's effects on estradiol synthesis. Similarity analysis showed that CLOCK is highly conserved between pigs and other species. The phylogenetic tree analysis indicated that porcine CLOCK was most closely related to that in Arabian camels. CLOCK significantly reduced E2 synthesis in GCs. CLOCK reduced the expression of steroidogenesis-related genes at the mRNA and protein levels, including CYP19A1, CYP11A1, and StAR. CYP17A1 levels were significantly downregulated. We demonstrated that CLOCK dramatically decreased ATP content, mitochondrial copy number, and mitochondrial membrane potential (MMP) and increased reactive oxygen species levels in GCs. We observed that mitochondria were severely damaged with fuzzy and fractured cristae and swollen matrix. These findings suggest that mitochondrial function and E2 synthesis are impaired following the alteration of CLOCK gene expression in porcine ovarian GCs.}, } @article {pmid36921606, year = {2023}, author = {Muñoz-Gómez, SA and Cadena, LR and Gardiner, AT and Leger, MM and Sheikh, S and Connell, LB and Bilý, T and Kopejtka, K and Beatty, JT and Koblížek, M and Roger, AJ and Slamovits, CH and Lukeš, J and Hashimi, H}, title = {Intracytoplasmic-membrane development in alphaproteobacteria involves the homolog of the mitochondrial crista-developing protein Mic60.}, journal = {Current biology : CB}, volume = {33}, number = {6}, pages = {1099-1111.e6}, doi = {10.1016/j.cub.2023.02.059}, pmid = {36921606}, issn = {1879-0445}, mesh = {*Mitochondrial Proteins/metabolism ; *Alphaproteobacteria/genetics/metabolism ; Mitochondrial Membranes/metabolism ; Mitochondria/metabolism ; Biological Evolution ; }, abstract = {Mitochondrial cristae expand the surface area of respiratory membranes and ultimately allow for the evolutionary scaling of respiration with cell volume across eukaryotes. The discovery of Mic60 homologs among alphaproteobacteria, the closest extant relatives of mitochondria, suggested that cristae might have evolved from bacterial intracytoplasmic membranes (ICMs). Here, we investigated the predicted structure and function of alphaproteobacterial Mic60, and a protein encoded by an adjacent gene Orf52, in two distantly related purple alphaproteobacteria, Rhodobacter sphaeroides and Rhodopseudomonas palustris. In addition, we assessed the potential physical interactors of Mic60 and Orf52 in R. sphaeroides. We show that the three α helices of mitochondrial Mic60's mitofilin domain, as well as its adjacent membrane-binding amphipathic helix, are present in alphaproteobacterial Mic60. The disruption of Mic60 and Orf52 caused photoheterotrophic growth defects, which are most severe under low light conditions, and both their disruption and overexpression led to enlarged ICMs in both studied alphaproteobacteria. We also found that alphaproteobacterial Mic60 physically interacts with BamA, the homolog of Sam50, one of the main physical interactors of eukaryotic Mic60. This interaction, responsible for making contact sites at mitochondrial envelopes, has been conserved in modern alphaproteobacteria despite more than a billion years of evolutionary divergence. Our results suggest a role for Mic60 in photosynthetic ICM development and contact site formation at alphaproteobacterial envelopes. Overall, we provide support for the hypothesis that mitochondrial cristae evolved from alphaproteobacterial ICMs and have therefore improved our understanding of the nature of the mitochondrial ancestor.}, } @article {pmid36921696, year = {2023}, author = {Lee, C and Ruhlman, TA and Jansen, RK}, title = {Rate accelerations in plastid and mitochondrial genomes of Cyperaceae occur in the same clades.}, journal = {Molecular phylogenetics and evolution}, volume = {182}, number = {}, pages = {107760}, doi = {10.1016/j.ympev.2023.107760}, pmid = {36921696}, issn = {1095-9513}, mesh = {Phylogeny ; Genome, Plant ; *Cyperaceae/genetics ; *Genome, Mitochondrial ; Evolution, Molecular ; *Magnoliopsida/genetics ; Plastids/genetics ; *Genome, Plastid ; }, abstract = {Cyperaceae, the second largest family in the monocot order Poales, comprises >5500 species and includes the genus Eleocharis with ∼ 250 species. A previous study of complete plastomes of two Eleocharis species documented extensive structural heteroplasmy, gene order changes, high frequency of dispersed repeats along with gene losses and duplications. To better understand the phylogenetic distribution of gene and intron content as well as rates and patterns of sequence evolution within and between mitochondrial and plastid genomes of Eleocharis and Cyperaceae, an additional 29 Eleocharis organelle genomes were sequenced and analyzed. Eleocharis experienced extensive gene loss in both genomes while loss of introns was mitochondria-specific. Eleocharis has higher rates of synonymous (dS) and nonsynonymous (dN) substitutions in the plastid and mitochondrion than most sampled angiosperms, and the pattern was distinct from other eudicot lineages with accelerated rates. Several clades showed higher dS and dN in mitochondrial genes than in plastid genes. Furthermore, nucleotide substitution rates of mitochondrial genes were significantly accelerated on the branch leading to Cyperaceae compared to most angiosperms. Mitochondrial genes of Cyperaceae exhibited dramatic loss of RNA editing sites and a negative correlation between RNA editing and dS values was detected among angiosperms. Mutagenic retroprocessing and dysfunction of DNA replication, repair and recombination genes are the most likely cause of striking rate accelerations and loss of edit sites and introns in Eleocharis and Cyperaceae organelle genomes.}, } @article {pmid36929911, year = {2023}, author = {Biot-Pelletier, D and Bettinazzi, S and Gagnon-Arsenault, I and Dubé, AK and Bédard, C and Nguyen, THM and Fiumera, HL and Breton, S and Landry, CR}, title = {Evolutionary Trajectories are Contingent on Mitonuclear Interactions.}, journal = {Molecular biology and evolution}, volume = {40}, number = {4}, pages = {}, pmid = {36929911}, issn = {1537-1719}, mesh = {*DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Eukaryota/genetics ; Genotype ; *Genome, Mitochondrial ; Cell Nucleus/genetics ; }, abstract = {Critical mitochondrial functions, including cellular respiration, rely on frequently interacting components expressed from both the mitochondrial and nuclear genomes. The fitness of eukaryotic organisms depends on a tight collaboration between both genomes. In the face of an elevated rate of evolution in mtDNA, current models predict that the maintenance of mitonuclear compatibility relies on compensatory evolution of the nuclear genome. Mitonuclear interactions would therefore exert an influence on evolutionary trajectories. One prediction from this model is that the same nuclear genome evolving with different mitochondrial haplotypes would follow distinct molecular paths toward higher fitness. To test this prediction, we submitted 1,344 populations derived from 7 mitonuclear genotypes of Saccharomyces cerevisiae to >300 generations of experimental evolution in conditions that either select for a mitochondrial function or do not strictly require respiration for survival. Performing high-throughput phenotyping and whole-genome sequencing on independently evolved individuals, we identified numerous examples of gene-level evolutionary convergence among populations with the same mitonuclear background. Phenotypic and genotypic data on strains derived from this evolution experiment identify the nuclear genome and the environment as the main determinants of evolutionary divergence, but also show a modulating role for the mitochondrial genome exerted both directly and via interactions with the two other components. We finally recapitulated a subset of prominent loss-of-function alleles in the ancestral backgrounds and confirmed a generalized pattern of mitonuclear-specific and highly epistatic fitness effects. Together, these results demonstrate how mitonuclear interactions can dictate evolutionary divergence of populations with identical starting nuclear genotypes.}, } @article {pmid36938916, year = {2023}, author = {Jiao, J and Wang, X and Wei, C and Zhao, Y}, title = {Bioinspired Electrode for the Production and Timely Separation of Nitrile and Hydrogen.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {19}, number = {26}, pages = {e2208044}, doi = {10.1002/smll.202208044}, pmid = {36938916}, issn = {1613-6829}, support = {22102049//National Natural Science Foundation of China/ ; U22A20437//National Natural Science Foundation of China/ ; 222301420005//Joint Fund of Science and Technology R&D Plan of Henan Province/ ; }, abstract = {Replacing electrocatalytic oxygen evolution reaction (OER) with amine oxidation reaction is adopted to boost clean and environment-friendly energy source hydrogen (H2) in water. However, the electrocatalytic reaction is severely restricted by the strong adsorption of product on the catalyst surface. Inspired by the cooperation of flavin adenine dinucleotide and mitochondria membrane in biological system, the catalysis-separation complex electrodes are introduced to promote the desorption of product and hinder its readsorption by applying polytetrafluoroethylene (PTFE)-separation membrane on the one side of electrode, which is benefit for the cleanness of active sites on the catalyst surface for the continuous production and timely separation of nitrile and hydrogen. With the intermolecular force between PTFE and nitrile, the nitrile droplets can be quickly desorbed and separated from catalyst surface of anode, and the size of nitrile droplets on the catalyst surface is only 0.23% to that without PTFE. As a result, the current at 1.49 VRHE from the catalyst with PTFE membrane is about 33 times to that of catalyst without PTFE after long-term operation. Moreover, the cathode with PTFE membrane also achieves the rapid desorption of H2 bubbles and stable cathodic current because of the strong absorption of PTFE to H2 .}, } @article {pmid36939357, year = {2023}, author = {Macher, JN and Coots, NL and Poh, YP and Girard, EB and Langerak, A and Muñoz-Gómez, SA and Sinha, SD and Jirsová, D and Vos, R and Wissels, R and Gile, GH and Renema, W and Wideman, JG}, title = {Single-Cell Genomics Reveals the Divergent Mitochondrial Genomes of Retaria (Foraminifera and Radiolaria).}, journal = {mBio}, volume = {14}, number = {2}, pages = {e0030223}, pmid = {36939357}, issn = {2150-7511}, mesh = {Animals ; *Foraminifera/genetics ; *Genome, Mitochondrial ; Phylogeny ; Codon, Terminator ; *Rhizaria/genetics ; Genomics ; Eukaryota/genetics ; Amino Acids/genetics ; DNA, Mitochondrial/genetics ; }, abstract = {Mitochondria originated from an ancient bacterial endosymbiont that underwent reductive evolution by gene loss and endosymbiont gene transfer to the nuclear genome. The diversity of mitochondrial genomes published to date has revealed that gene loss and transfer processes are ongoing in many lineages. Most well-studied eukaryotic lineages are represented in mitochondrial genome databases, except for the superphylum Retaria-the lineage comprising Foraminifera and Radiolaria. Using single-cell approaches, we determined two complete mitochondrial genomes of Foraminifera and two nearly complete mitochondrial genomes of radiolarians. We report the complete coding content of an additional 14 foram species. We show that foraminiferan and radiolarian mitochondrial genomes contain a nearly fully overlapping but reduced mitochondrial gene complement compared to other sequenced rhizarians. In contrast to animals and fungi, many protists encode a diverse set of proteins on their mitochondrial genomes, including several ribosomal genes; however, some aerobic eukaryotic lineages (euglenids, myzozoans, and chlamydomonas-like algae) have reduced mitochondrial gene content and lack all ribosomal genes. Similar to these reduced outliers, we show that retarian mitochondrial genomes lack ribosomal protein and tRNA genes, contain truncated and divergent small and large rRNA genes, and contain only 14 or 15 protein-coding genes, including nad1, -3, -4, -4L, -5, and -7, cob, cox1, -2, and -3, and atp1, -6, and -9, with forams and radiolarians additionally carrying nad2 and nad6, respectively. In radiolarian mitogenomes, a noncanonical genetic code was identified in which all three stop codons encode amino acids. Collectively, these results add to our understanding of mitochondrial genome evolution and fill in one of the last major gaps in mitochondrial sequence databases. IMPORTANCE We present the reduced mitochondrial genomes of Retaria, the rhizarian lineage comprising the phyla Foraminifera and Radiolaria. By applying single-cell genomic approaches, we found that foraminiferan and radiolarian mitochondrial genomes contain an overlapping but reduced mitochondrial gene complement compared to other sequenced rhizarians. An alternative genetic code was identified in radiolarian mitogenomes in which all three stop codons encode amino acids. Collectively, these results shed light on the divergent nature of the mitochondrial genomes from an ecologically important group, warranting further questions into the biological underpinnings of gene content variability and genetic code variation between mitochondrial genomes.}, } @article {pmid36944856, year = {2023}, author = {Niedziałkowska, M and Tarnowska, E and Babik, W and Konczal, M and Gharbi, K and Cezard, T and Jędrzejewska, B}, title = {Different waves of postglacial recolonisation and genomic structure of bank vole populations in NE Poland.}, journal = {Heredity}, volume = {130}, number = {5}, pages = {269-277}, pmid = {36944856}, issn = {1365-2540}, mesh = {Humans ; Animals ; Poland ; Phylogeny ; *DNA, Mitochondrial/genetics ; *Genomics ; Arvicolinae/genetics ; Genetic Variation ; }, abstract = {Previous studies indicated that in some species phylogeographic patterns obtained in the analysis of nuclear and mitochondrial DNA (mtDNA) markers can be different. Such mitonuclear discordance can have important evolutionary and ecological consequences. In the present study, we aimed to check whether there was any discordance between mtDNA and nuclear DNA in the bank vole population in the contact zone of its two mtDNA lineages. We analysed the population genetic structure of bank voles using genome-wide genetic data (SNPs) and diversity of sequenced heart transcriptomes obtained from selected individuals from three populations inhabiting areas outside the contact zone. The SNP genetic structure of the populations confirmed the presence of at least two genetic clusters, and such division was concordant with the patterns obtained in the analysis of other genetic markers and functional genes. However, genome-wide SNP analyses revealed the more detailed structure of the studied population, consistent with more than two bank vole recolonisation waves, as recognised previously in the study area. We did not find any significant differences between individuals representing two separate mtDNA lineages of the species in functional genes coding for protein-forming complexes, which are involved in the process of cell respiration in mitochondria. We concluded that the contemporary genetic structure of the populations and the width of the contact zone were shaped by climatic and environmental factors rather than by genetic barriers. The studied populations were likely isolated in separate Last Glacial Maximum refugia for insufficient amount of time to develop significant genetic differentiation.}, } @article {pmid36944988, year = {2023}, author = {Yu, X and Wei, P and Chen, Z and Li, X and Zhang, W and Yang, Y and Liu, C and Zhao, S and Li, X and Liu, X}, title = {Comparative analysis of the organelle genomes of three Rhodiola species provide insights into their structural dynamics and sequence divergences.}, journal = {BMC plant biology}, volume = {23}, number = {1}, pages = {156}, pmid = {36944988}, issn = {1471-2229}, support = {XZ202001YD0028C//Local Development Funds of Science and Technology Department of Tibet/ ; 413100105//Plateau Ecology Youth Innovative Fund of Wuhan University/ ; }, mesh = {*Rhodiola/genetics ; Phylogeny ; *Genome, Plastid ; Tibet ; Mitochondria/genetics ; *Genome, Mitochondrial/genetics ; Evolution, Molecular ; }, abstract = {BACKGROUND: Plant organelle genomes are a valuable resource for evolutionary biology research, yet their genome architectures, evolutionary patterns and environmental adaptations are poorly understood in many lineages. Rhodiola species is a type of flora mainly distributed in highland habitats, with high medicinal value. Here, we assembled the organelle genomes of three Rhodiola species (R. wallichiana, R. crenulata and R. sacra) collected from the Qinghai-Tibet plateau (QTP), and compared their genome structure, gene content, structural rearrangements, sequence transfer and sequence evolution rates.

RESULTS: The results demonstrated the contrasting evolutionary pattern between plastomes and mitogenomes in three Rhodiola species, with the former possessing more conserved genome structure but faster evolutionary rates of sequence, while the latter exhibiting structural diversity but slower rates of sequence evolution. Some lineage-specific features were observed in Rhodiola mitogenomes, including chromosome fission, gene loss and structural rearrangement. Repeat element analysis shows that the repeats occurring between the two chromosomes may mediate the formation of multichromosomal structure in the mitogenomes of Rhodiola, and this multichromosomal structure may have recently formed. The identification of homologous sequences between plastomes and mitogenomes reveals several unidirectional protein-coding gene transfer events from chloroplasts to mitochondria. Moreover, we found that their organelle genomes contained multiple fragments of nuclear transposable elements (TEs) and exhibited different preferences for TEs insertion type. Genome-wide scans of positive selection identified one gene matR from the mitogenome. Since the matR is crucial for plant growth and development, as well as for respiration and stress responses, our findings suggest that matR may participate in the adaptive response of Rhodiola species to environmental stress of QTP.

CONCLUSION: The study analyzed the organelle genomes of three Rhodiola species and demonstrated the contrasting evolutionary pattern between plastomes and mitogenomes. Signals of positive selection were detected in the matR gene of Rhodiola mitogenomes, suggesting the potential role of this gene in Rhodiola adaptation to QTP. Together, the study is expected to enrich the genomic resources and provide valuable insights into the structural dynamics and sequence divergences of Rhodiola species.}, } @article {pmid36948134, year = {2023}, author = {Celik, A and Orfany, A and Dearling, J and Del Nido, PJ and McCully, JD and Bakar-Ates, F}, title = {Mitochondrial transplantation: Effects on chemotherapy in prostate and ovarian cancer cells in vitro and in vivo.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {161}, number = {}, pages = {114524}, doi = {10.1016/j.biopha.2023.114524}, pmid = {36948134}, issn = {1950-6007}, mesh = {Male ; Female ; Humans ; Animals ; Mice ; Prostate/pathology ; Apoptosis ; Cell Line, Tumor ; *Ovarian Neoplasms/pathology ; Mitochondria ; Cisplatin/pharmacology ; Drug Resistance, Neoplasm ; *Antineoplastic Agents/pharmacology/therapeutic use ; }, abstract = {Prostate and ovarian cancers affect the male and female reproductive organs and are among the most common cancers in developing countries. Previous studies have demonstrated that cancer cells have a high rate of aerobic glycolysis that is present in nearly all invasive human cancers and persists even under normoxic conditions. Aerobic glycolysis has been correlated with chemotherapeutic resistance and tumor aggressiveness. These data suggest that mitochondrial dysfunction may confer a significant proliferative advantage during the somatic evolution of cancer. In this study we investigated the effect of direct mitochondria transplantation on cancer cell proliferation and chemotherapeutic sensitivity in prostate and ovarian cancer models, both in vitro and in vivo. Our results show that the transplantation of viable, respiration competent mitochondria has no effect on cancer cell proliferation but significantly decreases migration and alters cell cycle checkpoints. Our results further demonstrate that mitochondrial transplantation significantly increases chemotherapeutic sensitivity, providing similar apoptotic levels with low-dose chemotherapy as that achieved with high-dose chemotherapy. These results suggest that mitochondria transplantation provides a novel approach for early prostate and ovarian cancer therapy, significantly increasing chemotherapeutic sensitivity in in vitro and in vivo murine models.}, } @article {pmid36948470, year = {2023}, author = {Cayuela, H and Gaillard, JM and Vieira, C and Ronget, V and Gippet, JMW and Conde García, T and Marais, GAB and Lemaître, JF}, title = {Sex differences in adult lifespan and aging rate across mammals: A test of the 'Mother Curse hypothesis'.}, journal = {Mechanisms of ageing and development}, volume = {212}, number = {}, pages = {111799}, doi = {10.1016/j.mad.2023.111799}, pmid = {36948470}, issn = {1872-6216}, mesh = {Humans ; Animals ; Female ; Male ; *Longevity/genetics ; *Mothers ; Sex Characteristics ; Aging ; DNA, Mitochondrial/genetics ; Drosophila ; Mammals ; }, abstract = {In many animal species, including humans, males have shorter lifespan and show faster survival aging than females. This differential increase in mortality between sexes could result from the accumulation of deleterious mutations in the mitochondrial genome of males due to the maternal mode of mtDNA inheritance. To date, empirical evidence supporting the existence of this mechanism - called the Mother Curse hypothesis - remains largely limited to a few study cases in humans and Drosophila. In this study, we tested whether the Mother Curse hypothesis accounts for sex differences in lifespan and aging rate across 128 populations of mammals (60 and 68 populations studied in wild and captive conditions, respectively) encompassing 104 species. We found that adult lifespan decreases with increasing mtDNA neutral substitution rate in both sexes in a similar way in the wild - but not in captivity. Moreover, the aging rate marginally increased with neutral substitution rate in males and females in the wild. Overall, these results indicate that the Mother Curse hypothesis is not supported across mammals. We further discuss the implication of these findings for our understanding of the evolution of sex differences in mortality and aging.}, } @article {pmid36949187, year = {2023}, author = {Mühleip, A and Flygaard, RK and Baradaran, R and Haapanen, O and Gruhl, T and Tobiasson, V and Maréchal, A and Sharma, V and Amunts, A}, title = {Structural basis of mitochondrial membrane bending by the I-II-III2-IV2 supercomplex.}, journal = {Nature}, volume = {615}, number = {7954}, pages = {934-938}, pmid = {36949187}, issn = {1476-4687}, support = {MR/M00936X/1/MRC_/Medical Research Council/United Kingdom ; MR/T032154/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Cryoelectron Microscopy ; Electron Transport ; *Electron Transport Complex III/chemistry/metabolism/ultrastructure ; *Electron Transport Complex IV/chemistry/metabolism/ultrastructure ; *Mitochondria/chemistry/enzymology/metabolism/ultrastructure ; *Mitochondrial Membranes/chemistry/enzymology/metabolism/ultrastructure ; *Electron Transport Complex II/chemistry/metabolism/ultrastructure ; *Electron Transport Complex I/chemistry/metabolism/ultrastructure ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Molecular Dynamics Simulation ; Binding Sites ; Evolution, Molecular ; }, abstract = {Mitochondrial energy conversion requires an intricate architecture of the inner mitochondrial membrane[1]. Here we show that a supercomplex containing all four respiratory chain components contributes to membrane curvature induction in ciliates. We report cryo-electron microscopy and cryo-tomography structures of the supercomplex that comprises 150 different proteins and 311 bound lipids, forming a stable 5.8-MDa assembly. Owing to subunit acquisition and extension, complex I associates with a complex IV dimer, generating a wedge-shaped gap that serves as a binding site for complex II. Together with a tilted complex III dimer association, it results in a curved membrane region. Using molecular dynamics simulations, we demonstrate that the divergent supercomplex actively contributes to the membrane curvature induction and tubulation of cristae. Our findings highlight how the evolution of protein subunits of respiratory complexes has led to the I-II-III2-IV2 supercomplex that contributes to the shaping of the bioenergetic membrane, thereby enabling its functional specialization.}, } @article {pmid36951086, year = {2023}, author = {Sloan, DB and DeTar, RA and Warren, JM}, title = {Aminoacyl-tRNA Synthetase Evolution within the Dynamic Tripartite Translation System of Plant Cells.}, journal = {Genome biology and evolution}, volume = {15}, number = {4}, pages = {}, pmid = {36951086}, issn = {1759-6653}, mesh = {Animals ; *Amino Acyl-tRNA Synthetases/genetics/metabolism ; Plant Cells/metabolism ; Amino Acid Sequence ; Cytosol/metabolism ; RNA, Transfer/genetics/metabolism ; }, abstract = {Eukaryotes maintain separate protein translation systems for nuclear and organellar genes, including distinct sets of tRNAs and aminoacyl-tRNA synthetases (aaRSs). In animals, mitochondrial-targeted aaRSs are expressed at lower levels and are less conserved in sequence than cytosolic aaRSs involved in translation of nuclear mRNAs, likely reflecting lower translational demands in mitochondria. In plants, translation is further complicated by the presence of plastids, which share most aaRSs with mitochondria. In addition, plant mitochondrial tRNA pools have a dynamic history of gene loss and functional replacement by tRNAs from other compartments. To investigate the consequences of these distinctive features of translation in plants, we analyzed sequence evolution in angiosperm aaRSs. In contrast to previously studied eukaryotic systems, we found that plant organellar and cytosolic aaRSs exhibit only a small difference in expression levels, and organellar aaRSs are slightly more conserved than cytosolic aaRSs. We hypothesize that these patterns result from high translational demands associated with photosynthesis in mature chloroplasts. We also investigated aaRS evolution in Sileneae, an angiosperm lineage with extensive mitochondrial tRNA replacement and aaRS retargeting. We predicted positive selection for changes in aaRS sequence resulting from these recent changes in subcellular localization and tRNA substrates but found little evidence for accelerated sequence divergence. Overall, the complex tripartite translation system in plant cells appears to have imposed more constraints on the long-term evolutionary rates of organellar aaRSs compared with other eukaryotic lineages, and plant aaRS protein sequences appear largely robust to more recent perturbations in subcellular localization and tRNA interactions.}, } @article {pmid36964263, year = {2023}, author = {Jablonski, D and Ribeiro-Júnior, MA and Simonov, E and Šoltys, K and Meiri, S}, title = {A new, rare, small-ranged, and endangered mountain snake of the genus Elaphe from the Southern Levant.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {4839}, pmid = {36964263}, issn = {2045-2322}, mesh = {Animals ; Phylogeny ; *Colubridae ; Mitochondria/genetics ; Lebanon ; Syria ; DNA, Mitochondrial/genetics ; }, abstract = {The genus Elaphe Fitzinger, 1833 includes 17 species of charismatic, large-sized, non-venomous, Eurasian snakes. In the Western Palearctic, the genus is represented by three species from the Elaphe quatuorlineata group ranging from the Apennine peninsula to Central Asia. The southernmost population of this group is distributed in the mountains of the Southern Levant, with more than 400 km gap to other Elaphe populations. This population has been known to science for only 50 years and is virtually unstudied due to its extreme rarity. We studied these snakes' morphological and genetic variation from the three countries where they are known to occur, i.e., Israel (Hermon, the Israeli-controlled Golan Heights), Lebanon, and Syria. We used nine mitochondrial and nuclear genes, complete mitogenome sequences, and a comprehensive morphological examination including published data, our own field observations, and museum specimens, to study its relationship to other species in the group. The three currently recognized species of the group (E. quatuorlineata, E. sauromates, E. urartica), and the Levant population, form four deeply divergent, strongly supported clades. Three of these clades correspond to the abovementioned species while the Southern Levant clade, which is genetically and morphologically distinct from all named congeners, is described here as a new species, Elaphe druzei sp. nov. The basal divergence of this group is estimated to be the Late Miocene with subsequent radiation from 5.1 to 3.9 Mya. The revealed biogeography of the E. quatuorlineata group supports the importance of the Levant as a major center of endemism and diversity of biota in Eurasia. The new species is large-sized and is one of the rarest snakes in the Western Palearctic. Because of its small mountain distribution range, in an area affected by land use and climate change, the new Elaphe urgently needs strict protection. Despite political issues, we hope this will be based on the cooperation of all countries where the new species occurs.}, } @article {pmid36965057, year = {2023}, author = {Speijer, D}, title = {How mitochondria showcase evolutionary mechanisms and the importance of oxygen.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {45}, number = {6}, pages = {e2300013}, doi = {10.1002/bies.202300013}, pmid = {36965057}, issn = {1521-1878}, mesh = {*Biological Evolution ; *Oxygen/metabolism ; Eukaryota/metabolism ; Bacteria/genetics/metabolism ; Mitochondria/metabolism ; }, abstract = {Darwinian evolution can be simply stated: natural selection of inherited variations increasing differential reproduction. However, formulated thus, links with biochemistry, cell biology, ecology, and population dynamics remain unclear. To understand interactive contributions of chance and selection, higher levels of biological organization (e.g., endosymbiosis), complexities of competing selection forces, and emerging biological novelties (such as eukaryotes or meiotic sex), we must analyze actual examples. Focusing on mitochondria, I will illuminate how biology makes sense of life's evolution, and the concepts involved. First, looking at the bacterium - mitochondrion transition: merging with an archaeon, it lost its independence, but played a decisive role in eukaryogenesis, as an extremely efficient aerobic ATP generator and internal ROS source. Second, surveying later mitochondrion adaptations and diversifications illustrates concepts such as constructive neutral evolution, dynamic interactions between endosymbionts and hosts, the contingency of life histories, and metabolic reprogramming. Without oxygen, mitochondria disappear; with (intermittent) oxygen diversification occurs in highly complex ways, especially upon (temporary) phototrophic substrate supply. These expositions show the Darwinian model to be a highly fruitful paradigm.}, } @article {pmid36966978, year = {2023}, author = {Edera, AA and Howell, KA and Nevill, PG and Small, I and Sanchez-Puerta, MV}, title = {Evolution of cox2 introns in angiosperm mitochondria and efficient splicing of an elongated cox2i691 intron.}, journal = {Gene}, volume = {869}, number = {}, pages = {147393}, doi = {10.1016/j.gene.2023.147393}, pmid = {36966978}, issn = {1879-0038}, mesh = {Introns/genetics ; *Magnoliopsida/genetics ; Mitochondria/genetics ; RNA Splicing ; Base Sequence ; }, abstract = {In angiosperms, the mitochondrial cox2 gene harbors up to two introns, commonly referred to as cox2i373 and cox2i691. We studied the cox2 from 222 fully-sequenced mitogenomes from 30 angiosperm orders and analyzed the evolution of their introns. Unlike cox2i373, cox2i691 shows a distribution among plants that is shaped by frequent intron loss events driven by localized retroprocessing. In addition, cox2i691 exhibits sporadic elongations, frequently in domain IV of introns. Such elongations are poorly related to repeat content and two of them showed the presence of LINE transposons, suggesting that increasing intron size is very likely due to nuclear intracelular DNA transfer followed by incorporation into the mitochondrial DNA. Surprisingly, we found that cox2i691 is erroneously annotated as absent in 30 mitogenomes deposited in public databases. Although each of the cox2 introns is ∼1.5 kb in length, a cox2i691 of 4.2 kb has been reported in Acacia ligulata (Fabaceae). It is still unclear whether its unusual length is due to a trans-splicing arrangement or the loss of functionality of the interrupted cox2. Through analyzing short-read RNA sequencing of Acacia with a multi-step computational strategy, we found that the Acacia cox2 is functional and its long intron is spliced in cis in a very efficient manner despite its length.}, } @article {pmid36971557, year = {2023}, author = {Shaliutina-Loginova, A and Francetic, O and Doležal, P}, title = {Bacterial Type II Secretion System and Its Mitochondrial Counterpart.}, journal = {mBio}, volume = {14}, number = {2}, pages = {e0314522}, pmid = {36971557}, issn = {2150-7511}, mesh = {*Type II Secretion Systems/metabolism ; Bacterial Proteins/genetics/metabolism ; Gram-Negative Bacteria/metabolism ; Periplasm/metabolism ; Bacterial Secretion Systems/metabolism ; }, abstract = {Over the billions of years that bacteria have been around, they have evolved several sophisticated protein secretion nanomachines to deliver toxins, hydrolytic enzymes, and effector proteins into their environments. Of these, the type II secretion system (T2SS) is used by Gram-negative bacteria to export a wide range of folded proteins from the periplasm across the outer membrane. Recent findings have demonstrated that components of the T2SS are localized in mitochondria of some eukaryotic lineages, and their behavior is consistent with the presence of a mitochondrial T2SS-derived system (miT2SS). This review focuses on recent advances in the field and discusses open questions concerning the function and evolution of miT2SSs.}, } @article {pmid36972795, year = {2023}, author = {Benites, P and Zaldívar-Riverón, A and Meza-Lázaro, RN and Samacá-Sáenz, E and Gutiérrez-Rodríguez, J and Hernández-López, A}, title = {Multiple introgression events during the diversification history of the edible Mexican grasshopper genus Sphenarium (Orthoptera: Pyrgomorphidae).}, journal = {Molecular phylogenetics and evolution}, volume = {183}, number = {}, pages = {107774}, doi = {10.1016/j.ympev.2023.107774}, pmid = {36972795}, issn = {1095-9513}, mesh = {Animals ; Phylogeny ; *Grasshoppers/genetics ; Mexico ; DNA, Mitochondrial/genetics/chemistry ; Mitochondria/genetics ; }, abstract = {Speciation with gene flow often leads to ambiguous phylogenetic reconstructions, reticulate patterns of relatedness and conflicting nuclear versus mitochondrial (mt) lineages. Here we employed a fragment of the COI mtDNA gene and nuclear genome-wide data (3RAD) to assess the diversification history of Sphenarium, an orthopteran genus of great economic importance in Mexico that is presumed to have experienced hybridisation events in some of its species. We carried out separate phylogenetic analyses to evaluate the existence of mito-nuclear discordance in the species relationships, and also assessed the genomic diversity and population genomic structure and investigated the existence of interspecific introgression and species limits of the taxa involved based on the nuclear dataset. The species delineation analyses discriminated all the currently recognised species, but also supported the existence of four undescribed species. The mt and nuclear topologies had four discordant species relationships that can be explained by mt introgression, where the mt haplotypes of S. purpurascens appear to have replaced those of S. purpurascens A and B, S. variabile and S. zapotecum. Moreover, our analyses supported the existence of nuclear introgression events between four species pairs that are distributed in the Sierra Madre del Sur province in southeast Mexico, with three of them occurring in the Tehuantepec Isthmus region. Our study highlights the relevance of genomic data to address the relative importance of allopatric isolation versus gene flow in speciation.}, } @article {pmid36977381, year = {2023}, author = {Michels, PAM and Ginger, ML}, title = {Evolution: 'Millefoglie' origin of mitochondrial cristae.}, journal = {Current biology : CB}, volume = {33}, number = {6}, pages = {R219-R221}, doi = {10.1016/j.cub.2023.02.037}, pmid = {36977381}, issn = {1879-0445}, mesh = {*Mitochondria/genetics/metabolism ; *Mitochondrial Proteins/genetics/metabolism ; Mitochondrial Membranes/metabolism ; }, abstract = {Striated intracytoplasmic membranes in alphaproteobacteria are often reminiscent of millefoglie pastries. A new study reveals a protein complex homologous to that responsible for mitochondrial cristae formation drives intracytoplasmic membrane formation, thereby establishing bacterial ancestry for the biogenesis of mitochondrial cristae.}, } @article {pmid36980901, year = {2023}, author = {Hammar, F and Miller, DL}, title = {Genetic Diversity in the mtDNA of Physarum polycephalum.}, journal = {Genes}, volume = {14}, number = {3}, pages = {}, pmid = {36980901}, issn = {2073-4425}, mesh = {*Physarum polycephalum/genetics ; DNA, Mitochondrial/genetics ; Base Sequence ; Mitochondria/genetics ; Genetic Variation/genetics ; }, abstract = {The mtDNA of the myxomycete Physarum polycephalum can contain as many as 81 genes. These genes can be grouped in three different categories. The first category includes 46 genes that are classically found on the mtDNA of many organisms. However, 43 of these genes are cryptogenes that require a unique type of RNA editing (MICOTREM). A second category of gene is putative protein-coding genes represented by 26 significant open reading frames. However, these genes do not appear to be transcribed during the growth of the plasmodium and are currently unassigned since they do not have any apparent similarity to other classical mitochondrial protein-coding genes. The third category of gene is found in the mtDNA of some strains of P. polycephalum. These genes derive from a linear mitochondrial plasmid with nine significant, but unassigned, open reading frames which can integrate into the mitochondrial DNA by recombination. Here, we review the mechanism and evolution of the RNA editing necessary for cryptogene expression, discuss possible origins for the 26 unassigned open reading frames based on tentative identification of their protein product, and discuss the implications to mtDNA structure and replication of the integration of the linear mitochondrial plasmid.}, } @article {pmid36981035, year = {2023}, author = {Kundu, S and Kamalakannan, M and Mukherjee, T and Banerjee, D and Kim, HW}, title = {Genetic Characterization and Insular Habitat Enveloping of Endangered Leaf-Nosed Bat, Hipposideros nicobarulae (Mammalia: Chiroptera) in India: Phylogenetic Inference and Conservation Implication.}, journal = {Genes}, volume = {14}, number = {3}, pages = {}, pmid = {36981035}, issn = {2073-4425}, mesh = {Animals ; *Chiroptera/genetics ; Phylogeny ; Bayes Theorem ; Mammals ; Mitochondria ; }, abstract = {The Nicobar leaf-nosed Bat (Hipposideros nicobarulae) was described in the early 20th century; however, its systematic classification has been debated for over 100 years. This endangered and endemic species has achieved species status through morphological data in the last 10 years. However, the genetic information and phylogenetic relationships of H. nicobarulae remain neglected. The generated mitochondrial cytochrome b gene (mtCytb) sequences (438 bp) of H. nicobarulae contains 53.42-53.65% AT composition and 1.82% variable sites. The studied species, H. nicobarulae maintains an 8.1% to 22.6% genetic distance from other Hipposideros species. The genetic divergence estimated in this study is congruent with the concept of gene speciation in bats. The Bayesian and Maximum-Likelihood phylogenies clearly discriminated all Hipposideros species and showed a sister relationship between H. nicobarulae and H. cf. antricola. Current mtCytb-based investigations of H. nicobarulae have confirmed the species status at the molecular level. Further, the MaxEnt-based species distribution modelling illustrates the most suitable habitat of H. nicobarulae (294 km[2]), of which the majority (171 km[2]) is located on Great Nicobar Island. The present study suggests rigorous sampling across the range, taxonomic coverage, the generation of multiple molecular markers (mitochondrial and nuclear), as well as more ecological information, which will help in understanding population genetic structure, habitat suitability, and the implementation of appropriate conservation action plans for H. nicobarulae and other Hipposideros species.}, } @article {pmid36993903, year = {2023}, author = {Dalle Carbonare, L and Jiménez, JC and Lichtenauer, S and van Veen, H}, title = {Plant responses to limited aeration: Advances and future challenges.}, journal = {Plant direct}, volume = {7}, number = {3}, pages = {e488}, pmid = {36993903}, issn = {2475-4455}, abstract = {Limited aeration that is caused by tissue geometry, diffusion barriers, high elevation, or a flooding event poses major challenges to plants and is often, but not exclusively, associated with low oxygen. These processes span a broad interest in the research community ranging from whole plant and crop responses, post-harvest physiology, plant morphology and anatomy, fermentative metabolism, plant developmental processes, oxygen sensing by ERF-VIIs, gene expression profiles, the gaseous hormone ethylene, and O2 dynamics at cellular resolution. The International Society for Plant Anaerobiosis (ISPA) gathers researchers from all over the world contributing to understand the causes, responses, and consequences of limited aeration in plants. During the 14th ISPA meeting, major research progress was related to the evolution of O2 sensing mechanisms and the intricate network that balances low O2 signaling. Here, the work moved beyond flooding stress and emphasized novel underexplored roles of low O2 and limited aeration in altitude adaptation, fruit development and storage, and the vegetative development of growth apices. Regarding tolerance towards flooding, the meeting stressed the relevance and regulation of developmental plasticity, aerenchyma, and barrier formation to improve internal aeration. Additional newly explored flood tolerance traits concerned resource balance, senescence, and the exploration of natural genetic variation for novel tolerance loci. In this report, we summarize and synthesize the major progress and future challenges for low O2 and aeration research presented at the conference.}, } @article {pmid36994538, year = {2023}, author = {Qiu, L and Dong, J and Li, X and Parey, SH and Tan, K and Orr, M and Majeed, A and Zhang, X and Luo, S and Zhou, X and Zhu, C and Ji, T and Niu, Q and Liu, S and Zhou, X}, title = {Defining honeybee subspecies in an evolutionary context warrants strategized conservation.}, journal = {Zoological research}, volume = {44}, number = {3}, pages = {483-493}, pmid = {36994538}, issn = {2095-8137}, mesh = {Bees/genetics ; Animals ; Phylogeny ; Phenotype ; *Mitochondria ; }, abstract = {Despite the urgent need for conservation consideration, strategic action plans for the preservation of the Asian honeybee, Apis cerana Fabricius, 1793, remain lacking. Both the convergent and divergent adaptations of this widespread insect have led to confusing phenotypical traits and inconsistent infraspecific taxonomy. Unclear subspecies boundaries pose a significant challenge to honeybee conservation efforts, as it is difficult to effectively prioritize conservation targets without a clear understanding of subspecies identities. Here, we investigated genome variations in 362 worker bees representing almost all populations of mainland A. cerana to understand how evolution has shaped its population structure. Whole-genome single nucleotide polymorphisms (SNPs) based on nuclear sequences revealed eight putative subspecies, with all seven peripheral subspecies exhibiting mutually exclusive monophyly and distinct genetic divergence from the widespread central subspecies. Our results demonstrated that most classic morphological traits, including body size, were related to the climatic variables of the local habitats and did not reflect the true evolutionary history of the organism. Thus, such morphological traits were not suitable for subspecific delineation. Conversely, wing vein characters showed relative independence to the environment and supported the subspecies boundaries inferred from nuclear genomes. Mitochondrial phylogeny further indicated that the present subspecies structure was a result of multiple waves of population divergence from a common ancestor. Based on our findings, we propose that criteria for subspecies delineation should be based on evolutionary independence, trait distinction, and geographic isolation. We formally defined and described eight subspecies of mainland A. cerana. Elucidation of the evolutionary history and subspecies boundaries enables a customized conservation strategy for both widespread and endemic honeybee conservation units, guiding colony introduction and breeding.}, } @article {pmid37009644, year = {2023}, author = {Cheng, B and Zhou, M and Tang, T and Hassan, MJ and Zhou, J and Tan, M and Li, Z and Peng, Y}, title = {A Trifolium repens flavodoxin-like quinone reductase 1 (TrFQR1) improves plant adaptability to high temperature associated with oxidative homeostasis and lipids remodeling.}, journal = {The Plant journal : for cell and molecular biology}, volume = {115}, number = {2}, pages = {369-385}, doi = {10.1111/tpj.16230}, pmid = {37009644}, issn = {1365-313X}, support = {sccxtd-2020-16//Sichuan Forage Innovation Team Program/ ; 2022YFH0059//Sichuan Science and Technology Program/ ; }, mesh = {*Trifolium/genetics/metabolism ; Flavodoxin/genetics/metabolism ; Diglycerides/metabolism ; Phylogeny ; Temperature ; Plant Proteins/genetics/metabolism ; Oxidative Stress ; *Arabidopsis/genetics/metabolism ; Homeostasis ; Gene Expression Regulation, Plant ; Plants, Genetically Modified/metabolism ; }, abstract = {Maintenance of stable mitochondrial respiratory chains could enhance adaptability to high temperature, but the potential mechanism was not elucidated clearly in plants. In this study, we identified and isolated a TrFQR1 gene encoding the flavodoxin-like quinone reductase 1 (TrFQR1) located in mitochondria of leguminous white clover (Trifolium repens). Phylogenetic analysis indicated that amino acid sequences of FQR1 in various plant species showed a high degree of similarities. Ectopic expression of TrFQR1 protected yeast (Saccharomyces cerevisiae) from heat damage and toxic levels of benzoquinone, phenanthraquinone and hydroquinone. Transgenic Arabidopsis thaliana and white clover overexpressing TrFQR1 exhibited significantly lower oxidative damage and better photosynthetic capacity and growth than wild-type in response to high-temperature stress, whereas AtFQR1-RNAi A. thaliana showed more severe oxidative damage and growth retardation under heat stress. TrFQR1-transgenic white clover also maintained better respiratory electron transport chain than wild-type plants, as manifested by significantly higher mitochondrial complex II and III activities, alternative oxidase activity, NAD(P)H content, and coenzyme Q10 content in response to heat stress. In addition, overexpression of TrFQR1 enhanced the accumulation of lipids including phosphatidylglycerol, monogalactosyl diacylglycerol, sulfoquinovosyl diacylglycerol and cardiolipin as important compositions of bilayers involved in dynamic membrane assembly in mitochondria or chloroplasts positively associated with heat tolerance. TrFQR1-transgenic white clover also exhibited higher lipids saturation level and phosphatidylcholine:phosphatidylethanolamine ratio, which could be beneficial to membrane stability and integrity during a prolonged period of heat stress. The current study proves that TrFQR1 is essential for heat tolerance associated with mitochondrial respiratory chain, cellular reactive oxygen species homeostasis, and lipids remodeling in plants. TrFQR1 could be selected as a key candidate marker gene to screen heat-tolerant genotypes or develop heat-tolerant crops via molecular-based breeding.}, } @article {pmid37017198, year = {2023}, author = {Parida, M and Gouda, G and Chidambaranathan, P and Umakanta, N and Katara, JL and Sai, CB and Samantaray, S and Patra, BC and Mohapatra, T}, title = {Mitochondrial markers differentiate two distinct phylogenetic groups in indigenous rice landraces of northeast India: an evolutionary insight.}, journal = {Journal of genetics}, volume = {102}, number = {}, pages = {}, pmid = {37017198}, issn = {0973-7731}, mesh = {Phylogeny ; *Oryza/genetics ; India ; }, abstract = {The inheritance of the mitochondria genome and its diversity is unique for genetic and evolutionary studies relative to nuclear genomes. Northeast India and Himalayan regions are considered as one of the centres of indica rice origin. Also, rice diversity in northeast India is very distinct and highly suited for evolutionary studies. Although reports are available on the genetic diversity of indigenous northeast rice landraces, its relationship with the wild relatives is not yet properly explored and understood. In an attempt, mitochondrial markers were used to study the evolutionary relationship between the 68 landraces of northeast India and wild relatives (O. rufipogon and O. nivara) along with IR64 (indica) and Nipponbare (japonica) were taken as reference cultivars. Phylogenetically, the findings include two distinct clusters in the indigenous northeast India landraces representing indica and japonica groups. Further, the wild relatives and ~60% of northeast India landraces were identified to be closely related to the Nipponbare cluster. Besides, landraces of northeast India grouping with the indica group (IR64) are characterized by the absence of wild relatives. This indicates that there are two distinct evolutionary paths in the origin of northeast Indian rice landraces based on mitochondrial markers diversity and it is proposed that the inheritance of mitochondria, mitonuclear genome interactions, and bottleneck events could have genetically separated these two phylogenetically unique groups of northeast rice landraces.}, } @article {pmid37021319, year = {2023}, author = {Grosser, MR and Sites, SK and Murata, MM and Lopez, Y and Chamusco, KC and Love Harriage, K and Grosser, JW and Graham, JH and Gmitter, FG and Chase, CD}, title = {Plant mitochondrial introns as genetic markers - conservation and variation.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1116851}, pmid = {37021319}, issn = {1664-462X}, abstract = {Plant genomes are comprised of nuclear, plastid and mitochondrial components characterized by different patterns of inheritance and evolution. Genetic markers from the three genomes provide complementary tools for investigations of inheritance, genetic relationships and phenotypic contributions. Plant mitochondrial genomes are challenging for universal marker development because they are highly variable in terms of size, gene order and intergenic sequences and highly conserved with respect to protein-coding sequences. PCR amplification of introns with primers that anneal to conserved, flanking exons is effective for the development of polymorphic nuclear genome markers. The potential for plant mitochondrial intron polymorphisms to distinguish between congeneric species or intraspecific varieties has not been systematically investigated and is possibly constrained by requirements for intron secondary structure and interactions with co-evolved organelle intron splicing factors. To explore the potential for broadly applicable plant mitochondrial intron markers, PCR primer sets based upon conserved sequences flanking 11 introns common to seven angiosperm species were tested across a range of plant orders. PCR-amplified introns were screened for indel polymorphisms among a group of cross-compatible Citrus species and relatives; two Raphanus sativus mitotypes; representatives of the two Phaseolus vulgaris gene pools; and congeneric pairs of Cynodon, Cenchrus, Solanum, and Vaccinium species. All introns were successfully amplified from each plant entry. Length polymorphisms distinguishable by gel electrophoresis were common among genera but infrequent within genera. Sequencing of three introns amplified from 16 entries identified additional short indel polymorphisms and nucleotide substitutions that separated Citrus, Cynodon, Cenchrus and Vaccinium congeners, but failed to distinguish Solanum congeners or representatives of the Phaseolus vulgaris major gene pools. The ability of primer sets to amplify a wider range of plant species' introns and the presence of intron polymorphisms that distinguish congeners was confirmed by in silico analysis. While mitochondrial intron variation is limited in comparison to nuclear introns, these exon-based primer sets provide robust tools for the amplification of mitochondrial introns across a wide range of plant species wherein useful polymorphisms can be identified.}, } @article {pmid37023388, year = {2023}, author = {Danial, JSH and Jenner, A and Garcia-Saez, AJ and Cosentino, K}, title = {Real-Time Growth Kinetics Analysis of Macromolecular Assemblies in Cells with Single Molecule Resolution.}, journal = {The journal of physical chemistry. A}, volume = {127}, number = {15}, pages = {3490-3496}, doi = {10.1021/acs.jpca.3c00368}, pmid = {37023388}, issn = {1520-5215}, mesh = {Kinetics ; *Software ; }, abstract = {Single molecule fluorescence microscopy has the unique advantage to provide real-time information on the spatiotemporal assembly of individual protein complexes in cellular membranes. This includes the assembly of proteins into oligomer species of numerous copy numbers. However, there is a need for improved tracing analysis of the real-time growth kinetics of these assemblies in cells with single molecule resolution. Here, we present an automated analysis software to accurately measure the real-time kinetics of assembly of individual high-order oligomer complexes. Our software comes with a simple Graphical User Interface (GUI), is available as a source code and an executable, and can analyze a full data set of several hundred to thousand molecules in less than 2 minutes. Importantly, this software is suitable for the analysis of intracellular protein oligomers, whose stoichiometry is usually more difficult to quantify due to variability in signal detection in the different areas of the cell. We validated our method with simulated ground-truth data and time-lapse images of diffraction-limited oligomeric assemblies of BAX and BAK proteins on mitochondria of cells undergoing apoptosis. Our approach provides the broad community of biologists with a fast, user-friendly tool to trace the compositional evolution of macromolecular assemblies, and potentially model their growth for a deeper understanding of the structural and biophysical mechanisms underlying their functions.}, } @article {pmid37029959, year = {2023}, author = {Galindo, LJ and Prokina, K and Torruella, G and López-García, P and Moreira, D}, title = {Maturases and Group II Introns in the Mitochondrial Genomes of the Deepest Jakobid Branch.}, journal = {Genome biology and evolution}, volume = {15}, number = {4}, pages = {}, pmid = {37029959}, issn = {1759-6653}, mesh = {Humans ; Introns ; Phylogeny ; *Genome, Mitochondrial ; Eukaryota/genetics ; Eukaryotic Cells ; }, abstract = {Ophirinina is a recently described suborder of jakobid protists (Excavata) with only one described species to date, Ophirina amphinema. Despite the acquisition and analysis of massive transcriptomic and mitogenomic sequence data from O. amphinema, its phylogenetic position among excavates remained inconclusive, branching as sister group either to all Jakobida or to all Discoba. From a morphological perspective, it has not only several typical jakobid features but also unusual traits for this group, including the morphology of mitochondrial cristae (sac-shaped to flattened-curved cristae) and the presence of two flagellar vanes. In this study, we have isolated, morphologically characterized, and sequenced genome and transcriptome data of two new Ophirinina species: Ophirina chinija sp. nov. and Agogonia voluta gen. et sp. nov. Ophirina chinija differs from O. amphinema in having rounded cell ends, subapically emerging flagella and a posterior cell protrusion. The much more distantly related A. voluta has several unique ultrastructural characteristics, including sac-shaped mitochondrial cristae and a complex "B" fiber. Phylogenomic analyses with a large conserved-marker dataset supported the monophyly of Ophirina and Agogonia within the Ophirinina and, more importantly, resolved the conflicting position of ophirinids as the sister clade to all other jakobids. The characterization of the mitochondrial genomes showed that Agogonia differs from all known gene-rich jakobid mitogenomes by the presence of two group II introns and their corresponding maturase protein genes. A phylogenetic analysis of the diversity of known maturases confirmed that the Agogonia proteins are highly divergent from each other and define distant families among the prokaryotic and eukaryotic maturases. This opens the intriguing possibility that, compared to other jakobids, Ophirinina may have retained additional mitochondrial elements that may help to understand the early diversification of eukaryotes and the evolution of mitochondria.}, } @article {pmid37039888, year = {2023}, author = {Zuccoli, GS and Nascimento, JM and Moraes-Vieira, PM and Rehen, SK and Martins-de-Souza, D}, title = {Mitochondrial, cell cycle control and neuritogenesis alterations in an iPSC-based neurodevelopmental model for schizophrenia.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {273}, number = {8}, pages = {1649-1664}, pmid = {37039888}, issn = {1433-8491}, support = {2016/04912-2//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2018/14666-4//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2014/21035-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2015/15626-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2017/25588-1//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2019/00098-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2018/01410-1//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Adult ; Humans ; *Schizophrenia/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; Cell Differentiation/genetics ; Reactive Oxygen Species/metabolism ; Proteomics ; Cell Cycle Checkpoints ; Mitochondria/metabolism ; }, abstract = {Schizophrenia is a severe psychiatric disorder of neurodevelopmental origin that affects around 1% of the world's population. Proteomic studies and other approaches have provided evidence of compromised cellular processes in the disorder, including mitochondrial function. Most of the studies so far have been conducted on postmortem brain tissue from patients, and therefore, do not allow the evaluation of the neurodevelopmental aspect of the disorder. To circumvent that, we studied the mitochondrial and nuclear proteomes of neural stem cells (NSCs) and neurons derived from induced pluripotent stem cells (iPSCs) from schizophrenia patients versus healthy controls to assess possible alterations related to energy metabolism and mitochondrial function during neurodevelopment in the disorder. Our results revealed differentially expressed proteins in pathways related to mitochondrial function, cell cycle control, DNA repair and neuritogenesis and their possible implication in key process of neurodevelopment, such as neuronal differentiation and axonal guidance signaling. Moreover, functional analysis of NSCs revealed alterations in mitochondrial oxygen consumption in schizophrenia-derived cells and a tendency of higher levels of intracellular reactive oxygen species (ROS). Hence, this study shows evidence that alterations in important cellular processes are present during neurodevelopment and could be involved with the establishment of schizophrenia, as well as the phenotypic traits observed in adult patients. Neural stem cells (NSCs) and neurons were derived from induced pluripotent stem cells (iPSCs) from schizophrenia patients and controls. Proteomic analyses were performed on the enriched mitochondrial and nuclear fractions of NSCs and neurons. Whole-cell proteomic analysis was also performed in neurons. Our results revealed alteration in proteins related to mitochondrial function, cell cycle control, among others. We also performed energy pathway analysis and reactive oxygen species (ROS) analysis of NSCs, which revealed alterations in mitochondrial oxygen consumption and a tendency of higher levels of intracellular ROS in schizophrenia-derived cells.}, } @article {pmid37042115, year = {2023}, author = {Metcalfe, NB and Bellman, J and Bize, P and Blier, PU and Crespel, A and Dawson, NJ and Dunn, RE and Halsey, LG and Hood, WR and Hopkins, M and Killen, SS and McLennan, D and Nadler, LE and Nati, JJH and Noakes, MJ and Norin, T and Ozanne, SE and Peaker, M and Pettersen, AK and Przybylska-Piech, A and Rathery, A and Récapet, C and Rodríguez, E and Salin, K and Stier, A and Thoral, E and Westerterp, KR and Westerterp-Plantenga, MS and Wojciechowski, MS and Monaghan, P}, title = {Solving the conundrum of intra-specific variation in metabolic rate: A multidisciplinary conceptual and methodological toolkit: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {45}, number = {6}, pages = {e2300026}, doi = {10.1002/bies.202300026}, pmid = {37042115}, issn = {1521-1878}, support = {MC_UU_00014/4/MRC_/Medical Research Council/United Kingdom ; RG/17/12/33167/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Animals ; Humans ; *Basal Metabolism ; Phenotype ; }, abstract = {Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals.}, } @article {pmid37044183, year = {2023}, author = {Chen, H and Huang, L and Yu, J and Miao, Y and Liu, C}, title = {Mitochondrial genome of Artemisia argyi L. suggested conserved mitochondrial protein-coding genes among genera Artemisia, Tanacetum and Chrysanthemum.}, journal = {Gene}, volume = {871}, number = {}, pages = {147427}, doi = {10.1016/j.gene.2023.147427}, pmid = {37044183}, issn = {1879-0038}, mesh = {Humans ; *Genome, Mitochondrial ; *Artemisia/genetics ; *Tanacetum/genetics ; *Chrysanthemum/genetics ; Phylogeny ; Mitochondria/genetics ; Mitochondrial Proteins/genetics ; }, abstract = {BACKGROUND: Artemisia argyi L., also known as mugwort, is a perennial herb whose leaves are commonly used as a source of traditional medicines. However, the evolution and structure of the mitochondrial genome (mitogenome) in A. argyi remain unclear. In this study, the mitogenome of A. argyi was assembled and characterized for the first time.

RESULTS: The mitogenome of A. argyi was a circular molecule of 229,354 bp. It encodes 56 genes, including 33 protein-coding genes (PCGs), 20 tRNA genes, and three rRNA genes, and three pseudogenes. Five trans-spliced introns were observed in three PCGs namely, nad1, nad2 and nad5. Repeat analysis identified 65 SSRs, 14 tandem repeats, and 167 dispersed repeats. The A. argyi mitogenome contains 12 plastid transfer sequences from 79 bp to 2552 bp. Five conserved MTPTs were identified in all 18 Asteraceae species. Comparison of mitogenome between A. argyi and one Artemisia specie and two Chrysanthemum species showed 14 conserved gene clusters. Phylogenetic analysis with organelle genomes of A. argyi and 18 other Anthemideae plants showed inconsistent phylogenetic trees, which implied that the evolutionary rates of PCGs and rrna genes derived from mitochondrion and plastid were incongruent. The Ka/Ks ratio of the 27 shared protein-coding genes in the 18 Anthemideae species are all less than 1 indicating that these genes were under the effect of purifying selection. Lastly, a total of 568 RNA editing sites in PCGs were further identified. The average editing frequency of non-synonymous changes was significantly higher than that of synonymous changes (one-sample Student's t-test, p-values ≤ 0.05) in three tissues (root, leaf and stem).

CONCLUSIONS: In this study, the gene content, genome size, genome comparison, mitochondrial plastid sequences, dN/dS analysis of mitochondrial protein-coding genes, and RNA-editing events in A. argyi mitogenome were determined, providing insights into the phylogenetic relationships of Asteraceae plant.}, } @article {pmid37045317, year = {2022}, author = {Opler, PA and Stout, TL and Back, W and Zhang, J and Cong, Q and Shen, J and Grishin, NV}, title = {DNA barcodes reveal different speciation scenarios in the four North American Anthocharis Boisduval, Rambur, [Duménil] & Graslin, [1833] (Lepidoptera: Pieridae: Pierinae: Anthocharidini) species groups.}, journal = {Zootaxa}, volume = {5194}, number = {4}, pages = {519-539}, doi = {10.11646/zootaxa.5194.4.3}, pmid = {37045317}, issn = {1175-5334}, mesh = {Animals ; *DNA Barcoding, Taxonomic ; *Butterflies/genetics ; DNA, Mitochondrial/genetics ; Mitochondria ; Phylogeny ; }, abstract = {The mitochondrial DNA COI barcode segment sequenced from American Anthocharis specimens across their distribution ranges partitions them into four well-separated species groups and reveals different levels of differentiation within these groups. The lanceolata group experienced the deepest divergence. About 2.7% barcode difference separates the two species: A. lanceolata Lucas, 1852 including A. lanceolata australis (F. Grinnell, 1908), from A. desertolimbus J. Emmel, T. Emmel & Mattoon, 1998. The sara group consists of three species distinctly defined by more than 2% sequence divergence: A. sara Lucas, 1852, A. julia W. H. Edwards, 1872, and A. thoosa (Scudder, 1878). Our treatment is fully consistent with morphological evidence largely based on the characters of fifth instar larvae and pupal cone curvature (Stout, 2005, 2018). In barcodes, it is not possible to see evidence of introgression or hybridization between the three species, and identification by morphology of immature stages always agrees with DNA barcode identification. Interestingly, A. thoosa exhibited the largest intraspecific divergence in DNA barcodes, and several of its metapopulations are identifiable by haplotypes. The cethura group is characterized by the smallest divergence and is best considered as a single species variable in expression of yellow coloration: A cethura C. Felder & R. Felder, 1865. Notably, the most sexually dimorphic subspecies A. cethura morrisoni W. H. Edwards, 1881 is the most distinct by the barcodes. Finally, the midea group barcodes do not always separate A. midea (Hübner, [1809]) and A. limonea (A. Butler, 1871) and we observe gradual accumulation of differences from north (northeastern USA) to south (Hidalgo, Mexico). This barcode gradient suggests a recent origin of the two midea group species and provides another example of vicariant sister species well defined by morphology, ecology and geography, but not necessarily by DNA barcodes.}, } @article {pmid37045318, year = {2022}, author = {Hasan, ME and Hasan, A and Béarez, P and Shen, KN and Chang, CW and Tran, TTV and Golani, D and Al-Saboonchi, A and Siddiqui, PJA and Durand, JD}, title = {Planiliza lauvergnii (Eydoux & Souleyet, 1850), a senior synonym of Planiliza affinis (Günther, 1861) with a re-evaluation of keeled back mullets (Mugiliformes: Mugilidae).}, journal = {Zootaxa}, volume = {5194}, number = {4}, pages = {497-518}, doi = {10.11646/zootaxa.5194.4.2}, pmid = {37045318}, issn = {1175-5334}, mesh = {Animals ; *Smegmamorpha ; Phylogeny ; Fishes/genetics ; Biological Evolution ; Mitochondria ; }, abstract = {The taxonomic status of the keeled back mullets (Teleostei: Mugilidae) has been reinvestigated. Two nominal mugilid species having keeled backs from East Asia: Mugil lauvergnii Eydoux & Souleyet, 1850 and Mugil affinis Günther, 1861 have been re-evaluated through examination of the holotypes and fresh specimens. Comparison of morpho-meristic characters of the holotypes shows that both species are identical. Phylogenetic analysis based on mitochondrial cytochrome c oxidase 1 (CO1) confirmed morphological data by highlighting presence of a single clade from East Asia. Mugil lauvergnii (=Planiliza lauvergnii) is thus the sole keeled back mullet from East Asia and a senior synonym of Mugil affinis (=Planiliza affinis). The taxonomic status of two other keeled back mullets, Planiliza carinata and P. klunzingeri, is also contentious due to their similar morphology. Meristic and morphometric variation as well as sequence divergence between the two species are limited but phylogenetic analyses delineate well-supported clades consistent with biogeography and currently accepted taxonomy. Planiliza carinata and P. klunzingeri share a recent common ancestor in a Maximum Likelihood tree, with separate distribution ranges while P. lauvergnii formed a paraphyletic lineage. Based on present findings, we suggest maintenance of the taxonomic distinction of P. klunzingeri and P. carinata and discuss its evolutionary significance.}, } @article {pmid37063179, year = {2023}, author = {Tyszka, AS and Bretz, EC and Robertson, HM and Woodcock-Girard, MD and Ramanauskas, K and Larson, DA and Stull, GW and Walker, JF}, title = {Characterizing conflict and congruence of molecular evolution across organellar genome sequences for phylogenetics in land plants.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1125107}, pmid = {37063179}, issn = {1664-462X}, abstract = {Chloroplasts and mitochondria each contain their own genomes, which have historically been and continue to be important sources of information for inferring the phylogenetic relationships among land plants. The organelles are predominantly inherited from the same parent, and therefore should exhibit phylogenetic concordance. In this study, we examine the mitochondrion and chloroplast genomes of 226 land plants to infer the degree of similarity between the organelles' evolutionary histories. Our results show largely concordant topologies are inferred between the organelles, aside from four well-supported conflicting relationships that warrant further investigation. Despite broad patterns of topological concordance, our findings suggest that the chloroplast and mitochondrial genomes evolved with significant differences in molecular evolution. The differences result in the genes from the chloroplast and the mitochondrion preferentially clustering with other genes from their respective organelles by a program that automates selection of evolutionary model partitions for sequence alignments. Further investigation showed that changes in compositional heterogeneity are not always uniform across divergences in the land plant tree of life. These results indicate that although the chloroplast and mitochondrial genomes have coexisted for over 1 billion years, phylogenetically, they are still evolving sufficiently independently to warrant separate models of evolution. As genome sequencing becomes more accessible, research into these organelles' evolution will continue revealing insight into the ancient cellular events that shaped not only their history, but the history of plants as a whole.}, } @article {pmid37070190, year = {2023}, author = {Schönherr, S and Weissensteiner, H and Kronenberg, F and Forer, L}, title = {Haplogrep 3 - an interactive haplogroup classification and analysis platform.}, journal = {Nucleic acids research}, volume = {51}, number = {W1}, pages = {W263-W268}, pmid = {37070190}, issn = {1362-4962}, mesh = {Humans ; Phylogeny ; *Software ; *DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Biological Evolution ; }, abstract = {Over the last decade, Haplogrep has become a standard tool for haplogroup classification in the field of human mitochondrial DNA and is widely used by medical, forensic, and evolutionary researchers. Haplogrep scales well for thousands of samples, supports many file formats and provides an intuitive graphical web interface. Nevertheless, the currently available version has limitations when applying it to large biobank-scale data. In this paper, we present a major upgrade to the software by adding (a) haplogroup summary statistics and variant annotations from various publicly available genome databases, (b) an interface to connect new phylogenetic trees, (c) a new state-of-the-art web framework managing large scale data, (d) algorithmic adaptions to improve FASTA classification using BWA-specific alignment rules and (e) a pre-classification quality control step for VCF samples. These improvements will give researchers the opportunity to classify thousands of samples as usual but providing additional ways to investigate the dataset directly in the browser. The web service and its documentation can be accessed freely without any registration at https://haplogrep.i-med.ac.at.}, } @article {pmid37071674, year = {2023}, author = {Libby, E and Kempes, CP and Okie, JG}, title = {Metabolic compatibility and the rarity of prokaryote endosymbioses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {17}, pages = {e2206527120}, pmid = {37071674}, issn = {1091-6490}, mesh = {Phylogeny ; *Symbiosis/genetics ; *Prokaryotic Cells/metabolism ; Eukaryota/genetics ; Eukaryotic Cells/metabolism ; Biological Evolution ; }, abstract = {The evolution of the mitochondria was a significant event that gave rise to the eukaryotic lineage and most large complex life. Central to the origins of the mitochondria was an endosymbiosis between prokaryotes. Yet, despite the potential benefits that can stem from a prokaryotic endosymbiosis, their modern occurrence is exceptionally rare. While many factors may contribute to their rarity, we lack methods for estimating the extent to which they constrain the appearance of a prokaryotic endosymbiosis. Here, we address this knowledge gap by examining the role of metabolic compatibility between a prokaryotic host and endosymbiont. We use genome-scale metabolic flux models from three different collections (AGORA, KBase, and CarveMe) to assess the viability, fitness, and evolvability of potential prokaryotic endosymbioses. We find that while more than half of host-endosymbiont pairings are metabolically viable, the resulting endosymbioses have reduced growth rates compared to their ancestral metabolisms and are unlikely to gain mutations to overcome these fitness differences. In spite of these challenges, we do find that they may be more robust in the face of environmental perturbations at least in comparison with the ancestral host metabolism lineages. Our results provide a critical set of null models and expectations for understanding the forces that shape the structure of prokaryotic life.}, } @article {pmid37072481, year = {2023}, author = {Christinaki, AC and Theelen, B and Zania, A and Coutinho, SDA and Cabañes, JF and Boekhout, T and Kouvelis, VN}, title = {Co-evolution of large inverted repeats and G-quadruplex DNA in fungal mitochondria may facilitate mitogenome stability: the case of Malassezia.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {6308}, pmid = {37072481}, issn = {2045-2322}, mesh = {Humans ; *Malassezia/genetics ; Phylogeny ; *Genome, Mitochondrial/genetics ; *G-Quadruplexes ; Mitochondria/genetics ; DNA ; }, abstract = {Mitogenomes are essential due to their contribution to cell respiration. Recently they have also been implicated in fungal pathogenicity mechanisms. Members of the basidiomycetous yeast genus Malassezia are an important fungal component of the human skin microbiome, linked to various skin diseases, bloodstream infections, and they are increasingly implicated in gut diseases and certain cancers. In this study, the comparative analysis of Malassezia mitogenomes contributed to phylogenetic tree construction for all species. The mitogenomes presented significant size and gene order diversity which correlates to their phylogeny. Most importantly, they showed the inclusion of large inverted repeats (LIRs) and G-quadruplex (G4) DNA elements, rendering Malassezia mitogenomes a valuable test case for elucidating the evolutionary mechanisms responsible for this genome diversity. Both LIRs and G4s coexist and convergently evolved to provide genome stability through recombination. This mechanism is common in chloroplasts but, hitherto, rarely found in mitogenomes.}, } @article {pmid37074804, year = {2023}, author = {Mcguire, JA and Huang, X and Reilly, SB and Iskandar, DT and Wang-Claypool, CY and Werning, S and Chong, RA and Lawalata, SZS and Stubbs, AL and Frederick, JH and Brown, RM and Evans, BJ and Arifin, U and Riyanto, A and Hamidy, A and Arida, E and Koo, MS and Supriatna, J and Andayani, N and Hall, R}, title = {Species Delimitation, Phylogenomics, and Biogeography of Sulawesi Flying Lizards: A Diversification History Complicated by Ancient Hybridization, Cryptic Species, and Arrested Speciation.}, journal = {Systematic biology}, volume = {72}, number = {4}, pages = {885-911}, pmid = {37074804}, issn = {1076-836X}, support = {S10 RR027303/RR/NCRR NIH HHS/United States ; S10 RR029668/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Phylogeny ; Indonesia ; *Lizards/genetics ; Phylogeography ; Genetics, Population ; Genetic Speciation ; }, abstract = {The biota of Sulawesi is noted for its high degree of endemism and for its substantial levels of in situ biological diversification. While the island's long period of isolation and dynamic tectonic history have been implicated as drivers of the regional diversification, this has rarely been tested in the context of an explicit geological framework. Here, we provide a tectonically informed biogeographical framework that we use to explore the diversification history of Sulawesi flying lizards (the Draco lineatus Group), a radiation that is endemic to Sulawesi and its surrounding islands. We employ a framework for inferring cryptic speciation that involves phylogeographic and genetic clustering analyses as a means of identifying potential species followed by population demographic assessment of divergence-timing and rates of bi-directional migration as means of confirming lineage independence (and thus species status). Using this approach, phylogenetic and population genetic analyses of mitochondrial sequence data obtained for 613 samples, a 50-SNP data set for 370 samples, and a 1249-locus exon-capture data set for 106 samples indicate that the current taxonomy substantially understates the true number of Sulawesi Draco species, that both cryptic and arrested speciations have taken place, and that ancient hybridization confounds phylogenetic analyses that do not explicitly account for reticulation. The Draco lineatus Group appears to comprise 15 species-9 on Sulawesi proper and 6 on peripheral islands. The common ancestor of this group colonized Sulawesi ~11 Ma when proto-Sulawesi was likely composed of two ancestral islands, and began to radiate ~6 Ma as new islands formed and were colonized via overwater dispersal. The enlargement and amalgamation of many of these proto-islands into modern Sulawesi, especially during the past 3 Ma, set in motion dynamic species interactions as once-isolated lineages came into secondary contact, some of which resulted in lineage merger, and others surviving to the present. [Genomics; Indonesia; introgression; mitochondria; phylogenetics; phylogeography; population genetics; reptiles.].}, } @article {pmid37077029, year = {2023}, author = {Park, D and Yu, Y and Kim, JH and Lee, J and Park, J and Hong, K and Seo, JK and Lim, C and Min, KT}, title = {Suboptimal Mitochondrial Activity Facilitates Nuclear Heat Shock Responses for Proteostasis and Genome Stability.}, journal = {Molecules and cells}, volume = {46}, number = {6}, pages = {374-386}, pmid = {37077029}, issn = {0219-1032}, mesh = {Humans ; *Proteostasis ; Reactive Oxygen Species/metabolism ; *Heat-Shock Response/genetics ; HSP70 Heat-Shock Proteins/metabolism ; Mitochondria/metabolism ; Nuclear Proteins/metabolism ; Genomic Instability ; }, abstract = {Thermal stress induces dynamic changes in nuclear proteins and relevant physiology as a part of the heat shock response (HSR). However, how the nuclear HSR is fine-tuned for cellular homeostasis remains elusive. Here, we show that mitochondrial activity plays an important role in nuclear proteostasis and genome stability through two distinct HSR pathways. Mitochondrial ribosomal protein (MRP) depletion enhanced the nucleolar granule formation of HSP70 and ubiquitin during HSR while facilitating the recovery of damaged nuclear proteins and impaired nucleocytoplasmic transport. Treatment of the mitochondrial proton gradient uncoupler masked MRP-depletion effects, implicating oxidative phosphorylation in these nuclear HSRs. On the other hand, MRP depletion and a reactive oxygen species (ROS) scavenger non-additively decreased mitochondrial ROS generation during HSR, thereby protecting the nuclear genome from DNA damage. These results suggest that suboptimal mitochondrial activity sustains nuclear homeostasis under cellular stress, providing plausible evidence for optimal endosymbiotic evolution via mitochondria-to-nuclear communication.}, } @article {pmid37082671, year = {2023}, author = {Ibodeng, GO and Uche, IN and Mokua, R and Galo, M and Odigwe, B and Galeas, JN and Dasgupta, S}, title = {A snapshot of lung cancer: where are we now?-a narrative review.}, journal = {Annals of translational medicine}, volume = {11}, number = {6}, pages = {261}, pmid = {37082671}, issn = {2305-5839}, abstract = {BACKGROUND AND OBJECTIVE: The global impact of cancer and cancer-related deaths has been a huge challenge and continues to be a setback in the health sector and beyond even in recent times. Cancer is the second leading cause of death globally with lung cancer (LC) being the second most prevalent malignancy and the leading cause of mortality amongst cancers in men and women worldwide. LC still constitutes a major burden despite recent advances in diagnostic and treatment tools. In this article, we review the trends in LC with an emphasis on non-small cell LC. We aimed to identify nuclear and mitochondrial genetic alterations, microbiome dysbiosis, and their significance in non-small cell LC tumorigenesis as well as its relevance in the future management of LCs.

METHODS: We identified studies for this review by searching the PubMed, Cochrane, Education Resources Information Center (ERIC), and Surveillance, Epidemiology, and End Results (SEER) databases for English-Language articles published from January 1, 2000 through to July 30, 2022, using keywords: lung cancer, non-small cell lung cancer, early detection, treatment, mitochondria, microbiome and epigenetics.

KEY CONTENT AND FINDINGS: This review will highlight the genomic environment, mitochondrial and nuclear alterations that play a role in the etiopathogenesis of LC and its application in the progression as well as management of the disease. We also elaborate on current molecular tumor biomarkers and their therapeutic targets.

CONCLUSIONS: LC remains the leading cause of cancer-related deaths globally with poor prognosis despite available treatment options and even recent advances in both diagnostic tools and management guidelines. Human nuclear and mitochondrial alterations clearly play a role in tumorigenesis and progressive genomic evolution is crucial in the early carcinogenesis of LC which is strongly influenced by host immune surveillance. It is imperative that more research and clinical trials be undertaken to appreciate an in-depth understanding of LC from the molecular level to facilitate the discovery of more targeted therapy and overall better management of LC.}, } @article {pmid37087094, year = {2023}, author = {Carella, F and De Vico, G}, title = {Pathology, epidemiology, and phylogeny of mussel egg disease due to the microsporidian Steinhausia mytilovum (Field, 1924) in the Mediterranean mussel (Mytilus galloprovincialis).}, journal = {Journal of invertebrate pathology}, volume = {198}, number = {}, pages = {107927}, doi = {10.1016/j.jip.2023.107927}, pmid = {37087094}, issn = {1096-0805}, mesh = {Female ; Animals ; *Mytilus/microbiology ; *Microsporidia/genetics ; Phylogeny ; Italy ; Seafood ; }, abstract = {Microsporidia are well known fungal pathogens of aquatic animals. However, the taxonomy of microsporidia is generally poorly resolved, which has consequently constrained our understanding of their pathology and epidemiology in marine animals. To date, microsporidia have been reported in both bivalves and gastropods, and microsporidia from mollusks have been classified in different genera. Despite ongoing work to better describe these genera, including detailed microscopic and ultrastructural images, so far we lack information on microsporidian phylogeny and pathogenicity of species within these genera. Here we investigate the microsporidian parasite Steinhausia mytilovum associated with the mussel, Mytilus galloprovincialis, in natural beds and farms along coast of southern Italy. A survey of M. galloprovincialis was conducted in 13 mussel farms and one natural bed between 2009 and 2020. We found the presence of S. mytilovum in 10 of the investigated farms, with a prevalence ranging between 14 and 100% of female mussels, depending on the population and season in which they were sampled. The parasite developed in the oocytes within a sporophorous vesicle (SV) where it produced 1-3 spores per cell, both in the cytoplasm and in the nucleus. Stenhausia mytilovum elicited an infiltrative (24.8%) or a strong capsular inflammatory response (43.4%) at gonadal follicles and surrounding vesicular connective tissue, in some cases accompanied by gonadal atresia (24.8%), leading to loss of gonadal architecture. In 7% of cases no reaction was observed. Ultrastructural observations revealed a mitochondrial re-organization to interact with all the phases of parasite development; the mitochondria were arranged outside the parasitophorous vesicle (PV) or directly interacting with the spore inside vesicle. There are five taxonomic clades of microsporidians as identified by SSU ribosomal gene sequence data. Maximum likelihood analysis assigned S. mytilovum within the Clade IV, defined as the Class Terresporidia, with closest genetic relationship (83.6% identity) to an undetermined invertebrate ovarian microsporidian. The constant presence, prevalence, and severity of S. mytilovum in coastline populations of M. galloprovincialis populations in southern Italy may indirectly reflect immunocompetence at both individual and population levels.}, } @article {pmid37100315, year = {2023}, author = {Françoso, E and Zuntini, AR and Ricardo, PC and Santos, PKF and de Souza Araujo, N and Silva, JPN and Gonçalves, LT and Brito, R and Gloag, R and Taylor, BA and Harpur, BA and Oldroyd, BP and Brown, MJF and Arias, MC}, title = {Rapid evolution, rearrangements and whole mitogenome duplication in the Australian stingless bees Tetragonula (Hymenoptera: Apidae): A steppingstone towards understanding mitochondrial function and evolution.}, journal = {International journal of biological macromolecules}, volume = {242}, number = {Pt 1}, pages = {124568}, doi = {10.1016/j.ijbiomac.2023.124568}, pmid = {37100315}, issn = {1879-0003}, mesh = {Animals ; Australia ; *Bees/genetics ; *Genome, Mitochondrial/genetics ; Mitochondria/genetics ; Phylogeny ; }, abstract = {The extreme conservation of mitochondrial genomes in metazoans poses a significant challenge to understanding mitogenome evolution. However, the presence of variation in gene order or genome structure, found in a small number of taxa, can provide unique insights into this evolution. Previous work on two stingless bees in the genus Tetragonula (T. carbonaria and T. hockingsi) revealed highly divergent CO1 regions between them and when compared to the bees from the same tribe (Meliponini), indicating rapid evolution. Using mtDNA isolation and Illumina sequencing, we elucidated the mitogenomes of both species. In both species, there has been a duplication of the whole mitogenome to give a total genome size of 30,666 bp in T. carbonaria; and 30,662 bp in T. hockingsi. These duplicated genomes present a circular structure with two identical and mirrored copies of all 13 protein coding genes and 22 tRNAs, with the exception of a few tRNAs that are present as single copies. In addition, the mitogenomes are characterized by rearrangements of two block of genes. We believe that rapid evolution is present in the whole Indo-Malay/Australasian group of Meliponini but is extraordinarily elevated in T. carbonaria and T. hockingsi, probably due to founder effect, low effective population size and the mitogenome duplication. All these features - rapid evolution, rearrangements, and duplication - deviate significantly from the vast majority of the mitogenomes described so far, making the mitogenomes of Tetragonula unique opportunities to address fundamental questions of mitogenome function and evolution.}, } @article {pmid37107542, year = {2023}, author = {De, AK and Sawhney, S and Sunder, J and Muthiyan, R and Ponraj, P and Sujatha, T and Malakar, D and Mondal, S and Bera, AK and Kumar, A and Chakurkar, EB and Bhattacharya, D}, title = {Peeping into Mitochondrial Diversity of Andaman Goats: Unveils Possibility of Maritime Transport with Diversified Geographic Signaling.}, journal = {Genes}, volume = {14}, number = {4}, pages = {}, pmid = {37107542}, issn = {2073-4425}, mesh = {Animals ; Cattle ; Swine ; *Goats/genetics ; Phylogeny ; *DNA, Mitochondrial/genetics ; Sequence Analysis, DNA ; Mitochondria/genetics ; }, abstract = {Andaman and Nicobar Islands, a part of South-East Asia, is enriched with the presence of native breeds of livestock (cattle, pig, goat) and poultry. There are two native goat breeds, viz., Andaman local goat and Teressa goat in Andaman and Nicobar Islands. However, to date, the origin and genetic makeup of these two breeds have not been detailed. Therefore, the present study describes the genetic makeup of Andaman goats through analysis of mitochondrial D-loop sequence for sequence polymorphism, phylogeographical signaling and population expansion events. The genetic diversity of the Teressa goat was less compared to the Andaman local goat due to its sole presence on Teressa Island. Out of 38 well-defined haplotypes of Andaman goats, the majority of haplotypes belonged to haplogroup A followed by haplogroup B and haplogroup D. The result of mismatch distribution and neutrality tests indicated no population expansion event of haplogroup A and B. Finally, based on poor geographical signaling, we hypothesize that Andaman goats have been imported to these Islands either through multidirectional diffusion or unidirectional diffusion. We justify our hypothesis of multidirectional diffusion on the basis of observation of the haplotype and nucleotide diversity of Andaman goats. Simultaneously, the probability of unidirectional diffusion of goats in these islands from the Indian subcontinent in different spells of domestication events through maritime routes cannot be ignored.}, } @article {pmid37107622, year = {2023}, author = {Li, X and Zhe, M and Huang, Y and Fan, W and Yang, J and Zhu, A}, title = {The Evolution of Mitochondrial Genomes between Two Cymbidium Sister Species: Dozens of Circular Chromosomes and the Maintenance and Deterioration of Genome Synteny.}, journal = {Genes}, volume = {14}, number = {4}, pages = {}, pmid = {37107622}, issn = {2073-4425}, mesh = {*Genome, Mitochondrial/genetics ; Synteny ; Introns ; Chromosomes ; *Orchidaceae ; }, abstract = {Plant mitochondrial genomes (mitogenomes) exhibit fluid genome architectures, which could lead to the rapid erosion of genome synteny over a short evolutionary time scale. Among the species-rich orchid family, the leafy Cymbidium lancifolium and leafless Cymbidium macrorhizon are sister species with remarkable differences in morphology and nutritional physiology. Although our understanding of the evolution of mitochondria is incomplete, these sister taxa are ideal for examining this subject. In this study, the complete mitogenomes of C. lancifolium and C. macrorhizon, totaling 704,244 bp and 650,751 bp, respectively, were assembled. In the 2 mitogenomes, 38 protein-coding genes, 18 cis- and 6 trans-spliced introns, and approximately 611 Kb of homologous sequences are identical; overall, they have 99.4% genome-wide similarity. Slight variations in the mitogenomes of C. lancifolium and C. macrorhizon in repeat content (21.0 Kb and 21.6 Kb, respectively) and mitochondrial DNA of plastid origin (MIPT; 38.2 Kb and 37.5 Kb, respectively) were observed. The mitogenome architectures of C. lancifolium and C. macrorhizon are complex and comprise 23 and 22 mini-circular chromosomes, respectively. Pairwise comparisons indicate that the two mitogenomes are largely syntenic, and the disparity in chromosome numbers is likely due to repeat-mediated rearrangements among different chromosomes. Notably, approximately 93.2 Kb C. lancifolium mitochondrial sequences lack any homology in the C. macrorhizon mitogenome, indicating frequent DNA gains and losses, which accounts mainly for the size variation. Our findings provide unique insights into mitogenome evolution in leafy and leafless plants of sister species and shed light on mitogenome dynamics during the transition from mixotrophy to mycoheterotrophy.}, } @article {pmid37113597, year = {2023}, author = {Mahati, K and Padmasree, K}, title = {Brassinolide promotes interaction between chloroplasts and mitochondria during the optimization of photosynthesis by the mitochondrial electron transport chain in mesophyll cell protoplasts of Arabidopsis thaliana.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1099474}, pmid = {37113597}, issn = {1664-462X}, abstract = {The current experimental data unveils the role of brassinolide (BL), a phytohormone of class brassinosteroids (BRs), in augmenting the cross-talk between the mitochondrial electron transport chain (mETC) and chloroplasts to strengthen the efficiency of the Calvin-Benson cycle (CBC) for higher assimilation of carbon dioxide in the mesophyll cell protoplasts (MCP) of Arabidopsis thaliana. The outcome of total respiration (TR) and photosynthetic carbon assimilation (PCA) was monitored as O2 uptake under dark and NaHCO3-dependent O2 evolution under light, respectively, after pre-incubation of MCP at a broad spectrum of BL concentration from 0.05 pM to 5 pM at 25 °C and optimum light intensity of 1000 μmol m[-2] s[-1]. The addition of optimal concentration (0.5 pM) of BL to MCP stimulated the (i) TR, (ii) PCA, and (iii) para-benzoquinone-dependent O2 evolution (PSII activity). Further, in response to BL, the enzyme activity or transcript levels of redox-regulated CBC enzymes and glucose-6-phosphate raised considerably. Also, the addition of BL to MCP remarkably accelerated the capacity of the cytochrome oxidase (COX) and alternative oxidase (AOX) pathways concurrently with an increase in total cellular pyruvate and reactive oxygen species (ROS) levels. Besides, malate valve components (Malate, Chl-MDH, M-MDH) increased in response to BL. At the same time, the cellular redox ratios of pyridine nucleotides (NADPH and NADH) were kept low in the presence of BL. However, BL could not keep up the CBC activity of photosynthesis along with its associated light-activated enzymes/transcripts when mETC through COX or AOX pathway is restricted by antimycin A (AA) or salicylhydroxamic acid (SHAM), respectively. In contrast, adding BL to MCP under restricted mETC showed aggravation in total cellular ROS, pyruvate, malate, and redox ratio of pyridine nucleotides with a concomitant increase in transcripts associated with malate valve and antioxidant systems. These results suggest that BL enhances the PCA by coordinating in cross-talk of chloroplasts and mitochondria to regulate the cellular redox ratio or ROS through the involvement of COX and AOX pathways along with the malate valve and antioxidant systems.}, } @article {pmid37115919, year = {2023}, author = {Al Jewari, C and Baldauf, SL}, title = {An excavate root for the eukaryote tree of life.}, journal = {Science advances}, volume = {9}, number = {17}, pages = {eade4973}, pmid = {37115919}, issn = {2375-2548}, mesh = {*Eukaryota/genetics ; *Eukaryotic Cells ; Biological Evolution ; Phylogeny ; Evolution, Molecular ; }, abstract = {Much of the higher-order phylogeny of eukaryotes is well resolved, but the root remains elusive. We assembled a dataset of 183 eukaryotic proteins of archaeal ancestry to test this root. The resulting phylogeny identifies four lineages of eukaryotes currently classified as "Excavata" branching separately at the base of the tree. Thus, Parabasalia appear as the first major branch of eukaryotes followed sequentially by Fornicata, Preaxostyla, and Discoba. All four excavate branch points receive full statistical support from analyses with commonly used evolutionary models, a protein structure partition model that we introduce here, and various controls for deep phylogeny artifacts. The absence of aerobic mitochondria in Parabasalia, Fornicata, and Preaxostyla suggests that modern eukaryotes arose under anoxic conditions, probably much earlier than expected, and without the benefit of mitochondrial respiration.}, } @article {pmid37116483, year = {2023}, author = {George, EE and Barcytė, D and Lax, G and Livingston, S and Tashyreva, D and Husnik, F and Lukeš, J and Eliáš, M and Keeling, PJ}, title = {A single cryptomonad cell harbors a complex community of organelles, bacteria, a phage, and selfish elements.}, journal = {Current biology : CB}, volume = {33}, number = {10}, pages = {1982-1996.e4}, doi = {10.1016/j.cub.2023.04.010}, pmid = {37116483}, issn = {1879-0445}, mesh = {*Cryptophyta ; *Genome ; Eukaryota/genetics ; Cell Nucleus/genetics ; Plastids/genetics ; Bacteria/genetics ; Symbiosis/genetics ; Phylogeny ; }, abstract = {Symbiosis between prokaryotes and microbial eukaryotes (protists) has broadly impacted both evolution and ecology. Endosymbiosis led to mitochondria and plastids, the latter spreading across the tree of eukaryotes by subsequent rounds of endosymbiosis. Present-day endosymbionts in protists remain both common and diverse, although what function they serve is often unknown. Here, we describe a highly complex community of endosymbionts and a bacteriophage (phage) within a single cryptomonad cell. Cryptomonads are a model for organelle evolution because their secondary plastid retains a relict endosymbiont nucleus, but only one previously unidentified Cryptomonas strain (SAG 25.80) is known to harbor bacterial endosymbionts. We carried out electron microscopy and FISH imaging as well as genomic sequencing on Cryptomonas SAG 25.80, which revealed a stable, complex community even after over 50 years in continuous cultivation. We identified the host strain as Cryptomonas gyropyrenoidosa, and sequenced genomes from its mitochondria, plastid, and nucleomorph (and partially its nucleus), as well as two symbionts, Megaira polyxenophila and Grellia numerosa, and one phage (MAnkyphage) infecting M. polyxenophila. Comparing closely related endosymbionts from other hosts revealed similar metabolic and genomic features, with the exception of abundant transposons and genome plasticity in M. polyxenophila from Cryptomonas. We found an abundance of eukaryote-interacting genes as well as many toxin-antitoxin systems, including in the MAnkyphage genome that also encodes several eukaryotic-like proteins. Overall, the Cryptomonas cell is an endosymbiotic conglomeration with seven distinct evolving genomes that all show evidence of inter-lineage conflict but nevertheless remain stable, even after more than 4,000 generations in culture.}, } @article {pmid37126705, year = {2023}, author = {Espino-Sanchez, TJ and Wienkers, H and Marvin, RG and Nalder, SA and García-Guerrero, AE and VanNatta, PE and Jami-Alahmadi, Y and Mixon Blackwell, A and Whitby, FG and Wohlschlegel, JA and Kieber-Emmons, MT and Hill, CP and Sigala, PA}, title = {Direct tests of cytochrome c and c1 functions in the electron transport chain of malaria parasites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {19}, pages = {e2301047120}, pmid = {37126705}, issn = {1091-6490}, support = {P30 GM133894/GM/NIGMS NIH HHS/United States ; T32 DK007115/DK/NIDDK NIH HHS/United States ; R25 HL108828/HL/NHLBI NIH HHS/United States ; R01 GM089778/GM/NIGMS NIH HHS/United States ; U54 DK110858/DK/NIDDK NIH HHS/United States ; R35 GM133764/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cytochromes c ; Electron Transport ; *Parasites ; *Antimalarials ; *Malaria, Falciparum ; Eukaryota ; Cytochromes c1 ; }, abstract = {The mitochondrial electron transport chain (ETC) of Plasmodium malaria parasites is a major antimalarial drug target, but critical cytochrome (cyt) functions remain unstudied and enigmatic. Parasites express two distinct cyt c homologs (c and c-2) with unusually sparse sequence identity and uncertain fitness contributions. P. falciparum cyt c-2 is the most divergent eukaryotic cyt c homolog currently known and has sequence features predicted to be incompatible with canonical ETC function. We tagged both cyt c homologs and the related cyt c1 for inducible knockdown. Translational repression of cyt c and cyt c1 was lethal to parasites, which died from ETC dysfunction and impaired ubiquinone recycling. In contrast, cyt c-2 knockdown or knockout had little impact on blood-stage growth, indicating that parasites rely fully on the more conserved cyt c for ETC function. Biochemical and structural studies revealed that both cyt c and c-2 are hemylated by holocytochrome c synthase, but UV-vis absorbance and EPR spectra strongly suggest that cyt c-2 has an unusually open active site in which heme is stably coordinated by only a single axial amino acid ligand and can bind exogenous small molecules. These studies provide a direct dissection of cytochrome functions in the ETC of malaria parasites and identify a highly divergent Plasmodium cytochrome c with molecular adaptations that defy a conserved role in eukaryotic evolution.}, } @article {pmid37127113, year = {2023}, author = {Hausdorf, B and Xu, J}, title = {Speciation of rock-dwelling snail species: Disjunct ranges and mosaic patterns reveal the importance of long-distance dispersal in Chilostoma (Cingulifera) in the European Southern Alps.}, journal = {Molecular phylogenetics and evolution}, volume = {184}, number = {}, pages = {107788}, doi = {10.1016/j.ympev.2023.107788}, pmid = {37127113}, issn = {1095-9513}, mesh = {Animals ; Phylogeny ; *Snails/genetics ; Europe ; *Mitochondria ; Genetic Variation ; }, abstract = {To better understand the origin of the high diversity and endemism in the Southern Alps of Europe, we investigated the phylogeny and population structure of the rock-dwelling snail group Chilostoma (Cingulifera) in the Southern Alps. We generated genomic ddRAD data and mitochondrial sequences of 104 Cingulifera specimens from 28 populations and 14 other Ariantinae. Until recently, about 30 Cingulifera taxa were classified as subspecies of a single polytypic species. The phylogenetic and population genetic analyses of the ddRAD data and mitochondrial sequences revealed that Cingulifera in the Southern Alps is differentiated into three species. Each of the three Chilostoma (Cingulifera) species occupies disjunct sub-areas, which are separated by areas occupied by other Chilostoma taxa. Neighbouring populations of different species show little or no admixture. Tests indicating that the genetic differentiation of the three Cingulifera taxa cannot be explained by isolation by distance confirmed their species status. The disjunct range patterns demonstrate the importance of stochastic events such as passive long-distance dispersal for the evolution of population structure and speciation in these snails, and of priority effects and ecological competition as important factors influencing species distributions.}, } @article {pmid37141262, year = {2023}, author = {Squires, TE and Rödin-Mörch, P and Formenti, G and Tracey, A and Abueg, L and Brajuka, N and Jarvis, E and Halapi, EC and Melsted, P and Höglund, J and Magnússon, KP}, title = {A chromosome-level genome assembly for the Rock Ptarmigan (Lagopus muta).}, journal = {G3 (Bethesda, Md.)}, volume = {13}, number = {7}, pages = {}, pmid = {37141262}, issn = {2160-1836}, mesh = {Animals ; Female ; *Quail ; *Galliformes/genetics ; Repetitive Sequences, Nucleic Acid ; Chromosomes/genetics ; Genome ; Phylogeny ; }, abstract = {The Rock Ptarmigan (Lagopus muta) is a cold-adapted, largely sedentary, game bird with a Holarctic distribution. The species represents an important example of an organism likely to be affected by ongoing climatic shifts across a disparate range. We provide here a high-quality reference genome and mitogenome for the Rock Ptarmigan assembled from PacBio HiFi and Hi-C sequencing of a female bird from Iceland. The total size of the genome is 1.03 Gb with a scaffold N50 of 71.23 Mb and a contig N50 of 17.91 Mb. The final scaffolds represent all 40 predicted chromosomes, and the mitochondria with a BUSCO score of 98.6%. Gene annotation resulted in 16,078 protein-coding genes out of a total 19,831 predicted (81.08% excluding pseudogenes). The genome included 21.07% repeat sequences, and the average length of genes, exons, and introns were 33605, 394, and 4265 bp, respectively. The availability of a new reference-quality genome will contribute to understanding the Rock Ptarmigan's unique evolutionary history, vulnerability to climate change, and demographic trajectories around the globe while serving as a benchmark for species in the family Phasianidae (order Galliformes).}, } @article {pmid37152468, year = {2023}, author = {Kannan, B and Arumugam, P}, title = {The implication of mitochondrial DNA mutation and dysfunction in periodontal diseases.}, journal = {Journal of Indian Society of Periodontology}, volume = {27}, number = {2}, pages = {126-130}, pmid = {37152468}, issn = {0972-124X}, abstract = {Periodontitis is a chronic oral inflammatory disease that is caused by dental plaque pathogens. Periodontal disease development and evolution are based on the host immune system, humoral and cellular immunity, the integrity of the tissues, and certain endocrine and nutritional factors. Mitochondria are significantly involved in periodontal infections and inflammation, which play a role in the inflammatory response in a variety of ways. In general, oxidative stress causes a stressful environment that subsequently leads to tissue damage and chronic inflammation. Several mutations and alterations in mitochondrial DNA lead the disease to an aggressive condition, by causing dysregulated mitochondrial function. Such mutations are significantly associated with various diseases. Numerous studies indicate chronic periodontitis patients have a decreased level of mitochondrial membrane potential, as well as adenosine triphosphate, and an increased level of reactive oxygen species production, which causes cell death in the periodontium and affects tissue growth. Further studies into the association between mitochondria and periodontitis might be helpful for the treatment and prevention of the diseases.}, } @article {pmid37153218, year = {2023}, author = {Xu, J and Li, B and Jiang, Z and Wang, W and Yang, Y and Yang, M and Ye, X}, title = {Genomic analyses provide insights into the genome evolution and environmental adaptation of the tobacco moth Ephestia elutella.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1187522}, pmid = {37153218}, issn = {1664-042X}, abstract = {Ephestia elutella is a major pest responsible for significant damage to stored tobacco over many years. Here, we conduct a comparative genomic analysis on this pest, aiming to explore the genetic bases of environmental adaptation of this species. We find gene families associated with nutrient metabolism, detoxification, antioxidant defense and gustatory receptors are expanded in the E. elutella genome. Detailed phylogenetic analysis of P450 genes further reveals obvious duplications in the CYP3 clan in E. elutella compared to the closely related species, the Indianmeal moth Plodia interpunctella. We also identify 229 rapidly evolving genes and 207 positively selected genes in E. elutella, respectively, and highlight two positively selected heat shock protein 40 (Hsp40) genes. In addition, we find a number of species-specific genes related to diverse biological processes, such as mitochondria biology and development. These findings advance our understanding of the mechanisms underlying processes of environmental adaptation on E. elutella and will enable the development of novel pest management strategies.}, } @article {pmid37156858, year = {2023}, author = {Smirnova, J and Loerke, J and Kleinau, G and Schmidt, A and Bürger, J and Meyer, EH and Mielke, T and Scheerer, P and Bock, R and Spahn, CMT and Zoschke, R}, title = {Structure of the actively translating plant 80S ribosome at 2.2 Å resolution.}, journal = {Nature plants}, volume = {9}, number = {6}, pages = {987-1000}, pmid = {37156858}, issn = {2055-0278}, support = {416210002//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 221545957//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 394046635//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 421152132//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; ZO 302/5-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB-TRR 175 (A4)//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 956314//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; }, mesh = {Cytosol ; *RNA, Ribosomal/chemistry ; Cryoelectron Microscopy ; Phylogeny ; Models, Molecular ; *Ribosomes/chemistry ; Plants/genetics ; Nicotiana/genetics ; }, abstract = {In plant cells, translation occurs in three compartments: the cytosol, the plastids and the mitochondria. While the structures of the (prokaryotic-type) ribosomes in plastids and mitochondria are well characterized, high-resolution structures of the eukaryotic 80S ribosomes in the cytosol have been lacking. Here the structure of translating tobacco (Nicotiana tabacum) 80S ribosomes was solved by cryo-electron microscopy with a global resolution of 2.2 Å. The ribosome structure includes two tRNAs, decoded mRNA and the nascent peptide chain, thus providing insights into the molecular underpinnings of the cytosolic translation process in plants. The map displays conserved and plant-specific rRNA modifications and the positions of numerous ionic cofactors, and it uncovers the role of monovalent ions in the decoding centre. The model of the plant 80S ribosome enables broad phylogenetic comparisons that reveal commonalities and differences in the ribosomes of plants and those of other eukaryotes, thus putting our knowledge about eukaryotic translation on a firmer footing.}, } @article {pmid37158879, year = {2023}, author = {Shamanskiy, V and Mikhailova, AA and Tretiakov, EO and Ushakova, K and Mikhailova, AG and Oreshkov, S and Knorre, DA and Ree, N and Overdevest, JB and Lukowski, SW and Gostimskaya, I and Yurov, V and Liou, CW and Lin, TK and Kunz, WS and Reymond, A and Mazunin, I and Bazykin, GA and Fellay, J and Tanaka, M and Khrapko, K and Gunbin, K and Popadin, K}, title = {Secondary structure of the human mitochondrial genome affects formation of deletions.}, journal = {BMC biology}, volume = {21}, number = {1}, pages = {103}, pmid = {37158879}, issn = {1741-7007}, support = {DOC 33/FWF_/Austrian Science Fund FWF/Austria ; UL1 TR001873/TR/NCATS NIH HHS/United States ; K23 DC019678/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Genome, Mitochondrial ; Mitochondria ; DNA, Mitochondrial/genetics ; Genome, Human ; Protein Structure, Secondary ; DNA, Single-Stranded ; Mammals ; }, abstract = {BACKGROUND: Aging in postmitotic tissues is associated with clonal expansion of somatic mitochondrial deletions, the origin of which is not well understood. Such deletions are often flanked by direct nucleotide repeats, but this alone does not fully explain their distribution. Here, we hypothesized that the close proximity of direct repeats on single-stranded mitochondrial DNA (mtDNA) might play a role in the formation of deletions.

RESULTS: By analyzing human mtDNA deletions in the major arc of mtDNA, which is single-stranded during replication and is characterized by a high number of deletions, we found a non-uniform distribution with a "hot spot" where one deletion breakpoint occurred within the region of 6-9 kb and another within 13-16 kb of the mtDNA. This distribution was not explained by the presence of direct repeats, suggesting that other factors, such as the spatial proximity of these two regions, can be the cause. In silico analyses revealed that the single-stranded major arc may be organized as a large-scale hairpin-like loop with a center close to 11 kb and contacting regions between 6-9 kb and 13-16 kb, which would explain the high deletion activity in this contact zone. The direct repeats located within the contact zone, such as the well-known common repeat with a first arm at 8470-8482 bp (base pair) and a second arm at 13,447-13,459 bp, are three times more likely to cause deletions compared to direct repeats located outside of the contact zone. A comparison of age- and disease-associated deletions demonstrated that the contact zone plays a crucial role in explaining the age-associated deletions, emphasizing its importance in the rate of healthy aging.

CONCLUSIONS: Overall, we provide topological insights into the mechanism of age-associated deletion formation in human mtDNA, which could be used to predict somatic deletion burden and maximum lifespan in different human haplogroups and mammalian species.}, } @article {pmid37162347, year = {2023}, author = {Ezawa, T and Silvestri, A and Maruyama, H and Tawaraya, K and Suzuki, M and Duan, Y and Turina, M and Lanfranco, L}, title = {Structurally distinct mitoviruses: are they an ancestral lineage of the Mitoviridae exclusive to arbuscular mycorrhizal fungi (Glomeromycotina)?.}, journal = {mBio}, volume = {14}, number = {4}, pages = {e0024023}, pmid = {37162347}, issn = {2150-7511}, mesh = {*Mycorrhizae/genetics ; Symbiosis ; Phylogeny ; Ecosystem ; *Glomeromycota/genetics ; Plants/microbiology ; *RNA Viruses/genetics ; RNA-Dependent RNA Polymerase/genetics ; }, abstract = {Mitoviruses in the family Mitoviridae are the mitochondria-replicating "naked RNA viruses" with genomes encoding only the replicase RNA-dependent RNA polymerase (RdRp) and prevalent across fungi, plants, and invertebrates. Arbuscular mycorrhizal fungi in the subphylum Glomeromycotina are obligate plant symbionts that deliver water and nutrients to the host. We discovered distinct mitoviruses in glomeromycotinian fungi, namely "large duamitovirus," encoding unusually large RdRp with a unique N-terminal motif that is endogenized in some host genomes. More than 400 viral sequences similar to the large duamitoviruses are present in metatranscriptome databases. They are globally distributed in soil ecosystems, consistent with the cosmopolitan distribution of glomeromycotinian fungi, and formed the most basal clade of the Mitoviridae in phylogenetic analysis. Given that glomeromycotinian fungi are the only confirmed hosts of these viruses, we propose the hypothesis that large duamitoviruses are the most ancestral lineage of the Mitoviridae that have been maintained exclusively in glomeromycotinian fungi.}, } @article {pmid37166629, year = {2023}, author = {Agrawal, RK and Majumdar, S}, title = {Evolution: Mitochondrial Ribosomes Across Species.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2661}, number = {}, pages = {7-21}, pmid = {37166629}, issn = {1940-6029}, support = {R01 GM061576/GM/NIGMS NIH HHS/United States ; R01 GM139277/GM/NIGMS NIH HHS/United States ; R01 AI132422/AI/NIAID NIH HHS/United States ; R01 AI155473/AI/NIAID NIH HHS/United States ; }, mesh = {*Mitochondrial Ribosomes/metabolism ; *Mitochondria/genetics/metabolism ; Ribosomes/metabolism ; Eukaryota/genetics/metabolism ; Eukaryotic Cells/metabolism ; Mitochondrial Proteins/metabolism ; Cryoelectron Microscopy ; Ribosomal Proteins/metabolism ; }, abstract = {The ribosome is among the most complex and ancient cellular macromolecular assemblies that plays a central role in protein biosynthesis in all living cells. Its function of translation of genetic information encoded in messenger RNA into protein molecules also extends to subcellular compartments in eukaryotic cells such as apicoplasts, chloroplasts, and mitochondria. The origin of mitochondria is primarily attributed to an early endosymbiotic event between an alpha-proteobacterium and a primitive (archaeal) eukaryotic cell. The timeline of mitochondrial acquisition, the nature of the host, and their diversification have been studied in great detail and are continually being revised as more genomic and structural data emerge. Recent advancements in high-resolution cryo-EM structure determination have provided architectural details of mitochondrial ribosomes (mitoribosomes) from various species, revealing unprecedented diversifications among them. These structures provide novel insights into the evolution of mitoribosomal structure and function. Here, we present a brief overview of the existing mitoribosomal structures in the context of the eukaryotic evolution tree showing their diversification from their last common ancestor.}, } @article {pmid37166631, year = {2023}, author = {Chrzanowska-Lightowlers, ZM and Lightowlers, RN}, title = {Translation in Mitochondrial Ribosomes.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2661}, number = {}, pages = {53-72}, pmid = {37166631}, issn = {1940-6029}, support = {203105/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Mitochondrial Ribosomes/metabolism ; Cryoelectron Microscopy ; *Mitochondria/genetics/metabolism ; Protein Biosynthesis ; Oxidative Phosphorylation ; Mitochondrial Proteins/genetics/metabolism ; }, abstract = {Mitochondrial protein synthesis is essential for the life of aerobic eukaryotes. Without it, oxidative phosphorylation cannot be coupled. Evolution has shaped a battery of factors and machinery that are key to production of just a handful of critical proteins. In this general concept chapter, we attempt to briefly summarize our current knowledge of the overall process in mitochondria from a variety of species, breaking this down to the four parts of translation: initiation, elongation, termination, and recycling. Where appropriate, we highlight differences between species and emphasize gaps in our understanding. Excitingly, with the current revolution in cryoelectron microscopy and mitochondrial genome editing, it is highly likely that many of these gaps will be resolved in the near future. However, the absence of a faithful in vitro reconstituted system to study mitochondrial translation is still problematic.}, } @article {pmid37166639, year = {2023}, author = {Maiti, P and Fontanesi, F}, title = {Metabolic Labeling of Mitochondrial Translation Products in Whole Cells and Isolated Organelles.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2661}, number = {}, pages = {193-215}, pmid = {37166639}, issn = {1940-6029}, mesh = {Animals ; *Protein Biosynthesis ; *Mitochondria/metabolism ; Methionine/metabolism ; Amino Acids/metabolism ; Mitochondrial Proteins/metabolism ; Saccharomyces cerevisiae/genetics ; Mammals/genetics ; }, abstract = {Mitochondria retain their own genome and translational apparatus that is highly specialized in the synthesis of a handful of proteins, essential components of the oxidative phosphorylation system. During evolution, the players and mechanisms involved in mitochondrial translation have acquired some unique features, which we have only partially disclosed. The study of the mitochondrial translation process has been historically hampered by the lack of an in vitro translational system and has largely relied on the analysis of the incorporation rate of radiolabeled amino acids into mitochondrial proteins in cellulo or in organello. In this chapter, we describe methods to monitor mitochondrial translation by labeling newly synthesized mitochondrial polypeptides with [S[35]]-methionine in either yeast or mammalian whole cells or isolated mitochondria.}, } @article {pmid37171259, year = {2023}, author = {Dowling, DK and Wolff, JN}, title = {Evolutionary genetics of the mitochondrial genome: insights from Drosophila.}, journal = {Genetics}, volume = {224}, number = {3}, pages = {}, pmid = {37171259}, issn = {1943-2631}, mesh = {Animals ; *Drosophila/genetics ; *Genome, Mitochondrial ; Eukaryota/genetics ; Mitochondria/genetics ; Oxidative Phosphorylation ; DNA, Mitochondrial ; }, abstract = {Mitochondria are key to energy conversion in virtually all eukaryotes. Intriguingly, despite billions of years of evolution inside the eukaryote, mitochondria have retained their own small set of genes involved in the regulation of oxidative phosphorylation (OXPHOS) and protein translation. Although there was a long-standing assumption that the genetic variation found within the mitochondria would be selectively neutral, research over the past 3 decades has challenged this assumption. This research has provided novel insight into the genetic and evolutionary forces that shape mitochondrial evolution and broader implications for evolutionary ecological processes. Many of the seminal studies in this field, from the inception of the research field to current studies, have been conducted using Drosophila flies, thus establishing the species as a model system for studies in mitochondrial evolutionary biology. In this review, we comprehensively review these studies, from those focusing on genetic processes shaping evolution within the mitochondrial genome, to those examining the evolutionary implications of interactions between genes spanning mitochondrial and nuclear genomes, and to those investigating the dynamics of mitochondrial heteroplasmy. We synthesize the contribution of these studies to shaping our understanding of the evolutionary and ecological implications of mitochondrial genetic variation.}, } @article {pmid37175542, year = {2023}, author = {Ke, SJ and Liu, DK and Tu, XD and He, X and Zhang, MM and Zhu, MJ and Zhang, DY and Zhang, CL and Lan, SR and Liu, ZJ}, title = {Apostasia Mitochondrial Genome Analysis and Monocot Mitochondria Phylogenomics.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37175542}, issn = {1422-0067}, support = {72202200205//Fujian Agriculture and Forestry University/ ; }, mesh = {Phylogeny ; *Genome, Mitochondrial ; Mitochondria/genetics ; RNA, Ribosomal/genetics ; *Orchidaceae/genetics ; }, abstract = {Apostasia shenzhenica belongs to the subfamily Apostasioideae and is a primitive group located at the base of the Orchidaceae phylogenetic tree. However, the A. shenzhenica mitochondrial genome (mitogenome) is still unexplored, and the phylogenetic relationships between monocots mitogenomes remain unexplored. In this study, we discussed the genetic diversity of A. shenzhenica and the phylogenetic relationships within its monocotyledon mitogenome. We sequenced and assembled the complete mitogenome of A. shenzhenica, resulting in a circular mitochondrial draft of 672,872 bp, with an average read coverage of 122× and a GC content of 44.4%. A. shenzhenica mitogenome contained 36 protein-coding genes, 16 tRNAs, two rRNAs, and two copies of nad4L. Repeat sequence analysis revealed a large number of medium and small repeats, accounting for 1.28% of the mitogenome sequence. Selection pressure analysis indicated high mitogenome conservation in related species. RNA editing identified 416 sites in the protein-coding region. Furthermore, we found 44 chloroplast genomic DNA fragments that were transferred from the chloroplast to the mitogenome of A. shenzhenica, with five plastid-derived genes remaining intact in the mitogenome. Finally, the phylogenetic analysis of the mitogenomes from A. shenzhenica and 28 other monocots showed that the evolution and classification of most monocots were well determined. These findings enrich the genetic resources of orchids and provide valuable information on the taxonomic classification and molecular evolution of monocots.}, } @article {pmid37179826, year = {2023}, author = {Casanova, A and Wevers, A and Navarro-Ledesma, S and Pruimboom, L}, title = {Mitochondria: It is all about energy.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1114231}, pmid = {37179826}, issn = {1664-042X}, abstract = {Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron and calcium homeostasis to the production of hormones and neurotransmitters, such as melatonin. They enable and influence communication at all physical levels through interaction with other organelles, the nucleus, and the outside environment. The literature suggests crosstalk mechanisms between mitochondria and circadian clocks, the gut microbiota, and the immune system. They might even be the hub supporting and integrating activity across all these domains. Hence, they might be the (missing) link in both health and disease. Mitochondrial dysfunction is related to metabolic syndrome, neuronal diseases, cancer, cardiovascular and infectious diseases, and inflammatory disorders. In this regard, diseases such as cancer, Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), and chronic pain are discussed. This review focuses on understanding the mitochondrial mechanisms of action that allow for the maintenance of mitochondrial health and the pathways toward dysregulated mechanisms. Although mitochondria have allowed us to adapt to changes over the course of evolution, in turn, evolution has shaped mitochondria. Each evolution-based intervention influences mitochondria in its own way. The use of physiological stress triggers tolerance to the stressor, achieving adaptability and resistance. This review describes strategies that could recover mitochondrial functioning in multiple diseases, providing a comprehensive, root-cause-focused, integrative approach to recovering health and treating people suffering from chronic diseases.}, } @article {pmid37188954, year = {2023}, author = {Lee, SY and Cheah, JS and Zhao, B and Xu, C and Roh, H and Kim, CK and Cho, KF and Udeshi, ND and Carr, SA and Ting, AY}, title = {Engineered allostery in light-regulated LOV-Turbo enables precise spatiotemporal control of proximity labeling in living cells.}, journal = {Nature methods}, volume = {20}, number = {6}, pages = {908-917}, pmid = {37188954}, issn = {1548-7105}, support = {R01 DK121409/DK/NIDDK NIH HHS/United States ; RC2 DK129964/DK/NIDDK NIH HHS/United States ; T32 GM007276/GM/NIGMS NIH HHS/United States ; R01 DA026223/DA/NIDA NIH HHS/United States ; }, mesh = {*Proteomics ; *Mitochondria ; Endoplasmic Reticulum ; Biotin ; }, abstract = {The incorporation of light-responsive domains into engineered proteins has enabled control of protein localization, interactions and function with light. We integrated optogenetic control into proximity labeling, a cornerstone technique for high-resolution proteomic mapping of organelles and interactomes in living cells. Through structure-guided screening and directed evolution, we installed the light-sensitive LOV domain into the proximity labeling enzyme TurboID to rapidly and reversibly control its labeling activity with low-power blue light. 'LOV-Turbo' works in multiple contexts and dramatically reduces background in biotin-rich environments such as neurons. We used LOV-Turbo for pulse-chase labeling to discover proteins that traffic between endoplasmic reticulum, nuclear and mitochondrial compartments under cellular stress. We also showed that instead of external light, LOV-Turbo can be activated by bioluminescence resonance energy transfer from luciferase, enabling interaction-dependent proximity labeling. Overall, LOV-Turbo increases the spatial and temporal precision of proximity labeling, expanding the scope of experimental questions that can be addressed with proximity labeling.}, } @article {pmid37198654, year = {2023}, author = {Kienzle, L and Bettinazzi, S and Choquette, T and Brunet, M and Khorami, HH and Jacques, JF and Moreau, M and Roucou, X and Landry, CR and Angers, A and Breton, S}, title = {A small protein coded within the mitochondrial canonical gene nd4 regulates mitochondrial bioenergetics.}, journal = {BMC biology}, volume = {21}, number = {1}, pages = {111}, pmid = {37198654}, issn = {1741-7007}, mesh = {Humans ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial ; HeLa Cells ; Mitochondria/genetics ; Open Reading Frames ; Peptides ; *NADH Dehydrogenase/genetics ; }, abstract = {BACKGROUND: Mitochondria have a central role in cellular functions, aging, and in certain diseases. They possess their own genome, a vestige of their bacterial ancestor. Over the course of evolution, most of the genes of the ancestor have been lost or transferred to the nucleus. In humans, the mtDNA is a very small circular molecule with a functional repertoire limited to only 37 genes. Its extremely compact nature with genes arranged one after the other and separated by short non-coding regions suggests that there is little room for evolutionary novelties. This is radically different from bacterial genomes, which are also circular but much larger, and in which we can find genes inside other genes. These sequences, different from the reference coding sequences, are called alternatives open reading frames or altORFs, and they are involved in key biological functions. However, whether altORFs exist in mitochondrial protein-coding genes or elsewhere in the human mitogenome has not been fully addressed.

RESULTS: We found a downstream alternative ATG initiation codon in the + 3 reading frame of the human mitochondrial nd4 gene. This newly characterized altORF encodes a 99-amino-acid-long polypeptide, MTALTND4, which is conserved in primates. Our custom antibody, but not the pre-immune serum, was able to immunoprecipitate MTALTND4 from HeLa cell lysates, confirming the existence of an endogenous MTALTND4 peptide. The protein is localized in mitochondria and cytoplasm and is also found in the plasma, and it impacts cell and mitochondrial physiology.

CONCLUSIONS: Many human mitochondrial translated ORFs might have so far gone unnoticed. By ignoring mtaltORFs, we have underestimated the coding potential of the mitogenome. Alternative mitochondrial peptides such as MTALTND4 may offer a new framework for the investigation of mitochondrial functions and diseases.}, } @article {pmid37199915, year = {2023}, author = {Begeman, A and Babaian, A and Lewis, SC}, title = {Metatranscriptomic analysis uncovers prevalent viral ORFs compatible with mitochondrial translation.}, journal = {mSystems}, volume = {8}, number = {3}, pages = {e0100222}, pmid = {37199915}, issn = {2379-5077}, support = {R00 GM129456/GM/NIGMS NIH HHS/United States ; R35 GM147218/GM/NIGMS NIH HHS/United States ; T32 GM007232/GM/NIGMS NIH HHS/United States ; R00GM129456/NH/NIH HHS/United States ; }, mesh = {Open Reading Frames ; *RNA Viruses/genetics ; *Viruses/genetics ; Codon ; RNA-Dependent RNA Polymerase/genetics ; }, abstract = {RNA viruses are ubiquitous components of the global virosphere, yet relatively little is known about their genetic diversity or the cellular mechanisms by which they exploit the biology of their diverse eukaryotic hosts. A hallmark of (+)ssRNA (positive single-stranded RNA) viruses is the ability to remodel host endomembranes for their own replication. However, the subcellular interplay between RNA viruses and host organelles that harbor gene expression systems, such as mitochondria, is complex and poorly understood. Here we report the discovery of 763 new virus sequences belonging to the family Mitoviridae by metatranscriptomic analysis, the identification of previously uncharacterized mitovirus clades, and a putative new viral class. With this expanded understanding of the diversity of mitovirus and encoded RNA-dependent RNA polymerases (RdRps), we annotate mitovirus-specific protein motifs and identify hallmarks of mitochondrial translation, including mitochondrion-specific codons. This study expands the known diversity of mitochondrial viruses and provides additional evidence that they co-opt mitochondrial biology for their survival. IMPORTANCE Metatranscriptomic studies have rapidly expanded the cadre of known RNA viruses, yet our understanding of how these viruses navigate the cytoplasmic milieu of their hosts to survive remains poorly characterized. In this study, we identify and assemble 763 new viral sequences belonging to the Mitoviridae, a family of (+)ssRNA viruses thought to interact with and remodel host mitochondria. We exploit this genetic diversity to identify new clades of Mitoviridae, annotate clade-specific sequence motifs that distinguish the mitoviral RdRp, and reveal patterns of RdRp codon usage consistent with translation on host cell mitoribosomes. These results serve as a foundation for understanding how mitoviruses co-opt mitochondrial biology for their proliferation.}, } @article {pmid37208299, year = {2023}, author = {Dapper, AL and Diegel, AE and Wade, MJ}, title = {Relative rates of evolution of male-beneficial nuclear compensatory mutations and male-harming Mother's Curse mitochondrial alleles.}, journal = {Evolution; international journal of organic evolution}, volume = {77}, number = {9}, pages = {1945-1955}, doi = {10.1093/evolut/qpad087}, pmid = {37208299}, issn = {1558-5646}, mesh = {Female ; Animals ; Male ; Humans ; *Mothers ; Alleles ; *Mitochondria/genetics ; Cell Nucleus/genetics ; Mutation ; }, abstract = {Mother's Curse alleles represent a significant source of potential male fitness defects. The maternal inheritance of mutations with the pattern of sex-specific fitness effects, s♀>0>s♂, allows Mother's Curse alleles to spread through a population even though they reduce male fitness. Although the mitochondrial genomes of animals contain only a handful of protein-coding genes, mutations in many of these genes have been shown to have a direct effect on male fertility. The evolutionary process of nuclear compensation is hypothesized to counteract the male-limited mitochondrial defects that spread via Mother's Curse. Here we use population genetic models to investigate the evolution of compensatory autosomal nuclear mutations that act to restore the loss of fitness caused by mitochondrial mutation pressures. We derive the rate of male fitness deterioration by Mother's Curse and the rate of restoration by nuclear compensatory evolution. We find that the rate of nuclear gene compensation is many times slower than that of its deterioration by cytoplasmic mutation pressure, resulting in a significant lag in the recovery of male fitness. Thus, the numbers of nuclear genes capable of restoring male mitochondrial fitness defects must be large in order to sustain male fitness in the face of mutation pressures.}, } @article {pmid37212044, year = {2023}, author = {Postel, Z and Sloan, DB and Gallina, S and Godé, C and Schmitt, E and Mangenot, S and Drouard, L and Varré, JS and Touzet, P}, title = {The decoupled evolution of the organellar genomes of Silene nutans leads to distinct roles in the speciation process.}, journal = {The New phytologist}, volume = {239}, number = {2}, pages = {766-777}, doi = {10.1111/nph.18966}, pmid = {37212044}, issn = {1469-8137}, mesh = {*Silene/genetics ; Plant Breeding ; Cell Nucleus/genetics ; Mitochondria/genetics ; *Genome, Mitochondrial/genetics ; Evolution, Molecular ; Phylogeny ; }, abstract = {There is growing evidence that cytonuclear incompatibilities (i.e. disruption of cytonuclear coadaptation) might contribute to the speciation process. In a former study, we described the possible involvement of plastid-nuclear incompatibilities in the reproductive isolation between four lineages of Silene nutans (Caryophyllaceae). Because organellar genomes are usually cotransmitted, we assessed whether the mitochondrial genome could also be involved in the speciation process, knowing that the gynodioecious breeding system of S. nutans is expected to impact the evolutionary dynamics of this genome. Using hybrid capture and high-throughput DNA sequencing, we analyzed diversity patterns in the genic content of the organellar genomes in the four S. nutans lineages. Contrary to the plastid genome, which exhibited a large number of fixed substitutions between lineages, extensive sharing of polymorphisms between lineages was found in the mitochondrial genome. In addition, numerous recombination-like events were detected in the mitochondrial genome, loosening the linkage disequilibrium between the organellar genomes and leading to decoupled evolution. These results suggest that gynodioecy shaped mitochondrial diversity through balancing selection, maintaining ancestral polymorphism and, thus, limiting the involvement of the mitochondrial genome in evolution of hybrid inviability between S. nutans lineages.}, } @article {pmid37214873, year = {2023}, author = {Cronin, SJF and Yu, W and Hale, A and Licht-Mayer, S and Crabtree, MJ and Korecka, JA and Tretiakov, EO and Sealey-Cardona, M and Somlyay, M and Onji, M and An, M and Fox, JD and Turnes, BL and Gomez-Diaz, C and da Luz Scheffer, D and Cikes, D and Nagy, V and Weidinger, A and Wolf, A and Reither, H and Chabloz, A and Kavirayani, A and Rao, S and Andrews, N and Latremoliere, A and Costigan, M and Douglas, G and Freitas, FC and Pifl, C and Walz, R and Konrat, R and Mahad, DJ and Koslov, AV and Latini, A and Isacson, O and Harkany, T and Hallett, PJ and Bagby, S and Woolf, CJ and Channon, KM and Je, HS and Penninger, JM}, title = {Crucial neuroprotective roles of the metabolite BH4 in dopaminergic neurons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37214873}, issn = {2692-8205}, support = {DOC 33/FWF_/Austrian Science Fund FWF/Austria ; R01 NS112266/NS/NINDS NIH HHS/United States ; R35 NS105076/NS/NINDS NIH HHS/United States ; RG/F/22/110085/BHF_/British Heart Foundation/United Kingdom ; }, abstract = {Dopa-responsive dystonia (DRD) and Parkinson's disease (PD) are movement disorders caused by the dysfunction of nigrostriatal dopaminergic neurons. Identifying druggable pathways and biomarkers for guiding therapies is crucial due to the debilitating nature of these disorders. Recent genetic studies have identified variants of GTP cyclohydrolase-1 (GCH1), the rate-limiting enzyme in tetrahydrobiopterin (BH4) synthesis, as causative for these movement disorders. Here, we show that genetic and pharmacological inhibition of BH4 synthesis in mice and human midbrain-like organoids accurately recapitulates motor, behavioral and biochemical characteristics of these human diseases, with severity of the phenotype correlating with extent of BH4 deficiency. We also show that BH4 deficiency increases sensitivities to several PD-related stressors in mice and PD human cells, resulting in worse behavioral and physiological outcomes. Conversely, genetic and pharmacological augmentation of BH4 protects mice from genetically- and chemically induced PD-related stressors. Importantly, increasing BH4 levels also protects primary cells from PD-affected individuals and human midbrain-like organoids (hMLOs) from these stressors. Mechanistically, BH4 not only serves as an essential cofactor for dopamine synthesis, but also independently regulates tyrosine hydroxylase levels, protects against ferroptosis, scavenges mitochondrial ROS, maintains neuronal excitability and promotes mitochondrial ATP production, thereby enhancing mitochondrial fitness and cellular respiration in multiple preclinical PD animal models, human dopaminergic midbrain-like organoids and primary cells from PD-affected individuals. Our findings pinpoint the BH4 pathway as a key metabolic program at the intersection of multiple protective mechanisms for the health and function of midbrain dopaminergic neurons, identifying it as a potential therapeutic target for PD.}, } @article {pmid37221210, year = {2023}, author = {Paukszto, Ł and Górski, P and Krawczyk, K and Maździarz, M and Szczecińska, M and Ślipiko, M and Sawicki, J}, title = {The organellar genomes of Pellidae (Marchantiophyta): the evidence of cryptic speciation, conflicting phylogenies and extraordinary reduction of mitogenomes in simple thalloid liverwort lineage.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {8303}, pmid = {37221210}, issn = {2045-2322}, mesh = {*Hepatophyta ; *Genome, Mitochondrial ; Phylogeny ; Mitochondria ; *Genome, Plastid ; *Anemone ; }, abstract = {Organellar genomes of liverworts are considered as one of the most stable among plants, with rare events of gene loss and structural rearrangements. However, not all lineages of liverworts are equally explored in the field of organellar genomics, and subclass Pellidae is one of the less known. Hybrid assembly, using both short- and long-read technologies enabled the assembly of repeat-rich mitogenomes of Pellia and Apopellia revealing extraordinary reduction of length in the latter which impacts only intergenic spacers. The mitogenomes of Apopellia were revealed to be the smallest among all known liverworts-109 k bp, despite retaining all introns. The study also showed the loss of one tRNA gene in Apopellia mitogenome, although it had no impact on the codon usage pattern of mitochondrial protein coding genes. Moreover, it was revealed that Apopellia and Pellia differ in codon usage by plastome CDSs, despite identical tRNA gene content. Molecular identification of species is especially important where traditional taxonomic methods fail, especially within Pellidae where cryptic speciation is well recognized. The simple morphology of these species and a tendency towards environmental plasticity make them complicated in identification. Application of super-barcodes, based on complete mitochondrial or plastid genomes sequences enable identification of all cryptic lineages within Apopellia and Pellia genera, however in some particular cases, mitogenomes were more efficient in species delimitation than plastomes.}, } @article {pmid29483657, year = {2018}, author = {Curson, ARJ and Williams, BT and Pinchbeck, BJ and Sims, LP and Martínez, AB and Rivera, PPL and Kumaresan, D and Mercadé, E and Spurgin, LG and Carrión, O and Moxon, S and Cattolico, RA and Kuzhiumparambil, U and Guagliardo, P and Clode, PL and Raina, JB and Todd, JD}, title = {DSYB catalyses the key step of dimethylsulfoniopropionate biosynthesis in many phytoplankton.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {430-439}, doi = {10.1038/s41564-018-0119-5}, pmid = {29483657}, issn = {2058-5276}, mesh = {Chloroplasts/*enzymology/genetics/metabolism ; Diatoms/enzymology/genetics ; Dinoflagellida/enzymology/genetics ; Haptophyta/*enzymology/genetics ; Methyltransferases/*genetics/metabolism ; Mitochondria/*enzymology/genetics/metabolism ; Phytoplankton/metabolism ; Sulfonium Compounds/*metabolism ; }, abstract = {Dimethylsulfoniopropionate (DMSP) is a globally important organosulfur molecule and the major precursor for dimethyl sulfide. These compounds are important info-chemicals, key nutrients for marine microorganisms, and are involved in global sulfur cycling, atmospheric chemistry and cloud formation[1-3]. DMSP production was thought to be confined to eukaryotes, but heterotrophic bacteria can also produce DMSP through the pathway used by most phytoplankton [4] , and the DsyB enzyme catalysing the key step of this pathway in bacteria was recently identified [5] . However, eukaryotic phytoplankton probably produce most of Earth's DMSP, yet no DMSP biosynthesis genes have been identified in any such organisms. Here we identify functional dsyB homologues, termed DSYB, in many phytoplankton and corals. DSYB is a methylthiohydroxybutryate methyltransferase enzyme localized in the chloroplasts and mitochondria of the haptophyte Prymnesium parvum, and stable isotope tracking experiments support these organelles as sites of DMSP synthesis. DSYB transcription levels increased with DMSP concentrations in different phytoplankton and were indicative of intracellular DMSP. Identification of the eukaryotic DSYB sequences, along with bacterial dsyB, provides the first molecular tools to predict the relative contributions of eukaryotes and prokaryotes to global DMSP production. Furthermore, evolutionary analysis suggests that eukaryotic DSYB originated in bacteria and was passed to eukaryotes early in their evolution.}, } @article {pmid29486209, year = {2019}, author = {Kenny, NJ and Noreña, C and Damborenea, C and Grande, C}, title = {Probing recalcitrant problems in polyclad evolution and systematics with novel mitochondrial genome resources.}, journal = {Genomics}, volume = {111}, number = {3}, pages = {343-355}, doi = {10.1016/j.ygeno.2018.02.009}, pmid = {29486209}, issn = {1089-8646}, mesh = {Animals ; *Evolution, Molecular ; *Genome, Mitochondrial ; *Phylogeny ; Platyhelminths/classification/*genetics ; }, abstract = {For their apparent morphological simplicity, the Platyhelminthes or "flatworms" are a diverse clade found in a broad range of habitats. Their body plans have however made them difficult to robustly classify. Molecular evidence is only beginning to uncover the true evolutionary history of this clade. Here we present nine novel mitochondrial genomes from the still undersampled orders Polycladida and Rhabdocoela, assembled from short Illumina reads. In particular we present for the first time in the literature the mitochondrial sequence of a Rhabdocoel, Bothromesostoma personatum (Typhloplanidae, Mesostominae). The novel mitochondrial genomes examined generally contained the 36 genes expected in the Platyhelminthes, with all possessing 12 of the 13 protein-coding genes normally found in metazoan mitochondrial genomes (ATP8 being absent from all Platyhelminth mtDNA sequenced to date), along with two ribosomal RNA genes. The majority presented possess 22 transfer RNA genes, and a single tRNA gene was absent from two of the nine assembled genomes. By comparison of mitochondrial gene order and phylogenetic analysis of the protein coding and ribosomal RNA genes contained within these sequences with those of previously sequenced species we are able to gain a firm molecular phylogeny for the inter-relationships within this clade. Our phylogenetic reconstructions, using both nucleotide and amino acid sequences under several models and both Bayesian and Maximum Likelihood methods, strongly support the monophyly of Polycladida, and the monophyly of Acotylea and Cotylea within that clade. They also allow us to speculate on the early emergence of Macrostomida, the monophyly of a "Turbellarian-like" clade, the placement of Rhabditophora, and that of Platyhelminthes relative to the Lophotrochozoa (=Spiralia). The data presented here therefore represent a significant advance in our understanding of platyhelminth phylogeny, and will form the basis of a range of future research in the still-disputed classifications within this taxon.}, } @article {pmid29486692, year = {2017}, author = {Skulachev, MV and Skulachev, VP}, title = {Programmed Aging of Mammals: Proof of Concept and Prospects of Biochemical Approaches for Anti-aging Therapy.}, journal = {Biochemistry. Biokhimiia}, volume = {82}, number = {12}, pages = {1403-1422}, doi = {10.1134/S000629791712001X}, pmid = {29486692}, issn = {1608-3040}, mesh = {Aging/drug effects/*physiology ; Animals ; Antioxidants/pharmacology ; Humans ; Longevity/drug effects ; Mitochondria/metabolism ; Mole Rats ; Plastoquinone/analogs & derivatives/pharmacology ; Reactive Oxygen Species/metabolism ; }, abstract = {(i) In 2015-2017 we compared possible reasons for longevity of two mammalian highly social species, i.e. naked mole rats and humans. We proposed that in both cases longevity is a result of neoteny, prolongation of youth by deceleration of late ontogeny (Skulachev, V. P. (2015) Abst. 11th Conf. on Mitochondrial Physiology (MiP2015), Lucni Bouda, Czech Republic, pp. 64-66; Skulachev, V. P., Holtze, S., Vyssokikh, M. Y., Bakeeva, L. E., Skulachev, M. V., Markov, A. V., Hildebrandt, T. B., and Sadovnichii, V. A. (2017) Physiol. Rev., 97, 699-720). Both naked mole rats and humans strongly decreased the pressure of natural selection, although in two different manners. Naked mole rats preferred an "aristocratic" pathway when reproduction (and, hence, involvement in evolution) is monopolized by the queen and her several husbands. Huge number of subordinates who have no right to take part in reproduction and hence in evolution serves the small queen's family. Humans used an alternative, "democratic" pathway, namely technical progress facilitating adaptation to the changing environmental conditions. This pathway is open to all humankind. (ii) As a result, aging as a mechanism increasing evolvability by means of facilitation of natural selection became unnecessary for naked mole rats and humans due to strong attenuation of this selection. This is apparently why aging became a counterproductive atavism for these two species and was strongly shifted to late ages. This shift is direct evidence of the hypothesis that aging is programmed, being the last step of late ontogeny. (iii) Further deceleration of aging for humans by means of neoteny is unrealistic since the development of neoteny probably takes million years. (iv) However, if biological aging is a program, an alternative and much simpler way to avoid it seems possible. We mean inhibition of an essential step of this program. (v) At present, the most probable scheme of the aging program assumes that it is a mechanism of slow poisoning of an organism by reactive oxygen species produced by mitochondria. If this is the case, a mitochondria-targeted antioxidant might be an inhibitor of the aging program. During the last 12 years, such an antioxidant, namely SkQ1, was synthesized and studied in detail in our group. It consists of plastoquinone and decyltriphenylphosphonium (a penetrating cation responsible for electrophoretic accumulation of SkQ1 in mitochondria). It was shown that long-term treatment with SkQ1 increased the lifespan of plants, fungi, invertebrates, fish, and mammals. Moreover, SkQ1 is effective in the therapy of various age-related diseases. It was also shown that a single SkQ1 injection could save life in certain models of sudden death of animals. (vi) A tentative scheme is proposed considering aging as a process of chronic phenoptosis, which eventually results in initiation of acute phenoptosis and death. This scheme also suggests that under certain conditions chronic phenoptosis can be neutralized by an anti-aging program that is activated by food restriction regarded by an organism as a signal of starvation. As for acute phenoptosis, it is apparently controlled by receptors responsible for measuring key parameters of homeostasis. The first experimental indications have been already obtained indicating that both chronic and acute phenoptosis are suppressed by SkQ1.}, } @article {pmid29487229, year = {2018}, author = {Weiss, AKH and Loeffler, JR and Liedl, KR and Gstach, H and Jansen-Dürr, P}, title = {The fumarylacetoacetate hydrolase (FAH) superfamily of enzymes: multifunctional enzymes from microbes to mitochondria.}, journal = {Biochemical Society transactions}, volume = {46}, number = {2}, pages = {295-309}, doi = {10.1042/BST20170518}, pmid = {29487229}, issn = {1470-8752}, mesh = {Amino Acid Sequence ; Carboxy-Lyases/metabolism ; Humans ; Hydrolases/chemistry/*metabolism ; *Microbiota ; Mitochondria/*enzymology ; Sequence Homology, Amino Acid ; Tyrosine/metabolism ; }, abstract = {Prokaryotic and eukaryotic fumarylacetoacetate hydrolase (FAH) superfamily members, sharing conserved regions that form the so-called FAH-domain, catalyze a remarkable variety of reactions. These enzymes are essential in the metabolic pathways to degrade aromatic compounds in prokaryotes and eukaryotes. It appears that prokaryotic FAH superfamily members evolved mainly to allow microbes to generate energy and useful metabolites from complex carbon sources. We review recent findings, indicating that both prokaryotic and eukaryotic members of the FAH superfamily also display oxaloacetate decarboxylase (ODx) activity. The identification of human FAH domain-containing protein 1 as mitochondrial ODx regulating mitochondrial function supports the new concept that, during evolution, eukaryotic FAH superfamily members have acquired important regulatory functions beyond catabolism of complex carbon sources. Molecular studies on the evolution and function of FAH superfamily members are expected to provide new mechanistic insights in their physiological roles.}, } @article {pmid29491956, year = {2016}, author = {Milani, L and Ghiselli, F and Passamonti, M}, title = {Mitochondrial selfish elements and the evolution of biological novelties.}, journal = {Current zoology}, volume = {62}, number = {6}, pages = {687-697}, pmid = {29491956}, issn = {1674-5507}, abstract = {We report the present knowledge about RPHM21, a novel male-specific mitochondrial protein with a putative role in the paternal inheritance of sperm mitochondria in the Manila clam Ruditapes philippinarum, a species with doubly uniparental inheritance of mitochondria (DUI). We review all the available data on rphm21 transcription and translation, analyze in detail its female counterpart, RPHF22, discuss the homology with RPHM21, the putative function and origin, and analyze their polymorphism. The available evidence is compatible with a viral origin of RPHM21 and supports its activity during spermatogenesis. RPHM21 is progressively accumulated in mitochondria and nuclei of spermatogenic cells, and we hypothesize it can influence mitochondrial inheritance and sexual differentiation. We propose a testable model that describes how the acquisition of selfish features by a mitochondrial lineage might have been responsible for the emergence of DUI, and for the evolution of separate sexes (gonochorism) from hermaphroditism. The appearance of DUI most likely entailed the invasion of at least 1 selfish element, and the extant DUI systems can be seen as resolved conflicts. It was proposed that hermaphroditism was the ancestral condition of bivalves, and a correlation between DUI and gonochorism was documented. We hypothesize that DUI might have driven the shift from hermaphroditism to gonochorism, with androdioecy as transition state. The invasion of sex-ratio distorters and the evolution of suppressors can prompt rapid changes among sex-determination mechanisms, and DUI might have been responsible for one of such changes in some bivalve species. If true, DUI would represent the first animal sex-determination system involving mtDNA-encoded proteins.}, } @article {pmid29495437, year = {2018}, author = {Mansilla, N and Racca, S and Gras, DE and Gonzalez, DH and Welchen, E}, title = {The Complexity of Mitochondrial Complex IV: An Update of Cytochrome c Oxidase Biogenesis in Plants.}, journal = {International journal of molecular sciences}, volume = {19}, number = {3}, pages = {}, pmid = {29495437}, issn = {1422-0067}, mesh = {Animals ; Catalytic Domain ; Electron Transport Complex IV/chemistry/genetics/*metabolism ; *Energy Metabolism ; Enzyme Activation ; Gene Expression Regulation, Plant ; Humans ; Mammals/genetics/metabolism ; Mitochondria/genetics/*metabolism ; Mutation ; Plant Development ; Plant Physiological Phenomena ; Plants/genetics/*metabolism ; Protein Subunits ; Yeasts/genetics/metabolism ; }, abstract = {Mitochondrial respiration is an energy producing process that involves the coordinated action of several protein complexes embedded in the inner membrane to finally produce ATP. Complex IV or Cytochrome c Oxidase (COX) is the last electron acceptor of the respiratory chain, involved in the reduction of O2 to H2O. COX is a multimeric complex formed by multiple structural subunits encoded in two different genomes, prosthetic groups (heme a and heme a3), and metallic centers (CuA and CuB). Tens of accessory proteins are required for mitochondrial RNA processing, synthesis and delivery of prosthetic groups and metallic centers, and for the final assembly of subunits to build a functional complex. In this review, we perform a comparative analysis of COX composition and biogenesis factors in yeast, mammals and plants. We also describe possible external and internal factors controlling the expression of structural proteins and assembly factors at the transcriptional and post-translational levels, and the effect of deficiencies in different steps of COX biogenesis to infer the role of COX in different aspects of plant development. We conclude that COX assembly in plants has conserved and specific features, probably due to the incorporation of a different set of subunits during evolution.}, } @article {pmid29509408, year = {2018}, author = {Wisnovsky, S and Sack, T and Pagliarini, DJ and Laposa, RR and Kelley, SO}, title = {DNA Polymerase θ Increases Mutational Rates in Mitochondrial DNA.}, journal = {ACS chemical biology}, volume = {13}, number = {4}, pages = {900-908}, pmid = {29509408}, issn = {1554-8937}, support = {R01 GM115591/GM/NIGMS NIH HHS/United States ; R01 GM116886/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; DNA Replication ; DNA, Mitochondrial/*genetics ; DNA-Directed DNA Polymerase/*physiology ; Humans ; *Mutation Rate ; Neoplasms/genetics ; Oxidative Stress ; DNA Polymerase theta ; }, abstract = {Replication and maintenance of mitochondrial DNA (mtDNA) is essential for cellular function, yet few DNA polymerases are known to function in mitochondria. Here, we conclusively demonstrate that DNA polymerase θ (Polθ) localizes to mitochondria and explore whether this protein is overexpressed in patient-derived cells and tumors. Polθ appears to play an important role in facilitating mtDNA replication under conditions of oxidative stress, and this error-prone polymerase was found to introduce mutations into mtDNA. In patient-derived cells bearing a pathogenic mtDNA mutation, Polθ expression levels were increased, indicating that the oxidative conditions in these cells promote higher expression levels for Polθ. Heightened Polθ expression levels were also associated with elevated mtDNA mutation rates in a selected panel of human tumor tissues, suggesting that this protein can influence mutational frequencies in tumors. The results reported indicate that the mitochondrial function of Polθ may have relevance to human disease.}, } @article {pmid29511984, year = {2018}, author = {Zhao, YQ and Mu, DL and Wang, D and Han, YL and Hou, CC and Zhu, JQ}, title = {Analysis of the function of KIF3A and KIF3B in the spermatogenesis in Boleophthalmus pectinirostris.}, journal = {Fish physiology and biochemistry}, volume = {44}, number = {3}, pages = {769-788}, pmid = {29511984}, issn = {1573-5168}, support = {No. 31272642//National Natural Science Foundation of China (CN)/ ; No. 2015C110005//Scientific and Technical Project of Ningbo/ ; No.2016A610081//Ningbo Natural Science Foundation/ ; }, mesh = {Animals ; *Fish Proteins/chemistry/genetics/metabolism ; Gills/metabolism ; Kidney/metabolism ; *Kinesins/chemistry/genetics/metabolism ; Liver/metabolism ; Male ; Microscopy, Electron, Transmission ; Muscles/metabolism ; Myocardium/metabolism ; *Perciformes ; Phylogeny ; RNA, Messenger/metabolism ; Sequence Analysis, DNA ; Spermatogenesis/genetics/*physiology ; Spermatozoa/metabolism/ultrastructure ; Spleen/metabolism ; Testis/metabolism ; }, abstract = {Spermatogenesis represents one of the most complicated morphological transformation procedures. During this process, the assembly and maintenance of the flagella and intracellular transport of membrane-bound organelles required KIF3A and KIF3B. Our main goal was to test KIF3A and KIF3B location during spermatogenesis of Boleophthalmus pectinirostris. We cloned complete cDNA of KIF3A/3B from the testis of B. pectinirostris by PCR and rapid amplification of cDNA ends (RACE). The predicted secondary and tertiary structures of B. pectinirostris KIF3A/3B contained three domains: (a) the head region, (b) the stalk region, and (c) the tail region. Real-time quantitative PCR (qPCR) results revealed that KIF3A and KIF3B mRNA were presented in all the tissues examined, with the highest expression seen in the testis. In situ hybridization (ISH) showed that KIF3A and KIF3B were distributed in the periphery of the nuclear in the spermatocyte and the early spermatid. In the late spermatid and mature sperm, the KIF3A and KIF3B mRNA were gradually gathered to one side where the flagella formed. Immunofluorescence (IF) showed that KIF3A, tubulin, and mitochondria were co-localized in different stages during spermiogenesis in B. pectinirostris. The temporal and spatial expression dynamics of KIF3A/3B indicate that KIF3A and KIF3B might be involved in flagellar assembly and maintenance at the mRNA and protein levels. Moreover, these proteins may transport the mitochondria resulting in flagellum formation in B. pectinirostris.}, } @article {pmid29514071, year = {2018}, author = {Zeng, R and Smith, E and Barrientos, A}, title = {Yeast Mitoribosome Large Subunit Assembly Proceeds by Hierarchical Incorporation of Protein Clusters and Modules on the Inner Membrane.}, journal = {Cell metabolism}, volume = {27}, number = {3}, pages = {645-656.e7}, pmid = {29514071}, issn = {1932-7420}, support = {R01 GM112179/GM/NIGMS NIH HHS/United States ; R35 GM118141/GM/NIGMS NIH HHS/United States ; }, mesh = {Membrane Proteins/*metabolism ; Mitochondria/*metabolism ; Mitochondrial Membranes/*metabolism ; Mitochondrial Proteins/*metabolism ; Mitochondrial Ribosomes/*metabolism ; Protein Biosynthesis ; Ribosomal Proteins/*metabolism ; Saccharomyces cerevisiae/*metabolism ; }, abstract = {Mitoribosomes are specialized for the synthesis of hydrophobic membrane proteins encoded by mtDNA, all essential for oxidative phosphorylation. Despite their linkage to human mitochondrial diseases and the recent cryoelectron microscopy reconstruction of yeast and mammalian mitoribosomes, how they are assembled remains obscure. Here, we dissected the yeast mitoribosome large subunit (mtLSU) assembly process by systematic genomic deletion of 44 mtLSU proteins (MRPs). Analysis of the strain collection unveiled 37 proteins essential for functional mtLSU assembly, three of which are critical for mtLSU 21S rRNA stability. Hierarchical cluster analysis of mtLSU subassemblies accumulated in mutant strains revealed co-operative assembly of protein sets forming structural clusters and preassembled modules. It also indicated crucial roles for mitochondrion-specific membrane-binding MRPs in anchoring newly transcribed 21S rRNA to the inner membrane, where assembly proceeds. Our results define the yeast mtLSU assembly landscape in vivo and provide a foundation for studies of mitoribosome assembly across evolution.}, } @article {pmid29515095, year = {2018}, author = {Suwannapoom, C and Wu, YJ and Chen, X and Adeola, AC and Chen, J and Wang, WZ}, title = {Complete mitochondrial genome of the Thai Red Junglefowl (Gallus gallus) and phylogenetic analysis.}, journal = {Zoological research}, volume = {39}, number = {2}, pages = {127-129}, pmid = {29515095}, issn = {2095-8137}, mesh = {Animals ; Chickens/*genetics ; DNA, Mitochondrial/genetics ; Genome/genetics ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics ; Phylogeny ; Thailand ; }, abstract = {In this study, we sequenced the complete mitochondrial genome (mitogenome) of the Thai Red Junglefowl (RJF; Gallus gallus) using the next-generation sequencing (NGS) platform of the Ion Torrent PGM. Samples were taken from Mae Wang District, Chiang Mai Province, northern Thailand. Our data showed the complete mitogenome to be 16 785 bp in length, composed by 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and one control region. The genome nucleotide composition was 30.3% A, 23.7% T, 32.5% C, and 13.5% G, resulting in a high percentage of A+T (50.4%). Phylogenetic analysis revealed that the mitogenome belonged to haplogroup X, whereas those of all domestic chickens belong to haplogroups A to G. This newly released mitogenome sequence will advance further evolutionary and population genetics study of the RJF and domestic chicken. The availability of the G. gallus mitogenome will also contribute to further conservation genetics research of a unique species, listed as 'data deficient' in Thailand.}, } @article {pmid29517737, year = {1986}, author = {Koll, F}, title = {Does nuclear integration of mitochondrial sequences occur during senescence in Podospora?.}, journal = {Nature}, volume = {324}, number = {6097}, pages = {597-599}, doi = {10.1038/324597a0}, pmid = {29517737}, issn = {1476-4687}, abstract = {Observations in various organisms[1-3] suggest that the transfer of mitochondrial DNA sequences to the nucleus has occurred in the course of evolution. Wright and Cummings have reported[4], on the basis of hybridization experiments, that there is such a transposition in the fungus Podospora anserina during senescence[5] (arrest of vegetative growth) which is accompanied by amplification of specific mitochondrial sequences[6-9]. They suggested that this transposition could explain senescence, and, as it could be regularly observed under laboratory conditions, senescence in Podospora could constitute a model system to study the molecular mechanisms of the transfer of DNA sequences from mitochondria to the nucleus. We report here experiments similar to those of Wright and Cummings[4] but include additional critical controls. Our results do not confirm the data of Wright and Cummings; the only positive signals we observed after hybridization of mitochondrial DNA sequences on nuclear DNAs can be attributed to contaminating DNA from mitochondria or plasmids.}, } @article {pmid29521101, year = {2018}, author = {Wyżewski, Z and Gregorczyk, KP and Szczepanowska, J and Szulc-Dąbrowska, L}, title = {Functional role of Hsp60 as a positive regulator of human viral infection progression.}, journal = {Acta virologica}, volume = {62}, number = {1}, pages = {33-40}, doi = {10.4149/av_2018_104}, pmid = {29521101}, issn = {0001-723X}, mesh = {Chaperonin 60/genetics/*metabolism ; HIV Infections/*metabolism ; Hepatitis B/*metabolism ; Humans ; Influenza, Human/*metabolism ; Mitochondrial Proteins/genetics/*metabolism ; }, abstract = {Heat shock proteins (Hsps) are a family of proteins highly conserved in evolution. Members of the Hsp family are mainly responsible for proper protein folding, however they perform many other functions in living organisms. Hsp60 is a molecular chaperone that is present in mitochondria and cytosol of eukaryotic cells, as well as on their surface. It is also found in the extracellular space and in the peripheral blood. Apart from its role in assisting protein folding in cooperation with Hsp10, Hsp60 contributes to regulation of apoptosis, as well as participates in modulation of the immune system activity. Hsp60 may favor oncogenesis by promoting survival or growth of some tumor cell types. Hsp60 is a subject of medical research due to its role in pathogenesis of certain tumors and infectious diseases. In this review we discuss mechanisms by which Hsp60 promotes development and progression of infections caused by three human viruses: hepatitis B virus (HBV), human immunodeficiency virus (HIV) and influenza A virus.}, } @article {pmid29523798, year = {2018}, author = {Fu, YB}, title = {Oat evolution revealed in the maternal lineages of 25 Avena species.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {4252}, pmid = {29523798}, issn = {2045-2322}, mesh = {Avena/*genetics ; *Evolution, Molecular ; Genetic Speciation ; Genome, Chloroplast ; Genome, Mitochondrial ; Ploidies ; Polymorphism, Single Nucleotide ; }, abstract = {Cultivated hexaploid oat has three different sets of nuclear genomes (A, C, D), but its evolutionary history remains elusive. A multiplexed shotgun sequencing procedure was explored to acquire maternal phylogenetic signals from chloroplast and mitochondria genomes of 25 Avena species. Phylogenetic analyses of the acquired organelle SNP data revealed a new maternal pathway towards hexaploids of oat genome evolution involving three diploid species (A. ventricosa, A. canariensis and A. longiglumis) and two tetraploid species (A. insularis and A. agadiriana). Cultivated hexaploid A. sativa acquired its maternal genome from an AC genome tetraploid close to A. insularis. Both AC genome A. insularis and AB genome A. agadiriana obtained a maternal genome from an ancient A, not C, genome diploid close to A. longiglumis. Divergence dating showed the major divergences of C genome species 19.9-21.2 million years ago (Mya), of the oldest A genome A. canariensis 13-15 Mya, and of the clade with hexaploids 8.5-9.5 Mya. These findings not only advance our knowledge on oat genome evolution, but also have implications for oat germplasm conservation and utilization in breeding.}, } @article {pmid29524652, year = {2018}, author = {Berriman, JS and Ellingson, RA and Awbrey, JD and Rico, DM and Valdés, ÁA and Wilson, NG and Aguilar, A and Herbert, DG and Hirano, YM and Trowbridge, CD and Krug, PJ}, title = {A biting commentary: Integrating tooth characters with molecular data doubles known species diversity in a lineage of sea slugs that consume "killer algae".}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {356-370}, pmid = {29524652}, issn = {1095-9513}, support = {R25 GM061331/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bayes Theorem ; Biodiversity ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/genetics ; Eukaryota/*physiology ; Gastropoda/*physiology ; Genetic Variation ; Haplotypes/genetics ; Mitochondria/genetics ; *Phylogeny ; Species Specificity ; Tooth/*physiology ; }, abstract = {Predicting biotic resistance to highly invasive strains of "killer algae" (Caulerpa spp.) requires understanding the diversity and feeding preferences of native consumers, including sea slugs in family Oxynoidae. Past studies reported low algal host specificity for Oxynoe (6 spp.) and Lobiger (4 spp.), but these taxonomically challenging slugs may represent species complexes of unrecognized specialists that prefer different Caulerpa spp. Here, we assess global diversity of these genera by integrating gene sequences with morphological data from microscopic teeth and internal shells, the only hard parts in these soft-bodied invertebrates. Four delimitation methods applied to datasets comprising mtDNA and/or nuclear alleles yielded up to 16 species hypotheses for samples comprising five nominal taxa, including five highly divergent species in Lobiger and five in Oxynoe. Depending on the analysis, a further four to six species were recovered in the O. antillarum-viridis complex, a clade in which mitochondrial divergence was low and nuclear alleles were shared among lineages. Bayesian species delimitation using only morphological data supported most candidate species, however, and integrative analyses combining morphological and genetic data fully supported all complex members. Collectively, our findings double the recognized biodiversity in Oxynoidae, and illustrate the value of including data from traits that mediate fast-evolving ecological interactions during species delimitation. Preference for Caulerpa spp. and radular tooth characteristics covaried among newly delimited species, highlighting an unappreciated degree of host specialization and coevolution in these taxa that may help predict their role in containing outbreaks of invasive algae.}, } @article {pmid29529025, year = {2018}, author = {Tas, D and Stickley, L and Miozzo, F and Koch, R and Loncle, N and Sabado, V and Gnägi, B and Nagoshi, E}, title = {Parallel roles of transcription factors dFOXO and FER2 in the development and maintenance of dopaminergic neurons.}, journal = {PLoS genetics}, volume = {14}, number = {3}, pages = {e1007271}, pmid = {29529025}, issn = {1553-7404}, mesh = {Animals ; Autophagy ; Basic Helix-Loop-Helix Proteins/genetics/*metabolism ; Cell Survival ; Dopaminergic Neurons/*metabolism/*pathology ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; Forkhead Transcription Factors/genetics/*metabolism ; Mitochondria/metabolism ; Mutation ; *Neuroprotection ; Parkinson Disease/metabolism/*pathology ; }, abstract = {Forkhead box (FOXO) proteins are evolutionarily conserved, stress-responsive transcription factors (TFs) that can promote or counteract cell death. Mutations in FOXO genes are implicated in numerous pathologies, including age-dependent neurodegenerative disorders, such as Parkinson's disease (PD). However, the complex regulation and downstream mechanisms of FOXOs present a challenge in understanding their roles in the pathogenesis of PD. Here, we investigate the involvement of FOXO in the death of dopaminergic (DA) neurons, the key pathological feature of PD, in Drosophila. We show that dFOXO null mutants exhibit a selective loss of DA neurons in the subgroup crucial for locomotion, the protocerebral anterior medial (PAM) cluster, during development as well as in adulthood. PAM neuron-targeted adult-restricted knockdown demonstrates that dFOXO in adult PAM neurons tissue-autonomously promotes neuronal survival during aging. We further show that dFOXO and the bHLH-TF 48-related-2 (FER2) act in parallel to protect PAM neurons from different forms of cellular stress. Remarkably, however, dFOXO and FER2 share common downstream processes leading to the regulation of autophagy and mitochondrial morphology. Thus, overexpression of one can rescue the loss of function of the other. These results indicate a role of dFOXO in neuroprotection and highlight the notion that multiple genetic and environmental factors interact to increase the risk of DA neuron degeneration and the development of PD.}, } @article {pmid29529094, year = {2018}, author = {Bourret, TB and Choudhury, RA and Mehl, HK and Blomquist, CL and McRoberts, N and Rizzo, DM}, title = {Multiple origins of downy mildews and mito-nuclear discordance within the paraphyletic genus Phytophthora.}, journal = {PloS one}, volume = {13}, number = {3}, pages = {e0192502}, pmid = {29529094}, issn = {1932-6203}, mesh = {Cell Nucleus/genetics ; Likelihood Functions ; Mitochondria/genetics ; Peronospora/*genetics ; *Phylogeny ; Phytophthora/*genetics ; Plant Diseases/parasitology ; }, abstract = {Phylogenetic relationships between thirteen species of downy mildew and 103 species of Phytophthora (plant-pathogenic oomycetes) were investigated with two nuclear and four mitochondrial loci, using several likelihood-based approaches. Three Phytophthora taxa and all downy mildew taxa were excluded from the previously recognized subgeneric clades of Phytophthora, though all were strongly supported within the paraphyletic genus. Downy mildews appear to be polyphyletic, with graminicolous downy mildews (GDM), brassicolous downy mildews (BDM) and downy mildews with colored conidia (DMCC) forming a clade with the previously unplaced Phytophthora taxon totara; downy mildews with pyriform haustoria (DMPH) were placed in their own clade with affinities to the obligate biotrophic P. cyperi. Results suggest the recognition of four additional clades within Phytophthora, but few relationships between clades could be resolved. Trees containing all twenty extant downy mildew genera were produced by adding partial coverage of seventeen additional downy mildew taxa; these trees supported the monophyly of the BDMs, DMCCs and DMPHs but suggested that the GDMs are paraphyletic in respect to the BDMs or polyphyletic. Incongruence between nuclear-only and mitochondrial-only trees suggests introgression may have occurred between several clades, particularly those containing biotrophs, questioning whether obligate biotrophic parasitism and other traits with polyphyletic distributions arose independently or were horizontally transferred. Phylogenetic approaches may be limited in their ability to resolve some of the complex relationships between the "subgeneric" clades of Phytophthora, which include twenty downy mildew genera and hundreds of species.}, } @article {pmid29530548, year = {2018}, author = {Zhang, P and Liu, Y and Wang, M and Dong, M and Liu, Z and Jia, Z and Wang, W and Zhang, A and Wang, L and Song, L}, title = {Chinese mitten crab (Eriocheir sinensis) iron-sulphur cluster assembly protein 2 (EsIscA2) is differentially regulated after immune and oxidative stress challenges.}, journal = {Developmental and comparative immunology}, volume = {84}, number = {}, pages = {343-352}, doi = {10.1016/j.dci.2018.03.007}, pmid = {29530548}, issn = {1879-0089}, mesh = {Aeromonas hydrophila/*immunology ; Animals ; Arthropod Proteins/genetics/*metabolism ; Brachyura/*physiology ; Cells, Cultured ; Cloning, Molecular ; Gene Expression Regulation ; Gram-Negative Bacterial Infections/*immunology ; Hemocytes/*physiology ; Immunity, Innate/genetics ; Invertebrates ; Iron/metabolism ; Iron-Sulfur Proteins/genetics/*metabolism ; Lipopolysaccharides/immunology ; Mitochondria/*physiology ; Oxidative Stress/genetics ; Protein Binding ; Sequence Alignment ; }, abstract = {Iron-sulphur clusters (ISCs), one of the oldest and most versatile cofactors of proteins, are involved in catalysis reactions, electron transport reactions, regulation processes as well as sensing of ambient conditions. Iron-sulphur cluster assembly protein (IscA) is a scaffold protein member of ISC formation system, which plays a significant role in the assembly and maturation process of ISC proteins. In the present study, the cDNA sequence of iron-sulphur cluster assembly protein 2 (designated as EsIscA2) was cloned from Eriocheir sinensis. The open reading frame (ORF) of EsIscA2 was of 507 bp, encoding a peptide of 168 amino acids with a typically conserved Fe-S domain. A tetrameric form was predicated by the SWISS-MODEL prediction algorithm, and three conserved cysteine residues (Cys-93, Cys-158, Cys-160) from each IscA monomer were predicted to form a 'cysteine pocket'. The deduced amino acid sequence of EsIscA2 shared over 50% similarity with that of other IscAs. EsIscA2 was clustered with IscA2 proteins from invertebrates and vertebrates, indicating that the protein was highly conservative in the evolution. rEsIscA2 exhibited a high iron binding affinity in the concentration ranging from 2 to 200 μM. EsIscA2 transcripts were detected in all the tested tissues including gonad, hemocytes, gill, muscle, heart, hepatopancreas and eyestalk, and EsIscA2 protein was detected in the mitochondria of hemocytes. The highest mRNA expression level of EsIscA2 was detected in muscle and hepatopancreas, which was about 34.66-fold (p < 0.05) and 27.07-fold (p < 0.05) of that in hemocytes, respectively. After Aeromonas hydrophila and lipopolysaccharide (LPS) stimulations, the mRNA expression of EsIscA2 in hemocytes was down-regulated and reached the lowest level at 24 h (0.31-fold, p < 0.05) and 48 h (0.29-fold, p < 0.05) compared to control group, respectively. And the expression of EsIscA2 mRNA in hepatopancreas was repressed from 6 h to 48 h post stimulation (p < 0.05). When the primary cultured crab hemocytes were incubated with different concentrations of H2O2 for 15 min, the expression level of EsIscA2 mRNA was significantly repressed to the 0.34-0.44-fold of that in the control group. After A. hydrophila stimulation, the mRNA expression of EsGrx2 was up-regulated at 3 h (3.22-fold compared to control group, p < 0.05) and reached the peak at 12 h (4.88-fold, p < 0.05). All these results suggested that EsIscA2 had iron-binding capabilities as observed in IscA proteins from other organisms, supporting the role of EsIscA2 as a mitochondrial iron donor for ISC synthesis in Chinese mitten crab. Its differential mRNA expression after immune and oxidative stress challenges suggested the adaptations of ISC synthesis rates to these stress conditions.}, } @article {pmid29531011, year = {2018}, author = {Wolters, JF and Charron, G and Gaspary, A and Landry, CR and Fiumera, AC and Fiumera, HL}, title = {Mitochondrial Recombination Reveals Mito-Mito Epistasis in Yeast.}, journal = {Genetics}, volume = {209}, number = {1}, pages = {307-319}, pmid = {29531011}, issn = {1943-2631}, support = {R01 GM101320/GM/NIGMS NIH HHS/United States ; }, mesh = {DNA, Mitochondrial ; *Epistasis, Genetic ; Genotype ; Haplotypes ; Mitochondria/*genetics ; Quantitative Trait Loci ; *Recombination, Genetic ; Stress, Physiological ; Yeasts/*genetics ; }, abstract = {Genetic variation in mitochondrial DNA (mtDNA) provides adaptive potential although the underlying genetic architecture of fitness components within mtDNAs is not known. To dissect functional variation within mtDNAs, we first identified naturally occurring mtDNAs that conferred high or low fitness in Saccharomyces cerevisiae by comparing growth in strains containing identical nuclear genotypes but different mtDNAs. During respiratory growth under temperature and oxidative stress conditions, mitotype effects were largely independent of nuclear genotypes even in the presence of mito-nuclear interactions. Recombinant mtDNAs were generated to determine fitness components within high- and low-fitness mtDNAs. Based on phenotypic distributions of isogenic strains containing recombinant mtDNAs, we found that multiple loci contributed to mitotype fitness differences. These mitochondrial loci interacted in epistatic, nonadditive ways in certain environmental conditions. Mito-mito epistasis (i.e., nonadditive interactions between mitochondrial loci) influenced fitness in progeny from four different crosses, suggesting that mito-mito epistasis is a widespread phenomenon in yeast and other systems with recombining mtDNAs. Furthermore, we found that interruption of coadapted mito-mito interactions produced recombinant mtDNAs with lower fitness. Our results demonstrate that mito-mito epistasis results in functional variation through mitochondrial recombination in fungi, providing modes for adaptive evolution and the generation of mito-mito incompatibilities.}, } @article {pmid29533769, year = {2018}, author = {Marsit, S and Dion-Côté, AM and Barbash, DA}, title = {Did Mitochondria Kill the Frog?.}, journal = {Developmental cell}, volume = {44}, number = {5}, pages = {539-541}, doi = {10.1016/j.devcel.2018.02.020}, pmid = {29533769}, issn = {1878-1551}, mesh = {*Genome ; Genomics ; Hybridization, Genetic ; Mitochondria ; *Reproductive Isolation ; }, abstract = {Genomic divergence can cause reproductive isolation between species. The molecular mechanisms underlying reproductive isolation can thus reveal which genomic features evolve rapidly and become unstable or incompatible in hybrids. In a recent paper in Nature, Gibeaux et al. (2018) report paternal genome instability and metabolic imbalance in hybrids between frog species.}, } @article {pmid29538419, year = {2018}, author = {Bocak, L and Motyka, M and Bocek, M and Bocakova, M}, title = {Incomplete sclerotization and phylogeny: The phylogenetic classification of Plastocerus (Coleoptera: Elateroidea).}, journal = {PloS one}, volume = {13}, number = {3}, pages = {e0194026}, pmid = {29538419}, issn = {1932-6203}, mesh = {Animals ; Coleoptera/*genetics ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Female ; Luminescence ; Male ; Mitochondria/genetics ; Phylogeny ; }, abstract = {The relationships of the monogeneric family Plastoceridae Crowson, 1972 (Coleoptera: Elateroidea) have remained contentious due to its modified morphology, incorrect information on incomplete metamorphosis of females and the absence of molecular data. We produced the sequences for P. angulosus (Germar, 1844) (the type-species of Plastocerus Schaum, 1852) and performed molecular phylogenetic analyses to estimate its position. The analyses of Elateroidea (186 spp.) and Elateridae (110 spp.) molecular datasets of two mitochondrial and two nuclear gene fragments repeatedly placed Plastocerus Schaum, 1852 in relationships with the elaterid genera Oxynopterus Hope, 1842 and Pectocera Hope, 1842. Alternative topologies were rejected by likelihood tests. Therefore, Plastoceridae Crowson, 1972 are down-ranked to the subfamily Plastocerinae in Elateridae Leach, 1815. We suggest that the morphology-based placement and high rank for some elateroid lineages were inferred from the presence of homoplasies which evolved due to incomplete sclerotization. Distantly related soft-bodied elateroids share freely movable and transverse coxae, a shortened prosternum, and a weakly sclerotized abdomen with free ventrites. Importantly, the apomorphic structures characteristic for their closest relatives, such as the prosternal process, mesoventral cavity, and intercoxal keel in the first abdominal ventrite are regularly absent. Consequently, morphology-based phylogenetic analyses suggest deeply rooted positions for lineages without expressed apomorphic character states. Molecular data represent an independent character system that is not affected by the convergent morphological evolution, and therefore molecular phylogenies can elucidate the relationships of incompletely sclerotized lineages.}, } @article {pmid29540429, year = {2018}, author = {Czarnoleski, M and Labecka, AM and Dragosz-Kluska, D and Pis, T and Pawlik, K and Kapustka, F and Kilarski, WM and Kozłowski, J}, title = {Concerted evolution of body mass and cell size: similar patterns among species of birds (Galliformes) and mammals (Rodentia).}, journal = {Biology open}, volume = {7}, number = {4}, pages = {}, pmid = {29540429}, issn = {2046-6390}, abstract = {Cell size plays a role in body size evolution and environmental adaptations. Addressing these roles, we studied body mass and cell size in Galliformes birds and Rodentia mammals, and collected published data on their genome sizes. In birds, we measured erythrocyte nuclei and basal metabolic rates (BMRs). In birds and mammals, larger species consistently evolved larger cells for five cell types (erythrocytes, enterocytes, chondrocytes, skin epithelial cells, and kidney proximal tubule cells) and evolved smaller hepatocytes. We found no evidence that cell size differences originated through genome size changes. We conclude that the organism-wide coordination of cell size changes might be an evolutionarily conservative characteristic, and the convergent evolutionary body size and cell size changes in Galliformes and Rodentia suggest the adaptive significance of cell size. Recent theory predicts that species evolving larger cells waste less energy on tissue maintenance but have reduced capacities to deliver oxygen to mitochondria and metabolize resources. Indeed, birds with larger size of the abovementioned cell types and smaller hepatocytes have evolved lower mass-specific BMRs. We propose that the inconsistent pattern in hepatocytes derives from the efficient delivery system to hepatocytes, combined with their intense involvement in supracellular function and anabolic activity.}, } @article {pmid29543809, year = {2018}, author = {Abdollahi, N and Albani, A and Anthony, E and Baud, A and Cardon, M and Clerc, R and Czernecki, D and Conte, R and David, L and Delaune, A and Djerroud, S and Fourgoux, P and Guiglielmoni, N and Laurentie, J and Lehmann, N and Lochard, C and Montagne, R and Myrodia, V and Opuu, V and Parey, E and Polit, L and Privé, S and Quignot, C and Ruiz-Cuevas, M and Sissoko, M and Sompairac, N and Vallerix, A and Verrecchia, V and Delarue, M and Guérois, R and Ponty, Y and Sacquin-Mora, S and Carbone, A and Froidevaux, C and Le Crom, S and Lespinet, O and Weigt, M and Abboud, S and Bernardes, J and Bouvier, G and Dequeker, C and Ferré, A and Fuchs, P and Lelandais, G and Poulain, P and Richard, H and Schweke, H and Laine, E and Lopes, A}, title = {Meet-U: Educating through research immersion.}, journal = {PLoS computational biology}, volume = {14}, number = {3}, pages = {e1005992}, pmid = {29543809}, issn = {1553-7358}, mesh = {Computational Biology/*education/*methods ; Humans ; Research/*education ; Research Design ; Students ; Universities ; }, abstract = {We present a new educational initiative called Meet-U that aims to train students for collaborative work in computational biology and to bridge the gap between education and research. Meet-U mimics the setup of collaborative research projects and takes advantage of the most popular tools for collaborative work and of cloud computing. Students are grouped in teams of 4-5 people and have to realize a project from A to Z that answers a challenging question in biology. Meet-U promotes "coopetition," as the students collaborate within and across the teams and are also in competition with each other to develop the best final product. Meet-U fosters interactions between different actors of education and research through the organization of a meeting day, open to everyone, where the students present their work to a jury of researchers and jury members give research seminars. This very unique combination of education and research is strongly motivating for the students and provides a formidable opportunity for a scientific community to unite and increase its visibility. We report on our experience with Meet-U in two French universities with master's students in bioinformatics and modeling, with protein-protein docking as the subject of the course. Meet-U is easy to implement and can be straightforwardly transferred to other fields and/or universities. All the information and data are available at www.meet-u.org.}, } @article {pmid29543844, year = {2018}, author = {Bekker, EI and Karabanov, DP and Galimov, YR and Haag, CR and Neretina, TV and Kotov, AA}, title = {Phylogeography of Daphnia magna Straus (Crustacea: Cladocera) in Northern Eurasia: Evidence for a deep longitudinal split between mitochondrial lineages.}, journal = {PloS one}, volume = {13}, number = {3}, pages = {e0194045}, pmid = {29543844}, issn = {1932-6203}, mesh = {Animals ; Cell Lineage/*genetics ; Cladocera/*genetics ; DNA, Mitochondrial/genetics ; Daphnia/*genetics ; Europe ; Asia, Eastern ; Haplotypes/genetics ; Lakes ; Mitochondria/*genetics ; North America ; Phylogeny ; Phylogeography/methods ; Siberia ; }, abstract = {Species with a large geographic distributions present a challenge for phylogeographic studies due to logistic difficulties of obtaining adequate sampling. For instance, in most species with a Holarctic distribution, the majority of studies has concentrated on the European or North American part of the distribution, with the Eastern Palearctic region being notably understudied. Here, we study the phylogeography of the freshwater cladoceran Daphnia magna Straus, 1820 (Crustacea: Cladocera), based on partial mitochondrial COI sequences and using specimens from populations spread longitudinally from westernmost Europe to easternmost Asia, with many samples from previously strongly understudied regions in Siberia and Eastern Asia. The results confirm the previously suspected deep split between Eastern and Western mitochondrial haplotype super-clades. We find a narrow contact zone between these two super-clades in the eastern part of Western Siberia, with proven co-occurrence in a single lake in the Novosibirsk region. However, at present there is no evidence suggesting that the two mitochondrial super-clades represent cryptic species. Rather, they may be explained by secondary contact after expansion from different refugia. Interestingly, Central Siberia has previously been found to be an important contact zone also in other cladoceran species, and may thus be a crucial area for understanding the Eurasian phylogeography of freshwater invertebrates. Together, our study provides an unprecedented complete, while still not global, picture of the phylogeography of this important model species.}, } @article {pmid29543917, year = {2018}, author = {Visser, JH and Bennett, NC and Jansen van Vuuren, B}, title = {Spatial genetic diversity in the Cape mole-rat, Georychus capensis: Extreme isolation of populations in a subterranean environment.}, journal = {PloS one}, volume = {13}, number = {3}, pages = {e0194165}, pmid = {29543917}, issn = {1932-6203}, mesh = {Animal Distribution ; Animals ; Cytochromes b/genetics ; Ecosystem ; *Genetic Variation ; Genetics, Population ; Mitochondria/genetics ; Mole Rats/*genetics ; Phylogeny ; Phylogeography ; South Africa ; }, abstract = {The subterranean niche harbours animals with extreme adaptations. These adaptations decrease the vagility of taxa and, along with other behavioural adaptations, often result in isolated populations characterized by small effective population sizes, high inbreeding, population bottlenecks, genetic drift and consequently, high spatial genetic structure. Although information is available for some species, estimates of genetic diversity and whether this variation is spatially structured, is lacking for the Cape mole-rat (Georychus capensis). By adopting a range-wide sampling regime and employing two variable mitochondrial markers (cytochrome b and control region), we report on the effects that life-history, population demography and geographic barriers had in shaping genetic variation and population genetic patterns in G. capensis. We also compare our results to information available for the sister taxon of the study species, Bathyergus suillus. Our results show that Georychus capensis exhibits low genetic diversity relative to the concomitantly distributed B. suillus, most likely due to differences in habitat specificity, habitat fragmentation and historical population declines. In addition, the isolated nature of G. capensis populations and low levels of population connectivity has led to small effective population sizes and genetic differentiation, possibly aided by genetic drift. Not surprisingly therefore, G. capensis exhibits pronounced spatial structure across its range in South Africa. Along with geographic distance and demography, other factors shaping the genetic structure of G. capensis include the historical and contemporary impacts of mountains, rivers, sea-level fluctuations and elevation. Given the isolation and differentiation among G. capensis populations, the monotypic genus Georychus may represent a species complex.}, } @article {pmid29547666, year = {2018}, author = {Oxusoff, L and Préa, P and Perez, Y}, title = {A complete logical approach to resolve the evolution and dynamics of mitochondrial genome in bilaterians.}, journal = {PloS one}, volume = {13}, number = {3}, pages = {e0194334}, pmid = {29547666}, issn = {1932-6203}, mesh = {Algorithms ; *Evolution, Molecular ; *Genome, Mitochondrial ; *Genomics/methods ; Mitochondria/genetics ; Models, Genetic ; Phylogeny ; RNA, Ribosomal/genetics ; RNA, Transfer/genetics ; }, abstract = {Investigating how recombination might modify gene order during the evolution has become a routine part of mitochondrial genome analysis. A new method of genomic maps analysis based on formal logic is described. The purpose of this method is to 1) use mitochondrial gene order of current taxa as datasets 2) calculate rearrangements between all mitochondrial gene orders and 3) reconstruct phylogenetic relationships according to these calculated rearrangements within a tree under the assumption of maximum parsimony. Unlike existing methods mainly based on the probabilistic approach, the main strength of this new approach is that it calculates all the exact tree solutions with completeness and provides logical consequences as highly robust results. Moreover, this method infers all possible hypothetical ancestors and reconstructs character states for all internal nodes of the trees. We started by testing our method using the deuterostomes as a study case. Then, with sponges as an outgroup, we investigated the evolutionary history of mitochondrial genomes of 47 bilaterian phyla and emphasised the peculiar case of chaetognaths. This pilot work showed that the use of formal logic in a hypothetico-deductive background such as phylogeny (where experimental testing of hypotheses is impossible) is very promising to explore mitochondrial gene order in deuterostomes and should be applied to many other bilaterian clades.}, } @article {pmid29551757, year = {2018}, author = {McLean, BS and Nyamsuren, B and Tchabovsky, A and Cook, JA}, title = {Impacts of late Quaternary environmental change on the long-tailed ground squirrel (Urocitellus undulatus) in Mongolia.}, journal = {Zoological research}, volume = {39}, number = {5}, pages = {364-372}, pmid = {29551757}, issn = {2095-8137}, mesh = {Animals ; Climate Change ; Cytochromes b/genetics ; Electron Transport Complex IV/genetics ; Environment ; Genotyping Techniques ; Mitochondria/genetics ; Mongolia ; Phylogeny ; Phylogeography ; Sciuridae/classification/*genetics ; }, abstract = {Impacts of Quaternary environmental changes on mammal faunas of central Asia remain poorly understood due to a lack of geographically comprehensive phylogeographic sampling for most species. To help address this knowledge gap, we conducted the most extensive molecular analysis to date of the long-tailed ground squirrel (Urocitellus undulatus Pallas 1778) in Mongolia, a country that comprises the southern core of this species' range. Drawing on material from recent collaborative field expeditions, we genotyped 128 individuals at 2 mitochondrial genes (cytochrome b and cytochrome oxidase I; 1 797 bp total). Phylogenetic inference supports the existence of two deeply divergent infraspecific lineages (corresponding to subspecies U. u. undulatus and U. u. eversmanni), a result in agreement with previous molecular investigations but discordant with patterns of range-wide craniometric and external phenotypic variation. In the widespread westerneversmanni lineage, we recovered geographically-associated clades from the: (a) Khangai, (b) Mongolian Altai, and (c) Govi Altai mountain ranges. Phylogeographic structure in U. u. eversmanni is consistent with an isolation-by-distance model; however, genetic distances are significantly lower than among subspecies, and intra-clade relationships are largely unresolved. The latter patterns, as well as the relatively higher nucleotide polymorphism of populations from the Great Lakes Depression of northwestern Mongolia, suggest a history of range shifts into these lowland areas in response to Pleistocene glaciation and environmental change, followed by upslope movements and mitochondrial lineage sorting with Holocene aridification. Our study illuminates possible historical mechanisms responsible for U. undulatus genetic structure and contributes to a framework for ongoing exploration of mammalian response to past and present climate change in central Asia.}, } @article {pmid29554738, year = {2018}, author = {Braz-Mota, S and Campos, DF and MacCormack, TJ and Duarte, RM and Val, AL and Almeida-Val, VMF}, title = {Mechanisms of toxic action of copper and copper nanoparticles in two Amazon fish species: Dwarf cichlid (Apistogramma agassizii) and cardinal tetra (Paracheirodon axelrodi).}, journal = {The Science of the total environment}, volume = {630}, number = {}, pages = {1168-1180}, doi = {10.1016/j.scitotenv.2018.02.216}, pmid = {29554738}, issn = {1879-1026}, mesh = {Animals ; Characidae/*physiology ; Cichlids/*physiology ; Copper/*toxicity ; Metal Nanoparticles/*toxicity ; Mitochondria/drug effects ; Stress, Physiological/drug effects ; Toxicity Tests ; Water Pollutants, Chemical/*toxicity ; }, abstract = {Copper oxide nanoparticles (nCuO) are widely used in boat antifouling paints and are released into the environment, potentially inducing toxicity to aquatic organisms. The present study aimed to understand the effects of nCuO and dissolved copper (Cu) on two ornamental Amazon fish species: dwarf cichlid (Apistogramma agassizii) and cardinal tetra (Paracheirodon axelrodi). Fish were exposed to 50% of the LC50 for nCuO (dwarf cichlid 58.31μgL[-1] and cardinal tetra 69.6μgL[-1]) and Cu (dwarf cichlid 20μgL[-1] and cardinal tetra 22.9μgL[-1]) for 24, 48, 72 and 96h. Following exposure, aerobic metabolic rate (ṀO2), gill osmoregulatory physiology and mitochondrial function, oxidative stress markers, and morphological damage were evaluated. Our results revealed species specificity in metabolic stress responses. An increase of ṀO2 was noted in cardinal tetra exposed to Cu, but not nCuO, whereas ṀO2 in dwarf cichlid showed little change with either treatment. In contrast, mitochondria from dwarf cichlid exhibited increased proton leak and a resulting decrease in respiratory control ratios in response to nCuO and Cu exposure. This uncoupling was directly related to an increase in reactive oxygen species (ROS) levels. Our findings reveal different metabolic responses between these two species in response to nCuO and Cu, which are probably caused by the differences between species natural histories, indicating that different mechanisms of toxic action of the contaminants are associated to differential osmoregulatory strategies among species.}, } @article {pmid29555947, year = {2018}, author = {Islam, T and Ghosh, A}, title = {Genome-wide dissection and expression profiling of unique glyoxalase III genes in soybean reveal the differential pattern of transcriptional regulation.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {4848}, pmid = {29555947}, issn = {2045-2322}, mesh = {Aldehyde Oxidoreductases/chemistry/*genetics ; Amino Acid Sequence ; Environment ; Evolution, Molecular ; *Gene Expression Profiling ; *Genomics ; Glycine max/*genetics/growth & development ; *Transcription, Genetic ; }, abstract = {Reactive carbonyl species, such as methylglyoxal and glyoxal are very toxic in nature and can inactivate various cellular macromolecules such as DNA, RNA, and protein by forming advanced glycation end products. Conventional glyoxalase pathway with two enzymes- glyoxalase I and glyoxalase II, detoxify MG into D-lactate with the help of reduced glutathione. However, DJ-1/PfpI domain(s) containing DJ-1/ Hsp31 proteins do the same in a single step, and thus termed as "glyoxalase III". A comprehensive genome-wide analysis of soybean identified eleven putative glyoxalase III proteins with DJ-1/PfpI domain encoded by seven genes. Most of these proteins are predicted to be mitochondria and chloroplast localized. In spite of similar function, a differential evolution pattern was observed between Hsp31 and DJ-1 proteins. Expression of GmDJ-1A, GmDJ-1B, and GmDJ-1D2 transcripts was found to be constitutive in different tissues and developmental stages. Transcript profiling revealed the strong substrate-specific upregulation of GmDJ-1 genes in response to exogenous methylglyoxal exposure. Out of seven genes, GmDJ-1D1 and GmDJ-1D2 showed maximum upregulation against salinity, dehydration, and oxidative stresses. Moreover, GmDJ-1D2 showed functional glyoxalase III enzyme activity by utilizing MG as a substrate. Overall, this study identifies some novel tissue-specific and abiotic stress-responsive GmDJ-1 genes that could be investigated further.}, } @article {pmid29562168, year = {2018}, author = {Haroon, S and Li, A and Weinert, JL and Fritsch, C and Ericson, NG and Alexander-Floyd, J and Braeckman, BP and Haynes, CM and Bielas, JH and Gidalevitz, T and Vermulst, M}, title = {Multiple Molecular Mechanisms Rescue mtDNA Disease in C. elegans.}, journal = {Cell reports}, volume = {22}, number = {12}, pages = {3115-3125}, pmid = {29562168}, issn = {2211-1247}, support = {R01 CA204894/CA/NCI NIH HHS/United States ; T32 ES019851/ES/NIEHS NIH HHS/United States ; R01 ES026222/ES/NIEHS NIH HHS/United States ; R01 GM124532/GM/NIGMS NIH HHS/United States ; R37 AG047182/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*metabolism ; DNA, Mitochondrial/*genetics ; Disease Progression ; Mice ; Mitochondria/*metabolism ; Models, Animal ; }, abstract = {Genetic instability of the mitochondrial genome (mtDNA) plays an important role in human aging and disease. Thus far, it has proven difficult to develop successful treatment strategies for diseases that are caused by mtDNA instability. To address this issue, we developed a model of mtDNA disease in the nematode C. elegans, an animal model that can rapidly be screened for genes and biological pathways that reduce mitochondrial pathology. These worms recapitulate all the major hallmarks of mtDNA disease in humans, including increased mtDNA instability, loss of respiration, reduced neuromuscular function, and a shortened lifespan. We found that these phenotypes could be rescued by intervening in numerous biological pathways, including IGF-1/insulin signaling, mitophagy, and the mitochondrial unfolded protein response, suggesting that it may be possible to ameliorate mtDNA disease through multiple molecular mechanisms.}, } @article {pmid29563878, year = {2018}, author = {Zeth, K and Zachariae, U}, title = {Ten Years of High Resolution Structural Research on the Voltage Dependent Anion Channel (VDAC)-Recent Developments and Future Directions.}, journal = {Frontiers in physiology}, volume = {9}, number = {}, pages = {108}, pmid = {29563878}, issn = {1664-042X}, abstract = {Mitochondria are evolutionarily related to Gram-negative bacteria and both comprise two membrane systems with strongly differing protein composition. The major protein in the outer membrane of mitochondria is the voltage-dependent anion channel (VDAC), which mediates signal transmission across the outer membrane but also the exchange of metabolites, most importantly ADP and ATP. More than 30 years after its discovery three identical high-resolution structures were determined in 2008. These structures show a 19-stranded anti-parallel beta-barrel with an N-terminal helix located inside. An odd number of beta-strands is also shared by Tom40, another member of the VDAC superfamily. This indicates that this superfamily is evolutionarily relatively young and that it has emerged in the context of mitochondrial evolution. New structural information obtained during the last decade on Tom40 can be used to cross-validate the structure of VDAC and vice versa. Interpretation of biochemical and biophysical studies on both protein channels now rests on a solid basis of structural data. Over the past 10 years, complementary structural and functional information on proteins of the VDAC superfamily has been collected from in-organello, in-vitro, and in silico studies. Most of these findings have confirmed the validity of the original structures. This short article briefly reviews the most important advances on the structure and function of VDAC superfamily members collected during the last decade and summarizes how they enhanced our understanding of the channel.}, } @article {pmid29567505, year = {2018}, author = {O'Connell, KA and Smith, EN}, title = {The effect of missing data on coalescent species delimitation and a taxonomic revision of whipsnakes (Colubridae: Masticophis).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {356-366}, doi = {10.1016/j.ympev.2018.03.018}, pmid = {29567505}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Biodiversity ; Cell Nucleus/genetics ; Colubridae/*classification ; Cytochromes c/genetics ; Geography ; Mitochondria/genetics ; *Phylogeny ; Species Specificity ; }, abstract = {A stable alpha taxonomy is essential to understanding evolutionary processes and achieving effective conservation aims. Taxonomy depends on the identification of independently evolving lineages, and the delimitation of these lineages based on multiple lines of evidence. Coalescent species delimitation within an integrative framework has increased the rigor of the delimitation process. Here we use genome-wide SNP data and coalescent species delimitation to explore lineage relationships within several North American whipsnake species, test the species status of several lineages, and test the effect of missing data on species delimitation. We find support for the elevation of several previously recognized subspecies to full species status, and formally elevate two species. This study demonstrates the power of molecular data and model-based delimitation methods to identify evolutionary relationships, and finds that missing data have little impact on the outcome of delimitation analyses.}, } @article {pmid29575366, year = {2018}, author = {Ivanov, V and Lee, KM and Mutanen, M}, title = {Mitonuclear discordance in wolf spiders: Genomic evidence for species integrity and introgression.}, journal = {Molecular ecology}, volume = {27}, number = {7}, pages = {1681-1695}, doi = {10.1111/mec.14564}, pmid = {29575366}, issn = {1365-294X}, mesh = {Animals ; Cell Nucleus/*genetics ; Electron Transport Complex IV/genetics ; Genetic Loci ; *Genome, Mitochondrial ; *Genomics ; Likelihood Functions ; Mitochondria/genetics ; Phylogeny ; Species Specificity ; Spiders/*genetics ; }, abstract = {Systematists and taxonomists have benefited greatly from the emergence of molecular methods. Species identification has become straightforward through DNA barcoding and the rapid build-up of massive DNA barcode reference libraries. In animals, mitonuclear discordance can significantly complicate the process of species identification and delimitation. The causes of mitonuclear discordance are either biological (e.g., introgression, incomplete lineage sorting, horizontal gene transfer androgenesis) or induced by operational factors (e.g., human error with specimen misidentification or incorrect species delimitation). Moreover, endosymbionts may play an important role in promoting fixation of mitochondrial genomes. Here, we study the mitonuclear discordance of wolf spiders species (Lycosidae) (independent cases from Alopecosa aculeata and Pardosa pullata groups) that share identical COI DNA barcodes. We approached the case utilizing double-digest restriction site-associated DNA sequencing (ddRADseq) to obtain and analyse genomic-scale data. Our results suggest that the observed cases of mitonuclear discordance are not due to operational reasons but result from biological processes. Further analysis indicated introgression and that incomplete lineage sorting is unlikely to have been responsible for the observed discrepancy. Additional survey of endosymbionts provided ideas on further research and their role in shaping mitochondrial DNA distribution patterns. Thus, ddRADseq grants an efficient way to study the taxonomy of problematic groups with insight into underlying evolutionary processes.}, } @article {pmid29579296, year = {2018}, author = {Caspermeyer, J}, title = {Cockroach Ancient Geographic and Genomic History Traced Back to Last Supercontinent.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {1035}, doi = {10.1093/molbev/msy039}, pmid = {29579296}, issn = {1537-1719}, mesh = {Animals ; *Cockroaches ; Genomics ; Mitochondria ; *Phylogeny ; }, } @article {pmid29587633, year = {2018}, author = {Chase, EE and Robicheau, BM and Veinot, S and Breton, S and Stewart, DT}, title = {The complete mitochondrial genome of the hermaphroditic freshwater mussel Anodonta cygnea (Bivalvia: Unionidae): in silico analyses of sex-specific ORFs across order Unionoida.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {221}, pmid = {29587633}, issn = {1471-2164}, support = {217175//Natural Sciences and Engineering Research Council of Canada/International ; }, mesh = {Animals ; Computer Simulation ; DNA, Mitochondrial/genetics ; Disorders of Sex Development/*genetics ; Female ; Fresh Water ; *Genome, Mitochondrial ; Male ; Mitochondrial Proteins/genetics ; *Open Reading Frames ; Phylogeny ; Sex Factors ; Unionidae/classification/*genetics ; }, abstract = {BACKGROUND: Doubly uniparental inheritance (DUI) of mitochondrial DNA in bivalves is a fascinating exception to strictly maternal inheritance as practiced by all other animals. Recent work on DUI suggests that there may be unique regions of the mitochondrial genomes that play a role in sex determination and/or sexual development in freshwater mussels (order Unionoida). In this study, one complete mitochondrial genome of the hermaphroditic swan mussel, Anodonta cygnea, is sequenced and compared to the complete mitochondrial genome of the gonochoric duck mussel, Anodonta anatina. An in silico assessment of novel proteins found within freshwater bivalve species (known as F-, H-, and M-open reading frames or ORFs) is conducted, with special attention to putative transmembrane domains (TMs), signal peptides (SPs), signal cleavage sites (SCS), subcellular localization, and potential control regions. Characteristics of TMs are also examined across freshwater mussel lineages.

RESULTS: In silico analyses suggests the presence of SPs and SCSs and provides some insight into possible function(s) of these novel ORFs. The assessed confidence in these structures and functions was highly variable, possibly due to the novelty of these proteins. The number and topology of putative TMs appear to be maintained among both F- and H-ORFs, however, this is not the case for M-ORFs. There does not appear to be a typical control region in H-type mitochondrial DNA, especially given the loss of tandem repeats in unassigned regions when compared to F-type mtDNA.

CONCLUSION: In silico analyses provides a useful tool to discover patterns in DUI and to navigate further in situ analyses related to DUI in freshwater mussels. In situ analysis will be necessary to further explore the intracellular localizations and possible role of these open reading frames in the process of sex determination in freshwater mussel.}, } @article {pmid29594864, year = {2017}, author = {Enomoto, M and Nishikawa, T and Siddiqui, N and Chung, S and Ikura, M and Stathopulos, PB}, title = {From Stores to Sinks: Structural Mechanisms of Cytosolic Calcium Regulation.}, journal = {Advances in experimental medicine and biology}, volume = {981}, number = {}, pages = {215-251}, doi = {10.1007/978-3-319-55858-5_10}, pmid = {29594864}, issn = {0065-2598}, support = {MOP-13552//CIHR/Canada ; }, mesh = {Animals ; Calcium/chemistry/*metabolism ; Calcium Channels/chemistry/metabolism ; Calcium Signaling/*physiology ; Cytosol/chemistry/*metabolism ; Endoplasmic Reticulum/chemistry/*metabolism ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/chemistry/metabolism ; Mitochondria, Muscle/chemistry/*metabolism ; Muscle, Skeletal/chemistry/metabolism ; Neoplasm Proteins/chemistry/metabolism ; ORAI1 Protein/chemistry/metabolism ; Stromal Interaction Molecule 1/chemistry/metabolism ; }, abstract = {All eukaryotic cells have adapted the use of the calcium ion (Ca[2+]) as a universal signaling element through the evolution of a toolkit of Ca[2+] sensor, buffer and effector proteins. Among these toolkit components, integral and peripheral proteins decorate biomembranes and coordinate the movement of Ca[2+] between compartments, sense these concentration changes and elicit physiological signals. These changes in compartmentalized Ca[2+] levels are not mutually exclusive as signals propagate between compartments. For example, agonist induced surface receptor stimulation can lead to transient increases in cytosolic Ca[2+] sourced from endoplasmic reticulum (ER) stores; the decrease in ER luminal Ca[2+] can subsequently signal the opening surface channels which permit the movement of Ca[2+] from the extracellular space to the cytosol. Remarkably, the minuscule compartments of mitochondria can function as significant cytosolic Ca[2+] sinks by taking up Ca[2+] in a coordinated manner. In non-excitable cells, inositol 1,4,5 trisphosphate receptors (IP3Rs) on the ER respond to surface receptor stimulation; stromal interaction molecules (STIMs) sense the ER luminal Ca[2+] depletion and activate surface Orai1 channels; surface Orai1 channels selectively permit the movement of Ca[2+] from the extracellular space to the cytosol; uptake of Ca[2+] into the matrix through the mitochondrial Ca[2+] uniporter (MCU) further shapes the cytosolic Ca[2+] levels. Recent structural elucidations of these key Ca[2+] toolkit components have improved our understanding of how they function to orchestrate precise cytosolic Ca[2+] levels for specific physiological responses. This chapter reviews the atomic-resolution structures of IP3R, STIM1, Orai1 and MCU elucidated by X-ray crystallography, electron microscopy and NMR and discusses the mechanisms underlying their biological functions in their respective compartments within the cell.}, } @article {pmid29609620, year = {2018}, author = {Hornok, S and Beck, R and Farkas, R and Grima, A and Otranto, D and Kontschán, J and Takács, N and Horváth, G and Szőke, K and Szekeres, S and Majoros, G and Juhász, A and Salant, H and Hofmann-Lehmann, R and Stanko, M and Baneth, G}, title = {High mitochondrial sequence divergence in synanthropic flea species (Insecta: Siphonaptera) from Europe and the Mediterranean.}, journal = {Parasites & vectors}, volume = {11}, number = {1}, pages = {221}, pmid = {29609620}, issn = {1756-3305}, support = {115854//OTKA/International ; }, mesh = {Animals ; *Base Sequence ; Ctenocephalides/classification/genetics ; Europe ; Flea Infestations/parasitology ; *Genetic Variation ; Haplotypes ; Humans ; Insect Vectors/classification/genetics ; Mediterranean Region ; Mitochondria/*genetics ; Phylogeny ; Siphonaptera/*classification/*genetics ; }, abstract = {BACKGROUND: Adult fleas are haematophagous ectoparasites of warm-blooded vertebrates, particularly mammals. Among them, the cat flea (Ctenocephalides felis) and the human flea (Pulex irritans) have high veterinary-medical significance, owing to their cosmopolitan distribution and role in the transmission of important vector-borne pathogens. While the taxonomy of Ct. felis has been investigated on a morphological basis during the past decades, its molecular-phylogenetic analyses have been only recently conducted. This study expands the knowledge on Ct. felis from hitherto less studied geographical regions, and includes representatives from additional flea families, less investigated with molecular approaches.

METHODS: Fleas were collected in four countries of the Mediterranean Basin (Croatia, Italy, Malta and Israel), as well as in Hungary, from domestic and wild carnivores, rodents and humans. The DNA extracts of representative fleas (n = 148), belonging to ten species of eight genera, were used for PCR amplification of part of their cytochrome c oxidase subunits 1, 2 (cox1, cox2) and 18S rRNA genes, followed by sequencing and phylogenetic analyses.

RESULTS: The majority (65.6%) of Ct. felis felis cox2 sequences showed 99.4-100% similarity to each other (haplogroup A), whereas those from Malta and Israel had 98.1-98.7% sequence similarity (haplogroup B), and a third sequence from Israel (haplotype C) had as low as 96.3% sequence similarity in comparison with a reference sequence from group "A". Except for the shape of the head, no consistent morphological differences (e.g. in chaetotaxy) were found between haplogroups "A" and "C". Haplotypes of Ct. canis were genetically more homogenous, with 99.6-100% sequence similarity to each other. However, when P. irritans collected from humans was compared to those from three species of wild carnivores, these only had 96.6% cox2 similarity. The mouse flea, Leptopsylla segnis and the northern rat flea, Nosopsyllus fasciatus were both shown to have haplotypes with low intraspecific cox2 similarities (96.2 and 94.4%, respectively). Taken together, differences between mitochondrial lineages within four flea species exceeded that observed between two Chaetopsylla spp. (which had 97.3% cox2 similarity). The topologies of cox1 and cox2 phylogenetic trees were in line with relevant sequence comparisons. Conversely, 18S rRNA gene analyses only resolved differences above the species level.

CONCLUSIONS: Ctenocephalides felis felis, P. irritans, L. segnis and N. fasciatus were shown to have such a high level of mitochondrial gene heterogeneity, that the uniformity of these flea taxa should be reconsidered. Although the present results are limited (especially in the case of L. segnis and N. fasciatus), there appears to be no geographical or host restriction, which could explain the divergence of these genetic lineages.}, } @article {pmid29614345, year = {2018}, author = {Fan, Z and Zhou, A and Osada, N and Yu, J and Jiang, J and Li, P and Du, L and Niu, L and Deng, J and Xu, H and Xing, J and Yue, B and Li, J}, title = {Ancient hybridization and admixture in macaques (genus Macaca) inferred from whole genome sequences.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {376-386}, doi = {10.1016/j.ympev.2018.03.038}, pmid = {29614345}, issn = {1095-9513}, support = {R00 HG005846/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; *Gene Flow ; Genetic Variation ; *Genome ; Heterozygote ; *Hybridization, Genetic ; Macaca mulatta/*genetics ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Principal Component Analysis ; *Whole Genome Sequencing ; }, abstract = {The evolutionary history of the stump-tailed macaque (Macaca arctoides) and its genetic relationship to other macaques is a subject of continuing controversy. Here, we have reported the first genome sequences of two stump-tailed macaques and one Assamese macaque (M. assamensis). Additionally, we have investigated the genetic diversity between macaque species and analyzed ancient hybridization events. Genome-wide analyses demonstrated that the stump-tailed macaque is more closely related to sinica species than to fascicularis/mulatta species. This topology contradicts the mitochondrial sequence-based phylogeny that places the stump-tailed macaque into the fascicularis/mulatta group. However, our results further show that stump-tailed macaques have genetic backgrounds distinct from sinica species, and present evidence of gene flows with rhesus macaques. We suggest that an ancient introgression occurred after stump-tailed macaques diverged from sinica species. The distinct gene flow between proto-arctoides and proto-mulatta resulted in the transfer of rhesus macaque-type mitochondria into proto-arctoides. The rhesus macaque-type mitochondria remained in populations because of genetic drift during the bottleneck. The PSMC results and morphological and geographic evidence are consistent with the mitochondria capture pattern in the stump-tailed macaque. The molecular clock estimates suggest that the mitochondrial transference into stump-tailed macaques occurred 0.4-1.4 million years ago. Furthermore, we detected extensive admixtures between different macaque species, indicating that gene flow has played an important role in the evolutionary history of the genus Macaca.}, } @article {pmid29616678, year = {2018}, author = {Nie, WH and Wang, JH and Su, WT and Hu, Y and He, SW and Jiang, XL and He, K}, title = {Species identification of crested gibbons (Nomascus) in captivity in China using karyotyping- and PCR-based approaches.}, journal = {Zoological research}, volume = {39}, number = {5}, pages = {356-363}, pmid = {29616678}, issn = {2095-8137}, mesh = {Animals ; Animals, Zoo ; Cell Nucleus/genetics ; China ; Endangered Species ; Genes/genetics ; Hylobates/classification/*genetics ; In Situ Hybridization, Fluorescence ; Karyotype ; Karyotyping ; Mitochondria/genetics ; Polymerase Chain Reaction ; }, abstract = {Gibbons and siamangs (Hylobatidae) are well-known for their rapid chromosomal evolution, which has resulted in high speciation rate within the family. On the other hand, distinct karyotypes do not prevent speciation, allowing interbreeding between individuals in captivity, and the unwanted hybrids are ethically problematic as all gibbon species are endangered or critically endangered. Thus, accurate species identification is crucial for captive breeding, particularly in China where studbooks are unavailable. Identification based on external morphology is difficult, especially for hybrids, because species are usually similar in appearance. In this study, we employed G-banding karyotyping and fluorescence in situ hybridization (FISH) as well as a PCR-based approach to examine karyotypic characteristics and identify crested gibbons of the genus Nomascus from zoos and nature reserves in China. We characterized and identified five karyotypes from 21 individuals of Nomascus. Using karyotypes and mitochondrial and nuclear genes, we identified three purebred species and three hybrids, including one F2 hybrid between N. gabriellae and N. siki. Our results also supported that N. leucogenys and N. siki shared the same inversion on chromosome 7, which resolves arguments from previous studies. Our results demonstrated that both karyotyping and DNA-based approaches were suitable for identifying purebred species, though neither was ideal for hybrid identification. The advantages and disadvantages of both approaches are discussed. Our results further highlight the importance of animal ethics and welfare, which are critical for endangered species in captivity.}, } @article {pmid29618295, year = {2018}, author = {Derbikova, KS and Levitsky, SA and Chicherin, IV and Vinogradova, EN and Kamenski, PA}, title = {Activation of Yeast Mitochondrial Translation: Who Is in Charge?.}, journal = {Biochemistry. Biokhimiia}, volume = {83}, number = {2}, pages = {87-97}, doi = {10.1134/S0006297918020013}, pmid = {29618295}, issn = {1608-3040}, mesh = {Cytochromes b/genetics/metabolism ; Electron Transport Complex IV/genetics/metabolism ; Mitochondria/genetics/*metabolism ; Mitochondrial Proteins/genetics/metabolism ; RNA, Messenger/metabolism ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Transcriptional Activation ; }, abstract = {Mitochondrial genome has undergone significant reduction in a course of evolution; however, it still contains a set of protein-encoding genes and requires translational machinery for their expression. Mitochondrial translation is of the prokaryotic type with several remarkable differences. This review is dedicated to one of the most puzzling features of mitochondrial protein synthesis, namely, the system of translational activators, i.e., proteins that specifically regulate translation of individual mitochondrial mRNAs and couple protein biosynthesis with the assembly of mitochondrial respiratory chain complexes. The review does not claim to be a comprehensive analysis of all published data; it is rather focused on the idea of the "core component" of the translational activator system.}, } @article {pmid29618317, year = {2018}, author = {Doyle, JM and Bell, DA and Bloom, PH and Emmons, G and Fesnock, A and Katzner, TE and LaPré, L and Leonard, K and SanMiguel, P and Westerman, R and Andrew DeWoody, J}, title = {New insights into the phylogenetics and population structure of the prairie falcon (Falco mexicanus).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {233}, pmid = {29618317}, issn = {1471-2164}, support = {L12AC20102, L11PX02237, L12AC2010//U.S. Bureau of Land Management/ ; University Faculty Scholar program//Provost's Office at Purdue University/ ; PINN645-21//National Park Service/ ; BIO170038//XSEDE/ ; }, mesh = {Animals ; Avian Proteins/*genetics ; California ; Falconiformes/*classification/genetics ; Female ; Genetics, Population ; Idaho ; Mitochondria/genetics ; Phylogeny ; Phylogeography ; *Polymorphism, Single Nucleotide ; Whole Genome Sequencing/*veterinary ; }, abstract = {BACKGROUND: Management requires a robust understanding of between- and within-species genetic variability, however such data are still lacking in many species. For example, although multiple population genetics studies of the peregrine falcon (Falco peregrinus) have been conducted, no similar studies have been done of the closely-related prairie falcon (F. mexicanus) and it is unclear how much genetic variation and population structure exists across the species' range. Furthermore, the phylogenetic relationship of F. mexicanus relative to other falcon species is contested. We utilized a genomics approach (i.e., genome sequencing and assembly followed by single nucleotide polymorphism genotyping) to rapidly address these gaps in knowledge.

RESULTS: We sequenced the genome of a single female prairie falcon and generated a 1.17 Gb (gigabases) draft genome assembly. We generated maximum likelihood phylogenetic trees using complete mitochondrial genomes as well as nuclear protein-coding genes. This process provided evidence that F. mexicanus is an outgroup to the clade that includes the peregrine falcon and members of the subgenus Hierofalco. We annotated > 16,000 genes and almost 600,000 high-quality single nucleotide polymorphisms (SNPs) in the nuclear genome, providing the raw material for a SNP assay design featuring > 140 gene-associated markers and a molecular-sexing marker. We subsequently genotyped ~ 100 individuals from California (including the San Francisco East Bay Area, Pinnacles National Park and the Mojave Desert) and Idaho (Snake River Birds of Prey National Conservation Area). We tested for population structure and found evidence that individuals sampled in California and Idaho represent a single panmictic population.

CONCLUSIONS: Our study illustrates how genomic resources can rapidly shed light on genetic variability in understudied species and resolve phylogenetic relationships. Furthermore, we found evidence of a single, randomly mating population of prairie falcons across our sampling locations. Prairie falcons are highly mobile and relatively rare long-distance dispersal events may promote gene flow throughout the range. As such, California's prairie falcons might be managed as a single population, indicating that management actions undertaken to benefit the species at the local level have the potential to influence the species as a whole.}, } @article {pmid29621569, year = {2018}, author = {Seligmann, H}, title = {Alignment-based and alignment-free methods converge with experimental data on amino acids coded by stop codons at split between nuclear and mitochondrial genetic codes.}, journal = {Bio Systems}, volume = {167}, number = {}, pages = {33-46}, doi = {10.1016/j.biosystems.2018.03.002}, pmid = {29621569}, issn = {1872-8324}, mesh = {Amino Acid Sequence ; Amino Acids/*genetics ; Animals ; Anticodon/genetics ; Cell Nucleus/*genetics ; Codon, Terminator/*genetics ; Data Interpretation, Statistical ; Evolution, Molecular ; Genetic Code/*genetics ; Humans ; Mitochondria/*genetics ; }, abstract = {Genetic codes mainly evolve by reassigning punctuation codons, starts and stops. Previous analyses assuming that undefined amino acids translate stops showed greater divergence between nuclear and mitochondrial genetic codes. Here, three independent methods converge on which amino acids translated stops at split between nuclear and mitochondrial genetic codes: (a) alignment-free genetic code comparisons inserting different amino acids at stops; (b) alignment-based blast analyses of hypothetical peptides translated from non-coding mitochondrial sequences, inserting different amino acids at stops; (c) biases in amino acid insertions at stops in proteomic data. Hence short-term protein evolution models reconstruct long-term genetic code evolution. Mitochondria reassign stops to amino acids otherwise inserted at stops by codon-anticodon mismatches (near-cognate tRNAs). Hence dual function (translation termination and translation by codon-anticodon mismatch) precedes mitochondrial reassignments of stops to amino acids. Stop ambiguity increases coded information, compensates endocellular mitogenome reduction. Mitochondrial codon reassignments might prevent viral infections.}, } @article {pmid29623424, year = {2018}, author = {Peña-Diaz, P and Lukeš, J}, title = {Fe-S cluster assembly in the supergroup Excavata.}, journal = {Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry}, volume = {23}, number = {4}, pages = {521-541}, pmid = {29623424}, issn = {1432-1327}, mesh = {Eukaryota/cytology/*metabolism ; Iron/metabolism ; Iron-Sulfur Proteins/*metabolism ; Mitochondria/metabolism ; }, abstract = {The majority of established model organisms belong to the supergroup Opisthokonta, which includes yeasts and animals. While enlightening, this focus has neglected protists, organisms that represent the bulk of eukaryotic diversity and are often regarded as primitive eukaryotes. One of these is the "supergroup" Excavata, which comprises unicellular flagellates of diverse lifestyles and contains species of medical importance, such as Trichomonas, Giardia, Naegleria, Trypanosoma and Leishmania. Excavata exhibits a continuum in mitochondrial forms, ranging from classical aerobic, cristae-bearing mitochondria to mitochondria-related organelles, such as hydrogenosomes and mitosomes, to the extreme case of a complete absence of the organelle. All forms of mitochondria house a machinery for the assembly of Fe-S clusters, ancient cofactors required in various biochemical activities needed to sustain every extant cell. In this review, we survey what is known about the Fe-S cluster assembly in the supergroup Excavata. We aim to bring attention to the diversity found in this group, reflected in gene losses and gains that have shaped the Fe-S cluster biogenesis pathways.}, } @article {pmid29626207, year = {2018}, author = {Bundus, JD and Wang, D and Cutter, AD}, title = {Genetic basis to hybrid inviability is more complex than hybrid male sterility in Caenorhabditis nematodes.}, journal = {Heredity}, volume = {121}, number = {2}, pages = {169-182}, pmid = {29626207}, issn = {1365-2540}, mesh = {Animals ; Biological Evolution ; Caenorhabditis/classification/*genetics ; Cell Nucleus/*genetics ; Crosses, Genetic ; Female ; Genomics ; Infertility, Male/*genetics ; Male ; Mitochondria/*genetics ; *Models, Genetic ; }, abstract = {Hybrid male sterility often evolves before female sterility or inviability of hybrids, implying that the accumulation of divergence between separated lineages should lead hybrid male sterility to have a more polygenic basis. However, experimental evidence is mixed. Here, we use the nematodes Caenorhabditis remanei and C. latens to characterize the underlying genetic basis of asymmetric hybrid male sterility and hybrid inviability. We demonstrate that hybrid male sterility is consistent with a simple genetic basis, involving a single X-autosome incompatibility. We also show that hybrid inviability involves more genomic compartments, involving diverse nuclear-nuclear incompatibilities, a mito-nuclear incompatibility, and maternal effects. These findings demonstrate that male sensitivity to genetic perturbation may be genetically simple compared to hybrid inviability in Caenorhabditis and motivates tests of generality for the genetic architecture of hybrid incompatibility across the breadth of phylogeny.}, } @article {pmid29636759, year = {2018}, author = {Shibata, S and Arimura, SI and Ishikawa, T and Awai, K}, title = {Alterations of Membrane Lipid Content Correlated With Chloroplast and Mitochondria Development in Euglena gracilis.}, journal = {Frontiers in plant science}, volume = {9}, number = {}, pages = {370}, pmid = {29636759}, issn = {1664-462X}, abstract = {Euglenoids are unique protists that can grow photoautotrophically, photomixotrophically, and heterotrophically. Here we grew Euglena gracilis under these different growth conditions and determined cellular contents of seven membrane lipids and one storage lipid (triacylglycerol), which account for more than 94 mol% of total membrane lipids. We also describe the relationship among chloroplast and mitochondria developments with lipid contents, protein contents, and oxygen evolution/consumption rates. In photoautotrophic growth conditions, E. gracilis cells accumulated chlorophyll, photosynthetic proteins, and glycolipids typical to thylakoid membranes. The same occurred for the cells grown under photomixotrophic conditions with higher respiration rates. In heterotrophic conditions, E. gracilis cells had higher respiration rates compared to cells grown in other conditions with the accumulation of pyruvate: NADP+ oxidoreductase, a mitochondrial protein and phospholipid common in mitochondria. Cells were also observed using a confocal laser scanning microscope and found to show more chlorophyll autofluorescence when grown photoautotrophically and photomixotrophycally, and fluorescence of MitoTracker when grown photomixotrophically and heterotrophically. These results suggest that under illumination, E. gracilis develops functional thylakoid membranes with membrane lipids and proteins for photosynthesis. In the medium with glucose, the cells develop mitochondria with phospholipids and proteins for respiration. Possible application based on lipid analysis for the enhancement of wax ester or alkene synthesis is discussed.}, } @article {pmid29643269, year = {2018}, author = {Mori, S and Matsunami, M}, title = {Signature of positive selection in mitochondrial DNA in Cetartiodactyla.}, journal = {Genes & genetic systems}, volume = {93}, number = {2}, pages = {65-73}, doi = {10.1266/ggs.17-00015}, pmid = {29643269}, issn = {1880-5779}, mesh = {Amino Acid Substitution ; Animals ; Artiodactyla/*genetics ; Biological Evolution ; Cetacea/*genetics ; DNA, Mitochondrial/*genetics ; Databases, Genetic ; Evolution, Molecular ; Genomics ; Mammals/genetics ; Mitochondria/genetics ; Phylogeny ; Selection, Genetic/genetics ; }, abstract = {Acceleration of the amino acid substitution rate is a good indicator of positive selection in adaptive evolutionary changes of functional genes. Genomic information about mammals has become readily available in recent years, as many researchers have attempted to clarify the adaptive evolution of mammals by examining evolutionary rate change based on multiple loci. The order Cetartiodactyla (Artiodactyla and Cetacea) is one of the most diverse orders of mammals. Species in this order are found throughout all continents and seas, except Antarctica, and they exhibit wide variation in morphology and habitat. Here, we focused on the metabolism-related genes of mitochondrial DNA (mtDNA) in species of the order Cetartiodactyla using 191 mtDNA sequences available in databases. Based on comparisons of the dN/dS ratio (ω) in 12 protein-coding genes, ATP8 was shown to have a higher ω value (ω = 0.247) throughout Cetartiodactyla than the other 11 genes (ω < 0.05). In a branch-site analysis of ATP8 sequences, a markedly higher ω value of 0.801 was observed in the ancestral lineage of the clade of Cetacea, which is indicative of adaptive evolution. Through efforts to detect positively selected amino acids, codon positions 52 and 54 of ATP8 were shown to have experienced positive selective pressure during the course of evolution; multiple substitutions have occurred at these sites throughout the cetacean lineage. At position 52, glutamic acid was replaced with asparagine, and, at position 54, lysine was replaced with non-charged amino acids. These sites are conserved in most Artiodactyla. These results imply that the ancestor of cetaceans underwent accelerated amino acid changes in ATP8 and replacements at codons 52 and 54, which adjusted metabolism to adapt to the marine environment.}, } @article {pmid29653091, year = {2018}, author = {Islam, W and Lin, W and Qasim, M and Islam, SU and Ali, H and Adnan, M and Arif, M and Du, Z and Wu, Z}, title = {A nation-wide genetic survey revealed a complex population structure of Bemisia tabaci in Pakistan.}, journal = {Acta tropica}, volume = {183}, number = {}, pages = {119-125}, doi = {10.1016/j.actatropica.2018.04.015}, pmid = {29653091}, issn = {1873-6254}, mesh = {Agriculture ; Animals ; Base Sequence ; Electron Transport Complex IV/genetics ; Genetic Speciation ; Genetic Variation ; Hemiptera/*genetics ; Insect Proteins/genetics ; Mitochondria/genetics ; *Molecular Epidemiology ; Pakistan ; *Phylogeny ; }, abstract = {The whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a cryptic species complex distributed worldwide. In Pakistan, B. tabaci poses a serious threat to agriculture production. To understand its diversity in Pakistan, a large-scale sampling was conducted from various locations of all four provinces of the country and Mitochondrial cytochrome oxidase I (mtCOI) gene sequencing was used to determine the whiteflies genetically. The study revealed the presence of five different cryptic species in Pakistan namely Asia II-1, Asia II-5, Asia II-7, Asia II-8 and MEAM-1, respectively. Among them, Asia II-1, which was previously reported from a few areas in the country, had been found now to be prevalent all over the country covering 88.7% of all the sequenced samples. Based on the mtCOI sequences and genetic distance analyses, the diversity of Asia II-1 was much greater than all other cryptic species, which exist only in small patches.}, } @article {pmid29654216, year = {2018}, author = {Reichold, M and Klootwijk, ED and Reinders, J and Otto, EA and Milani, M and Broeker, C and Laing, C and Wiesner, J and Devi, S and Zhou, W and Schmitt, R and Tegtmeier, I and Sterner, C and Doellerer, H and Renner, K and Oefner, PJ and Dettmer, K and Simbuerger, JM and Witzgall, R and Stanescu, HC and Dumitriu, S and Iancu, D and Patel, V and Mozere, M and Tekman, M and Jaureguiberry, G and Issler, N and Kesselheim, A and Walsh, SB and Gale, DP and Howie, AJ and Martins, JR and Hall, AM and Kasgharian, M and O'Brien, K and Ferreira, CR and Atwal, PS and Jain, M and Hammers, A and Charles-Edwards, G and Choe, CU and Isbrandt, D and Cebrian-Serrano, A and Davies, B and Sandford, RN and Pugh, C and Konecki, DS and Povey, S and Bockenhauer, D and Lichter-Konecki, U and Gahl, WA and Unwin, RJ and Warth, R and Kleta, R}, title = {Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {29}, number = {7}, pages = {1849-1858}, pmid = {29654216}, issn = {1533-3450}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Aged ; Amidinotransferases/*genetics/metabolism ; Animals ; Computer Simulation ; Fanconi Syndrome/complications/*genetics/metabolism/pathology ; Female ; Heterozygote ; Humans ; Infant ; Inflammasomes/metabolism ; Kidney Failure, Chronic/etiology/*genetics/metabolism/pathology ; Male ; Mice ; Mice, Knockout ; Mitochondria/*metabolism/*pathology ; Molecular Conformation ; Mutation ; Mutation, Missense ; Pedigree ; Reactive Oxygen Species/metabolism ; Sequence Analysis, DNA ; Young Adult ; }, abstract = {Background For many patients with kidney failure, the cause and underlying defect remain unknown. Here, we describe a novel mechanism of a genetic order characterized by renal Fanconi syndrome and kidney failure.Methods We clinically and genetically characterized members of five families with autosomal dominant renal Fanconi syndrome and kidney failure. We performed genome-wide linkage analysis, sequencing, and expression studies in kidney biopsy specimens and renal cells along with knockout mouse studies and evaluations of mitochondrial morphology and function. Structural studies examined the effects of recognized mutations.Results The renal disease in these patients resulted from monoallelic mutations in the gene encoding glycine amidinotransferase (GATM), a renal proximal tubular enzyme in the creatine biosynthetic pathway that is otherwise associated with a recessive disorder of creatine deficiency. In silico analysis showed that the particular GATM mutations, identified in 28 members of the five families, create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells. GATM aggregates-containing mitochondria were elongated and associated with increased ROS production, activation of the NLRP3 inflammasome, enhanced expression of the profibrotic cytokine IL-18, and increased cell death.Conclusions In this novel genetic disorder, fully penetrant heterozygous missense mutations in GATM trigger intramitochondrial fibrillary deposition of GATM and lead to elongated and abnormal mitochondria. We speculate that this renal proximal tubular mitochondrial pathology initiates a response from the inflammasome, with subsequent development of kidney fibrosis.}, } @article {pmid29656105, year = {2018}, author = {Dias, C and Lima, KA and Araripe, J and Aleixo, A and Vallinoto, M and Sampaio, I and Schneider, H and Rêgo, PSD}, title = {Mitochondrial introgression obscures phylogenetic relationships among manakins of the genus Lepidothrix (Aves: Pipridae).}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {314-320}, doi = {10.1016/j.ympev.2018.04.017}, pmid = {29656105}, issn = {1095-9513}, mesh = {Animals ; DNA, Mitochondrial/genetics ; Haplotypes/genetics ; Mitochondria/*genetics ; Passeriformes/*classification/*genetics ; *Phylogeny ; }, abstract = {Lepidothrix is the most diverse genus of the family Pipridae, with eight recognized species. Although the genus' monophyly has been supported by both molecular and morphological characters, phylogenetic relationships and species limits within Lepidothrix remain uncertain. In the present study, we combined molecular sequences of mitochondrial (ND2 and COI) and nuclear (MYO, G3PDh and I5BF) markers in a multilocus analysis, to evaluate relationships and inter-specific limits among L. iris, L. nattereri, and L. vilasboasi, which are known to hybridize in eastern Amazonia. The results revealed a complex pattern, whereby events of secondary contact and gene flow after isolation and genetic and phenotypic differentiation prevented the recuperation of reciprocal monophyly among the studied taxa. The mitochondrial data indicate that L. nattereri is divided into two non-sister groups, one monophyletic, and the other, paraphyletic, with L. iris iris being more closely related to one of the two L. nattereri groups, while L. iris eucephala forms an undifferentiated clade with L. vilasboasi, probably resulting from an extensive process of mitochondrial introgression. In agreement with a previous study based on Single Nucleotide Polymorphism (SNP) data, mitochondrial haplotype networks also support that L. vilasboasi does not represent a recent "hybrid swarm" between L. iris and L. nattereri, but instead a genetically divergent lineage with a separate species status. Finally, the sister relationship recovered herein between L. iris iris and some western populations of L. nattereri currently in allopatry is also apparently explained by mitochondrial introgression, as also supported for nuclear genes by SNP data, indicating a complex scenario of past contact and gene flow between currently geographically distant Lepidothrix lineages.}, } @article {pmid29664320, year = {2018}, author = {Nakano, M}, title = {16S rRNA Gene Primer Validation for Bacterial Diversity Analysis of Vegetable Products.}, journal = {Journal of food protection}, volume = {81}, number = {5}, pages = {848-859}, doi = {10.4315/0362-028X.JFP-17-346}, pmid = {29664320}, issn = {1944-9097}, mesh = {Animals ; Bacteria/genetics ; Bacterial Load ; DNA Primers/genetics ; DNA, Bacterial/genetics ; High-Throughput Nucleotide Sequencing ; Microbiota ; RNA, Ribosomal, 16S/*genetics ; Vegetable Products/*microbiology ; }, abstract = {High-throughput sequencing of the 16S rRNA gene enhances understanding of microbial diversity from complex environmental samples. The 16S rRNA gene is currently the most important target in bacterial evolution and ecology studies, particularly for determination of phylogenetic relationships among taxa, exploration of bacterial diversity in a given environment, and quantification of the relative abundance of taxa at various levels. However, some parts of the conserved region of the bacterial 16S rRNA gene are similar to the conserved regions of plant chloroplasts and eukaryotic mitochondria. Therefore, if DNA contains a large amount of nontarget DNA, this nontarget DNA can be coamplified and consequently produce useless sequence reads. We experimentally assessed the primer pair 335f/769r and the widely used bacterial primer pair SD (S-D-Bact-0341-b-S-17/S-D-Bact-0785-a-A-21). The primer pair 335f/769r was examined for its ability to amplify bacterial DNA in plant and animal feed samples by using the single-strand confirmation polymorphism method. In our present study, these primer pairs were validated for microbial community structure analysis with complex food matrices by using next-generation sequencing. The sequencing results revealed that the primer pair 335f/769r successfully resulted in fewer chloroplast and mitochondrial sequence reads than generated by the universal primer pair SD and therefore is comparatively suitable for metagenomic analyses of complex food matrices, particularly those that are rich in plant DNA. Additionally, some taxonomic groups were missed entirely when only the SD primer pair was used.}, } @article {pmid29665772, year = {2018}, author = {Padilla-Jacobo, G and Cano-Camacho, H and López-Zavala, R and Cornejo-Pérez, ME and Zavala-Páramo, MG}, title = {Evolutionary history of Mexican domesticated and wild Meleagris gallopavo.}, journal = {Genetics, selection, evolution : GSE}, volume = {50}, number = {1}, pages = {19}, pmid = {29665772}, issn = {1297-9686}, support = {Scholarship No. 359650//Consejo Nacional de Ciencia y Tecnología/International ; Scholarship//Consejo Nacional de Ciencia y Tecnología/International ; 2004-C01-201//Consejo Nacional de Ciencia y Tecnología-SAGARPA (MX)/International ; 2009-05-115938//Fondos Mixtos Consejo Nacional de Ciencia y Tecnología Gobierno del Estado de Michoacán (MX)/International ; }, mesh = {Animals ; Animals, Domestic/*genetics ; Animals, Wild/genetics ; Canada ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Genetic Variation ; Guatemala ; Haplotypes ; Mexico ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA/*veterinary ; Turkeys/classification/*genetics ; }, abstract = {BACKGROUND: The distribution of the wild turkey (Meleagris gallopavo) extends from Mexico to southeastern Canada and to the eastern and southern regions of the USA. Six subspecies have been described based on morphological characteristics and/or geographical variations in wild and domesticated populations. In this paper, based on DNA sequence data from the mitochondrial D-loop, we investigated the genetic diversity and structure, genealogical relationships, divergence time and demographic history of M. gallopavo populations including domesticated individuals.

RESULTS: Analyses of 612 wild and domesticated turkey mitochondrial D-loop sequences, including 187 that were collected for this study and 425 from databases, revealed 64 haplotypes with few mutations, some of which are shared between domesticated and wild turkeys. We found a high level of haplotype and nucleotide diversity, which suggests that the total population of this species is large and stable with an old evolutionary history. The results of genetic differentiation, haplotype network, and genealogical relationships analyses revealed three main genetic groups within the species: mexicana as a population relict (C1), merriami (C2), and mexicana/intermedia/silvestris/osceola (C3). Haplotypes detected in domesticated turkeys belong to group C3. Estimates of divergence times agree with range expansion and diversification events of the relict population of M. gallopavo in northwestern Mexico during the Pliocene-Pleistocene and Pleistocene-Holocene boundaries. Demographic reconstruction showed that an expansion of the population occurred 110,000 to 130,000 years ago (Kya), followed by a stable period 100 Kya and finally a decline ~ 10 Kya (Pleistocene-Holocene boundary). In Mexico, the Trans-Mexican Volcanic Belt may be responsible for the range expansion of the C3 group. Two haplotypes with different divergence times, MGMDgoB/MICH1 and MICH2, are dominant in domesticated and commercial turkeys.

CONCLUSIONS: During the Pleistocene, a large and stable population of M. gallopavo covered a wide geographic distribution from the north to the center of America (USA and Mexico). The mexicana, merriami, and mexicana/intermedia/silvestris/osceola genetic groups originated after divergence and range expansion from northwestern Mexico during the Pliocene-Pleistocene and Pleistocene-Holocene boundaries. Old and new maternal lines of the mexicana/intermedia/silvestris/osceola genetic group were distributed within the Trans-Mexican Volcanic Belt where individuals were captured for domestication. Two haplotypes are the main founder maternal lines of domesticated turkeys.}, } @article {pmid29671881, year = {2018}, author = {Demain, LAM and Antunes, D and O'Sullivan, J and Bhaskhar, SS and O'Keefe, RT and Newman, WG}, title = {A known pathogenic variant in the essential mitochondrial translation gene RMND1 causes a Perrault-like syndrome with renal defects.}, journal = {Clinical genetics}, volume = {94}, number = {2}, pages = {276-277}, doi = {10.1111/cge.13255}, pmid = {29671881}, issn = {1399-0004}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Cell Cycle Proteins/*genetics ; Female ; *Genetic Predisposition to Disease ; Gonadal Dysgenesis, 46,XX/complications/*genetics/pathology ; Hearing Loss, Sensorineural/complications/*genetics/pathology ; Humans ; Kidney Diseases/complications/*genetics/pathology ; Mitochondria/genetics ; Exome Sequencing ; }, } @article {pmid29675831, year = {2018}, author = {Kauko, A and Lehto, K}, title = {Eukaryote specific folds: Part of the whole.}, journal = {Proteins}, volume = {86}, number = {8}, pages = {868-881}, doi = {10.1002/prot.25517}, pmid = {29675831}, issn = {1097-0134}, mesh = {Archaea/genetics ; Bacteria/classification ; Biological Evolution ; Databases, Protein ; Eukaryota/*classification ; Eukaryotic Cells/classification ; Evolution, Molecular ; Genes, Bacterial ; Genes, Mitochondrial ; Mitochondria/genetics ; Phylogeny ; Proteins/genetics ; Symbiosis/*genetics ; }, abstract = {The origin of eukaryotes is one of the central transitions in the history of life; without eukaryotes there would be no complex multicellular life. The most accepted scenarios suggest the endosymbiosis of a mitochondrial ancestor with a complex archaeon, even though the details regarding the host and the triggering factors are still being discussed. Accordingly, phylogenetic analyses have demonstrated archaeal affiliations with key informational systems, while metabolic genes are often related to bacteria, mostly to the mitochondrial ancestor. Despite of this, there exists a large number of protein families and folds found only in eukaryotes. In this study, we have analyzed structural superfamilies and folds that probably appeared during eukaryogenesis. These folds typically represent relatively small binding domains of larger multidomain proteins. They are commonly involved in biological processes that are particularly complex in eukaryotes, such as signaling, trafficking/cytoskeleton, ubiquitination, transcription and RNA processing, but according to recent studies, these processes also have prokaryotic roots. Thus the folds originating from an eukaryotic stem seem to represent accessory parts that have contributed in the expansion of several prokaryotic processes to a new level of complexity. This might have taken place as a co-evolutionary process where increasing complexity and fold innovations have supported each other.}, } @article {pmid29675902, year = {2018}, author = {Morin, PA and Foote, AD and Baker, CS and Hancock-Hanser, BL and Kaschner, K and Mate, BR and Mesnick, SL and Pease, VL and Rosel, PE and Alexander, A}, title = {Demography or selection on linked cultural traits or genes? Investigating the driver of low mtDNA diversity in the sperm whale using complementary mitochondrial and nuclear genome analyses.}, journal = {Molecular ecology}, volume = {27}, number = {11}, pages = {2604-2619}, doi = {10.1111/mec.14698}, pmid = {29675902}, issn = {1365-294X}, mesh = {Animals ; Cell Nucleus/*genetics ; DNA, Mitochondrial/*genetics ; Demography ; Genetic Variation/*genetics ; Genetics, Population/methods ; Haplotypes/genetics ; Mitochondria/*genetics ; Phylogeny ; Phylogeography/methods ; Population Density ; Sperm Whale/*genetics ; }, abstract = {Mitochondrial DNA has been heavily utilized in phylogeography studies for several decades. However, underlying patterns of demography and phylogeography may be misrepresented due to coalescence stochasticity, selection, variation in mutation rates and cultural hitchhiking (linkage of genetic variation to culturally-transmitted traits affecting fitness). Cultural hitchhiking has been suggested as an explanation for low genetic diversity in species with strong social structures, counteracting even high mobility, abundance and limited barriers to dispersal. One such species is the sperm whale, which shows very limited phylogeographic structure and low mtDNA diversity despite a worldwide distribution and large population. Here, we use analyses of 175 globally distributed mitogenomes and three nuclear genomes to evaluate hypotheses of a population bottleneck/expansion vs. a selective sweep due to cultural hitchhiking or selection on mtDNA as the mechanism contributing to low worldwide mitochondrial diversity in sperm whales. In contrast to mtDNA control region (CR) data, mitogenome haplotypes are largely ocean-specific, with only one of 80 shared between the Atlantic and Pacific. Demographic analyses of nuclear genomes suggest low mtDNA diversity is consistent with a global reduction in population size that ended approximately 125,000 years ago, correlated with the Eemian interglacial. Phylogeographic analysis suggests that extant sperm whales descend from maternal lineages endemic to the Pacific during the period of reduced abundance and have subsequently colonized the Atlantic several times. Results highlight the apparent impact of past climate change, and suggest selection and hitchhiking are not the sole processes responsible for low mtDNA diversity in this highly social species.}, } @article {pmid29678141, year = {2018}, author = {Beltrán-López, RG and Domínguez-Domínguez, O and Pérez-Rodríguez, R and Piller, K and Doadrio, I}, title = {Evolving in the highlands: the case of the Neotropical Lerma live-bearing Poeciliopsis infans (Woolman, 1894) (Cyprinodontiformes: Poeciliidae) in Central Mexico.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {56}, pmid = {29678141}, issn = {1471-2148}, mesh = {Animals ; Bayes Theorem ; *Biological Evolution ; Climate ; Cyprinodontiformes/genetics/*physiology ; Cytochromes b/genetics ; DNA, Mitochondrial/genetics ; *Ecosystem ; Fresh Water ; Genes, Mitochondrial ; Genetic Variation ; Genetics, Population ; Geography ; Haplotypes/genetics ; Mexico ; Mitochondria/genetics ; Phylogeny ; Species Specificity ; Time Factors ; *Tropical Climate ; }, abstract = {BACKGROUND: Volcanic and tectonic activities in conjunction with Quaternary climate are the main events that shaped the geographical distribution of genetic variation of many lineages. Poeciliopsis infans is the only poeciliid species that was able to colonize the temperate highlands of central Mexico. We inferred the phylogenetic relationships, biogeographic history, and historical demography in the widespread Neotropical species P. infans and correlated this with geological events and the Quaternary glacial-interglacial climate in the highlands of central Mexico, using the mitochondrial genes Cytochrome b and Cytochrome oxidase I and two nuclear loci, Rhodopsin and ribosomal protein S7.

RESULTS: Populations of P. infans were recovered in two well-differentiated clades. The maximum genetic distances between the two clades were 3.3% for cytb, and 1.9% for coxI. The divergence of the two clades occurred ca. 2.83 Myr. Ancestral area reconstruction revealed a complex biogeographical history for P. infans. The Bayesian Skyline Plot showed a demographic decline, although more visible for clade A, and more recently showed a population expansion in the last 0.025 Myr. Finally, the habitat suitability modelling showed that during the LIG, clade B had more areas with high probabilities of presence in comparison to clade A, whereas for the LGM, clade A showed more areas with high probabilities of presence in comparisons to clade B.

CONCLUSIONS: Poeciliopsis infans has had a complex evolutionary and biogeographic history, which, as in other co-distributed freshwater fishes, seems to be linked to the volcanic and tectonic activities during the Pliocene or early Pleistocene. Populations of P. infans distributed in lowlands showed a higher level of genetic diversity than populations distributed in highlands, which could be linked to more stable and higher temperatures in lowland areas. The fluctuations in population size through time are in agreement with the continuous fluctuations of the climate of central Mexico.}, } @article {pmid29689215, year = {2018}, author = {McBride, HM}, title = {Mitochondria and endomembrane origins.}, journal = {Current biology : CB}, volume = {28}, number = {8}, pages = {R367-R372}, doi = {10.1016/j.cub.2018.03.052}, pmid = {29689215}, issn = {1879-0445}, mesh = {Animals ; Biological Evolution ; Eukaryota ; Evolution, Molecular ; Humans ; Intracellular Membranes/*physiology ; Mitochondria/*metabolism/*physiology ; Mitochondrial Membranes/metabolism/physiology ; }, abstract = {In this Guest Editorial, Heidi McBride introduces our special issue on membranes with a discussion of the contribution of mitochondria to the emergence of the endomembrane system.}, } @article {pmid29689791, year = {2018}, author = {Sadasivan, K and Ramesh, MB and Palot, MJ and Ambekar, M and Mirza, ZA}, title = {A new species of fan-throated lizard of the genus Sitana Cuvier, 1829 from coastal Kerala, southern India.}, journal = {Zootaxa}, volume = {4374}, number = {4}, pages = {545-564}, doi = {10.11646/zootaxa.4374.4.5}, pmid = {29689791}, issn = {1175-5334}, mesh = {Animals ; India ; *Lizards ; Mitochondria ; Phylogeny ; }, abstract = {We here describe Sitana attenboroughii sp. nov., a new species of fan-throated lizard of the genus Sitana Cuvier, 1829 from coastal Kerala in southern India. The new species morphologically is closer to Sitana visiri Deepak, 2016 (in Deepak et al. 2016a), however, differs in having higher numbers of ventral scales and a comparatively short but richly colored dewlap. Genetically the new species shows affinity to Sitana marudhamneydhal Deepak, Khandekar, Varma Chaitanya, 2016 from which it differs in an uncorrected pairwise sequence divergence of 2.2% for a fragment of mitochondrial Nicotinamide adenine dinucleotide dehydrogenase (NADH) subunit 2 gene.}, } @article {pmid29691935, year = {2018}, author = {Henry, LP and Newton, ILG}, title = {Mitochondria and Wolbachia titers are positively correlated during maternal transmission.}, journal = {Molecular ecology}, volume = {27}, number = {11}, pages = {2634-2646}, doi = {10.1111/mec.14700}, pmid = {29691935}, issn = {1365-294X}, mesh = {Animals ; Biological Evolution ; Drosophila melanogaster/genetics ; Female ; Gene Expression/genetics ; Genotype ; Infectious Disease Transmission, Vertical ; Mitochondria/*genetics ; NADH Dehydrogenase/genetics ; Symbiosis/genetics ; Wolbachia/*genetics ; }, abstract = {Mothers provide their offspring with symbionts. Maternally transmitted, intracellular symbionts must disperse from mother to offspring with other cytoplasmic elements, like mitochondria. Here, we investigated how the intracellular symbiont Wolbachia interacts with mitochondria during maternal transmission. Mitochondria and Wolbachia may interact antagonistically and compete as each population tries to ensure its own evolutionary success. Alternatively, mitochondria and Wolbachia may cooperate as both benefit from ensuring the fitness of the mother. We characterized the relationship between mitochondria and Wolbachia titers in ovaries of Drosophila melanogaster. We found that mitochondria and Wolbachia titers are positively correlated in common laboratory genotypes of D. melanogaster. We attempted to perturb this covariation through the introduction of Wolbachia variants that colonize at different titers. We also attempted to perturb the covariation through manipulating the female reproductive tract to disrupt maternal transmission. Finally, we also attempted to disrupt the covariation by knocking down gene expression for two loci involved in mitochondrial metabolism: NADH dehydrogenase and a mitochondrial transporter. Overall, we find that mitochondria and Wolbachia titers are commonly positively correlated, but this positive covariation is disrupted at high titers of Wolbachia. Our results suggest that mitochondria and Wolbachia have likely evolved mechanisms to stably coexist, but the competitive dynamics change at high Wolbachia titers. We provide future directions to better understand how their interaction influences the maintenance of the symbiosis.}, } @article {pmid29695865, year = {2018}, author = {Martijn, J and Vosseberg, J and Guy, L and Offre, P and Ettema, TJG}, title = {Deep mitochondrial origin outside the sampled alphaproteobacteria.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {101-105}, doi = {10.1038/s41586-018-0059-5}, pmid = {29695865}, issn = {1476-4687}, mesh = {Alphaproteobacteria/*cytology/*genetics ; Atlantic Ocean ; Genome, Bacterial/genetics ; Genomics ; Metagenome/genetics ; Mitochondria/*genetics/*metabolism ; Pacific Ocean ; *Phylogeny ; }, abstract = {Mitochondria are ATP-generating organelles, the endosymbiotic origin of which was a key event in the evolution of eukaryotic cells [1] . Despite strong phylogenetic evidence that mitochondria had an alphaproteobacterial ancestry [2] , efforts to pinpoint their closest relatives among sampled alphaproteobacteria have generated conflicting results, complicating detailed inferences about the identity and nature of the mitochondrial ancestor. While most studies support the idea that mitochondria evolved from an ancestor related to Rickettsiales[3-9], an order that includes several host-associated pathogenic and endosymbiotic lineages[10,11], others have suggested that mitochondria evolved from a free-living group[12-14]. Here we re-evaluate the phylogenetic placement of mitochondria. We used genome-resolved binning of oceanic metagenome datasets and increased the genomic sampling of Alphaproteobacteria with twelve divergent clades, and one clade representing a sister group to all Alphaproteobacteria. Subsequent phylogenomic analyses that specifically address long branch attraction and compositional bias artefacts suggest that mitochondria did not evolve from Rickettsiales or any other currently recognized alphaproteobacterial lineage. Rather, our analyses indicate that mitochondria evolved from a proteobacterial lineage that branched off before the divergence of all sampled alphaproteobacteria. In light of this new result, previous hypotheses on the nature of the mitochondrial ancestor[6,15,16] should be re-evaluated.}, } @article {pmid29697049, year = {2018}, author = {Stairs, CW and Eme, L and Muñoz-Gómez, SA and Cohen, A and Dellaire, G and Shepherd, JN and Fawcett, JP and Roger, AJ}, title = {Microbial eukaryotes have adapted to hypoxia by horizontal acquisitions of a gene involved in rhodoquinone biosynthesis.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {29697049}, issn = {2050-084X}, support = {MOP 341174//CIHR/Canada ; MOP 142349//CIHR/Canada ; R15 GM096398/GM/NIGMS NIH HHS/United States ; 1R15GM096398-01/NH/NIH HHS/United States ; }, mesh = {*Adaptation, Biological ; *Anaerobiosis ; Bacteria/genetics ; Electron Transport Complex II/*genetics/metabolism ; Eukaryota/*genetics/*physiology ; Fumarates/metabolism ; *Gene Transfer, Horizontal ; Genetic Variation ; Oxidation-Reduction ; Phylogeny ; Ubiquinone/*analogs & derivatives/biosynthesis ; }, abstract = {Under hypoxic conditions, some organisms use an electron transport chain consisting of only complex I and II (CII) to generate the proton gradient essential for ATP production. In these cases, CII functions as a fumarate reductase that accepts electrons from a low electron potential quinol, rhodoquinol (RQ). To clarify the origins of RQ-mediated fumarate reduction in eukaryotes, we investigated the origin and function of rquA, a gene encoding an RQ biosynthetic enzyme. RquA is very patchily distributed across eukaryotes and bacteria adapted to hypoxia. Phylogenetic analyses suggest lateral gene transfer (LGT) of rquA from bacteria to eukaryotes occurred at least twice and the gene was transferred multiple times amongst protists. We demonstrate that RquA functions in the mitochondrion-related organelles of the anaerobic protist Pygsuia and is correlated with the presence of RQ. These analyses reveal the role of gene transfer in the evolutionary remodeling of mitochondria in adaptation to hypoxia.}, } @article {pmid29698456, year = {2018}, author = {Peña-Diaz, P and Mach, J and Kriegová, E and Poliak, P and Tachezy, J and Lukeš, J}, title = {Trypanosomal mitochondrial intermediate peptidase does not behave as a classical mitochondrial processing peptidase.}, journal = {PloS one}, volume = {13}, number = {4}, pages = {e0196474}, pmid = {29698456}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Down-Regulation ; Electron Transport Complex IV/metabolism ; Metalloendopeptidases/antagonists & inhibitors/classification/genetics/*metabolism ; Microscopy, Fluorescence ; Mitochondria/*enzymology ; Phylogeny ; Protein Subunits/antagonists & inhibitors/genetics/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism ; Substrate Specificity ; Trypanosoma brucei brucei/*metabolism ; Mitochondrial Processing Peptidase ; }, abstract = {Upon their translocation into the mitochondrial matrix, the N-terminal pre-sequence of nuclear-encoded proteins undergoes cleavage by mitochondrial processing peptidases. Some proteins require more than a single processing step, which involves several peptidases. Down-regulation of the putative Trypanosoma brucei mitochondrial intermediate peptidase (MIP) homolog by RNAi renders the cells unable to grow after 48 hours of induction. Ablation of MIP results in the accumulation of the precursor of the trypanosomatid-specific trCOIV protein, the largest nuclear-encoded subunit of the cytochrome c oxidase complex in this flagellate. However, the trCOIV precursor of the same size accumulates also in trypanosomes in which either alpha or beta subunits of the mitochondrial processing peptidase (MPP) have been depleted. Using a chimeric protein that consists of the N-terminal sequence of a putative subunit of respiratory complex I fused to a yellow fluorescent protein, we assessed the accumulation of the precursor protein in trypanosomes, in which RNAi was induced against the alpha or beta subunits of MPP or MIP. The observed accumulation of precursors indicates MIP depletion affects the activity of the cannonical MPP, or at least one of its subunits.}, } @article {pmid29703131, year = {2018}, author = {Arafat, H and Alamaru, A and Gissi, C and Huchon, D}, title = {Extensive mitochondrial gene rearrangements in Ctenophora: insights from benthic Platyctenida.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {65}, pmid = {29703131}, issn = {1471-2148}, support = {161/15//Israel Science Foundation/International ; }, mesh = {Animals ; Biological Evolution ; Conserved Sequence/genetics ; Ctenophora/*genetics ; DNA, Mitochondrial/genetics ; Gene Order ; *Gene Rearrangement ; *Genes, Mitochondrial ; Genome, Mitochondrial ; Mitochondria/genetics ; Molecular Sequence Annotation ; Open Reading Frames/genetics ; Phylogeny ; RNA, Ribosomal/genetics ; }, abstract = {BACKGROUND: Complete mitochondrial (mt) genomes have been sequenced for thousands of animals and represent a molecule of choice for many evolutionary studies. Nevertheless, some animal groups have remained under-sampled. Ctenophora (comb jellies) is one such example, with only two complete mt sequences determined hitherto for this phylum, which encompasses ca. 150-200 described species. This lack of data derives from the extremely fast mt evolutionary rate in this lineage, complicating primer design and DNA amplification. Indeed, in the two ctenophore mt genomes sequenced to date, i.e. those of Mnemiopsis leidyi (order Lobata) and Pleurobrachia bachei (order Cydippida), both rRNA and protein coding genes exhibit an extraordinary size reduction and have highly derived sequences. Additionally, all tRNAs, and the atp6 and atp8 genes are absent. In order to determine whether these characteristics are shared by other ctenophores, we obtained the complete mt genomes of three benthic ctenophores belonging to the so far unsampled order of Platyctenida: Coeloplana loyai, Coeloplana yulianicorum and Vallicula multiformis.

RESULTS: The mt genomes of benthic ctenophores reveal the same peculiarities found in Mnemiopsis and Pleurobrachia, demonstrating that the fast evolutionary rate is a general trait of the ctenophore mt genomes. Our results also indicate that this high evolutionary rate not only affects the nucleotide substitution but also gene rearrangements. Indeed, gene order was highly rearranged among representatives of the different taxonomic orders in which it was close to random, but also quite variable within Platyctenida, in which the genera Coeloplana and Vallicula share only four conserved synteny blocks. However, the two congeneric Coeloplana species display exactly the same gene order. Because of the extreme evolutionary rate, our phylogenetic analyses were unable to resolve the phylogenetic position of ctenophores within metazoans or the relationships among the different Ctenophora orders. Comparative sequence-analyses allowed us to correct the annotation of the Pleurobrachia mt genome, confirming the absence of tRNAs, the presence of both rRNA genes, and the existence of a reassignment of codon TGA from tryptophan to serine for this species.

CONCLUSIONS: Since Platyctenida is an early diverging lineage among Ctenophora, our findings suggest that the mt traits described above are ancestral characteristics of this phylum.}, } @article {pmid29706933, year = {2018}, author = {Goetzman, ES and Prochownik, EV}, title = {The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic Tissues.}, journal = {Frontiers in endocrinology}, volume = {9}, number = {}, pages = {129}, pmid = {29706933}, issn = {1664-2392}, support = {R01 CA174713/CA/NCI NIH HHS/United States ; R01 DK090242/DK/NIDDK NIH HHS/United States ; }, abstract = {That cancer cells show patterns of metabolism different from normal cells has been known for over 50 years. Yet, it is only in the past decade or so that an appreciation of the benefits of these changes has begun to emerge. Altered cancer cell metabolism was initially attributed to defective mitochondria. However, we now realize that most cancers do not have mitochondrial mutations and that normal cells can transiently adopt cancer-like metabolism during periods of rapid proliferation. Indeed, an encompassing, albeit somewhat simplified, conceptual framework to explain both normal and cancer cell metabolism rests on several simple premises. First, the metabolic pathways used by cancer cells and their normal counterparts are the same. Second, normal quiescent cells use their metabolic pathways and the energy they generate largely to maintain cellular health and organelle turnover and, in some cases, to provide secreted products necessary for the survival of the intact organism. By contrast, undifferentiated cancer cells minimize the latter functions and devote their energy to producing the anabolic substrates necessary to maintain high rates of unremitting cellular proliferation. Third, as a result of the uncontrolled proliferation of cancer cells, a larger fraction of the metabolic intermediates normally used by quiescent cells purely as a source of energy are instead channeled into competing proliferation-focused and energy-consuming anabolic pathways. Fourth, cancer cell clones with the most plastic and rapidly adaptable metabolism will eventually outcompete their less well-adapted brethren during tumor progression and evolution. This attribute becomes increasingly important as tumors grow and as their individual cells compete in a constantly changing and inimical environment marked by nutrient, oxygen, and growth factor deficits. Here, we review some of the metabolic pathways whose importance has gained center stage for tumor growth, particularly those under the control of the c-Myc (Myc) oncoprotein. We discuss how these pathways differ functionally between quiescent and proliferating normal cells, how they are kidnapped and corrupted during the course of transformation, and consider potential therapeutic strategies that take advantage of common features of neoplastic and metabolic disorders.}, } @article {pmid29718949, year = {2018}, author = {Lv, C and Li, Q and Kong, L}, title = {Comparative analyses of the complete mitochondrial genomes of Dosinia clams and their phylogenetic position within Veneridae.}, journal = {PloS one}, volume = {13}, number = {5}, pages = {e0196466}, pmid = {29718949}, issn = {1932-6203}, mesh = {Animals ; Base Composition/genetics ; Base Sequence/genetics ; Bayes Theorem ; Bivalvia/*genetics ; Genome, Mitochondrial/*genetics ; Mitochondria/*genetics ; Phylogeny ; RNA, Ribosomal/genetics ; RNA, Transfer/genetics ; Sequence Analysis, DNA ; }, abstract = {Mitochondrial genomes have proved to be a powerful tool in resolving phylogenetic relationship. In order to understand the mitogenome characteristics and phylogenetic position of the genus Dosinia, we sequenced the complete mitochondrial genomes of Dosinia altior and Dosinia troscheli (Bivalvia: Veneridae), compared them with that of Dosinia japonica and established a phylogenetic tree for Veneridae. The mitogenomes of D. altior (17,536 bp) and D. troscheli (17,229 bp) are the two smallest in Veneridae, which include 13 protein-coding genes, 2 ribosomal RNA genes, 22 tRNA genes, and non-coding regions. The mitogenomes of the Dosinia species are similar in size, gene content, AT content, AT- and GC- skews, and gene arrangement. The phylogenetic relationships of family Veneridae were established based on 12 concatenated protein-coding genes using maximum likelihood and Bayesian analyses, which supported that Dosininae and Meretricinae have a closer relationship, with Tapetinae being the sister taxon. The information obtained in this study will contribute to further understanding of the molecular features of bivalve mitogenomes and the evolutionary history of the genus Dosinia.}, } @article {pmid29720079, year = {2018}, author = {Dufresnes, C and Lymberakis, P and Kornilios, P and Savary, R and Perrin, N and Stöck, M}, title = {Phylogeography of Aegean green toads (Bufo viridis subgroup): continental hybrid swarm vs. insular diversification with discovery of a new island endemic.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {67}, pmid = {29720079}, issn = {1471-2148}, support = {STO 493/2-2//Deutsche Forschungsgemeinschaft/International ; P2LAP3_171818//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; }, mesh = {Animals ; Base Sequence ; *Biodiversity ; Bufonidae/*classification ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Gene Flow ; Genetic Drift ; Genetics, Population ; Genome ; Greece ; *Islands ; Likelihood Functions ; Mitochondria/genetics ; Phylogeny ; *Phylogeography ; Reproductive Isolation ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Debated aspects in speciation research concern the amount of gene flow between incipient species under secondary contact and the modes by which post-zygotic isolation accumulates. Secondary contact zones of allopatric lineages, involving varying levels of divergence, provide natural settings for comparative studies, for which the Aegean (Eastern Mediterranean) geography offers unique scenarios. In Palearctic green toads (Bufo viridis subgroup or Bufotes), Plio-Pleistocene (~ 2.6 Mya) diverged species show a sharp transition without contemporary gene flow, while younger lineages, diverged in the Lower-Pleistocene (~ 1.9 Mya), admix over tens of kilometers. Here, we conducted a fine-scale multilocus phylogeographic analysis of continental and insular green toads from the Aegean, where a third pair of taxa, involving Mid-Pleistocene diverged (~ 1.5 Mya) mitochondrial lineages, earlier tentatively named viridis and variabilis, (co-)occurs.

RESULTS: We discovered a new lineage, endemic to Naxos (Central Cyclades), while coastal islands and Crete feature weak genetic differentiation from the continent. In continental Greece, both lineages, viridis and variabilis, form a hybrid swarm, involving massive mitochondrial and nuclear admixture over hundreds of kilometers, without obvious selection against hybrids.

CONCLUSIONS: The genetic signatures of insular Aegean toads appear governed by bathymetry and Quaternary sea level changes, resulting in long-term isolation (Central Cyclades: Naxos) and recent land-bridges (coastal islands). Conversely, Crete has been isolated since the end of the Messinian salinity crisis (5.3 My) and Cretan populations thus likely result from human-mediated colonization, at least since Antiquity, from Peloponnese and Anatolia. Comparisons of green toad hybrid zones support the idea that post-zygotic hybrid incompatibilities accumulate gradually over the genome. In this radiation, only one million years of divergence separate a scenario of complete reproductive isolation, from a secondary contact resulting in near panmixia.}, } @article {pmid29722901, year = {2018}, author = {McManus, HA and Fučíková, K and Lewis, PO and Lewis, LA and Karol, KG}, title = {Organellar phylogenomics inform systematics in the green algal family Hydrodictyaceae (Chlorophyceae) and provide clues to the complex evolutionary history of plastid genomes in the green algal tree of life.}, journal = {American journal of botany}, volume = {105}, number = {3}, pages = {315-329}, doi = {10.1002/ajb2.1066}, pmid = {29722901}, issn = {1537-2197}, mesh = {Base Sequence ; Chlorophyceae/*genetics ; Chlorophyta/*genetics ; Chloroplasts ; DNA, Chloroplast/analysis ; DNA, Mitochondrial/analysis ; *Evolution, Molecular ; Genes, Plant ; *Genome, Mitochondrial ; Genome, Plant ; *Genome, Plastid ; Genomics ; Mitochondria ; Organelles/*genetics ; *Phylogeny ; }, abstract = {PREMISE OF THE STUDY: Phylogenomic analyses across the green algae are resolving relationships at the class, order, and family levels and highlighting dynamic patterns of evolution in organellar genomes. Here we present a within-family phylogenomic study to resolve genera and species relationships in the family Hydrodictyaceae (Chlorophyceae), for which poor resolution in previous phylogenetic studies, along with divergent morphological traits, have precluded taxonomic revisions.

METHODS: Complete plastome sequences and mitochondrial protein-coding gene sequences were acquired from representatives of the Hydrodictyaceae using next-generation sequencing methods. Plastomes were characterized, and gene order and content were compared with plastomes spanning the Sphaeropleales. Single-gene and concatenated-gene phylogenetic analyses of plastid and mitochondrial genes were performed.

KEY RESULTS: The Hydrodictyaceae contain the largest sphaeroplealean plastomes thus far fully sequenced. Conservation of plastome gene order within Hydrodictyaceae is striking compared with more dynamic patterns revealed across Sphaeropleales. Phylogenetic analyses resolve Hydrodictyon sister to a monophyletic Pediastrum, though the morphologically distinct P. angulosum and P. duplex continue to be polyphyletic. Analyses of plastid data supported the neochloridacean genus Chlorotetraëdron as sister to Hydrodictyaceae, while conflicting signal was found in the mitochondrial data.

CONCLUSIONS: A phylogenomic approach resolved within-family relationships not obtainable with previous phylogenetic analyses. Denser taxon sampling across Sphaeropleales is necessary to capture patterns in plastome evolution, and further taxa and studies are needed to fully resolve the sister lineage to Hydrodictyaceae and polyphyly of Pediastrum angulosum and P. duplex.}, } @article {pmid29723685, year = {2019}, author = {Samuilov, VD and Kiselevsky, DB and Oleskin, AV}, title = {Mitochondria-targeted quinones suppress the generation of reactive oxygen species, programmed cell death and senescence in plants.}, journal = {Mitochondrion}, volume = {46}, number = {}, pages = {164-171}, doi = {10.1016/j.mito.2018.04.008}, pmid = {29723685}, issn = {1872-8278}, mesh = {Antioxidants/metabolism ; Apoptosis/*drug effects ; Arabidopsis/drug effects ; Mitochondria/*drug effects/*metabolism ; Pisum sativum/drug effects ; Plant Cells/*drug effects ; Quinones/*metabolism ; Reactive Oxygen Species/*antagonists & inhibitors ; Triticum/drug effects ; }, abstract = {This work focuses on the effect of mitochondria-targeted quinones (SkQs) on plants. SkQs with antioxidant properties are accumulated in the mitochondria of pea cells and suppress the generation of reactive oxygen species. At nanomolar concentrations, SkQs prevented the death of pea leaf epidermal or guard cells caused by chitosan, bacterial lipopolysaccharide or KCN. The protective effect of SkQs was removed by a protonophoric uncoupler. SkQs at micromolar concentrations inhibited the O2 evolution by illuminated chloroplasts and stimulated the respiration of mitochondria. SkQs slowed down the senescence and the death of Arabidopsis thaliana leaves and improved the wheat crop structure.}, } @article {pmid29724860, year = {2018}, author = {Garg, SG and Martin, WF}, title = {Asking endosymbionts to do an enzyme's job.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4543-E4544}, pmid = {29724860}, issn = {1091-6490}, mesh = {*Biological Evolution ; Enzymes/*metabolism ; Mitochondria ; *Symbiosis ; }, } @article {pmid29728774, year = {2018}, author = {Gong, S and Vamberger, M and Auer, M and Praschag, P and Fritz, U}, title = {Millennium-old farm breeding of Chinese softshell turtles (Pelodiscus spp.) results in massive erosion of biodiversity.}, journal = {Die Naturwissenschaften}, volume = {105}, number = {5-6}, pages = {34}, pmid = {29728774}, issn = {1432-1904}, support = {31471966//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Biodiversity ; *Breeding ; China ; DNA, Mitochondrial/genetics ; Microsatellite Repeats/genetics ; Phylogeny ; Turtles/*classification/*genetics ; }, abstract = {Chinese softshell turtles (Pelodiscus spp.) are widely distributed, ranging from the Amur and Ussuri Rivers in the Russian Far East through the Korean Peninsula, Japan, and eastern, central, and southern China to southern Vietnam. In East and Southeast Asia, Chinese softshell turtles are traditionally exploited for food and have been farm-bred in China since the Spring and Autumn Period, more than 2400 years ago. Currently, the annual production of Pelodiscus amounts to 340,000 t in China alone. Using mitochondrial DNA (2428 bp) and five nuclear loci (3704 bp), we examined broad sampling of wild and farm-bred Pelodiscus to infer genetic and taxonomic differentiation. We discovered four previously unknown mitochondrial lineages, all from China. One lineage from Jiangxi is deeply divergent and sister to the mitochondrial lineage of Pelodiscus axenaria. The nuclear loci supported species status for P. axenaria and the new lineage from Jiangxi. Pelodiscus maackii and P. parviformis, both harboring distinct mitochondrial lineages, were not differentiated from P. sinensis in the studied nuclear markers. The same is true for two new mitochondrial lineages from Zhejiang, China, represented by only one individual each, and another new lineage from Anhui, Guangdong, Jiangxi and Zhejiang, China. However, Vietnamese turtles yielding a mitochondrial lineage clustering within P. sinensis were distinct in nuclear markers, suggesting that these populations could represent another unknown species with introgressed mitochondria. Its species status is also supported by the syntopic occurrence with P. sinensis in northern Vietnam and by morphology. In addition, we confirmed sympatry of P. axenaria and P. parviformis in Guangxi, China, and found evidence for sympatry of P. sinensis and the new putative species from Jiangxi, China. We also discovered evidence for hybridization in turtle farms and for the occurrence of alien lineages in the wild (Zhejiang, China), highlighting the risk of genetic pollution of native stock. In the face of the large-scale breeding of Pelodiscus, we claim that the long-term survival of distinct genetic lineages and species can only be assured when an upscale market segment for pure-bred softshell turtles is established, making the breeding of pure lineages lucrative for turtle farms. Our findings underline that the diversity of Pelodiscus is currently underestimated and threatened by anthropogenic admixture. We recommend mass screening of genetic and morphological variation of Chinese softshell turtles as a first step to understand and preserve their diversity.}, } @article {pmid29730527, year = {2018}, author = {van der Hoek, MD and Madsen, O and Keijer, J and van der Leij, FR}, title = {Evolutionary analysis of the carnitine- and choline acyltransferases suggests distinct evolution of CPT2 versus CPT1 and related variants.}, journal = {Biochimica et biophysica acta. Molecular and cell biology of lipids}, volume = {1863}, number = {8}, pages = {909-918}, doi = {10.1016/j.bbalip.2018.05.001}, pmid = {29730527}, issn = {1388-1981}, mesh = {Animals ; Caenorhabditis elegans/enzymology/genetics ; Carnitine/metabolism ; Carnitine O-Palmitoyltransferase/*genetics/metabolism ; Choline/metabolism ; Drosophila/enzymology/genetics ; *Evolution, Molecular ; Exons/genetics ; Introns/genetics ; Isoenzymes/genetics/metabolism ; Mitochondria/*enzymology ; *Phylogeny ; Yeasts/enzymology/genetics ; }, abstract = {Carnitine/choline acyltransferases play diverse roles in energy metabolism and neuronal signalling. Our knowledge of their evolutionary relationships, important for functional understanding, is incomplete. Therefore, we aimed to determine the evolutionary relationships of these eukaryotic transferases. We performed extensive phylogenetic and intron position analyses. We found that mammalian intramitochondrial CPT2 is most closely related to cytosolic yeast carnitine transferases (Sc-YAT1 and 2), whereas the other members of the family are related to intraorganellar yeast Sc-CAT2. Therefore, the cytosolically active CPT1 more closely resembles intramitochondrial ancestors than CPT2. The choline acetyltransferase is closely related to carnitine acetyltransferase and shows lower evolutionary rates than long chain acyltransferases. In the CPT1 family several duplications occurred during animal radiation, leading to the isoforms CPT1A, CPT1B and CPT1C. In addition, we found five CPT1-like genes in Caenorhabditis elegans that strongly group to the CPT1 family. The long branch leading to mammalian brain isoform CPT1C suggests that either strong positive or relaxed evolution has taken place on this node. The presented evolutionary delineation of carnitine/choline acyltransferases adds to current knowledge on their functions and provides tangible leads for further experimental research.}, } @article {pmid29731304, year = {2018}, author = {Maclean, AE and Hertle, AP and Ligas, J and Bock, R and Balk, J and Meyer, EH}, title = {Absence of Complex I Is Associated with Diminished Respiratory Chain Function in European Mistletoe.}, journal = {Current biology : CB}, volume = {28}, number = {10}, pages = {1614-1619.e3}, doi = {10.1016/j.cub.2018.03.036}, pmid = {29731304}, issn = {1879-0445}, mesh = {Electron Transport/*physiology ; Electron Transport Complex I/*genetics/metabolism ; Mitochondria/*metabolism ; Oxidative Phosphorylation ; Viscum album/*genetics/metabolism ; }, abstract = {Parasitism is a life history strategy found across all domains of life whereby nutrition is obtained from a host. It is often associated with reductive evolution of the genome, including loss of genes from the organellar genomes [1, 2]. In some unicellular parasites, the mitochondrial genome (mitogenome) has been lost entirely, with far-reaching consequences for the physiology of the organism [3, 4]. Recently, mitogenome sequences of several species of the hemiparasitic plant mistletoe (Viscum sp.) have been reported [5, 6], revealing a striking loss of genes not seen in any other multicellular eukaryotes. In particular, the nad genes encoding subunits of respiratory complex I are all absent and other protein-coding genes are also lost or highly diverged in sequence, raising the question what remains of the respiratory complexes and mitochondrial functions. Here we show that oxidative phosphorylation (OXPHOS) in European mistletoe, Viscum album, is highly diminished. Complex I activity and protein subunits of complex I could not be detected. The levels of complex IV and ATP synthase were at least 5-fold lower than in the non-parasitic model plant Arabidopsis thaliana, whereas alternative dehydrogenases and oxidases were higher in abundance. Carbon flux analysis indicates that cytosolic reactions including glycolysis are greater contributors to ATP synthesis than the mitochondrial tricarboxylic acid (TCA) cycle. Our results describe the extreme adjustments in mitochondrial functions of the first reported multicellular eukaryote without complex I.}, } @article {pmid29738865, year = {2018}, author = {Feng, S and Stejskal, V and Wang, Y and Li, Z}, title = {The mitochondrial genomes of the barklice, Lepinotus reticulatus and Dorypteryx domestica (Psocodea: Trogiomorpha): Insight into phylogeny of the order Psocodea.}, journal = {International journal of biological macromolecules}, volume = {116}, number = {}, pages = {247-254}, doi = {10.1016/j.ijbiomac.2018.05.021}, pmid = {29738865}, issn = {1879-0003}, mesh = {Animals ; Base Sequence ; Evolution, Molecular ; Gene Order/genetics ; Genome, Mitochondrial/*genetics ; Insecta/*genetics ; Mitochondria/*genetics ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {The order Psocodea which has incorporated the two former orders Psocoptera (barklice and booklice) and Phthiraptera (parasitic lice) attracts much attention for its unusual mitochondrial (mt) genome rearrangements. Available phylogenetic analysis for Psocodea is subjected to partial taxa and a complete one is needed. To further explore the genome rearrangement and phylogeny in Psocodea, we sequenced the mt genomes of two barklice, Lepinotus reticulatus (collected from China) and Dorypteryx domestica (collected from Czech Republic). Both of newly sequenced barklice had typical one-chromosome mt genomes and the same mt gene arrangement with the reported Lepidopsocidae sp. The mt genomes of L. reticulatus and D. domestica contained 37 genes typical of bilateral animals. In contrast with the recent report mt genome of D. domestica, our strain was found with many single nucleotide polymorphisms in intra-specific difference. Phylogenetic relationships were inferred from all available mt genomes of Psocodea data using Maximum Likelihood and Bayesian methods. The mt genome of L. reticulatus is the first representative with complete sequences of the family Trogiidae and our D. domestica data enriched the family Psyllipsocidae, which will contribute to the further study of mt gene rearrangement and phylogeny of Psocodea.}, } @article {pmid29743632, year = {2018}, author = {Sinha, S and Bheemsetty, VA and Inamdar, MS}, title = {A double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {7362}, pmid = {29743632}, issn = {2045-2322}, mesh = {Amino Acid Motifs ; Animals ; Cell Line ; Cell Movement ; Conserved Sequence ; Endosomes/metabolism ; Evolution, Molecular ; Gene Duplication ; Gene Expression Regulation ; Humans ; Mitochondria/metabolism ; Neoplasm Proteins/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Conformation, alpha-Helical ; Protein Transport ; STAT3 Transcription Factor/*metabolism ; }, abstract = {The Ovarian Carcinoma Immunoreactive Antigen domain (OCIAD) - containing proteins OCIAD1/Asrij and OCIAD2, are implicated in several cancers and neurodegenerative diseases. While Asrij has a conserved role in facilitating STAT3 activation for JAK/STAT signaling, the expression and function of OCIAD2 in non-cancerous contexts remains unknown. Here, we report that ociad2 neighbors ociad1/asrij in most vertebrate genomes, and the two genes likely arose by tandem gene duplication, probably somewhere between the Ordovician and Silurian eras. We show that ociad2 expression is higher in the mouse kidney, liver and brain relative to other tissues. OCIAD2 localizes to early endosomes and mitochondria, and interacts with Asrij and STAT3. Knockdown and overexpression studies showed that OCIAD2 is essential for STAT3 activation and cell migration, which could contribute to its role in tumor metastasis. Structure prediction programs, protein disruption studies, biochemical and functional assays revealed a double helical motif in the OCIA domain that is necessary and sufficient for its localization, interactions and STAT3 activation. Given the importance of JAK/STAT signaling in development and disease, our studies shed light on the evolution and conserved function of the OCIA domain in regulating this pathway and will be critical for understanding this clinically important protein family.}, } @article {pmid29747566, year = {2018}, author = {Oetjens, MT and Martin, A and Veeramah, KR and Kidd, JM}, title = {Analysis of the canid Y-chromosome phylogeny using short-read sequencing data reveals the presence of distinct haplogroups among Neolithic European dogs.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {350}, pmid = {29747566}, issn = {1471-2164}, support = {R01 GM103961/GM/NIGMS NIH HHS/United States ; R01GM103961//National Institute of General Medical Sciences/ ; }, mesh = {Animals ; Coyotes/classification/*genetics ; DNA, Mitochondrial/genetics ; Dogs/classification/*genetics ; *Evolution, Molecular ; Genetic Variation ; Genome ; *Haplotypes ; Male ; *Phylogeny ; Sequence Analysis, DNA/*methods ; Wolves/classification/*genetics ; *Y Chromosome ; }, abstract = {BACKGROUND: Most genetic analyses of ancient and modern dogs have focused on variation in the autosomes or on the mitochondria. Mitochondrial DNA is more easily obtained from ancient samples than nuclear DNA and mitochondrial analyses have revealed important insights into the evolutionary history of canids. Utilizing a recently published dog Y-chromosome reference, we analyzed Y-chromosome sequence across a diverse collection of canids and determined the Y haplogroup of three ancient European dogs.

RESULTS: We identified 1121 biallelic Y-chromosome SNVs using whole-genome sequences from 118 canids and defined variants diagnostic to distinct dog Y haplogroups. Similar to that of the mitochondria and previous more limited studies of Y diversity, we observe several deep splits in the Y-chromosome tree which may be the result of retained Y-chromosome diversity which predates dog domestication or post-domestication admixture with wolves. We find that Y-chromosomes from three ancient European dogs (4700-7000 years old) belong to distinct clades.

CONCLUSIONS: We estimate that the time to the most recent comment ancestor of dog Y haplogroups is 68-151 thousand years ago. Analysis of three Y-chromosomes from the Neolithic confirms long stranding population structure among European dogs.}, } @article {pmid29752470, year = {2018}, author = {Goodall-Copestake, WP}, title = {nrDNA:mtDNA copy number ratios as a comparative metric for evolutionary and conservation genetics.}, journal = {Heredity}, volume = {121}, number = {2}, pages = {105-111}, pmid = {29752470}, issn = {1365-2540}, mesh = {Animals ; Cell Nucleus/*genetics ; *DNA Copy Number Variations ; DNA, Mitochondrial/*genetics ; DNA, Ribosomal/*genetics ; Evolution, Molecular ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics ; Muscles/metabolism ; Urochordata/*genetics ; }, abstract = {Identifying genetic cues of functional relevance is key to understanding the drivers of evolution and increasingly important for the conservation of biodiversity. This study introduces nuclear ribosomal DNA (nrDNA) to mitochondrial DNA (mtDNA) copy number ratios as a metric with which to screen for this functional genetic variation prior to more extensive omics analyses. To illustrate the metric, quantitative PCR was used to estimate nrDNA (18S) to mtDNA (16S) copy number ratios in muscle tissue from samples of two zooplankton species: Salpa thompsoni caught near Elephant Island (Southern Ocean) and S. fusiformis sampled off Gough Island (South Atlantic). Average 18S:16S ratios in these samples were 9:1 and 3:1, respectively. nrDNA 45S arrays and mitochondrial genomes were then deep sequenced to uncover the sources of intra-individual genetic variation underlying these 18S:16S copy number differences. The deep sequencing profiles obtained were consistent with genetic changes resulting from adaptive processes, including an expansion of nrDNA and damage to mtDNA in S. thompsoni, potentially in response to the polar environment. Beyond this example from zooplankton, nrDNA:mtDNA copy number ratios offer a promising metric to help identify genetic variation of functional relevance in animals more broadly.}, } @article {pmid29754387, year = {2018}, author = {Zhu, C and Chen, P and Han, Y and Ruan, L}, title = {Low Genetic Diversity and Low Gene Flow Corresponded to a Weak Genetic Structure of Ruddy-Breasted Crake (Porzana fusca) in China.}, journal = {Biochemical genetics}, volume = {56}, number = {6}, pages = {586-617}, doi = {10.1007/s10528-018-9862-9}, pmid = {29754387}, issn = {1573-4927}, support = {NSFC no. 30960052//National Science Foundation of China/ ; no. 31260510//National Science Foundation of China/ ; no. KT201537//Water - resource Department of Jiangxi Province Science and Technological Project/ ; }, mesh = {Animals ; Birds/*genetics ; DNA, Mitochondrial ; *Gene Flow ; *Genetic Structures ; *Genetic Variation ; *Genetics, Population ; Haplotypes ; Microsatellite Repeats ; Mitochondria/genetics ; Phylogeny ; }, abstract = {The Ruddy-breasted Crake (Porzana fusca) is an extremely poorly known species. Although it is not listed as globally endangered, in recent years, with the interference of climate change and human activities, its habitat is rapidly disappearing and its populations have been shrinking. There are two different life history traits for Ruddy-breasted Crake in China, i.e., non-migratory population in the south and migratory population in the north of China. In this study, mitochondrial control sequences and microsatellite datasets of 88 individuals sampled from 8 sites were applied to analyze their genetic diversity, genetic differentiation, and genetic structure. Our results indicated that low genetic diversity and genetic differentiation exit in most populations. The neutrality test suggested significantly negative Fu's Fs value, which, in combination with detection of the mismatch distribution, indicated that population expansion occurred in the interglacier approximately 98,000 years ago, and the time of the most recent common ancestor (TMRCA) was estimated to about 202,705 years ago. Gene flow analysis implied that the gene flow was low, but gene exchange was frequent among adjacent populations. Both phylogenetic and STRUCTURE analyses implied weak genetic structure. In general, the genetic diversity, gene flow, and genetic structure of Ruddy-breasted Crake were low.}, } @article {pmid29757366, year = {2018}, author = {Dobler, R and Dowling, DK and Morrow, EH and Reinhardt, K}, title = {A systematic review and meta-analysis reveals pervasive effects of germline mitochondrial replacement on components of health.}, journal = {Human reproduction update}, volume = {24}, number = {5}, pages = {519-534}, doi = {10.1093/humupd/dmy018}, pmid = {29757366}, issn = {1460-2369}, mesh = {Animals ; Basal Metabolism/genetics ; Gene Expression Regulation/genetics ; Genetic Variation ; Haplotypes ; Humans ; Mitochondria/*genetics ; Mitochondrial Replacement Therapy/*adverse effects ; Risk Assessment ; }, abstract = {BACKGROUND: Mitochondrial replacement, a form of nuclear transfer, has been proposed as a germline therapy to prevent the transmission of mitochondrial diseases. Mitochondrial replacement therapy has been licensed for clinical application in the UK, and already carried out in other countries, but little is known about negative or unintended effects on the health of offspring born using this technique.

OBJECTIVE AND RATIONALE: Studies in invertebrate models have used techniques that achieve mitochondrial replacement to create offspring with novel combinations of mitochondrial and nuclear genotype. These have demonstrated that the creation of novel mitochondrial-nuclear interactions can lead to alterations in offspring characteristics, such as development rates, fertility and longevity. However, it is currently unclear whether such interactions could similarly affect the outcomes of vertebrate biomedical studies, which have sought to assess the efficacy of the replacement therapy.

SEARCH METHODS: This systematic review addresses whether the effects of mitochondrial replacement on offspring characteristics differ in magnitude between biological (conducted on invertebrate models, with an ecological or evolutionary focus) and biomedical studies (conducted on vertebrate models, with a clinical focus). Studies were selected based on a key-word search in 'Web of Science', complemented by backward searches of reviews on the topic of mitochondrial-nuclear (mito-nuclear) interactions. In total, 43 of the resulting 116 publications identified in the search contained reliable data to estimate effect sizes of mitochondrial replacement. We found no evidence of publication bias when examining effect-size estimates across sample sizes.

OUTCOMES: Mitochondrial replacement consistently altered the phenotype, with significant effects at several levels of organismal performance and health, including gene expression, anatomy, metabolism and life-history. Biomedical and biological studies, while differing in the methods used to achieve mitochondrial replacement, showed only marginally significant differences in effect-size estimates (-0.233 [CI: -0.495 to -0.011]), with larger effect-size estimates in biomedical studies (0.697 [CI: 0.450-0.956]) than biological studies (0.462 [CI: 0.287-0.688]). Humans showed stronger effects than other species. Effects of mitochondrial replacement were also stronger in species with a higher basal metabolic rate. Based on our results, we conducted the first formal risk analysis of mitochondrial replacement, and conservatively estimate negative effects in at least one in every 130 resulting offspring born to the therapy.

WIDER IMPLICATIONS: Our findings suggest that mitochondrial replacement may routinely affect offspring characteristics across a wide array of animal species, and that such effects are likely to extend to humans. Studies in invertebrate models have confirmed mito-nuclear interactions as the underpinning cause of organismal effects following mitochondrial replacement. This therefore suggests that mito-nuclear interactions are also likely to be contributing to effects seen in biomedical studies, on vertebrate models, whose effect sizes exceeded those of biological studies. Our results advocate the use of safeguards that could offset any negative effects (defining any unintended effect as being negative) mediated by mito-nuclear interactions following mitochondrial replacement in humans, such as mitochondrial genetic matching between donor and recipient. Our results also suggest that further research into the molecular nature of mito-nuclear interactions would be beneficial in refining the clinical application of mitochondrial replacement, and in establishing what degree of variation between donor and patient mitochondrial DNA haplotypes is acceptable to ensure 'haplotype matching'.}, } @article {pmid29760081, year = {2018}, author = {Sharp, NP and Sandell, L and James, CG and Otto, SP}, title = {The genome-wide rate and spectrum of spontaneous mutations differ between haploid and diploid yeast.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5046-E5055}, pmid = {29760081}, issn = {1091-6490}, mesh = {DNA Breaks, Double-Stranded ; DNA Repair/genetics ; DNA Replication/genetics ; DNA, Fungal/*genetics ; *Diploidy ; Genes, Fungal/genetics ; *Haploidy ; Mitochondria/genetics ; Mutation/*genetics ; Mutation Rate ; Saccharomyces cerevisiae/*genetics ; }, abstract = {By altering the dynamics of DNA replication and repair, alternative ploidy states may experience different rates and types of new mutations, leading to divergent evolutionary outcomes. We report a direct comparison of the genome-wide spectrum of spontaneous mutations arising in haploids and diploids following a mutation-accumulation experiment in the budding yeast Saccharomyces cerevisiae Characterizing the number, types, locations, and effects of thousands of mutations revealed that haploids were more prone to single-nucleotide mutations (SNMs) and mitochondrial mutations, while larger structural changes were more common in diploids. Mutations were more likely to be detrimental in diploids, even after accounting for the large impact of structural changes, contrary to the prediction that mutations would have weaker effects, due to masking, in diploids. Haploidy is expected to reduce the opportunity for conservative DNA repair involving homologous chromosomes, increasing the insertion-deletion rate, but we found little support for this idea. Instead, haploids were more susceptible to SNMs in late-replicating genomic regions, resulting in a ploidy difference in the spectrum of substitutions. In diploids, we detect mutation rate variation among chromosomes in association with centromere location, a finding that is supported by published polymorphism data. Diploids are not simply doubled haploids; instead, our results predict that the spectrum of spontaneous mutations will substantially shape the dynamics of genome evolution in haploid and diploid populations.}, } @article {pmid29761268, year = {2018}, author = {Edera, AA and Gandini, CL and Sanchez-Puerta, MV}, title = {Towards a comprehensive picture of C-to-U RNA editing sites in angiosperm mitochondria.}, journal = {Plant molecular biology}, volume = {97}, number = {3}, pages = {215-231}, pmid = {29761268}, issn = {1573-5028}, mesh = {Base Pair Mismatch ; Codon/genetics ; Genes, Plant/genetics ; Genome, Mitochondrial/genetics ; Magnoliopsida/*genetics ; Mitochondria/*genetics ; Phylogeny ; *RNA Editing/genetics ; Thymidine ; Transcriptome/genetics ; }, abstract = {Our understanding of the dynamic and evolution of RNA editing in angiosperms is in part limited by the few editing sites identified to date. This study identified 10,217 editing sites from 17 diverse angiosperms. Our analyses confirmed the universality of certain features of RNA editing, and offer new evidence behind the loss of editing sites in angiosperms. RNA editing is a post-transcriptional process that substitutes cytidines (C) for uridines (U) in organellar transcripts of angiosperms. These substitutions mostly take place in mitochondrial messenger RNAs at specific positions called editing sites. By means of publicly available RNA-seq data, this study identified 10,217 editing sites in mitochondrial protein-coding genes of 17 diverse angiosperms. Even though other types of mismatches were also identified, we did not find evidence of non-canonical editing processes. The results showed an uneven distribution of editing sites among species, genes, and codon positions. The analyses revealed that editing sites were conserved across angiosperms but there were some species-specific sites. Non-synonymous editing sites were particularly highly conserved (~ 80%) across the plant species and were efficiently edited (80% editing extent). In contrast, editing sites at third codon positions were poorly conserved (~ 30%) and only partially edited (~ 40% editing extent). We found that the loss of editing sites along angiosperm evolution is mainly occurring by replacing editing sites with thymidines, instead of a degradation of the editing recognition motif around editing sites. Consecutive and highly conserved editing sites had been replaced by thymidines as result of retroprocessing, by which edited transcripts are reverse transcribed to cDNA and then integrated into the genome by homologous recombination. This phenomenon was more pronounced in eudicots, and in the gene cox1. These results suggest that retroprocessing is a widespread driving force underlying the loss of editing sites in angiosperm mitochondria.}, } @article {pmid29769322, year = {2018}, author = {Krah, A and Zarco-Zavala, M and McMillan, DGG}, title = {Insights into the regulatory function of the ɛ subunit from bacterial F-type ATP synthases: a comparison of structural, biochemical and biophysical data.}, journal = {Open biology}, volume = {8}, number = {5}, pages = {}, pmid = {29769322}, issn = {2046-2441}, mesh = {Adenosine Triphosphate/metabolism ; Bacillaceae/*enzymology/genetics ; Bacillus/enzymology/genetics ; Bacterial Proteins/chemistry/genetics/metabolism ; Binding Sites ; Crystallography, X-Ray ; Escherichia coli/*enzymology/genetics ; Mitochondrial Proton-Translocating ATPases/*chemistry/genetics/*metabolism ; Models, Molecular ; Mutation ; Protein Conformation ; }, abstract = {ATP synthases catalyse the formation of ATP, the most common chemical energy storage unit found in living cells. These enzymes are driven by an electrochemical ion gradient, which allows the catalytic evolution of ATP by a binding change mechanism. Most ATP synthases are capable of catalysing ATP hydrolysis to varying degrees, and to prevent wasteful ATP hydrolysis, bacteria and mitochondria have regulatory mechanisms such as ADP inhibition. Additionally, ɛ subunit inhibition has also been described in three bacterial systems, Escherichia coli, Bacillus PS3 and Caldalkalibacillus thermarum TA2.A1. Previous studies suggest that the ɛ subunit is capable of undergoing an ATP-dependent conformational change from the ATP hydrolytic inhibitory 'extended' conformation to the ATP-induced non-inhibitory 'hairpin' conformation. A recently published crystal structure of the F1 domain of the C. thermarum TA2.A1 F1Fo ATP synthase revealed a mutant ɛ subunit lacking the ability to bind ATP in a hairpin conformation. This is a surprising observation considering it is an organism that performs no ATP hydrolysis in vivo, and appears to challenge the current dogma on the regulatory role of the ɛ subunit. This has prompted a re-examination of present knowledge of the ɛ subunits role in different organisms. Here, we compare published biochemical, biophysical and structural data involving ɛ subunit-mediated ATP hydrolysis regulation in a variety of organisms, concluding that the ɛ subunit from the bacterial F-type ATP synthases is indeed capable of regulating ATP hydrolysis activity in a wide variety of bacteria, making it a potentially valuable drug target, but its exact role is still under debate.}, } @article {pmid29770661, year = {2018}, author = {Cang-Lin, Z and Jia, P and Zhen, R and Jin-Rong, Z and Ya-Ming, Y}, title = {[Genotyping and polymorphism analysis of cytochrome c oxidase subunit Ⅰ gene of Pomacea canaliculata from Lincang City in Yunnan Province].}, journal = {Zhongguo xue xi chong bing fang zhi za zhi = Chinese journal of schistosomiasis control}, volume = {30}, number = {2}, pages = {179-183}, doi = {10.16250/j.32.1374.2017163}, pmid = {29770661}, issn = {1005-6661}, mesh = {Angiostrongylus cantonensis ; Animals ; China ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/*genetics ; Gastropoda/enzymology/*genetics ; Genotype ; Haplotypes ; Phylogeny ; }, abstract = {OBJECTIVE: To analyze the genetic diversity of Pomacea canaliculata based on the mitochondria DNA cytochrome c oxidase subunit Ⅰ (mtDNA COⅠ) gene as a molecular marker in Lincang City of Yunnan Province, so as to provide the scientific data for monitoring Angiostrongylus cantonensis in local areas.

METHODS: The genotypes and polymorphisms of 38 specimens of P. canaliculata collected from Mengding Town of Lincang City were analyzed by sequencing COⅠ gene. The phylogenetic tree and genetic distances were produced based on the haplotypes from GenBank and the present study by using the neighbourjoining method with the software MEGA version 6.06.

RESULTS: Totally 31 sequences were acquired in the present study and they produced 3 unique haplotypes. Haplotype 1 showed a higher frequency compared to the others and it accounted for 83.9 % (26/31). The data showed that the least genetic distances ranged from 0 to 0.052 between P. canaliculata and 3 haplotypes, as well as the largest genetic distances ranged from 0.021 to 0.239 between Pila conica and 3 haplotypes. Otherwise, the analysis of the phylogenetic trees based on COⅠ gene sequences of P. canaliculata indicated that all of 3 haplotypes clustered into one big clade with that from Japan (GenBank accession number: AB433769), China (GenBank accession number: KT313034) and USA (GenBank accession number: EU523129), which owned the closet relationship amongst them. Their genetic relationships were distantly related to the GenBank's reference sequences of P. insularum (GenBank accession number: EF514942), P. camena (GenBank accession number: EF515059) and so on.

CONCLUSIONS: There is a P. canaliculata species in Lincang City of Yunnan Province as well as a high genetic diversity amongst the acquired 3 haplotypes in this study.}, } @article {pmid29779502, year = {2018}, author = {Buysse, M and Duron, O}, title = {Multi-locus phylogenetics of the Midichloria endosymbionts reveals variable specificity of association with ticks.}, journal = {Parasitology}, volume = {145}, number = {14}, pages = {1969-1978}, doi = {10.1017/S0031182018000793}, pmid = {29779502}, issn = {1469-8161}, mesh = {Alphaproteobacteria/*classification ; Animals ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Female ; Genetic Variation ; Host Specificity ; Ixodes/*microbiology ; Male ; Multilocus Sequence Typing ; *Phylogeny ; *Symbiosis ; }, abstract = {Candidatus Midichloria mitochondrii is a maternally inherited bacterium of ticks with a unique intra-mitochondrial lifestyle. Here, we investigate on the evolutionary history of these associations and the degree of Midichloria-tick specificity. While previous surveys used the 16S rRNA gene as an exclusive molecular marker, we rather developed a multi-locus typing method based on four more variable housekeeping genes (groEL, rpoB, dnaK and ftsZ) and on one flagellum gene (fliC) present in Midichloria genomes. Using this method, multi-locus phylogenetic analyses revealed the structuring of a wide Midichloria genetic diversity into three distinct lineages associated with ticks. Overall, two distinct evolutionary strategies are obvious depending on lineage: two Midichloria lineages are generalists with infections acquired through horizontal transfers between distantly related tick species but one other Midichloria lineage rather show a high specificity degree to the Ixodes tick genus. This pattern suggests a capacity of certain Midichloria strains to maintain infections in only limited range of related tick species. These different infection strategies of Midichloria highlight an unexpected variability in their dependency to their tick hosts. We further conjecture that this pattern is also likely to indicate variability in their effects on ticks.}, } @article {pmid29787548, year = {2018}, author = {Kaczmarek, E and Hauser, CJ and Kwon, WY and Riça, I and Chen, L and Sandler, N and Otterbein, LE and Campbell, Y and Cook, CH and Yaffe, MB and Marusich, MF and Itagaki, K}, title = {A subset of five human mitochondrial formyl peptides mimics bacterial peptides and functionally deactivates human neutrophils.}, journal = {The journal of trauma and acute care surgery}, volume = {85}, number = {5}, pages = {936-943}, doi = {10.1097/TA.0000000000001971}, pmid = {29787548}, issn = {2163-0763}, mesh = {Calcium/metabolism ; Cells, Cultured ; Chemokine CXCL1/pharmacology ; Chemotaxis/*drug effects ; Computational Biology ; Cyclooxygenase 1/genetics/metabolism ; Cytosol/metabolism ; Electron Transport Complex I/genetics/metabolism ; Evolution, Molecular ; Humans ; Leukotriene B4/pharmacology ; Mitochondria/metabolism ; Mitochondrial Proteins/genetics/metabolism ; N-Formylmethionine Leucyl-Phenylalanine/chemistry/pharmacology ; NADH Dehydrogenase/genetics/metabolism ; Neutrophils/*physiology ; Peptides/*blood/chemistry/genetics/*pharmacology ; Receptors, Formyl Peptide/antagonists & inhibitors/metabolism ; Signal Transduction ; Wounds and Injuries/*blood ; }, abstract = {BACKGROUND: Trauma causes inflammation by releasing mitochondria that act as Danger-Associated Molecular Patterns (DAMPs). Trauma also increases susceptibility to infection. Human mitochondria contain 13 N-formyl peptides (mtFPs). We studied whether mtFPs released into plasma by clinical injury induce neutrophil (PMN) inflammatory responses, whether their potency reflects their similarity to bacterial FPs and how their presence at clinically relevant concentration affects PMN function.

METHODS: N-terminal sequences of the 13 mtFPs were synthesized. Changes in human PMN cytosolic Ca concentration ([Ca]i) and chemotactic responses to mtFPs were studied. Sequence similarity of mtFPs to the canonical bacterial peptide f-Met-Leu-Phe (fMLF/fMLP) was studied using the BLOcks SUbstitution Matrix 62 (BLOSUM 62) system. The presence of mtFPs in plasma of trauma patients was assayed by Enzyme-linked immunosorbent assay (ELISA). The effects of the most potent mtFP (ND6) on PMN signaling and function were then studied at ambient clinical concentrations by serial exposure of native PMN to ND6, chemokines and leukotrienes.

RESULTS: Five mtFPs (ND6, ND3, ND4, ND5, and Cox 1) induced [Ca]i flux and chemotaxis in descending order of potency. Evolutionary similarity to fMLF predicted [Ca]i flux and chemotactic potency linearly (R = 0.97, R = 0.95). Chemoattractant potency was also linearly related to [Ca]i flux induction (R = 0.92). Active mtFPs appear to circulate in significant amounts immediately after trauma and persist through the first week. The most active mtFP, ND6, suppresses responses to physiologic alveolar chemoattractants (CXCL-1, leukotriene B4) as well as to fMLF where CXCL-1 and leukotriene B4 do not suppress N-formyl peptide receptor (FPR)-1 responses to mtFPs. Prior FPR-1 inhibition rescues PMN from heterologous suppression of CXCR-1 and BLT-1 by mtFPs.

CONCLUSION: The data suggest mtFPs released by injured tissue may attract PMN to trauma sites while suppressing PMN responses to other chemoattractants. Inhibition of mtFP-FPR1 interactions might increase PMN recruitment to lung bacterial inoculation after trauma. These findings suggest new paradigms for preventing infections after trauma.

LEVEL OF EVIDENCE: Therapeutic, Level IV.}, } @article {pmid29787733, year = {2018}, author = {Younas, F and Soltanmohammadi, N and Knapp, O and Benz, R}, title = {The major outer membrane protein of Legionella pneumophila Lpg1974 shows pore-forming characteristics similar to the human mitochondrial outer membrane pore, hVDAC1.}, journal = {Biochimica et biophysica acta. Biomembranes}, volume = {1860}, number = {8}, pages = {1544-1553}, doi = {10.1016/j.bbamem.2018.05.008}, pmid = {29787733}, issn = {0005-2736}, mesh = {Amino Acid Sequence ; Bacterial Outer Membrane Proteins/chemistry/classification/genetics/*metabolism ; Escherichia coli/metabolism ; Humans ; Legionella pneumophila/*metabolism ; Lipid Bilayers/chemistry/metabolism ; Phylogeny ; Protein Structure, Secondary ; Recombinant Proteins/biosynthesis/chemistry/isolation & purification ; Sequence Alignment ; Voltage-Dependent Anion Channel 1/chemistry/*metabolism ; }, abstract = {Legionella pneumophila is an aerobic and nonspore-forming pathogenic Gram-negative bacterium of the genus Legionella. It is the causative agent of Legionnaires' disease, also known as Legionellosis. The hosts of this organism are diverse, ranging from simple water borne protozoans such as amoebae to more complex hosts such as macrophages in humans. Genome analyses have shown the presence of genes coding for eukaryotic like proteins in several Legionella species. The presence of these proteins may assist L. pneumophila in its adaptation to the eukaryotic host. We studied the characteristics of a protein (Lpg1974) of L. pneumophila that shows remarkable homologies in length of the primary sequence and for the identity/homology of many amino acids to the voltage dependent anion channel (human VDAC1, Porin 31HL) of human mitochondria. Two different forms of Lpg1974 were overexpressed in Escherichia coli and purified to homogeneity: the one containing a putative N-terminal signal sequence and one without it. Reconstituted protein containing the signal sequence formed ion-permeable pores in lipid bilayer membranes with a conductance of approximately 5.4 nS in 1 M KCl. When the predicted N-terminal signal peptide of Lpg1974 comprising an α-helical structure similar to that at the N-terminus of hVDAC1 was removed, the channels formed in reconstitution experiments had a conductance of 7.6 nS in 1 M KCl. Both Lpg1974 proteins formed pores that were voltage-dependent and anion-selective similar to the pores formed by hVDAC1. These results suggest that Lpg1974 of L. pneumophila is indeed a structural and functional homologue to hVDAC1.}, } @article {pmid29787825, year = {2018}, author = {Long, Z and Li, H and Du, Y and Han, B}, title = {Congenital sideroblastic anemia: Advances in gene mutations and pathophysiology.}, journal = {Gene}, volume = {668}, number = {}, pages = {182-189}, doi = {10.1016/j.gene.2018.05.074}, pmid = {29787825}, issn = {1879-0038}, mesh = {Anemia, Sideroblastic/congenital/*genetics/metabolism ; Heme/biosynthesis ; Humans ; Iron/metabolism ; Mitochondrial Proteins/biosynthesis ; *Mutation ; }, abstract = {Congenital sideroblastic anemia (CSA) is a series of rare, heterogeneous disorders, characterized by iron overload in the mitochondria of erythroblasts and ringed sideroblasts in bone marrow. In recent years, rapid development of next-generation sequencing technology brings great advance in understanding of genetic and pathophysiologic features of CSA. Based on the pathophysiology of mitochondrial iron metabolism, causative genes of CSA can be divided into three subtypes: heme biosynthesis related; iron‑sulfur cluster biosynthesis and transportation related; and mitochondrial respiratory chain synthesis related. Patients with CSA present various clinical manifestation due to relevant mutation gene and require different treatment strategies. The recognition of the causative genes and evolution of pathogenicity is critical. In this review, we summarize the recent progress in mutation genes of CSA, and its potential role in the pathogenesis, diagnosis and treatment.}, } @article {pmid29792772, year = {2018}, author = {Xia, C and Wang, M and Yin, C and Cornejo, OE and Hulbert, SH and Chen, X}, title = {Genome Sequence Resources for the Wheat Stripe Rust Pathogen (Puccinia striiformis f. sp. tritici) and the Barley Stripe Rust Pathogen (Puccinia striiformis f. sp. hordei).}, journal = {Molecular plant-microbe interactions : MPMI}, volume = {31}, number = {11}, pages = {1117-1120}, doi = {10.1094/MPMI-04-18-0107-A}, pmid = {29792772}, issn = {0894-0282}, mesh = {Basidiomycota/*genetics ; Genome, Fungal/*genetics ; *Genomics ; Genotype ; High-Throughput Nucleotide Sequencing ; Hordeum/*microbiology ; Phenotype ; Plant Diseases/*microbiology ; Sequence Analysis, RNA ; Triticum/*microbiology ; }, abstract = {Puccinia striiformis f. sp. tritici causes devastating stripe (yellow) rust on wheat and P. striiformis f. sp. hordei causes stripe rust on barley. Several P. striiformis f. sp. tritici genomes are available, but no P. striiformis f. sp. hordei genome is available. More genomes of P. striiformis f. sp. tritici and P. striiformis f. sp. hordei are needed to understand the genome evolution and molecular mechanisms of their pathogenicity. We sequenced P. striiformis f. sp. tritici isolate 93-210 and P. striiformis f. sp. hordei isolate 93TX-2, using PacBio and Illumina technologies and RNA sequencing. Their genomic sequences were assembled to contigs with high continuity and showed significant structural differences. The circular mitochondria genomes of both were complete. These genomes provide high-quality resources for deciphering the genomic basis of rapid evolution and host adaptation, identifying genes for avirulence and other important traits, and studying host-pathogen interactions.}, } @article {pmid29794041, year = {2018}, author = {Camus, MF and Dowling, DK}, title = {Mitochondrial genetic effects on reproductive success: signatures of positive intrasexual, but negative intersexual pleiotropy.}, journal = {Proceedings. Biological sciences}, volume = {285}, number = {1879}, pages = {}, pmid = {29794041}, issn = {1471-2954}, mesh = {Animals ; Drosophila melanogaster/genetics/*physiology ; Female ; Genes, Mitochondrial/*genetics ; *Genetic Pleiotropy ; *Genetic Variation ; *Haplotypes ; Male ; Reproduction ; }, abstract = {Theory predicts that maternal inheritance of mitochondria will facilitate the accumulation of mtDNA mutations that are male biased, or even sexually antagonistic, in effect. While there are many reported cases of mtDNA mutations conferring cytoplasmic male sterility in plants, historically it was assumed such mutations would not persist in the streamlined mitochondrial genomes of bilaterian metazoans. Intriguingly, recent cases of mitochondrial variants exerting male biases in effect have come to light in bilaterians. These cases aside, it remains unknown whether the mitochondrial genetic variation affecting phenotypic expression, and in particular reproductive performance, in bilaterians is routinely composed of sex-biased or sex-specific variation. If selection consistently favours mtDNA variants that augment female fitness, but at cost to males, this could shape patterns of pleiotropy and lead to negative intersexual correlations across mtDNA haplotypes. Here, we show that genetic variation across naturally occurring mitochondrial haplotypes affects components of reproductive success in both sexes, in the fruit fly Drosophila melanogaster We find that intrasexual correlations across mitochondrial haplotypes, for components of reproductive success, are generally positive, while intersexual correlations are negative. These results accord with theoretical predictions, suggesting that maternal inheritance has led to the fixation of numerous mutations of sexually antagonistic effect.}, } @article {pmid29794164, year = {2018}, author = {Ries, LNA and José de Assis, L and Rodrigues, FJS and Caldana, C and Rocha, MC and Malavazi, I and Bayram, Ö and Goldman, GH}, title = {The Aspergillus nidulans Pyruvate Dehydrogenase Kinases Are Essential To Integrate Carbon Source Metabolism.}, journal = {G3 (Bethesda, Md.)}, volume = {8}, number = {7}, pages = {2445-2463}, pmid = {29794164}, issn = {2160-1836}, mesh = {Aspergillus nidulans/classification/genetics/*metabolism ; Carbon/*metabolism ; Catabolite Repression ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Fungal ; Glucose/metabolism ; Hydrolysis ; Metabolic Networks and Pathways ; Metabolome ; Metabolomics/methods ; Multigene Family ; Phylogeny ; Protein Interaction Mapping ; Protein Interaction Maps ; Protein Serine-Threonine Kinases/genetics/*metabolism ; Protein Transport ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase ; }, abstract = {The pyruvate dehydrogenase complex (PDH), that converts pyruvate to acetyl-coA, is regulated by pyruvate dehydrogenase kinases (PDHK) and phosphatases (PDHP) that have been shown to be important for morphology, pathogenicity and carbon source utilization in different fungal species. The aim of this study was to investigate the role played by the three PDHKs PkpA, PkpB and PkpC in carbon source utilization in the reference filamentous fungus Aspergillus nidulans, in order to unravel regulatory mechanisms which could prove useful for fungal biotechnological and biomedical applications. PkpA and PkpB were shown to be mitochondrial whereas PkpC localized to the mitochondria in a carbon source-dependent manner. Only PkpA was shown to regulate PDH activity. In the presence of glucose, deletion of pkpA and pkpC resulted in reduced glucose utilization, which affected carbon catabolite repression (CCR) and hydrolytic enzyme secretion, due to de-regulated glycolysis and TCA cycle enzyme activities. Furthermore, PkpC was shown to be required for the correct metabolic utilization of cellulose and acetate. PkpC negatively regulated the activity of the glyoxylate cycle enzyme isocitrate lyase (ICL), required for acetate metabolism. In summary, this study identified PDHKs important for the regulation of central carbon metabolism in the presence of different carbon sources, with effects on the secretion of biotechnologically important enzymes and carbon source-related growth. This work demonstrates how central carbon metabolism can affect a variety of fungal traits and lays a basis for further investigation into these characteristics with potential interest for different applications.}, } @article {pmid29799088, year = {2018}, author = {Li, Q and Chen, C and Xiong, C and Jin, X and Chen, Z and Huang, W}, title = {Comparative mitogenomics reveals large-scale gene rearrangements in the mitochondrial genome of two Pleurotus species.}, journal = {Applied microbiology and biotechnology}, volume = {102}, number = {14}, pages = {6143-6153}, doi = {10.1007/s00253-018-9082-6}, pmid = {29799088}, issn = {1432-0614}, support = {2016NZ0042//The National Science & Technology Pillar Program of Sichuan/ ; 2016NZ0103//the Crop Molecular Breeding Platform in Sichuan/ ; }, mesh = {DNA, Mitochondrial/genetics ; Gene Rearrangement/*genetics ; Genome, Mitochondrial/*genetics ; Phylogeny ; Pleurotus/classification/*genetics ; Species Specificity ; }, abstract = {In the present study, we assembled the mitogenomes of Pleurotus citrinopileatus and Pleurotus platypus. The circular mitogenome of the two Pleurotus species comprises a set of 14 conserved protein-encoding genes (PEGs), 2 RNA genes (small subunit ribosomal RNA and large subunit ribosomal RNA), and 24 tRNAs, with sizes of 60,694 and 73,807 bp, respectively. They contain 4 and 10 introns with 3 and 10 intronic open reading frames (ORFs), respectively. Thirteen position classes (Pcls) of introns were found in the cox1 gene of four Pleurotus species. The number and class of Pcl varied among different Pleurotus species, indicating that numerous events of loss and gain occurred during evolution of Pleurotus. Comparative mitogenomic and collinearity analyses reveal that large-scale gene rearrangements may have occurred during the evolution of Pleurotus citrinopileatus and Pleurotus platypus, including gene rearrangements and inversions, which may be related to the observed high amounts of repetitive DNA elements (5.62 and 5.45%, respectively). Phylogenetic analysis based on concatenated mitochondrial protein sequences reveals that concatenated mitochondrial genes are suitable as molecular markers for phylogenetic analysis. This serves as the first report on large-scale rearrangements in the mitochondria of the genus Pleurotus, thereby improving our understanding of the evolution of the Pleurotus genus and other macrofungi.}, } @article {pmid29802659, year = {2018}, author = {Tilquin, A and Christie, JR and Kokko, H}, title = {Mitochondrial complementation: a possible neglected factor behind early eukaryotic sex.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1152-1164}, doi = {10.1111/jeb.13293}, pmid = {29802659}, issn = {1420-9101}, mesh = {Animals ; *Biological Evolution ; Eukaryota/*genetics/*physiology ; *Mitochondria ; Models, Biological ; Reproduction/*genetics/*physiology ; }, abstract = {Sex is ancestral in eukaryotes. Meiotic sex differs from bacterial ways of exchanging genetic material by involving the fusion of two cells. We examine the hypothesis that fusion evolved in early eukaryotes because it was directly beneficial, rather than a passive side effect of meiotic sex. We assume that the uptake of (proto)mitochondria into eukaryotes preceded the evolution of cell fusion and that Muller's ratchet operating within symbiont lineages led to the accumulation of lineage-specific sets of mutations in asexual host cells. We examine whether cell fusion, and the consequent biparental inheritance of symbionts, helps to mitigate the effects of this mutational meltdown of mitochondria. In our model, host cell fitness improves when two independently evolved mitochondrial strains co-inhabit a single cytoplasm, mirroring mitochondrial complementation found in modern eukaryotes. If fusion incurs no cost, we find that an allele coding for fusion can invade a population of nonfusers. If fusion is costly, there are two thresholds. The first describes a maximal fusing rate (probability of fusion per round of cell division) that is able to fix. An allele that codes for a rate above this threshold can reach a polymorphic equilibrium with nonfusers, as long as the rate is below the second threshold, above which the fusion allele is counter-selected. Whenever it evolves, fusion increases the population-wide level of heteroplasmy, which allows mitochondrial complementation and increases population fitness. We conclude that beneficial interactions between mitochondria are a potential factor that selected for cell fusion in early eukaryotes.}, } @article {pmid29806019, year = {2018}, author = {Taborsky, M and Schütz, D and Goffinet, O and van Doorn, GS}, title = {Alternative male morphs solve sperm performance/longevity trade-off in opposite directions.}, journal = {Science advances}, volume = {4}, number = {5}, pages = {eaap8563}, pmid = {29806019}, issn = {2375-2548}, mesh = {Animals ; Cell Survival ; *Cichlids ; Male ; Reproduction ; Semen Analysis ; *Sexual Behavior, Animal ; Sperm Motility ; Spermatozoa/*physiology ; }, abstract = {Males pursuing alternative reproductive tactics have been predicted to face a trade-off between maximizing either swimming performance or endurance of their sperm. However, empirical evidence for this trade-off is equivocal, which may be due to simplistic assumptions. In the shell-brooding cichlid fish Lamprologus callipterus, two Mendelian male morphs compete for fertilization by divergent means: Bourgeois nest males ejaculate sperm, on average, about six times farther from the unfertilized ova than do parasitic dwarf males. This asymmetry is opposite to the usual situation, in which bourgeois males typically benefit from superior fertilization opportunities, suggesting that nest males' sperm should persist longer than dwarf male sperm. The assumed trade-off between sperm swimming performance and longevity predicts that, in turn, sperm of dwarf males should outperform that of nest males in swimming efficiency. Measurement of sperm performance and endurance reveals that dwarf male spermatozoa swim straighter initially than those of nest males, but their motility declines earlier and their velocity slows down more abruptly. Nest male sperm survives longer, which relates to a larger sperm head plus midpiece, implying more mitochondria. Thus, the trade-off between sperm performance and endurance is optimized in opposite directions by alternative male morphs. We argue that the relative success of alternative sperm performance strategies can be influenced strongly by environmental factors such as the time window between gamete release and fertilization, and the position of gamete release. This is an important yet little understood aspect of gametic adaptations to sperm competition.}, } @article {pmid29808012, year = {2018}, author = {Yuan, L and Zhai, L and Qian, L and Huang, D and Ding, Y and Xiang, H and Liu, X and Thompson, JW and Liu, J and He, YH and Chen, XQ and Hu, J and Kong, QP and Tan, M and Wang, XF}, title = {Switching off IMMP2L signaling drives senescence via simultaneous metabolic alteration and blockage of cell death.}, journal = {Cell research}, volume = {28}, number = {6}, pages = {625-643}, pmid = {29808012}, issn = {1748-7838}, support = {R01 CA154586/CA/NCI NIH HHS/United States ; UL1 TR001117/TR/NCATS NIH HHS/United States ; }, mesh = {Aging ; Animals ; Apoptosis Inducing Factor/*metabolism ; Cell Death ; Cell Line ; *Cellular Senescence ; Endopeptidases/*metabolism ; Glycerolphosphate Dehydrogenase/*metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Mice, Inbred C57BL ; Oxidative Stress ; *Signal Transduction ; }, abstract = {Cellular senescence is a fundamental cell fate playing a significant role throughout the natural aging process. However, the molecular determinants distinguishing senescence from other cell-cycle arrest states such as quiescence and post-mitotic state, and the specified mechanisms underlying cell-fate decisions towards senescence versus cell death in response to cellular stress stimuli remain less understood. Employing multi-omics approaches, we revealed that switching off the specific mitochondrial processing machinery involving the peptidase IMMP2L serves as the foundation of the senescence program, which was also observed during the mammalian aging process. Mechanistically, we demonstrate that IMMP2L processes and thus activates at least two substrates, mitochondrial metabolic enzyme glycerol-3-phosphate dehydrogenase (GPD2) and cell death regulator apoptosis-inducing factor (AIF). For cells destined to senesce, concerted shutdown of the IMMP2L-GPD2 and IMMP2L-AIF signaling axes collaboratively drives the senescent process by reprogramming mitochondria-associated redox status, phospholipid metabolism and signaling network, and simultaneously blocking cell death under oxidative stress conditions.}, } @article {pmid29842994, year = {2018}, author = {Weerts, MJA and Timmermans, EC and van de Stolpe, A and Vossen, RHAM and Anvar, SY and Foekens, JA and Sleijfer, S and Martens, JWM}, title = {Tumor-Specific Mitochondrial DNA Variants Are Rarely Detected in Cell-Free DNA.}, journal = {Neoplasia (New York, N.Y.)}, volume = {20}, number = {7}, pages = {687-696}, pmid = {29842994}, issn = {1476-5586}, mesh = {Aged ; Aged, 80 and over ; Alleles ; *Biomarkers, Tumor ; *Circulating Tumor DNA ; Computational Biology/methods ; *DNA, Mitochondrial ; *DNA, Neoplasm ; Female ; Gene Frequency ; Genetic Heterogeneity ; *Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Neoplasms/*genetics/pathology ; Phylogeny ; }, abstract = {The use of blood-circulating cell-free DNA (cfDNA) as a "liquid biopsy" in oncology is being explored for its potential as a cancer biomarker. Mitochondria contain their own circular genomic entity (mitochondrial DNA, mtDNA), up to even thousands of copies per cell. The mutation rate of mtDNA is several orders of magnitude higher than that of the nuclear DNA. Tumor-specific variants have been identified in tumors along the entire mtDNA, and their number varies among and within tumors. The high mtDNA copy number per cell and the high mtDNA mutation rate make it worthwhile to explore the potential of tumor-specific cf-mtDNA variants as cancer marker in the blood of cancer patients. We used single-molecule real-time (SMRT) sequencing to profile the entire mtDNA of 19 tissue specimens (primary tumor and/or metastatic sites, and tumor-adjacent normal tissue) and 9 cfDNA samples, originating from 8 cancer patients (5 breast, 3 colon). For each patient, tumor-specific mtDNA variants were detected and traced in cfDNA by SMRT sequencing and/or digital PCR to explore their feasibility as cancer biomarker. As a reference, we measured other blood-circulating biomarkers for these patients, including driver mutations in nuclear-encoded cfDNA and cancer-antigen levels or circulating tumor cells. Four of the 24 (17%) tumor-specific mtDNA variants were detected in cfDNA, however at much lower allele frequencies compared to mutations in nuclear-encoded driver genes in the same samples. Also, extensive heterogeneity was observed among the heteroplasmic mtDNA variants present in an individual. We conclude that there is limited value in tracing tumor-specific mtDNA variants in blood-circulating cfDNA with the current methods available.}, } @article {pmid29843598, year = {2018}, author = {Perry, KD and Baker, GJ and Powis, KJ and Kent, JK and Ward, CM and Baxter, SW}, title = {Cryptic Plutella species show deep divergence despite the capacity to hybridize.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {77}, pmid = {29843598}, issn = {1471-2148}, support = {UA00146//University of Adelaide/International ; DAS00094//Grains Research and Development Corporation/International ; DAS00155//Grains Research and Development Corporation/International ; DAS00155//Grains Research and Development Corporation/International ; DAS00155//Grains Research and Development Corporation/International ; DP120100047//Australian Research Council/International ; FT140101303//Australian Research Council/International ; }, mesh = {Animals ; Australia ; Biological Assay ; Crosses, Genetic ; DNA, Mitochondrial/genetics ; Female ; Fertility ; *Genetic Variation ; Genetics, Population ; Geography ; Haplotypes/genetics ; Heterozygote ; *Hybridization, Genetic/drug effects ; Insecticide Resistance/drug effects/genetics ; Insecticides/toxicity ; Likelihood Functions ; Male ; Mitochondria/genetics ; Moths/*genetics/microbiology ; Phylogeny ; Species Specificity ; Sympatry ; Wolbachia/drug effects/physiology ; }, abstract = {BACKGROUND: Understanding genomic and phenotypic diversity among cryptic pest taxa has important implications for the management of pests and diseases. The diamondback moth, Plutella xylostella L., has been intensively studied due to its ability to evolve insecticide resistance and status as the world's most destructive pest of brassicaceous crops. The surprise discovery of a cryptic species endemic to Australia, Plutella australiana Landry & Hebert, raised questions regarding the distribution, ecological traits and pest status of the two species, the capacity for gene flow and whether specific management was required. Here, we collected Plutella from wild and cultivated brassicaceous plants from 75 locations throughout Australia and screened 1447 individuals to identify mtDNA lineages and Wolbachia infections. We genotyped genome-wide SNP markers using RADseq in coexisting populations of each species. In addition, we assessed reproductive compatibility in crossing experiments and insecticide susceptibility phenotypes using bioassays.

RESULTS: The two Plutella species coexisted on wild brassicas and canola crops, but only 10% of Plutella individuals were P. australiana. This species was not found on commercial Brassica vegetable crops, which are routinely sprayed with insecticides. Bioassays found that P. australiana was 19-306 fold more susceptible to four commonly-used insecticides than P. xylostella. Laboratory crosses revealed that reproductive isolation was incomplete but directionally asymmetric between the species. However, genome-wide nuclear SNPs revealed striking differences in genetic diversity and strong population structure between coexisting wild populations of each species. Nuclear diversity was 1.5-fold higher in P. australiana, yet both species showed limited variation in mtDNA. Infection with a single Wolbachia subgroup B strain was fixed in P. australiana, suggesting that a selective sweep contributed to low mtDNA diversity, while a subgroup A strain infected just 1.5% of P. xylostella.

CONCLUSIONS: Despite sympatric distributions and the capacity to hybridize, strong genomic and phenotypic divergence exists between these Plutella species that is consistent with contrasting colonization histories and reproductive isolation after secondary contact. Although P. australiana is a potential pest of brassicaceous crops, it is of secondary importance to P. xylostella.}, } @article {pmid29843612, year = {2018}, author = {Hartmann, T and Bernt, M and Middendorf, M}, title = {EqualTDRL: illustrating equivalent tandem duplication random loss rearrangements.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {192}, pmid = {29843612}, issn = {1471-2105}, mesh = {DNA, Intergenic ; *Evolution, Molecular ; Gene Duplication ; Gene Order ; Genes, Duplicate ; *Genome, Mitochondrial ; *Software ; }, abstract = {BACKGROUND: To study the differences between two unichromosomal circular genomes, e.g., mitochondrial genomes, under the tandem duplication random loss (TDRL) rearrangement it is important to consider the whole set of potential TDRL rearrangement events that could have taken place. The reason is that for two given circular gene orders there can exist different TDRL rearrangements that transform one of the gene orders into the other. Hence, a TDRL event cannot always be reconstructed only from the knowledge of the circular gene order before a TDRL event and the circular gene order after it.

RESULTS: We present the program EqualTDRL that computes and illustrates the complete set of TDRLs for pairs of circular gene orders that differ by only one TDRL. EqualTDRL considers the circularity of the given genomes and certain restrictions on the TDRL rearrangements. Examples for the latter are sequences of genes that have to be conserved during a TDRL or pairs of genes that frame intergenic regions which might represent remnants of duplicated genes. Additionally, EqualTDRL allows to determine the set of TDRLs that are minimum with respect to the number of duplicated genes.

CONCLUSION: EqualTDRL supports scientists to study the complete set of TDRLs that possibly could have taken place in the evolution of mitochondrial genomes. EqualTDRL is implemented in C++ using the ggplot2 package of the open source programming language R and is freely available from http://pacosy.informatik.uni-leipzig.de/equaltdrl .}, } @article {pmid29848286, year = {2018}, author = {Darbani, B and Kell, DB and Borodina, I}, title = {Energetic evolution of cellular Transportomes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {418}, pmid = {29848286}, issn = {1471-2164}, support = {BB/P009042/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 757384//H2020 European Research Council/ ; NNF10CC1016517//The Novo Nordisk Foundation Center for Biosustainability/ ; BB/M006891/1, BB/M017702/1 and BB/P009042/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Energy Metabolism ; *Evolution, Molecular ; *Genomics ; Membrane Transport Proteins/*metabolism ; }, abstract = {BACKGROUND: Transporter proteins mediate the translocation of substances across the membranes of living cells. Many transport processes are energetically expensive and the cells use 20 to 60% of their energy to power the transportomes. We hypothesized that there may be an evolutionary selection pressure for lower energy transporters.

RESULTS: We performed a genome-wide analysis of the compositional reshaping of the transportomes across the kingdoms of bacteria, archaea, and eukarya. We found that the share of ABC transporters is much higher in bacteria and archaea (ca. 27% of the transportome) than in primitive eukaryotes (13%), algae and plants (10%) and in fungi and animals (5-6%). This decrease is compensated by an increased occurrence of secondary transporters and ion channels. The share of ion channels is particularly high in animals (ca. 30% of the transportome) and algae and plants with (ca. 13%), when compared to bacteria and archaea with only 6-7%. Therefore, our results show a move to a preference for the low-energy-demanding transporters (ion channels and carriers) over the more energy-costly transporter classes (ATP-dependent families, and ABCs in particular) as part of the transition from prokaryotes to eukaryotes. The transportome analysis also indicated seven bacterial species, including Neorickettsia risticii and Neorickettsia sennetsu, as likely origins of the mitochondrion in eukaryotes, based on the phylogenetically restricted presence therein of clear homologues of modern mitochondrial solute carriers.

CONCLUSIONS: The results indicate that the transportomes of eukaryotes evolved strongly towards a higher energetic efficiency, as ATP-dependent transporters diminished and secondary transporters and ion channels proliferated. These changes have likely been important in the development of tissues performing energetically costly cellular functions.}, } @article {pmid29848319, year = {2018}, author = {Bronstein, O and Kroh, A and Haring, E}, title = {Mind the gap! The mitochondrial control region and its power as a phylogenetic marker in echinoids.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {80}, pmid = {29848319}, issn = {1471-2148}, support = {P 29508/FWF_/Austrian Science Fund FWF/Austria ; P 29508-B25//Austrian Science Fund/International ; }, mesh = {Algorithms ; Animals ; Base Sequence ; DNA Primers/metabolism ; DNA, Mitochondrial/genetics ; Genes, Mitochondrial ; Genetic Markers ; *Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; RNA, Transfer/genetics ; Sea Urchins/*genetics ; }, abstract = {BACKGROUND: In Metazoa, mitochondrial markers are the most commonly used targets for inferring species-level molecular phylogenies due to their extremely low rate of recombination, maternal inheritance, ease of use and fast substitution rate in comparison to nuclear DNA. The mitochondrial control region (CR) is the main non-coding area of the mitochondrial genome and contains the mitochondrial origin of replication and transcription. While sequences of the cytochrome oxidase subunit 1 (COI) and 16S rRNA genes are the prime mitochondrial markers in phylogenetic studies, the highly variable CR is typically ignored and not targeted in such analyses. However, the higher substitution rate of the CR can be harnessed to infer the phylogeny of closely related species, and the use of a non-coding region alleviates biases resulting from both directional and purifying selection. Additionally, complete mitochondrial genome assemblies utilizing next generation sequencing (NGS) data often show exceptionally low coverage at specific regions, including the CR. This can only be resolved by targeted sequencing of this region.

RESULTS: Here we provide novel sequence data for the echinoid mitochondrial control region in over 40 species across the echinoid phylogenetic tree. We demonstrate the advantages of directly targeting the CR and adjacent tRNAs to facilitate complementing low coverage NGS data from complete mitochondrial genome assemblies. Finally, we test the performance of this region as a phylogenetic marker both in the lab and in phylogenetic analyses, and demonstrate its superior performance over the other available mitochondrial markers in echinoids.

CONCLUSIONS: Our target region of the mitochondrial CR (1) facilitates the first thorough investigation of this region across a wide range of echinoid taxa, (2) provides a tool for complementing missing data in NGS experiments, and (3) identifies the CR as a powerful, novel marker for phylogenetic inference in echinoids due to its high variability, lack of selection, and high compatibility across the entire class, outperforming conventional mitochondrial markers.}, } @article {pmid29850800, year = {2018}, author = {Guillory, WX and Onyshchenko, A and Ruck, EC and Parks, M and Nakov, T and Wickett, NJ and Alverson, AJ}, title = {Recurrent Loss, Horizontal Transfer, and the Obscure Origins of Mitochondrial Introns in Diatoms (Bacillariophyta).}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1504-1515}, pmid = {29850800}, issn = {1759-6653}, mesh = {DNA, Mitochondrial/genetics ; Diatoms/*genetics ; Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; Genome, Mitochondrial/*genetics ; Introns/*genetics ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA/methods ; }, abstract = {We sequenced mitochondrial genomes from five diverse diatoms (Toxarium undulatum, Psammoneis japonica, Eunotia naegelii, Cylindrotheca closterium, and Nitzschia sp.), chosen to fill important phylogenetic gaps and help us characterize broadscale patterns of mitochondrial genome evolution in diatoms. Although gene content was strongly conserved, intron content varied widely across species. The vast majority of introns were of group II type and were located in the cox1 or rnl genes. Although recurrent intron loss appears to be the principal underlying cause of the sporadic distributions of mitochondrial introns across diatoms, phylogenetic analyses showed that intron distributions superficially consistent with a recurrent-loss model were sometimes more complicated, implicating horizontal transfer as a likely mechanism of intron acquisition as well. It was not clear, however, whether diatoms were the donors or recipients of horizontally transferred introns, highlighting a general challenge in resolving the evolutionary histories of many diatom mitochondrial introns. Although some of these histories may become clearer as more genomes are sampled, high rates of intron loss suggest that the origins of many diatom mitochondrial introns are likely to remain unclear.}, } @article {pmid29851233, year = {2018}, author = {Solari, KA and Hadly, EA}, title = {Evolution for extreme living: variation in mitochondrial cytochrome c oxidase genes correlated with elevation in pikas (genus Ochotona).}, journal = {Integrative zoology}, volume = {13}, number = {5}, pages = {517-535}, doi = {10.1111/1749-4877.12332}, pmid = {29851233}, issn = {1749-4877}, mesh = {Adaptation, Physiological/*genetics ; Altitude ; Animals ; *Biological Evolution ; Ecosystem ; Electron Transport Complex IV/genetics/*metabolism ; Gene Expression Regulation, Enzymologic ; Lagomorpha/genetics/*physiology ; Mitochondria/*enzymology ; Phylogeny ; }, abstract = {The genus Ochotona (pikas) is a clade of cold-tolerant lagomorphs that includes many high-elevation species. Pikas offer a unique opportunity to study adaptations and potential limitations of an ecologically important mammal to high-elevation hypoxia. We analyzed the evolution of 3 mitochondrial genes encoding the catalytic core of cytochrome c oxidase (COX) in 10 pika species occupying elevations from sea level to 5000 m. COX is an enzyme highly reliant on oxygen and essential for cell function. One amino acid property, the equilibrium constant (ionization of COOH), was found to be under selection in the overall protein complex. We observed a strong relationship between the net value change in this property and the elevation each species occupies, with higher-elevation species having potentially more efficient proteins. We also found evidence of selection in low-elevation species for potentially less efficient COX, perhaps trading efficiency for heat production in the absence of hypoxia. Our results suggest that different pika species may have evolved elevation-specific COX proteins, specialization that may indicate limitations in their ability to shift their elevational ranges in response to future climate change.}, } @article {pmid29852093, year = {2018}, author = {Li, Z and You, XL and Wang, LL and Yan, ZT and Zhou, ZY}, title = {Spore morphology and ultrastructure of an Ascosphaera apis strain from the honeybees (Apis mellifera) in southwest China.}, journal = {Mycologia}, volume = {110}, number = {2}, pages = {325-338}, doi = {10.1080/00275514.2018.1442084}, pmid = {29852093}, issn = {1557-2536}, mesh = {Animals ; Bees/*microbiology ; Cell Wall/chemistry ; China ; Chitin/analysis ; Cluster Analysis ; DNA, Fungal/chemistry/genetics ; DNA, Ribosomal Spacer/chemistry/genetics ; Microscopy ; Microscopy, Confocal ; Microscopy, Electron, Transmission ; Onygenales/classification/*cytology/isolation & purification/*ultrastructure ; Organelles/ultrastructure ; Phylogeny ; RNA, Ribosomal, 5.8S ; Sequence Analysis, DNA ; Spores, Fungal/*cytology/*ultrastructure ; }, abstract = {Ascosphaera apis is an intestinally infective, spore-forming, filamentous fungus that infects honeybees and causes deadly chalkbrood disease. Although A. apis has been known for 60 y, little is known about the ultrastructure of the spores. In this study, the fine morphology and ultrastructure of an isolate, A. apis CQ1 from southwest China, was comprehensively identified by transmission electron microscopy, confocal laser scanning microscopy, scanning electron microscopy, and optical microscopy. The high sequence similarity and phylogenetic data based on nuc rDNA ITS1-5.8S-ITS2 (ITS) supported the hypothesis that the CQ1 strain is a new member of the A. apis species. Morphological observation indicated that the mature spores are long ovals with an average size of 2 × 1.2 µm and are tightly packed inside spherical spore balls. More than 10 spore balls that were 8-16 µm in diameter were wrapped and formed a spherical, nearly hyaline spore cyst of 50-60 µm in diameter. Ultrastructural analysis showed that mature spores have two nuclei with distinctly different sizes. A large nucleus with double nuclear membranes was found in the center of the spore, whereas the small nucleus was only one-fifth of the large nucleus volume and was located near the end of the spore. Numerous ribosomes filled the cytoplasm, and many mitochondria with well-defined structures were arranged along the inner spore wall. The spore wall consists of an electron-dense outer surface layer, an electron-lucent layer, and an inner plasma membrane. Chitin is the major component of the spore wall. The germinated spore was observed as an empty spore coat, whereas the protoplasts, including the nuclei, mitochondria, and ribosomes, had been discharged. In addition to these typical fungal spore organelles, an unknown electron-dense regular structure might be the growing mycelium, which was arranged close to the inner spore wall and almost covered the entire wall area.}, } @article {pmid29852202, year = {2018}, author = {Wang, M and Teng, Y}, title = {Genome-wide identification and analysis of MICU genes in land plants and their potential role in calcium stress.}, journal = {Gene}, volume = {670}, number = {}, pages = {174-181}, doi = {10.1016/j.gene.2018.05.102}, pmid = {29852202}, issn = {1879-0038}, mesh = {Calcium/metabolism ; Calcium-Binding Proteins/chemistry/*genetics/metabolism ; Down-Regulation ; Embryophyta/classification/genetics/*metabolism ; Evolution, Molecular ; Phylogeny ; Plant Proteins/chemistry/genetics/metabolism ; Protein Domains ; Signal Transduction ; *Stress, Physiological ; }, abstract = {Mitochondrial calcium uptake (MICU) plays a vital role in the regulation of mitochondrial calcium homeostasis, and, consequently, influences calcium signaling transduction. Although genes involved in mitochondrial calcium uptake have been well studied in animals, less is known about their ubiquity and function in plants. In this study, we identified 96 MICU genes in land plants. On the basis of phylogenetic analysis of MICU proteins, they were classified into three clades: MICU from eudicots (Clade I), from monocots (Clade II), and from a basal angiosperm, a bryophyte, and a lycophyte (Clade III). Pairwise identity analysis across all MICU proteins showed that they are highly conserved among land plants at the protein level. Conserved motif analysis showed that most MICU proteins contained three EF-hands, and an additional EF-hand motif first identified in the MICU of Arabidopsis thaliana but not mammals was found in all 96 putative MICU proteins. This suggests that a cellular pathway of calcium uptake and signaling that requires three EF-hand motifs is evolutionarily conserved in plants. In addition, we discovered that MICU-defective mutants of Arabidopsis thaliana exhibited longer roots than wild-type under high calcium stress. Concurrently, the mRNA transcription levels of MICU were decreased under high calcium conditions. These results suggest that loss-of-function mutations of MICU may have potential roles in helping plants resist high calcium stress. This study provides clues to the possible role of plant MICU in mitochondrial calcium uptake, as well as useful information to support further studies on MICU function in plants.}, } @article {pmid29852663, year = {1998}, author = {Tudge, CC and Scheltinga, DM and Jamieson, BGM}, title = {Spermatozoal ultrastructure in the spiny lobster Jasus novaehollandiae Holthuis, 1963 (Palinuridae, Palinura, Decapoda).}, journal = {Journal of morphology}, volume = {236}, number = {2}, pages = {117-126}, doi = {10.1002/(SICI)1097-4687(199805)236:2<117::AID-JMOR3>3.0.CO;2-2}, pmid = {29852663}, issn = {1097-4687}, abstract = {The spermatozoal ultrastructure of the spiny lobster Jasus novaehollandiae is most similar to that in other investigated palinurans and, in particular, to the spermatozoa of Panulirus species. Shared characters include the globular nucleus penetrated by the bases of three or more microtubular arms; an anteriorly situated cytoplasmic zone with mitochondria and conspicuous lamellar bodies; a complex, four-zoned acrosomal vesicle (however, lacking the crystalline region present in Panulirus) with a homogeneous region; a scroll region; a flocculent region; and a region of periacrosomal material that forms finger-like involutions into the flocculent region. The related scyllarid slipper lobsters (Scyllarus and Thenus) possess spermatozoa with acrosome morphology similar to that of Jasus, but the sperm is generally more flattened, numerous radiating acrosome fins are present, and the microtubular arms (in Scyllarus) are cytoplasmic in origin and not nuclear. Sperm morphology provides preliminary evidence in support of the hypothesis of two independent lines of evolution in the Palinuridae but investigation into additional taxa within this group is required. J. Morphol. 236:117-126, 1998. © 1998 Wiley-Liss, Inc.}, } @article {pmid29855375, year = {2018}, author = {Amzati, GS and Pelle, R and Muhigwa, JB and Kanduma, EG and Djikeng, A and Madder, M and Kirschvink, N and Marcotty, T}, title = {Mitochondrial phylogeography and population structure of the cattle tick Rhipicephalus appendiculatus in the African Great Lakes region.}, journal = {Parasites & vectors}, volume = {11}, number = {1}, pages = {329}, pmid = {29855375}, issn = {1756-3305}, support = {ABC089//Africa Biosciences Challenge Fund (ABCF) program, BecA-ILRI Hub/ ; S0020***10402//Agence Universitaire de la Francophonie/ ; IFS-92890CA3//International Foundation for Science/ ; Bourses institutionnelles-Ceruna//Université de Namur/ ; 006/014//Communauté économique des pays des Grands Lacs (CEPGL)/ ; }, mesh = {Africa/epidemiology ; Animals ; Arachnid Vectors/*genetics/parasitology ; Cattle ; Genetic Structures ; *Genetic Variation ; Genetics, Population ; Mitochondria/genetics ; Phylogeny ; Phylogeography ; Population Dynamics ; Rhipicephalus/*genetics/parasitology ; Theileria parva/*physiology ; Theileriasis/epidemiology/*parasitology ; }, abstract = {BACKGROUND: The ixodid tick Rhipicephalus appendiculatus is the main vector of Theileria parva, wich causes the highly fatal cattle disease East Coast fever (ECF) in sub-Saharan Africa. Rhipicephalus appendiculatus populations differ in their ecology, diapause behaviour and vector competence. Thus, their expansion in new areas may change the genetic structure and consequently affect the vector-pathogen system and disease outcomes. In this study we investigated the genetic distribution of R. appendiculatus across agro-ecological zones (AEZs) in the African Great Lakes region to better understand the epidemiology of ECF and elucidate R. appendiculatus evolutionary history and biogeographical colonization in Africa.

METHODS: Sequencing was performed on two mitochondrial genes (cox1 and 12S rRNA) of 218 ticks collected from cattle across six AEZs along an altitudinal gradient in the Democratic Republic of Congo, Rwanda, Burundi and Tanzania. Phylogenetic relationships between tick populations were determined and evolutionary population dynamics models were assessed by mismach distribution.

RESULTS: Population genetic analysis yielded 22 cox1 and 9 12S haplotypes in a total of 209 and 126 nucleotide sequences, respectively. Phylogenetic algorithms grouped these haplotypes for both genes into two major clades (lineages A and B). We observed significant genetic variation segregating the two lineages and low structure among populations with high degree of migration. The observed high gene flow indicates population admixture between AEZs. However, reduced number of migrants was observed between lowlands and highlands. Mismatch analysis detected a signature of rapid demographic and range expansion of lineage A. The star-like pattern of isolated and published haplotypes indicates that the two lineages evolve independently and have been subjected to expansion across Africa.

CONCLUSIONS: Two sympatric R. appendiculatus lineages occur in the Great Lakes region. Lineage A, the most diverse and ubiquitous, has experienced rapid population growth and range expansion in all AEZs probably through cattle movement, whereas lineage B, the less abundant, has probably established a founder population from recent colonization events and its occurrence decreases with altitude. These two lineages are sympatric in central and eastern Africa and allopatric in southern Africa. The observed colonization pattern may strongly affect the transmission system and may explain ECF endemic instability in the tick distribution fringes.}, } @article {pmid29857468, year = {2018}, author = {Avelange-Macherel, MH and Candat, A and Neveu, M and Tolleter, D and Macherel, D}, title = {Decoding the Divergent Subcellular Location of Two Highly Similar Paralogous LEA Proteins.}, journal = {International journal of molecular sciences}, volume = {19}, number = {6}, pages = {}, pmid = {29857468}, issn = {1422-0067}, mesh = {Amino Acid Sequence ; Arabidopsis/genetics/metabolism ; Mitochondrial Proteins/chemistry/genetics/metabolism ; Multigene Family ; Mutation ; Plant Proteins/chemistry/*genetics/*metabolism ; Protein Binding ; Protein Transport ; Proteolysis ; Structure-Activity Relationship ; }, abstract = {Many mitochondrial proteins are synthesized as precursors in the cytosol with an N-terminal mitochondrial targeting sequence (MTS) which is cleaved off upon import. Although much is known about import mechanisms and MTS structural features, the variability of MTS still hampers robust sub-cellular software predictions. Here, we took advantage of two paralogous late embryogenesis abundant proteins (LEA) from Arabidopsis with different subcellular locations to investigate structural determinants of mitochondrial import and gain insight into the evolution of the LEA genes. LEA38 and LEA2 are short proteins of the LEA_3 family, which are very similar along their whole sequence, but LEA38 is targeted to mitochondria while LEA2 is cytosolic. Differences in the N-terminal protein sequences were used to generate a series of mutated LEA2 which were expressed as GFP-fusion proteins in leaf protoplasts. By combining three types of mutation (substitution, charge inversion, and segment replacement), we were able to redirect the mutated LEA2 to mitochondria. Analysis of the effect of the mutations and determination of the LEA38 MTS cleavage site highlighted important structural features within and beyond the MTS. Overall, these results provide an explanation for the likely loss of mitochondrial location after duplication of the ancestral gene.}, } @article {pmid29864497, year = {2018}, author = {Banerjee, B and Koner, D and Bhuyan, G and Saha, N}, title = {Differential expression of multiple glutamine synthetase genes in air-breathing magur catfish, Clarias magur and their induction under hyper-ammonia stress.}, journal = {Gene}, volume = {671}, number = {}, pages = {85-95}, doi = {10.1016/j.gene.2018.05.111}, pmid = {29864497}, issn = {1879-0038}, mesh = {Ammonia/*pharmacology ; Animals ; Brain/metabolism ; Catfishes/*genetics/metabolism ; Cytosol/metabolism ; Gene Expression Profiling/*methods ; Gene Expression Regulation/drug effects ; Gills/metabolism ; Glutamate-Ammonia Ligase/*genetics ; Kidney/metabolism ; Liver/metabolism ; Mitochondria/metabolism ; Muscle Cells/metabolism ; Phylogeny ; Sequence Analysis, DNA ; Stress, Physiological ; Tissue Distribution ; *Up-Regulation ; }, abstract = {The present study demonstrates the unique presence of three different gs genes (cmgs01, cmgs02, and cmgs03) in air-breathing ureogenic magur catfish (Clarias magur), which is otherwise reported to be encoded by a single gene in higher vertebrates. Of these three genes, two (cmgs01and cmgs03) were identified as 'liver' form, predominantly expressed in liver cells, and the third one as 'brain' form (cmgs02), expressed chiefly in brain cells. Molecular characterization studies have revealed conservation of homologous active site residues in all the three gs genes. In silico analysis, accompanied by GS enzyme assay and Western blot analysis of different GS isoforms in different subcellular fractions indicated the mitochondrial localization of cmGS01 and cmGS03 in liver and kidney cells and cytosolic localization of cmGS02 in brain cells. Further, exposure of magur catfish to high external ammonia (HEA; 25 mM NH4Cl) led to a significant induction of multiple gs genes as evidenced by higher expression of different gs mRNAs at variable levels in different tissues. The cmgs01 and cmgs03 mRNA levels elevated significantly in liver, kidney, muscle, and gills, whereas the cmgs02 mRNA level increased considerably in the brain after 14 days of exposure to HEA. These increases in mRNA levels were associated with a significant rise in cmGS01 and cmGS03 proteins in liver, kidney, muscle, and gills, and the cmGS02 protein in the brain after 14 days of exposure to HEA. Therefore, it can be concluded that the unique differential expression of three gs genes and their induction under high ammonia level probably helps in detoxification of ammonia to glutamine and further to urea via the ornithine-urea cycle in ureogenic as well as non-ureogenic tissues of these magur catfish.}, } @article {pmid29870859, year = {2018}, author = {Bolstad, KSR and Braid, HE and Strugnell, JM and Lindgren, AR and Lischka, A and Kubodera, T and Laptikhovsky, VL and Roura Labiaga, A}, title = {A mitochondrial phylogeny of the family Onychoteuthidae (Cephalopoda: Oegopsida).}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {88-97}, doi = {10.1016/j.ympev.2018.05.032}, pmid = {29870859}, issn = {1095-9513}, mesh = {Animals ; Cephalopoda/*classification/genetics ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/genetics ; Mitochondria/*genetics ; *Phylogeny ; Species Specificity ; }, abstract = {The oegopsid squid family Onychoteuthidae was recently revised based on morphology, but sufficient material for a complementary molecular analysis has not been available until now. In the present study, over 250 sequences of cytochrome c oxidase subunit I (COI) and 16S rRNA for 222 individuals were analysed to create a combined phylogeny for the family. Results support monophyly for the family and all seven onychoteuthid genera (including Moroteuthopsis, established herein as the senior genus name for species formerly attributed to Kondakovia); 29 genetically distinct species were recovered, with the BIN (Barcode Index Number) analysis for COI showing good congruence overall with morphological species groupings. No sequences were available for five additional known species, making the total family diversity likely to exceed 34 species. Seven of the BINs formed in this study appear to represent undescribed taxa, suggesting that even in this relatively well-studied family, much additional work remains before a comprehensive understanding of the diversity and evolutionary relationships for the Onychoteuthidae can be achieved.}, } @article {pmid29873740, year = {2018}, author = {Scott, GR and Guo, KH and Dawson, NJ}, title = {The Mitochondrial Basis for Adaptive Variation in Aerobic Performance in High-Altitude Deer Mice.}, journal = {Integrative and comparative biology}, volume = {58}, number = {3}, pages = {506-518}, doi = {10.1093/icb/icy056}, pmid = {29873740}, issn = {1557-7023}, mesh = {*Acclimatization ; *Altitude ; Animals ; Mitochondria/*physiology ; Peromyscus/*physiology ; }, abstract = {Mitochondria play a central role in aerobic performance. Studies aimed at elucidating how evolved variation in mitochondrial physiology contributes to adaptive variation in aerobic performance can therefore provide a unique and powerful lens to understanding the evolution of complex physiological traits. Here, we review our ongoing work on the importance of changes in mitochondrial quantity and quality to adaptive variation in aerobic performance in high-altitude deer mice. Whole-organism aerobic capacity in hypoxia (VO2max) increases in response to hypoxia acclimation in this species, but high-altitude populations have evolved consistently greater VO2max than populations from low altitude. The evolved increase in VO2max in highlanders is associated with an evolved increase in the respiratory capacity of the gastrocnemius muscle. This appears to result from highlanders having more mitochondria in this tissue, attributed to a higher proportional abundance of oxidative fiber-types and a greater mitochondrial volume density within oxidative fibers. The latter is primarily caused by an over-abundance of subsarcolemmal mitochondria in high-altitude mice, which is likely advantageous for mitochondrial O2 supply because more mitochondria are situated adjacent to the cell membrane and close to capillaries. Evolved changes in gastrocnemius phenotype appear to be underpinned by population differences in the expression of genes involved in energy metabolism, muscle development, and vascular development. Hypoxia acclimation has relatively little effect on respiratory capacity of the gastrocnemius, but it increases respiratory capacity of the diaphragm. However, the mechanisms responsible for this increase differ between populations: lowlanders appear to adjust mitochondrial quantity and quality (i.e., increases in citrate synthase [CS] activity, and mitochondrial respiration relative to CS activity) and they exhibit higher rates of mitochondrial release of reactive oxygen species, whereas highlanders only increase mitochondrial quantity in response to hypoxia acclimation. In contrast to the variation in skeletal muscles, the respiratory capacity of cardiac muscle does not appear to be affected by hypoxia acclimation and varies little between populations. Therefore, evolved changes in mitochondrial quantity and quality make important tissue-specific contributions to adaptive variation in aerobic performance in high-altitude deer mice.}, } @article {pmid29875327, year = {2018}, author = {Bonsack, F and Sukumari-Ramesh, S}, title = {TSPO: An Evolutionarily Conserved Protein with Elusive Functions.}, journal = {International journal of molecular sciences}, volume = {19}, number = {6}, pages = {}, pmid = {29875327}, issn = {1422-0067}, mesh = {Animals ; Conserved Sequence ; Disease Susceptibility ; Evolution, Molecular ; Humans ; Ligands ; Mitochondria/genetics/metabolism ; Molecular Targeted Therapy ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Receptors, GABA/chemistry/*genetics/*metabolism ; Steroids/biosynthesis ; }, abstract = {TSPO (18 kDa translocator protein) was identified decades ago in a search for peripheral tissue binding sites for benzodiazepines, and was formerly called the peripheral benzodiazepine receptor. TSPO is a conserved protein throughout evolution and it is implicated in the regulation of many cellular processes, including inflammatory responses, oxidative stress, and mitochondrial homeostasis. TSPO, apart from its broad expression in peripheral tissues, is highly expressed in neuroinflammatory cells, such as activated microglia. In addition, emerging studies employing the ligands of TSPO suggest that TSPO plays an important role in neuropathological settings as a biomarker and therapeutic target. However, the precise molecular function of this protein in normal physiology and neuropathology remains enigmatic. This review provides an overview of recent advances in our understanding of this multifaceted molecule and identifies the knowledge gap in the field for future functional studies.}, } @article {pmid29879897, year = {2018}, author = {Hein, A and Knoop, V}, title = {Expected and unexpected evolution of plant RNA editing factors CLB19, CRR28 and RARE1: retention of CLB19 despite a phylogenetically deep loss of its two known editing targets in Poaceae.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {85}, pmid = {29879897}, issn = {1471-2148}, mesh = {Arabidopsis/genetics ; Base Sequence ; Cell Nucleus/metabolism ; Chloroplasts/genetics ; *Evolution, Molecular ; Mitochondria/genetics ; *Phylogeny ; Plant Proteins/*genetics/metabolism ; Poaceae/*genetics ; RNA Editing/*genetics ; RNA, Messenger/genetics/metabolism ; RNA, Plant/*genetics/metabolism ; RNA-Binding Proteins/*genetics ; Species Specificity ; }, abstract = {BACKGROUND: C-to-U RNA editing in mitochondria and chloroplasts and the nuclear-encoded, RNA-binding PPR proteins acting as editing factors present a wide field of co-evolution between the different genetic systems in a plant cell. Recent studies on chloroplast editing factors RARE1 and CRR28 addressing one or two chloroplast editing sites, respectively, found them strictly conserved among 65 flowering plants as long as one of their RNA editing targets remained present.

RESULTS: Extending the earlier sampling to 117 angiosperms with high-quality genome or transcriptome data, we find more evidence confirming previous conclusions but now also identify cases for expected evolutionary transition states such as retention of RARE1 despite loss of its editing target or the degeneration of CRR28 truncating its carboxyterminal DYW domain. The extended angiosperm set was now used to explore CLB19, an "E+"-type PPR editing factor targeting two chloroplast editing sites, rpoAeU200SF and clpPeU559HY, in Arabidopsis thaliana. We found CLB19 consistently conserved if one of the two targets was retained and three independent losses of CLB19 after elimination of both targets. The Ericales show independent regains of the ancestrally lost clpPeU559HY editing, further explaining why multiple-target editing factors are lost much more rarely than single target factors like RARE1. The retention of CLB19 despite loss of both editing targets in some Ericaceae, Apocynaceae and in Camptotheca (Nyssaceae) likely represents evolutionary transitions. However, the retention of CLB19 after a phylogenetic deep loss in the Poaceae rather suggests a yet unrecognized further editing target, for which we suggest editing event ndhAeU473SL.

CONCLUSION: Extending the scope of studies on plant organelle RNA editing to further taxa and additional nuclear cofactors reveals expected evolutionary transitions, strikingly different evolutionary dynamics for multiple-target editing factors like CLB19 and CRR28 and suggests additional functions for editing factor CLB19 among the Poaceae.}, } @article {pmid29880721, year = {2018}, author = {Zhang, H and Burr, SP and Chinnery, PF}, title = {The mitochondrial DNA genetic bottleneck: inheritance and beyond.}, journal = {Essays in biochemistry}, volume = {62}, number = {3}, pages = {225-234}, doi = {10.1042/EBC20170096}, pmid = {29880721}, issn = {1744-1358}, support = {101876/Z/13/Z//Wellcome Trust/United Kingdom ; MC_UP_1501/2//Medical Research Council/United Kingdom ; G0601943//Medical Research Council/United Kingdom ; }, mesh = {Animals ; DNA, Mitochondrial/*genetics ; Gene-Environment Interaction ; Genetic Drift ; *Genetic Predisposition to Disease ; Humans ; Mitochondria/physiology ; Organelle Biogenesis ; Selection, Genetic ; }, abstract = {mtDNA is a multicopy genome. When mutations exist, they can affect a varying proportion of the mtDNA present within every cell (heteroplasmy). Heteroplasmic mtDNA mutations can be maternally inherited, but the proportion of mutated alleles differs markedly between offspring within one generation. This led to the genetic bottleneck hypothesis, explaining the rapid changes in allele frequency seen during transmission from one generation to the next. Although a physical reduction in mtDNA has been demonstrated in several species, a comprehensive understanding of the molecular mechanisms is yet to be revealed. Several questions remain, including the role of selection for and against specific alleles, whether all bottlenecks are the same, and precisely how the bottleneck is controlled during development. Although originally thought to be limited to the germline, there is evidence that bottlenecks exist in other cell types during development, perhaps explaining why different tissues in the same organism contain different levels of mutated mtDNA. Moreover, tissue-specific bottlenecks may occur throughout life in response to environmental influences, adding further complexity to the situation. Here we review key recent findings, and suggest ways forward that will hopefully advance our understanding of the role of mtDNA in human disease.}, } @article {pmid29883862, year = {2018}, author = {Tyagi, A and Pramanik, R and Vishnubhatla, S and Ali, S and Bakhshi, R and Chopra, A and Singh, A and Bakhshi, S}, title = {Pattern of mitochondrial D-loop variations and their relation with mitochondrial encoded genes in pediatric acute myeloid leukemia.}, journal = {Mutation research}, volume = {810}, number = {}, pages = {13-18}, doi = {10.1016/j.mrfmmm.2018.05.002}, pmid = {29883862}, issn = {1873-135X}, mesh = {Adolescent ; Base Sequence ; Child ; Child, Preschool ; Cyclooxygenase 1/*genetics ; Cytochromes b/*genetics ; DNA, Mitochondrial/*genetics ; Electron Transport Complex I/*genetics ; Humans ; Infant ; Leukemia, Myeloid, Acute/*genetics ; Mitochondria/*genetics ; Mitochondrial Proton-Translocating ATPases/*genetics ; *Mutation Rate ; Prospective Studies ; Sequence Analysis, DNA ; }, abstract = {Role of mitochondrial DNA variations, particularly in D loop region, remains investigational in acute myeloid leukaemia (AML). Consecutive 151 pediatric AML patients were prospectively enrolled from June 2013 to August 2016, for evaluating pattern of variations in mitochondrial D-loop region and to determine their association, if any, with expression of mitochondrial-encoded genes. For each patient, D-loop region was sequenced on baseline bone marrow, buccal swab and mother's blood sample. Real time PCR was used for relative gene expression of four mitochondrial DNA encoded genes viz. Nicotinamide-adenine-dineucleotide-dehydrogenase subunit 3 (ND3), Cytochrome-B (Cyt-B), Cytochrome c oxidase-I (COX1) and ATP-synthetase F0 subunit-6 (ATP6). Total 1490 variations were found at 237 positions in D-Loop; 1206 (80.9%) were germline and 284 (19.1%) were somatic. Positions 73-263 were identified as a probable hotspot region. G bases appeared to be most stable nucleotide (least number of single base substitutions) whereas T appeared to be most susceptible to variations with germline T-C being the commonest. Gene expression of Cyt-B was found to be significantly higher for any variation (somatic or germline) at positions 16,192 and 16,327 while it was significantly lower for variations at positions 16,051 and 207. Any variation at positions 152, 207 and 513 significantly decreased COX1 expression while those at positions 16,051 and 152 attenuated ATP6 expression. This first study evaluated type and overall pattern of D-loop variations in AML, and also showed that some of these variations in D loop region might have an effect on the mitochondrial-encoded genes which is new and valuable information in AML genomics.}, } @article {pmid29885222, year = {2017}, author = {Rydin, C and Wikström, N and Bremer, B}, title = {Conflicting results from mitochondrial genomic data challenge current views of Rubiaceae phylogeny.}, journal = {American journal of botany}, volume = {104}, number = {10}, pages = {1522-1532}, doi = {10.3732/ajb.1700255}, pmid = {29885222}, issn = {1537-2197}, mesh = {Genome, Mitochondrial/*genetics ; Genome, Plant/*genetics ; High-Throughput Nucleotide Sequencing ; Mitochondria/genetics ; Phylogeny ; Rubiaceae/*genetics ; Sequence Analysis, DNA ; }, abstract = {PREMISE OF THE STUDY: Reconstruction of plant phylogeny has heavily relied on single-gene or multigene plastid data. New sequencing methods have led to an increasing number of studies based on data from the entire plastid, but the mitochondrion has rarely been used to infer plant phylogeny because of an assumed information poverty and demonstrated lateral transfer of mitochondrial gene regions between distantly related species.

METHODS: We explored phylogenetic information from the plant mitochondrion using 57 representatives of the species-rich coffee family as study system and assessed consistency with previous results based (mostly) on plastid data.

KEY RESULTS: We showed that the mitochondrial genome can provide structured and statistically significant information on plant phylogeny. While most of our results are consistent with those based on plastid data, some surprising and statistically significant conflicts emerge, and our study demonstrates with striking clarity that the phylogeny of Rubiaceae is far from resolved.

CONCLUSIONS: It appears unlikely that conflicts between results retrieved from the different genomic compartments would be restricted to Rubiaceae. Rather, they are probably a general phenomenon and an important factor behind longstanding "difficult" phylogenetic questions. The biological processes responsible for the conflicting results detected here are unclear, but some conflicts are likely caused by hybridization events that occurred tens of millions of years ago. Whether such ancient events can be reconstructed based on molecular data from extant plants remains to be seen, but future studies of the nuclear genome may provide a way forward.}, } @article {pmid29892953, year = {2018}, author = {Liu, W and Hu, C and Xie, W and Chen, P and Zhang, Y and Yao, R and Li, K and Chang, Q}, title = {The mitochondrial genome of red-necked phalarope Phalaropus lobatus (Charadriiformes: Scolopacidae) and phylogeny analysis among Scolopacidae.}, journal = {Genes & genomics}, volume = {40}, number = {5}, pages = {455-463}, pmid = {29892953}, issn = {2092-9293}, mesh = {Animals ; Base Composition/genetics ; Base Sequence/genetics ; Birds/genetics ; Charadriiformes/*genetics ; DNA, Mitochondrial/genetics ; Genome, Mitochondrial/*genetics ; Mitochondria/genetics ; Nucleic Acid Conformation ; Phylogeny ; RNA, Ribosomal/genetics ; RNA, Transfer/genetics ; Sequence Analysis, DNA ; }, abstract = {The red-necked phalarope is a wonderful species with specific morphological characters and lifestyles. Mitochondrial genomes, encoding necessary proteins involved in the system of energy metabolism, are important for the evolution and adaption of species. In this study, we determined the complete mitogenome sequence of Phalaropus lobatus (Charadriiformes: Scolopacidae). The circular genome is 16714 bp in size, containing 13 PCGs, two ribosomal RNAs and 22 tRNAs and a high AT-rich control region. The AT skew and GC skew of major strand is positive and negative respectively. Most of PCGs are biased towards A-rich except ND1. A codon usage analysis shows that 3 start codons (ATG, GTG and ATA), 4 stop codons (TAA, TAG, AGG, AGA) and two incomplete terminate codons (T-). Twenty two transfer RNAs have the typical cloverleaf structure, and a total of ten base pairs are mismatched throughout the nine tRNA genes. The phylogenetic tree based on 13 PCGs and 2 rRNA genes indicates that monophyly of the family and genus Phalaropus is close to genus Xenus plus Tringa. The analysis of selective pressure shows 13 protein-coding genes are evolving under the purifying selection and P. lobatus is different from other Scolopacidae species on the selective pressure of gene ND4. This study helps us know the inherent mechanism of mitochondrial structure and natural selection.}, } @article {pmid29893915, year = {2018}, author = {Chen, N and Wang, P and Li, C and Wang, Q and Pan, J and Xiao, F and Wang, Y and Zhang, K and Li, C and Yang, B and Sun, C and Deng, X}, title = {A Single Nucleotide Mutation of the IspE Gene Participating in the MEP Pathway for Isoprenoid Biosynthesis Causes a Green-Revertible Yellow Leaf Phenotype in Rice.}, journal = {Plant & cell physiology}, volume = {59}, number = {9}, pages = {1905-1917}, doi = {10.1093/pcp/pcy108}, pmid = {29893915}, issn = {1471-9053}, mesh = {Base Sequence ; Chloroplasts/*metabolism ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Genetic Complementation Test ; Mitochondria/metabolism ; Oryza/*genetics ; Photosynthesis/genetics/physiology ; Phylogeny ; Plant Leaves/*metabolism ; Plant Proteins/metabolism ; *Polymorphism, Single Nucleotide ; Terpenes/*metabolism ; }, abstract = {Plant isoprenoids are dependent on two independent pathways, the cytosolic mevalonate (MVA) pathway and the plastidic methylerythritol phosphate (MEP) pathway. IspE is one of seven known enzymes in the MEP pathway. Currently, no IspE gene has been identified in rice. In addition, no virescent mutants have been reported to result from a gene mutation affecting the MEP pathway. In this study, we isolated a green-revertible yellow leaf mutant gry340 in rice. The mutant exhibited a reduced level of photosynthetic pigments, and an arrested development of chloroplasts and mitochondria in its yellow leaves. Map-based cloning revealed a missense mutation in OsIspE (LOC_Os01g58790) in gry340 mutant plants. OsIspE is constitutively expressed in all tissues, and its encoded protein is targeted to the chloroplast. Further, the mutant phenotype of gry340 was rescued by introduction of the wild-type gene. Therefore, we have successfully identified an IspE gene in monocotyledons via map-based cloning, and confirmed that the green-revertible yellow leaf phenotype of gry340 does result from a single nucleotide mutation in the IspE gene. In addition, the ispE ispF double mutant displayed an etiolation lethal phenotype, indicating that the isoprenoid precursors from the cytosol cannot efficiently compensate for the deficiency of the MEP pathway in rice chloroplasts. Furthermore, real-time quantitative reverse transcription-PCR suggested that this functional defect in OsIspE affected the expression of not only other MEP pathway genes but also that of MVA pathway genes, photosynthetic genes and mitochondrial genes.}, } @article {pmid29897900, year = {2018}, author = {Chadha, S and Vijayan, R and Gupta, S and Munde, M and Gourinath, S and Madhubala, R}, title = {Genetic manipulation of Leishmania donovani threonyl tRNA synthetase facilitates its exploration as a potential therapeutic target.}, journal = {PLoS neglected tropical diseases}, volume = {12}, number = {6}, pages = {e0006575}, pmid = {29897900}, issn = {1935-2735}, mesh = {Drug Delivery Systems ; Escherichia coli/enzymology/genetics ; Fatty Alcohols/pharmacology ; Gene Expression ; Humans ; Leishmania donovani/drug effects/*enzymology/genetics/pathogenicity ; Leishmaniasis, Visceral/*parasitology ; Organisms, Genetically Modified ; Phylogeny ; Protein Domains ; Protein Transport ; Protozoan Proteins/antagonists & inhibitors/genetics/isolation & purification/metabolism ; Recombinant Proteins ; Sequence Deletion ; Threonine-tRNA Ligase/antagonists & inhibitors/*genetics/isolation & purification/metabolism ; }, abstract = {BACKGROUND: Aminoacyl tRNA synthetases are central enzymes required for protein synthesis. These enzymes are the known drug targets in bacteria and fungi. Here, we for the first time report the functional characterization of threonyl tRNA synthetase (LdThrRS) of Leishmania donovani, a protozoan parasite, the primary causative agent of visceral leishmaniasis.

METHODOLOGY: Recombinant LdThrRS (rLdThrRS) was expressed in E. coli and purified. The kinetic parameters for rLdThrRS were determined. The subcellular localization of LdThrRS was done by immunofluorescence analysis. Heterozygous mutants of LdThrRS were generated in Leishmania promastigotes. These genetically manipulated parasites were checked for their proliferation, virulence, aminoacylation activity and sensitivity to the known ThrRS inhibitor, borrelidin. An in silico generated structural model of L. donovani ThrRS was compared to that of human.

CONCLUSIONS: Recombinant LdThrRS displayed aminoacylation activity, and the protein is possibly localized to both the cytosol and mitochondria. The comparison of the 3D-model of LdThrRS to human ThrRS displayed considerable similarity. Heterozygous parasites showed restrictive growth phenotype and had attenuated infectivity. These heterozygous parasites were more susceptible to inhibition by borrelidin. Several attempts to obtain ThrRS homozygous null mutants were not successful, indicating its essentiality for the Leishmania parasite. Borrelidin showed a strong affinity for LdThrRS (KD: 0.04 μM) and was effective in inhibiting the aminoacylation activity of the rLdThrRS (IC50: 0.06 μM). Borrelidin inhibited the promastigotes (IC50: 21 μM) stage of parasites. Our data shows that LdThrRS is essential for L. donovani survival and is likely to bind with small drug-like molecules with strong affinity, thus making it a potential target for drug discovery efforts.}, } @article {pmid29902241, year = {2018}, author = {Yoshino, H and Yamaji, F and Ohsawa, TA}, title = {Genetic structure and dispersal patterns in Limnoria nagatai (Limnoriidae, Isopoda) dwelling in non-buoyant kelps, Eisenia bicyclis and E. arborea, in Japan.}, journal = {PloS one}, volume = {13}, number = {6}, pages = {e0198451}, pmid = {29902241}, issn = {1932-6203}, mesh = {Animals ; Demography ; Electron Transport Complex IV/*genetics ; Gene Flow ; Isopoda/*classification/physiology ; Japan ; Kelp/*classification/physiology ; Mitochondria/genetics ; Pacific Ocean ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA/*methods ; }, abstract = {The marine isopod genus Limnoria contains algae-eating species. Previous phylogeographic studies have suggested that Limnoria species feeding on buoyant kelp underwent low genetic differentiation on a large spatial scale because rafting on floating host kelps promotes high levels of gene flow. In this paper, we survey the genetic structure of Limnoria nagatai, which bores into the non-buoyant kelps Eisenia bicyclis and E. arborea. We analyze the mitochondrial DNA (cytochrome oxidase subunit I [COI] gene) and morphological traits of L. nagatai, and the host kelps E. bicyclis and E. arborea from 14 populations along the Japanese archipelago of the Pacific Ocean and the Sea of Japan. Four major lineages are recognized within L. nagatai: three lineages in the Pacific Ocean, and one lineage in the Sea of Japan which might be a cryptic species. For L. nagatai, we show high genetic differentiation between geographically separated habitats in the Pacific Ocean, while low differentiation is found among continuous host kelps habitats in the Pacific Ocean as well as the Sea of Japan. L. nagatai in E. bicyclis in the Pacific Ocean has experienced large population expansion after the Last Glacial Maximum (LGM), whereas the lineage in E. bicyclis in the Sea of Japan has not. We suggest that Limnoria feeding on non-buoyant kelps, may attain low genetic differentiation because they might be able to disperse long distance if the habitat of host kelps is continuous. The historical events affecting Limnoria after the LGM may differ between the coasts of the Pacific Ocean and the Sea of Japan.}, } @article {pmid29902489, year = {2018}, author = {Uzarska, MA and Przybyla-Toscano, J and Spantgar, F and Zannini, F and Lill, R and Mühlenhoff, U and Rouhier, N}, title = {Conserved functions of Arabidopsis mitochondrial late-acting maturation factors in the trafficking of iron‑sulfur clusters.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {1865}, number = {9}, pages = {1250-1259}, doi = {10.1016/j.bbamcr.2018.06.003}, pmid = {29902489}, issn = {0167-4889}, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Cloning, Molecular ; DNA-Binding Proteins/genetics/metabolism ; Evolution, Molecular ; Iron/metabolism ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Saccharomyces cerevisiae/genetics/*growth & development ; Sulfur/metabolism ; }, abstract = {Numerous proteins require iron‑sulfur (Fe-S) clusters as cofactors for their function. Their biogenesis is a multi-step process occurring in the cytosol and mitochondria of all eukaryotes and additionally in plastids of photosynthetic eukaryotes. A basic model of Fe-S protein maturation in mitochondria has been obtained based on studies achieved in mammals and yeast, yet some molecular details, especially of the late steps, still require investigation. In particular, the late-acting biogenesis factors in plant mitochondria are poorly understood. In this study, we expressed the factors belonging to NFU, BOLA, SUFA/ISCA and IBA57 families in the respective yeast mutant strains. Expression of the Arabidopsis mitochondrial orthologs was usually sufficient to rescue the growth defects observed on specific media and/or to restore the abundance or activity of the defective Fe-S or lipoic acid-dependent enzymes. These data demonstrate that the plant mitochondrial counterparts, including duplicated isoforms, likely retained their ancestral functions. In contrast, the SUFA1 and IBA57.2 plastidial isoforms cannot rescue the lysine and glutamate auxotrophies of the respective isa1-isa2Δ and iba57Δ strains or of the isa1-isa2-iba57Δ triple mutant when expressed in combination. This suggests a specialization of the yeast mitochondrial and plant plastidial factors in these late steps of Fe-S protein biogenesis, possibly reflecting substrate-specific interactions in these different compartments.}, } @article {pmid29904051, year = {2018}, author = {Chen, N and Cai, Y and Chen, Q and Li, R and Wang, K and Huang, Y and Hu, S and Huang, S and Zhang, H and Zheng, Z and Song, W and Ma, Z and Ma, Y and Dang, R and Zhang, Z and Xu, L and Jia, Y and Liu, S and Yue, X and Deng, W and Zhang, X and Sun, Z and Lan, X and Han, J and Chen, H and Bradley, DG and Jiang, Y and Lei, C}, title = {Whole-genome resequencing reveals world-wide ancestry and adaptive introgression events of domesticated cattle in East Asia.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {2337}, pmid = {29904051}, issn = {2041-1723}, support = {31501918//National Natural Science Foundation of China (National Science Foundation of China)/International ; }, mesh = {Animals ; *Breeding ; Cattle/*genetics ; China ; Chromosomes/ultrastructure ; Domestication ; Female ; Genetic Variation ; *Genetics, Population ; *Genome ; Geography ; Haplotypes ; Male ; Mitochondria ; Models, Statistical ; Phylogeny ; Polymorphism, Single Nucleotide ; Species Specificity ; Tibet ; }, abstract = {Cattle domestication and the complex histories of East Asian cattle breeds warrant further investigation. Through analysing the genomes of 49 modern breeds and eight East Asian ancient samples, worldwide cattle are consistently classified into five continental groups based on Y-chromosome haplotypes and autosomal variants. We find that East Asian cattle populations are mainly composed of three distinct ancestries, including an earlier East Asian taurine ancestry that reached China at least ~3.9 kya, a later introduced Eurasian taurine ancestry, and a novel Chinese indicine ancestry that diverged from Indian indicine approximately 36.6-49.6 kya. We also report historic introgression events that helped domestic cattle from southern China and the Tibetan Plateau achieve rapid adaptation by acquiring ~2.93% and ~1.22% of their genomes from banteng and yak, respectively. Our findings provide new insights into the evolutionary history of cattle and the importance of introgression in adaptation of cattle to new environmental challenges in East Asia.}, } @article {pmid29909242, year = {2018}, author = {Pinheiro, GMS and Ramos, CHI}, title = {Initial characterization of newly identified mitochondrial and chloroplast small HSPs from sugarcane shows that these chaperones have different oligomerization states and substrate specificities.}, journal = {Plant physiology and biochemistry : PPB}, volume = {129}, number = {}, pages = {285-294}, doi = {10.1016/j.plaphy.2018.06.002}, pmid = {29909242}, issn = {1873-2690}, mesh = {Chloroplasts/*metabolism ; Chromatography, Gel ; Cloning, Molecular ; Heat-Shock Proteins/chemistry/genetics/isolation & purification/*metabolism ; Mitochondria/*metabolism ; Phylogeny ; Plant Proteins/chemistry/genetics/isolation & purification/*metabolism ; Saccharum/genetics/*metabolism ; Sequence Alignment ; Spectrometry, Fluorescence ; Substrate Specificity ; }, abstract = {Chaperones belonging to the small heat shock protein (sHSP) family are ubiquitous and exhibit elevated expression under stresses conditions to protect proteins against aggregation, thereby contributing to the stress tolerance of the organism. Tropical plants are constantly exposed to high temperatures, and the mechanisms by which these plants tolerate heat stress are of foremost importance to basic science as well as applied agrobiotechnology. Therefore, this study aims to characterize sHSPs from different organelles from sugarcane, an important crop that is associated with sugar and bioenergy production. An expression sequence tag database of sugarcane was searched, and sHsp genes of mitochondrial and chloroplast organelles were selected and cloned. The proteins were expressed in Escherichia coli and isolated and purified by two chromatographic steps with high purity as single species. Circular dichroism and fluorescence spectroscopy showed that both proteins were purified in their folded states with a predominant β-sheet secondary structure. Determination of the molecular weight, diffusion coefficient and Stokes radius parameters showed that both chaperones form large spherical-like oligomers in solution. The two sHSPs had different oligomeric states and substrate specificities. The mitochondrial sHSP was a 20-mer with ability to protect model substrates that differ from that of the 16-meric sHSP from chloroplasts. These results indicate that both sHSPs are key agents to protect against stress confirming the importance of the great diversity of sHSP chaperones in plants for homeostasis maintenance. Moreover, to our knowledge, this is the first report about small HSPs from sugarcane organelles.}, } @article {pmid29910126, year = {2018}, author = {Zambelli, F and Mertens, J and Dziedzicka, D and Sterckx, J and Markouli, C and Keller, A and Tropel, P and Jung, L and Viville, S and Van de Velde, H and Geens, M and Seneca, S and Sermon, K and Spits, C}, title = {Random Mutagenesis, Clonal Events, and Embryonic or Somatic Origin Determine the mtDNA Variant Type and Load in Human Pluripotent Stem Cells.}, journal = {Stem cell reports}, volume = {11}, number = {1}, pages = {102-114}, pmid = {29910126}, issn = {2213-6711}, mesh = {Alleles ; Cell Culture Techniques ; Cell Differentiation/*genetics ; Chromosome Aberrations ; Clonal Evolution/*genetics ; *DNA, Mitochondrial ; Fibroblasts/metabolism ; Gene Expression Profiling ; Genetic Heterogeneity ; Genetic Variation ; Genomic Instability ; Genotype ; Humans ; Mosaicism ; *Mutagenesis ; Pluripotent Stem Cells/*metabolism ; }, abstract = {In this study, we deep-sequenced the mtDNA of human embryonic and induced pluripotent stem cells (hESCs and hiPSCs) and their source cells and found that the majority of variants pre-existed in the cells used to establish the lines. Early-passage hESCs carried few and low-load heteroplasmic variants, similar to those identified in oocytes and inner cell masses. The number and heteroplasmic loads of these variants increased with prolonged cell culture. The study of 120 individual cells of early- and late-passage hESCs revealed a significant diversity in mtDNA heteroplasmic variants at the single-cell level and that the variants that increase during time in culture are always passenger to the appearance of chromosomal abnormalities. We found that early-passage hiPSCs carry much higher loads of mtDNA variants than hESCs, which single-fibroblast sequencing proved pre-existed in the source cells. Finally, we show that these variants are stably transmitted during short-term differentiation.}, } @article {pmid29913080, year = {2018}, author = {Wilkerson, CD and Mahoney, SP and Carr, SM}, title = {Post-glacial recolonization of insular Newfoundland across the Strait of Belle Isle gave rise to an endemic subspecies of woodland caribou, Rangifer tarandus terranovae (Bangs, 1896): evidence from mtDNA haplotypes.}, journal = {Genome}, volume = {61}, number = {8}, pages = {575-585}, doi = {10.1139/gen-2017-0199}, pmid = {29913080}, issn = {1480-3321}, mesh = {Animals ; DNA, Mitochondrial/*genetics ; Forests ; *Genetic Speciation ; Haplotypes/genetics ; Microsatellite Repeats/*genetics ; Mitochondria/genetics ; Newfoundland and Labrador ; Reindeer/*genetics ; }, abstract = {Post-glacial origins of woodland caribou (Rangifer tarandus subsp.) on the island of Newfoundland and their relationship to mainland populations have been uncertain. Sequence analysis of 2223 bp of the mitochondrial DNA control region and cytochrome b gene from 233 Newfoundland caribou identified 32 haplotypes in four major clades. Comparison with other Nearctic caribou confirms a closer affinity of the basal Clade A with animals from the mainland, and as an outgroup to Clades B, C, and D that are endemic to the island. This indicates re-entry of caribou to post-glacial Newfoundland across the Strait of Belle Isle from Labrador, rather than from southern coastal refugia. Newfoundland caribou are a distinct subspecies, Rangifer tarandus terranovae (Bangs, 1896). Hierarchical AMOVA shows significant clinal differentiation of the major clades from northwest to southeast across the island. The isolated Avalon Peninsula population in the extreme southeast is genetically depauperate. Founder effects are evident in herds introduced to previously unoccupied areas by wildlife managers over the past 40-50 years. Reindeer introduced in the early 20th century have not contributed to mtDNA diversity in Newfoundland caribou.}, } @article {pmid29913250, year = {2018}, author = {Seligmann, H}, title = {Giant viruses as protein-coated amoeban mitochondria?.}, journal = {Virus research}, volume = {253}, number = {}, pages = {77-86}, doi = {10.1016/j.virusres.2018.06.004}, pmid = {29913250}, issn = {1872-7492}, mesh = {Acanthamoeba/genetics/metabolism/*virology ; *Biological Evolution ; Gene Order ; Genome Size ; Genome, Viral ; Giant Viruses/*genetics/physiology ; Mitochondria/genetics/metabolism/*virology ; Phylogeny ; Protozoan Proteins/genetics/*metabolism ; }, abstract = {Mimivirus' genome includes parts of 5S, 16S and 23S ribosomal RNAs encoded by Acanthamoeba's mitogenome, the giant virus' host. Two non-exclusive hypotheses for rRNA remnants in giant viruses are examined: 1. mitogenomes invade viral genomes as they do for nuclear chromosomes (producing numts); 2. megaviral genomes evolved from an ancestral mitogenome. Alignment analyses confirm mitochondrial, rather than alphaproteobacterial origins of megaviral rRNAs. Other mitogenes have likely megaviral homologues. These megaviral homologues coevolve to much larger extents than candidate rRNA homologues, suggesting rRNA decay in viruses. Megaviral mitogene homologues overall follow mitochondrial gene order, suggesting mitogenome ancestry. Ancestral synteny decreases with megaviral genome size, suggesting that subsequent mitogene insertions blur ancestral gene order. Putative defenses against DNA invasion conserve mitogene order in short megaviral genomes. Synteny between mitogenome and megaviral genomes confirms the RNA/DNA polymerase-homologies-based hypothesis that giant viruses have mitochondrial-like ancestors, viral rRNA remnants are corollary of mitogenomic origins of megaviral genomes. Note that giant viruses, mitochondria and bacterial spores all have double membranes, spores and viruses have protein coats. Mitochondria might occasionally form spore-like structures that drifted into megaviruses. These missing links could confirm mitogenome ancestry of giant viruses rather than giant virus ancestry of mitochondria.}, } @article {pmid29916730, year = {2018}, author = {Chang, CH and Dai, WY and Chen, TY and Lee, AH and Hou, HY and Liu, SH and Jang-Liaw, NH}, title = {DNA barcoding reveals CITES-listed species among Taiwanese government-seized chelonian specimens.}, journal = {Genome}, volume = {61}, number = {8}, pages = {615-624}, doi = {10.1139/gen-2017-0264}, pmid = {29916730}, issn = {1480-3321}, mesh = {Animals ; *DNA Barcoding, Taxonomic ; Electron Transport Complex IV/*genetics ; Genetic Markers ; Government ; Mitochondria/*genetics ; Phylogeny ; Species Specificity ; Taiwan ; Turtles/classification/*genetics ; }, abstract = {Compared to traditional morphological identification, DNA barcoding-molecular identification based on sequencing of a segment of mitochondrial cytochrome c oxidase subunit I (COI)-provides a shortcut to authenticating chelonian identifications. Here, we selected 63 government-seized chelonian specimens deposited at Taipei Zoo for DNA barcoding analysis. DNA barcoding and subsequent phylogenetic analysis successfully authenticated 36 chelonian species, including five that are listed in CITES Appendix I. Approximately 90% (57/63) of the specimens were successfully authenticated by our molecular approach, but lack or error of BOLD reference sequences, biological processes such as hybridization, and uncertain species delimitation all reduced the accuracy of DNA barcoding. To increase the accuracy of DNA barcoding, Taipei Zoo will continue to enrich the BOLD database and also establish a genetic database, to include additional genetic markers, by using government-seized chelonian specimens. A fast and accurate method to authenticate seized samples could assist law enforcement agencies to prosecute criminals and restrict illegal exploitation of wild chelonian resources.}, } @article {pmid29923828, year = {2018}, author = {Tokatlidis, K}, title = {Shaping the import system of mitochondria.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {29923828}, issn = {2050-084X}, support = {MC_PC_17190/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Mitochondria ; *Mitochondrial Membranes ; }, abstract = {Evidence is accumulating that unrelated species have independently evolved the same way of importing proteins in their mitochondria.}, } @article {pmid29923829, year = {2018}, author = {Vitali, DG and Käser, S and Kolb, A and Dimmer, KS and Schneider, A and Rapaport, D}, title = {Independent evolution of functionally exchangeable mitochondrial outer membrane import complexes.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {29923829}, issn = {2050-084X}, support = {ITN TAMPting, 607072//Marie Curie/United Kingdom ; }, mesh = {Biological Coevolution ; Gene Deletion ; *Gene Expression Regulation, Fungal ; Genetic Complementation Test ; Membrane Proteins/*genetics/metabolism ; Mitochondria/genetics/metabolism ; Mitochondrial Membrane Transport Proteins/*genetics/metabolism ; Mitochondrial Membranes/*metabolism ; Organelle Biogenesis ; Phosphorylation ; Protein Isoforms/genetics/metabolism ; Protozoan Proteins/*genetics/metabolism ; Saccharomyces cerevisiae/*genetics/metabolism ; Saccharomyces cerevisiae Proteins/*genetics/metabolism ; Trypanosoma brucei brucei/*genetics/metabolism ; }, abstract = {Assembly and/or insertion of a subset of mitochondrial outer membrane (MOM) proteins, including subunits of the main MOM translocase, require the fungi-specific Mim1/Mim2 complex. So far it was unclear which proteins accomplish this task in other eukaryotes. Here, we show by reciprocal complementation that the MOM protein pATOM36 of trypanosomes is a functional analogue of yeast Mim1/Mim2 complex, even though these proteins show neither sequence nor topological similarity. Expression of pATOM36 rescues almost all growth, mitochondrial biogenesis, and morphology defects in yeast cells lacking Mim1 and/or Mim2. Conversely, co-expression of Mim1 and Mim2 restores the assembly and/or insertion defects of MOM proteins in trypanosomes ablated for pATOM36. Mim1/Mim2 and pATOM36 form native-like complexes when heterologously expressed, indicating that additional proteins are not part of these structures. Our findings indicate that Mim1/Mim2 and pATOM36 are the products of convergent evolution and arose only after the ancestors of fungi and trypanosomatids diverged.}, } @article {pmid29924334, year = {2018}, author = {Chowdhury, A and Ogura, T and Esaki, M}, title = {Two Cdc48 cofactors Ubp3 and Ubx2 regulate mitochondrial morphology and protein turnover.}, journal = {Journal of biochemistry}, volume = {164}, number = {5}, pages = {349-358}, doi = {10.1093/jb/mvy057}, pmid = {29924334}, issn = {1756-2651}, mesh = {Carrier Proteins/genetics/*metabolism ; Endopeptidases/genetics/*metabolism ; GTP Phosphohydrolases/*metabolism ; Membrane Proteins/*metabolism ; Mitochondria/*metabolism ; Mitochondrial Proteins/*metabolism ; Saccharomyces cerevisiae/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; }, abstract = {Mitochondria continuously undergo coordinated fusion and fission during vegetative growth to keep their homogeneity and to remove damaged components. A cytosolic AAA ATPase, Cdc48, is implicated in the mitochondrial fusion event and turnover of a fusion-responsible GTPase in the mitochondrial outer membrane, Fzo1, suggesting a possible linkage of mitochondrial fusion and Fzo1 turnover. Here, we identified two Cdc48 cofactor proteins, Ubp3 and Ubx2, involving mitochondria regulation. In the absence of UBP3, mitochondrial fragmentation and aggregation were observed. The turnover of Fzo1 was not affected in Δubp3, but instead a deubiquitylase Ubp12 that removes fusion-required polyubiquitin chains from Fzo1 was stabilized. Thus, excess amount of Ubp12 may lead to mitochondrial fragmentation by removal of fusion-competent ubiquitylated Fzo1. In contrast, deletion of UBX2 perturbed disassembly of Fzo1 oligomers and their degradation without alteration of mitochondrial morphology. The UBX2 deletion led to destabilization of Ubp2 that negatively regulates Fzo1 turnover by removing degradation-signalling polyubiquitin chains, suggesting that Ubx2 would directly facilitate Fzo1 degradation. These results indicated that two different Cdc48-cofactor complexes independently regulate mitochondrial fusion and Fzo1 turnover.}, } @article {pmid29934612, year = {2018}, author = {Lajbner, Z and Pnini, R and Camus, MF and Miller, J and Dowling, DK}, title = {Experimental evidence that thermal selection shapes mitochondrial genome evolution.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {9500}, pmid = {29934612}, issn = {2045-2322}, mesh = {Animals ; Drosophila melanogaster/genetics ; *Evolution, Molecular ; Female ; Genome, Mitochondrial/*genetics ; Male ; *Selection, Genetic ; *Temperature ; }, abstract = {Mitochondria are essential organelles, found within eukaryotic cells, which contain their own DNA. Mitochondrial DNA (mtDNA) has traditionally been used in population genetic and biogeographic studies as a maternally-inherited and evolutionary-neutral genetic marker. However, it is now clear that polymorphisms within the mtDNA sequence are routinely non-neutral, and furthermore several studies have suggested that such mtDNA polymorphisms are also sensitive to thermal selection. These observations led to the formulation of the "mitochondrial climatic adaptation" hypothesis, for which all published evidence to date is correlational. Here, we use laboratory-based experimental evolution in the fruit fly, Drosophila melanogaster, to test whether thermal selection can shift population frequencies of two mtDNA haplogroups whose natural frequencies exhibit clinal associations with latitude along the Australian east-coast. We present experimental evidence that the thermal regime in which the laboratory populations were maintained drove changes in haplogroup frequencies across generations. Our results strengthen the emerging view that intra-specific mtDNA variants are sensitive to selection, and suggest spatial distributions of mtDNA variants in natural populations of metazoans might reflect adaptation to climatic environments rather than within-population coalescence and diffusion of selectively-neutral haplotypes across populations.}, } @article {pmid29938587, year = {2019}, author = {Gvozdanović, K and Margeta, V and Margeta, P and Djurkin Kušec, I and Galović, D and Dovč, P and Kušec, G}, title = {Genetic diversity of autochthonous pig breeds analyzed by microsatellite markers and mitochondrial DNA D-loop sequence polymorphism.}, journal = {Animal biotechnology}, volume = {30}, number = {3}, pages = {242-251}, doi = {10.1080/10495398.2018.1478847}, pmid = {29938587}, issn = {1532-2378}, mesh = {Animals ; Breeding ; DNA, Mitochondrial/genetics ; Female ; Gene Frequency ; *Genetic Variation ; Haplotypes ; Male ; Microsatellite Repeats/*genetics ; Mitochondria/genetics ; Phylogeny ; Polymorphism, Genetic ; Sus scrofa ; Swine/*genetics ; }, abstract = {The evaluation of the genetic structure of autochthonous pig breeds is very important for conservation of local pig breeds and preservation of diversity. In this study, 18 microsatellite loci were used to detect genetic relationship between autochthonous pig breeds [Black Slavonian (BS), Turopolje pig (TP), and Croatian wild boar] and to determine phylogenetic relationship among Croatian autochthonous pig breeds and certain Asian and European pigs using the mitochondrial DNA (mtDNA) D-loop sequence polymorphism. Relatively high degree of genetic variation was found between the observed populations. The analysis of mtDNA showed that haplotypes of the studied pig populations are different from the other European and Chinese haplotypes. BS pigs showed some similarities with Mangalitsa and Duroc breeds. The genetic distances of TP can be explained by high degree of inbreeding during the past century. Despite the European origin of Croatian pig breeds with some impact of Chinese breeds in the past, the results of present study show that genetic diversity is still pronounced within investigated breeds. Furthermore, the genetic diversity is even more pronounced between Croatian breeds and other European and Chinese pig breeds. Thus, conservation of Croatian pig breeds will contribute to overall genetic diversity preservation of pig breeds.}, } @article {pmid29940392, year = {2018}, author = {Wang, Q and Lu, W and Yang, J and Jiang, L and Zhang, Q and Kan, X and Yang, X}, title = {Comparative transcriptomics in three Passerida species provides insights into the evolution of avian mitochondrial complex I.}, journal = {Comparative biochemistry and physiology. Part D, Genomics & proteomics}, volume = {28}, number = {}, pages = {27-36}, doi = {10.1016/j.cbd.2018.06.002}, pmid = {29940392}, issn = {1878-0407}, mesh = {Animals ; Avian Proteins/*genetics ; DNA, Mitochondrial/genetics ; Electron Transport Complex I/*genetics ; Evolution, Molecular ; *Genes, Mitochondrial ; Genomics ; Phylogeny ; Selection, Genetic ; Sparrows/*genetics ; Species Specificity ; *Transcriptome ; }, abstract = {Recent studies have shown that mitochondria play a crucial role in cellular energy production through the oxidative phosphorylation (OXPHOS) system. Complex I (NADH:ubiquinone oxidoreductase), the first and largest enzyme complex of the OXPHOS system, includes both nuclear- and mitochondrial-encoded proteins. However, the patterns of natural selection and phylogenetic implications of complex I in birds still remain unclear. In this study, we combined transcriptomic and phylogenetic analyses to comprehensively determine the evolution of avian complex I. The transcriptomes of three Passerida species (Leiothrix lutea, Spodiopsar sericeus, and Passer montanus) were obtained using the Illumina HiSeq™ 2500 system. More than 192,000,000 clean reads were assembled in a total of 828,267 transcripts. Evolutionary selection analysis suggested that six genes of the core subunits in avian complex I may have undergone putative positive selection. Notably, we found that the mean dN/dS (ω) ratio for mitochondrial genes of core subunits was significantly lower than that for nuclear genes of non-core subunits within complex I. The constructed maximum-parsimony, maximum-likelihood, and Bayesian inference phylogenetic trees were based on 44 complex I genes. We verified that the family Paridae (represented by Parus major and Pseudopodoces humilis) was clustered with Musicicapoidea. Our results provide new insights into the evolution of avian mitochondrial complex I.}, } @article {pmid29942045, year = {2018}, author = {Li, D and Waite, DW and Fan, QH and George, S and Semeraro, L and Blacket, MJ}, title = {Molecular detection of small hive beetle Aethina tumida Murray (Coleoptera: Nitidulidae): DNA barcoding and development of a real-time PCR assay.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {9623}, pmid = {29942045}, issn = {2045-2322}, mesh = {Animals ; *Bees ; Coleoptera/*classification/*genetics ; *DNA Barcoding, Taxonomic ; Electron Transport Complex IV/genetics ; Mitochondria/enzymology ; Phylogeny ; *Real-Time Polymerase Chain Reaction ; }, abstract = {Small hive beetle (SHB), Aethina tumida can feed on honey, pollen and brood in honey bee colonies. It was endemic to Africa, but since 1996 has been detected in a number of countries worldwide, including Australia, Brazil, Canada, Italy, Mexico, South Korea, Philippines and the USA where it has had economic effects on local apiculture. To improve SHB identification, we obtained the first reference sequences from the DNA barcoding 5' COI gene region for SHB and some species of the family Nitidulidae associated with beehives. Phylogenetic analysis of SHB COI sequences (3' COI) revealed two divergent lineages, with those from Australia and USA being genetically different from the recent detection in Italy. Many countries, including New Zealand, are currently free from SHB, and require a rapid detection method for biosecurity. Here we present the development and validation of a real-time PCR assay for detection of SHB. The assay showed high specificity and sensitivity for detecting SHB, with no cross-reaction observed with closely related species, such as A. concolor. The real-time PCR is sensitive, detecting the target sequences up to 100 copies/µL. This assay should prove a useful biosecurity tool for rapid detection of SHB worldwide.}, } @article {pmid29944924, year = {2018}, author = {Chakrabarty, S and Kabekkodu, SP and Singh, RP and Thangaraj, K and Singh, KK and Satyamoorthy, K}, title = {Mitochondria in health and disease.}, journal = {Mitochondrion}, volume = {43}, number = {}, pages = {25-29}, doi = {10.1016/j.mito.2018.06.006}, pmid = {29944924}, issn = {1872-8278}, mesh = {Animals ; Biomedical Research/*trends ; Disease Models, Animal ; Humans ; India ; Mitochondria/*physiology ; Mitochondrial Diseases/diagnosis/*pathology/*physiopathology/therapy ; }, abstract = {Mitochondrial biology has become an area of intense research owing to the unique physiology of the organelle and its role in several types of cancers and other disorders. It has been found that mitochondria-encoded proteins, mitochondrial DNA and even RNA influence the functioning of the cell in more ways than were previously imagined. This may contribute to disease phenotypes which require detailed investigation and communication to the community health care providers. Additionally, this provides several novel avenues in drug designing against various cancers, neurodegenerative diseases and other metabolic disorders. The sixth annual conference of the Society for Mitochondrial Research and Medicine - India (SMRM) titled, 'Mitochondria in Health and Disease' was organized by Rana P. Singh at the School of Life Sciences, Jawaharlal Nehru University in New Delhi, India from 10th to 11th February 2017. The underlying objective of the conference was to provide a platform to discuss the recent advances in basic and translational research in mitochondrial biology and diseases. The conference aimed to translate academic research into clinical practice by providing a forum for basic researchers and clinicians to share their knowledge and build collaborations towards development of advanced therapeutic in mitochondrial diseases. To facilitate the knowledge-sharing, six major themes for the scientific sessions were (1) understanding of mitochondrial biology in disease progression, (2) advances in basic and translational mitochondrial research, (3) mitochondria in evolution and development, (4) targeting mitochondria for cancer prevention and treatment, (5) mitochondria in metabolic and neurological disorders and (6) mitochondria in stem cell and regeneration biology. This report summarizes the major outcomes of the discussions at the conference.}, } @article {pmid29945242, year = {2018}, author = {Buchanan, JL and Meiklejohn, CD and Montooth, KL}, title = {Mitochondrial Dysfunction and Infection Generate Immunity-Fecundity Tradeoffs in Drosophila.}, journal = {Integrative and comparative biology}, volume = {58}, number = {3}, pages = {591-603}, pmid = {29945242}, issn = {1557-7023}, support = {R01 GM067862/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Drosophila melanogaster/genetics/*physiology ; Drosophila simulans/genetics/*physiology ; Female ; Fertility ; *Genotype ; Hybridization, Genetic ; Immunity, Innate ; *Life History Traits ; Male ; Mitochondria/*physiology ; Nutritional Status ; Oxidative Phosphorylation ; Stress, Physiological ; }, abstract = {Physiological responses to short-term environmental stressors, such as infection, can have long-term consequences for fitness, particularly if the responses are inappropriate or nutrient resources are limited. Genetic variation affecting energy acquisition, storage, and usage can limit cellular energy availability and may influence resource-allocation tradeoffs even when environmental nutrients are plentiful. Here, we utilized Drosophila mitochondrial-nuclear genotypes to test whether disrupted mitochondrial function interferes with nutrient-sensing pathways, and whether this disruption has consequences for tradeoffs between immunity and fecundity. We found that an energetically-compromised genotype was relatively resistant to rapamycin-a drug that targets nutrient-sensing pathways and mimics resource limitation. Dietary resource limitation decreased survival of energetically-compromised flies. Furthermore, survival of infection with a natural pathogen was decreased in this genotype, and females of this genotype experienced immunity-fecundity tradeoffs that were not evident in genotypic controls with normal energy metabolism. Together, these results suggest that this genotype may have little excess energetic capacity and fewer cellular nutrients, even when environmental nutrients are not limiting. Genetic variation in energy metabolism may therefore act to limit the resources available for allocation to life-history traits in ways that generate tradeoffs even when environmental resources are not limiting.}, } @article {pmid29945248, year = {2018}, author = {Bize, P and Lowe, I and Lehto Hürlimann, M and Heckel, G}, title = {Effects of the Mitochondrial and Nuclear Genomes on Nonshivering Thermogenesis in a Wild Derived Rodent.}, journal = {Integrative and comparative biology}, volume = {58}, number = {3}, pages = {532-543}, doi = {10.1093/icb/icy072}, pmid = {29945248}, issn = {1557-7023}, mesh = {Adipose Tissue, Brown/*physiology ; Animals ; Arvicolinae/classification/genetics/*physiology ; Cell Nucleus/genetics ; Female ; Genome/*physiology ; Genome, Mitochondrial/physiology ; Male ; Thermogenesis/*genetics ; }, abstract = {A key adaptation of mammals to their environment is their ability to maintain a constant high body temperature, even at rest, under a wide range of ambient temperatures. In cold climates, this is achieved by an adaptive production of endogenous heat, known as nonshivering thermogenesis (NST), in the brown adipose tissue (BAT). This organ, unique to mammals, contains a very high density of mitochondria, and BAT correct functioning relies on the correct functioning of its mitochondria. Mitochondria enclose proteins encoded both in the maternally inherited mitochondrial genome and in the biparentally inherited nuclear genome, and one overlooked hypothesis is that both genomes and their interaction may shape NST. By housing under standardized conditions wild-derived common voles (Microtus arvalis) from two distinct evolutionary lineages (Western [W] and Central [C]), we show that W voles had greater NST than C voles. By introgressing those two lineages over at least nine generations, we then experimentally tested the influence of the nuclear and mitochondrial genomes on NST and related phenotypic traits. We found that between-lineage variation in NST and BAT size were significantly influenced by the mitochondrial and nuclear genomes, respectively, with the W mitochondrial genotype being associated with higher NST and the W nuclear genotype with a larger BAT. There were significant mito-nuclear interactions on whole animal body weight and resting metabolic rate (RMR). Hybrid voles were lighter and had higher RMR. Overall, our findings turn new light on the influence of the mitochondrial and nuclear genomes on thermogenesis and building adaptation to the environment in mammals.}, } @article {pmid29945721, year = {2018}, author = {Barshad, G and Marom, S and Cohen, T and Mishmar, D}, title = {Mitochondrial DNA Transcription and Its Regulation: An Evolutionary Perspective.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {9}, pages = {682-692}, doi = {10.1016/j.tig.2018.05.009}, pmid = {29945721}, issn = {0168-9525}, mesh = {Animals ; DNA, Mitochondrial/*genetics ; DNA-Binding Proteins/genetics ; DNA-Directed RNA Polymerases/genetics ; *Evolution, Molecular ; Gene Expression Regulation/genetics ; Humans ; Mitochondria/*genetics ; Mitochondrial Proteins/genetics ; Shelterin Complex ; Telomere-Binding Proteins/genetics ; Transcription Factors/genetics ; *Transcription, Genetic ; }, abstract = {The bacterial heritage of mitochondria, as well as its independent genome [mitochondrial DNA (mtDNA)] and polycistronic transcripts, led to the view that mitochondrial transcriptional regulation relies on an evolutionarily conserved, prokaryotic-like system that is separated from the rest of the cell. Indeed, mtDNA transcription was previously thought to be governed by a few dedicated direct regulators, namely, the mitochondrial RNA polymerase (POLRMT), two transcription factors (TFAM and TF2BM), one transcription elongation (TEFM), and one known transcription termination factor (mTERF1). Recent findings have, however, revealed that known nuclear gene expression regulators are also involved in mtDNA transcription and have identified novel transcriptional features consistent with adaptation of the mitochondria to the regulatory environment of the precursor of the eukaryotic cell. Finally, whereas mammals follow the human mtDNA transcription pattern, other organisms notably diverge in terms of mtDNA transcriptional regulation. Hence, mtDNA transcriptional regulation is likely more evolutionary diverse than once thought.}, } @article {pmid29946965, year = {2018}, author = {Sharma, M and Bennewitz, B and Klösgen, RB}, title = {Rather rule than exception? How to evaluate the relevance of dual protein targeting to mitochondria and chloroplasts.}, journal = {Photosynthesis research}, volume = {138}, number = {3}, pages = {335-343}, pmid = {29946965}, issn = {1573-5079}, mesh = {Biological Assay ; Biological Evolution ; Chloroplasts/*metabolism ; Mitochondria/*metabolism ; Protein Transport ; Symbiosis ; }, abstract = {Dual targeting of a nuclearly encoded protein into two different cell organelles is an exceptional event in eukaryotic cells. Yet, the frequency of such dual targeting is remarkably high in case of mitochondria and chloroplasts, the two endosymbiotic organelles of plant cells. In most instances, it is mediated by "ambiguous" transit peptides, which recognize both organelles as the target. A number of different approaches including in silico, in organello as well as both transient and stable in vivo assays are established to determine the targeting specificity of such transit peptides. In this review, we will describe and compare these approaches and discuss the potential role of this unusual targeting process. Furthermore, we will present a hypothetical scenario how dual targeting might have arisen during evolution.}, } @article {pmid29948332, year = {2018}, author = {van der Sluis, R}, title = {Analyses of the genetic diversity and protein expression variation of the acyl: CoA medium-chain ligases, ACSM2A and ACSM2B.}, journal = {Molecular genetics and genomics : MGG}, volume = {293}, number = {5}, pages = {1279-1292}, pmid = {29948332}, issn = {1617-4623}, support = {Self-Initiated research grant//South African Medical Research Council/ ; 99323//National Research Foundation/ ; }, mesh = {Coenzyme A Ligases/*genetics/metabolism ; *Genetic Variation ; Glycine/metabolism ; *Haplotypes ; Humans ; Mitochondria, Liver/*enzymology ; Phylogeny ; Substrate Specificity ; Xenobiotics/*metabolism ; }, abstract = {Benzoate (found in milk and widely used as preservative), salicylate (present in fruits and the active component of aspirin), dietary polyphenols produced by gut microbiota, metabolites from organic acidemias, and medium-chain fatty acids (MCFAs) are all metabolised/detoxified by the glycine conjugation pathway. Xenobiotics are first activated to an acyl-CoA by the mitochondrial xenobiotic/medium-chain fatty acid: CoA ligases (ACSMs) and subsequently conjugated to glycine by glycine N-acyltransferase (GLYAT). The MCFAs are activated to acyl-CoA by the ACSMs before entering mitochondrial β-oxidation. This two-step enzymatic pathway has, however, not been thoroughly investigated and the biggest gap in the literature remains the fact that studies continuously characterise the pathway as a one-step reaction. There are no studies available on the interaction/competition of the various substrates involved in the pathway, whilst very little research has been done on the ACSM ligases. To identify variants/haplotypes that should be characterised in future detoxification association studies, this study assessed the naturally observed sequence diversity and protein expression variation of ACSM2A and ACSM2B. The allelic variation, haplotype diversity, Tajima's D values, and phylogenetic analyses indicated that ACSM2A and ACSM2B are highly conserved. This confirmed an earlier hypothesis that the glycine conjugation pathway is highly conserved and essential for life as it maintains the CoA and glycine homeostasis in the liver mitochondria. The protein expression analyses showed that ACSM2A is the predominant transcript in liver. Future studies should investigate the effect of the variants identified in this study on the substrate specificity of these proteins.}, } @article {pmid29948488, year = {2018}, author = {Yoshida, Y}, title = {The cellular machineries responsible for the division of endosymbiotic organelles.}, journal = {Journal of plant research}, volume = {131}, number = {5}, pages = {727-734}, pmid = {29948488}, issn = {1618-0860}, support = {K05 DA000049/DA/NIDA NIH HHS/United States ; Career Development Award/CDA00049/2018-C//Human Frontier Science Program/ ; KAKENHI/JP18K06325//Japan Society for the Promotion of Science/ ; }, mesh = {Cell Division ; Chloroplasts/physiology/ultrastructure ; Mitochondria/physiology/ultrastructure ; Organelles/physiology/*ultrastructure ; Plastids/physiology/ultrastructure ; Rhodophyta/physiology/*ultrastructure ; *Symbiosis ; }, abstract = {Chloroplasts (plastids) and mitochondria evolved from endosymbiotic bacteria. These organelles perform vital functions in photosynthetic eukaryotes, such as harvesting and converting energy for use in biological processes. Consistent with their evolutionary origins, plastids and mitochondria proliferate by the binary fission of pre-existing organelles. Here, I review the structures and functions of the supramolecular machineries driving plastid and mitochondrial division, which were discovered and first studied in the primitive red alga Cyanidioschyzon merolae. In the past decade, intact division machineries have been isolated from plastids and mitochondria and examined to investigate their underlying structure and molecular mechanisms. A series of studies has elucidated how these division machineries assemble and transform during the fission of these organelles, and which of the component proteins generate the motive force for their contraction. Plastid- and mitochondrial-division machineries have important similarities in their structures and mechanisms despite sharing no component proteins, implying that these division machineries evolved in parallel. The establishment of these division machineries might have enabled the host eukaryotic ancestor to permanently retain these endosymbiotic organelles by regulating their binary fission and the equal distribution of resources to daughter cells. These findings provide key insights into the establishment of endosymbiotic organelles and have opened new avenues of research into their evolution and mechanisms of proliferation.}, } @article {pmid29949074, year = {2018}, author = {Zhang, R and Wang, X}, title = {Characterization and phylogenetic analysis of the complete mitogenome of a rare cavefish, Sinocyclocheilus multipunctatus (Cypriniformes: Cyprinidae).}, journal = {Genes & genomics}, volume = {40}, number = {10}, pages = {1033-1040}, pmid = {29949074}, issn = {2092-9293}, mesh = {Animals ; Base Composition ; Contig Mapping ; Cyprinidae/*genetics ; Genome Size ; *Genome, Mitochondrial ; Mitochondria/*genetics ; Molecular Sequence Annotation ; Phylogeny ; Sequence Analysis, DNA/*methods ; }, abstract = {The genus Sinocyclocheilus is a representative group of cave creatures. However, genetic studies on Sinocyclocheilus are rare. The primary objective of this study was to explore the structure and feature of the complete mitochondrial genome of S. multipunctatus, and reconstruct the mitogenomic phylogeny of Sinocyclocheilus. The mitochondrial DNA of S. multipunctatus was amplified by overlapping PCR fragments. The mitogenome was assembled by the SeqMan and annotated using MitoAnnotator. The phylogenetic tree was established using the Bayesian inference and Maximum likelihood methods. The mitogenome of S. multipunctatus is a typical circular molecule of 16,586 bp with base composition A (31.25%), T (25.90%), G (16.35%), and C (26.50%), and consists of 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs) genes, two ribosomal RNAs, and a 931 bp control region. Phylogenetic analysis reveals two clades in the Sinocyclocheilus with robust support. S. multipunctatus is close to a newly discovered cavefish, S. ronganensis. We obtained and described the complete mitogenome of S. multipunctatus, and investigated its phylogenetic status, which may provide a valuable resource for future phylogenetic analyses and population genetic studies in Sinocyclocheilus.}, } @article {pmid29949077, year = {2018}, author = {Lu, Y and Liu, N and Xu, L and Fang, J and Wang, S}, title = {The complete mitochondrial genome of Vanessa indica and phylogenetic analyses of the family Nymphalidae.}, journal = {Genes & genomics}, volume = {40}, number = {10}, pages = {1011-1022}, pmid = {29949077}, issn = {2092-9293}, support = {J10118516034//Undergraduate student scientific research innovation projects of Anhui university/International ; }, mesh = {Animals ; Base Composition ; Butterflies/*classification/cytology/genetics ; Evolution, Molecular ; Genome Size ; *Genome, Mitochondrial ; Mitochondria/*genetics ; Nucleic Acid Conformation ; Phylogeny ; RNA, Ribosomal/chemistry ; RNA, Ribosomal, 16S/chemistry ; RNA, Transfer/chemistry ; Sequence Analysis, DNA/*methods ; }, abstract = {Vanessa indica is a small butterfly lacking historical molecular and biological research. Vanessa indica belongs to the family Nymphalidae (Lepidoptera: Papilionoidea), which is the largest group of butterflies and are nearly ubiquitous. However, after more than a century of taxonomic and molecular studies, there is no consensus for family classification, and the phylogenetic relationships within Nymphalidae are controversial. The first objective was to sequence and characterize the complete mitochondrial genome of V. indica. The most important objective was to completely reconstruct the phylogenetic relationships for family members within Nymphalidae. The mitochondrial genomic DNA (mtDNA) of V. indica was extracted and amplified by polymerase chain reaction. The complete mitochondrial sequence was annotated and characterized by analyzing sequences with SeqMan program. The phylogenetic analyses were conducted on thirteen protein coding genes (PCGs) in 95 mtDNA of Nymphalidae downloaded from GenBank for reference using the maximum likelihood method and Bayesian inference to ensure the validity of the results. The complete mitogenome was a circular molecule with 15,191 bp consisting of 13 protein coding genes, two ribosomal RNA genes (16S rRNA and 12S rRNA), 22 transfer RNA (tRNA) genes, and an A + T-rich region (D-loop). The nucleotide composition of the genome was highly biased for A + T content, which accounts for 80.0% of the nucleotides. All the tRNAs have putative secondary structures that are characteristic of mitochondrial tRNAs, except tRNA[Ser(AGN)]. All the PCGs started with ATN codons, except cytochrome c oxidase subunit 1 (COX1), which was found to start with an unusual CGA codon. Four genes were observed to have unusual codons: COX1 terminated with atypical TT and the other three genes terminated with a single T. The A + T rich region of 327 bp consisted of repetitive sequences, including a ATAGA motif, a 19-bp poly-T stretch, and two microsatellite-like regions (TA)8. The phylogenetic analyses consistently placed Biblidinae as a sister cluster to Heliconiinae and Calinaginae as a sister clade to Satyrinae. Moreover, the phylogenetic tree identified Libytheinae as a monophyletic group within Nymphalidae. The complete mitogenome of V. indica was 15,191 bp with mitochondrial characterizations common for lepidopteran species, which enriched the mitochondria data of Nymphalid species. And the phylogenetic analysis revealed different classifications and relationships than those previously described. Our results are significant because they would be useful in further understanding of the evolutionary biology of Nymphalidae.}, } @article {pmid29950419, year = {2018}, author = {Bilz, NC and Jahn, K and Lorenz, M and Lüdtke, A and Hübschen, JM and Geyer, H and Mankertz, A and Hübner, D and Liebert, UG and Claus, C}, title = {Rubella Viruses Shift Cellular Bioenergetics to a More Oxidative and Glycolytic Phenotype with a Strain-Specific Requirement for Glutamine.}, journal = {Journal of virology}, volume = {92}, number = {17}, pages = {}, pmid = {29950419}, issn = {1098-5514}, mesh = {A549 Cells ; Endothelial Cells/metabolism/virology ; *Energy Metabolism ; Glucose/metabolism/pharmacology ; Glutamine/*metabolism/pharmacology ; Glycolysis/*drug effects ; Homeostasis ; Humans ; Kynurenine/metabolism ; Metabolic Networks and Pathways/drug effects ; Mitochondria/metabolism ; Nucleotides/biosynthesis ; Oxidation-Reduction ; Oxidative Stress ; Oxygen Consumption/drug effects/*physiology ; Phenotype ; Pyruvic Acid/metabolism/pharmacology ; Rubella virus/*metabolism ; Virus Replication/drug effects ; }, abstract = {The flexible regulation of cellular metabolic pathways enables cellular adaptation to changes in energy demand under conditions of stress such as posed by a virus infection. To analyze such an impact on cellular metabolism, rubella virus (RV) was used in this study. RV replication under selected substrate supplementation with glucose, pyruvate, and glutamine as essential nutrients for mammalian cells revealed its requirement for glutamine. The assessment of the mitochondrial respiratory (based on the oxygen consumption rate) and glycolytic (based on the extracellular acidification rate) rate and capacity by respective stress tests through Seahorse technology enabled determination of the bioenergetic phenotype of RV-infected cells. Irrespective of the cellular metabolic background, RV infection induced a shift of the bioenergetic state of epithelial cells (Vero and A549) and human umbilical vein endothelial cells to a higher oxidative and glycolytic level. Interestingly there was a RV strain-specific, but genotype-independent demand for glutamine to induce a significant increase in metabolic activity. While glutaminolysis appeared to be rather negligible for RV replication, glutamine could serve as donor of its amide nitrogen in biosynthesis pathways for important metabolites. This study suggests that the capacity of RVs to induce metabolic alterations could evolve differently during natural infection. Thus, changes in cellular bioenergetics represent an important component of virus-host interactions and could complement our understanding of the viral preference for a distinct host cell population.IMPORTANCE RV pathologies, especially during embryonal development, could be connected with its impact on mitochondrial metabolism. With bioenergetic phenotyping we pursued a rather novel approach in virology. For the first time it was shown that a virus infection could shift the bioenergetics of its infected host cell to a higher energetic state. Notably, the capacity to induce such alterations varied among different RV isolates. Thus, our data add viral adaptation of cellular metabolic activity to its specific needs as a novel aspect to virus-host evolution. In addition, this study emphasizes the implementation of different viral strains in the study of virus-host interactions and the use of bioenergetic phenotyping of infected cells as a biomarker for virus-induced pathological alterations.}, } @article {pmid29950599, year = {2018}, author = {Burgstaller, JP and Kolbe, T and Havlicek, V and Hembach, S and Poulton, J and Piálek, J and Steinborn, R and Rülicke, T and Brem, G and Jones, NS and Johnston, IG}, title = {Large-scale genetic analysis reveals mammalian mtDNA heteroplasmy dynamics and variance increase through lifetimes and generations.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {2488}, pmid = {29950599}, issn = {2041-1723}, support = {MR/J010448/1/MRC_/Medical Research Council/United Kingdom ; MR/J013617/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Age Factors ; Animals ; DNA Copy Number Variations/*genetics ; DNA, Mitochondrial/*genetics ; Datasets as Topic ; Female ; Genome, Mitochondrial/*genetics ; Haplotypes/genetics ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism ; Models, Animal ; Oocytes/cytology/immunology ; }, abstract = {Vital mitochondrial DNA (mtDNA) populations exist in cells and may consist of heteroplasmic mixtures of mtDNA types. The evolution of these heteroplasmic populations through development, ageing, and generations is central to genetic diseases, but is poorly understood in mammals. Here we dissect these population dynamics using a dataset of unprecedented size and temporal span, comprising 1947 single-cell oocyte and 899 somatic measurements of heteroplasmy change throughout lifetimes and generations in two genetically distinct mouse models. We provide a novel and detailed quantitative characterisation of the linear increase in heteroplasmy variance throughout mammalian life courses in oocytes and pups. We find that differences in mean heteroplasmy are induced between generations, and the heteroplasmy of germline and somatic precursors diverge early in development, with a haplotype-specific direction of segregation. We develop stochastic theory predicting the implications of these dynamics for ageing and disease manifestation and discuss its application to human mtDNA dynamics.}, } @article {pmid29953866, year = {2018}, author = {Woodling, NS and Partridge, L}, title = {Parkinson's Disease: Mitochondria Parked at the ER Hit the Snooze Button.}, journal = {Neuron}, volume = {98}, number = {6}, pages = {1059-1061}, doi = {10.1016/j.neuron.2018.06.025}, pmid = {29953866}, issn = {1097-4199}, mesh = {Humans ; Lipids ; Mitochondria ; Mutation ; Neurons ; *Parkinson Disease ; Ubiquitin-Protein Ligases/genetics ; }, abstract = {Parkinson's disease patients report sleep disturbances well ahead of motor symptoms. In this issue of Neuron, Valadas et al. (2018) report that the disease genes pink1 and parkin exert novel, cell-type-specific effects to modulate ER-mitochondria contacts, neuropeptidergic transmission, and sleep patterns.}, } @article {pmid29955026, year = {2018}, author = {Liu, SY and He, K and Chen, SD and Jin, W and Murphy, RW and Tang, MK and Liao, R and Li, FJ}, title = {How many species of Apodemus and Rattus occur in China? A survey based on mitochondrial cyt b and morphological analyses.}, journal = {Zoological research}, volume = {39}, number = {5}, pages = {309-320}, pmid = {29955026}, issn = {2095-8137}, mesh = {Animals ; China ; Cytochromes b/*genetics ; Mitochondria/*genetics ; Murinae/anatomy & histology/*genetics ; Phylogeny ; Rats/anatomy & histology/*genetics ; Skull/anatomy & histology ; Surveys and Questionnaires ; Tooth/anatomy & histology ; }, abstract = {Apodemus (mice) and Rattus (rats) are the top rodent reservoirs for zoonoses in China, yet little is known about their diversity. We reexamined the alpha diversity of these two genera based on a new collection of specimens from China and their cyt b sequences in GenBank. We also tested whether species could be identified using external and craniodental measurements exclusively. Measurements from 147 specimens of Apodemus and 236 specimens of Rattus were used for morphological comparisons. We analysed 74 cyt b sequences of Apodemus and 100 cyt b sequences of Rattus to facilitate phylogenetic estimations. Results demonstrated that nine species of Apodemus and seven species of Rattus, plus a new subspecies of Rattus nitidus, are distributed in China. Principal component analysis using external and craniodental measurements revealed that measurements alone could not separate the recognized species. The occurrence of Rattus pyctoris in China remains uncertain.}, } @article {pmid29959984, year = {2018}, author = {Uribe, JE and Zardoya, R and Puillandre, N}, title = {Phylogenetic relationships of the conoidean snails (Gastropoda: Caenogastropoda) based on mitochondrial genomes.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {898-906}, doi = {10.1016/j.ympev.2018.06.037}, pmid = {29959984}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Gene Order ; *Genome, Mitochondrial ; Mitochondria/genetics ; Open Reading Frames/genetics ; *Phylogeny ; Snails/*genetics ; }, abstract = {With more than 5,000 species, Conoidea is one of the most diversified superfamilies of Gastropoda. Recently, the family-level classification of these venomous predator snails has undergone substantial changes, on the basis of a phylogenetic tree reconstructed combining partial mitochondrial and nuclear gene sequences, and up to 16 families are now recognized. However, phylogenetic relationships among these families remain largely unresolved. Here, we sequenced 20 complete or nearly complete mitochondrial (mt) genomes, which were combined with mt genomes available in GenBank to construct a dataset that included representatives of 80% of the known families, although for some we had only one species or genus as representative. Most of the sequenced conoidean mt genomes shared a constant genome organization, and observed rearrangements were limited exclusively to tRNA genes in a few lineages. Phylogenetic trees were reconstructed using probabilistic methods. Two main monophyletic groups, termed "Clade A" and "Clade B", were recovered with strong support within a monophyletic Conoidea. Clade A (including families Clavatulidae, Horaiclavidae, Turridae s.s., Terebridae, Drilliidae, Pseudomelatomidae, and Cochlespiridae) was composed of four main lineages, one of which was additionally supported by a rearrangement in the gene order. Clade B (including families Conidae, Borsoniidae, Clathurellidae, Mangeliidae, Raphitomidae, and Mitromorphidae) was composed of five main lineages. The reconstructed phylogeny rejected the monophyly of Clavatulidae, Horaiclavidae, Turridae, Pseudomelatomidae, and Conidae, indicating that several of the currently accepted families may be ill-defined. The reconstructed tree also revealed new phylogenetic positions for genera characterized as tentative (Gemmuloborsonia, Lucerapex, and Leucosyrinx), enigmatic (Marshallena) or challenging to place (Fusiturris), which will potentially impact the classification of the Conoidea.}, } @article {pmid29967381, year = {2018}, author = {Pietras, Z and Wojcik, MA and Borowski, LS and Szewczyk, M and Kulinski, TM and Cysewski, D and Stepien, PP and Dziembowski, A and Szczesny, RJ}, title = {Dedicated surveillance mechanism controls G-quadruplex forming non-coding RNAs in human mitochondria.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {2558}, pmid = {29967381}, issn = {2041-1723}, support = {UMO-2014/12/W/NZ1/00463 to RJS//Narodowe Centrum Nauki (National Science Centre)/International ; UMO-2014/13/D/NZ2/01114 to RJS//Narodowe Centrum Nauki (National Science Centre)/International ; UMO-2013/11/13/NZ1/00089 to PPS//Narodowe Centrum Nauki (National Science Centre)/International ; 309419 PAPs & PUPs to AD//EC | European Research Council (ERC)/International ; }, mesh = {Animals ; DEAD-box RNA Helicases/metabolism ; Endoribonucleases/metabolism ; Exoribonucleases/genetics/metabolism ; *G-Quadruplexes ; Genome, Mitochondrial/*genetics ; HEK293 Cells ; HeLa Cells ; Humans ; Mitochondria/genetics/*metabolism ; Multienzyme Complexes/metabolism ; Phylogeny ; Poly(A)-Binding Proteins/genetics/*metabolism ; Polyribonucleotide Nucleotidyltransferase/metabolism ; RNA Helicases/metabolism ; RNA, Small Interfering/metabolism ; RNA, Untranslated/genetics/*metabolism ; Mitochondrial Proteins ; }, abstract = {The GC skew in vertebrate mitochondrial genomes results in synthesis of RNAs that are prone to form G-quadruplexes (G4s). Such RNAs, although mostly non-coding, are transcribed at high rates and are degraded by an unknown mechanism. Here we describe a dedicated mechanism of degradation of G4-containing RNAs, which is based on cooperation between mitochondrial degradosome and quasi-RNA recognition motif (qRRM) protein GRSF1. This cooperation prevents accumulation of G4-containing transcripts in human mitochondria. In vitro reconstitution experiments show that GRSF1 promotes G4 melting that facilitates degradosome-mediated decay. Among degradosome and GRSF1 regulated transcripts we identified one that undergoes post-transcriptional modification. We show that GRSF1 proteins form a distinct qRRM group found only in vertebrates. The appearance of GRSF1 coincided with changes in the mitochondrial genome, which allows the emergence of G4-containing RNAs. We propose that GRSF1 appearance is an evolutionary adaptation enabling control of G4 RNA.}, } @article {pmid29970001, year = {2018}, author = {Lenz, H and Hein, A and Knoop, V}, title = {Plant organelle RNA editing and its specificity factors: enhancements of analyses and new database features in PREPACT 3.0.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {255}, pmid = {29970001}, issn = {1471-2105}, mesh = {Computational Biology/*methods ; Plant Proteins/*genetics ; RNA Editing/*genetics ; RNA, Plant/*genetics ; }, abstract = {BACKGROUND: Gene expression in plant chloroplasts and mitochondria is affected by RNA editing. Numerous C-to-U conversions, accompanied by reverse U-to-C exchanges in some plant clades, alter the genetic information encoded in the organelle genomes. Predicting and analyzing RNA editing, which ranges from only few sites in some species to thousands in other taxa, is bioinformatically demanding.

RESULTS: Here, we present major enhancements and extensions of PREPACT, a WWW-based service for analysing, predicting and cataloguing plant-type RNA editing. New features in PREPACT's core include direct GenBank accession query input and options to restrict searches to candidate U-to-C editing or to sites where editing has been documented previously in the references. The reference database has been extended by 20 new organelle editomes. PREPACT 3.0 features new modules "EdiFacts" and "TargetScan". EdiFacts integrates information on pentatricopeptide repeat (PPR) proteins characterized as site-specific RNA editing factors. PREPACT's editome references connect into EdiFacts, linking editing events to specific co-factors where known. TargetScan allows position-weighted querying for sequence motifs in the organelle references, optionally restricted to coding regions or sequences around editing sites, or in queries uploaded by the user. TargetScan is mainly intended to evaluate and further refine the proposed PPR-RNA recognition code but may be handy for other tasks as well. We present an analysis for the immediate sequence environment of more than 15,000 documented editing sites finding strong and different bias in the editome data sets.

CONCLUSIONS: We exemplarily present the novel features of PREPACT 3.0 aimed to enhance the analyses of plant-type RNA editing, including its new modules EdiFacts integrating information on characterized editing factors and TargetScan aimed to analyse RNA editing site recognition specificities.}, } @article {pmid29973152, year = {2018}, author = {Vanhove, MPM and Briscoe, AG and Jorissen, MWP and Littlewood, DTJ and Huyse, T}, title = {The first next-generation sequencing approach to the mitochondrial phylogeny of African monogenean parasites (Platyhelminthes: Gyrodactylidae and Dactylogyridae).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {520}, pmid = {29973152}, issn = {1471-2164}, support = {BR/132/PI/TILAPIA//Federaal Wetenschapsbeleid/ ; GB-TAF-2984//SYNTHESYS/ ; GB-TAF-4940//SYNTHESYS/ ; ZRDC2014MP084//Vlaamse Interuniversitaire Raad/ ; P505/12/G112 (ECIP)//Grantová Agentura České Republiky/ ; K220314N//Fonds Wetenschappelijk Onderzoek/ ; Mbisa Congo project//Belgian Development Cooperation/ ; BOF Reserve Fellowship//Universiteit Hasselt/ ; }, mesh = {Animals ; Cichlids/*parasitology ; DNA, Protozoan/chemistry/isolation & purification/metabolism ; Gene Order ; Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing ; Mitochondria/classification/*genetics ; Phylogeny ; Platyhelminths/*genetics ; Protozoan Proteins/classification/genetics ; RNA, Ribosomal/classification/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Monogenean flatworms are the main ectoparasites of fishes. Representatives of the species-rich families Gyrodactylidae and Dactylogyridae, especially those infecting cichlid fishes and clariid catfishes, are important parasites in African aquaculture, even more so due to the massive anthropogenic translocation of their hosts worldwide. Several questions on their evolution, such as the phylogenetic position of Macrogyrodactylus and the highly speciose Gyrodactylus, remain unresolved with available molecular markers. Also, diagnostics and population-level research would benefit from the development of higher-resolution genetic markers. We aim to offer genetic resources for work on African monogeneans by providing mitogenomic data of four species (two belonging to Gyrodactylidae, two to Dactylogyridae), and analysing their gene sequences and gene order from a phylogenetic perspective.

RESULTS: Using Illumina technology, the first four mitochondrial genomes of African monogeneans were assembled and annotated for the cichlid parasites Gyrodactylus nyanzae, Cichlidogyrus halli, Cichlidogyrus mbirizei (near-complete mitogenome) and the catfish parasite Macrogyrodactylus karibae (near-complete mitogenome). Complete nuclear ribosomal operons were also retrieved, as molecular vouchers. The start codon TTG is new for Gyrodactylus and for Dactylogyridae, as is the incomplete stop codon TA for Dactylogyridae. Especially the nad2 gene is promising for primer development. Gene order was identical for protein-coding genes and differed between the African representatives of these families only in a tRNA gene transposition. A mitochondrial phylogeny based on an alignment of nearly 12,500 bp including 12 protein-coding and two ribosomal RNA genes confirms that the Neotropical oviparous Aglaiogyrodactylus forficulatus takes a sister group position with respect to the other gyrodactylids, instead of the supposedly 'primitive' African Macrogyrodactylus. Inclusion of the African Gyrodactylus nyanzae confirms the paraphyly of Gyrodactylus. The position of the African dactylogyrid Cichlidogyrus is unresolved, although gene order suggests it is closely related to marine ancyrocephalines.

CONCLUSIONS: The amount of mitogenomic data available for gyrodactylids and dactylogyrids is increased by roughly one-third. Our study underscores the potential of mitochondrial genes and gene order in flatworm phylogenetics, and of next-generation sequencing for marker development for these non-model helminths for which few primers are available.}, } @article {pmid29976842, year = {2018}, author = {He, K and Chen, X and Chen, P and He, SW and Cheng, F and Jiang, XL and Campbell, K}, title = {A new genus of Asiatic short-tailed shrew (Soricidae, Eulipotyphla) based on molecular and morphological comparisons.}, journal = {Zoological research}, volume = {39}, number = {5}, pages = {321-334}, pmid = {29976842}, issn = {2095-8137}, mesh = {Animals ; Biological Evolution ; China ; Mitochondria/genetics ; North America ; Sequence Analysis, DNA ; Shrews/*anatomy & histology/classification/genetics ; Skull/anatomy & histology ; }, abstract = {Blarinellini is a tribe of soricine shrews comprised of nine fossil genera and one extant genus. Blarinelline shrews were once widely distributed throughout Eurasia and North America, though only members of the Asiatic short-tailed shrew genus Blarinella currently persist (mostly in southwestern China and adjacent areas). Only three forms of Blarinella have been recognized as either species or subspecies. However, recent molecular studies indicated a strikingly deep divergence within the genus, implying the existence of a distinct genus-level lineage. We sequenced the complete mitochondrial genomes and one nuclear gene of three Asiatic short-tailed and two North American shrews and analyzed them morphometrically and morphologically. Our molecular analyses revealed that specimens ascribed to B. griselda formed two deeply diverged lineages, one a close relative to B. quadraticauda, whereas the other - comprised of topotype specimens from southern Gansu - diverged from other Blarinella in the middle Miocene (ca. 18.2 million years ago (Ma), 95% confidence interval=13.4-23.6 Ma). Although the skulls were similarly shaped in both lineages, we observed several diagnostic characteristics, including the shape of the upper P[4]. In consideration of the molecular and morphological evidence, we recognize B. griselda as the sole species of a new genus, namely, Pantherina gen. nov. Interestingly, some characteristics of Pantherina griselda are more similar to fossil genera, suggesting it represents an evolutionarily more primitive form than Blarinella. Recognition of this new genus sheds light on the systematics and evolutionary history of the tribe Blarinellini throughout Eurasia and North America.}, } @article {pmid29984192, year = {2018}, author = {MacDonald, JA and Fowle, WH and Shin, E and Woods, DC}, title = {A method for freeze-fracture and scanning electron microscopy of isolated mitochondria.}, journal = {MethodsX}, volume = {5}, number = {}, pages = {593-598}, pmid = {29984192}, issn = {2215-0161}, abstract = {Electron microscopy as a methodology for the study of mitochondria based on morphological features is a standard technique that has experienced little evolution over the course of several decades. This technology has identified heterogeneity of mitochondria populations across both whole tissues, as well between individual cells, using primarily ultrathin sections for transmission electron microscopy (TEM). However, this technique constrains the evaluation of a sample to a single two-dimensional plane. To overcome this limitation, scanning electron microscopy (SEM) has been successfully utilized to observe three-dimensional mitochondria structures within the complex microenvironment containing total cellular components. In response to these dual technical caveats of existing electron microscopy protocols, we developed a methodology to evaluate the three-dimensional ultrastructure of isolated mitochondria, utilizing a freeze-fracture step and rigorous preservation of sample morphology. This protocol allows for a more high-throughput analysis of mitochondria populations from a specimen of interest, as the sample has been previously purified, as well as a finer resolution of complex intra-mitochondrial structures, using the depth of field created by SEM. •Protocol designed for SEM of isolated mitochondria samples.•SEM visualizes mitochondria ultrastructure in 3-D.•Freeze-fracture creates cross-sectional plane for view of interior organelle structures.}, } @article {pmid29986214, year = {2018}, author = {Angers, B and Chapdelaine, V and Deremiens, L and Vergilino, R and Leung, C and Doucet, SL and Glémet, H and Angers, A}, title = {Gene flow prevents mitonuclear co-adaptation: A comparative portrait of sympatric wild types and cybrids in the fish Chrosomus eos.}, journal = {Comparative biochemistry and physiology. Part D, Genomics & proteomics}, volume = {27}, number = {}, pages = {77-84}, doi = {10.1016/j.cbd.2018.06.007}, pmid = {29986214}, issn = {1878-0407}, mesh = {Animals ; Cell Nucleus/genetics ; Cyprinidae/*genetics ; DNA, Mitochondrial/*genetics ; Epigenesis, Genetic ; Female ; *Gene Flow ; Genetic Speciation ; Male ; Mitochondria/genetics ; Sympatry ; }, abstract = {Allospecific mtDNA can occasionally be beneficial for the fitness of populations. It is, however, difficult to assess the effect of mtDNA in natural conditions due to genetic and/or environmental interactions. In the fish Chrosomus eos, the transfer of C. neogaeus mitochondria occurs in a single generation and results in natural cybrids. For a few lakes in Quebec, C. eos can harbor either a C. eos mtDNA (wild types) or a C. neogaeus mtDNA (cybrids). Moreover, mtDNA of cybrids originated either from Mississippian or Atlantic glacial refuges. Such diversity provides a useful system for in situ assessment of allospecific mtDNA effects. We determined genetic, epigenetic and transcriptomic variation as well as mitochondrial enzymatic activity (complex IV) changes among wild types and cybrids either in sympatry or allopatry. Wild types and cybrids did not segregate spatially within a lake. Moreover, no significant genetic differentiation was detected among wild types and cybrids indicating sustained gene flow. Mitochondrial complex IV activity was higher for cybrids in both sympatry and allopatry while no difference was detected among cybrid haplotypes. Epigenetic and transcriptomic analyses revealed only subtle differences between sympatric wild types and cybrids compared to differences between sites. Altogether, these results indicate a limited influence of allospecific mtDNA in nuclear gene expression when controlling for genetic and environmental effects. The absence of a reproductive barrier between wild types and cybrids results in random association of either C. eos or C. neogaeus mtDNA with C. eos nDNA at each generation, and prevents mitonuclear co-adaptation in sympatry.}, } @article {pmid29986779, year = {2019}, author = {Wang, HB and Zhang, HJ and Song, LL and Zhu, L and Chen, M and Ren, GJ and Liu, GH and Zhao, GH}, title = {Morphological and molecular confirmation of the validity of Trichuris rhinopiptheroxella in the endangered golden snub-nosed monkey (Rhinopithecus roxellana).}, journal = {Journal of helminthology}, volume = {93}, number = {5}, pages = {601-607}, doi = {10.1017/S0022149X18000500}, pmid = {29986779}, issn = {1475-2697}, mesh = {Animals ; Base Sequence ; China/epidemiology ; Colobinae/*parasitology ; DNA, Mitochondrial/genetics ; Endangered Species ; Female ; Genome, Mitochondrial ; Male ; Mitochondria/genetics ; Phylogeny ; Trichuriasis/epidemiology/*veterinary ; Trichuris/*anatomy & histology/*classification ; }, abstract = {The golden snub-nosed monkey (Rhinopithecus roxellana) is an endangered species endemic to China. Relatively little is known about the taxonomic status of soil-transmitted helminths (STH) in these monkeys. Trichuris spp. (syn. Trichocephalus) are among the most important STHs, causing significant socio-economic losses and public health concerns. To date, five Trichuris species have been reported in golden monkeys, including a novel species, T. rhinopiptheroxella, based on morphology. In the present study, molecular and morphological analysis was conducted on adult Trichuris worms obtained from a dead golden snub-nosed monkey, to better understand their taxonomic status. Morphology indicated that the adult Trichuris worms were similar to T. rhinopiptheroxella. To further ascertain their phylogenetic position, the complete mitochondrial (mt) genome of these worms was sequenced and characterized. The mt genome of T. rhinopiptheroxella is 14,186 bp, encoding 37 genes. Phylogenetic analysis based on the concatenated amino acids of 12 protein-coding genes (with the exception of atp8) indicated that T. rhinopiptheroxella was genetically distinct and exhibited 27.5-27.8% genetic distance between T. rhinopiptheroxella and other Trichuris spp. Our results support T. rhinopiptheroxella as a valid Trichuris species and suggest that mt DNA could serve as a marker for future studies on the classification, evolution and molecular epidemiology of Trichuris spp. from golden snub-nosed monkeys.}, } @article {pmid29987711, year = {2018}, author = {Maréchal, E}, title = {Primary Endosymbiosis: Emergence of the Primary Chloroplast and the Chromatophore, Two Independent Events.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1829}, number = {}, pages = {3-16}, doi = {10.1007/978-1-4939-8654-5_1}, pmid = {29987711}, issn = {1940-6029}, mesh = {Alphaproteobacteria/genetics ; Cell Membrane/metabolism ; Chlamydia/genetics/metabolism ; Chloroplasts/*pathology ; Chromatophores/*physiology ; Cyanobacteria/metabolism ; Eukaryota/physiology ; Gene Transfer, Horizontal ; Genes, Bacterial ; Glaucophyta/genetics/metabolism ; Inheritance Patterns ; Mitochondria/genetics/metabolism ; Rhizaria ; *Symbiosis ; }, abstract = {The emergence of semiautonomous organelles, such as the mitochondrion, the chloroplast, and more recently, the chromatophore, are critical steps in the evolution of eukaryotes. They resulted from primary endosymbiotic events that seem to share general features, i.e., an acquisition of a bacterium/cyanobacteria likely via a phagocytic membrane, a genome reduction coinciding with an escape of genes from the organelle to the nucleus, and finally the appearance of an active system translocating nuclear-encoded proteins back to the organelles. An intense mobilization of foreign genes of bacterial origin, via horizontal gene transfers, plays a critical role. Some third partners, like Chlamydia, might have facilitated the transition from cyanobacteria to the early chloroplast. This chapter describes our current understanding of primary endosymbiosis, with a specific focus on primary chloroplasts considered to have emerged more than one billion years ago, and on the chromatophore, having emerged about one hundred million years ago.}, } @article {pmid29987715, year = {2018}, author = {Rolland, N and Bouchnak, I and Moyet, L and Salvi, D and Kuntz, M}, title = {The Main Functions of Plastids.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1829}, number = {}, pages = {73-85}, doi = {10.1007/978-1-4939-8654-5_5}, pmid = {29987715}, issn = {1940-6029}, mesh = {Biological Evolution ; Energy Metabolism ; Plastids/*physiology/ultrastructure ; }, abstract = {Plastids are semiautonomous organelles like mitochondria, and derive from a cyanobacterial ancestor that was engulfed by a host cell. During evolution, they have recruited proteins originating from the nuclear genome, and only parts of their ancestral metabolic properties were conserved and optimized to limit functional redundancy with other cell compartments. Furthermore, large disparities in metabolic functions exist among various types of plastids, and the characterization of their various metabolic properties is far from being accomplished. In this review, we provide an overview of the main functions, known to be achieved by plastids or shared by plastids and other compartments of the cell. In short, plastids appear at the heart of all main plant functions.}, } @article {pmid29989670, year = {2018}, author = {Iha, C and Grassa, CJ and Lyra, GM and Davis, CC and Verbruggen, H and Oliveira, MC}, title = {Organellar genomics: a useful tool to study evolutionary relationships and molecular evolution in Gracilariaceae (Rhodophyta).}, journal = {Journal of phycology}, volume = {54}, number = {6}, pages = {775-787}, doi = {10.1111/jpy.12765}, pmid = {29989670}, issn = {1529-8817}, support = {152939/2014-8//CNPq/International ; 301491/2013-5//CNPq/International ; 406351/2016-3//CNPq/International ; 88881.134422/2016-01//CAPES/International ; TO INT0001/2016//FAPESB/International ; 2013/11833-3//Biota-FAPESP/International ; 2015/50078-1//FAPESP/International ; }, mesh = {*Evolution, Molecular ; Genome, Chloroplast/*genetics ; Genome, Mitochondrial/*genetics ; Phylogeny ; Rhodophyta/*genetics ; Sequence Analysis, DNA ; }, abstract = {Gracilariaceae has a worldwide distribution including numerous economically important species. We applied high-throughput sequencing to obtain organellar genomes (mitochondria and chloroplast) from 10 species of Gracilariaceae and, combined with published genomes, to infer phylogenies and compare genome architecture among species representing main lineages. We obtained similar topologies between chloroplast and mitochondrial genomes phylogenies. However, the chloroplast phylogeny was better resolved with full support. In this phylogeny, Melanthalia intermedia is sister to a monophyletic clade including Gracilaria and Gracilariopsis, which were both resolved as monophyletic genera. Mitochondrial and chloroplast genomes were highly conserved in gene synteny, and variation mainly occurred in regions where insertions of plasmid-derived sequences (PDS) were found. In mitochondrial genomes, PDS insertions were observed in two regions where the transcription direction changes: between the genes cob and trnL, and trnA and trnN. In chloroplast genomes, PDS insertions were in different positions, but generally found between psdD and rrs genes. Gracilariaceae is a good model system to study the impact of PDS in genome evolution due to the frequent presence of these insertions in organellar genomes. Furthermore, the bacterial leuC/leuD operon was found in chloroplast genomes of Gracilaria tenuistipitata, G. chilensis, and M. intermedia, and in extrachromosomal plasmid of G. vermiculophylla. Phylogenetic trees show two different origins of leuC/leuD: genes found in chloroplast and plasmid were placed with proteobacteria, and genes encoded in the nucleus were close to Viridiplantae and cyanobacteria.}, } @article {pmid29991771, year = {2018}, author = {Okatsu, K and Sato, Y and Yamano, K and Matsuda, N and Negishi, L and Takahashi, A and Yamagata, A and Goto-Ito, S and Mishima, M and Ito, Y and Oka, T and Tanaka, K and Fukai, S}, title = {Structural insights into ubiquitin phosphorylation by PINK1.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {10382}, pmid = {29991771}, issn = {2045-2322}, support = {JP15J10559//Japan Society for the Promotion of Science (JSPS)/International ; JP24687012//Japan Society for the Promotion of Science (JSPS)/International ; JP15H01175//Japan Society for the Promotion of Science (JSPS)/International ; JP16K18545//Japan Society for the Promotion of Science (JSPS)/International ; 17H05888//Japan Society for the Promotion of Science (JSPS)/International ; JP26000014//Japan Society for the Promotion of Science (JSPS)/International ; JP24247014//Japan Society for the Promotion of Science (JSPS)/International ; PRESTO//Japan Science and Technology Agency (JST)/International ; JPMJCR13M3//JST | Core Research for Evolutional Science and Technology (CREST)/International ; JPMJCR12M5//JST | Core Research for Evolutional Science and Technology (CREST)/International ; }, mesh = {Adenosine Triphosphate/metabolism ; Crystallography, X-Ray ; Humans ; Mutation ; Parkinsonian Disorders/etiology ; Phosphorylation ; Protein Binding ; Protein Conformation ; Protein Domains ; Protein Kinases/chemistry/*metabolism ; Ubiquitin/*metabolism ; Ubiquitin-Protein Ligases/metabolism ; PTEN-Induced Putative Kinase ; }, abstract = {Mutations of PTEN-induced putative kinase 1 (PINK1) and the E3 ubiquitin (Ub) ligase parkin can cause familial parkinsonism. These two proteins are essential for ubiquitylation of damaged mitochondria and subsequent degradation. PINK1 phosphorylates Ser65 of Ub and the Ub-like (UBL) domain of parkin to allosterically relieve the autoinhibition of parkin. To understand the structural mechanism of the Ub/UBL-specific phosphorylation by PINK1, we determined the crystal structure of Tribolium castaneum PINK1 kinase domain (TcPINK1) in complex with a nonhydrolyzable ATP analogue at 2.5 Å resolution. TcPINK1 consists of the N- and C-terminal lobes with the PINK1-specific extension. The ATP analogue is bound in the cleft between the N- and C-terminal lobes. The adenine ring of the ATP analogue is bound to a hydrophobic pocket, whereas the triphosphate group of the ATP analogue and two coordinated Mg ions interact with the catalytic hydrophilic residues. Comparison with protein kinases A and C (PKA and PKC, respectively) unveils a putative Ub/UBL-binding groove, which is wider than the peptide-binding groove of PKA or PKC to accommodate the globular head of Ub or UBL. Further crosslinking analyses suggested a PINK1-interacting surface of Ub. Structure-guided mutational analyses support the findings from the present structural analysis of PINK1.}, } @article {pmid29992378, year = {2018}, author = {Kasperski, A and Kasperska, R}, title = {Bioenergetics of life, disease and death phenomena.}, journal = {Theory in biosciences = Theorie in den Biowissenschaften}, volume = {137}, number = {2}, pages = {155-168}, pmid = {29992378}, issn = {1611-7530}, mesh = {Adenosine Triphosphate/chemistry ; Animals ; *Cell Biology ; DNA/analysis ; *Energy Metabolism ; Genome, Human ; Glucose/chemistry ; Humans ; Mitochondria/metabolism ; Models, Biological ; Mutation ; Neoplasms/*genetics/*pathology ; Oxygen/chemistry ; Reactive Oxygen Species/chemistry ; }, abstract = {In this article, some new aspects of unified cell bioenergetics are presented. From the perspective of unified cell bioenergetics certain subsequent stages of cancer development, from initiation stage, through transformation to metastasis, are analyzed. Here we show that after transformation, cancer cells are permanently exposed to reactive oxygen species, that causes continual random DNA mutations and as a result genome and chromosomal destabilizations. The modern cancer attractor hypothesis has been extended in explaining cancer development. Discussion is conducted in light of current cancerogenesis research, including bioenergetic cancer initiation, the somatic mutation theory and the tissue organization field theory. In the article reasons complicating the discovery of patterns of cancer genome changes and cancer evolution are presented. In addition certain cancer therapeutic aspects are given attention to.}, } @article {pmid30003876, year = {2018}, author = {Katane, M and Ariyoshi, M and Tateishi, S and Koiwai, S and Takaku, K and Nagai, K and Nakayama, K and Saitoh, Y and Miyamoto, T and Sekine, M and Mita, M and Hamase, K and Matoba, S and Homma, H}, title = {Structural and enzymatic properties of mammalian d-glutamate cyclase.}, journal = {Archives of biochemistry and biophysics}, volume = {654}, number = {}, pages = {10-18}, doi = {10.1016/j.abb.2018.07.005}, pmid = {30003876}, issn = {1096-0384}, mesh = {Animals ; Catalysis ; Dimerization ; Electrophoresis, Polyacrylamide Gel ; Glutamic Acid/metabolism ; Hydro-Lyases/*chemistry/isolation & purification/*metabolism ; Hydrogen-Ion Concentration ; Kinetics ; Manganese/metabolism ; Mice ; Mitochondria/metabolism ; Proline/metabolism ; Protein Conformation ; Recombinant Proteins/chemistry/isolation & purification/metabolism ; Substrate Specificity ; }, abstract = {d-Glutamate cyclase (DGLUCY) is a unique enzyme that reversibly converts free d-glutamate to 5-oxo-d-proline and H2O. Mammalian DGLUCY is highly expressed in the mitochondrial matrix in the heart, and its downregulation disrupts d-glutamate and/or 5-oxo-d-proline levels, contributing to the onset and/or exacerbation of heart failure. However, detailed characterisation of DGLUCY has not yet been performed. Herein, the structural and enzymatic properties of purified recombinant mouse DGLUCY were examined. The results revealed a dimeric oligomerisation state, and both d-glutamate-to-5-oxo-d-proline and 5-oxo-d-proline-to-d-glutamate reactions were catalysed in a stereospecific manner. Catalytic activity is modulated by divalent cations and nucleotides including ATP and ADP. Interestingly, the presence of Mn[2+] completely abolished the 5-oxo-d-proline-to-d-glutamate reaction but stimulated the d-glutamate-to-5-oxo-d-proline reaction. The optimum pH is ∼8.0, similar to that in the mitochondrial matrix, and the catalytic efficiency for d-glutamate is markedly higher than that for 5-oxo-d-proline. These findings suggest that DGLUCY functions as a metalloenzyme that degrades d-glutamate in the mitochondrial matrix in mammalian cells. The results also provide insight into the correlation between DGLUCY enzyme activity and the physiological and pathological roles of d-glutamate and 5-oxo-d-proline in cardiac function, which is of relevance to the risk of onset of heart failure.}, } @article {pmid30005062, year = {2018}, author = {Salunke, R and Mourier, T and Banerjee, M and Pain, A and Shanmugam, D}, title = {Highly diverged novel subunit composition of apicomplexan F-type ATP synthase identified from Toxoplasma gondii.}, journal = {PLoS biology}, volume = {16}, number = {7}, pages = {e2006128}, pmid = {30005062}, issn = {1545-7885}, mesh = {Amino Acid Sequence ; Animals ; Conserved Sequence ; Gene Expression Regulation ; Genetic Variation ; Hemagglutinins/metabolism ; Mitochondria/metabolism ; Mitochondrial Proton-Translocating ATPases/*metabolism ; Parasites/metabolism ; Phylogeny ; Plasmodium falciparum/metabolism ; Protein Multimerization ; Protein Subunits/*metabolism ; Proteome/metabolism ; Proteomics ; Protozoan Proteins/chemistry/isolation & purification/metabolism ; Recombinant Fusion Proteins/metabolism ; Toxoplasma/*enzymology ; }, abstract = {The mitochondrial F-type ATP synthase, a multisubunit nanomotor, is critical for maintaining cellular ATP levels. In T. gondii and other apicomplexan parasites, many subunit components necessary for proper assembly and functioning of this enzyme appear to be missing. Here, we report the identification of 20 novel subunits of T. gondii F-type ATP synthase from mass spectrometry analysis of partially purified monomeric (approximately 600 kDa) and dimeric (>1 MDa) forms of the enzyme. Despite extreme sequence diversification, key FO subunits a, b, and d can be identified from conserved structural features. Orthologs for these proteins are restricted to apicomplexan, chromerid, and dinoflagellate species. Interestingly, their absence in ciliates indicates a major diversion, with respect to subunit composition of this enzyme, within the alveolate clade. Discovery of these highly diversified novel components of the apicomplexan F-type ATP synthase complex could facilitate the development of novel antiparasitic agents. Structural and functional characterization of this unusual enzyme complex will advance our fundamental understanding of energy metabolism in apicomplexan species.}, } @article {pmid30011013, year = {2018}, author = {Hood, WR and Zhang, Y and Mowry, AV and Hyatt, HW and Kavazis, AN}, title = {Life History Trade-offs within the Context of Mitochondrial Hormesis.}, journal = {Integrative and comparative biology}, volume = {58}, number = {3}, pages = {567-577}, pmid = {30011013}, issn = {1557-7023}, support = {R03 HD083654/HD/NICHD NIH HHS/United States ; }, mesh = {Biological Evolution ; Hormesis/*physiology ; *Life History Traits ; Longevity/*physiology ; Mitochondria/*physiology ; Oxidative Stress/physiology ; Reactive Oxygen Species/metabolism ; Reproduction/*physiology ; }, abstract = {Evolutionary biologists have been interested in the negative interactions among life history traits for nearly a century, but the mechanisms that would create this negative interaction remain poorly understood. One variable that has emerged as a likely link between reproductive effort and longevity is oxidative stress. Specifically, it has been proposed that reproduction generates free radicals that cause oxidative stress and, in turn, oxidative stress damages cellular components and accelerates senescence. We propose that there is limited support for the hypothesis because reactive oxygen species (ROS), the free radicals implicated in oxidative damage, are not consistently harmful. With this review, we define the hormetic response of mitochondria to ROS, termed mitochondrial hormesis, and describe how to test for a mitohormetic response. We interpret existing data using our model and propose that experimental manipulations will further improve our knowledge of this response. Finally, we postulate how the mitohormetic response curve applies to variation in animal performance and longevity.}, } @article {pmid30016998, year = {2018}, author = {Marais, GAB and Gaillard, JM and Vieira, C and Plotton, I and Sanlaville, D and Gueyffier, F and Lemaitre, JF}, title = {Sex gap in aging and longevity: can sex chromosomes play a role?.}, journal = {Biology of sex differences}, volume = {9}, number = {1}, pages = {33}, pmid = {30016998}, issn = {2042-6410}, mesh = {*Aging ; Animals ; Humans ; *Sex Characteristics ; *Sex Chromosomes ; }, abstract = {It is well known that women live longer than men. This gap is observed in most human populations and can even reach 10-15 years. In addition, most of the known super centenarians (i.e., humans who lived for > 110 years) are women. The differences in life expectancy between men and women are often attributed to cultural differences in common thinking. However, sex hormones seem to influence differences in the prevalence of diseases, in the magnitude of aging, and in the longevity between men and women. Moreover, far from being human specific, the sex gap in longevity is extremely common in non-human animals, especially in mammals. Biological factors clearly contribute to such a sex gap in aging and longevity. Different hypotheses have been proposed to explain why males and females age and die differently. The cost of sexual selection and sexual dimorphism has long been considered the best explanation for the observed sex gap in aging/longevity. However, the way mitochondria are transmitted (i.e., through females in most species) could have an effect, called the mother's curse. Recent data suggest that sex chromosomes may also contribute to the sex gap in aging/longevity through several potential mechanisms, including the unguarded X/Z, the toxic Y/W and the loss of Y/W. We discuss future research directions to test these ideas.}, } @article {pmid30017823, year = {2018}, author = {Chesser, RT and Vaseghi, H and Hosner, PA and Bergner, LM and Cortes-Rodriguez, MN and Welch, AJ and Collins, CT}, title = {Molecular systematics of swifts of the genus Chaetura (Aves: Apodiformes: Apodidae).}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {162-171}, doi = {10.1016/j.ympev.2018.07.006}, pmid = {30017823}, issn = {1095-9513}, mesh = {Animals ; Birds/*classification ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; North America ; Panama ; Phylogeny ; Seasons ; South America ; Species Specificity ; }, abstract = {Phylogenetic relationships among swifts of the morphologically conservative genus Chaetura were studied using mitochondrial and nuclear DNA sequences. Taxon sampling included all species and 21 of 30 taxa (species and subspecies) within Chaetura. Our results indicate that Chaetura is monophyletic and support the division of the genus into the two subgenera previously identified using plumage characters. However, our genetic data, when considered in combination with phenotypic data, appear to be at odds with the current classification of some species of Chaetura. We recommend that C. viridipennis, currently generally treated as specifically distinct from C. chapmani, be returned to its former status as C. chapmani viridipennis, and that C. andrei, now generally regarded as synonymous with C. vauxi aphanes, again be recognized as a valid species. Widespread Neotropical species C. spinicaudus is paraphyletic with respect to more range-restricted species C. fumosa, C. egregia, and C. martinica. Geographically structured genetic variation within some other species of Chaetura, especially notable in C. cinereiventris, suggests that future study may lead to recognition of additional species in this genus. Biogeographic analysis indicated that Chaetura originated in South America and identified several dispersal events to Middle and North America following the formation of the Isthmus of Panama.}, } @article {pmid30019754, year = {2018}, author = {Xiao, H and Zhang, Q and Qin, X and Xu, Y and Ni, C and Huang, J and Zhu, L and Zhong, F and Liu, W and Yao, G and Zhu, Y and Hu, J}, title = {Rice PPS1 encodes a DYW motif-containing pentatricopeptide repeat protein required for five consecutive RNA-editing sites of nad3 in mitochondria.}, journal = {The New phytologist}, volume = {220}, number = {3}, pages = {878-892}, doi = {10.1111/nph.15347}, pmid = {30019754}, issn = {1469-8137}, support = {2016YFD0100804//National Key Research and Development Program of China/International ; 31371698//National Natural Science Foundation of China/International ; 31670310//National Natural Science Foundation of China/International ; SNG2017061//Suzhou science and technology project/International ; }, mesh = {Amino Acid Motifs ; Base Sequence ; Cell Nucleus/metabolism ; Conserved Sequence ; Electron Transport ; Evolution, Molecular ; Gene Expression Regulation, Plant ; Mitochondria/*metabolism/ultrastructure ; Mitochondrial Proteins/chemistry/metabolism ; Oryza/*genetics/ultrastructure ; Phenotype ; Plant Proteins/*chemistry/*metabolism ; Pollen/metabolism/ultrastructure ; Protein Binding ; RNA Editing/*genetics ; RNA Interference ; RNA, Messenger/genetics/metabolism ; Time Factors ; }, abstract = {The pentatricopeptide repeat (PPR) protein family is a large family characterized by tandem arrays of a degenerate 35-amino-acid motif whose members function as important regulators of organelle gene expression at the post-transcriptional level. Despite the roles of PPRs in RNA editing in organelles, their editing activities and the underlying mechanism remain obscure. Here, we show that a novel DYW motif-containing PPR protein, PPS1, is associated with five conserved RNA-editing sites of nad3 located in close proximity to each other in mitochondria, all of which involve conversion from proline to leucine in rice. Both pps1 RNAi and heterozygous plants are characterized by delayed development and partial pollen sterility at vegetative stages and reproductive stage. RNA electrophoresis mobility shift assays (REMSAs) and reciprocal competition assays using different versions of nad3 probes confirm that PPS1 can bind to cis-elements near the five affected sites, which is distinct from the existing mode of PPR-RNA binding because of the continuity of the editing sites. Loss of editing at nad3 in pps1 reduces the activity of several complexes in the mitochondrial electron transport chain and affects mitochondrial morphology. Taken together, our results indicate that PPS1 is required for specific editing sites in nad3 in rice.}, } @article {pmid30021129, year = {2018}, author = {Sun, S and Sha, Z and Wang, Y}, title = {Complete mitochondrial genome of the first deep-sea spongicolid shrimp Spongiocaris panglao (Decapoda: Stenopodidea): Novel gene arrangement and the phylogenetic position and origin of Stenopodidea.}, journal = {Gene}, volume = {676}, number = {}, pages = {123-138}, doi = {10.1016/j.gene.2018.07.026}, pmid = {30021129}, issn = {1879-0038}, mesh = {Animals ; Base Composition ; Decapoda/*genetics ; Gene Order ; Genome Size ; Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing/*methods ; Mitochondria/*genetics ; Nucleic Acid Conformation ; Phylogeny ; RNA/chemistry ; RNA, Mitochondrial ; Sequence Analysis, DNA/*methods ; }, abstract = {Stenopodidea Claus, 1872 (Crustacea: Decapoda) is one of the major groups of decapods crustaceans. Hitherto, only one complete mitochondrial genome (mitogenome) from the family Stenopodidae is available for the infraorder Stenopodidea. Here, we determined the complete mitogenome of Spongiocaris panglao de Grave and Saito, 2016 using Illumina sequencing, representing the first species from the family Spongicolidae. The 15,909 bp genome is a circular molecule and consists of 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes and one control region. Although the overall genome organization is typical for metazoans, the mitogenome of S. panglao shows some derived characters. A + T content of 77.42% in S. pamglao mitogenome is second-highest among the dacapods described to date. The trnR gene exhibit modified secondary structure with the TψC loop completely missing, which might be a putative autapomorphy of S. pamglao mitogenome. Compared with the shallow-water stenopodidean species S. hispidus, the control region of S. pamglao exhibits three characteristics: larger size, higher A + T content, and more tandem repeat sequences. The gene order exhibited difference from the ancestral mitogenome pattern of the Pancrustacea, with 5 tRNA genes rearrangement. The result from BI was agreed with most morphological characters and molecular evidences, revealing that Stenopodidea and Reptantia had the closest relationship, as the sister group of Caridea. Still, the alternative hypothesis supported from ML topology cannot be completely rejected based on the current data. Estimated times revealed that the two stenopodideans families Stenopodidae and Spongicolidae diverged from each other around 122 Mya. The divergence time of spongicolid shrimp is in good agreement with the origin of their hexactinellid hosts (78-144 Mya).}, } @article {pmid30022808, year = {2018}, author = {Lang, SA and Shain, DH}, title = {Atypical Evolution of the F1Fo Adenosine Triphosphate Synthase Regulatory ATP6 subunit in Glacier Ice Worms (Annelida: Clitellata: Mesenchytraeus).}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318788076}, pmid = {30022808}, issn = {1176-9343}, support = {R15 GM093685/GM/NIGMS NIH HHS/United States ; }, abstract = {The glacier ice worm, Mesenchytraeus solifugus, is among a few animals that reside permanently in glacier ice. Their adaptation to cold temperature has been linked to relatively high intracellular adenosine triphosphate (ATP) levels, which compensate for reductions in molecular motion at low physiological temperatures. Here, we show that ATP6-the critical regulatory subunit of the F1Fo-ATP synthase and primary target of mitochondrial disease-acquired an unprecedented histidine-rich, 18-amino acid carboxy-terminal extension, which counters the strong evolutionary trend of mitochondrial genome compaction. Furthermore, sequence analysis suggests that this insertion is not of metazoan origin, but rather is a product of horizontal gene transfer from a microbial dietary source, and may act as a proton shuttle to accelerate the rate of ATP synthesis.}, } @article {pmid30026124, year = {2018}, author = {Ferreira, M and Fernandes, AM and Aleixo, A and Antonelli, A and Olsson, U and Bates, JM and Cracraft, J and Ribas, CC}, title = {Evidence for mtDNA capture in the jacamar Galbula leucogastra/chalcothorax species-complex and insights on the evolution of white-sand ecosystems in the Amazon basin.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {149-157}, doi = {10.1016/j.ympev.2018.07.007}, pmid = {30026124}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; *Biological Evolution ; Birds/*genetics ; Brazil ; Cell Nucleus/genetics ; DNA, Mitochondrial/*genetics ; *Ecosystem ; Gene Flow ; Genetic Loci ; Genome, Mitochondrial ; Haplotypes/genetics ; Mitochondria/genetics ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Jacamar species occur throughout Amazonia, with most species occupying forested habitats. One species-complex, Galbula leucogastra/chalcothorax, is associated to white sand ecosystems (WSE). Previous studies of WSE bird species recovered shallow genetic structure in mtDNA coupled with signs of gene flow among WSE patches. Here, we characterize diversification of the G. leucogastra/chalcothorax species-complex with dense sampling across its distribution using mitochondrial and genomic (Ultraconserved Elements, UCEs) DNA sequences. We performed concatenated likelihood and Bayesian analysis, as well as a species-tree analysis using [∗]BEAST, to establish the phylogenetic relationships among populations. The mtDNA results recovered at least six geographically-structured lineages, with G. chalcothorax embedded within lineages of G. leucogastra. In contrast, both concatenated and species-tree analyses of UCE data recovered G. chalcothorax as sister to all G. leucogastra lineages. We hypothesize that the mitochondrial genome of one of the G. leucogastra lineage (Madeira) was captured into G. chalcothorax in the past. We discuss how WSE evolution and the coevolution of mtDNA and nuclear genes might have played a role in this apparently rare event.}, } @article {pmid30032461, year = {2018}, author = {Sylvester, C and Krishna, MS and Rao, JS and Chandrasekar, A}, title = {Neolithic phylogenetic continuity inferred from complete mitochondrial DNA sequences in a tribal population of Southern India.}, journal = {Genetica}, volume = {146}, number = {4-5}, pages = {383-389}, pmid = {30032461}, issn = {1573-6857}, mesh = {Asian People/genetics ; DNA, Mitochondrial/*genetics ; Ethnicity/*genetics ; Female ; Genetic Variation/genetics ; Genetics, Population/methods ; Genome, Mitochondrial/*genetics ; Haplotypes/genetics ; Humans ; India/ethnology ; Male ; Mitochondria/genetics ; Phylogeny ; Phylogeography/methods ; Sequence Analysis, DNA/methods ; }, abstract = {The subsequent human migrations that dispersed out of Africa, both prehistoric and historic and colonization of India by modern humans is unanimous, and phylogeny of major mitochondrial DNA haplogroups have played a key role in assessing the genetic origin of people of India. To address more such events, complete mitogenomes of 113 Melakudiya tribe of Southern India were sequenced and 46 individuals showed the presence of west Eurasian autochthonous haplogroups HV14 and U7. Phylogenetic analysis revealed two novel subclades HV14a1b and HV14a1b1 and sequences representing haplogroup U7 were included under previously described subclade U7a3a1a2* specific to India. Moreover, the present analysis on complete mtDNA reveals addition information of the spread and distribution of west Eurasian haplogroups in southern India, in tracing an unexplored genetic link between Melakudiya tribe with the people of Iranian Plateau, South Caucasus, and Central Asia. Coalescence ages of HV14 and U7a3a1a2* trees in the present study dates ~ 16.1 ± 4.3 and ~ 13.4 ± 5.6 kya respectively.}, } @article {pmid30040943, year = {2018}, author = {Gawryluk, RMR}, title = {Evolutionary Biology: A New Home for the Powerhouse?.}, journal = {Current biology : CB}, volume = {28}, number = {14}, pages = {R798-R800}, doi = {10.1016/j.cub.2018.05.073}, pmid = {30040943}, issn = {1879-0445}, mesh = {*Alphaproteobacteria ; Biological Evolution ; Biology ; Oceans and Seas ; Phylogeny ; }, abstract = {Metagenomic assemblies of oceanic datasets have unearthed novel and diverse alphaproteobacterial groups. Sophisticated phylogenetic analyses based on these metagenomes suggest that mitochondria do not descend from within Alphaproteobacteria, as typically thought, but from a still undiscovered sister lineage.}, } @article {pmid30041026, year = {2018}, author = {Bogarín, D and Pérez-Escobar, OA and Groenenberg, D and Holland, SD and Karremans, AP and Lemmon, EM and Lemmon, AR and Pupulin, F and Smets, E and Gravendeel, B}, title = {Anchored hybrid enrichment generated nuclear, plastid and mitochondrial markers resolve the Lepanthes horrida (Orchidaceae: Pleurothallidinae) species complex.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {27-47}, doi = {10.1016/j.ympev.2018.07.014}, pmid = {30041026}, issn = {1095-9513}, mesh = {Cell Nucleus/*genetics ; Cluster Analysis ; Databases, Genetic ; Flowers/anatomy & histology ; Genetic Loci ; Genetic Markers ; *Hybridization, Genetic ; Likelihood Functions ; Mitochondria/*genetics ; Orchidaceae/*genetics ; Phylogeny ; Plastids/*genetics ; Species Specificity ; }, abstract = {Phylogenetic relationships in species complexes and lineages derived from rapid diversifications are often challenging to resolve using morphology or standard DNA barcoding markers. The hyper-diverse genus Lepanthes from Neotropical cloud forest includes over 1200 species and many recent, explosive diversifications that have resulted in poorly supported nodes and morphological convergence across clades. Here, we assess the performance of 446 nuclear-plastid-mitochondrial markers derived from an anchored hybrid enrichment approach (AHE) coupled with coalescence- and species network-based inferences to resolve phylogenetic relationships and improve species recognition in the Lepanthes horrida species group. In addition to using orchid-specific probes to increase enrichment efficiency, we improved gene tree resolution by extending standard angiosperm targets into adjacent exons. We found high topological discordance among individual gene trees, suggesting that hybridization/polyploidy may have promoted speciation in the lineage via formation of new hybrid taxa. In addition, we identified ten loci with the highest phylogenetic informativeness values from these genomes. Most previous phylogenetic sampling in the Pleurothallidinae relies on two regions (ITS and matK), therefore, the evaluation of other markers such as those shown here may be useful in future phylogenetic studies in the orchid family. Coalescent-based species tree estimation methods resolved the phylogenetic relationships of the L. horrida species group. The resolution of the phylogenetic estimations was improved with the inclusion of extended anchor targets. This approach produced longer loci with higher discriminative power. These analyses also disclosed two undescribed species, L. amicitiae and L. genetoapophantica, formally described here, which are also supported by morphology. Our study demonstrates the utility of combined genomic evidence to disentangle phylogenetic relationships at very shallow levels of the tree of life, and in clades showing convergent trait evolution. With a fully resolved phylogeny, is it possible to disentangle traits evolving in parallel or convergently across these orchid lineages such as flower color and size from diagnostic traits such as the shape and orientation of the lobes of the petals and lip.}, } @article {pmid30042493, year = {2019}, author = {Lionnard, L and Duc, P and Brennan, MS and Kueh, AJ and Pal, M and Guardia, F and Mojsa, B and Damiano, MA and Mora, S and Lassot, I and Ravichandran, R and Cochet, C and Aouacheria, A and Potts, PR and Herold, MJ and Desagher, S and Kucharczak, J}, title = {TRIM17 and TRIM28 antagonistically regulate the ubiquitination and anti-apoptotic activity of BCL2A1.}, journal = {Cell death and differentiation}, volume = {26}, number = {5}, pages = {902-917}, pmid = {30042493}, issn = {1476-5403}, mesh = {Apoptosis/*genetics ; Cell Death/genetics ; Cell Line, Tumor ; Doxycycline/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects ; Glycogen Synthase Kinase 3/genetics ; Humans ; Minor Histocompatibility Antigens/*genetics ; Neoplasms/drug therapy/*genetics/pathology ; Phosphorylation/genetics ; Proteasome Endopeptidase Complex/genetics ; Protein Binding/genetics ; Protein Stability ; Proteolysis/drug effects ; Proto-Oncogene Proteins c-bcl-2/*genetics ; Tripartite Motif Proteins/*genetics ; Tripartite Motif-Containing Protein 28/*genetics ; Ubiquitin-Protein Ligases/*genetics ; Ubiquitination/genetics ; }, abstract = {BCL2A1 is an anti-apoptotic member of the BCL-2 family that contributes to chemoresistance in a subset of tumors. BCL2A1 has a short half-life due to its constitutive processing by the ubiquitin-proteasome system. This constitutes a major tumor-suppressor mechanism regulating BCL2A1 function. However, the enzymes involved in the regulation of BCL2A1 protein stability are currently unknown. Here, we provide the first insight into the regulation of BCL2A1 ubiquitination. We present evidence that TRIM28 is an E3 ubiquitin-ligase for BCL2A1. Indeed, endogenous TRIM28 and BCL2A1 bind to each other at the mitochondria and TRIM28 knock-down decreases BCL2A1 ubiquitination. We also show that TRIM17 stabilizes BCL2A1 by blocking TRIM28 from binding and ubiquitinating BCL2A1, and that GSK3 is involved in the phosphorylation-mediated inhibition of BCL2A1 degradation. BCL2A1 and its close relative MCL1 are thus regulated by common factors but with opposite outcome. Finally, overexpression of TRIM28 or knock-out of TRIM17 reduced BCLA1 protein levels and restored sensitivity of melanoma cells to BRAF-targeted therapy. Therefore, our data describe a molecular rheostat in which two proteins of the TRIM family antagonistically regulate BCL2A1 stability and modulate cell death.}, } @article {pmid30042786, year = {2018}, author = {Riggs, CL and Summers, A and Warren, DE and Nilsson, GE and Lefevre, S and Dowd, WW and Milton, S and Podrabsky, JE}, title = {Small Non-coding RNA Expression and Vertebrate Anoxia Tolerance.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {230}, pmid = {30042786}, issn = {1664-8021}, abstract = {Background: Extreme anoxia tolerance requires a metabolic depression whose modulation could involve small non-coding RNAs (small ncRNAs), which are specific, rapid, and reversible regulators of gene expression. A previous study of small ncRNA expression in embryos of the annual killifish Austrofundulus limnaeus, the most anoxia-tolerant vertebrate known, revealed a specific expression pattern of small ncRNAs that could play important roles in anoxia tolerance. Here, we conduct a comparative study on the presence and expression of small ncRNAs in the most anoxia-tolerant representatives of several major vertebrate lineages, to investigate the evolution of and mechanisms supporting extreme anoxia tolerance. The epaulette shark (Hemiscyllium ocellatum), crucian carp (Carassius carassius), western painted turtle (Chrysemys picta bellii), and leopard frog (Rana pipiens) were exposed to anoxia and recovery, and small ncRNAs were sequenced from the brain (one of the most anoxia-sensitive tissues) prior to, during, and following exposure to anoxia. Results: Small ncRNA profiles were broadly conserved among species under normoxic conditions, and these expression patterns were largely conserved during exposure to anoxia. In contrast, differentially expressed genes are mostly unique to each species, suggesting that each species may have evolved distinct small ncRNA expression patterns in response to anoxia. Mitochondria-derived small ncRNAs (mitosRNAs) which have a robust response to anoxia in A. limnaeus embryos, were identified in the other anoxia tolerant vertebrates here but did not display a similarly robust response to anoxia. Conclusion: These findings support an overall stabilization of the small ncRNA transcriptome during exposure to anoxic insults, but also suggest that multiple small ncRNA expression pathways may support anoxia tolerance, as no conserved small ncRNA response was identified among the anoxia-tolerant vertebrates studied. This may reflect divergent strategies to achieve the same endpoint: anoxia tolerance. However, it may also indicate that there are multiple cellular pathways that can trigger the same cellular and physiological survival processes, including hypometabolism.}, } @article {pmid30046113, year = {2018}, author = {Dhir, A and Dhir, S and Borowski, LS and Jimenez, L and Teitell, M and Rötig, A and Crow, YJ and Rice, GI and Duffy, D and Tamby, C and Nojima, T and Munnich, A and Schiff, M and de Almeida, CR and Rehwinkel, J and Dziembowski, A and Szczesny, RJ and Proudfoot, NJ}, title = {Mitochondrial double-stranded RNA triggers antiviral signalling in humans.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {238-242}, pmid = {30046113}, issn = {1476-4687}, support = {107928/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; MC_UU_00008/8/MRC_/Medical Research Council/United Kingdom ; 339270/ERC_/European Research Council/International ; GM073981/GM/NIGMS NIH HHS/United States ; R01 GM114188/GM/NIGMS NIH HHS/United States ; 107928/WT_/Wellcome Trust/United Kingdom ; R01 GM073981/GM/NIGMS NIH HHS/United States ; MC_UU_12010/8/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; DEAD-box RNA Helicases/deficiency/genetics/metabolism ; Endoribonucleases/metabolism ; Exoribonucleases/deficiency/genetics/metabolism ; Gene Expression Regulation/immunology ; HeLa Cells ; Herpesvirus 1, Human/genetics/*immunology ; Humans ; Interferon Type I/antagonists & inhibitors/immunology ; Interferon-Induced Helicase, IFIH1/metabolism ; Mice ; Mice, Inbred C57BL ; Multienzyme Complexes/metabolism ; Mutation ; Polyribonucleotide Nucleotidyltransferase/metabolism ; RNA Helicases/metabolism ; RNA, Double-Stranded/*immunology ; RNA, Mitochondrial/*immunology ; Single-Cell Analysis ; bcl-2 Homologous Antagonist-Killer Protein/metabolism ; bcl-2-Associated X Protein/metabolism ; Mitochondrial Proteins ; }, abstract = {Mitochondria are descendants of endosymbiotic bacteria and retain essential prokaryotic features such as a compact circular genome. Consequently, in mammals, mitochondrial DNA is subjected to bidirectional transcription that generates overlapping transcripts, which are capable of forming long double-stranded RNA structures[1,2]. However, to our knowledge, mitochondrial double-stranded RNA has not been previously characterized in vivo. Here we describe the presence of a highly unstable native mitochondrial double-stranded RNA species at single-cell level and identify key roles for the degradosome components mitochondrial RNA helicase SUV3 and polynucleotide phosphorylase PNPase in restricting the levels of mitochondrial double-stranded RNA. Loss of either enzyme results in massive accumulation of mitochondrial double-stranded RNA that escapes into the cytoplasm in a PNPase-dependent manner. This process engages an MDA5-driven antiviral signalling pathway that triggers a type I interferon response. Consistent with these data, patients carrying hypomorphic mutations in the gene PNPT1, which encodes PNPase, display mitochondrial double-stranded RNA accumulation coupled with upregulation of interferon-stimulated genes and other markers of immune activation. The localization of PNPase to the mitochondrial inter-membrane space and matrix suggests that it has a dual role in preventing the formation and release of mitochondrial double-stranded RNA into the cytoplasm. This in turn prevents the activation of potent innate immune defence mechanisms that have evolved to protect vertebrates against microbial and viral attack.}, } @article {pmid30055249, year = {2018}, author = {Torrezan-Nitao, E and Figueiredo, RCBQ and Marques-Santos, LF}, title = {Mitochondrial permeability transition pore in sea urchin female gametes.}, journal = {Mechanisms of development}, volume = {154}, number = {}, pages = {208-218}, doi = {10.1016/j.mod.2018.07.008}, pmid = {30055249}, issn = {1872-6356}, mesh = {Animals ; Calcium/metabolism ; Cyclosporine/metabolism ; Female ; Germ Cells/*metabolism ; Membrane Potential, Mitochondrial/physiology ; Mitochondria/*metabolism/physiology ; Mitochondrial Membrane Transport Proteins/*metabolism ; Mitochondrial Permeability Transition Pore ; Sea Urchins/*metabolism/physiology ; }, abstract = {Mitochondrial permeability transition pore (MPTP) has been associated to calcium homeostasis and reactive oxygen species (ROS) generation in several cell types. While extensively investigated in somatic cells, there are few data regarding MPTP phenomenon in gametes. The aim of the present work was to investigate MPTP occurrence in sea urchin female gametes. The protonophores CCCP and FCCP, and the Ca[2+] ionophore ionomycin, were used as pore inductors. Pore opening was monitored by mitochondrial potential sensitive probes and cobalt-quenched calcein assay. The pore desensitizer cyclosporin A (CsA) prevented the loss of mitochondrial inner membrane potential (ΔΨm) and pore opening induced by MPTP activators. The disruption of ΔΨm led to an increase in ROS generation, which was completely prevented by CsA. Our data also demonstrated that the increase in ROS production induced by MPTP opening requires extracellular Ca[2+]. In summary, the current study provides evidence about the occurrence of MPTP in sea urchin eggs in a similar manner as described in vertebrate somatic cells - CsA-sensitive, voltage- and Ca[2+]-triggered - and shows MPTP as a highly conserved physiological event through the evolution.}, } @article {pmid30055354, year = {2018}, author = {Linard, B and Crampton-Platt, A and Moriniere, J and Timmermans, MJTN and Andújar, C and Arribas, P and Miller, KE and Lipecki, J and Favreau, E and Hunter, A and Gómez-Rodríguez, C and Barton, C and Nie, R and Gillett, CPDT and Breeschoten, T and Bocak, L and Vogler, AP}, title = {The contribution of mitochondrial metagenomics to large-scale data mining and phylogenetic analysis of Coleoptera.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {1-11}, doi = {10.1016/j.ympev.2018.07.008}, pmid = {30055354}, issn = {1095-9513}, mesh = {Algorithms ; Animals ; Base Sequence ; Coleoptera/classification/*genetics ; Databases, Genetic ; *Metagenomics ; Mitochondria/*genetics ; *Phylogeny ; }, abstract = {A phylogenetic tree at the species level is still far off for highly diverse insect orders, including the Coleoptera, but the taxonomic breadth of public sequence databases is growing. In addition, new types of data may contribute to increasing taxon coverage, such as metagenomic shotgun sequencing for assembly of mitogenomes from bulk specimen samples. The current study explores the application of these techniques for large-scale efforts to build the tree of Coleoptera. We used shotgun data from 17 different ecological and taxonomic datasets (5 unpublished) to assemble a total of 1942 mitogenome contigs of >3000 bp. These sequences were combined into a single dataset together with all mitochondrial data available at GenBank, in addition to nuclear markers widely used in molecular phylogenetics. The resulting matrix of nearly 16,000 species with two or more loci produced trees (RAxML) showing overall congruence with the Linnaean taxonomy at hierarchical levels from suborders to genera. We tested the role of full-length mitogenomes in stabilizing the tree from GenBank data, as mitogenomes might link terminals with non-overlapping gene representation. However, the mitogenome data were only partly useful in this respect, presumably because of the purely automated approach to assembly and gene delimitation, but improvements in future may be possible by using multiple assemblers and manual curation. In conclusion, the combination of data mining and metagenomic sequencing of bulk samples provided the largest phylogenetic tree of Coleoptera to date, which represents a summary of existing phylogenetic knowledge and a defensible tree of great utility, in particular for studies at the intra-familial level, despite some shortcomings for resolving basal nodes.}, } @article {pmid30056805, year = {2018}, author = {Seixas, FA and Boursot, P and Melo-Ferreira, J}, title = {The genomic impact of historical hybridization with massive mitochondrial DNA introgression.}, journal = {Genome biology}, volume = {19}, number = {1}, pages = {91}, pmid = {30056805}, issn = {1474-760X}, support = {FCT-ANR/BIA-EVF/0250/2012//Fundação para a Ciência e a Tecnologia/International ; IF/00033/2014/CP1256/CT0005//Fundação para a Ciência e a Tecnologia/International ; SFRH/BD/87126/2012//Fundação para a Ciência e a Tecnologia/International ; ANR-12-ISV7-0002-01//Agence Nationale de la Recherche/International ; NORTE-01-0145-FEDER-000007//NORTE2020, ERDF/International ; }, mesh = {Adaptation, Biological/genetics ; *Animal Migration ; Animals ; Cell Nucleus/genetics ; DNA, Mitochondrial/*genetics ; Europe ; Genetics, Population ; *Genome ; *Hybridization, Genetic ; Lagomorpha/classification/*genetics ; Mitochondria/genetics ; Models, Genetic ; Phylogeny ; Recombination, Genetic ; Selection, Genetic ; Whole Genome Sequencing ; X Chromosome/chemistry ; }, abstract = {BACKGROUND: The extent to which selection determines interspecific patterns of genetic exchange enlightens the role of adaptation in evolution and speciation. Often reported extensive interspecific introgression could be selection-driven, but also result from demographic processes, especially in cases of invasive species replacements, which can promote introgression at their invasion front. Because invasion and selective sweeps similarly mold variation, population genetics evidence for selection can only be gathered in an explicit demographic framework. The Iberian hare, Lepus granatensis, displays in its northern range extensive mitochondrial DNA introgression from L. timidus, an arctic/boreal species that it replaced locally after the last glacial maximum. We use whole-genome sequencing to infer geographic and genomic patterns of nuclear introgression and fit a neutral model of species replacement with hybridization, allowing us to evaluate how selection influenced introgression genome-wide, including for mtDNA.

RESULTS: Although the average nuclear and mtDNA introgression patterns contrast strongly, they fit a single demographic model of post-glacial invasive replacement of timidus by granatensis. Outliers of elevated introgression include several genes related to immunity, spermatogenesis, and mitochondrial metabolism. Introgression is reduced on the X chromosome and in low recombining regions.

CONCLUSIONS: General nuclear and mtDNA patterns of introgression can be explained by purely demographic processes. Hybrid incompatibilities and interplay between selection and recombination locally modulate levels of nuclear introgression. Selection promoted introgression of some genes involved in conflicts, either interspecific (parasites) or possibly cytonuclear. In the latter case, nuclear introgression could mitigate the potential negative effects of alien mtDNA on mitochondrial metabolism and male-specific traits.}, } @article {pmid30057120, year = {2018}, author = {Zhang, Q and Wu, X and Chen, P and Liu, L and Xin, N and Tian, Y and Dillin, A}, title = {The Mitochondrial Unfolded Protein Response Is Mediated Cell-Non-autonomously by Retromer-Dependent Wnt Signaling.}, journal = {Cell}, volume = {174}, number = {4}, pages = {870-883.e17}, pmid = {30057120}, issn = {1097-4172}, support = {P40 OD010440/OD/NIH HHS/United States ; R01 ES021667/ES/NIEHS NIH HHS/United States ; R37 AG024365/AG/NIA NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Animals, Genetically Modified/genetics/growth & development/*metabolism ; Caenorhabditis elegans/genetics/growth & development/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Carrier Proteins/genetics/metabolism ; Glycoproteins/genetics/metabolism ; Intracellular Signaling Peptides and Proteins ; Mitochondria/genetics/*metabolism ; Neurons/cytology/metabolism ; Polyubiquitin/*metabolism ; Unfolded Protein Response/*physiology ; Vesicular Transport Proteins/genetics/metabolism ; Wnt Proteins/genetics/*metabolism ; }, abstract = {The mitochondrial unfolded protein response (UPR[mt]) can be triggered in a cell-non-autonomous fashion across multiple tissues in response to mitochondrial dysfunction. The ability to communicate information about the presence of mitochondrial stress enables a global response that can ultimately better protect an organism from local mitochondrial challenges. We find that animals use retromer-dependent Wnt signaling to propagate mitochondrial stress signals from the nervous system to peripheral tissues. Specifically, the polyQ40-triggered activation of mitochondrial stress or reduction of cco-1 (complex IV subunit) in neurons of C. elegans results in the Wnt-dependent induction of cell-non-autonomous UPR[mt] in peripheral cells. Loss-of-function mutations of retromer complex components that are responsible for recycling the Wnt secretion-factor/MIG-14 prevent Wnt secretion and thereby suppress cell-non-autonomous UPR[mt]. Neuronal expression of the Wnt ligand/EGL-20 is sufficient to induce cell-non-autonomous UPR[mt] in a retromer complex-, Wnt signaling-, and serotonin-dependent manner, clearly implicating Wnt signaling as a strong candidate for the "mitokine" signal.}, } @article {pmid30059499, year = {2018}, author = {Gao, B and Peng, C and Chen, Q and Zhang, J and Shi, Q}, title = {Mitochondrial genome sequencing of a vermivorous cone snail Conus quercinus supports the correlative analysis between phylogenetic relationships and dietary types of Conus species.}, journal = {PloS one}, volume = {13}, number = {7}, pages = {e0193053}, pmid = {30059499}, issn = {1932-6203}, mesh = {Animals ; Annelida ; Base Composition ; Base Sequence ; Biological Evolution ; Chromosome Mapping ; Conotoxins/*genetics ; Conus Snail/classification/*genetics ; Food Chain ; Gene Ontology ; Genome Size ; *Genome, Mitochondrial ; Mitochondria/*genetics ; Molecular Sequence Annotation ; Open Reading Frames ; Phylogeny ; RNA, Ribosomal/*genetics ; RNA, Transfer/*genetics ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; Tandem Repeat Sequences ; }, abstract = {Complete mitochondrial genome (mitogenome) sequence of a worm-hunting cone snail, Conus quercinus, was reported in this study. Its mitogenome, the longest one (16,460 bp) among reported Conus specie, is composed of 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes and one D-loop region. The mitochondrial gene arrangement is highly-conserved and identical to other reported. However, the D-loop region of C. quercinus is the longest (943 bp) with the higher A+T content (71.3%) and a long AT tandem repeat stretch (68 bp). Subsequent phylogenetic analysis demonstrated that three different dietary types (vermivorous, molluscivorous and piscivorous) of cone snails are clustered separately, suggesting that the phylogenetics of cone snails is related to their dietary types. In conclusion, our current work improves our understanding of the mitogenomic structure and evolutionary status of the vermivorous C. quercinus, which support the putative hypothesis that the Conus ancestor was vermivorous.}, } @article {pmid30060189, year = {2018}, author = {Río Bártulos, C and Rogers, MB and Williams, TA and Gentekaki, E and Brinkmann, H and Cerff, R and Liaud, MF and Hehl, AB and Yarlett, NR and Gruber, A and Kroth, PG and van der Giezen, M}, title = {Mitochondrial Glycolysis in a Major Lineage of Eukaryotes.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2310-2325}, pmid = {30060189}, issn = {1759-6653}, support = {//Wellcome Trust/United Kingdom ; 078566/A/05/Z//Wellcome Trust/United Kingdom ; }, mesh = {Biological Evolution ; Blastocystis/cytology/enzymology/genetics/*metabolism ; Diatoms/cytology/enzymology/genetics/*metabolism ; Energy Metabolism ; Genome, Mitochondrial ; *Glycolysis ; Mitochondria/genetics/*metabolism ; Symbiosis ; Transformation, Genetic ; }, abstract = {The establishment of the mitochondrion is seen as a transformational step in the origin of eukaryotes. With the mitochondrion came bioenergetic freedom to explore novel evolutionary space leading to the eukaryotic radiation known today. The tight integration of the bacterial endosymbiont with its archaeal host was accompanied by a massive endosymbiotic gene transfer resulting in a small mitochondrial genome which is just a ghost of the original incoming bacterial genome. This endosymbiotic gene transfer resulted in the loss of many genes, both from the bacterial symbiont as well the archaeal host. Loss of genes encoding redundant functions resulted in a replacement of the bulk of the host's metabolism for those originating from the endosymbiont. Glycolysis is one such metabolic pathway in which the original archaeal enzymes have been replaced by bacterial enzymes from the endosymbiont. Glycolysis is a major catabolic pathway that provides cellular energy from the breakdown of glucose. The glycolytic pathway of eukaryotes appears to be bacterial in origin, and in well-studied model eukaryotes it takes place in the cytosol. In contrast, here we demonstrate that the latter stages of glycolysis take place in the mitochondria of stramenopiles, a diverse and ecologically important lineage of eukaryotes. Although our work is based on a limited sample of stramenopiles, it leaves open the possibility that the mitochondrial targeting of glycolytic enzymes in stramenopiles might represent the ancestral state for eukaryotes.}, } @article {pmid30060640, year = {1983}, author = {Ruppert, EE and Travis, PB}, title = {Hemoglobin-containing cells of Neodasys (Gastrotricha, Chaetonotida). I. Morphology and ultrastructure.}, journal = {Journal of morphology}, volume = {175}, number = {1}, pages = {57-64}, doi = {10.1002/jmor.1051750106}, pmid = {30060640}, issn = {1097-4687}, abstract = {The overall anatomy of Neodasys as well as data for hemoglobin-containing cells are described. Hemoglobin-containing cells are shown to be mesodermal specializations constituting approximately 14% of the animal's total body volume (4.87 ± 10[4] μl). These globular cells (10-14 μm) are situated in two longitudinal rows, each dorsolateral to the straight gut. Branches from the cells enwrap perikarya of muscle and nerve cells whose mitochondria are found just below their respective plasmalemmata in intimate association with the hemoglobin-containing cells. The ground substance of the cytoplasm and nucleoplasm of these nearly organelle-free cells is extremely electron-dense and is presumed to represent the hemoglobin molecules. Locomotion analyses indicate that the cells can undergo a threefold change in linear dimension in 0.25 seconds, raising the possibility of convective mixing in these cells. Structural and ultrastructural comparisons with similar cells in adults of other species of Gastrotricha indicate that the hemoglobin-containing cells of Neodasys may be homologous to the socalled Y cells of other species, some of which contain myofilaments. A muscle-cell origin is considered for the evolution of hemoglobin-containing cells of Neodasys.}, } @article {pmid30061407, year = {2018}, author = {Nagano, H and Hashimoto, N and Nakayama, A and Suzuki, S and Miyabayashi, Y and Yamato, A and Higuchi, S and Fujimoto, M and Sakuma, I and Beppu, M and Yokoyama, M and Suzuki, Y and Sugano, S and Ikeda, K and Tatsuno, I and Manabe, I and Yokote, K and Inoue, S and Tanaka, T}, title = {p53-inducible DPYSL4 associates with mitochondrial supercomplexes and regulates energy metabolism in adipocytes and cancer cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8370-8375}, pmid = {30061407}, issn = {1091-6490}, mesh = {Adenosine Triphosphate/biosynthesis ; Adipocytes/*metabolism ; Animals ; Cell Line, Tumor ; *Energy Metabolism ; Humans ; Male ; Mice ; Mice, SCID ; Mitochondria/*metabolism ; Neoplasms/*metabolism ; Nerve Tissue Proteins/*physiology ; Obesity/metabolism ; Oxygen Consumption ; Tumor Suppressor Protein p53/*physiology ; Tumor Suppressor Proteins/physiology ; }, abstract = {The tumor suppressor p53 regulates multiple cellular functions, including energy metabolism. Metabolic deregulation is implicated in the pathogenesis of some cancers and in metabolic disorders and may result from the inactivation of p53 functions. Using RNA sequencing and ChIP sequencing of cancer cells and preadipocytes, we demonstrate that p53 modulates several metabolic processes via the transactivation of energy metabolism genes including dihydropyrimidinase-like 4 (DPYSL4). DPYSL4 is a member of the collapsin response mediator protein family, which is involved in cancer invasion and progression. Intriguingly, DPYSL4 overexpression in cancer cells and preadipocytes up-regulated ATP production and oxygen consumption, while DPYSL4 knockdown using siRNA or CRISPR/Cas9 down-regulated energy production. Furthermore, DPYSL4 was associated with mitochondrial supercomplexes, and deletion of its dihydropyrimidinase-like domain abolished its association and its ability to stimulate ATP production and suppress the cancer cell invasion. Mouse-xenograft and lung-metastasis models indicated that DPYSL4 expression compromised tumor growth and metastasis in vivo. Consistently, database analyses demonstrated that low DPYSL4 expression was significantly associated with poor survival of breast and ovarian cancers in accordance with its reduced expression in certain types of cancer tissues. Moreover, immunohistochemical analysis using the adipose tissue of obese patients revealed that DPYSL4 expression was positively correlated with INFg and body mass index in accordance with p53 activation. Together, these results suggest that DPYSL4 plays a key role in the tumor-suppressor function of p53 by regulating oxidative phosphorylation and the cellular energy supply via its association with mitochondrial supercomplexes, possibly linking to the pathophysiology of both cancer and obesity.}, } @article {pmid30063873, year = {2019}, author = {Kumar Jadav, K and Pratap Singh, A and Srivastav, AB and Sarkhel, BC}, title = {Molecular characterization of the complete mitochondrial genome sequence of Indian wild pig (Sus scrofa cristatus).}, journal = {Animal biotechnology}, volume = {30}, number = {2}, pages = {186-191}, doi = {10.1080/10495398.2018.1469506}, pmid = {30063873}, issn = {1532-2378}, mesh = {Animals ; Breeding ; Genome, Mitochondrial/*genetics ; High-Throughput Nucleotide Sequencing/veterinary ; Male ; Mitochondria/genetics ; Phylogeny ; Sequence Analysis, DNA/veterinary ; Sus scrofa/*genetics ; }, abstract = {The Indian wild pig is a sub-species (Sus scrofa cristatus) which is different from the other pig breeds and is protected under Schedule-III of the Indian Wildlife (Protection) Act, 1972. In this study, complete mitogenome of two Indian wild pigs was sequenced and characterized by shotgun sequencing and de novo assembly, which revealed sequence size of 16,738 and 16,251 bp, respectively, (Accession no. MG725630 and MG725631). The mitogenome sequence in this study displayed 98% homology with previously reported mitogenome of pigs from different parts of the world. Mitogenome analysis by MITOS Web server revealed similarity of gene organization with the other vertebrates (13 protein-coding, 22 tRNAs, 2 rRNAs genes, and a control region). The mitogenomic sequences of Indian wild pig maintained a separate clade in the phylogenetic tree constructed by using 62 whole mitogenome sequences across the world. The phylogeny derived from mitogenomic sequences revealed distinct separate European-American and Asiatic pig clades. It was concluded that whole mitogenome sequencing using NGS without designing mitogenome-specific primer for amplification, is possible thereby reducing the cost and labor. This study is the first report of complete sequence of mitogenome of Indian wild pig.}, } @article {pmid30067212, year = {2018}, author = {Barthole, G}, title = {[Never alone. Microorganism, ecology, evolution].}, journal = {Medecine sciences : M/S}, volume = {34}, number = {6-7}, pages = {604-607}, doi = {10.1051/medsci/20183406023}, pmid = {30067212}, issn = {1958-5381}, mesh = {Animals ; *Biological Evolution ; Civilization ; *Ecosystem ; Endophytes/*physiology ; Host Microbial Interactions/physiology ; Humans ; Microbial Interactions/physiology ; Mitochondria/physiology ; Plants/microbiology ; Symbiosis/*physiology ; }, } @article {pmid30071011, year = {2018}, author = {Grinter, R and Hay, ID and Song, J and Wang, J and Teng, D and Dhanesakaran, V and Wilksch, JJ and Davies, MR and Littler, D and Beckham, SA and Henderson, IR and Strugnell, RA and Dougan, G and Lithgow, T}, title = {FusC, a member of the M16 protease family acquired by bacteria for iron piracy against plants.}, journal = {PLoS biology}, volume = {16}, number = {8}, pages = {e2006026}, pmid = {30071011}, issn = {1545-7885}, support = {106077/Z/14/Z//Wellcome Trust/United Kingdom ; }, mesh = {Bacteria/metabolism ; Bacterial Outer Membrane Proteins/metabolism ; Bacterial Proteins/metabolism ; Ferredoxins/metabolism ; Iron/*metabolism ; Membrane Transport Proteins/*metabolism ; Metalloendopeptidases/metabolism ; Pectobacterium/*metabolism ; Phylogeny ; Plant Proteins/metabolism ; Plants/metabolism ; Protein Transport/physiology ; Mitochondrial Processing Peptidase ; }, abstract = {Iron is essential for life. Accessing iron from the environment can be a limiting factor that determines success in a given environmental niche. For bacteria, access of chelated iron from the environment is often mediated by TonB-dependent transporters (TBDTs), which are β-barrel proteins that form sophisticated channels in the outer membrane. Reports of iron-bearing proteins being used as a source of iron indicate specific protein import reactions across the bacterial outer membrane. The molecular mechanism by which a folded protein can be imported in this way had remained mysterious, as did the evolutionary process that could lead to such a protein import pathway. How does the bacterium evolve the specificity factors that would be required to select and import a protein encoded on another organism's genome? We describe here a model whereby the plant iron-bearing protein ferredoxin can be imported across the outer membrane of the plant pathogen Pectobacterium by means of a Brownian ratchet mechanism, thereby liberating iron into the bacterium to enable its growth in plant tissues. This import pathway is facilitated by FusC, a member of the same protein family as the mitochondrial processing peptidase (MPP). The Brownian ratchet depends on binding sites discovered in crystal structures of FusC that engage a linear segment of the plant protein ferredoxin. Sequence relationships suggest that the bacterial gene encoding FusC has previously unappreciated homologues in plants and that the protein import mechanism employed by the bacterium is an evolutionary echo of the protein import pathway in plant mitochondria and plastids.}, } @article {pmid30071112, year = {2018}, author = {Caza, M and Hu, G and Nielson, ED and Cho, M and Jung, WH and Kronstad, JW}, title = {The Sec1/Munc18 (SM) protein Vps45 is involved in iron uptake, mitochondrial function and virulence in the pathogenic fungus Cryptococcus neoformans.}, journal = {PLoS pathogens}, volume = {14}, number = {8}, pages = {e1007220}, pmid = {30071112}, issn = {1553-7374}, support = {R01 AI053721/AI/NIAID NIH HHS/United States ; MOP13234/CAPMC/CIHR/Canada ; }, mesh = {Animals ; Biological Transport ; Cryptococcosis/metabolism/microbiology/pathology ; *Cryptococcus neoformans/genetics/metabolism/pathogenicity ; Female ; Fungal Proteins/*physiology ; Iron/*metabolism ; Mice ; Mice, Inbred BALB C ; Mitochondria/*physiology ; Organisms, Genetically Modified ; Phylogeny ; Virulence/*genetics ; Virulence Factors/genetics/*physiology ; }, abstract = {The battle for iron between invading microorganisms and mammalian hosts is a pivotal determinant of the outcome of infection. The pathogenic fungus, Cryptococcus neoformans, employs multiple mechanisms to compete for iron during cryptococcosis, a disease primarily of immunocompromised hosts. In this study, we examined the role of endocytic trafficking in iron uptake by characterizing a mutant defective in the Sec1/Munc18 (SM) protein Vps45. This protein is known to regulate the machinery for vesicle trafficking and fusion via interactions with SNARE proteins. As expected, a vps45 deletion mutant was impaired in endocytosis and showed sensitivity to trafficking inhibitors. The mutant also showed poor growth on iron-limited media and a defect in transporting the Cfo1 ferroxidase of the high-affinity iron uptake system from the plasma membrane to the vacuole. Remarkably, we made the novel observation that Vps45 also contributes to mitochondrial function in that a Vps45-Gfp fusion protein associated with mitotracker, and a vps45 mutant showed enhanced sensitivity to inhibitors of electron transport complexes as well as changes in mitochondrial membrane potential. Consistent with mitochondrial function, the vps45 mutant was impaired in calcium homeostasis. To assess the relevance of these defects for virulence, we examined cell surface properties of the vps45 mutant and found increased sensitivity to agents that challenge cell wall integrity and to antifungal drugs. A change in cell wall properties was consistent with our observation of altered capsule polysaccharide attachment, and with attenuated virulence in a mouse model of cryptococcosis. Overall, our studies reveal a novel role for Vps45-mediated trafficking for iron uptake, mitochondrial function and virulence.}, } @article {pmid30074999, year = {2018}, author = {Brew-Appiah, RAT and York, ZB and Krishnan, V and Roalson, EH and Sanguinet, KA}, title = {Genome-wide identification and analysis of the ALTERNATIVE OXIDASE gene family in diploid and hexaploid wheat.}, journal = {PloS one}, volume = {13}, number = {8}, pages = {e0201439}, pmid = {30074999}, issn = {1932-6203}, mesh = {Aegilops/*genetics ; Diploidy ; Gene Expression Regulation, Developmental/physiology ; Gene Expression Regulation, Plant/physiology ; Genes, Plant/*genetics ; Genome, Plant/genetics ; Herbicide Resistance/genetics ; Mitochondrial Proteins/*genetics ; Multigene Family/*genetics ; Oxidoreductases/*genetics ; Phylogeny ; Plant Proteins/*genetics ; Polyploidy ; Stress, Physiological/physiology ; Triticum/genetics/*physiology ; Whole Genome Sequencing ; Alternative Oxidase ; }, abstract = {A comprehensive understanding of wheat responses to environmental stress will contribute to the long-term goal of feeding the planet. ALERNATIVE OXIDASE (AOX) genes encode proteins involved in a bypass of the electron transport chain and are also known to be involved in stress tolerance in multiple species. Here, we report the identification and characterization of the AOX gene family in diploid and hexaploid wheat. Four genes each were found in the diploid ancestors Triticum urartu, and Aegilops tauschii, and three in Aegilops speltoides. In hexaploid wheat (Triticum aestivum), 20 genes were identified, some with multiple splice variants, corresponding to a total of 24 proteins for those with observed transcription and translation. These proteins were classified as AOX1a, AOX1c, AOX1e or AOX1d via phylogenetic analysis. Proteins lacking most or all signature AOX motifs were assigned to putative regulatory roles. Analysis of protein-targeting sequences suggests mixed localization to the mitochondria and other organelles. In comparison to the most studied AOX from Trypanosoma brucei, there were amino acid substitutions at critical functional domains indicating possible role divergence in wheat or grasses in general. In hexaploid wheat, AOX genes were expressed at specific developmental stages as well as in response to both biotic and abiotic stresses such as fungal pathogens, heat and drought. These AOX expression patterns suggest a highly regulated and diverse transcription and expression system. The insights gained provide a framework for the continued and expanded study of AOX genes in wheat for stress tolerance through breeding new varieties, as well as resistance to AOX-targeted herbicides, all of which can ultimately be used synergistically to improve crop yield.}, } @article {pmid30075756, year = {2018}, author = {Burke, SV and Ungerer, MC and Duvall, MR}, title = {Investigation of mitochondrial-derived plastome sequences in the Paspalum lineage (Panicoideae; Poaceae).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {152}, pmid = {30075756}, issn = {1471-2229}, support = {DEB-1120856//National Science Foundation/ ; DEB-1120761//National Science Foundation/ ; }, mesh = {DNA, Intergenic/genetics ; DNA, Plant/genetics ; Mitochondria/*genetics ; Paspalum/*genetics ; Phylogeny ; Plastids/*genetics ; Poaceae/genetics ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; }, abstract = {BACKGROUND: The grass family (Poaceae), ca. 12,075 species, is a focal point of many recent studies that aim to use complete plastomes to reveal and strengthen relationships within the family. The use of Next Generation Sequencing technology has revealed intricate details in many Poaceae plastomes; specifically the trnI - trnL intergenic spacer region. This study investigates this region and the putative mitochondrial inserts within it in complete plastomes of Paspalum and other Poaceae.

RESULTS: Nine newly sequenced plastomes, seven of which contain an insert within the trnI - trnL intergenic spacer, were combined into plastome phylogenomic and divergence date analyses with 52 other species. A robust Paspalum topology was recovered, originating at 10.6 Ma, with the insert arising at 8.7 Ma. The alignment of the insert across Paspalum reveals 21 subregions with pairwise homology in 19. In an analysis of emergent self-organizing maps of tetranucleotide frequencies, the Paspalum insert grouped with mitochondrial DNA.

CONCLUSIONS: A hypothetical ancestral insert, 17,685 bp in size, was found in the trnI - trnL intergenic spacer for the Paspalum lineage. A different insert, 2808 bp, was found in the same region for Paraneurachne muelleri. Seven different intrastrand deletion events were found within the Paspalum lineage, suggesting selective pressures to remove large portions of noncoding DNA. Finally, a tetranucleotide frequency analysis was used to determine that the origin of the insert in the Paspalum lineage is mitochondrial DNA.}, } @article {pmid30076323, year = {2018}, author = {Duong, NT and Macholdt, E and Ton, ND and Arias, L and Schröder, R and Van Phong, N and Thi Bich Thuy, V and Ha, NH and Thi Thu Hue, H and Thi Xuan, N and Thi Phuong Oanh, K and Hien, LTT and Hoang, NH and Pakendorf, B and Stoneking, M and Van Hai, N}, title = {Complete human mtDNA genome sequences from Vietnam and the phylogeography of Mainland Southeast Asia.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {11651}, pmid = {30076323}, issn = {2045-2322}, mesh = {Asia, Southeastern ; Asian People/genetics ; Chromosomes, Human, Y/genetics ; DNA, Mitochondrial/*genetics ; Ethnicity/genetics ; *Genetics, Population ; Haplotypes ; Humans ; Mitochondria/genetics ; Phylogeny ; *Phylogeography ; Taiwan ; Whole Genome Sequencing ; }, abstract = {Vietnam is an important crossroads within Mainland Southeast Asia (MSEA) and a gateway to Island Southeast Asia, and as such exhibits high levels of ethnolinguistic diversity. However, comparatively few studies have been undertaken of the genetic diversity of Vietnamese populations. In order to gain comprehensive insights into MSEA mtDNA phylogeography, we sequenced 609 complete mtDNA genomes from individuals belonging to five language families (Austroasiatic, Tai-Kadai, Hmong-Mien, Sino-Tibetan and Austronesian) and analyzed them in comparison with sequences from other MSEA countries and Taiwan. Within Vietnam, we identified 399 haplotypes belonging to 135 haplogroups; among the five language families, the sequences from Austronesian groups differ the most from the other groups. Phylogenetic analysis revealed 111 novel Vietnamese mtDNA lineages. Bayesian estimates of coalescence times and associated 95% HPD for these show a peak of mtDNA diversification around 2.5-3 kya, which coincides with the Dong Son culture, and thus may be associated with the agriculturally-driven expansion of this culture. Networks of major MSEA haplogroups emphasize the overall distinctiveness of sequences from Taiwan, in keeping with previous studies that suggested at most a minor impact of the Austronesian expansion from Taiwan on MSEA. We also see evidence for population expansions across MSEA geographic regions and language families.}, } @article {pmid30086701, year = {2018}, author = {Skoracka, A and Lopes, LF and Alves, MJ and Miller, A and Lewandowski, M and Szydło, W and Majer, A and Różańska, E and Kuczyński, L}, title = {Genetics of lineage diversification and the evolution of host usage in the economically important wheat curl mite, Aceria tosichella Keifer, 1969.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {122}, pmid = {30086701}, issn = {1471-2148}, support = {No. 01/KNOW2/2014//Funding for open access charge: Ministry of Science and Higher Education of the Republic of Poland, from the quality promoting subsidy, under the Leading National Research Centre (KNOW) program for the years 2014-2019/International ; 2011/03/B/NZ8/00129//Narodowe Centrum Nauki/International ; 2011/01/N/NZ8/04540//Narodowe Centrum Nauki/International ; UID/BIA/00329/2013//Fundação para a Ciência e a Tecnologia/International ; UID/BIA/00329/2013//Fundação para a Ciência e a Tecnologia/International ; }, mesh = {Animals ; Base Sequence ; Bayes Theorem ; Calibration ; DNA, Mitochondrial/genetics ; Demography ; Gene Flow ; Genetic Variation ; Host-Pathogen Interactions/*genetics ; Mites/*classification/*genetics ; Mitochondria/genetics ; *Phylogeny ; Plant Diseases/*parasitology ; Time Factors ; Triticum/*parasitology ; }, abstract = {BACKGROUND: Understanding the mechanisms that underlie the diversification of herbivores through interactions with their hosts is important for their diversity assessment and identification of expansion events, particularly in a human-altered world where evolutionary processes can be exacerbated. We studied patterns of host usage and genetic structure in the wheat curl mite complex (WCM), Aceria tosichella, a major pest of the world's grain industry, to identify the factors behind its extensive diversification.

RESULTS: We expanded on previous phylogenetic research, demonstrating deep lineage diversification within the taxon, a complex of distinctive host specialist and generalist lineages more diverse than previously assumed. Time-calibrated phylogenetic reconstruction inferred from mitochondrial DNA sequence data suggests that lineage diversification pre-dates the influence of agricultural practices, and lineages started to radiate in the mid Miocene when major radiations of C4 grasses is known to have occurred. Furthermore, we demonstrated that host specificity is not phylogenetically constrained, while host generalization appears to be a more derived trait coinciding with the expansion of the world's grasslands. Demographic history of specialist lineages have been more stable when compared to generalists, and their expansion pre-dated all generalist lineages. The lack of host-associated genetic structure of generalists indicates gene flow between mite populations from different hosts.

CONCLUSIONS: Our analyses demonstrated that WCM is an unexpectedly diverse complex of genetic lineages and its differentiation is likely associated with the time of diversification and expansion of its hosts. Signatures of demographic histories and expansion of generalists are consistent with the observed proliferation of the globally most common lineages. The apparent lack of constrains on host use, coupled with a high colonization potential, hinders mite management, which may be further compromised by host range expansion. This study provides a significant contribution to the growing literature on host-association and diversification in herbivorous invertebrates.}, } @article {pmid30086814, year = {2018}, author = {Yurchenko, V and Lukeš, J}, title = {Parasites and their (endo)symbiotic microbes.}, journal = {Parasitology}, volume = {145}, number = {10}, pages = {1261-1264}, doi = {10.1017/S0031182018001257}, pmid = {30086814}, issn = {1469-8161}, mesh = {Animals ; Biological Evolution ; Organelles ; Parasites/*microbiology ; *Symbiosis ; }, abstract = {Thanks to modern molecular biology methods, our understanding of the impact of (endo)symbiotic bacteria on parasitic protists and helminths is growing fast. In this issue, 9 papers have been brought together that describe various facets of the relationships between these microorganisms, reveal their range and high frequency, as well as their capacity to create novel biological complexity. Comparative analyses of these host-endosymbiont interactions indicate that there may be no discrete types of relationships but rather a continuum ranging from a dispensable endosymbiont minimally integrated within the host cell to organelles, such as mitochondria and plastids that evolved into an indispensable, deeply integrated components of the cell. We hope that this series of studies on parasites and (endo)symbiotic bacteria will increase awareness about these relationships and their representation in microbial ecology models.}, } @article {pmid30097722, year = {2018}, author = {Ding, CQ and Ng, S and Wang, L and Wang, YC and Li, NN and Hao, XY and Zeng, JM and Wang, XC and Yang, YJ}, title = {Genome-wide identification and characterization of ALTERNATIVE OXIDASE genes and their response under abiotic stresses in Camellia sinensis (L.) O. Kuntze.}, journal = {Planta}, volume = {248}, number = {5}, pages = {1231-1247}, pmid = {30097722}, issn = {1432-2048}, support = {1610212017003//Central Public-interest Scientific Institution Basal Research Fund/ ; CARS-19//Earmarked Fund for China Agriculture Research System/ ; 2016C02053-4//The Major Project of Agricultural Science and Technology in Breeding of Tea Plant Variety in Zhejiang Province/ ; ALTF1239-2015//European Molecular Biology Organization/ ; LTFCOFUND2013//FP PEOPLE: Marie cutie actions/ ; GA-2013-609409//FP PEOPLE: Marie cutie actions/ ; }, mesh = {Camellia sinensis/enzymology/*genetics/physiology ; Cloning, Molecular ; Conserved Sequence/genetics ; Gene Expression Regulation, Plant ; Genes, Plant/genetics ; Genome, Plant/*genetics ; Mitochondrial Proteins/*genetics/physiology ; Oxidoreductases/*genetics/physiology ; Phylogeny ; Plant Proteins/*genetics/physiology ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Stress, Physiological ; Transcriptome ; Alternative Oxidase ; }, abstract = {Four typical ALTERNATIVE OXIDASE genes have been identified in tea plants, and their sequence features and gene expression profiles have provided useful information for further studies on function and regulation. Alternative oxidase (AOX) is a terminal oxidase located in the respiratory electron transport chain. AOX catalyzes the oxidation of quinol and the reduction of oxygen into water. In this study, a genome-wide search and subsequent DNA cloning were performed to identify and characterize AOX genes in tea plant (Camellia sinensis (L.) O. Kuntze cv. Longjing43). Our results showed that tea plant possesses four AOX genes, i.e., CsAOX1a, CsAOX1d, CsAOX2a and CsAOX2b. Gene structure and protein sequence analyses revealed that all CsAOXs share a four-exon/three-intron structure with highly conserved regions and amino acid residues, which are necessary for AOX secondary structures, catalytic activities and post-translational regulations. All CsAOX were shown to localize in mitochondria using the green fluorescent protein (GFP)-targeting assay. Both CsAOX1a and CsAOX1d were induced by cold, salt and drought stresses, and with different expression patterns in young and mature leaves. Reactive oxygen species (ROS) accumulated strongly after 72 and 96 h cold treatments in both young and mature leaves, while the polyphenol and total catechin decreased significantly only in mature leaves. In comparison to AtAOX1a in Arabidopsis thaliana, CsAOX1a lost almost all of the stress-responsive cis-acting regulatory elements in its promoter region (1500 bp upstream), but possesses a flavonoid biosynthesis-related MBSII cis-acting regulatory element. These results suggest a link between CsAOX1a function and the metabolism of some secondary metabolites in tea plant. Our studies provide a basis for the further elucidation of the biological function and regulation of the AOX pathway in tea plants.}, } @article {pmid30102371, year = {2018}, author = {Hillebrand, A and Matz, JM and Almendinger, M and Müller, K and Matuschewski, K and Schmitz-Linneweber, C}, title = {Identification of clustered organellar short (cos) RNAs and of a conserved family of organellar RNA-binding proteins, the heptatricopeptide repeat proteins, in the malaria parasite.}, journal = {Nucleic acids research}, volume = {46}, number = {19}, pages = {10417-10431}, pmid = {30102371}, issn = {1362-4962}, mesh = {Chloroplasts/genetics ; Genome/genetics ; Malaria, Falciparum/*genetics/parasitology ; Mitochondria/chemistry/genetics ; Organelles/*genetics ; Peptides/chemistry/genetics ; Phylogeny ; Plasmodium falciparum/*genetics/pathogenicity ; RNA, Ribosomal/chemistry/genetics ; RNA-Binding Proteins/chemistry/*genetics ; Ribosomes/chemistry/genetics ; }, abstract = {Gene expression in mitochondria of Plasmodium falciparum is essential for parasite survival. The molecular mechanisms of Plasmodium organellar gene expression remain poorly understood. This includes the enigmatic assembly of the mitochondrial ribosome from highly fragmented rRNAs. Here, we present the identification of clustered organellar short RNA fragments (cosRNAs) that are possible footprints of RNA-binding proteins (RBPs) in Plasmodium organelles. In plants, RBPs of the pentatricopeptide repeat (PPR) class produce footprints as a consequence of their function in processing organellar RNAs. Intriguingly, many of the Plasmodium cosRNAs overlap with 5'-ends of rRNA fragments. We hypothesize that these are footprints of RBPs involved in assembling the rRNA fragments into a functioning ribosome. A bioinformatics search of the Plasmodium nuclear genome identified a hitherto unrecognized organellar helical-hairpin-repeat protein family that we term heptatricopeptide repeat (HPR) proteins. We demonstrate that selected HPR proteins are targeted to mitochondria in P. berghei and that one of them, PbHPR1, associates with RNA, but not DNA in vitro. A phylogenetic search identified HPR proteins in a wide variety of eukaryotes. We hypothesize that HPR proteins are required for processing and stabilizing RNAs in Apicomplexa and other taxa.}, } @article {pmid30102976, year = {2018}, author = {Baron, S and van der Merwe, NA and Maritz-Olivier, C}, title = {The genetic relationship between R. microplus and R. decoloratus ticks in South Africa and their population structure.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {60-69}, doi = {10.1016/j.ympev.2018.08.003}, pmid = {30102976}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Cattle ; Cell Nucleus/genetics ; DNA, Ribosomal Spacer/genetics ; Electron Transport Complex IV/genetics ; Genetic Markers ; Genetic Variation ; Genetics, Population ; Geography ; Likelihood Functions ; Microsatellite Repeats/genetics ; Mitochondria/genetics ; Phylogeny ; Rhipicephalus/classification/*genetics ; South Africa ; }, abstract = {Rhipicephalus microplus and R. decoloratus are one-host ticks that preferentially feed on cattle. They are capable of transmitting various tick-borne pathogens which may be detrimental to the agricultural and livestock industry in South Africa. Previous studies have shown that R. microplus forms five lineages in the R. microplus complex, segregating into different geographical areas based on mitochondrial markers. This study examined the phylogenetic relationship within and between R. microplus and R. decoloratus using the nuclear internal transcribed spacer 2 (ITS2) and mitochondrial cytochrome oxidase subunit I (COI) genes. The results showed that the nuclear ITS2 marker is informative for interspecific variation but lacks the resolution for intraspecific variation. Analysis of the mitochondrial COI gene revealed that R. microplus ticks from South Africa grouped into a clade comprised of ticks from Asia and South America. The population structure of these two tick species was also investigated using novel microsatellite markers. Population structure analyses revealed that both the R. microplus and R. decoloratus populations presented with two genetic clusters. Rhipicephalus microplus ticks from the Kwa-Zulu Natal (KZN) province belonged to cluster 1, and those from the Eastern Cape (EC) province predominantly grouped into cluster 2. No observable population structure was noted for R. decoloratus. The overlap of genetic clusters in both species could be attributed to inbreeding between the regions by unrestricted movement of cattle across provinces. Such movement promotes tick mobility, gene flow and the homogenisation of tick populations.}, } @article {pmid30107223, year = {2018}, author = {Reyes-Ramos, CA and Peregrino-Uriarte, AB and Cota-Ruiz, K and Valenzuela-Soto, EM and Leyva-Carrillo, L and Yepiz-Plascencia, G}, title = {Phosphoenolpyruvate carboxykinase cytosolic and mitochondrial isoforms are expressed and active during hypoxia in the white shrimp Litopenaeus vannamei.}, journal = {Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology}, volume = {226}, number = {}, pages = {1-9}, doi = {10.1016/j.cbpb.2018.08.001}, pmid = {30107223}, issn = {1879-1107}, mesh = {Amino Acid Sequence ; Animals ; Aquaculture ; Conserved Sequence ; Cytosol/*enzymology/metabolism ; Databases, Protein ; *Gene Expression Regulation, Developmental ; Gills/enzymology/growth & development/metabolism ; Hepatopancreas/enzymology/growth & development/metabolism ; Hypoxia/*enzymology/metabolism ; Isoenzymes/genetics/metabolism ; Mitochondria/*enzymology/metabolism ; Muscle, Skeletal/enzymology/growth & development/metabolism ; Organ Specificity ; Penaeidae/growth & development/*physiology ; Phosphoenolpyruvate Carboxykinase (GTP)/chemistry/genetics/*metabolism ; Phylogeny ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {Hypoxic zones in marine environments are spreading around the world affecting the survival of many organisms. Marine animals have several strategies to respond to hypoxia, including the regulation of gluconeogenesis. Phosphoenolpyruvate carboxykinase (PEPCK) is a key regulatory enzyme of gluconeogenesis. The objective of this work was to study two isoforms of PEPCK, one mitochondrial (PEPKC-M) and one cytosolic (PEPCK-C), from the white shrimp Litopenaeus vannamei and the response to hypoxia. Both PEPCK isoforms are 72 kDa proteins and have 92% identity at the amino acid level. The mitochondrial isoform has a N-terminal signal peptide for mitochondrial import. Gene expression and enzymatic activity in subcellular fractions were detected in gills, hepatopancreas and muscle in normoxic and hypoxic conditions. Expression of PEPCK-C was higher than PEPCK-M in all the tissues and induced in response to hypoxia at 48 h in hepatopancreas, while the enzymatic activity of PEPCK-M was higher than PEPCK-C in gills and hepatopancreas, but not in muscle and also increased in response to hypoxia in hepatopancreas but decreased in gills and muscle. During limiting oxygen conditions, shrimp tissues obtain energy by inducing anaerobic glycolysis, and although gluconeogenesis implies energy investment, due to the need to maintain glucose homeostasis, these gluconeogenic enzymes are active with contrasting behaviors in the cytosol and mitochondrial cell compartments and appear to be up-regulated in hepatopancreas indicating this tissue pivotal role in gluconeogenesis during the response to hypoxia.}, } @article {pmid30107780, year = {2018}, author = {Dong, S and Zhao, C and Chen, F and Liu, Y and Zhang, S and Wu, H and Zhang, L and Liu, Y}, title = {The complete mitochondrial genome of the early flowering plant Nymphaea colorata is highly repetitive with low recombination.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {614}, pmid = {30107780}, issn = {1471-2164}, support = {31470314//National Natural Science Foundation of China/ ; 31600171//National Natural Science Foundation of China/ ; FLSF2017-03//National Natural Science Foundation of China/ ; 201520//Shenzhen Urban Management Bureau Fund/ ; DEB-1240045//National Science Foundation/ ; JCYJ20150529150409546//Shenzhen Municipal Government of China/ ; }, mesh = {*Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing/methods ; Mitochondria/*genetics ; Nymphaea/*genetics/growth & development ; *Recombination, Genetic ; Repetitive Sequences, Nucleic Acid ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Mitochondrial genomes of flowering plants (angiosperms) are highly dynamic in genome structure. The mitogenome of the earliest angiosperm Amborella is remarkable in carrying rampant foreign DNAs, in contrast to Liriodendron, the other only known early angiosperm mitogenome that is described as 'fossilized'. The distinctive features observed in the two early flowering plant mitogenomes add to the current confusions of what early flowering plants look like. Expanded sampling would provide more details in understanding the mitogenomic evolution of early angiosperms. Here we report the complete mitochondrial genome of water lily Nymphaea colorata from Nymphaeales, one of the three orders of the earliest angiosperms.

RESULTS: Assembly of data from Pac-Bio long-read sequencing yielded a circular mitochondria chromosome of 617,195 bp with an average depth of 601×. The genome encoded 41 protein coding genes, 20 tRNA and three rRNA genes with 25 group II introns disrupting 10 protein coding genes. Nearly half of the genome is composed of repeated sequences, which contributed substantially to the intron size expansion, making the gross intron length of the Nymphaea mitochondrial genome one of the longest among angiosperms, including an 11.4-Kb intron in cox2, which is the longest organellar intron reported to date in plants. Nevertheless, repeat mediated homologous recombination is unexpectedly low in Nymphaea evidenced by 74 recombined reads detected from ten recombinationally active repeat pairs among 886,982 repeat pairs examined. Extensive gene order changes were detected in the three early angiosperm mitogenomes, i.e. 38 or 44 events of inversions and translocations are needed to reconcile the mitogenome of Nymphaea with Amborella or Liriodendron, respectively. In contrast to Amborella with six genome equivalents of foreign mitochondrial DNA, not a single horizontal gene transfer event was observed in the Nymphaea mitogenome.

CONCLUSIONS: The Nymphaea mitogenome resembles the other available early angiosperm mitogenomes by a similarly rich 64-coding gene set, and many conserved gene clusters, whereas stands out by its highly repetitive nature and resultant remarkable intron expansions. The low recombination level in Nymphaea provides evidence for the predominant master conformation in vivo with a highly substoichiometric set of rearranged molecules.}, } @article {pmid30109028, year = {2018}, author = {Wideman, JG and Balacco, DL and Fieblinger, T and Richards, TA}, title = {PDZD8 is not the 'functional ortholog' of Mmm1, it is a paralog.}, journal = {F1000Research}, volume = {7}, number = {}, pages = {1088}, pmid = {30109028}, issn = {2046-1402}, mesh = {Animals ; Humans ; Mitochondrial Proteins/*genetics ; *Phylogeny ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/*genetics ; }, abstract = {Authors of a recent paper demonstrate that, like ERMES (ER-mitochondria encounter structure) in fungal cells, PDZD8 (PDZ domain containing 8) tethers mitochondria to the ER in mammalian cells. However, identifying PDZD8 as a "functional ortholog" of yeast Mmm1 (maintenance of mitochondrial morphology protein 1) is at odds with the phylogenetic data. PDZD8 and Mmm1 are paralogs, not orthologs, which affects the interpretation of the data with respect to the evolution of ER-mitochondria tethering. Our phylogenetic analyses show that PDZD8 co-occurs with ERMES components in lineages closely related to animals solidifying its identity as a paralog of Mmm1. Additionally, we identify two related paralogs, one specific to flagellated fungi, and one present only in unicellular relatives of animals. These results point to a complex evolutionary history of ER-mitochondria tethering involving multiple gene gains and losses in the lineage leading to animals and fungi.}, } @article {pmid30110634, year = {2018}, author = {Vazquez, JM and Sulak, M and Chigurupati, S and Lynch, VJ}, title = {A Zombie LIF Gene in Elephants Is Upregulated by TP53 to Induce Apoptosis in Response to DNA Damage.}, journal = {Cell reports}, volume = {24}, number = {7}, pages = {1765-1776}, doi = {10.1016/j.celrep.2018.07.042}, pmid = {30110634}, issn = {2211-1247}, mesh = {Animals ; Apoptosis/genetics ; Biological Evolution ; Body Size ; DNA Damage ; Elephants/*genetics/metabolism ; *Gene Dosage ; Gene Duplication ; Gene Expression Regulation ; Humans ; Mitochondria/genetics/metabolism ; Neoplasms/prevention & control ; Phylogeny ; Proboscidea Mammal/classification/genetics ; Protein Isoforms/genetics/metabolism ; Pseudogenes ; Receptors, OSM-LIF/*genetics/metabolism ; Response Elements ; Transcription, Genetic ; Tumor Suppressor Protein p53/*genetics/metabolism ; bcl-2 Homologous Antagonist-Killer Protein/*genetics/metabolism ; bcl-2-Associated X Protein/*genetics/metabolism ; }, abstract = {Large-bodied organisms have more cells that can potentially turn cancerous than small-bodied organisms, imposing an increased risk of developing cancer. This expectation predicts a positive correlation between body size and cancer risk; however, there is no correlation between body size and cancer risk across species ("Peto's paradox"). Here, we show that elephants and their extinct relatives (proboscideans) may have resolved Peto's paradox in part through refunctionalizing a leukemia inhibitory factor pseudogene (LIF6) with pro-apoptotic functions. LIF6 is transcriptionally upregulated by TP53 in response to DNA damage and translocates to the mitochondria where it induces apoptosis. Phylogenetic analyses of living and extinct proboscidean LIF6 genes indicates that its TP53 response element evolved coincident with the evolution of large body sizes in the proboscidean stem lineage. These results suggest that refunctionalizing of a pro-apoptotic LIF pseudogene may have been permissive (although not sufficient) for the evolution of large body sizes in proboscideans.}, } @article {pmid30114187, year = {2018}, author = {Weiss, MC and Preiner, M and Xavier, JC and Zimorski, V and Martin, WF}, title = {The last universal common ancestor between ancient Earth chemistry and the onset of genetics.}, journal = {PLoS genetics}, volume = {14}, number = {8}, pages = {e1007518}, pmid = {30114187}, issn = {1553-7404}, mesh = {Archaea/genetics ; Bacteria/genetics ; Eukaryota/genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal ; Genetic Code ; Genome ; Mitochondria/genetics ; Nucleic Acid Conformation ; Origin of Life ; *Phylogeny ; Prokaryotic Cells ; }, abstract = {All known life forms trace back to a last universal common ancestor (LUCA) that witnessed the onset of Darwinian evolution. One can ask questions about LUCA in various ways, the most common way being to look for traits that are common to all cells, like ribosomes or the genetic code. With the availability of genomes, we can, however, also ask what genes are ancient by virtue of their phylogeny rather than by virtue of being universal. That approach, undertaken recently, leads to a different view of LUCA than we have had in the past, one that fits well with the harsh geochemical setting of early Earth and resembles the biology of prokaryotes that today inhabit the Earth's crust.}, } @article {pmid30114217, year = {2018}, author = {Shi, Y and Liu, Y and Zhang, S and Zou, R and Tang, J and Mu, W and Peng, Y and Dong, S}, title = {Assembly and comparative analysis of the complete mitochondrial genome sequence of Sophora japonica 'JinhuaiJ2'.}, journal = {PloS one}, volume = {13}, number = {8}, pages = {e0202485}, pmid = {30114217}, issn = {1932-6203}, mesh = {Base Composition ; DNA, Mitochondrial/genetics ; DNA, Plant/genetics ; Genes, Plant ; *Genome, Mitochondrial ; Homologous Recombination ; Introns ; Mitochondria/genetics ; Phylogeny ; Plant Proteins/genetics ; RNA, Plant/genetics ; RNA, Ribosomal/genetics ; RNA, Transfer/genetics ; Sequence Analysis, DNA ; Sophora/*genetics ; Whole Genome Sequencing ; }, abstract = {Sophora japonica L. (Faboideae, Leguminosae) is an important traditional Chinese herb with a long history of cultivation. Its flower buds and fruits contain abundant flavonoids, and therefore, the plants are cultivated for the industrial extraction of rutin. Here, we determined the complete nucleotide sequence of the mitochondrial genome of S. japonica 'JinhuaiJ2', the most widely planted variety in Guangxi region of China. The total length of the mtDNA sequence is 484,916 bp, with a GC content of 45.4%. Sophora japonica mtDNA harbors 32 known protein-coding genes, 17 tRNA genes, and three rRNA genes with 17 cis-spliced and five trans-spliced introns disrupting eight protein-coding genes. The gene coding and intron regions, and intergenic spacers account for 7.5%, 5.8% and 86.7% of the genome, respectively. The gene profile of S. japonica mitogenome differs from that of the other Faboideae species by only one or two gene gains or losses. Four of the 17 cis-spliced introns showed distinct length variations in the Faboideae, which could be attributed to the homologous recombination of the short repeats measuring a few bases located precisely at the edges of the putative deletions. This reflects the importance of small repeats in the sequence evolution in Faboideae mitogenomes. Repeated sequences of S. japonica mitogenome are mainly composed of small repeats, with only 20 medium-sized repeats, and one large repeat, adding up to 4% of its mitogenome length. Among the 25 pseudogene fragments detected in the intergenic spacer regions, the two largest ones and their corresponding functional gene copies located in two different sets of medium-sized repeats, point to their origins from homologous recombinations. As we further observed the recombined reads associated with the longest repeats of 2,160 bp with the PacBio long read data set of just 15 × in depth, repeat mediated homologous recombinations may play important role in the mitogenomic evolution of S. japonica. Our study provides insightful knowledge to the genetic background of this important herb species and the mitogenomic evolution in the Faboideae species.}, } @article {pmid30117257, year = {2018}, author = {Wang, L and Zhang, S and Li, JH and Zhang, YJ}, title = {Mitochondrial genome, comparative analysis and evolutionary insights into the entomopathogenic fungus Hirsutella thompsonii.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3393-3405}, doi = {10.1111/1462-2920.14379}, pmid = {30117257}, issn = {1462-2920}, support = {201601D011065//Natural Science Foundation of Shanxi Province/International ; }, mesh = {Acari/*microbiology ; Animals ; Evolution, Molecular ; Fungal Proteins/genetics ; Genome, Fungal ; *Genome, Mitochondrial ; Hypocreales/classification/*genetics/isolation & purification ; Introns ; Mitochondria/genetics ; Open Reading Frames ; Phylogeny ; }, abstract = {Nuclear genomes of two isolates of Hirsutella thompsonii, a pathogen causing epizootics among mites, have been reported; in contrast, its mitochondrial genome (mitogenome) has remained unknown, limiting our understanding of its evolution. Herein, we annotated the first complete mitogenome of H. thompsonii, which encoded all standard fungal mitochondrial genes plus three free-standing ORFs. Transcriptional analyses validated the expression of most conserved genes and revealed some interesting transcription patterns of mitochondrial genes. Phylogenetic analyses confirmed its placement in Ophiocordycipitaceae. Comparison of five different isolates originally collected from different locations revealed mitogenome size variations (60.3-66.4 kb) mainly due to different numbers of introns. A total of 15 intron loci were identified, with 11 existing in all 5 isolates and 4 showing presence/absence dynamics. These introns were most likely obtained through horizontal transfer from other fungal organisms. Those common introns might have been in H. thompsonii mitogenomes since the divergence of the fungus from its putative sister species H. minnesotensis, whereas those dynamic introns might have experienced 1-2 gain or loss events. We also detected evidence of degeneration for some introns. Overall, our study shed new insights into the mitochondrial evolution of the acaropathogenic fungus H. thompsonii.}, } @article {pmid30121730, year = {2019}, author = {Radzinski, M and Reichmann, D}, title = {Variety is the spice of life: how to explore a redox-dependent heterogeneity in genomically identical cellular populations.}, journal = {Current genetics}, volume = {65}, number = {1}, pages = {301-306}, pmid = {30121730}, issn = {1432-0983}, support = {1765/13//Israel Science Foundation/ ; 1649/16//legacy Heritage Biomedical Science Partnership/ ; CDA00064/2014//Human Frontier Science Program/ ; 2015056//United States - Israel Binational Science Foundation/ ; }, mesh = {Animals ; Cell Separation/methods ; Cellular Microenvironment/*genetics ; Flow Cytometry/methods ; *Genetic Heterogeneity ; Genomics/*methods ; Green Fluorescent Proteins/genetics/metabolism ; Humans ; Oxidation-Reduction ; Proteomics/*methods ; Saccharomyces cerevisiae/cytology/genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; }, abstract = {Cellular heterogeneity is a widespread phenomenon, existing across organisms and serving a crucial role in evolution and cell survival. Genetically identical cells may as a result present in a variety of forms with different gene and protein expressions, as well as oxidation level. As a result, a wide range of methodologies and techniques for dissecting different types of genetic, proteomic, and phenotypic heterogeneous traits have emerged in recent years in an effort to better understand how diversity exists within a single population and its effects therein. A key area of interest seeks to establish the ways in which cellular heterogeneity and aging processes interact with each other. Here, we discuss recent developments in defining cellular heterogeneity, specifically focusing on redox-dependent heterogeneity, its characterization, quantification, and behavior. We further expand on potential applications of a cell sorting-based methodology for distinguishing between cells harboring different redox statuses. As an example, we use organelle-specific fluorescence protein-based probes to examine the crosstalk between cytosol and mitochondria in a yeast strain lacking glutathione reductase. Together, these may have wide-reaching implications for future research into redox-associated factors, as well as mechanisms of redox-dependent heterogeneity and its influence on organelles and the cell at large.}, } @article {pmid30127539, year = {2018}, author = {Betts, HC and Puttick, MN and Clark, JW and Williams, TA and Donoghue, PCJ and Pisani, D}, title = {Integrated genomic and fossil evidence illuminates life's early evolution and eukaryote origin.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1556-1562}, pmid = {30127539}, issn = {2397-334X}, support = {BB/N000919/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Archaea/*genetics ; Bacteria/*genetics ; *Biological Evolution ; Eukaryota/*genetics ; *Fossils ; *Genome ; }, abstract = {Establishing a unified timescale for the early evolution of Earth and life is challenging and mired in controversy because of the paucity of fossil evidence, the difficulty of interpreting it and dispute over the deepest branching relationships in the tree of life. Surprisingly, it remains perhaps the only episode in the history of life where literal interpretations of the fossil record hold sway, revised with every new discovery and reinterpretation. We derive a timescale of life, combining a reappraisal of the fossil material with new molecular clock analyses. We find the last universal common ancestor of cellular life to have predated the end of late heavy bombardment (>3.9 billion years ago (Ga)). The crown clades of the two primary divisions of life, Eubacteria and Archaebacteria, emerged much later (<3.4 Ga), relegating the oldest fossil evidence for life to their stem lineages. The Great Oxidation Event significantly predates the origin of modern Cyanobacteria, indicating that oxygenic photosynthesis evolved within the cyanobacterial stem lineage. Modern eukaryotes do not constitute a primary lineage of life and emerged late in Earth's history (<1.84 Ga), falsifying the hypothesis that the Great Oxidation Event facilitated their radiation. The symbiotic origin of mitochondria at 2.053-1.21 Ga reflects a late origin of the total-group Alphaproteobacteria to which the free living ancestor of mitochondria belonged.}, } @article {pmid30137656, year = {2018}, author = {Kagda, MS and Vu, AL and Ah-Fong, AMV and Judelson, HS}, title = {Phosphagen kinase function in flagellated spores of the oomycete Phytophthora infestans integrates transcriptional regulation, metabolic dynamics and protein retargeting.}, journal = {Molecular microbiology}, volume = {110}, number = {2}, pages = {296-308}, doi = {10.1111/mmi.14108}, pmid = {30137656}, issn = {1365-2958}, mesh = {Adenosine Triphosphate/metabolism ; Animals ; Cytoplasm/enzymology ; Flagella/*enzymology ; Gene Expression Regulation/*physiology ; Solanum lycopersicum/genetics/parasitology ; Mitochondria/metabolism ; Phosphotransferases/genetics/*metabolism ; Phytophthora infestans/*enzymology/genetics ; Sporangia/enzymology ; Spores/*enzymology ; Taurine/analogs & derivatives/metabolism ; }, abstract = {Flagellated spores play important roles in the infection of plants and animals by many eukaryotic microbes. The oomycete Phytophthora infestans, which causes potato blight, expresses two phosphagen kinases (PKs). These enzymes store energy in taurocyamine, and are hypothesized to resolve spatial and temporal imbalances between rates of ATP creation and use in zoospores. A dimeric PK is found at low levels in vegetative mycelia, but high levels in ungerminated sporangia and zoospores. In contrast, a monomeric PK protein is at similar levels in all tissues, although is transcribed primarily in mycelia. Subcellular localization studies indicate that the monomeric PK is mitochondrial. In contrast, the dimeric PK is cytoplasmic in mycelia and sporangia but is retargeted to flagellar axonemes during zoosporogenesis. This supports a model in which PKs shuttle energy from mitochondria to and through flagella. Metabolite analysis indicates that deployment of the flagellar PK is coordinated with a large increase in taurocyamine, synthesized by sporulation-induced enzymes that were lost during the evolution of zoospore-lacking oomycetes. Thus, PK function is enabled by coordination of the transcriptional, metabolic and protein targeting machinery during the life cycle. Since plants lack PKs, the enzymes may be useful targets for inhibitors of oomycete plant pathogens.}, } @article {pmid30138782, year = {2018}, author = {Treitli, SC and Kotyk, M and Yubuki, N and Jirounková, E and Vlasáková, J and Smejkalová, P and Šípek, P and Čepička, I and Hampl, V}, title = {Molecular and Morphological Diversity of the Oxymonad Genera Monocercomonoides and Blattamonas gen. nov.}, journal = {Protist}, volume = {169}, number = {5}, pages = {744-783}, doi = {10.1016/j.protis.2018.06.005}, pmid = {30138782}, issn = {1618-0941}, mesh = {Genetic Variation ; Microscopy, Electron ; Oxymonadida/*genetics/*growth & development/ultrastructure ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Oxymonads are a group of flagellates living as gut symbionts of insects or vertebrates. They have several unique features, one of them being the absence of mitochondria. Diversity of this group is seriously understudied, which is particularly true for small species from the family Polymastigidae. We isolated 34 strains of oxymonads with Polymastigidae-like morphology from 24 host species and unused cesspits and sequenced the SSU rRNA gene. Our strains formed two clades in the phylogenetic tree with Streblomastix strix branching between them. This topology was also supported by a three-gene phylogenetic analysis. Despite considerable genetic differences between the clades, light and electron microscopy revealed only subtle differences. The larger clade is considered genus Monocercomonoides and the isolates belonging here were classified into three new species (including the first potentially free-living species), two previously described species, and three unclassified lineages. The smaller clade, here described as Blattamonas gen. nov., consists of three newly described species. Concomitantly with the description of Blattamonas, we elevate the Monocercomonoides subgenus Brachymonas to the genus level. Our study shows that, despite their conserved morphology, the molecular diversity of Polymastigidae-like oxymonads is broad and represents a substantial part of the diversity of oxymonads.}, } @article {pmid30139961, year = {2018}, author = {Liu, J and Kim, SY and Shin, S and Jung, SH and Yim, SH and Lee, JY and Lee, SH and Chung, YJ}, title = {Overexpression of TFF3 is involved in prostate carcinogenesis via blocking mitochondria-mediated apoptosis.}, journal = {Experimental & molecular medicine}, volume = {50}, number = {8}, pages = {1-11}, pmid = {30139961}, issn = {2092-6413}, mesh = {Annexin A5/metabolism ; *Apoptosis ; Carcinogenesis/metabolism/pathology ; Caspase 3/metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cytosol/metabolism ; Gene Silencing ; Humans ; Male ; Mitochondria/*metabolism ; Models, Biological ; Prostatic Neoplasms/*metabolism/*pathology ; Trefoil Factor-3/*metabolism ; }, abstract = {The overexpression of trefoil factor family 3 (TFF3) is observed in a variety of cancers, including prostate cancer (PCa), and its potential role in carcinogenesis, such as activating the PI3K/AKT pathway, is suggested. However, its role and its related mechanisms in prostate tumorigenesis remain unknown. To elucidate the role of TFF3 overexpression in PCa, we silenced TFF3 in two PCa cell lines that overexpressed TFF3 and explored the molecular mechanism behind its antiapoptotic role. We also examined TFF3 expression in 108 Korean PCa specimens and 106 normal prostate tissues by immunohistochemistry (IHC) analysis. The mean TFF3 IHC score in the tumor tissues was significantly higher than that in the normal tissues (4.702 vs. 0.311, P = 2.52 × 10[-24]). TFF3-silenced cells showed suppressed tumor cell growth and migration. TFF3 silencing decreased BCL2 and increased BAX expression. The translocation of BAX to the mitochondria was also confirmed. After TFF3 silencing, the expression of the mitochondrial proapoptotic proteins, cytochrome C and Smac/DIABLO, was elevated, and these proteins were released from the mitochondria to the cytosol. Downstream mediators of mitochondrial apoptosis, including cleaved caspase-3, caspase-9, and PARP, were also elevated. Accordingly, the proportion of apoptotic cells was significantly higher among TFF3-silenced cells. There was no difference in extrinsic apoptosis-related molecules after TFF3 silencing. All the results support that TFF3 silencing induces the downstream signaling pathway of mitochondria-mediated apoptosis. This study provides a better understanding of the mechanism of prostate tumorigenesis, suggesting TFF3 as a potential biomarker and therapeutic target of PCa.}, } @article {pmid30141728, year = {2018}, author = {Boratyński, JS and Szafrańska, PA}, title = {Does Basal Metabolism Set the Limit for Metabolic Downregulation during Torpor?.}, journal = {Physiological and biochemical zoology : PBZ}, volume = {91}, number = {5}, pages = {1057-1067}, doi = {10.1086/699917}, pmid = {30141728}, issn = {1537-5293}, mesh = {Animals ; Basal Metabolism/*physiology ; Body Mass Index ; Down-Regulation ; Mammals/*physiology ; Models, Biological ; Torpor/*physiology ; }, abstract = {The evolution of endothermic thermoregulation is rooted in the processes involving high metabolism, which allows the maintenance of high and stable body temperatures (Tb). In turn, selection for high endothermic metabolism correlates with increased size of metabolically active organs and thus with high basal metabolic rate (BMR). Endothermic animals are characterized by an MR several times that of similar-sized ectotherms. However, many small mammals are temporally heterothermic and are able to temporally decrease Tb and MR by entering daily torpor or hibernation. Both BMR and minimum MR during torpor (TMRmin) likely result from oxidative respiration in mitochondria of the same tissues. It should be expected that these two MRs are positively correlated, suggesting that the evolution of endothermy and higher BMR set the limit for the ability to reduce MR while entering torpor. Using published data for 96 mammal species, we tested the hypothesis that, among heterothermic mammals, the processes leading to the evolution of higher BMR limit the ability to downregulate metabolism during torpor. We found that body mass (mb)-adjusted BMR was positively correlated with mb- and Tb-adjusted TMRmin, in a phylogenetically corrected analysis. Phylogenetic path modeling indicated that the mechanisms underlying the evolutionary increase of BMR in endotherms most likely constrain their ability to reduce MR during torpor. Given that heterothermy is considered an ancestral state in mammals, these results suggest an increase in BMR during the evolution of endothermy in homeothermic animals, which leads to the loss of their ability to enter torpor.}, } @article {pmid30143614, year = {2018}, author = {Quintana-Cabrera, R and Quirin, C and Glytsou, C and Corrado, M and Urbani, A and Pellattiero, A and Calvo, E and Vázquez, J and Enríquez, JA and Gerle, C and Soriano, ME and Bernardi, P and Scorrano, L}, title = {The cristae modulator Optic atrophy 1 requires mitochondrial ATP synthase oligomers to safeguard mitochondrial function.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {3399}, pmid = {30143614}, issn = {2041-1723}, support = {IJCI-2015-26225//Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)/International ; JPMJCR13M4//JST | Core Research for Evolutional Science and Technology (CREST)/International ; GGP15091//Fondazione Telethon (Telethon Foundation)/International ; GGP14187//Fondazione Telethon (Telethon Foundation)/International ; FP7-282280//EC | European Research Council (ERC)/International ; IG-15748//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/International ; }, mesh = {Animals ; Antimycin A/pharmacology ; Cell Survival/drug effects ; Electrophoresis, Polyacrylamide Gel ; GTP Phosphohydrolases/genetics/*metabolism ; Immunoblotting ; Immunoprecipitation ; Mice ; Microscopy, Electron, Transmission ; Mitochondria/*metabolism ; Mitochondrial Proteins/genetics/metabolism ; Mitochondrial Proton-Translocating ATPases/genetics/*metabolism ; }, abstract = {It is unclear how the mitochondrial fusion protein Optic atrophy 1 (OPA1), which inhibits cristae remodeling, protects from mitochondrial dysfunction. Here we identify the mitochondrial F1Fo-ATP synthase as the effector of OPA1 in mitochondrial protection. In OPA1 overexpressing cells, the loss of proton electrochemical gradient caused by respiratory chain complex III inhibition is blunted and this protection is abolished by the ATP synthase inhibitor oligomycin. Mechanistically, OPA1 and ATP synthase can interact, but recombinant OPA1 fails to promote oligomerization of purified ATP synthase reconstituted in liposomes, suggesting that OPA1 favors ATP synthase oligomerization and reversal activity by modulating cristae shape. When ATP synthase oligomers are genetically destabilized by silencing the key dimerization subunit e, OPA1 is no longer able to preserve mitochondrial function and cell viability upon complex III inhibition. Thus, OPA1 protects mitochondria from respiratory chain inhibition by stabilizing cristae shape and favoring ATP synthase oligomerization.}, } @article {pmid30144423, year = {2018}, author = {Pustylnikov, S and Costabile, F and Beghi, S and Facciabene, A}, title = {Targeting mitochondria in cancer: current concepts and immunotherapy approaches.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {202}, number = {}, pages = {35-51}, pmid = {30144423}, issn = {1878-1810}, support = {R01 CA206012/CA/NCI NIH HHS/United States ; R01 CA219871/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; DNA, Mitochondrial/genetics ; Humans ; *Immunotherapy ; Mitochondria/*metabolism ; Mitochondrial Dynamics ; Neoplasms/*immunology/*therapy ; T-Lymphocytes/metabolism ; }, abstract = {An essential advantage during eukaryotic cell evolution was the acquisition of a network of mitochondria as a source of energy for cell metabolism and contrary to conventional wisdom, functional mitochondria are essential for the cancer cell. Multiple aspects of mitochondrial biology beyond bioenergetics support transformation including mitochondrial biogenesis, fission and fusion dynamics, cell death susceptibility, oxidative stress regulation, metabolism, and signaling. In cancer, the metabolism of cells is reprogrammed for energy generation from oxidative phosphorylation to aerobic glycolysis and impacts cancer mitochondrial function. Furthermore cancer cells can also modulate energy metabolism within the cancer microenvironment including immune cells and induce "metabolic anergy" of antitumor immune response. Classical approaches targeting the mitochondria of cancer cells usually aim at inducing changing energy metabolism or directly affecting functions of mitochondrial antiapoptotic proteins but most of such approaches miss the required specificity of action and carry important side effects. Several types of cancers harbor somatic mitochondrial DNA mutations and specific immune response to mutated mitochondrial proteins has been observed. An attractive alternative way to target the mitochondria in cancer cells is the induction of an adaptive immune response against mutated mitochondrial proteins. Here, we review the cancer cell-intrinsic and cell-extrinsic mechanisms through which mitochondria influence all steps of oncogenesis, with a focus on the therapeutic potential of targeting mitochondrial DNA mutations or Tumor Associated Mitochondria Antigens using the immune system.}, } @article {pmid30154842, year = {2018}, author = {Berzabá-Evoli, E and Zazueta, C and Cruz Hernández, JH and Gómez-Crisóstomo, NP and Juárez-Rojop, IE and De la Cruz-Hernández, EN and Martínez-Abundis, E}, title = {Leptin Modifies the Rat Heart Performance Associated with Mitochondrial Dysfunction Independently of Its Prohypertrophic Effects.}, journal = {International journal of endocrinology}, volume = {2018}, number = {}, pages = {6081415}, pmid = {30154842}, issn = {1687-8337}, abstract = {BACKGROUND: Functional receptors for leptin were described on the surface of cardiomyocytes, and there was a prohypertrophic effect with high concentrations of the cytokine. Therefore, leptin could be a link between obesity and the prevalence of cardiovascular diseases. On the other hand, a deleterious effect of leptin on mitochondrial performance was described, which was also associated with the evolution of cardiac hypertrophy to heart failure. The goal of our study was to analyze the effect of the exposure of rat hearts to a high concentration of leptin on cardiac and mitochondrial function.

METHODS: Rat hearts were perfused continuously with or without 3.1 nM leptin for 1, 2, 3, or 4 hours. Homogenates and mitochondria were prepared by centrifugation and analyzed for cardiac actin, STAT3, and pSTAT3 by Western blotting, as well as for mitochondrial oxidative phosphorylation, membrane potential, swelling, calcium transport, and content of oxidized lipids.

RESULTS: In our results, leptin induced an increased rate-pressure product as a result of increased heart rate and contraction force, as well oxidative stress. In addition, mitochondrial dysfunction expressed as a loss of membrane potential, decreased ability for calcium transport and retention, faster swelling, and less respiratory control was observed.

CONCLUSIONS: Our results support the role of leptin as a deleterious factor for cardiac function and indicates that mitochondrial dysfunction could be a trigger for cardiac hypertrophy and failure.}, } @article {pmid30158483, year = {2018}, author = {Kozieł, E and Otulak-Kozieł, K and Bujarski, JJ}, title = {Ultrastructural Analysis of Prune DwarfVirus Intercellular Transport and Pathogenesis.}, journal = {International journal of molecular sciences}, volume = {19}, number = {9}, pages = {}, pmid = {30158483}, issn = {1422-0067}, support = {505-10-011100-Q00190-99//Warsaw Univeristy of Life Sciences WULS-SGGW/ ; }, mesh = {Alfalfa mosaic virus/genetics/*pathogenicity/*ultrastructure ; Biological Transport/genetics/physiology ; Phylogeny ; RNA, Viral ; Viral Proteins/metabolism/ultrastructure ; }, abstract = {Prune dwarf virus (PDV) is an important viral pathogen of plum, sweet cherry, peach, and many herbaceous test plants. Although PDV has been intensively investigated, mainly in the context of phylogenetic relationship of its genes and proteins, many gaps exist in our knowledge about the mechanism of intercellular transport of this virus. The aim of this work was to investigate alterations in cellular organelles and the cell-to-cell transport of PDV in Cucumis sativus cv. Polan at ultrastructural level. To analyze the role of viral proteins in local transport, double-immunogold assays were applied to localize PDV coat protein (CP) and movement protein (MP). We observe structural changes in chloroplasts, mitochondria, and cellular membranes. We prove that PDV is transported as viral particles via MP-generated tubular structures through plasmodesmata. Moreover, the computer-run 3D modeling reveals structural resemblances between MPs of PDV and of Alfalfa mosaic virus (AMV), implying similarities of transport mechanisms for both viruses.}, } @article {pmid30160146, year = {2018}, author = {Goh, CJ and Park, D and Kim, H and Sebastiani, F and Hahn, Y}, title = {Novel Divavirus (the family Betaflexiviridae) and Mitovirus (the family Narnaviridae) species identified in basil (Ocimum basilicum).}, journal = {Acta virologica}, volume = {62}, number = {3}, pages = {304-309}, doi = {10.4149/av_2018_224}, pmid = {30160146}, issn = {0001-723X}, mesh = {Flexiviridae/classification/genetics/*isolation & purification/physiology ; Genome, Viral ; Ocimum basilicum/*virology ; Phylogeny ; Plant Diseases/*virology ; RNA-Dependent RNA Polymerase/genetics ; Viral Proteins/genetics ; }, abstract = {Transcriptome data obtained from a plant sample often contain a large number of reads that are derived from associated RNA virus genomes that were co-isolated during RNA preparation. These virus-derived reads can be assembled into a novel plant RNA genome sequence. Here, a basil (Ocimum basilicum) transcriptome dataset was analyzed to identify two new RNA viruses, which were named Ocimum basilicum RNA virus 1 (ObRV1) and Ocimum basilicum RNA virus 2 (ObRV2). A phylogenetic analysis of the ObRV1 RNA-dependent RNA polymerase (RdRp) motif indicated that ObRV1 is a novel species of the genus Divavirus of the family Betaflexiviridae. ObRV1 is the fourth divavirus species to be identified. The ObRV2 RdRp motif showed sequence similarity to viruses of the genus Mitovirus of the family Narnaviridae, which infect fungal mitochondria. Although most of the known mitoviruses do not produce a functional RdRp using the plant mitochondrial genetic code, the ObRV2 encodes a full-length RdRp using both the fungal and plant mitochondrial genetic codes.}, } @article {pmid30165810, year = {2018}, author = {Galen, SC and Nunes, R and Sweet, PR and Perkins, SL}, title = {Integrating coalescent species delimitation with analysis of host specificity reveals extensive cryptic diversity despite minimal mitochondrial divergence in the malaria parasite genus Leucocytozoon.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {128}, pmid = {30165810}, issn = {1471-2148}, support = {1358465//National Science Foundation/International ; }, mesh = {Animals ; Cytochromes b/genetics ; DNA, Mitochondrial/genetics ; Genetic Loci ; *Genetic Variation ; Haemosporida/*genetics ; Haplotypes/genetics ; *Host Specificity ; Malaria/*parasitology ; Mitochondria/*genetics ; Parasites/*genetics ; Phylogeny ; Songbirds/parasitology ; Species Specificity ; }, abstract = {BACKGROUND: Coalescent methods that use multi-locus sequence data are powerful tools for identifying putatively reproductively isolated lineages, though this approach has rarely been used for the study of microbial groups that are likely to harbor many unrecognized species. Among microbial symbionts, integrating genetic species delimitation methods with trait data that could indicate reproductive isolation, such as host specificity data, has rarely been used despite its potential to inform species limits. Here we test the ability of an integrative approach combining genetic and host specificity data to delimit species within the avian malaria parasite genus Leucocytozoon in central Alaska.

RESULTS: We sequenced seven nuclear loci for 69 Leucocytozoon samples and used multiple species delimitation methods (GMYC and BPP models), tested for differences in host infection patterns among putative species based on 406 individual infections, and characterized parasite morphology. We found that cryptic morphology has masked a highly diverse Leucocytozoon assemblage, with most species delimitation methods recovering support for at least 21 separate species that occur sympatrically and have divergent host infection patterns. Reproductive isolation among putative species appears to have evolved despite low mtDNA divergence, and in one instance two Leucocytozoon cytb haplotypes that differed by a single base pair (~ 0.2% divergence) were supported as separate species. However, there was no consistent association between mtDNA divergence and species limits. Among cytb haplotypes that differed by one to three base pairs we observed idiosyncratic patterns of nuclear and ecological divergence, with cytb haplotype pairs found to be either conspecific, reproductively isolated with no divergence in host specificity, or reproductively isolated with divergent patterns of host specialization.

CONCLUSION: Integrating multi-locus genetic species delimitation methods and non-traditional ecological data types such as host specificity provide a novel view of the diversity of avian malaria parasites that has been missed previously using morphology and mtDNA barcodes. Species delimitation methods show that Leucocytozoon is highly species-rich in Alaska, and the genus is likely to harbor extraordinary species-level diversity worldwide. Integrating genetic and ecological data will be an important approach for understanding the diversity and evolutionary history of microbial symbionts moving forward.}, } @article {pmid30166340, year = {2018}, author = {Valach, M and Léveillé-Kunst, A and Gray, MW and Burger, G}, title = {Respiratory chain Complex I of unparalleled divergence in diplonemids.}, journal = {The Journal of biological chemistry}, volume = {293}, number = {41}, pages = {16043-16056}, pmid = {30166340}, issn = {1083-351X}, support = {MOP-79309//CIHR/Canada ; }, mesh = {DNA, Mitochondrial/*metabolism ; Electron Transport ; Electron Transport Complex I/*metabolism ; Euglenozoa/*genetics/*metabolism ; Mass Spectrometry ; Mitochondria/metabolism ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/metabolism ; NADH Dehydrogenase/metabolism ; Phenylalanine/chemistry ; Phylogeny ; Protons ; RNA Editing ; RNA Splicing ; Ubiquinone/chemistry ; }, abstract = {Mitochondrial genes of Euglenozoa (Kinetoplastida, Diplonemea, and Euglenida) are notorious for being barely recognizable, raising the question of whether such divergent genes actually code for functional proteins. Here we demonstrate the translation and identify the function of five previously unassigned y genes encoded by mitochondrial DNA (mtDNA) of diplonemids. As is the rule in diplonemid mitochondria, y genes are fragmented, with gene pieces transcribed separately and then trans-spliced to form contiguous mRNAs. Further, y transcripts undergo massive RNA editing, including uridine insertions that generate up to 16-residue-long phenylalanine tracts, a feature otherwise absent from conserved mitochondrial proteins. By protein sequence analyses, MS, and enzymatic assays in Diplonema papillatum, we show that these y genes encode the subunits Nad2, -3, -4L, -6, and -9 of the respiratory chain Complex I (CI; NADH:ubiquinone oxidoreductase). The few conserved residues of these proteins are essentially those involved in proton pumping across the inner mitochondrial membrane and in coupling ubiquinone reduction to proton pumping (Nad2, -3, -4L, and -6) and in interactions with subunits containing electron-transporting Fe-S clusters (Nad9). Thus, in diplonemids, 10 CI subunits are mtDNA-encoded. Further, MS of D. papillatum CI allowed identification of 26 conventional and 15 putative diplonemid-specific nucleus-encoded components. Most conventional accessory subunits are well-conserved but unusually long, possibly compensating for the streamlined mtDNA-encoded components and for missing, otherwise widely distributed, conventional subunits. Finally, D. papillatum CI predominantly exists as a supercomplex I:III:IV that is exceptionally stable, making this protist an organism of choice for structural studies.}, } @article {pmid30172009, year = {2018}, author = {Pavón-Vázquez, CJ and García-Vázquez, UO and Bryson, RW and Feria-Ortiz, M and Manríquez-Morán, NL and de Oca, AN}, title = {Integrative species delimitation in practice: Revealing cryptic lineages within the short-nosed skink Plestiodon brevirostris (Squamata: Scincidae).}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {242-257}, doi = {10.1016/j.ympev.2018.08.020}, pmid = {30172009}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial/genetics ; Genetic Loci ; Geography ; Lizards/*classification/genetics ; Mexico ; Mitochondria/genetics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; Species Specificity ; Time Factors ; }, abstract = {Integrative taxonomy has been generally considered as a goal in systematics for more than a decade. Here, we employed environmental, molecular, and morphological data to evaluate the species boundaries within the short-nosed skink Plestiodon brevirostris from south-central Mexico, one member of the morphologically conservative P. brevirostris group. Our molecular dataset includes one mitochondrial and two nuclear loci. The mitochondrial fragment includes the full length of the gene coding for the NADH dehydrogenase subunit 1 protein, a segment of the gene coding for 16S ribosomal RNA, and flanking tRNAs. The nuclear dataset includes fragments of the genes coding for the megakaryoblastic leukemia 1 and RNA fingerprint 35 proteins. We employed phylogenetic reconstruction, analyses of population structure and morphological variation, and species delimitation methods (including the integration of the three kinds of data in a unified probabilistic framework) to evaluate species limits. Our results suggest that P. brevirostris represents four distinct species. The information provided by each kind of data allowed us to discern between alternative explanations for the observed patterns of geographic structure. Two of the newly recognized lineages are poorly differentiated morphologically but apparently differ in environmental preferences and are allopatric. Additionally, one lineage is microendemic and parapatric with respect to another one. Moreover, our phylogenetic analyses suggest that other taxa within the P. brevirostris group may represent species complexes. We discuss our results in the context of integrative species delimitation.}, } @article {pmid30176236, year = {2019}, author = {Virji, AZ and Thekkiniath, J and Ma, W and Lawres, L and Knight, J and Swei, A and Roch, KL and Mamoun, CB}, title = {Insights into the evolution and drug susceptibility of Babesia duncani from the sequence of its mitochondrial and apicoplast genomes.}, journal = {International journal for parasitology}, volume = {49}, number = {2}, pages = {105-113}, pmid = {30176236}, issn = {1879-0135}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 AI097218/AI/NIAID NIH HHS/United States ; S10 OD016290/OD/NIH HHS/United States ; S10 OD018521/OD/NIH HHS/United States ; R01 GM110506/GM/NIGMS NIH HHS/United States ; R01 AI123321/AI/NIAID NIH HHS/United States ; R43 AI136118/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Babesia/*drug effects/*genetics ; *Drug Resistance ; *Evolution, Molecular ; *Genome, Mitochondrial ; *Genome, Protozoan ; Humans ; Molecular Sequence Annotation ; United States ; Whole Genome Sequencing ; }, abstract = {Babesia microti and Babesia duncani are the main causative agents of human babesiosis in the United States. While significant knowledge about B. microti has been gained over the past few years, nothing is known about B. duncani biology, pathogenesis, mode of transmission or sensitivity to currently recommended therapies. Studies in immunocompetent wild type mice and hamsters have shown that unlike B. microti, infection with B. duncani results in severe pathology and ultimately death. The parasite factors involved in B. duncani virulence remain unknown. Here we report the first known completed sequence and annotation of the apicoplast and mitochondrial genomes of B. duncani. We found that the apicoplast genome of this parasite consists of a 34 kb monocistronic circular molecule encoding functions that are important for apicoplast gene transcription as well as translation and maturation of the organelle's proteins. The mitochondrial genome of B. duncani consists of a 5.9 kb monocistronic linear molecule with two inverted repeats of 48 bp at both ends. Using the conserved cytochrome b (Cytb) and cytochrome c oxidase subunit I (coxI) proteins encoded by the mitochondrial genome, phylogenetic analysis revealed that B. duncani defines a new lineage among apicomplexan parasites distinct from B. microti, Babesia bovis, Theileria spp. and Plasmodium spp. Annotation of the apicoplast and mitochondrial genomes of B. duncani identified targets for development of effective therapies. Our studies set the stage for evaluation of the efficacy of these drugs alone or in combination against B. duncani in culture as well as in animal models.}, } @article {pmid30176793, year = {2018}, author = {Yin, M and Wang, X and Ma, X and Gießler, S and Petrusek, A and Griebel, J and Hu, W and Wolinska, J}, title = {Cytonuclear diversity and shared mitochondrial haplotypes among Daphnia galeata populations separated by seven thousand kilometres.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {130}, pmid = {30176793}, issn = {1471-2148}, support = {31670380//National Natural Science Foundation of China/International ; 16ZR1402900//Natural Science Foundation of Shanghai/International ; WO 1587/6-1//German Science Foundation/International ; }, mesh = {Alleles ; Animals ; Bayes Theorem ; Cell Nucleus/*genetics ; China ; DNA/genetics ; DNA, Mitochondrial/genetics ; Daphnia/*genetics ; Europe ; Genes, Mitochondrial ; *Genetic Variation ; Genetics, Population ; Geography ; Haplotypes/*genetics ; Microsatellite Repeats/genetics ; Mitochondria/*genetics ; Phylogeny ; Zooplankton/genetics ; }, abstract = {BACKGROUND: The zooplanktonic cladocerans Daphnia, present in a wide range of water bodies, are an important component of freshwater ecosystems. In contrast to their high dispersal capacity through diapausing eggs carried by waterfowl, Daphnia often exhibit strong population genetic differentiation. Here, to test for common patterns in the population genetic structure of a widespread Holarctic species, D. galeata, we genotyped two sets of populations collected from geographically distant areas: across 13 lakes in Eastern China and 14 lakes in Central Europe. The majority of these populations were genotyped at two types of markers: a mitochondrial gene (for 12S rRNA) and 15 nuclear microsatellite loci.

RESULTS: Mitochondrial DNA demonstrated relatively shallow divergence within D. galeata, with distinct haplotype compositions in the two study regions but one widely distributed haplotype shared between several of the Chinese as well as European populations. At microsatellite markers, clear separation was observed at both large (between China and Europe) and small (within Europe) geographical scales, as demonstrated by Factorial Correspondence Analyses, Bayesian assignment and a clustering method based on genetic distances. Genetic diversity was comparable between the sets of Chinese and European D. galeata populations for both types of markers. Interestingly, we observed a significant association between genetic distance and geographical distance for D. galeata populations in China but not in Europe.

CONCLUSIONS: Our results indicate relatively recent spread of D. galeata across wide expanses of the Palaearctic, with one mtDNA lineage of D. galeata successfully establishing over large distances. Despite a clear differentiation of Chinese and European D. galeata at a nuclear level, the pattern of genetic variation is nevertheless similar between both regions. Overall, our findings provide insights into the genetic population structure of a cladoceran species with extremely wide geographical range.}, } @article {pmid30176805, year = {2018}, author = {Matthee, CA and Engelbrecht, A and Matthee, S}, title = {Comparative phylogeography of parasitic Laelaps mites contribute new insights into the specialist-generalist variation hypothesis (SGVH).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {131}, pmid = {30176805}, issn = {1471-2148}, support = {Incentive Funding//National Research Foundation/International ; }, mesh = {Animals ; Base Sequence ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Genetic Variation ; Geography ; Haplotypes/genetics ; Host Specificity ; Mites/*classification/genetics ; Mitochondria/genetics ; *Models, Biological ; Murinae/genetics/parasitology ; Parasites/*classification/genetics ; *Phylogeography ; }, abstract = {BACKGROUND: The specialist-generalist variation hypothesis (SGVH) in parasites suggests that, due to patchiness in habitat (host availability), specialist species will show more subdivided population structure when compared to generalist species. In addition, since specialist species are more prone to local stochastic extinction events with their hosts, they will show lower levels of intraspecific genetic diversity when compared to more generalist.

RESULTS: To test the wider applicability of the SGVH we compared 337 cytochrome oxidase I mitochondrial DNA and 268 nuclear tropomyosin DNA sequenced fragments derived from two co-distributed Laelaps mite species and compared the data to 294 COI mtDNA sequences derived from the respective hosts Rhabdomys dilectus, R. bechuanae, Mastomys coucha and M. natalensis. In support of the SGVH, the generalist L. muricola was characterized by a high mtDNA haplotypic diversity of 0.97 (±0.00) and a low level of population differentiation (mtDNA Fst = 0.56, p < 0.05; nuDNA Fst = 0.33, P < 0.05) while the specialist L. giganteus was overall characterized by a lower haplotypic diversity of 0.77 (±0.03) and comparatively higher levels of population differentiation (mtDNA Fst = 0.87, P < 0.05; nuDNA Fst = 0.48, P < 0.05). When the two specialist L. giganteus lineages, which occur on two different Rhabdomys species, are respectively compared to the generalist parasite, L. muricola, the SGVH is not fully supported. One of the specialist L. giganteus species occurring on R. dilectus shows similar low levels of population differentiation (mtDNA Fst = 0.53, P < 0.05; nuDNA Fst = 0.12, P < 0.05) than that found for the generalist L. muricola. This finding can be correlated to differences in host dispersal: R. bechuanae populations are characterized by a differentiated mtDNA Fst of 0.79 (P < 0.05) while R. dilectus populations are less structured with a mtDNA Fst = 0.18 (P < 0.05).

CONCLUSIONS: These findings suggest that in ectoparasites, host specificity and the vagility of the host are both important drivers for parasite dispersal. It is proposed that the SGHV hypothesis should also incorporate reference to host dispersal since in our case only the specialist species who occur on less mobile hosts showed more subdivided population structure when compared to generalist species.}, } @article {pmid30179526, year = {2018}, author = {Haenel, GJ and Del Gaizo Moore, V}, title = {Functional Divergence of Mitochondria and Coevolution of Genomes: Cool Mitochondria in Hot Lizards.}, journal = {Physiological and biochemical zoology : PBZ}, volume = {91}, number = {5}, pages = {1068-1081}, doi = {10.1086/699918}, pmid = {30179526}, issn = {1537-5293}, mesh = {Animals ; *Biological Coevolution ; Body Temperature ; Genome ; Hot Temperature ; Lizards/*genetics/*physiology ; Mitochondria/genetics/*physiology ; }, abstract = {Mitochondria play a key role in the ecology and evolution of species through their influence on aerobic metabolism. Mitochondrial DNA (mtDNA) and nuclear genomes must interact for optimal functioning of oxidative phosphorylation to produce ATP, and breakdown of coadaptation components from each may have important evolutionary consequences for hybridization. Introgression of mitochondria in natural populations through hybridization with unidirectional backcrossing allows the testing of coadaptation of mitochondria to different nuclear backgrounds. We compared the function of mitochondria isolated from two species of Urosaurus lizards and hybrid populations. Due to past introgression, hybrids contain the nuclear genome of the "hot-adapted" species (U. graciosus) but the mtDNA of the less heat-tolerant species (U. ornatus). It was found that the function of the parental forms of mitochondria had significantly diverged with the hot-adapted species. There was significant genotype × genotype × environment interactions for mitochondrial membrane potential and genotype × genotype interactions for ATP production. Membrane potential decreased less at a higher temperature, while ATP production was higher at both temperatures in introgressed mitochondria. Oxygen consumption was lower in U. graciosus than in U. ornatus parental-type mitochondria, indicating a likely response to living in hotter environments. Respiratory control ratio values, which provide an indication of the functional quality of isolated mitochondria, were lower in introgressed mitochondria than in parental U. ornatus types, indicating a negative impact on biological function in introgressed mitochondria.}, } @article {pmid30181603, year = {2018}, author = {Bisconti, R and Porretta, D and Arduino, P and Nascetti, G and Canestrelli, D}, title = {Hybridization and extensive mitochondrial introgression among fire salamanders in peninsular Italy.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {13187}, pmid = {30181603}, issn = {2045-2322}, mesh = {Animals ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Female ; Gene Flow ; Gene Frequency ; Genetics, Population ; Genomic Imprinting ; *Hybridization, Genetic ; Italy ; Male ; Mitochondria/*genetics ; Phylogeny ; Salamandra/*genetics ; }, abstract = {Discordance between mitochondrial and nuclear patterns of population genetic structure is providing key insights into the eco-evolutionary dynamics between and within species, and their assessment is highly relevant to biodiversity monitoring practices based on DNA barcoding approaches. Here, we investigate the population genetic structure of the fire salamander Salamandra salamandra in peninsular Italy. Both mitochondrial and nuclear markers clearly identified two main population groups. However, nuclear and mitochondrial zones of geographic transition between groups were located 600 km from one another. Recent population declines in central Italy partially erased the genetic imprints of past hybridization dynamics. However, the overall pattern of genetic variation, together with morphological and fossil data, suggest that a rampant mitochondrial introgression triggered the observed mitonuclear discordance, following a post-glacial secondary contact between lineages. Our results clearly show the major role played by reticulate evolution in shaping the structure of Salamandra salamandra populations and, together with similar findings in other regions of the species' range, contribute to identify the fire salamander as a particularly intriguing case to investigate the complexity of mechanisms triggering patterns of mitonuclear discordance in animals.}, } @article {pmid30185526, year = {2018}, author = {Abbasi, F and Miyata, H and Shimada, K and Morohoshi, A and Nozawa, K and Matsumura, T and Xu, Z and Pratiwi, P and Ikawa, M}, title = {RSPH6A is required for sperm flagellum formation and male fertility in mice.}, journal = {Journal of cell science}, volume = {131}, number = {19}, pages = {}, pmid = {30185526}, issn = {1477-9137}, support = {P01 HD087157/HD/NICHD NIH HHS/United States ; R01 HD088412/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; CRISPR-Cas Systems/genetics ; Conserved Sequence ; Evolution, Molecular ; *Fertility ; Flagella/*metabolism/ultrastructure ; HEK293 Cells ; Humans ; Male ; Mice ; Mice, Mutant Strains ; Mitochondria/metabolism ; Organ Specificity ; Phenotype ; Protein Binding ; Protein Transport ; Proteins/*metabolism ; Sperm Injections, Intracytoplasmic ; Sperm Tail/metabolism ; Spermatozoa/*metabolism/ultrastructure ; Testis/metabolism ; Tubulin/metabolism ; }, abstract = {The flagellum is an evolutionarily conserved appendage used for sensing and locomotion. Its backbone is the axoneme and a component of the axoneme is the radial spoke (RS), a protein complex implicated in flagellar motility regulation. Numerous diseases occur if the axoneme is improperly formed, such as primary ciliary dyskinesia (PCD) and infertility. Radial spoke head 6 homolog A (RSPH6A) is an ortholog of Chlamydomonas RSP6 in the RS head and is evolutionarily conserved. While some RS head proteins have been linked to PCD, little is known about RSPH6A. Here, we show that mouse RSPH6A is testis-enriched and localized in the flagellum. Rsph6a knockout (KO) male mice are infertile as a result of their short immotile spermatozoa. Observation of the KO testis indicates that the axoneme can elongate but is disrupted before accessory structures are formed. Manchette removal is also impaired in the KO testis. Further, RSPH9, another radial spoke protein, disappeared in the Rsph6a KO flagella. These data indicate that RSPH6A is essential for sperm flagellar assembly and male fertility in mice.This article has an associated First Person interview with the first author of the paper.}, } @article {pmid30187255, year = {2018}, author = {Eyenga, P and Roussel, D and Morel, J and Rey, B and Romestaing, C and Gueguen-Chaignon, V and Sheu, SS and Viale, JP}, title = {Time course of liver mitochondrial function and intrinsic changes in oxidative phosphorylation in a rat model of sepsis.}, journal = {Intensive care medicine experimental}, volume = {6}, number = {1}, pages = {31}, pmid = {30187255}, issn = {2197-425X}, abstract = {BACKGROUND: Tissue ATP depletion and oxidative stress have been associated with the severe outcomes of septic shock. One of the compensatory mechanisms to alleviate the sepsis-induced mitochondrial dysfunction could be the increase in oxidative phosphorylation efficiency (ATP/O). We propose to study liver mitochondrial function and oxidative stress and the regulatory mechanism of mitochondrial oxidative phosphorylation efficiency in an animal model of sepsis.

METHODS: We induced sepsis in rats by cecal ligation and perforation (CLP). Six, 24, or 36 h following CLP, we measured liver mitochondrial respiration, cytochrome c oxidase activity, and membrane permeability. We determine oxidative phosphorylation efficiency, by measuring ATP synthesis related to oxygen consumption at various exogenous ADP concentrations. Finally, we measured radical oxygen species (ROS) generation by liver mitochondria and mRNA concentrations of UCP2, biogenesis factors, and cytokines at the same end points.

RESULTS: CLP rats presented hypotension, lactic acidosis, liver cytolysis, and upregulation of proinflammatory cytokines mRNA as compared to controls. Liver mitochondria showed a decrease in ATP synthesis and oxygen consumption at 24 h following CLP. A marked uncoupling of oxidative phosphorylation appeared 36 h following CLP and was associated with a decrease in cytochrome c oxidase activity and content and ATP synthase subunit β content (slip mechanism) and an increase in mitochondrial oligomycin-insensitive respiration, but no change in mitochondrial inner membrane permeability (no leak). Upregulation of UCP2 mRNA resulted in a decrease in mitochondrial ROS generation 24 h after the onset of CLP, whereas ROS over-generation associated with slip at cytochrome c oxidase observed at 36 h was concomitant with a decrease in UCP2 mRNA expression.

CONCLUSIONS: Despite a compensatory increase in mitochondrial biogenesis factors, liver mitochondrial functions remain altered after CLP. This suggests that the functional compensatory mechanisms reported in the present study (slip at cytochrome c oxidase and biogenesis factors) were not strong enough to increase oxidative phosphorylation efficiency and failed to limit liver mitochondrial ROS over-generation. These data suggest that treatments based on cytochrome c infusion could have a role in mitochondrial dysfunction and/or ROS generation associated with sepsis.}, } @article {pmid30190598, year = {2018}, author = {Hillen, HS and Temiakov, D and Cramer, P}, title = {Structural basis of mitochondrial transcription.}, journal = {Nature structural & molecular biology}, volume = {25}, number = {9}, pages = {754-765}, pmid = {30190598}, issn = {1545-9985}, support = {R01 GM104231/GM/NIGMS NIH HHS/United States ; R01 GM118941/GM/NIGMS NIH HHS/United States ; }, mesh = {Evolution, Molecular ; Humans ; Mitochondria/enzymology/*metabolism ; Mitochondrial Proteins/*chemistry/*genetics ; Protein Conformation ; Terminator Regions, Genetic ; *Transcription, Genetic ; Transcriptional Elongation Factors/metabolism ; }, abstract = {The mitochondrial genome is transcribed by a single-subunit DNA-dependent RNA polymerase (mtRNAP) and its auxiliary factors. Structural studies have elucidated how mtRNAP cooperates with its dedicated transcription factors to direct RNA synthesis: initiation factors TFAM and TFB2M assist in promoter-DNA binding and opening by mtRNAP while the elongation factor TEFM increases polymerase processivity to the levels required for synthesis of long polycistronic mtRNA transcripts. Here, we review the emerging body of structural and functional studies of human mitochondrial transcription, provide a molecular movie that can be used for teaching purposes and discuss the open questions to guide future directions of investigation.}, } @article {pmid30194707, year = {2018}, author = {Grandi, G and Astolfi, G and Chicca, M and Pezzi, M}, title = {Ultrastructural investigations on spermatogenesis and spermatozoan morphology in the endangered Adriatic sturgeon, Acipenser naccarii (Chondrostei, Acipenseriformes).}, journal = {Journal of morphology}, volume = {279}, number = {10}, pages = {1376-1396}, doi = {10.1002/jmor.20847}, pmid = {30194707}, issn = {1097-4687}, support = {16-01-14404//Italian Ministry of University and Research (MIUR)/International ; }, mesh = {Acrosome/ultrastructure ; Animals ; *Endangered Species ; Fishes/*anatomy & histology ; Male ; Phylogeny ; Principal Component Analysis ; Spermatids/cytology/ultrastructure ; *Spermatogenesis ; Spermatogonia/ultrastructure ; Spermatozoa/cytology/*ultrastructure ; Testis/ultrastructure ; }, abstract = {Spermatogenesis was investigated in the Adriatic sturgeon, Acipenser naccarii, by light and electron microscopy. The testis of the unrestricted type had a germinal compartment composed of lobules containing germ cells and Sertoli cells, and separated by a basal lamina from the interstitial compartment, in which Leydig and myoid cells were detected for the first time in Acipenseridae. Spermatogenesis occurred in spermatocysts produced when Sertoli cells became associated with type A spermatogonia of subsequent generations, which produced a clone of synchronized aligned spermatogonia. In primary spermatocytes at zygo-pachytene stage, the large spherical nucleus contained synaptonemal complexes. The smaller secondary spermatocytes were ovoid with a central round nucleus and scarce cytoplasm. Spermatids were interconnected by cytoplasmic bridges until early spermiogenesis. Chromatin initially condensed as long, twisted, and nonhomogeneous fibers and finally as a compact structure made of thick filaments. Early spermatids showed the flagellum, the primordia of centriole complex and of "implantation fossa," followed by the acrosomal vesicle formed by Golgi complexes and a fibrous body associated to centriole complex. The spermatozoan head had 10 postero-lateral projections and a trapezoidal nucleus, a cylindrical midpiece with six to eight mitochondria, the centriole complex, and a "9 + 2" flagellum with a pair of lateral fins. Three helical endonuclear canals crossed the nucleus from the acrosome base to the implantation fossa; their spiralization and that of chromatin fibers suggest a spiral twisting of the nucleus during spermiogenesis. The Sertoli cells performed phagocytosis of degenerating spermatids and spermatozoa. Significant interindividual differences were detected in most morphological parameters of spermatozoa. Data on spermatogenesis in A. naccarii and morphometric measurements on mature spermatozoa provide information about the reproductive biology of the species useful not only for phylogenetic studies but also for evaluation of sperm quality for artificial reproduction projects and restocking of this and other critically endangered sturgeon species.}, } @article {pmid30195322, year = {2018}, author = {Verechshagina, NA and Konstantinov, YM and Kamenski, PA and Mazunin, IO}, title = {Import of Proteins and Nucleic Acids into Mitochondria.}, journal = {Biochemistry. Biokhimiia}, volume = {83}, number = {6}, pages = {643-661}, doi = {10.1134/S0006297918060032}, pmid = {30195322}, issn = {1608-3040}, mesh = {Biopolymers/metabolism ; Eukaryota/genetics/*metabolism ; Mitochondria/*genetics ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Nucleic Acids/*metabolism ; RNA, Transfer/metabolism ; }, abstract = {Many mitochondrial genes have been transferred to the nucleus in course of evolution. The products of expression of these genes, being still necessary for organelle function, are imported there from the cytosol. Molecular mechanisms of protein import are studied much deeper than those of nucleic acids. The latter, it seems to us, retards the development of mitochondrial genome editing technologies. In this review, we describe mechanisms of DNA, RNA, and protein import into mitochondria of different eukaryotes. The description is given for the natural processes, as well as for artificial targeting of macromolecules into mitochondria for therapy. Also, we discuss different approaches to introduce changes into the mitochondrial DNA sequence.}, } @article {pmid30196672, year = {2018}, author = {Eom, KS and Park, H and Lee, D and Choe, S and Kang, Y and Bia, MM and Lee, SH and Keyyu, J and Fyumagwa, R and Jeon, HK}, title = {Molecular and Morphologic Identification of Spirometra ranarum Found in the Stool of African Lion, Panthera leo in the Serengeti Plain of Tanzania.}, journal = {The Korean journal of parasitology}, volume = {56}, number = {4}, pages = {379-383}, pmid = {30196672}, issn = {1738-0006}, support = {2017R1D1A3B03035976//National Research Foundation of Korea/ ; PRB000720//Parasite Resource Bank of Korea/ ; }, mesh = {Animals ; Cyclooxygenase 1/genetics ; Feces/*parasitology ; Host-Parasite Interactions ; Lions/*parasitology ; Male ; Mitochondria/genetics ; NADH Dehydrogenase/genetics ; Phylogeny ; Spirometra/anatomy & histology/*genetics/*isolation & purification ; Tanzania ; }, abstract = {The present study was performed with morphological and molecular analysis (cox1 and nad1 mitochondrial genes) to identify the proglottids of spirometrid tapeworm found in the stool of an African lion, Panthera leo, in the Serengeti plain of Tanzania. A strand of tapeworm strobila, about 75 cm in length, was obtained in the stool of a male African lion in the Serengeti National Park (34˚ 50' E, 02˚ 30' S), Tanzania, in February 2012. The morphological features of the adult worm examined exhibited 3 uterine coils with a bow tie appearance and adopted a diagonal direction in the second turn. The posterior uterine coils are larger than terminal uterine ball and the feature of uteri are swirling rather than spirally coiling. The sequence difference between the Spirometra species (Tanzania origin) and S. erinaceieuropaei (GenBank no. KJ599680) was 9.4% while those of S. decipiens (GenBank no. KJ599679) differed by 2.1% in the cox1 and nad1 genes. Phylogenetic tree topologies generated using the 2 analytic methods were identical and presented high level of confidence values for the 3 major branches of the 3 Spirometra species in the cox1 gene. The morphological and molecular findings obtained in this study were nearly coincided with those of S. ranarum. Therefore, we can know for the first time that the African lion, Panthera leo, is to the definitive host of this tapeworm.}, } @article {pmid30201278, year = {2018}, author = {Santos, HJ and Makiuchi, T and Nozaki, T}, title = {Reinventing an Organelle: The Reduced Mitochondrion in Parasitic Protists.}, journal = {Trends in parasitology}, volume = {34}, number = {12}, pages = {1038-1055}, doi = {10.1016/j.pt.2018.08.008}, pmid = {30201278}, issn = {1471-5007}, mesh = {Animals ; Biodiversity ; Biological Evolution ; Eukaryota/classification/cytology/*physiology ; Mitochondria/*physiology ; Parasites/classification/cytology/*physiology ; }, abstract = {Mitochondria originated from the endosymbiotic event commencing from the engulfment of an ancestral α-proteobacterium by the first eukaryotic ancestor. Establishment of niches has led to various adaptations among eukaryotes. In anaerobic parasitic protists, the mitochondria have undergone modifications by combining features shared from the aerobic mitochondria with lineage-specific components and mechanisms; a diversified class of organelles emerged and are generally called mitochondrion-related organelles (MROs). In this review we summarize and discuss the recent advances in the knowledge of MROs from parasitic protists, particularly the themes such as metabolic functions, contribution to parasitism, dynamics, protein targeting, and novel lineage- specific proteins, with emphasis on the diversity among these organelles.}, } @article {pmid30204084, year = {2018}, author = {Seidi, A and Muellner-Wong, LS and Rajendran, E and Tjhin, ET and Dagley, LF and Aw, VY and Faou, P and Webb, AI and Tonkin, CJ and van Dooren, GG}, title = {Elucidating the mitochondrial proteome of Toxoplasma gondii reveals the presence of a divergent cytochrome c oxidase.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {30204084}, issn = {2050-084X}, support = {DP110103144//Australian Research Council/International ; }, mesh = {Animals ; Biotinylation ; Computational Biology ; Electron Transport Complex IV/*metabolism ; Gene Knockdown Techniques ; Mitochondria/*metabolism ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/metabolism ; Oxygen Consumption ; Parasites/growth & development/metabolism ; Phenotype ; Phylogeny ; Proteome/*metabolism ; Proteomics ; Protozoan Proteins/metabolism ; Toxoplasma/growth & development/*metabolism ; }, abstract = {The mitochondrion of apicomplexan parasites is critical for parasite survival, although the full complement of proteins that localize to this organelle has not been defined. Here we undertake two independent approaches to elucidate the mitochondrial proteome of the apicomplexan Toxoplasma gondii. We identify approximately 400 mitochondrial proteins, many of which lack homologs in the animals that these parasites infect, and most of which are important for parasite growth. We demonstrate that one such protein, termed TgApiCox25, is an important component of the parasite cytochrome c oxidase (COX) complex. We identify numerous other apicomplexan-specific components of COX, and conclude that apicomplexan COX, and apicomplexan mitochondria more generally, differ substantially in their protein composition from the hosts they infect. Our study highlights the diversity that exists in mitochondrial proteomes across the eukaryotic domain of life, and provides a foundation for defining unique aspects of mitochondrial biology in an important phylum of parasites.}, } @article {pmid30206380, year = {2018}, author = {Jebb, D and Foley, NM and Whelan, CV and Touzalin, F and Puechmaille, SJ and Teeling, EC}, title = {Population level mitogenomics of long-lived bats reveals dynamic heteroplasmy and challenges the Free Radical Theory of Ageing.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {13634}, pmid = {30206380}, issn = {2045-2322}, support = {ERC-2012-StG311000//EC | European Research Council (ERC)/International ; }, mesh = {Aging/*genetics/metabolism ; Animals ; Chiroptera/blood/*genetics ; DNA, Mitochondrial/*genetics ; Free Radicals ; High-Throughput Nucleotide Sequencing ; *Mutation ; }, abstract = {Bats are the only mammals capable of true, powered flight, which drives an extremely high metabolic rate. The "Free Radical Theory of Ageing" (FTRA) posits that a high metabolic rate causes mitochondrial heteroplasmy and the progressive ageing phenotype. Contrary to this, bats are the longest-lived order of mammals given their small size and high metabolic rate. To investigate if bats exhibit increased mitochondrial heteroplasmy with age, we performed targeted, deep sequencing of mitogenomes and measured point heteroplasmy in wild, long lived Myotis myotis. Blood was sampled from 195 individuals, aged between <1 and at 6+ years old, and whole mitochondria deep-sequenced, with a subset sampled over multiple years. The majority of heteroplasmies were at a low frequency and were transitions. Oxidative mutations were present in only a small number of individuals, suggesting local oxidative stress events. Cohort data showed no significant increase in heteroplasmy with age, while longitudinal data from recaptured individuals showed heteroplasmy is dynamic, and does not increase uniformly over time. We show that bats do not suffer from the predicted, inevitable increase in heteroplasmy as posited by the FRTA, instead heteroplasmy was found to be dynamic, questioning its presumed role as a primary driver of ageing.}, } @article {pmid30208106, year = {2018}, author = {Viret, A and Tsaparis, D and Tsigenopoulos, CS and Berrebi, P and Sabatini, A and Arculeo, M and Fassatoui, C and Magoulas, A and Marengo, M and Morales-Nin, B and Caill-Milly, N and Durieux, EDH}, title = {Absence of spatial genetic structure in common dentex (Dentex dentex Linnaeus, 1758) in the Mediterranean Sea as evidenced by nuclear and mitochondrial molecular markers.}, journal = {PloS one}, volume = {13}, number = {9}, pages = {e0203866}, pmid = {30208106}, issn = {1932-6203}, mesh = {Alleles ; Animals ; Atlantic Ocean ; Bayes Theorem ; Cell Nucleus/*genetics ; DNA, Mitochondrial/analysis/genetics ; Gene Flow ; Gene Frequency/genetics ; Genetic Variation ; Genetics, Population/methods ; Mediterranean Sea ; Microsatellite Repeats/genetics ; Mitochondria/*genetics ; Perciformes/*genetics ; Phylogeny ; }, abstract = {The common dentex, Dentex dentex, is a fish species which inhabits marine environments in the Mediterranean and Northeast Atlantic regions. This is an important species from an ecological, economic and conservation perspective, however critical information on its population genetic structure is lacking. Most samples were obtained from the Mediterranean Sea (17 sites) with an emphasis around Corsica (5 sites), plus one Atlantic Ocean site. This provided an opportunity to examine genetic structuring at local and broader scales to provide science based data for the management of fishing stocks in the region. Two mitochondrial regions were examined (D-loop and COI) along with eight microsatellite loci. The COI data was combined with publicly available sequences and demonstrated past misidentification of common dentex. All markers indicated the absence of population genetic structure from the Bay of Biscay to the eastern Mediterranean Sea. Bayesian approaches, as well as the statistical tests performed on the allelic frequencies from microsatellite loci, indicated low differentiation between samples; there was only a slight (p = 0.05) indication of isolation by distance. Common dentex is a marine fish species with a unique panmictic population in the Mediterranean and likely in the Atlantic Ocean as well.}, } @article {pmid30208839, year = {2018}, author = {Bono, JM and Pigage, HK and Wettstein, PJ and Prosser, SA and Pigage, JC}, title = {Genome-wide markers reveal a complex evolutionary history involving divergence and introgression in the Abert's squirrel (Sciurus aberti) species group.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {139}, pmid = {30208839}, issn = {1471-2148}, mesh = {Animals ; *Biological Evolution ; Cytochromes b/genetics ; DNA, Mitochondrial/genetics ; Genetic Markers ; *Genetic Variation ; *Genome ; Geography ; Haplotypes/genetics ; Likelihood Functions ; Mitochondria/genetics ; Phylogeography ; Polymorphism, Single Nucleotide/genetics ; Principal Component Analysis ; Sciuridae/*genetics ; }, abstract = {BACKGROUND: Genetic introgression between divergent lineages is now considered more common than previously appreciated, with potentially important consequences for adaptation and speciation. Introgression is often asymmetric between populations and patterns can vary for different types of loci (nuclear vs. organellar), complicating phylogeographic reconstruction. The taxonomy of the ecologically specialized Abert's squirrel species group has been controversial, and previous studies based on mitochondrial data have not fully resolved the evolutionary relationships among populations. Moreover, while these studies identified potential areas of secondary contact between divergent lineages, the possibility for introgression has not been tested.

RESULTS: We used RAD-seq to unravel the complex evolutionary history of the Abert's squirrel species group. Although some of our findings reinforce inferences based on mitochondrial data, we also find significant areas of discordance. Discordant signals generally arise from previously undetected introgression between divergent populations that differentially affected variation at mitochondrial and nuclear loci. Most notably, our results support earlier claims (disputed by mitochondrial data) that S. aberti kaibabensis, found only on the north rim of the Grand Canyon, is highly divergent from other populations. However, we also detected introgression of S. aberti kaibabensis DNA into other S. aberti populations, which likely accounts for the previously inferred close genetic relationship between this population and those south of the Grand Canyon.

CONCLUSIONS: Overall, the evolutionary history of Abert's squirrels appears to be shaped largely by divergence during periods of habitat isolation. However, we also found evidence for interbreeding during periods of secondary contact resulting in introgression, with variable effects on mitochondrial and nuclear markers. Our results support the emerging view that populations often diversify under scenarios involving both divergence in isolation and gene flow during secondary contact, and highlight the value of genome-wide datasets for resolving such complex evolutionary histories.}, } @article {pmid30209549, year = {2018}, author = {Sandor, S and Zhang, Y and Xu, J}, title = {Fungal mitochondrial genomes and genetic polymorphisms.}, journal = {Applied microbiology and biotechnology}, volume = {102}, number = {22}, pages = {9433-9448}, doi = {10.1007/s00253-018-9350-5}, pmid = {30209549}, issn = {1432-0614}, support = {531998//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {DNA, Mitochondrial/genetics ; *Evolution, Molecular ; Genes, Mitochondrial ; *Genome, Fungal ; *Genome, Mitochondrial ; Introns ; Mitochondria/*genetics ; Phylogeny ; *Polymorphism, Genetic ; }, abstract = {Mitochondria are the powerhouses of eukaryotic cells, responsible for ATP generation and playing a role in a diversity of cellular and organismal functions. Different from the majority of other intracellular membrane structures, mitochondria contain their own genetic materials that are capable of independent replication and inheritance. In this mini-review, we provide brief summaries of fungal mitochondrial genome structure, size, gene content, inheritance, and genetic variation. We pay special attention to the relative genetic polymorphisms of the mitochondrial vs nuclear genomes at the population level within individual fungal species. Among the 20 species/groups of species reviewed here, there is a range of variation among genes and species in the relative nuclear and mitochondrial genetic polymorphisms. Interestingly, most (15/20) showed a greater genetic diversity for nuclear genes and genomes than for mitochondrial genes and genomes, with the remaining five showing similar or slower nuclear genome genetic variations. This fungal pattern is different from the dominant pattern in animals, but more similar to that in plants. At present, the mechanisms for the variations among fungal species and the overall low level of mitochondrial sequence polymorphisms are not known. The increasing availability of population genomic data should help us reveal the potential genetic and ecological factors responsible for the observed variations.}, } @article {pmid30211573, year = {2018}, author = {Geary, DC}, title = {Efficiency of mitochondrial functioning as the fundamental biological mechanism of general intelligence (g).}, journal = {Psychological review}, volume = {125}, number = {6}, pages = {1028-1050}, doi = {10.1037/rev0000124}, pmid = {30211573}, issn = {1939-1471}, mesh = {Aging/*physiology ; *Biological Evolution ; *Health Status ; Humans ; Intelligence/genetics/*physiology ; Mitochondria/*physiology ; }, abstract = {General intelligence or g is one of the most thoroughly studied concepts in the behavioral sciences. Measures of intelligence are predictive of a wide range of educational, occupational, and life outcomes, including creative productivity and are systematically related to physical health and successful aging. The nexus of relations suggests 1 or several fundamental biological mechanisms underlie g, health, and aging, among other outcomes. Cell-damaging oxidative stress has been proposed as 1 of many potential mechanisms, but the proposal is underdeveloped and does not capture other important mitochondrial functions. I flesh out this proposal and argue that the overall efficiency of mitochondrial functioning is a core component of g; the most fundamental biological mechanism common to all brain and cognitive processes and that contributes to the relations among intelligence, health, and aging. The proposal integrates research on intelligence with models of the centrality of mitochondria to brain development and functioning, neurological diseases, and health more generally. Moreover, the combination of the maternal inheritance of mitochondrial DNA (mtDNA), the evolution of compensatory nuclear DNA, and the inability of evolutionary processes to purge deleterious mtDNA in males may contribute to the sex difference in variability in intelligence and in other cognitive domains. The proposal unifies many now disparate literatures and generates testable predictions for future studies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).}, } @article {pmid30213880, year = {2018}, author = {Ramrath, DJF and Niemann, M and Leibundgut, M and Bieri, P and Prange, C and Horn, EK and Leitner, A and Boehringer, D and Schneider, A and Ban, N}, title = {Evolutionary shift toward protein-based architecture in trypanosomal mitochondrial ribosomes.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {}, doi = {10.1126/science.aau7735}, pmid = {30213880}, issn = {1095-9203}, mesh = {*Evolution, Molecular ; Mitochondrial Ribosomes/*chemistry/ultrastructure ; Models, Molecular ; Protozoan Proteins/*chemistry/ultrastructure ; RNA, Ribosomal/chemistry/ultrastructure ; Ribosomal Proteins/*chemistry/ultrastructure ; Trypanosoma brucei brucei/*ultrastructure ; }, abstract = {Ribosomal RNA (rRNA) plays key functional and architectural roles in ribosomes. Using electron microscopy, we determined the atomic structure of a highly divergent ribosome found in mitochondria of Trypanosoma brucei, a unicellular parasite that causes sleeping sickness in humans. The trypanosomal mitoribosome features the smallest rRNAs and contains more proteins than all known ribosomes. The structure shows how the proteins have taken over the role of architectural scaffold from the rRNA: They form an autonomous outer shell that surrounds the entire particle and stabilizes and positions the functionally important regions of the rRNA. Our results also reveal the "minimal" set of conserved rRNA and protein components shared by all ribosomes that help us define the most essential functional elements.}, } @article {pmid30230466, year = {2018}, author = {Cordier-Bussat, M and Thibert, C and Sujobert, P and Genestier, L and Fontaine, É and Billaud, M}, title = {[Even the Warburg effect can be oxidized: metabolic cooperation and tumor development].}, journal = {Medecine sciences : M/S}, volume = {34}, number = {8-9}, pages = {701-708}, doi = {10.1051/medsci/20183408017}, pmid = {30230466}, issn = {1958-5381}, mesh = {Cell Transformation, Neoplastic/metabolism/pathology ; Energy Metabolism/*physiology ; Glycolysis/*physiology ; Humans ; Mitochondria/metabolism ; Neoplasms/*metabolism/*pathology ; Oxidation-Reduction ; Tumor Microenvironment/*physiology ; }, abstract = {During tumor development, malignant cells rewire their metabolism to meet the biosynthetic needs required to increase their biomass and to overcome their microenvironment constraints. The sustained activation of aerobic glycolysis, also called Warburg effect, is one of these adaptative mechanisms. The progresses in this area of research have revealed the flexibility of cancer cells that alternate between glycolytic and oxidative metabolism to cope with their conditions of development while sharing their energetic resources. In this survey, we review these recent breakthroughs and discuss a model that likens tumor to an evolutive metabolic ecosystem. We further emphasize the ensuing therapeutic applications that target metabolic weaknesses of neoplastic cells.}, } @article {pmid30230928, year = {2018}, author = {Isaac, RS and McShane, E and Churchman, LS}, title = {The Multiple Levels of Mitonuclear Coregulation.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {511-533}, doi = {10.1146/annurev-genet-120417-031709}, pmid = {30230928}, issn = {1545-2948}, support = {R01 GM123002/GM/NIGMS NIH HHS/United States ; F32 GM130028/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; Cell Nucleus/genetics ; Genome/*genetics ; Genome, Mitochondrial/*genetics ; Mitochondria/chemistry/genetics ; Mitochondrial Membranes/chemistry/metabolism ; *Oxidative Phosphorylation ; Protein Biosynthesis ; RNA Processing, Post-Transcriptional/genetics ; Transcription, Genetic ; }, abstract = {Together, the nuclear and mitochondrial genomes encode the oxidative phosphorylation (OXPHOS) complexes that reside in the mitochondrial inner membrane and enable aerobic life. Mitochondria maintain their own genome that is expressed and regulated by factors distinct from their nuclear counterparts. For optimal function, the cell must ensure proper stoichiometric production of OXPHOS subunits by coordinating two physically separated and evolutionarily distinct gene expression systems. Here, we review our current understanding of mitonuclear coregulation primarily at the levels of transcription and translation. Additionally, we discuss other levels of coregulation that may exist but remain largely unexplored, including mRNA modification and stability and posttranslational protein degradation.}, } @article {pmid30239783, year = {2018}, author = {Hood, WR and Austad, SN and Bize, P and Jimenez, AG and Montooth, KL and Schulte, PM and Scott, GR and Sokolova, I and Treberg, JR and Salin, K}, title = {The Mitochondrial Contribution to Animal Performance, Adaptation, and Life-History Variation.}, journal = {Integrative and comparative biology}, volume = {58}, number = {3}, pages = {480-485}, pmid = {30239783}, issn = {1557-7023}, support = {P30 DK079626/DK/NIDDK NIH HHS/United States ; }, mesh = {*Acclimatization ; Animals ; *Energy Metabolism ; *Life History Traits ; Mitochondria/*physiology ; }, abstract = {Animals display tremendous variation in their rates of growth, reproductive output, and longevity. While the physiological and molecular mechanisms that underlie this variation remain poorly understood, the performance of the mitochondrion has emerged as a key player. Mitochondria not only impact the performance of eukaryotes via their capacity to produce ATP, but they also play a role in producing heat and reactive oxygen species and function as a major signaling hub for the cell. The papers included in this special issue emerged from a symposium titled "Inside the Black Box: The Mitochondrial Basis of Life-history Variation and Animal Performance." Based on studies of diverse animal taxa, three distinct themes emerged from these papers. (1) When linking mitochondrial function to components of fitness, it is crucial that mitochondrial assays are performed in conditions as close as the intracellular conditions experienced by the mitochondria in vivo. (2) Functional plasticity allows mitochondria to retain their performance, as well as that of their host, over a range of exogenous conditions, and selection on mitochondrial and nuclear-derived proteins can optimize the match between the environment and the bioenergetic capacity of the mitochondrion. Finally, (3) studies of wild and wild-derived animals suggest that mitochondria play a central role in animal performance and life history strategy. Taken as a whole, we hope that these papers will foster discussion and inspire new hypotheses and innovations that will further our understanding of the mitochondrial processes that underlie variation in life history traits and animal performance.}, } @article {pmid30239827, year = {2019}, author = {Shang, Y and Ren, L and Chen, W and Zha, L and Cai, J and Dong, J and Guo, Y}, title = {Comparative Mitogenomic Analysis of Forensically Important Sarcophagid Flies (Diptera: Sarcophagidae) and Implications of Species Identification.}, journal = {Journal of medical entomology}, volume = {56}, number = {2}, pages = {392-407}, doi = {10.1093/jme/tjy162}, pmid = {30239827}, issn = {1938-2928}, mesh = {Amino Acid Substitution ; Animals ; Entomology/*methods ; Forensic Sciences/*methods ; *Genetic Techniques ; *Genome, Mitochondrial ; Phylogeny ; RNA, Ribosomal/chemistry ; RNA, Transfer/chemistry ; Sarcophagidae/classification/*genetics ; }, abstract = {The flesh flies (Diptera: Sarcophagidae) are significant in forensic investigations. The mitochondrial genome (mitogeome) has been widely used as genetic markers for phylogenetic analysis and species identification. To further understand the mitogenome-level features in Sarcophagidae, the complete mitogenome of Sarcophaga formosensis (Kirneret Lopes, 1961) (Diptera: Sarcophagidae) and Sarcophaga misera (Walker, 1849) (Diptera: Sarcophagidae) was firstly sequenced, annotated, and compared with other 13 Sarcophagidae species. The result indicated that the gene arrangement, gene content, base composition, and codon usage were conserved in the ancestral arthropod. Evolutionary rate of the mitogenome fragments revealed that the nonsynonymous and synonymous substitution rates (Ka and Ks) ratio was less than 1.00, indicating these variable sites under strong purifying selection. Almost all transfer RNA genes (tRNAs) have typical clover-leaf structures within these sarcophagid mitogenomes, except tRNA-Ser (AGN) is lack of the dihydrouridine arm. This comparative mitogenomic analysis sheds light on the architecture and evolution of mitogenomes in the Sarcophagidae. Phylogenetic analyses containing the interspecific distances from different regions in these species provided us new insights into the application of these effective genetic markers for species identification of flesh flies.}, } @article {pmid30246391, year = {2019}, author = {Shibata, D}, title = {Somatic cell evolution: how to improve with age.}, journal = {The Journal of pathology}, volume = {247}, number = {1}, pages = {3-5}, pmid = {30246391}, issn = {1096-9896}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; P30 CA014089/CA/NCI NIH HHS/United States ; P30CA014089/NH/NIH HHS/United States ; CA196569/NH/NIH HHS/United States ; P01 CA196569/CA/NCI NIH HHS/United States ; U54CA217376/NH/NIH HHS/United States ; }, mesh = {DNA, Mitochondrial/*genetics ; Mitochondria/genetics ; Mutation ; *Stem Cells ; United Kingdom ; }, abstract = {A recent article published in this journal illuminates a rare example of somatic evolution where cells improve rather than deteriorate with age. In mitotic intestinal crypts, stem cells with higher levels of a deleterious heteroplasmic germline mitochondrial mutation are purged through time, leading to crypts without the mutation. Similar somatic mitochondrial mutations are not purged from crypts, indicating that special conditions are needed to improve with age. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.}, } @article {pmid30256727, year = {2019}, author = {McClelland, GB and Scott, GR}, title = {Evolved Mechanisms of Aerobic Performance and Hypoxia Resistance in High-Altitude Natives.}, journal = {Annual review of physiology}, volume = {81}, number = {}, pages = {561-583}, doi = {10.1146/annurev-physiol-021317-121527}, pmid = {30256727}, issn = {1545-1585}, mesh = {Altitude ; Animals ; *Atmospheric Pressure ; *Biological Evolution ; Carbohydrate Metabolism ; Humans ; *Hypoxia ; Muscle, Skeletal ; Oxygen/*metabolism ; Oxygen Consumption ; Population Groups/*genetics ; Selection, Genetic ; *Thermogenesis ; }, abstract = {Comparative physiology studies of high-altitude species provide an exceptional opportunity to understand naturally evolved mechanisms of hypoxia resistance. Aerobic capacity (VO2max) is a critical performance trait under positive selection in some high-altitude taxa, and several high-altitude natives have evolved to resist the depressive effects of hypoxia on VO2max. This is associated with enhanced flux capacity through the O2 transport cascade and attenuation of the maladaptive responses to chronic hypoxia that can impair O2 transport. Some highlanders exhibit elevated rates of carbohydrate oxidation during exercise, taking advantage of its high ATP yield per mole of O2. Certain highland native animals have also evolved more oxidative muscles and can sustain high rates of lipid oxidation to support thermogenesis. The underlying mechanisms include regulatory adjustments of metabolic pathways and to gene expression networks. Therefore, the evolution of hypoxia resistance in high-altitude natives involves integrated functional changes in the pathways for O2 and substrate delivery and utilization by mitochondria.}, } @article {pmid30258733, year = {2018}, author = {Huang, Y and Zheng, S and Mei, X and Yu, B and Sun, B and Li, B and Wei, J and Chen, J and Li, T and Pan, G and Zhou, Z and Li, C}, title = {A secretory hexokinase plays an active role in the proliferation of Nosema bombycis.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e5658}, pmid = {30258733}, issn = {2167-8359}, abstract = {The microsporidian Nosema bombycis is an obligate intracellular parasite of Bombyx mori, that lost its intact tricarboxylic acid cycle and mitochondria during evolution but retained its intact glycolysis pathway. N. bombycis hexokinase (NbHK) is not only a rate-limiting enzyme of glycolysis but also a secretory protein. Indirect immunofluorescence assays and recombinant HK overexpressed in BmN cells showed that NbHK localized in the nucleus and cytoplasm of host cell during the meront stage. When N. bombycis matured, NbHK tended to concentrate at the nuclei of host cells. Furthermore, the transcriptional profile of NbHK implied it functioned during N. bombycis' proliferation stages. A knock-down of NbHK effectively suppressed the proliferation of N. bombycis indicating that NbHK is an important protein for parasite to control its host.}, } @article {pmid30265292, year = {2018}, author = {Pyrihová, E and Motycková, A and Voleman, L and Wandyszewska, N and Fišer, R and Seydlová, G and Roger, A and Kolísko, M and Doležal, P}, title = {A Single Tim Translocase in the Mitosomes of Giardia intestinalis Illustrates Convergence of Protein Import Machines in Anaerobic Eukaryotes.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2813-2822}, pmid = {30265292}, issn = {1759-6653}, support = {MOP-142349//CIHR/Canada ; }, mesh = {Amino Acid Sequence ; Anaerobiosis ; *Evolution, Molecular ; Giardia lamblia/*enzymology ; Mitochondria/*enzymology ; Mitochondrial Membrane Transport Proteins/*metabolism ; }, abstract = {Mitochondria have evolved diverse forms across eukaryotic diversity in adaptation to anoxia. Mitosomes are the simplest and the least well-studied type of anaerobic mitochondria. Transport of proteins via TIM complexes, composed of three proteins of the Tim17 protein family (Tim17/22/23), is one of the key unifying aspects of mitochondria and mitochondria-derived organelles. However, multiple experimental and bioinformatic attempts have so far failed to identify the nature of TIM in mitosomes of the anaerobic metamonad protist, Giardia intestinalis, one of the few experimental models for mitosome biology. Here, we present the identification of a single G. intestinalis Tim17 protein (GiTim17), made possible only by the implementation of a metamonad-specific hidden Markov model. While very divergent in primary sequence and in predicted membrane topology, experimental data suggest that GiTim17 is an inner membrane mitosomal protein, forming a disulphide-linked dimer. We suggest that the peculiar GiTim17 sequence reflects adaptation to the unusual, detergent resistant, inner mitosomal membrane. Specific pull-down experiments indicate interaction of GiTim17 with mitosomal Tim44, the tethering component of the import motor complex. Analysis of TIM complexes across eukaryote diversity suggests that a "single Tim" translocase is a convergent adaptation of mitosomes in anaerobic protists, with Tim22 and Tim17 (but not Tim23), providing the protein backbone.}, } @article {pmid30265295, year = {2018}, author = {Pereira, J and Lupas, AN}, title = {The Origin of Mitochondria-Specific Outer Membrane β-Barrels from an Ancestral Bacterial Fragment.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2759-2765}, pmid = {30265295}, issn = {1759-6653}, mesh = {Animals ; *Evolution, Molecular ; Mitochondrial Membranes ; Mitochondrial Proteins/*genetics ; }, abstract = {Outer membrane β-barrels (OMBBs) are toroidal arrays of antiparallel β-strands that span the outer membrane of Gram-negative bacteria and eukaryotic organelles. Although homologous, most families of bacterial OMBBs evolved through the independent amplification of an ancestral ββ-hairpin. In mitochondria, one family (SAM50) has a clear bacterial ancestry; the origin of the other family, consisting of 19-stranded OMBBs found only in mitochondria (MOMBBs), is substantially unclear. In a large-scale comparison of mitochondrial and bacterial OMBBs, we find evidence that the common ancestor of all MOMBBs emerged by the amplification of a double ββ-hairpin of bacterial origin, probably at the time of the Last Eukaryotic Common Ancestor. Thus, MOMBBs are indeed descended from bacterial OMBBs, but their fold formed independently in the proto-mitochondria, possibly in response to the need for a general-purpose polypeptide importer. This occurred by a process of amplification, despite the final fold having a prime number of strands.}, } @article {pmid30279542, year = {2018}, author = {Severgnini, M and Lazzari, B and Capra, E and Chessa, S and Luini, M and Bordoni, R and Castiglioni, B and Ricchi, M and Cremonesi, P}, title = {Genome sequencing of Prototheca zopfii genotypes 1 and 2 provides evidence of a severe reduction in organellar genomes.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {14637}, pmid = {30279542}, issn = {2045-2322}, mesh = {Chromosome Mapping ; DNA-Directed RNA Polymerases/genetics ; Genome, Mitochondrial ; Genome, Plant ; Genome, Plastid ; Host-Pathogen Interactions/genetics ; Mitochondria/*genetics ; Photosynthesis/*genetics ; Plastids/*genetics ; Prototheca/*classification/*genetics ; }, abstract = {Prototheca zopfii (P. zopfii, class Trebouxiophyceae, order Chlorellales, family Chlorellaceae), a non-photosynthetic predominantly free-living unicellular alga, is one of the few pathogens belonging to the plant kingdom. This alga can affect many vertebrate hosts, sustaining systemic infections and diseases such as mastitis in cows. The aim of our work was to sequence and assemble the P. zopfii genotype 1 and genotype 2 mitochondrial and plastid genomes. Remarkably, the P. zopfii mitochondrial (38 Kb) and plastid (28 Kb) genomes are models of compaction and the smallest known in the Trebouxiophyceae. As expected, the P. zopfii genotype 1 and 2 plastid genomes lack all the genes involved in photosynthesis, but, surprisingly, they also lack those coding for RNA polymerases. Our results showed that plastid genes are actively transcribed in P. zopfii, which suggests that the missing RNA polymerases are substituted by nuclear-encoded paralogs. The simplified architecture and highly-reduced gene complement of the P. zopfii mitochondrial and plastid genomes are closer to those of P. stagnora and the achlorophyllous obligate parasite Helicosporidium than to those of P. wickerhamii or P. cutis. This similarity is also supported by maximum likelihood phylogenetic analyses inferences. Overall, the P. zopfii sequences reported here, which include nuclear genome drafts for both genotypes, will help provide both a deeper understanding of the evolution of Prototheca spp. and insights into the corresponding host/pathogen interactions.}, } @article {pmid30280695, year = {2018}, author = {Önder, Z and İnci, A and Yıldırım, A and Çiloğlu, A and Düzlü, Ö}, title = {Molecular Characterization of Myiasis-Causing Moth Flies (Diptera: Psychodidae).}, journal = {Turkiye parazitolojii dergisi}, volume = {42}, number = {3}, pages = {223-228}, doi = {10.5152/tpd.2018.5943}, pmid = {30280695}, issn = {2146-3077}, mesh = {Animals ; Base Sequence ; DNA, Mitochondrial/chemistry ; Mitochondria/genetics ; Myiasis/*parasitology ; Phylogeny ; Psychodidae/classification/*genetics ; Sequence Alignment ; Turkey ; }, abstract = {OBJECTIVE: The aim of this study is to examine the molecular characterization of moth flies (Diptera: Psychodidae) based on their mitochondrial DNA sequences and determine the vectorial potential and damage caused by moth flies in future researches.

METHODS: A total of 240 adult moth flies were collected from toilet, bathroom, and basement walls of houses from different locations of the Kayseri region between May 2016 and April 2017. The polymerase chain reaction (PCR) analyses were performed using primer pairs, specificaly targeting the mitochondrial cytochrome oxidase c subunit I (mt-COI) gene of adult flies.

RESULTS: In total, five isolates were gel purified and sequenced for molecular characterization and phylogenetic analyses. Two species, namely Telmatoscopus albipunctatus (ERU-Telmatos3 and ERU-Telmatos6) and Psychodidae sp. (ERU-Psycho1,4,5), were successfully identified with the sequence alignment of isolates. According to the phylogenetic analysis, it was determined that the ERU-Telmatos3 and ERU-Telmatos6 isolates are clustered in the haplogroup A, while the ERU-Psycho1,4,5 isolate was clustered within the haplogroup B. The ERU-Psycho1 isolate was characterized as a new haplotype within the haplogroup B.

CONCLUSION: This study represents the first molecular characterization and phylogenetic status of moth flies in Turkey. The obtained findings should be the first step in the future investigation based on detecting the transmission of bacterial pathogens by moth flies.}, } @article {pmid30281880, year = {2018}, author = {Harborne, SPD and Kunji, ERS}, title = {Calcium-regulated mitochondrial ATP-Mg/Pi carriers evolved from a fusion of an EF-hand regulatory domain with a mitochondrial ADP/ATP carrier-like domain.}, journal = {IUBMB life}, volume = {70}, number = {12}, pages = {1222-1232}, pmid = {30281880}, issn = {1521-6551}, support = {MC_U105663139/MRC_/Medical Research Council/United Kingdom ; MC_UU_00015/7/MRC_/Medical Research Council/United Kingdom ; MC_UU_00015/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Amino Acid Transport Systems, Acidic/genetics/metabolism ; Animals ; Antiporters/*genetics/metabolism ; Calcium/metabolism ; Calcium Signaling/*genetics ; Calcium-Binding Proteins/metabolism ; Humans ; Mitochondria/*genetics/metabolism ; Mitochondrial ADP, ATP Translocases/*genetics ; Mitochondrial Proteins/*genetics ; Protein Conformation ; Protein Domains/genetics ; Saccharomyces cerevisiae/genetics/metabolism ; }, abstract = {The mitochondrial ATP-Mg/Pi carrier is responsible for the calcium-dependent regulation of adenosine nucleotide concentrations in the mitochondrial matrix, which allows mitochondria to respond to changing energy requirements of the cell. The carrier is expressed in mitochondria of fungi, plants and animals and belongs to the family of mitochondrial carriers. The carrier is unusual as it consists of three separate domains: (i) an N-terminal regulatory domain with four calcium-binding EF-hands similar to calmodulin, (ii) a loop domain containing an amphipathic α-helix and (iii) a mitochondrial carrier domain related to the mitochondrial ADP/ATP carrier. This striking example of three domains coming together from different origins to provide new functions represents an interesting quirk of evolution. In this review, we outline how the carrier was identified and how its physiological role was established with a focus on human isoforms. We exploit the sequence and structural information of the domains to explore the similarities and differences to their closest counterparts; mitochondrial ADP/ATP carriers and proteins with four EF-hands. We discuss how their combined function has led to a mechanism for calcium-regulated transport of adenosine nucleotides. Finally, we compare the ATP-Mg/Pi carrier with the mitochondrial aspartate/glutamate carrier, the only other mitochondrial carrier regulated by calcium, and we will argue that they have arisen by convergent rather than divergent evolution. © 2018 The Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 70(12):1222-1232, 2018.}, } @article {pmid30281911, year = {2018}, author = {van Esveld, SL and Huynen, MA}, title = {Does mitochondrial DNA evolution in metazoa drive the origin of new mitochondrial proteins?.}, journal = {IUBMB life}, volume = {70}, number = {12}, pages = {1240-1250}, doi = {10.1002/iub.1940}, pmid = {30281911}, issn = {1521-6551}, mesh = {Animals ; DNA, Mitochondrial/*genetics ; Eukaryota/genetics ; *Evolution, Molecular ; Humans ; Mitochondria/*genetics ; Mitochondrial Proteins/*genetics ; Nuclear Proteins/genetics ; Oxidative Phosphorylation ; }, abstract = {Most eukaryotic cells contain mitochondria with a genome that evolved from their α-proteobacterial ancestor. In the course of eukaryotic evolution, the mitochondrial genome underwent a dramatic reduction in size, caused by the loss and translocation of genes. This required adjustments in mitochondrial gene expression mechanisms and resulted in a complex collaborative system of mitochondrially encoded transfer RNAs and ribosomal RNAs with nuclear encoded proteins to express the mitochondrial encoded oxidative phosphorylation (OXPHOS) proteins. In this review, we examine mitochondrial gene expression from an evolutionary point of view: to what extent can we correlate changes in the mitochondrial genome in the evolutionary lineage leading to human with the origin of new nuclear encoded proteins. We dated the evolutionary origin of mitochondrial proteins that interact with mitochondrial DNA or its RNA and/or protein products in a systematic manner and compared them with documented changes in the mitochondrial DNA. We find anecdotal but accumulating evidence that metazoan RNA-interacting proteins arose in conjunction with changes of the mitochondrial DNA. We find no substantial evidence for such compensatory evolution in new OXPHOS proteins, which appear to be constrained by the ability to form supercomplexes. © 2018 IUBMB Life, 70(12):1240-1250, 2018.}, } @article {pmid30285603, year = {2018}, author = {Chen, G and Zou, Y and Hu, J and Ding, Y}, title = {Genome-wide analysis of the rice PPR gene family and their expression profiles under different stress treatments.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {720}, pmid = {30285603}, issn = {1471-2164}, support = {31471464//National Nature Science Foundation of China/ ; 2013CB126900//"973" Program of China/ ; }, mesh = {Chromosomes, Plant/genetics ; Droughts ; *Gene Expression Profiling ; Genome, Plant/genetics ; *Genomics ; Intracellular Space/metabolism ; MicroRNAs/genetics ; Oryza/drug effects/*genetics/metabolism/*physiology ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Protein Transport ; Salts/pharmacology ; Stress, Physiological/drug effects/*genetics ; Synteny ; }, abstract = {BACKGROUND: Pentatricopeptide-repeat proteins (PPRs) are characterized by tandem arrays of a degenerate 35-amino-acid (PPR motifs), which can bind RNA strands and participate in post-transcription. PPR proteins family is one of the largest families in land plants and play important roles in organelle RNA metabolism and plant development. However, the functions of PPR genes involved in biotic and abiotic stresses of rice (Oryza sativa L.) remain largely unknown.

RESULTS: In the present study, a comprehensive genome-wide analysis of PPR genes was performed. A total of 491 PPR genes were found in the rice genome, of which 246 PPR genes belong to the P subfamily, and 245 genes belong to the PLS subfamily. Gene structure analysis showed that most PPR genes lack intron. Chromosomal location analysis indicated that PPR genes were widely distributed in all 12 rice chromosomes. Phylogenetic relationship analysis revealed the distinct difference between the P and PLS subfamilies. Many PPR proteins are predicted to target chloroplasts or mitochondria, and a PPR protein (LOC_Os10g34310) was verified to localize in mitochondria. Furthermore, three PPR genes (LOC_Os03g17634,LOC_Os07g40820,LOC_Os04g51350) were verified as corresponding miRNA targets. The expression pattern analysis showed that many PPR genes could be induced under biotic and abiotic stresses. Finally, seven PPR genes were confirmed with their expression patterns under salinity or drought stress.

CONCLUSIONS: We found 491 PPR genes in the rice genome, and our genes structure analysis and syntenic analysis indicated that PPR genes might be derived from amplification by retro-transposition. The expression pattern present here suggested that PPR proteins have crucial roles in response to different abiotic stresses in rice. Taken together, our study provides a comprehensive analysis of the PPR gene family and will facilitate further studies on their roles in rice growth and development.}, } @article {pmid30286121, year = {2018}, author = {Ashrafzadeh, MR and Djan, M and Szendrei, L and Paulauskas, A and Scandura, M and Bagi, Z and Ilie, DE and Kerdikoshvili, N and Marek, P and Soós, N and Kusza, S}, title = {Large-scale mitochondrial DNA analysis reveals new light on the phylogeography of Central and Eastern-European Brown hare (Lepus europaeus Pallas, 1778).}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0204653}, pmid = {30286121}, issn = {1932-6203}, mesh = {Animals ; Cytochromes b/genetics ; DNA, Mitochondrial/*genetics ; Europe ; Haplotypes/genetics ; Hares/*genetics ; Hybridization, Genetic/genetics ; Mitochondria/*genetics ; Phylogeny ; Phylogeography/methods ; RNA, Transfer/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {European brown hare, Lepus europaeus, from Central and Eastern European countries (Hungary, Poland, Serbia, Lithuania, Romania, Georgia and Italy) were sampled, and phylogenetic analyses were carried out on two datasets: 1.) 137 sequences (358 bp) of control region mtDNA; and 2.) 105 sequences of a concatenated fragment (916 bp), including the cytochrome b, tRNA-Thr, tRNA-Pro and control region mitochondrial DNA. Our sequences were aligned with additional brown hare sequences from GenBank. A total of 52 and 51 haplotypes were detected within the two datasets, respectively, and assigned to two previously described major lineages: Anatolian/Middle Eastern (AME) and European (EUR). Furthermore, the European lineage was divided into two subclades including South Eastern European (SEE) and Central European (CE). Sympatric distribution of the lineages of the brown hare in South-Eastern and Eastern Europe revealed contact zones there. BAPS analysis assigned sequences from L. europaeus to five genetic clusters, whereas CE individuals were assigned to only one cluster, and AME and SEE sequences were each assigned to two clusters. Our findings uncover numerous novel haplotypes of Anatolian/Middle Eastern brown hare outside their main range, as evidence for the combined influence of Late Pleistocene climatic fluctuations and anthropogenic activities in shaping the phylogeographic structure of the species. Our results support the hypothesis of a postglacial brown hare expansion from Anatolia and the Balkan Peninsula to Central and Eastern Europe, and suggest some slight introgression of individual haplotypes from L. timidus to L. europaeus.}, } @article {pmid30289547, year = {2019}, author = {Hsu, YW and Juan, CT and Wang, CM and Jauh, GY}, title = {Mitochondrial Heat Shock Protein 60s Interact with What's This Factor 9 to Regulate RNA Splicing of ccmFC and rpl2.}, journal = {Plant & cell physiology}, volume = {60}, number = {1}, pages = {116-125}, doi = {10.1093/pcp/pcy199}, pmid = {30289547}, issn = {1471-9053}, mesh = {Amino Acid Sequence ; Arabidopsis/growth & development ; Arabidopsis Proteins/*metabolism ; Base Sequence ; Chaperonin 60/chemistry/*metabolism ; Introns/*genetics ; Mitochondria/*metabolism ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/metabolism ; Mutation/genetics ; Peptides/chemistry/metabolism ; Phenotype ; Protein Binding ; RNA Splicing/*genetics ; RNA-Binding Proteins/*metabolism ; }, abstract = {Mitochondrial intron splicing is a plant-specific feature that was acquired during the co-evolution of eukaryotic host cells and a-proteobacteria. The elimination of these introns is facilitated by mitochondrial-targeted proteins encoded by its host, nucleus. What's this factor 9 (WTF9), a nuclear-encoded plant organelle RNA recognition (PORR) protein, is involved in the splicing of the mitochondrial group II introns rpl2 and ccmFC. Disruption of WTF9 causes developmental defects associated with the loss of Cyt c and Cyt c1 in Arabidopsis. In the present study, using a co-immunoprecipitation assay, we found that HSP60s interacted with WTF9, which was further confirmed by a pull-down assay. HSP60s are molecular chaperones that assist with protein folding in both eukaryotic and prokaryotic cells. However, accumulating evidence suggests that HSP60s also participate in other biological functions such as RNA metabolism and RNA protection. In this study, we found that consistently with their interaction with WTF9, HSP60s interacted with 48 nucleotides of the ccmFC intron. In mutant studies, the double mutant hsp60-3a1hsp60-3b1 exhibited a small stature phenotype and reduced splicing efficiency for rpl2 and ccmFC. These observations were similar to those in wtf9 mutants and suggest that HSP60s are involved in the RNA splicing of rpl2 and ccmFC introns in mitochondria. Our findings suggest that HSP60s participate in mitochondrial RNA splicing through their RNA-binding ability.}, } @article {pmid30291814, year = {2018}, author = {Lukeš, J and Wheeler, R and Jirsová, D and David, V and Archibald, JM}, title = {Massive mitochondrial DNA content in diplonemid and kinetoplastid protists.}, journal = {IUBMB life}, volume = {70}, number = {12}, pages = {1267-1274}, pmid = {30291814}, issn = {1521-6551}, support = {MOP-115141//CIHR/Canada ; 103261/Z/13/Z//Wellcome Trust/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {DNA, Mitochondrial/*genetics/isolation & purification/ultrastructure ; Euglenozoa/*genetics ; Kinetoplastida/*genetics ; Mitochondria/*genetics ; Phylogeny ; Trans-Splicing/genetics ; }, abstract = {The mitochondrial DNA of diplonemid and kinetoplastid protists is known for its suite of bizarre features, including the presence of concatenated circular molecules, extensive trans-splicing and various forms of RNA editing. Here we report on the existence of another remarkable characteristic: hyper-inflated DNA content. We estimated the total amount of mitochondrial DNA in four kinetoplastid species (Trypanosoma brucei, Trypanoplasma borreli, Cryptobia helicis, and Perkinsela sp.) and the diplonemid Diplonema papillatum. Staining with 4',6-diamidino-2-phenylindole and RedDot1 followed by color deconvolution and quantification revealed massive inflation in the total amount of DNA in their organelles. This was further confirmed by electron microscopy. The most extreme case is the ∼260 Mbp of DNA in the mitochondrion of Diplonema, which greatly exceeds that in its nucleus; this is, to our knowledge, the largest amount of DNA described in any organelle. Perkinsela sp. has a total mitochondrial DNA content ~6.6× greater than its nuclear genome. This mass of DNA occupies most of the volume of the Perkinsela cell, despite the fact that it contains only six protein-coding genes. Why so much DNA? We propose that these bloated mitochondrial DNAs accumulated by a ratchet-like process. Despite their excessive nature, the synthesis and maintenance of these mtDNAs must incur a relatively low cost, considering that diplonemids are one of the most ubiquitous and speciose protist groups in the ocean. © 2018 IUBMB Life, 70(12):1267-1274, 2018.}, } @article {pmid30292820, year = {2018}, author = {Cogliati, S and Lorenzi, I and Rigoni, G and Caicci, F and Soriano, ME}, title = {Regulation of Mitochondrial Electron Transport Chain Assembly.}, journal = {Journal of molecular biology}, volume = {430}, number = {24}, pages = {4849-4873}, doi = {10.1016/j.jmb.2018.09.016}, pmid = {30292820}, issn = {1089-8638}, mesh = {Animals ; *Electron Transport ; Evolution, Molecular ; Gene Expression Regulation ; Humans ; Mitochondria/*genetics/metabolism ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/chemistry/genetics/*metabolism ; Multienzyme Complexes/chemistry/metabolism ; Oxidative Phosphorylation ; Phylogeny ; }, abstract = {Mitochondrial function depends on the correct synthesis, transport, and assembly of proteins and cofactors of the electron transport chain. The initial idea that the respiratory chain protein complexes (RCCs) were independent structures in the inner mitochondrial membrane evolved after the identification of higher quaternary structures called supercomplexes (SCs), whose formation is dynamically regulated in order to accommodate cellular metabolic demands. Due to the dual genetic origin of the mitochondrial proteome, electron transport chain and SCs formation must be tightly regulated to coordinate the expression and assembly of components encoded by both genomes. This regulation occurs at different levels from gene transcription to protein, complex or SCs assembly, and might involve the participation of factors that contribute to the formation and stability of the RCCs and SCs. Here we review the cellular pathways and assembly factors that regulate RCCs and SCs formation.}, } @article {pmid30297026, year = {2018}, author = {Porcelli, V and Vozza, A and Calcagnile, V and Gorgoglione, R and Arrigoni, R and Fontanesi, F and Marobbio, CMT and Castegna, A and Palmieri, F and Palmieri, L}, title = {Molecular identification and functional characterization of a novel glutamate transporter in yeast and plant mitochondria.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1859}, number = {11}, pages = {1249-1258}, doi = {10.1016/j.bbabio.2018.08.001}, pmid = {30297026}, issn = {1879-2650}, mesh = {Amino Acid Transport System X-AG/*metabolism ; Arabidopsis/*metabolism ; Arabidopsis Proteins/*metabolism ; Gene Deletion ; Glutamic Acid/metabolism ; Hydrogen-Ion Concentration ; Kinetics ; Membrane Transport Proteins/*metabolism ; Mitochondria/*metabolism ; Phylogeny ; Proteolipids ; Recombinant Proteins/metabolism ; Saccharomyces cerevisiae/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; Substrate Specificity ; Time Factors ; }, abstract = {The genome of Saccharomyces cerevisiae encodes 35 members of the mitochondrial carrier family (MCF) and 58 MCF members are coded by the genome of Arabidopsis thaliana, most of which have been functionally characterized. Here two members of this family, Ymc2p from S. cerevisiae and BOU from Arabidopsis, have been thoroughly characterized. These proteins were overproduced in bacteria and reconstituted into liposomes. Their transport properties and kinetic parameters demonstrate that Ymc2p and BOU transport glutamate, and to a much lesser extent L-homocysteinesulfinate, but not other amino acids and many other tested metabolites. Transport catalyzed by both carriers was saturable, inhibited by mercuric chloride and dependent on the proton gradient across the proteoliposomal membrane. The growth phenotype of S. cerevisiae cells lacking the genes ymc2 and agc1, which encodes the only other S. cerevisiae carrier capable to transport glutamate besides aspartate, was fully complemented by expressing Ymc2p, Agc1p or BOU. Mitochondrial extracts derived from ymc2Δagc1Δ cells, reconstituted into liposomes, exhibited no glutamate transport at variance with wild-type, ymc2Δ and agc1Δ cells, showing that S. cerevisiae cells grown in the presence of acetate do not contain additional mitochondrial transporters for glutamate besides Ymc2p and Agc1p. Furthermore, mitochondria isolated from wild-type, ymc2Δ and agc1Δ strains, but not from the double mutant ymc2Δagc1Δ strain, swell in isosmotic ammonium glutamate showing that glutamate is transported by Ymc2p and Agc1p together with a H[+]. It is proposed that the function of Ymc2p and BOU is to transport glutamate across the mitochondrial inner membrane and thereby play a role in intermediary metabolism, C1 metabolism and mitochondrial protein synthesis.}, } @article {pmid30300424, year = {2018}, author = {Kobayashi, G and Araya, JF}, title = {Southernmost records of Escarpia spicata and Lamellibrachia barhami (Annelida: Siboglinidae) confirmed with DNA obtained from dried tubes collected from undiscovered reducing environments in northern Chile.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0204959}, pmid = {30300424}, issn = {1932-6203}, mesh = {Animals ; Annelida/classification/*genetics/microbiology ; Bacteria/genetics/isolation & purification ; Chile ; DNA/*chemistry/isolation & purification/metabolism ; Electron Transport Complex IV/classification/genetics ; Hemoglobins/classification/genetics ; Mitochondria/genetics ; Phylogeny ; Protein Subunits/classification/genetics ; RNA, Ribosomal, 16S/chemistry/isolation & purification/metabolism ; Sequence Analysis, DNA ; Symbiosis ; }, abstract = {Deep-sea fishing bycatch enables collection of samples of rare species that are not easily accessible, for research purposes. However, these specimens are often degraded, losing diagnostic morphological characteristics. Several tubes of vestimentiferans, conspicuous annelids endemic to chemosynthetic environments, were obtained from a single batch of deep-sea fishing bycatch at depths of around 1,500 m off Huasco, northern Chile, as part of an ongoing study examining bycatch species. DNA sequences of the mitochondrial cytochrome c oxidase subunit I (COI) gene and an intron region within the hemoglobin subunit B2 (hbB2i) were successfully determined using vestimentiferans' dried-up tubes and their degraded inner tissue. Molecular phylogenetic analyses based on DNA sequence identified the samples as Escarpia spicata Jones, 1985, and Lamellibrachia barhami Webb, 1969. These are the southernmost records, vastly extending the geographical ranges of both species from Santa Catalina Island, California to northern Chile for E. spicata (over 8,000 km), and from Vancouver Island Margin to northern Chile for L. barhami (over 10,000 km). We also determined a 16S rRNA sequence of symbiotic bacteria of L. barhami. The sequence of the bacteria is the same as that of E. laminata, Lamellibrachia sp. 1, and Lamellibrachia sp.2 known from the Gulf of Mexico. The present study provides sound evidence forthe presence of reducing environments along the continental margin of northern Chile.}, } @article {pmid30304531, year = {2018}, author = {Urantówka, AD and Kroczak, A and Silva, T and Padrón, RZ and Gallardo, NF and Blanch, J and Blanch, B and Mackiewicz, P}, title = {New Insight into Parrots' Mitogenomes Indicates That Their Ancestor Contained a Duplicated Region.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2989-3009}, pmid = {30304531}, issn = {1537-1719}, mesh = {Animals ; *Gene Duplication ; Gene Order ; *Genome, Mitochondrial ; Longevity/genetics ; Parrots/anatomy & histology/*genetics ; Phylogeny ; }, abstract = {Mitochondrial genomes of vertebrates are generally thought to evolve under strong selection for size reduction and gene order conservation. Therefore, a growing number of mitogenomes with duplicated regions changes our view on the genome evolution. Among Aves, order Psittaciformes (parrots) is especially noteworthy because of its large morphological, ecological, and taxonomical diversity, which offers an opportunity to study genome evolution in various aspects. Former analyses showed that tandem duplications comprising the control region with adjacent genes are restricted to several lineages in which the duplication occurred independently. However, using an appropriate polymerase chain reaction strategy, we demonstrate that early diverged parrot groups contain mitogenomes with the duplicated region. These findings together with mapping duplication data from other mitogenomes onto parrot phylogeny indicate that the duplication was an ancestral state for Psittaciformes. The state was inherited by main parrot groups and was lost several times in some lineages. The duplicated regions were subjected to concerted evolution with a frequency higher than the rate of speciation. The duplicated control regions may provide a selective advantage due to a more efficient initiation of replication or transcription and a larger number of replicating genomes per organelle, which may lead to a more effective energy production by mitochondria. The mitogenomic duplications were associated with phenotypic features and parrots with the duplicated region can live longer, show larger body mass as well as predispositions to a more active flight. The results have wider implications on the presence of duplications and their evolution in mitogenomes of other avian groups.}, } @article {pmid30304578, year = {2018}, author = {Burger, G and Valach, M}, title = {Perfection of eccentricity: Mitochondrial genomes of diplonemids.}, journal = {IUBMB life}, volume = {70}, number = {12}, pages = {1197-1206}, doi = {10.1002/iub.1927}, pmid = {30304578}, issn = {1521-6551}, support = {MOP-79309//CIHR/Canada ; }, mesh = {Aquatic Organisms/*genetics ; DNA, Mitochondrial/genetics ; Euglenozoa/*genetics ; Genes, Mitochondrial/genetics ; Genome, Mitochondrial/*genetics ; Introns/genetics ; Mitochondria/*genetics ; }, abstract = {Mitochondria are the sandbox of evolution as exemplified most particularly by the diplonemids, a group of marine microeukaryotes. These protists are uniquely characterized by their highly multipartite mitochondrial genome and systematically fragmented genes whose pieces are spread out over several dozens of chromosomes. The type species Diplonema papillatum was the first member of this group in which the expression of fragmented mitochondrial genes was investigated experimentally. We now know that gene expression involves separate transcription of gene pieces (modules), RNA editing of module transcripts, and module joining to mature mRNAs and rRNAs. The mechanism of cognate module recognition and ligation is distinct from known intron splicing and remains to be uncovered. Here, we review the current status of research on mitochondrial genome architecture, as well as gene complement, structure, and expression modes in diplonemids. Further, we discuss the potential molecular mechanisms of posttranscriptional processing, and finally reflect on the evolutionary trajectories and trends of mtDNA evolution as seen in this protist group. © 2018 IUBMB Life, 70(12):1197-1206, 2018.}, } @article {pmid30308027, year = {2018}, author = {Perdices, A and Ozeren, CS and Erkakan, F and Freyhof, J}, title = {Diversity of spined loaches from Asia Minor in a phylogenetic context (Teleostei: Cobitidae).}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0205678}, pmid = {30308027}, issn = {1932-6203}, mesh = {Animals ; Cypriniformes/*genetics ; DNA, Mitochondrial/genetics ; Genetic Variation/genetics ; Homeodomain Proteins/genetics ; Mitochondria/genetics ; Phylogeny ; Turkey ; }, abstract = {Accurate determination of species diversity in areas of high endemicity, particularly those lacking comprehensive systematic knowledge, represents a challenge for both taxonomists and conservationists. This need is particularly evident in areas greatly affected by anthropogenic disturbances such as the Eastern Mediterranean and its freshwater environments. To improve our knowledge of Eastern Mediterranean freshwater fishes, we phylogenetically studied Western Palearctic Cobitis species, focusing on those found in Turkey. Overall, our results provide a robust framework to assess the number of species of Cobitis. Phylogenetic reconstructions based on mitochondrial (cyt b) and nuclear (RAG1) sequences show seven major clades (Clades 1-7) grouping all Western Palearctic Cobitis species, except C. melanoleuca. In general, each major clade comprises Cobitis species that inhabit geographically close areas and have similar secondary sexual characters. Multiple divergent lineages were identified in our analyses, some of which were highly divergent such as the ones inhabiting Turkish freshwaters. Moreover, in some analyses, several of the identified lineages were incongruent with a priori defined species. Furthermore, our analyses identified eight potentially new candidate species, six that had been suggested in previous studies and two that are reported here for the first time. Our results reveal Turkey as the area with the greatest diversity of spined loaches in the Mediterranean.}, } @article {pmid30309500, year = {2018}, author = {Miquel, J and Poonlaphdecha, S and Ribas, A}, title = {Spermatological characteristics of the family Glypthelminthidae (Digenea, Plagiorchioidea) inferred from the ultrastructural study of Glypthelmins staffordi Tubangui, 1928.}, journal = {Tissue & cell}, volume = {54}, number = {}, pages = {114-119}, doi = {10.1016/j.tice.2018.08.013}, pmid = {30309500}, issn = {1532-3072}, mesh = {Animals ; Male ; Phylogeny ; Spermatozoa/*ultrastructure ; Trematoda/*classification/*ultrastructure ; }, abstract = {The present study describes the ultrastructural organization of the mature spermatozoon of the digenean Glypthelmins staffordi (Glypthelminthidae) by means of transmission electron microscopy. Live digeneans were collected from the Chinese edible frog (Hoplobatrachus rugulosus) in Udon Thani Province (Thailand). The ultrastructural study reveals that the mature spermatozoon of G. staffordi is a filiform cell, which is tapered at both extremities. It exhibits the Bakhoum et al.'s type IV of spermatozoon of digeneans characterized by the 9+'1' axonemes of trepaxonematan Platyhelminthes, the presence of the association "external ornamentation-cortical microtubules", the external ornamentation located in the posterior part of the anterior region, the arrangement of parallel cortical microtubules in two bundles and with its maximum number located in the anterior part of the sperm cell, and the presence of two mitochondria. Other characteristics are the presence of spine-like bodies, a posterior extremity containing only the nucleus, and the presence of a large amount of glycogen granules. Results of the present study are particularly compared with the existing data in other families of the Plagiorchioidea, namely the Brachycoeliidae, the Haematoloechidae, the Omphalometridae and the Plagiorchiidae.}, } @article {pmid30311911, year = {2018}, author = {Fischer, J and Müller, SY and Netzker, T and Jäger, N and Gacek-Matthews, A and Scherlach, K and Stroe, MC and García-Altares, M and Pezzini, F and Schoeler, H and Reichelt, M and Gershenzon, J and Krespach, MK and Shelest, E and Schroeckh, V and Valiante, V and Heinzel, T and Hertweck, C and Strauss, J and Brakhage, AA}, title = {Chromatin mapping identifies BasR, a key regulator of bacteria-triggered production of fungal secondary metabolites.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {30311911}, issn = {2050-084X}, support = {SFB-F3703//Austrian Science Fund FWF/Austria ; }, mesh = {Acetylation ; Aspergillus nidulans/genetics/*metabolism ; Chromatin/*metabolism ; Fungal Proteins/genetics/*metabolism ; Gene Expression Regulation, Fungal ; Gene Ontology ; Genome, Fungal ; Histidine/metabolism ; Histones/metabolism ; Lysine/metabolism ; Mitochondria/metabolism ; Multigene Family ; Nitrogen/metabolism ; Phylogeny ; *Secondary Metabolism ; Signal Transduction ; Streptomyces/*metabolism ; Transcription Factors/metabolism ; }, abstract = {The eukaryotic epigenetic machinery can be modified by bacteria to reprogram the response of eukaryotes during their interaction with microorganisms. We discovered that the bacterium Streptomyces rapamycinicus triggered increased chromatin acetylation and thus activation of the silent secondary metabolism ors gene cluster in the fungus Aspergillus nidulans. Using this model, we aim understanding mechanisms of microbial communication based on bacteria-triggered chromatin modification. Using genome-wide ChIP-seq analysis of acetylated histone H3, we uncovered the unique chromatin landscape in A. nidulans upon co-cultivation with S. rapamycinicus and relate changes in the acetylation to that in the fungal transcriptome. Differentially acetylated histones were detected in genes involved in secondary metabolism, in amino acid and nitrogen metabolism, in signaling, and encoding transcription factors. Further molecular analyses identified the Myb-like transcription factor BasR as the regulatory node for transduction of the bacterial signal in the fungus and show its function is conserved in other Aspergillus species.}, } @article {pmid30313490, year = {2018}, author = {Katoh, TK and Zhang, G and Zhou, CJ and Gao, JJ}, title = {Taxonomy of the Hirtodrosophila melanderi species group (Diptera: Drosophilidae), with descriptions of four new species from southwestern China.}, journal = {Zootaxa}, volume = {4422}, number = {3}, pages = {345-365}, doi = {10.11646/zootaxa.4422.3.2}, pmid = {30313490}, issn = {1175-5334}, mesh = {Animals ; China ; *Diptera ; *Drosophilidae ; Mitochondria ; Phylogeny ; Tibet ; }, abstract = {The Hirtodrosophila melanderi species group contains nine known species recorded from either the Old or the New World. All these species were thought to be strict fungivorous drosophilids. In the present study, we give supplementary descriptions for three of these known species, all recorded from Yunnan, southwestern China, H. furcapenis, H. furcapenisoides, and H. longifurcapenis, by examining respective type specimen(s). We then describe four new species of the same group, H. seticlasper Katoh Gao, sp. nov., H. spinicerca Katoh Gao, sp. nov., H. serratifurcapenis Katoh Gao, sp. nov., and H. truncifurca Katoh Gao, sp. nov., all discovered recently from high altitudes (ca. 3,500 to 3,800 m a.s.l.) in Tibet (Xizang), southwestern China. The delimitation of these new species is firstly performed in light of morphology and further with the aid of DNA sequences of the mitochondrial COI (cytochrome c oxydase, subunits I) gene. In addition, a key to all the species of the species group is provided.}, } @article {pmid30316921, year = {2019}, author = {Gao, XM and Mu, DL and Hou, CC and Zhu, JQ and Jin, S and Wang, CL}, title = {Expression and putative functions of KIFC1 for nuclear reshaping and midpiece formation during spermiogenesis of Phascolosoma esculenta.}, journal = {Gene}, volume = {683}, number = {}, pages = {169-183}, doi = {10.1016/j.gene.2018.10.021}, pmid = {30316921}, issn = {1879-0038}, mesh = {Animals ; Binding Sites ; Cell Nucleus/metabolism ; Gene Expression Regulation ; Kinesins/chemistry/*genetics/*metabolism ; Male ; Microtubules/metabolism ; Models, Molecular ; Phylogeny ; Polychaeta/genetics/*physiology ; Protein Conformation ; Protein Domains ; Protein Transport ; *Spermatogenesis ; }, abstract = {Kinesin-14 KIFC1 plays an important role in vesicular transport, microtubule organization, and spermiogenesis. In this study, we first investigated the microtubule distribution and expression pattern of KIFC1 during spermiogenesis of P. esculenta. Microtubules are abundant during spermiogenesis of P. esculenta and may be related to the generation and maintenance of pseudopodia-like cytoplasmic protrusions and nuclear reshaping. The Pe-KIFC1 protein is conserved with a motor domain where microtubule and ATP binding sites are predicted, a coiled-coil domain and a divergent tail domain. The Pe-kifc1 gene was extensively expressed and showed the highest expression in coelomic fluid where spermiogenesis occurs. We further observed the expression of kifc1 mRNA and protein and found that Pe-KIFC1 protein primarily co-localized with microtubules during spermiogenesis, indicating that KIFC1 might play several roles during this process via its cargo transport and/or microtubule organization function. In addition, co-localization of mitochondria and KIFC1 was also detected during spermiogenesis, which were located in the midpiece in mature sperm, suggesting that mitochondria might be a cargo of Pe-KIFC1 that participates in the intracellular distribution of mitochondria and formation of the midpiece. Based on our detailed observations of the dynamic distribution of microtubules, KIFC1, and mitochondria during spermiogenesis and the conserved function of KIFC1 in cargo transport and microtubule organization, functional models of Pe-KIFC1 during spermiogenesis are proposed, including the participation of KIFC1 in nuclear reshaping and midpiece formation.}, } @article {pmid30318512, year = {2018}, author = {Ananieva, EA and Bostic, JN and Torres, AA and Glanz, HR and McNitt, SM and Brenner, MK and Boyer, MP and Addington, AK and Hutson, SM}, title = {Mice deficient in the mitochondrial branched-chain aminotransferase (BCATm) respond with delayed tumour growth to a challenge with EL-4 lymphoma.}, journal = {British journal of cancer}, volume = {119}, number = {8}, pages = {1009-1017}, pmid = {30318512}, issn = {1532-1827}, support = {R01 DK034738/DK/NIDDK NIH HHS/United States ; R56 DK034738/DK/NIDDK NIH HHS/United States ; }, mesh = {AMP-Activated Protein Kinases/metabolism ; Amino Acids, Branched-Chain/blood ; Animals ; Disease Progression ; Female ; Lymphoma/*pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/genetics/*metabolism ; Neoplasm Transplantation ; Phosphorylation ; Transaminases/*genetics/*metabolism ; }, abstract = {BACKGROUND: The mitochondrial branched-chain aminotransferase (BCATm) is a recently discovered cancer marker with a poorly defined role in tumour progression.

METHODS: To understand how a loss of function of BCATm affects cancer, the global knockout mouse BCATmKO was challenged with EL-4 lymphoma under different diet compositions with varying amounts of branched-chain amino acids (BCAAs). Next, the growth and metabolism of EL-4 cells were studied in the presence of different leucine concentrations in the growth medium.

RESULTS: BCATmKO mice experienced delayed tumour growth when fed standard rodent chow or a normal BCAA diet. Tumour suppression correlated with 37.6- and 18.9-fold increases in plasma and tumour BCAAs, 37.5% and 30.4% decreases in tumour glutamine and alanine, and a 3.5-fold increase in the phosphorylation of tumour AMPK in BCATmKO mice on standard rodent chow. Similar results were obtained with a normal but not with a choice BCAA diet.

CONCLUSIONS: Global deletion of BCATm caused a dramatic build-up of BCAAs, which could not be utilised for energy or amino acid synthesis, ultimately delaying the growth of lymphoma tumours. Furthermore, physiological, but not high, leucine concentrations promoted the growth of EL-4 cells. BCATm and BCAA metabolism were identified as attractive targets for anti-lymphoma therapy.}, } @article {pmid30326676, year = {1974}, author = {Hinsch, GW and Walker, MH}, title = {The vas deferens of the spider crab, Libinia emarginata.}, journal = {Journal of morphology}, volume = {143}, number = {1}, pages = {1-19}, doi = {10.1002/jmor.1051430102}, pmid = {30326676}, issn = {1097-4687}, abstract = {Sperm enter the anterior vas deferens individually in the spider crab male. There they become surrounded by secretion products from the cells of the vas deferens, and are compartmentalized into spermatophores of varying size. The anterior vas deferens can be divided into three regions. The epithelium of the anterior vas deferens varies regionally from low to high columnar. The cytoplasm contains vast arrays of rough endoplasmic reticulum and Golgi complexes but few mitochondria. Intercellular spaces contain septate junctions, gap junctions and vesicles. Once the spermatophores have been formed in the anterior vas deferens, they are moved posteriorly to the middle vas deferens where they are stored and surrounded by seminal fluids. The epithelial cells of the middle vas deferens contain large amounts of rough endoplasmic reticulum and Golgi complexes. Numerous micropinocytotic vesicles appear, forming at the cell surface and within the apical cytoplasm. Their suggested function is the resorption of secretion products of the anterior vas deferens which initiated compartmentalization of the spermatozoa into spermatophores. The posterior vas deferens functions primarily as a storage center for spermatophores until they are released at the time of copulation. Seminal fluid surrounding the spermatophores is produced in this region as well as in the middle vas deferens. The cells of this region contain vast arrays of vesicular rough endoplasmic reticulum and Golgi complexes. The cells are multinucleate. Microtubules are numerous throughout the length of the cells and appear to insert on the plasma membrane.}, } @article {pmid30326913, year = {2018}, author = {Zhu, Y and Gu, X and Xu, C}, title = {Mitochondrial DNA 7908-8816 region mutations in maternally inherited essential hypertensive subjects in China.}, journal = {BMC medical genomics}, volume = {11}, number = {1}, pages = {89}, pmid = {30326913}, issn = {1755-8794}, mesh = {Adenosine Triphosphatases/genetics/metabolism ; Aged ; Asian People/*genetics ; Case-Control Studies ; China ; Cyclooxygenase 2/genetics ; DNA, Mitochondrial/*genetics ; Female ; Humans ; Hypertension/*genetics/pathology ; Male ; Maternal Inheritance ; Middle Aged ; Mutation ; RNA, Transfer/genetics ; }, abstract = {BACKGROUND: Nuclear genes or family-based mitochondrial screening have been the focus of genetic studies into essential hypertension. Studies into the role of mitochondria in sporadic Chinese hypertensives are lacking. The objective of the study was to explore the relationship between mitochondrial DNA (mtDNA) variations and the development of maternally inherited essential hypertension (MIEH) in China.

METHODS: Yangzhou residents who were outpatients or in-patients at the Department of Cardiology in Northern Jiangsu People's Hospital (Jiangsu, China) from June 2009 to June 2015 were recruited in a 1:1 case control study of 600 gender-matched Chinese MIEH subjects and controls. Genomic DNA was isolated from whole blood cells. The most likely sites for hypertension were screened using oligodeoxynucleotides at positions 7908-8816, purified and subsequently analyzed by direct sequencing according to the revised consensus Cambridge sequence. The frequency, density, type and conservative evolution of mtDNA variations were comprehensively analyzed.

RESULTS: We found a statistical difference between the two groups for body mass index, waist circumference, abdominal circumference, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, uric acid, creatinine and blood urea nitrogen (P < 0.05). More amino-acid changes and RNA variants were found in MIEH subjects than the controls (P < 0.01). The detection system simultaneously identified 40 different heteroplasmic or homoplasmic mutations in 4 genes: COXII, tRNA[Lys], ATP8 and ATP 6. The mtDNA variations were mainly distributed in regions of ATP6 binding sites, and the site of highest mutation frequency was m. 8414C > T. Three changes in single bases (C8414T in ATP8, A8701G in ATP6 and G8584A in ATP6) were significantly different in the MIEH patients and the controls (P < 0.001). The m.8273_8281del mutation was identified from 59 MIEH patients.

CONCLUSIONS: Our results indicate that novel mtDNA mutations may be involved in the pathological process of MIEH, and mitochondrial genetic characteristics were identified in MIEH individuals.}, } @article {pmid30328102, year = {2018}, author = {Nakazawa, M and Ando, H and Nishimoto, A and Ohta, T and Sakamoto, K and Ishikawa, T and Ueda, M and Sakamoto, T and Nakano, Y and Miyatake, K and Inui, H}, title = {Anaerobic respiration coupled with mitochondrial fatty acid synthesis in wax ester fermentation by Euglena gracilis.}, journal = {FEBS letters}, volume = {592}, number = {24}, pages = {4020-4027}, pmid = {30328102}, issn = {1873-3468}, mesh = {Acyl-CoA Dehydrogenase/genetics/metabolism ; Adenosine Diphosphate/biosynthesis ; Adenosine Triphosphate/biosynthesis ; Anaerobiosis ; *Cell Respiration ; Esters/chemistry/*metabolism ; Euglena gracilis/cytology/genetics/*metabolism ; Fatty Acids/*biosynthesis ; *Fermentation ; Mitochondria/drug effects/*metabolism ; RNA Interference ; Rotenone/pharmacology ; Uncoupling Agents/pharmacology ; Waxes/chemistry/metabolism ; }, abstract = {In Euglena gracilis, wax ester fermentation produces ATP during anaerobiosis. Here, we report that anaerobic wax ester production is suppressed when the mitochondrial electron transport chain complex I is inhibited by rotenone, whereas it is increased by the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP). The ADP/ATP ratio in anaerobic cells is elevated by treatment with either rotenone or CCCP. Gene silencing experiments indicate that acyl-CoA dehydrogenase, electron transfer flavoprotein (ETF), and rhodoquinone (RQ) participate in wax ester production. These results suggest that fatty acids are synthesized in mitochondria by the reversal of β-oxidation, where trans-2-enoyl-CoA is reduced mainly by acyl-CoA dehydrogenase using the electrons provided by NADH via the electron transport chain complex I, RQ, and ETF, and that ATP production is highly supported by anaerobic respiration utilizing trans-2-enoyl-CoA as a terminal electron acceptor.}, } @article {pmid30328804, year = {2018}, author = {Cao, M and Chen, K and Li, W and Ma, J and Xiao, Z and Wang, H and Gao, J}, title = {Genetic characterization of human-derived hydatid fluid based on mitochondrial gene sequencing in individuals from northern and western China.}, journal = {Journal of helminthology}, volume = {94}, number = {}, pages = {e2}, doi = {10.1017/S0022149X18000883}, pmid = {30328804}, issn = {1475-2697}, mesh = {Animals ; China ; Echinococcosis/*parasitology ; Echinococcus/classification/*genetics/*isolation & purification ; Electron Transport Complex IV/genetics ; Genes, Mitochondrial ; Helminth Proteins/genetics ; Humans ; Mitochondria/*genetics ; NADH Dehydrogenase/genetics ; Phylogeny ; Tibet ; }, abstract = {This study investigated Echinococcus genotypes in patients with hydatidosis that reside in Inner Mongolia, Tibet or Qinghai Province by partially sequencing the cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase 1 (nad1) genes. Cyst fluids were collected from 23 patients with hydatidosis and DNA was extracted. Portions of the cox1 and nad1 genes were amplified and subsequently sequenced. Sequencing analysis determined that one of the isolates contained Echinococcus multilocularis, and the other 22 isolates contained E. granulosus sensu lato. The isolates were then further classified based on genotype, and E. granulosus sensu stricto (s.s.) G1 (n = 20), E. granulosus s.s. G3 (n = 1) and E. canadensis G6/7 (n = 1) were identified. Additionally, the sequences were concatenated (pcox1 + pnad1) and 11 haplotypes were identified among the E. granulosus s.s. isolates (G1 and G3), with a shared common haplotype (H1) identified. Overall, these findings provide further understanding of the genetic patterns of Echinococcus in western and northern China.}, } @article {pmid30333973, year = {2018}, author = {Lou, E and Zhai, E and Sarkari, A and Desir, S and Wong, P and Iizuka, Y and Yang, J and Subramanian, S and McCarthy, J and Bazzaro, M and Steer, CJ}, title = {Cellular and Molecular Networking Within the Ecosystem of Cancer Cell Communication via Tunneling Nanotubes.}, journal = {Frontiers in cell and developmental biology}, volume = {6}, number = {}, pages = {95}, pmid = {30333973}, issn = {2296-634X}, support = {UL1 TR000114/TR/NCATS NIH HHS/United States ; }, abstract = {Intercellular communication is vital to the ecosystem of cancer cell organization and invasion. Identification of key cellular cargo and their varied modes of transport are important considerations in understanding the basic mechanisms of cancer cell growth. Gap junctions, exosomes, and apoptotic bodies play key roles as physical modalities in mediating intercellular transport. Tunneling nanotubes (TNTs)-narrow actin-based cytoplasmic extensions-are unique structures that facilitate direct, long distance cell-to-cell transport of cargo, including microRNAs, mitochondria, and a variety of other sub cellular components. The transport of cargo via TNTs occurs between malignant and stromal cells and can lead to changes in gene regulation that propagate the cancer phenotype. More notably, the transfer of these varied molecules almost invariably plays a critical role in the communication between cancer cells themselves in an effort to resist death by chemotherapy and promote the growth and metastases of the primary oncogenic cell. The more traditional definition of "Systems Biology" is the computational and mathematical modeling of complex biological systems. The concept, however, is now used more widely in biology for a variety of contexts, including interdisciplinary fields of study that focus on complex interactions within biological systems and how these interactions give rise to the function and behavior of such systems. In fact, it is imperative to understand and reconstruct components in their native context rather than examining them separately. The long-term objective of evaluating cancer ecosystems in their proper context is to better diagnose, classify, and more accurately predict the outcome of cancer treatment. Communication is essential for the advancement and evolution of the tumor ecosystem. This interplay results in cancer progression. As key mediators of intercellular communication within the tumor ecosystem, TNTs are the central topic of this article.}, } @article {pmid30340785, year = {2018}, author = {Dos Santos, RF and Quendera, AP and Boavida, S and Seixas, AF and Arraiano, CM and Andrade, JM}, title = {Major 3'-5' Exoribonucleases in the Metabolism of Coding and Non-coding RNA.}, journal = {Progress in molecular biology and translational science}, volume = {159}, number = {}, pages = {101-155}, doi = {10.1016/bs.pmbts.2018.07.005}, pmid = {30340785}, issn = {1878-0814}, mesh = {Animals ; Disease ; Exoribonucleases/chemistry/*metabolism ; Humans ; Open Reading Frames/genetics ; Phylogeny ; RNA, Untranslated/*genetics ; Substrate Specificity ; }, abstract = {3'-5' exoribonucleases are key enzymes in the degradation of superfluous or aberrant RNAs and in the maturation of precursor RNAs into their functional forms. The major bacterial 3'-5' exoribonucleases responsible for both these activities are PNPase, RNase II and RNase R. These enzymes are of ancient nature with widespread distribution. In eukaryotes, PNPase and RNase II/RNase R enzymes can be found in the cytosol and in mitochondria and chloroplasts; RNase II/RNase R-like enzymes are also found in the nucleus. Humans express one PNPase (PNPT1) and three RNase II/RNase R family members (Dis3, Dis3L and Dis3L2). These enzymes take part in a multitude of RNA surveillance mechanisms that are critical for translation accuracy. Although active against a wide range of both coding and non-coding RNAs, the different 3'-5' exoribonucleases exhibit distinct substrate affinities. The latest studies on these RNA degradative enzymes have contributed to the identification of additional homologue proteins, the uncovering of novel RNA degradation pathways, and to a better comprehension of several disease-related processes and response to stress, amongst many other exciting findings. Here, we provide a comprehensive and up-to-date overview on the function, structure, regulation and substrate preference of the key 3'-5' exoribonucleases involved in RNA metabolism.}, } @article {pmid30341492, year = {2019}, author = {Arakawa, T and Ue, S and Sano, C and Matsunaga, M and Kagami, H and Yoshida, Y and Kuroda, Y and Taguchi, K and Kitazaki, K and Kubo, T}, title = {Identification and characterization of a semi-dominant restorer-of-fertility 1 allele in sugar beet (Beta vulgaris).}, journal = {TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik}, volume = {132}, number = {1}, pages = {227-240}, pmid = {30341492}, issn = {1432-2242}, support = {18K05564//Japan Society for the Promotion of Science/ ; 16J01146//Japan Society for the Promotion of Science/ ; Research program on development of innovative technology//Bio-oriented Technology Research Advancement Institution/ ; Grant Number 30001A//Bio-oriented Technology Research Advancement Institution/ ; }, mesh = {Alleles ; Beta vulgaris/*genetics/*physiology ; *Genes, Dominant ; *Genes, Plant ; Genotype ; Mitochondrial Proteins/genetics ; Plant Infertility/*genetics ; Plants, Genetically Modified/physiology ; }, abstract = {The sugar beet Rf1 locus has a number of molecular variants. We found that one of the molecular variants is a weak allele of a previously identified allele. Male sterility (MS) caused by nuclear-mitochondrial interaction is called cytoplasmic male sterility (CMS) in which MS-inducing mitochondria are suppressed by a nuclear gene, restorer-of-fertility. Rf and rf are the suppressing and non-suppressing alleles, respectively. This dichotomic view, however, seems somewhat unsatisfactory to explain the recently discovered molecular diversity of Rf loci. In the present study, we first identified sugar beet line NK-305 as a new source of Rf1. Our crossing experiment revealed that NK-305 Rf1 is likely a semi-dominant allele that restores partial fertility when heterozygous but full fertility when homozygous, whereas Rf1 from another sugar beet line appeared to be a dominant allele. Proper degeneration of anther tapetum is a prerequisite for pollen development; thus, we compared tapetal degeneration in the NK-305 Rf1 heterozygote and the homozygote. Degeneration occurred in both genotypes but to a lesser extent in the heterozygote, suggesting an association between NK-305 Rf1 dose and incompleteness of tapetal degeneration leading to partial fertility. Our protein analyses revealed a quantitative correlation between NK-305 Rf1 dose and a reduction in the accumulation of a 250 kDa mitochondrial protein complex consisting of a CMS-specific mitochondrial protein encoded by MS-inducing mitochondria. The abundance of Rf1 transcripts correlated with NK-305 Rf1 dose. The molecular organization of NK-305 Rf1 suggested that this allele evolved through intergenic recombination. We propose that the sugar beet Rf1 locus has a series of multiple alleles that differ in their ability to restore fertility and are reflective of the complexity of Rf evolution.}, } @article {pmid30343708, year = {2018}, author = {Tanaka, A and Leung, PSC and Gershwin, ME}, title = {Evolution of our understanding of PBC.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {34-35}, number = {}, pages = {3-9}, doi = {10.1016/j.bpg.2018.05.008}, pmid = {30343708}, issn = {1532-1916}, mesh = {Animals ; Autoantibodies/blood ; Autoantigens/immunology ; Epitopes ; Humans ; Liver Cirrhosis, Biliary/*immunology/*pathology ; Mitochondria/immunology ; }, abstract = {The discovery of mitochondrial autoantigens recognized by antimitochondrial antibodies (AMAs) in 1987 marked the dawn of a new era in primary biliary cholangitis (PBC) research. Since then, there has been substantial progress in our understanding of PBC partly bestowed by the development of innovative technologies in molecular biology, immunology, and genetics. Here, we review this evolutionary progress in understanding PBC. We now recognize that the epitopes of AMAs, CD4[+], and CD8[+] T cells are all mapped to the same region of the inner lipoyl domain of pyruvate dehydrogenase complex E2 subunit (PDC-E2), and that intrahepatic biliary epithelial cells (BECs) are exclusively targeted in PBC. BECs express PDC-E2 on apotopes in an immunologically intact form during apoptosis, but not other epithelial cells, which could explain the tissue specificity of PBC. In addition, genetic factors, environmental triggers, and epigenetic modifications play crucial roles in the development of PBC. Intact lipoylated PDC-E2, presumably after modification with xenobiotics such as 2-octynamide or 2-nonyamide that are abundantly present in the environment, is endocytosed by antigen-presenting cells and are presented to CD4[+] or CD8[+] T cells. An immune complex consisting of PDC-E2 and anti-PDC-E2 autoantibodies cross-present autoantigens in a more efficient manner. Finally, an adenylate uridine-rich element (ARE) Del -/- mouse model has been established, which presents a disease modeling human PBC, including female dominance as one of its most important features, and can be used to dissect the immunopathology of PBC. Expanding our knowledge of the pathology from a very early stage of the disease will provide the key to cure PBC.}, } @article {pmid30346990, year = {2018}, author = {Costa-Martins, AG and Lima, L and Alves, JMP and Serrano, MG and Buck, GA and Camargo, EP and Teixeira, MMG}, title = {Genome-wide identification of evolutionarily conserved Small Heat-Shock and eight other proteins bearing α-crystallin domain-like in kinetoplastid protists.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0206012}, pmid = {30346990}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Cilia/metabolism ; *Conserved Sequence ; Cytoskeleton/metabolism ; *Evolution, Molecular ; *Genome ; Heat-Shock Proteins, Small/*chemistry/*genetics ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; Phylogeny ; Prokaryotic Cells/metabolism ; Protein Domains ; Synteny/genetics ; Trypanosomatina/*genetics ; alpha-Crystallins/*chemistry ; }, abstract = {Small Heat-Shock Proteins (sHSPs) and other proteins bearing alpha-crystallin domains (ACD) participate in defense against heat and oxidative stress and play important roles in cell cycle, cytoskeleton dynamics, and immunological and pathological mechanisms in eukaryotes. However, little is known about these proteins in early-diverging lineages of protists such as the kinetoplastids. Here, ACD-like proteins (ACDp) were investigated in genomes of 61 species of 12 kinetoplastid genera, including Trypanosoma spp. (23 species of mammals, reptiles and frogs), Leishmania spp. (mammals and lizards), trypanosomatids of insects, Phytomonas spp. of plants, and bodonids. Comparison of ACDps based on domain architecture, predicted tertiary structure, phylogeny and genome organization reveals a kinetoplastid evolutionarily conserved repertoire, which diversified prior to trypanosomatid adaptation to parasitic life. We identified 9 ACDp orthologs classified in 8 families of TryACD: four previously recognized (HSP20, Tryp23A, Tryp23B and ATOM69), and four characterized for the first time in kinetoplastids (TryACDP, TrySGT1, TryDYX1C1 and TryNudC). A single copy of each ortholog was identified in each genome alongside TryNudC1/TrypNudC2 homologs and, overall, ACDPs were under strong selection pressures at main phylogenetic lineages. Transcripts of all ACDPs were identified across the life stages of T. cruzi, T. brucei and Leishmania spp., but proteomic profiles suggested that most ACDPs may be species- and stage-regulated. Our findings establish the basis for functional studies, and provided evolutionary and structural support for an underestimated repertoire of ACDps in the kinetoplastids.}, } @article {pmid30347227, year = {2019}, author = {Xin, L and Huang, B and Li, C and Bai, C and Wang, C}, title = {Characterization of a nucleus located mollusc mitoferrin and its response to OsHV-1 infection.}, journal = {Biochimica et biophysica acta. General subjects}, volume = {1863}, number = {1}, pages = {255-265}, doi = {10.1016/j.bbagen.2018.10.014}, pmid = {30347227}, issn = {1872-8006}, mesh = {Animals ; Cell Nucleus/*metabolism ; Computational Biology ; Cytosol/metabolism ; DNA Viruses/*physiology ; Female ; Ferritins/metabolism ; Herpesviridae Infections/*veterinary ; Humans ; Immunohistochemistry ; Iron/metabolism ; Membrane Transport Proteins/*chemistry ; Mice ; Mitochondria/metabolism ; Mollusca/*virology ; Phylogeny ; Protein Domains ; Recombinant Proteins/chemistry ; Tissue Distribution ; }, abstract = {Mitoferrin genes as members of SLC25 family are conservatively existed across species, mainly locate on mitochondria and serve an important role in the regulation of whole cellular iron metabolism. Available iron withholding from pathogens presents an important host defense strategy, while the regulation role of mitoferrin against invading pathogens is largely unknown. In this study, a unique mollusc mitoferrin gene was identified in ark clams, named SbmiFn, that showed conserved three-dimensional structure with other mitoferrins, and its iron binding activity was verified by iron chelating assay. Besides cytoplasmic distribution, colocalization between SbmiFn and nuclei was observed by immunohistochemistry assay. Moreover, the response of SbmiFn to viral pathogen OsHV-1 was investigated. The results showed that nucleus located signal of SbmiFn was enhanced, the expressions of SbmiFn and ferritin were coordinately decreased, which might assist host against OsHV-1 replication as the increase of OsHV-1 copies were hardly detected after that. These results refreshed our knowledge on the sequence, structure and functional characteristics of mitoferrin subfamily, and would contribute to further comparative studies on iron metabolism.}, } @article {pmid30347487, year = {2019}, author = {Ligas, J and Pineau, E and Bock, R and Huynen, MA and Meyer, EH}, title = {The assembly pathway of complex I in Arabidopsis thaliana.}, journal = {The Plant journal : for cell and molecular biology}, volume = {97}, number = {3}, pages = {447-459}, doi = {10.1111/tpj.14133}, pmid = {30347487}, issn = {1365-313X}, support = {PIRG256398/MCCC_/Marie Curie/United Kingdom ; }, mesh = {Arabidopsis/*enzymology/genetics ; Electron Transport ; Electron Transport Complex I/genetics/*metabolism ; Evolution, Molecular ; Mitochondria/metabolism ; Proteomics ; }, abstract = {All present-day mitochondria originate from a single endosymbiotic event that gave rise to the last eukaryotic common ancestor more than a billion years ago. However, to date, many aspects of mitochondrial evolution have remained unresolved. Comparative genomics and proteomics have revealed a complex evolutionary origin for many mitochondrial components. To understand the evolution of the respiratory chain, we have examined both the components and the mechanisms of the assembly pathway of complex I. Complex I represents the first enzyme in the respiratory chain, and complex I deficiencies have dramatic consequences in both animals and plants. The complex is located in the mitochondrial inner membrane and possesses two arms: one embedded in the inner membrane and one protruding in the matrix. Here, we describe the assembly pathway of complex I in the model plant Arabidopsis thaliana. Using a proteomics approach called complexome profiling, we have resolved the different steps in the assembly process in plants. We propose a model for the stepwise assembly of complex I, including every subunit. We then compare this pathway with the corresponding pathway in humans and find that complex I assembly in plants follows a different, and likely ancestral, pathway compared with the one in humans. We show that the main evolutionary changes in complex I structure and assembly in humans occurred at the level of the membrane arm, whereas the matrix arm remained rather conserved.}, } @article {pmid30350319, year = {2018}, author = {Temereva, EN and Kuzmina, TV}, title = {Spermatogenesis in the deep-sea brachiopod Pelagodiscus atlanticus and the phylogenetic significance of spermatozoon structure.}, journal = {Journal of morphology}, volume = {279}, number = {11}, pages = {1579-1589}, doi = {10.1002/jmor.20887}, pmid = {30350319}, issn = {1097-4687}, support = {17-04-00586//Russian Foundation for Basic Research/International ; #14-50-00034//Russian Science Foundation/International ; #18-14-00082//Russian Science Foundation/International ; }, mesh = {Animals ; Invertebrates/*classification/*physiology ; Male ; Models, Biological ; *Phylogeny ; *Spermatogenesis ; Spermatogonia/cytology/ultrastructure ; Spermatozoa/cytology/*ultrastructure ; }, abstract = {Details of spermatogenesis and sperm organization are often useful for reconstructing the phylogeny of closely related groups of invertebrates. Development in general and gametogenesis in particular usually differ in shallow water and deep-sea invertebrates. Here, the spermatogenesis and ultrastructure of sperm were studied in the deep-sea brachiopod Pelagodiscus atlanticus. The testes of P. atlanticus are voluminous sacs located along the lateral sides of the body. Germ cells develop around the blood capillaries, contact the basal lamina, and contain germ plasm, numerous mitochondria, Golgi apparatus, lipid droplets, and centrioles of the rudimentary cilium. During spermatogenesis, several proacrosomal vesicles appear at the posterior pole of the cell; these vesicles then fuse and migrate to the anterior pole. The spermatozoon has a head with an acrosome, nucleus, eight mitochondria, proximal and distal centrioles orthogonally arranged, and a long tail. Comparative analysis suggests that the spermatozoon of P. atlanticus can be considered the most ancestral among all brachiopods. Such an organization indicates that fertilization is external in this deep-sea species. Spermatozoa of other brachiopods should be regarded as derived from this ancestral type. The transformation of brachiopod spermatozoa might have occurred in three different ways that correspond to the three main clades of recent brachiopods: Linguliformea, Craniiformea, and Rhynchonelliformea.}, } @article {pmid30353148, year = {2018}, author = {Ng, NSR and Prawiradilaga, DM and Ng, EYX and Suparno, and Ashari, H and Trainor, C and Verbelen, P and Rheindt, FE}, title = {A striking new species of leaf warbler from the Lesser Sundas as uncovered through morphology and genomics.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {15646}, pmid = {30353148}, issn = {2045-2322}, mesh = {Acoustics ; Animals ; Cytochromes b/genetics ; *Genomics ; Geography ; Indonesia ; Islands ; Likelihood Functions ; Mitochondria/genetics ; Phylogeny ; Principal Component Analysis ; Songbirds/*anatomy & histology/*genetics ; Sound Spectrography ; Species Specificity ; }, abstract = {Leaf warblers (Aves; Phylloscopidae) are a diverse clade of insectivorous, canopy-dwelling songbirds widespread across the Old World. The taxonomy of Australasian leaf warblers is particularly complex, with multiple species-level divergences between island taxa in the region requiring further scrutiny. We use a combination of morphology, bioacoustics, and analysis of thousands of genome-wide markers to investigate and describe a new species of Phylloscopus leaf warbler from the island of Rote in the Lesser Sundas, Indonesia. We show that this new Rote Leaf Warbler is morphologically and genomically highly distinct from its congenerics, but do not find vocal differentiation between different island taxa. We discuss the behaviour and ecology of this highly distinctive new species, and make recommendations about its conservation status. We believe this constitutes the first description of a novel bird species that is partly based on insights from massive amounts of genome-wide DNA markers.}, } @article {pmid30356218, year = {2018}, author = {Katsyuba, E and Mottis, A and Zietak, M and De Franco, F and van der Velpen, V and Gariani, K and Ryu, D and Cialabrini, L and Matilainen, O and Liscio, P and Giacchè, N and Stokar-Regenscheit, N and Legouis, D and de Seigneux, S and Ivanisevic, J and Raffaelli, N and Schoonjans, K and Pellicciari, R and Auwerx, J}, title = {De novo NAD[+] synthesis enhances mitochondrial function and improves health.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {354-359}, pmid = {30356218}, issn = {1476-4687}, mesh = {Animals ; Caenorhabditis elegans/cytology/enzymology/metabolism ; Carboxy-Lyases/antagonists & inhibitors/chemistry/deficiency/*metabolism ; Cell Line ; Choline ; *Conserved Sequence ; Disease Models, Animal ; *Evolution, Molecular ; Female ; Gene Knockdown Techniques ; *Health ; Hepatocytes/cytology/drug effects ; Homeostasis/drug effects ; Humans ; Kidney/cytology/drug effects ; Liver/cytology/drug effects ; Longevity/drug effects ; Male ; Methionine/deficiency ; Mice ; Mice, Inbred C57BL ; Mitochondria/*physiology ; NAD/*biosynthesis ; Non-alcoholic Fatty Liver Disease/physiopathology/prevention & control ; Rats ; Sirtuins/metabolism ; }, abstract = {Nicotinamide adenine dinucleotide (NAD[+]) is a co-substrate for several enzymes, including the sirtuin family of NAD[+]-dependent protein deacylases. Beneficial effects of increased NAD[+] levels and sirtuin activation on mitochondrial homeostasis, organismal metabolism and lifespan have been established across species. Here we show that α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), the enzyme that limits spontaneous cyclization of α-amino-β-carboxymuconate-ε-semialdehyde in the de novo NAD[+] synthesis pathway, controls cellular NAD[+] levels via an evolutionarily conserved mechanism in Caenorhabditis elegans and mouse. Genetic and pharmacological inhibition of ACMSD boosts de novo NAD[+] synthesis and sirtuin 1 activity, ultimately enhancing mitochondrial function. We also characterize two potent and selective inhibitors of ACMSD. Because expression of ACMSD is largely restricted to kidney and liver, these inhibitors may have therapeutic potential for protection of these tissues from injury. In summary, we identify ACMSD as a key modulator of cellular NAD[+] levels, sirtuin activity and mitochondrial homeostasis in kidney and liver.}, } @article {pmid30358047, year = {2018}, author = {Gabaldón, T}, title = {Relative timing of mitochondrial endosymbiosis and the "pre-mitochondrial symbioses" hypothesis.}, journal = {IUBMB life}, volume = {70}, number = {12}, pages = {1188-1196}, pmid = {30358047}, issn = {1521-6551}, mesh = {Archaea/genetics/metabolism ; *Biological Evolution ; Eukaryotic Cells/metabolism ; Mitochondria/*genetics ; *Phylogeny ; Prokaryotic Cells/metabolism ; Symbiosis/*genetics ; }, abstract = {The origin of eukaryotes stands as a major open question in biology. Central to this question is the nature and timing of the origin of the mitochondrion, an ubiquitous eukaryotic organelle originated by the endosymbiosis of an alphaproteobacterial ancestor. Different hypotheses disagree, among other aspects, on whether mitochondria were acquired early or late during eukaryogenesis. Similarly, the nature and complexity of the receiving host is debated, with models ranging from a simple prokaryotic host to an already complex proto-eukaryote. Here, I will discuss recent findings from phylogenomics analyses of extant genomes that are shedding light into the evolutionary origins of the eukaryotic ancestor, and which suggest a later acquisition of alpha-proteobacterial derived proteins as compared to those with different bacterial ancestries. I argue that simple eukaryogenesis models that assume a binary symbiosis between an archaeon host and an alpha-proteobacterial proto-mitochondrion cannot explain the complex chimeric nature that is inferred for the eukaryotic ancestor. To reconcile existing hypotheses with the new data, I propose the "pre-mitochondrial symbioses" hypothesis that provides a framework for eukaryogenesis scenarios involving alternative symbiotic interactions that predate the acquisition of mitochondria. © 2018 The Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 70(12):1188-1196, 2018.}, } @article {pmid30358065, year = {2018}, author = {Paris, Z and Alfonzo, JD}, title = {How the intracellular partitioning of tRNA and tRNA modification enzymes affects mitochondrial function.}, journal = {IUBMB life}, volume = {70}, number = {12}, pages = {1207-1213}, pmid = {30358065}, issn = {1521-6551}, support = {R01 GM084065/GM/NIGMS NIH HHS/United States ; R56 AI131248/AI/NIAID NIH HHS/United States ; U01 AI131348/AI/NIAID NIH HHS/United States ; }, mesh = {Cytoplasm/genetics ; Genome, Mitochondrial/*genetics ; Intracellular Membranes ; Mitochondria/*genetics ; Mitochondrial Membranes/metabolism ; Protein Biosynthesis/*genetics ; RNA Processing, Post-Transcriptional/genetics ; RNA, Transfer/*genetics ; Symbiosis/genetics ; }, abstract = {Organisms have evolved different strategies to seclude certain molecules to specific locations of the cell. This is most pronounced in eukaryotes with their extensive intracellular membrane systems. Intracellular compartmentalization is particularly critical in genome containing organelles, which because of their bacterial evolutionary ancestry still maintain protein-synthesis machinery that resembles more their evolutionary origin than the extant eukaryotic cell they once joined as an endosymbiont. Despite this, it is clear that genome-containing organelles such as the mitochondria are not in isolation and many molecules make it across the mitochondrial membranes from the cytoplasm. In this realm the import of tRNAs and the enzymes that modify them prove most consequential. In this review, we discuss two recent examples of how modifications typically found in cytoplasmic tRNAs affect mitochondrial translation in organisms that forcibly import all their tRNAs from the cytoplasm. In our view, the combination of tRNA import and the compartmentalization of modification enzymes must have played a critical role in the evolution of the organelle. © 2018 IUBMB Life, 70(12):1207-1213, 2018.}, } @article {pmid30358089, year = {2018}, author = {Gray, MW and Mootha, VK}, title = {Evolutionary mitochondrial biology in titisee.}, journal = {IUBMB life}, volume = {70}, number = {12}, pages = {1184-1187}, doi = {10.1002/iub.1958}, pmid = {30358089}, issn = {1521-6551}, mesh = {*Evolution, Molecular ; Humans ; Mitochondria/*genetics/metabolism ; Molecular Biology/*trends ; }, } @article {pmid30358111, year = {2018}, author = {Yu, J and Zhang, L and Li, Y and Zhu, X and Xu, S and Zhou, XM and Wang, H and Zhang, H and Liang, B and Liu, P}, title = {The Adrenal Lipid Droplet is a New Site for Steroid Hormone Metabolism.}, journal = {Proteomics}, volume = {18}, number = {23}, pages = {e1800136}, doi = {10.1002/pmic.201800136}, pmid = {30358111}, issn = {1615-9861}, mesh = {Adrenal Glands/metabolism ; Animals ; Gonadal Steroid Hormones/metabolism ; HeLa Cells ; Humans ; Lipid Droplets/*metabolism ; Lipid Metabolism/physiology ; Macaca ; Progesterone Reductase/metabolism ; }, abstract = {Steroid hormones play essential roles for living organisms. It has been long and well established that the endoplasmic reticulum (ER) and mitochondria are essential sites for steroid hormone biosynthesis because several steroidogenic enzymes are located in these organelles. The adrenal gland lipid droplet (LD) proteomes from human, macaque monkey, and rodent are analyzed, revealing that steroidogenic enzymes are also present in abundance on LDs. The enzymes found include 3β-hydroxysteroid dehydrogenase (HSD3B) and estradiol 17β-dehydrogenase 11 (HSD17B11). Analyses by Western blot and subcellular localization consistently demonstrate that HSD3B2 is localized on LDs. Furthermore, in vitro experiments confirm that the isolated LDs from HeLa cell stably expressing HSD3B2 or from rat adrenal glands have the capacity to convert pregnenolone to progesterone. Collectively, these data suggest that LDs may be important sites of steroid hormone metabolism. These findings may bring novel insights into the biosynthesis and metabolism of steroid hormones and the development of treatments for adrenal disorders.}, } @article {pmid30364957, year = {2018}, author = {Lee, JM and Song, HJ and Park, SI and Lee, YM and Jeong, SY and Cho, TO and Kim, JH and Choi, HG and Choi, CG and Nelson, WA and Fredericq, S and Bhattacharya, D and Yoon, HS}, title = {Mitochondrial and Plastid Genomes from Coralline Red Algae Provide Insights into the Incongruent Evolutionary Histories of Organelles.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2961-2972}, pmid = {30364957}, issn = {1759-6653}, mesh = {*Biological Evolution ; *Genome, Mitochondrial ; *Genome, Plastid ; Rhodophyta/*genetics ; }, abstract = {Mitochondria and plastids are generally uniparentally inherited and have a conserved gene content over hundreds of millions of years, which makes them potentially useful phylogenetic markers. Organelle single gene-based trees have long been the basis for elucidating interspecies relationships that inform taxonomy. More recently, high-throughput genome sequencing has enabled the construction of massive organelle genome databases from diverse eukaryotes, and these have been used to infer species relationships in deep evolutionary time. Here, we test the idea that despite their expected utility, conflicting phylogenetic signal may exist in mitochondrial and plastid genomes from the anciently diverged coralline red algae (Rhodophyta). We generated complete organelle genome data from five coralline red algae (Lithothamnion sp., Neogoniolithon spectabile, Renouxia sp., Rhodogorgon sp., and Synarthrophyton chejuensis) for comparative analysis with existing organelle genome data from two other species (Calliarthron tuberculosum and Sporolithon durum). We find strong evidence for incongruent phylogenetic signal from both organelle genomes that may be explained by incomplete lineage sorting that has maintained anciently derived gene copies or other molecular evolutionary processes such as hybridization or gene flow during the evolutionary history of coralline red algae.}, } @article {pmid30368957, year = {2018}, author = {Olsson, M and Friesen, CR and Rollings, N and Sudyka, J and Lindsay, W and Whittington, CM and Wilson, M}, title = {Long-term effects of superoxide and DNA repair on lizard telomeres.}, journal = {Molecular ecology}, volume = {27}, number = {24}, pages = {5154-5164}, doi = {10.1111/mec.14913}, pmid = {30368957}, issn = {1365-294X}, support = {//Swedish Science Council/International ; //Australian Research Council/International ; }, mesh = {Animals ; Australia ; DNA Damage ; *DNA Repair ; Female ; In Situ Hybridization, Fluorescence ; Lizards/*genetics ; Male ; Mitochondria/genetics ; Oxidative Stress ; *Seasons ; Superoxides/*chemistry ; Telomere/*genetics ; Telomere Shortening ; }, abstract = {Telomeres are the non-coding protein-nucleotide "caps" at chromosome ends that contribute to chromosomal stability by protecting the coding parts of the linear DNA from shortening at cell division, and from erosion by reactive molecules. Recently, there has been some controversy between molecular and cell biologists, on the one hand, and evolutionary ecologists on the other, regarding whether reactive molecules erode telomeres during oxidative stress. Many studies of biochemistry and medicine have verified these relationships in cell culture, but other researchers have failed to find such effects in free-living vertebrates. Here, we use a novel approach to measure free radicals (superoxide), mitochondrial "content" (a combined measure of mitochondrial number and size in cells), telomere length and DNA damage at two primary time points during the mating season of an annual lizard species (Ctenophorus pictus). Superoxide levels early in the mating season vary widely and elevated levels predict shorter telomeres both at that time as well as several months later. These effects are likely driven by mitochondrial content, which significantly impacts late season superoxide (cells with more mitochondria have more superoxide), but superoxide effects on telomeres are counteracted by DNA repair as revealed by 8-hydroxy-2'-deoxyguanosine assays. We conclude that reactive oxygen species and DNA repair are fundamental for both short- and long-term regulation of lizard telomere length with pronounced effects of early season cellular stress detectable on telomere length near lizard death.}, } @article {pmid30373326, year = {2018}, author = {Bombaça, ACS and Dossow, DV and Barbosa, JMC and Paz, C and Burgos, V and Menna-Barreto, RFS}, title = {TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in Trypanosomacruzi.}, journal = {Molecules (Basel, Switzerland)}, volume = {23}, number = {11}, pages = {}, pmid = {30373326}, issn = {1420-3049}, mesh = {Autophagy/*drug effects ; Mitochondria/*drug effects/ultrastructure ; Molecular Structure ; Reactive Oxygen Species/*metabolism ; Sesquiterpenes/*chemistry/isolation & purification/*pharmacology ; Trypanocidal Agents/*chemistry/isolation & purification/*pharmacology ; Trypanosoma cruzi/*drug effects/*metabolism/ultrastructure ; }, abstract = {Chagas disease is a neglected tropical disease that is caused by the protozoan Trypanosomacruzi and represents a serious health problem, especially in Latin America. The clinical treatment of Chagas disease is based on two nitroderivatives that present severe side effects and important limitations. In folk medicine, natural products, including sesquiterpenoids, have been employed for the treatment of different parasitic diseases. In this study, the trypanocidal activity of compounds isolated from the Chilean plants Drimys winteri, Podanthus mitiquiand Maytenus boaria on three T. cruzi evolutive forms (epimastigote, trypomastigote and amastigote) was evaluated. Total extracts and seven isolated sesquiterpenoids were assayed on trypomastigotes and epimastigotes. Polygodial (Pgd) from D. winteri, total extract from P. mitiqui (PmTE) and the germacrane erioflorin (Efr) from P. mitiqui were the most bioactive substances. Pgd, Efr and PmTE also presented strong effects on intracellular amastigotes and low host toxicity. Many ultrastructural effects of these substances, including reservosome disruption, cytosolic vacuolization, autophagic phenotype and mitochondrial swelling (in the case of Pgd), were observed. Flow cytometric analysis demonstrated a reduction in mitochondrial membrane potential in treated epimastigotes and an increase in ROS production and high plasma membrane permeability after treatment with Pgd. The promising trypanocidal activity of these natural sesquiterpenoids may be a good starting point for the development of alternative treatmentsforChagas disease.}, } @article {pmid30373839, year = {2018}, author = {Mehta, AP and Supekova, L and Chen, JH and Pestonjamasp, K and Webster, P and Ko, Y and Henderson, SC and McDermott, G and Supek, F and Schultz, PG}, title = {Engineering yeast endosymbionts as a step toward the evolution of mitochondria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11796-11801}, pmid = {30373839}, issn = {1091-6490}, support = {P41 GM103445/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Bioengineering/*methods ; Biological Evolution ; Escherichia coli/genetics/metabolism ; Mitochondria/*genetics/metabolism ; Models, Biological ; Saccharomyces cerevisiae/genetics/metabolism ; Symbiosis/*genetics ; Thiamine/metabolism ; }, abstract = {It has been hypothesized that mitochondria evolved from a bacterial ancestor that initially became established in an archaeal host cell as an endosymbiont. Here we model this first stage of mitochondrial evolution by engineering endosymbiosis between Escherichia coli and Saccharomyces cerevisiae An ADP/ATP translocase-expressing E. coli provided ATP to a respiration-deficient cox2 yeast mutant and enabled growth of a yeast-E. coli chimera on a nonfermentable carbon source. In a reciprocal fashion, yeast provided thiamin to an endosymbiotic E. coli thiamin auxotroph. Expression of several SNARE-like proteins in E. coli was also required, likely to block lysosomal degradation of intracellular bacteria. This chimeric system was stable for more than 40 doublings, and GFP-expressing E. coli endosymbionts could be observed in the yeast by fluorescence microscopy and X-ray tomography. This readily manipulated system should allow experimental delineation of host-endosymbiont adaptations that occurred during evolution of the current, highly reduced mitochondrial genome.}, } @article {pmid30377874, year = {2018}, author = {Cai, C and Liu, F and Jiang, T and Wang, L and Jia, R and Zhou, L and Gu, K and Ren, J and He, P}, title = {Comparative study on mitogenomes of green tide algae.}, journal = {Genetica}, volume = {146}, number = {6}, pages = {529-540}, pmid = {30377874}, issn = {1573-6857}, support = {18ZR1417400//Shanghai Natural Science Fund/ ; 41576163//National Natural Science Foundation of China/ ; 2016YFC1402105//National Key R&D Program of China/ ; MATHAB2017010//Key Laboratory of Integrated Marine Monitoring and Applied Technologies for Harmful Algal Blooms, S.O.A./ ; }, mesh = {Codon/genetics ; Evolution, Molecular ; *Genome, Mitochondrial ; Microsatellite Repeats ; Open Reading Frames ; RNA, Transfer/genetics ; Sequence Homology, Nucleic Acid ; Ulva/classification/*genetics ; }, abstract = {Since 2007, the annual green tide disaster in the Yellow Sea has brought serious economic losses to China. There is no research on the genetic similarities of four constituent species of green tide algae at the genomic level. We previously determined the mitochondrial genomes of Ulva prolifera, Ulva linza and Ulva flexuosa. In the present work, the mitochondrial genome of another green tide (Ulva compressa) was sequenced and analyzed. With the length of 62,311 bp, it contained 29 encoding genes, 26 tRNAs and 10 open reading frames. By comparing these four mitochondrial genomes, we found that U. compressa was quite different from the other three types of Ulva species. However, there were similarities between U. prolifera and U. linza in the number, distribution and homology of open reading frames, evolutionary and codon variation of tRNA, evolutionary relationship and selection pressure of coding genes. Repetitive sequence analysis of simple sequence repeats, tandem repeat and forward repeats further supposed that they have evolved from the same origin. In addition, we directly analyzed gene homologies and translocation of four green tide algae by Mauve alignment. There were gene order rearrangements among them. With fast-evolving genomes, these four green algal mitochondria have both conservatism and variation, thus opening another window for the understanding of origin and evolution of Ulva.}, } @article {pmid30378025, year = {2018}, author = {Gabaldón, T}, title = {Evolution of the Peroxisomal Proteome.}, journal = {Sub-cellular biochemistry}, volume = {89}, number = {}, pages = {221-233}, doi = {10.1007/978-981-13-2233-4_9}, pmid = {30378025}, issn = {0306-0225}, mesh = {Eukaryota/cytology ; Eukaryotic Cells/cytology ; *Evolution, Molecular ; Peroxisomes/*chemistry/*metabolism ; *Phylogeny ; Proteome/*metabolism ; *Proteomics ; }, abstract = {Peroxisomes are single-membrane bound intracellular organelles that can be found in organisms across the tree of eukaryotes, and thus are likely to derive from an ancestral peroxisome in the last eukaryotic common ancestor (LECA). Yet, peroxisomes in different lineages can present a large diversity in terms of their metabolic capabilities, which reflects a highly variable proteomic content. Theories on the evolutionary origin of peroxisomes have shifted in the last decades from scenarios involving an endosymbiotic origin, similar to those of mitochondria and plastids, towards hypotheses purporting an endogenous origin from within the endomembrane system. The peroxisomal proteome is highly dynamic in evolutionary terms, and can evolve via differential loss and gain of proteins, as well as via relocalization of proteins from and to other sub-cellular compartments. Here, I review current knowledge and discussions on the diversity, origin, and evolution of the peroxisomal proteome.}, } @article {pmid30385240, year = {2018}, author = {Palozzi, JM and Jeedigunta, SP and Hurd, TR}, title = {Mitochondrial DNA Purifying Selection in Mammals and Invertebrates.}, journal = {Journal of molecular biology}, volume = {430}, number = {24}, pages = {4834-4848}, doi = {10.1016/j.jmb.2018.10.019}, pmid = {30385240}, issn = {1089-8638}, support = {FRN 159510//CIHR/Canada ; }, mesh = {Animals ; DNA, Mitochondrial/*genetics ; Evolution, Molecular ; Female ; Humans ; Invertebrates/*genetics/growth & development ; Mammals/*genetics/growth & development ; Maternal Inheritance ; Mitochondria/*genetics ; Ovum/chemistry/*cytology ; Quality Control ; Selection, Genetic ; }, abstract = {Numerous mitochondrial quality control mechanisms exist within cells, but none have been shown to effectively assess and control the quality of mitochondrial DNA (mtDNA). One reason such mechanisms have yet to be elucidated is that they do not appear to be particularly active in most somatic cells, where many studies are conducted. The female germline, the cell lineage that gives rise to eggs, appears to be an exception. In the germline, strong purifying selection pathways act to eliminate deleterious mtDNA. These pathways have apparently evolved to prevent pathogenic mtDNA mutations from accumulating over successive generations and causing a decline of species via Muller's ratchet. Despite their fundamental biological importance, the mechanisms underlying purifying selection remain poorly understood, with no genes involved in this process yet identified. In this review, we discuss recent studies exploring mechanisms of germline mtDNA purifying selection in both mammalian and invertebrate systems. We also discuss the challenges to future major advances. Understanding the molecular basis of purifying selection is not only a fundamental outstanding question in biology, but may also pave the way to controlling selection in somatic tissues, potentially leading to treatments for people suffering from mitochondrial diseases.}, } @article {pmid30385634, year = {2018}, author = {Loell, K and Nanda, V}, title = {Marginal protein stability drives subcellular proteome isoelectric point.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11778-11783}, pmid = {30385634}, issn = {1091-6490}, support = {80NSSC18K0093/NSSC/Shared Services Center NASA/United States ; DP2 OD006478/OD/NIH HHS/United States ; }, mesh = {Computer Simulation ; Databases, Protein ; Evolution, Molecular ; Humans ; Hydrogen-Ion Concentration ; Isoelectric Point ; Lysosomes/metabolism ; Protein Folding ; Protein Stability ; Proteome/*chemistry/metabolism ; Proteomics/*methods ; Subcellular Fractions/chemistry/metabolism ; }, abstract = {There exists a positive correlation between the pH of subcellular compartments and the median isoelectric point (pI) for the associated proteomes. Proteins in the human lysosome-a highly acidic compartment in the cell-have a median pI of ∼6.5, whereas proteins in the more basic mitochondria have a median pI of ∼8.0. Proposed mechanisms reflect potential adaptations to pH. For example, enzyme active site general acid/base residue pKs are likely evolved to match environmental pH. However, such effects would be limited to a few residues on specific proteins, and might not affect the proteome at large. A protein model that considers residue burial upon folding recapitulates the correlation between proteome pI and environmental pH. This correlation can be fully described by a neutral evolution process; no functional selection is included in the model. Proteins in acidic environments incur a lower energetic penalty for burying acidic residues than basic residues, resulting in a net accumulation of acidic residues in the protein core. The inverse is true under alkaline conditions. The pI distributions of subcellular proteomes are likely not a direct result of functional adaptations to pH, but a molecular spandrel stemming from marginal stability.}, } @article {pmid30390623, year = {2018}, author = {Portugez, S and Martin, WF and Hazkani-Covo, E}, title = {Mosaic mitochondrial-plastid insertions into the nuclear genome show evidence of both non-homologous end joining and homologous recombination.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {162}, pmid = {30390623}, issn = {1471-2148}, mesh = {Base Sequence ; Cell Nucleus/*genetics ; DNA End-Joining Repair/*genetics ; DNA, Mitochondrial/genetics ; *Genome, Plant ; Homologous Recombination/*genetics ; Mitochondria/*genetics ; *Mosaicism ; Mutagenesis, Insertional/*genetics ; Plastids/*genetics ; }, abstract = {BACKGROUND: Mitochondrial and plastid DNA fragments are continuously transferred into eukaryotic nuclear genomes, giving rise to nuclear copies of mitochondrial DNA (numts) and nuclear copies of plastid DNA (nupts). Numts and nupts are classified as simple if they are composed of a single organelle fragment or as complex if they are composed of multiple fragments. Mosaic insertions are complex insertions composed of fragments of both mitochondrial and plastid DNA. Simple numts and nupts in eukaryotes have been extensively studied, their mechanism of insertion involves non-homologous end joining (NHEJ). Mosaic insertions have been less well-studied and their mechanisms of integration are unknown.

RESULTS: Here we estimated the number of nuclear mosaic insertions (numins) in nine plant genomes. We show that numins compose up to 10% of the total nuclear insertions of organelle DNA in these plant genomes. The NHEJ hallmarks typical for numts and nupts were also identified in mosaic insertions. However, the number of identified insertions that integrated via NHEJ mechanism is underestimated, as NHEJ signatures are conserved only in recent insertions and mutationally eroded in older ones. A few complex insertions show signatures of long homology that cannot be attributed to NHEJ, a novel observation that implicates gene conversion or single strand annealing mechanisms in organelle nuclear insertions.

CONCLUSIONS: The common NHEJ signature that was identified here reveals that, in plant cells, mitochondria and plastid fragments in numins must meet during or prior to integration into the nuclear genome.}, } @article {pmid30391331, year = {2019}, author = {Xu, L and Peng, L and Gu, T and Yu, D and Yao, YG}, title = {The 3'UTR of human MAVS mRNA contains multiple regulatory elements for the control of protein expression and subcellular localization.}, journal = {Biochimica et biophysica acta. Gene regulatory mechanisms}, volume = {1862}, number = {1}, pages = {47-57}, doi = {10.1016/j.bbagrm.2018.10.017}, pmid = {30391331}, issn = {1876-4320}, mesh = {3' Untranslated Regions/*genetics ; AU Rich Elements ; Adaptor Proteins, Signal Transducing/*genetics ; Binding Sites ; Cell Line ; Cell Line, Tumor ; Gene Expression Regulation ; Humans ; *Immunity, Innate ; Intracellular Space/metabolism ; MicroRNAs/immunology/metabolism ; Mitochondrial Proteins ; Peptide Fragments ; RNA, Messenger/*genetics ; *Regulatory Sequences, Nucleic Acid ; Vesicular stomatitis Indiana virus/physiology ; Virus Diseases/immunology ; }, abstract = {Post-transcriptional regulation controls the mRNA stability, translation efficiency, and subcellular localization of a protein. The mitochondrial antiviral signaling protein (MAVS) plays a vital role in innate antiviral immunity. The MAVS mRNA has a long 3' untranslated region (UTR, >9 kb) and an understanding of this region may help to explain the post-transcriptional regulation in a key protein. In this study, we aimed to characterize the role of the MAVS 3'UTR during MAVS expression by truncating the 3'UTR into different fragments so as to identify the regulatory elements. We found that the different fragments (H1-H5) of the MAVS 3'UTR play different roles in regulating the subcellular localization and function of MAVS. Three AU-rich elements (AREs) in the MAVS 3'UTR H1 fragment (region 1-3445 in the 3'UTR) repressed MAVS expression by interacting with HuR to destabilize its mRNA. The MAVS 3'UTR H5 fragment (region 5955-7687 in the 3'UTR) affected the cellular localization of MAVS in mitochondria and influenced the subsequent antiviral function. Four miR-27a binding sites were recognized in the MAVS 3'UTR, and treatment of miR-27a inhibited MAVS expression and promoted the replication of the vesicular stomatitis virus (VSV). The identification of multiple regulatory elements in the MAVS 3'UTR offers new insights into the precise control of MAVS expression in innate immunity.}, } @article {pmid30394643, year = {2018}, author = {Rand, DM and Mossman, JA and Zhu, L and Biancani, LM and Ge, JY}, title = {Mitonuclear epistasis, genotype-by-environment interactions, and personalized genomics of complex traits in Drosophila.}, journal = {IUBMB life}, volume = {70}, number = {12}, pages = {1275-1288}, pmid = {30394643}, issn = {1521-6551}, support = {R01 GM067862/GM/NIGMS NIH HHS/United States ; R01 AG027849/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Cell Nucleus/genetics ; Drosophila melanogaster/genetics ; Epistasis, Genetic/*genetics ; *Gene-Environment Interaction ; Genome, Mitochondrial/genetics ; Genomics ; Genotype ; Haplotypes ; Humans ; Mitochondria/*genetics ; Multifactorial Inheritance/*genetics ; Phenotype ; Precision Medicine ; }, abstract = {Mitochondrial function requires the coordinated expression of dozens of gene products from the mitochondrial genome and hundreds from the nuclear genomes. The systems that emerge from these interactions convert the food we eat and the oxygen we breathe into energy for life, while regulating a wide range of other cellular processes. These facts beg the question of whether the gene-by-gene interactions (G x G) that enable mitochondrial function are distinct from the gene-by-environment interactions (G x E) that fuel mitochondrial activity. We examine this question using a Drosophila model of mitonuclear interactions in which experimental combinations of mtDNA and nuclear chromosomes generate pairs of mitonuclear genotypes to test for epistatic interactions (G x G). These mitonuclear genotypes are then exposed to altered dietary or oxygen environments to test for G x E interactions. We use development time to assess dietary effects, and genome wide RNAseq analyses to assess hypoxic effects on transcription, which can be partitioned in to mito, nuclear, and environmental (G x G x E) contributions to these complex traits. We find that mitonuclear epistasis is universal, and that dietary and hypoxic treatments alter the epistatic interactions. We further show that the transcriptional response to alternative mitonuclear interactions has significant overlap with the transcriptional response to alternative oxygen environments. Gene coexpression analyses suggest that these shared genes are more central in networks of gene interactions, implying some functional overlap between epistasis and genotype by environment interactions. These results are discussed in the context of evolutionary fitness, the genetic basis of complex traits, and the challenge of achieving precision in personalized medicine. © 2018 The Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 70(12):1275-1288, 2018.}, } @article {pmid30395972, year = {2019}, author = {Fan, PC and Zhang, Y and Wang, Y and Wei, W and Zhou, YX and Xie, Y and Wang, X and Qi, YZ and Chang, L and Jia, ZP and Zhou, Z and Guan, H and Zhang, H and Xu, P and Zhou, PK}, title = {Quantitative proteomics reveals mitochondrial respiratory chain as a dominant target for carbon ion radiation: Delayed reactive oxygen species generation caused DNA damage.}, journal = {Free radical biology & medicine}, volume = {130}, number = {}, pages = {436-445}, doi = {10.1016/j.freeradbiomed.2018.10.449}, pmid = {30395972}, issn = {1873-4596}, mesh = {Antioxidants/pharmacology ; Cell Line, Tumor ; DNA Damage/genetics/radiation effects ; DNA Repair/genetics/radiation effects ; Electron Transport/*radiation effects ; Heavy Ion Radiotherapy/adverse effects ; Humans ; Mitochondria/metabolism/*radiation effects ; Neoplasms/genetics/metabolism/*radiotherapy ; *Proteomics ; Reactive Oxygen Species/metabolism ; }, abstract = {Heavy ion radiotherapy has shown great promise for cancer therapy. Understanding the cellular response mechanism to heavy ion radiation is required to explore measures of overcoming devastating side effects. Here, we performed a quantitative proteomic analysis to investigate the mechanism of carbon ion irradiation on human AHH-1 lymphoblastoid cells. We identified 4602 proteins and quantified 4569 proteins showing high coverage in the mitochondria. Data are available via ProteomeXchange with identifier PXD008351. After stringent filtering, 290 proteins were found to be significantly up-regulated and 16 proteins were down-regulated. Functional analysis revealed that these up-regulated proteins were enriched in the process of DNA damage repair, mitochondrial ribosome, and particularly mitochondrial respiratory chain, accounting for approximately 50% of the accumulated proteins. Bioinformatics and functional analysis demonstrated that these up-regulated mitochondrial respiratory chain proteins enhanced ATP production and simultaneously reactive oxygen species release. More importantly, increased reactive oxygen species led to secondary organelle injury and lagged DNA double-strand breaks. Consistently, the expression of antioxidant enzymes was up-regulated for free radical scavenging. The mechanism of lagged secondary injury originated from disturbances in the mitochondrial respiratory chain. Our results provided a novel target for cell self-repair against heavy ion radiation-induced cellular damage.}, } @article {pmid30395997, year = {2019}, author = {López-Rubio, A and Suaza-Vasco, JD and Solari, S and Gutiérez-Builes, L and Porter, C and Uribe, SI}, title = {Intraspecific phylogeny of Anopheles (Kerteszia) neivai Howard, Dyar & Knab 1913, based on mitochondrial and nuclear ribosomal genes.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {67}, number = {}, pages = {183-190}, doi = {10.1016/j.meegid.2018.10.013}, pmid = {30395997}, issn = {1567-7257}, mesh = {Animals ; Anopheles/*classification/*genetics ; Central America/epidemiology ; *Genes, Mitochondrial ; Haplotypes ; Mitochondria/*genetics ; Phylogeny ; RNA, Ribosomal/*genetics ; South America/epidemiology ; }, abstract = {Three mitochondrial regions and a fragment of a large nuclear ribosomal subunit was used to study the evolutionary patterns of An. neivai, a mosquito inhabiting mangroves and tropical forest in the lowland and coastal areas of the Yucatan Peninsula through the Pacific Ecuadorian coast. This species exhibits epidemiological importance regarding Malaria transmission in natural ecosystems, particularly in rural areas of the Pacific Colombian coast. The results based on phylogenetic networks and Bayesian inference showed no robust evidence supporting the existence of previously suggested cryptic species. Diversification patterns in geographically widespread species such as this one, are complex and therefore could impact malaria control strategies. Further studies focused on behavior, morphology, and phylogenomics will improve the understanding of the evolutionary patterns within An. neivai and its role as a disease vector.}, } @article {pmid30403999, year = {2018}, author = {Wettmarshausen, J and Goh, V and Huang, KT and Arduino, DM and Tripathi, U and Leimpek, A and Cheng, Y and Pittis, AA and Gabaldón, T and Mokranjac, D and Hajnóczky, G and Perocchi, F}, title = {MICU1 Confers Protection from MCU-Dependent Manganese Toxicity.}, journal = {Cell reports}, volume = {25}, number = {6}, pages = {1425-1435.e7}, doi = {10.1016/j.celrep.2018.10.037}, pmid = {30403999}, issn = {2211-1247}, support = {R01 GM102724/GM/NIGMS NIH HHS/United States ; }, mesh = {Apoptosis/drug effects ; Calcium Channels/*metabolism ; Calcium-Binding Proteins/*metabolism ; Cation Transport Proteins/*metabolism ; *Cytoprotection/drug effects ; Eukaryota ; Evolution, Molecular ; HEK293 Cells ; HeLa Cells ; Humans ; Iron/toxicity ; Manganese/*toxicity ; Mitochondria/metabolism ; Mitochondrial Membrane Transport Proteins/*metabolism ; Phylogeny ; Saccharomyces cerevisiae/metabolism ; Stress, Physiological/drug effects ; }, abstract = {The mitochondrial calcium uniporter is a highly selective ion channel composed of species- and tissue-specific subunits. However, the functional role of each component still remains unclear. Here, we establish a synthetic biology approach to dissect the interdependence between the pore-forming subunit MCU and the calcium-sensing regulator MICU1. Correlated evolutionary patterns across 247 eukaryotes indicate that their co-occurrence may have conferred a positive fitness advantage. We find that, while the heterologous reconstitution of MCU and EMRE in vivo in yeast enhances manganese stress, this is prevented by co-expression of MICU1. Accordingly, MICU1 deletion sensitizes human cells to manganese-dependent cell death by disinhibiting MCU-mediated manganese uptake. As a result, manganese overload increases oxidative stress, which can be effectively prevented by NAC treatment. Our study identifies a critical contribution of MICU1 to the uniporter selectivity, with important implications for patients with MICU1 deficiency, as well as neurological disorders arising upon chronic manganese exposure.}, } @article {pmid30417348, year = {2019}, author = {Lasne, C and Van Heerwaarden, B and Sgrò, CM and Connallon, T}, title = {Quantifying the relative contributions of the X chromosome, autosomes, and mitochondrial genome to local adaptation.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {2}, pages = {262-277}, doi = {10.1111/evo.13647}, pmid = {30417348}, issn = {1558-5646}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Drosophila melanogaster/*genetics ; Female ; Food Deprivation ; Gene Expression Regulation ; Genes, X-Linked ; Genome, Mitochondrial/*genetics ; Hot Temperature ; Male ; Models, Biological ; Water Deprivation ; Wings, Animal/anatomy & histology ; *X Chromosome ; }, abstract = {During local adaptation with gene flow, some regions of the genome are inherently more responsive to selection than others. Recent theory predicts that X-linked genes should disproportionately contribute to local adaptation relative to other genomic regions, yet this prediction remains to be tested. We carried out a multigeneration crossing scheme, using two cline-end populations of Drosophila melanogaster, to estimate the relative contributions of the X chromosome, autosomes, and mitochondrial genome to divergence in four traits involved in local adaptation (wing size, resistance to heat, desiccation, and starvation stresses). We found that the mitochondrial genome and autosomes contributed significantly to clinal divergence in three of the four traits. In contrast, the X made no significant contribution to divergence in these traits. Given the small size of the mitochondrial genome, our results indicate that it plays a surprisingly large role in clinal adaptation. In contrast, the X, which represents roughly 20% of the Drosophila genome, contributes negligibly-a pattern that conflicts with theoretical predictions. These patterns reinforce recent work implying a central role of mitochondria in climatic adaptation, and suggest that different genomic regions may play fundamentally different roles in processes of divergence with gene flow.}, } @article {pmid30419142, year = {2018}, author = {Muthye, V and Lavrov, DV}, title = {Characterization of mitochondrial proteomes of nonbilaterian animals.}, journal = {IUBMB life}, volume = {70}, number = {12}, pages = {1289-1301}, doi = {10.1002/iub.1961}, pmid = {30419142}, issn = {1521-6551}, mesh = {Animals ; Cell Nucleus/genetics ; Computational Biology ; Ctenophora/*genetics ; DNA, Mitochondrial ; *Evolution, Molecular ; Humans ; Mitochondria/*genetics ; Mitochondrial Proteins/*genetics ; Phylogeny ; Proteome/genetics ; }, abstract = {Mitochondria require ~1,500 proteins for their maintenance and proper functionality, which constitute the mitochondrial proteome (mt-proteome). Although a few of these proteins, mostly subunits of the electron transport chain complexes, are encoded in mitochondrial DNA (mtDNA), the vast majority are encoded in the nuclear genome and imported to the organelle. Previous studies have shown a continuous and complex evolution of mt-proteome among eukaryotes. However, there was less attention paid to mt-proteome evolution within Metazoa, presumably because animal mtDNA and, by extension, animal mitochondria are often considered to be uniform. In this analysis, two bioinformatic approaches (Orthologue-detection and Mitochondrial Targeting Sequence prediction) were used to identify mt-proteins in 23 species from four nonbilaterian phyla: Cnidaria, Ctenophora, Placozoa, and Porifera, as well as two choanoflagellates, the closest animal relatives. Our results revealed a large variation in mt-proteome in nonbilaterian animals in size and composition. Myxozoans, highly reduced cnidarian parasites, possessed the smallest inferred mitochondrial proteomes, while calcareous sponges possessed the largest. About 513 mitochondrial orthologous groups were present in all nonbilaterian phyla and human. Interestingly, 42 human mitochondrial proteins were not identified in any nonbilaterian species studied and represent putative innovations along the bilaterian branch. Several of these proteins were involved in apoptosis and innate immunity, two processes known to evolve within Metazoa. Conversely, several proteins identified as mitochondrial in nonbilaterian phyla and animal outgroups were absent in human, representing cases of possible loss. Finally, a few human cytosolic proteins, such as histones and cytosolic ribosomal proteins, were predicted to be targeted to mitochondria in nonbilaterian animals. Overall, our analysis provides the first step in characterization of mt-proteomes in nonbilaterian animals and understanding evolution of animal mt-proteome. © 2018 IUBMB Life, 70(12):1289-1301, 2018.}, } @article {pmid30421421, year = {2019}, author = {Patten, MM}, title = {The X chromosome favors males under sexually antagonistic selection.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {1}, pages = {84-91}, doi = {10.1111/evo.13646}, pmid = {30421421}, issn = {1558-5646}, mesh = {Animals ; *Biological Evolution ; Female ; Male ; Models, Genetic ; *Selection, Genetic ; X Chromosome/*genetics ; }, abstract = {The X chromosome is found twice as often in females as males. This has led to an intuition that X-linked genes for traits experiencing sexually antagonistic selection should tend to evolve toward the female optimum. However, this intuition has never been formally examined. In this paper, I present a simple mathematical model and ask whether the X chromosome is indeed biased toward effecting female-optimal phenotypes. Counter to the intuition, I find that the exact opposite bias exists; the X chromosome is revealed to be a welcome spot for mutations that benefit males at the expense of females. Not only do male-beneficial alleles have an easier time of invading and spreading through a population, but they also achieve higher equilibrium frequencies than comparable female-beneficial alleles. The X chromosome is therefore expected over evolutionary time to nudge phenotypes closer to the male optimum. Consequently, the X chromosome should find itself engaged in perpetual intragenomic conflicts with the autosomes and the mitochondria over developmental outcomes. The X chromosome's male bias and the intragenomic conflicts that ensue bear on the evolution of gene regulation, speciation, and our concept of organismality.}, } @article {pmid30433779, year = {2018}, author = {Fujisawa, A and Tamura, T and Yasueda, Y and Kuwata, K and Hamachi, I}, title = {Chemical Profiling of the Endoplasmic Reticulum Proteome Using Designer Labeling Reagents.}, journal = {Journal of the American Chemical Society}, volume = {140}, number = {49}, pages = {17060-17070}, doi = {10.1021/jacs.8b08606}, pmid = {30433779}, issn = {1520-5126}, mesh = {Carboxy-Lyases/analysis/chemistry ; Chromatography, Liquid ; Cyclophilin A/analysis/chemistry ; Endoplasmic Reticulum/*chemistry/metabolism ; Endoplasmic Reticulum Stress/drug effects ; HeLa Cells ; Humans ; Molecular Probes/chemical synthesis/*chemistry ; Multifunctional Enzymes/analysis/chemistry ; Peptide Synthases/analysis/chemistry ; Proteome/*analysis/chemistry ; Proteomics/methods ; Tandem Mass Spectrometry ; Thioredoxins/analysis/chemistry ; Tunicamycin/pharmacology ; Unfolded Protein Response/drug effects ; Xanthenes/chemical synthesis/*chemistry ; }, abstract = {The endoplasmic reticulum (ER) is an organelle that performs a variety of essential cellular functions via interactions with other organelles. Despite its important role, chemical tools for profiling the composition and dynamics of ER proteins remain very limited because of the labile nature of these proteins. Here, we developed ER-localizable reactive molecules (called ERMs) as tools for ER-focused chemical proteomics. ERMs can spontaneously localize in the ER of living cells and selectively label ER-associated proteins with a combined affinity and imaging tag, enabling tag-mediated ER protein enrichment and identification with liquid chromatography tandem mass spectrometry (LC-MS/MS). Using this method, we performed proteomic analysis of the ER of HeLa cells and newly assigned three proteins, namely, PAICS, TXNL1, and PPIA, as ER-associated proteins. The ERM probes could be used simultaneously with the nucleus- and mitochondria-localizable reactive molecules previously developed by our group, which enabled orthogonal organellar chemoproteomics in a single biological sample. Moreover, quantitative analysis of the dynamic changes in ER-associated proteins in response to tunicamycin-induced ER stress was performed by combining ER-specific labeling with SILAC (stable isotope labeling by amino acids in cell culture)-based quantitative MS technology. Our results demonstrated that ERM-based chemical proteomics provides a powerful tool for labeling and profiling ER-related proteins in living cells.}, } @article {pmid30443184, year = {2018}, author = {Dou, X and Chen, L and Lei, M and Zellmer, L and Jia, Q and Ling, P and He, Y and Yang, W and Liao, DJ}, title = {Evaluating the Remote Control of Programmed Cell Death, with or without a Compensatory Cell Proliferation.}, journal = {International journal of biological sciences}, volume = {14}, number = {13}, pages = {1800-1812}, pmid = {30443184}, issn = {1449-2288}, mesh = {Animals ; Apoptosis/genetics/*physiology ; Cell Death/genetics/*physiology ; Cell Proliferation/genetics/*physiology ; Humans ; Necrosis ; }, abstract = {Organisms and their different component levels, whether organelle, cellular or other, come by birth and go by death, and the deaths are often balanced by new births. Evolution on the one hand has built demise program(s) in cells of organisms but on the other hand has established external controls on the program(s). For instance, evolution has established death program(s) in animal cells so that the cells can, when it is needed, commit apoptosis or senescent death (SD) in physiological situations and stress-induced cell death (SICD) in pathological situations. However, these programmed cell deaths are not predominantly regulated by the cells that do the dying but, instead, are controlled externally and remotely by the cells' superior(s), i.e. their host tissue or organ or even the animal's body. Currently, it is still unclear whether a cell has only one death program or has several programs respectively controlling SD, apoptosis and SICD. In animals, apoptosis exterminates, in a physiological manner, healthy but no-longer needed cells to avoid cell redundancy, whereas suicidal SD and SICD, like homicidal necrosis, terminate ill but useful cells, which may be followed by regeneration of the live cells and by scar formation to heal the damaged organ or tissue. Therefore, "who dies" clearly differentiates apoptosis from SD, SICD and necrosis. In animals, apoptosis can occur only in those cell types that retain a lifelong ability of proliferation and never occurs in those cell types that can no longer replicate in adulthood. In cancer cells, SICD is strengthened, apoptosis is dramatically weakened while SD has been lost. Most published studies professed to be about apoptosis are actually about SICD, which has four basic and well-articulated pathways involving caspases or involving pathological alterations in the mitochondria, endoplasmic reticula, or lysosomes.}, } @article {pmid30445187, year = {2019}, author = {Johnston, IG}, title = {Tension and Resolution: Dynamic, Evolving Populations of Organelle Genomes within Plant Cells.}, journal = {Molecular plant}, volume = {12}, number = {6}, pages = {764-783}, doi = {10.1016/j.molp.2018.11.002}, pmid = {30445187}, issn = {1752-9867}, mesh = {Cell Nucleus/metabolism ; Chloroplasts/metabolism ; Mitochondria/*metabolism ; Organelles/metabolism ; Plant Cells/*metabolism ; Plastids/metabolism ; }, abstract = {Mitochondria and plastids form dynamic, evolving populations physically embedded in the fluctuating environment of the plant cell. Their evolutionary heritage has shaped how the cell controls the genetic structure and the physical behavior of its organelle populations. While the specific genes involved in these processes are gradually being revealed, the governing principles underlying this controlled behavior remain poorly understood. As the genetic and physical dynamics of these organelles are central to bioenergetic performance and plant physiology, this challenges both fundamental biology and strategies to engineer better-performing plants. This article reviews current knowledge of the physical and genetic behavior of mitochondria and chloroplasts in plant cells. An overarching hypothesis is proposed whereby organelles face a tension between genetic robustness and individual control and responsiveness, and different species resolve this tension in different ways. As plants are immobile and thus subject to fluctuating environments, their organelles are proposed to favor individual responsiveness, sacrificing genetic robustness. Several notable features of plant organelles, including large genomes, mtDNA recombination, fragmented organelles, and plastid/mitochondrial differences may potentially be explained by this hypothesis. Finally, the ways that quantitative and systems biology can help shed light on the plethora of open questions in this field are highlighted.}, } @article {pmid30446790, year = {2019}, author = {Razzak, MA and Lee, J and Lee, DW and Kim, JH and Yoon, HS and Hwang, I}, title = {Expression of seven carbonic anhydrases in red alga Gracilariopsis chorda and their subcellular localization in a heterologous system, Arabidopsis thaliana.}, journal = {Plant cell reports}, volume = {38}, number = {2}, pages = {147-159}, pmid = {30446790}, issn = {1432-203X}, support = {2016R1E1A1A02922014//Ministry of Fisheries/ ; }, mesh = {Arabidopsis/*genetics ; Carbonic Anhydrases/classification/*metabolism ; Computer Simulation ; Endoplasmic Reticulum/metabolism ; Gene Expression Regulation, Enzymologic ; Glycosylation ; Golgi Apparatus/metabolism ; Green Fluorescent Proteins/metabolism ; Phylogeny ; Plants, Genetically Modified ; Protein Transport ; Protoplasts/metabolism ; Rhodophyta/*enzymology ; Subcellular Fractions/metabolism ; Vacuoles/metabolism ; }, abstract = {Red alga, Gracilariopsis chorda, contains seven carbonic anhydrases that can be grouped into α-, β- and γ-classes. Carbonic anhydrases (CAHs) are metalloenzymes that catalyze the reversible hydration of CO2. These enzymes are present in all living organisms and play roles in various cellular processes, including photosynthesis. In this study, we identified seven CAH genes (GcCAHs) from the genome sequence of the red alga Gracilariopsis chorda and characterized them at the molecular, cellular and biochemical levels. Based on sequence analysis, these seven isoforms were categorized into four α-class, one β-class, and two γ-class isoforms. RNA sequencing revealed that of the seven CAHs isoforms, six genes were expressed in G. chorda in light at room temperature. In silico analysis revealed that these seven isoforms localized to multiple subcellular locations such as the ER, mitochondria and cytosol. When expressed as green fluorescent protein fusions in protoplasts of Arabidopsis thaliana leaf cells, these seven isoforms showed multiple localization patterns. The four α-class GcCAHs with an N-terminal hydrophobic leader sequence localized to the ER and two of them were further targeted to the vacuole. GcCAHβ1 with no noticeable signal sequence localized to the cytosol. The two γ-class GcCAHs also localized to the cytosol, despite the presence of a predicted presequence. Based on these results, we propose that the red alga G. chorda also employs multiple CAH isoforms for various cellular processes such as photosynthesis.}, } @article {pmid30446962, year = {2019}, author = {Xie, T and Hu, L and Guo, YX and Li, YC and Chen, F and Zhu, BF}, title = {Genetic polymorphism analysis of mitochondrial DNA from Chinese Xinjiang Kazak ethnic group by a novel mitochondrial DNA genotyping panel.}, journal = {Molecular biology reports}, volume = {46}, number = {1}, pages = {17-25}, pmid = {30446962}, issn = {1573-4978}, support = {81525015//National Natural Science Foundation of China/ ; }, mesh = {Adult ; Alleles ; Asian People/*genetics ; China/ethnology ; DNA, Mitochondrial/blood/*genetics ; Ethnicity/genetics ; Female ; Gene Frequency/genetics ; Genetic Markers ; Genetics, Population/methods ; Genotype ; Genotyping Techniques/*methods ; Haplotypes/genetics ; Healthy Volunteers ; Humans ; Male ; Microsatellite Repeats/genetics ; Mitochondria/genetics ; Phylogeny ; Polymorphism, Genetic/genetics ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {Genetic polymorphism analysis of 60 mitochondrial DNA (mtDNA) loci in Chinese Xinjiang Kazak group was conducted in this study. Blood samples from 141 unrelated healthy volunteers were randomly collected from Chinese Kazak ethnic group in Ili, Xinjiang Uygur Autonomous region. Among these mtDNA loci, single nucleotide transition was the most commonly observed variant (87.93%). A total of 25 haplogroups and 79 haplotypes were found in Kazak group, and Haplogroup D4 was the most common haplogroup (21.28%). Among the entire 79 haplotypes, 53 of them were observed for only once, 14 for twice. The haplotype diversity was 0.978 ± 0.005, and the nucleotide diversity was 0.17449. The detection of (CA)n and 9-bp deletion polymorphisms could improve the discrimination power of the mtDNA genetic marker. Moreover, Xinjiang Kazak group was compared with other previously reported groups to infer its genetic background. The present results revealed that Xinjiang Kazak ethnic group was genetically closer related to Xinjiang Uygur, Xinjiang Uzbek and Xinjiang Han populations. Meanwhile, our results also indicated the potential closer genetic relationships among Xinjiang Kazak group with Altaian Kazak as well as Xinjiang Xibe group. In conclusion, this novel mtDNA panel could be effectively utilized for forensic applications. Additionally, to further reveal the genetic background of Chinese Kazak group, more relevant populations and genetic markers should be incorporated in our future study.}, } @article {pmid30456441, year = {2019}, author = {Serrano-Solís, V and Toscano Soares, PE and de Farías, ST}, title = {Genomic Signatures Among Acanthamoeba polyphaga Entoorganisms Unveil Evidence of Coevolution.}, journal = {Journal of molecular evolution}, volume = {87}, number = {1}, pages = {7-15}, pmid = {30456441}, issn = {1432-1432}, mesh = {Acanthamoeba/*genetics ; Amoeba/genetics ; Animals ; Bacteria/genetics ; Biological Coevolution/*genetics ; Codon/genetics ; Evolution, Molecular ; Genome, Viral ; Genomics ; Mimiviridae/*genetics ; Mitochondria/genetics ; Parasites/genetics ; Viral Proteins/genetics ; Virophages/genetics ; }, abstract = {The definition of a genomic signature (GS) is "the total net response to selective pressure". Recent isolation and sequencing of naturally occurring organisms, hereby named entoorganisms, within Acanthamoeba polyphaga, raised the hypothesis of a common genomic signature despite their diverse and unrelated evolutionary origin. Widely accepted and implemented tests for GS detection are oligonucleotide relative frequencies (OnRF) and relative codon usage (RCU) surveys. A common pattern and strong correlations were unveiled from OnRFs among A. polyphaga's Mimivirus and virophage Sputnik. RCU showed a common A-T bias at third codon position. We expanded tests to the amoebal mitochondrial genome and amoeba-resistant bacteria, achieving strikingly coherent results to the aforementioned viral analyses. The GSs in these entoorganisms of diverse evolutionary origin are coevolutionarily conserved within an intracellular environment that provides sanctuary for species of ecological and biomedical relevance.}, } @article {pmid30464337, year = {2018}, author = {Chen, YL and Chen, LJ and Chu, CC and Huang, PK and Wen, JR and Li, HM}, title = {TIC236 links the outer and inner membrane translocons of the chloroplast.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {125-129}, doi = {10.1038/s41586-018-0713-y}, pmid = {30464337}, issn = {1476-4687}, mesh = {Arabidopsis/*cytology/metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Bacterial Outer Membrane Proteins/metabolism ; Chloroplast Proteins/genetics/*metabolism ; Chloroplasts/genetics/*metabolism ; Escherichia coli Proteins/metabolism ; Evolution, Molecular ; Intracellular Membranes/*metabolism ; Membrane Proteins/genetics/*metabolism ; Membrane Transport Proteins/genetics/*metabolism ; Multiprotein Complexes/genetics/metabolism ; Mutation ; Pisum sativum/cytology ; Protein Binding ; Protein Precursors/metabolism ; Protein Transport ; }, abstract = {The two-membrane envelope is a defining feature of chloroplasts. Chloroplasts evolved from a Gram-negative cyanobacterial endosymbiont. During evolution, genes of the endosymbiont have been transferred to the host nuclear genome. Most chloroplast proteins are synthesized in the cytosol as higher-molecular-mass preproteins with an N-terminal transit peptide. Preproteins are transported into chloroplasts by the TOC and TIC (translocons at the outer- and inner-envelope membranes of chloroplasts, respectively) machineries[1,2], but how TOC and TIC are assembled together is unknown. Here we report the identification of the TIC component TIC236; TIC236 is an integral inner-membrane protein that projects a 230-kDa domain into the intermembrane space, which binds directly to the outer-membrane channel TOC75. The knockout mutation of TIC236 is embryonically lethal. In TIC236-knockdown mutants, a smaller amount of the inner-membrane channel TIC20 was associated with TOC75; the amount of TOC-TIC supercomplexes was also reduced. This resulted in a reduced import rate into the stroma, though outer-membrane protein insertion was unaffected. The size and the essential nature of TIC236 indicate that-unlike in mitochondria, in which the outer- and inner-membrane translocons exist as separate complexes and a supercomplex is only transiently assembled during preprotein translocation[3,4]-a long and stable protein bridge in the intermembrane space is required for protein translocation into chloroplasts. Furthermore, TIC236 and TOC75 are homologues of bacterial inner-membrane TamB[5] and outer-membrane BamA, respectively. Our evolutionary analyses show that, similar to TOC75, TIC236 is preserved only in plants and has co-evolved with TOC75 throughout the plant lineage. This suggests that the backbone of the chloroplast protein-import machinery evolved from the bacterial TamB-BamA protein-secretion system.}, } @article {pmid30466434, year = {2018}, author = {Petrů, M and Wideman, J and Moore, K and Alcock, F and Palmer, T and Doležal, P}, title = {Evolution of mitochondrial TAT translocases illustrates the loss of bacterial protein transport machines in mitochondria.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {141}, pmid = {30466434}, issn = {1741-7007}, mesh = {Escherichia coli/genetics ; Escherichia coli Proteins/chemistry/genetics/metabolism ; Eukaryota/*genetics ; *Evolution, Molecular ; Membrane Transport Proteins/*genetics/*metabolism ; Mitochondria/metabolism ; Protein Transport ; }, abstract = {BACKGROUND: Bacteria and mitochondria contain translocases that function to transport proteins across or insert proteins into their inner and outer membranes. Extant mitochondria retain some bacterial-derived translocases but have lost others. While BamA and YidC were integrated into general mitochondrial protein transport pathways (as Sam50 and Oxa1), the inner membrane TAT translocase, which uniquely transports folded proteins across the membrane, was retained sporadically across the eukaryote tree.

RESULTS: We have identified mitochondrial TAT machinery in diverse eukaryotic lineages and define three different types of eukaryote-encoded TatABC-derived machineries (TatAC, TatBC and TatC-only). Here, we investigate TatAC and TatC-only machineries, which have not been studied previously. We show that mitochondria-encoded TatAC of the jakobid Andalucia godoyi represent the minimal functional pathway capable of substituting for the Escherichia coli TatABC complex and can transport at least one substrate. However, selected TatC-only machineries, from multiple eukaryotic lineages, were not capable of supporting the translocation of this substrate across the bacterial membrane. Despite the multiple losses of the TatC gene from the mitochondrial genome, the gene was never transferred to the cell nucleus. Although the major constraint preventing nuclear transfer of mitochondrial TatC is likely its high hydrophobicity, we show that in chloroplasts, such transfer of TatC was made possible due to modifications of the first transmembrane domain.

CONCLUSIONS: At its origin, mitochondria inherited three inner membrane translocases Sec, TAT and Oxa1 (YidC) from its bacterial ancestor. Our work shows for the first time that mitochondrial TAT has likely retained its unique function of transporting folded proteins at least in those few eukaryotes with TatA and TatC subunits encoded in the mitochondrial genome. However, mitochondria, in contrast to chloroplasts, abandoned the machinery multiple times in evolution. The overall lower hydrophobicity of the Oxa1 protein was likely the main reason why this translocase was nearly universally retained in mitochondrial biogenesis pathways.}, } @article {pmid30466901, year = {2019}, author = {Hampl, V and Čepička, I and Eliáš, M}, title = {Was the Mitochondrion Necessary to Start Eukaryogenesis?.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {96-104}, doi = {10.1016/j.tim.2018.10.005}, pmid = {30466901}, issn = {1878-4380}, mesh = {Adenosine Triphosphate ; Archaea/physiology ; *Biological Evolution ; Eukaryota/genetics/*physiology ; Eukaryotic Cells/*physiology ; Genome ; Mitochondria/genetics/*physiology ; Phagocytosis ; Prokaryotic Cells/physiology ; Symbiosis ; }, abstract = {Arguments based on cell energetics favour the view that a mitochondrion capable of oxidative phosphorylation was a prerequisite for the evolution of other features of the eukaryotic cell, including increased volume, genome size and, eventually, phagotrophy. Contrary to this we argue that: (i) extant amitochondriate eukaryotes possess voluminous phagotrophic cells with large genomes; (ii) picoeukaryotes demonstrate that phagotrophy is feasible at prokaryotic cell sizes; and (iii) the assumption that evolution of complex features requires extra ATP, often mentioned in this context, is unfounded and should not be used in such considerations. We claim that the diversity of cell organisations and functions observed today in eukaryotes gives no reason to postulate that a mitochondrion must have preceded phagocytosis in eukaryogenesis.}, } @article {pmid30467693, year = {2019}, author = {Aw, WC and Garvin, MR and Ballard, JWO}, title = {Exogenous Factors May Differentially Influence the Selective Costs of mtDNA Mutations.}, journal = {Advances in anatomy, embryology, and cell biology}, volume = {231}, number = {}, pages = {51-74}, doi = {10.1007/102_2018_2}, pmid = {30467693}, issn = {0301-5556}, mesh = {Cell Nucleus/*metabolism ; DNA, Mitochondrial/*genetics ; Diet ; Electron Transport Complex I/*metabolism ; Energy Metabolism/*genetics/physiology ; Evolution, Molecular ; Genetic Fitness ; Humans ; Mitochondria/genetics/*metabolism ; Mutation ; Nutrients/*metabolism ; Signal Transduction/genetics ; Stress, Physiological ; Temperature ; }, abstract = {In this review, we provide evidence to suggest that the cost of specific mtDNA mutations can be influenced by exogenous factors. We focus on macronutrient-mitochondrial DNA interactions as factors that may differentially influence the consequences of a change as mitochondria must be flexible in its utilization of dietary proteins, carbohydrates, and fats. To understand this fundamental dynamic, we briefly discuss the energy processing pathways in mitochondria. Next, we explore the mitochondrial functions that are initiated during energy deficiency or when cells encounter cellular stress. We consider the anterograde response (nuclear control of mitochondrial function) and the retrograde response (nuclear changes in response to mitochondrial signaling) and how this mito-nuclear crosstalk may be influenced by exogenous factors such as temperature and diet. Finally, we employ Complex I of the mitochondrial electron transport system as a case study and discuss the potential role of the dietary macronutrient ratio as a strong selective force that may shape the frequencies of mitotypes in populations and species. We conclude that this underexplored field likely has implications in the fundamental disciplines of evolutionary biology and quantitative genetics and the more biomedical fields of nutrigenomics and pharmacogenomics.}, } @article {pmid30468939, year = {2019}, author = {Weber, AA and Stöhr, S and Chenuil, A}, title = {Species delimitation in the presence of strong incomplete lineage sorting and hybridization: Lessons from Ophioderma (Ophiuroidea: Echinodermata).}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {138-148}, doi = {10.1016/j.ympev.2018.11.014}, pmid = {30468939}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial ; Discriminant Analysis ; Echinodermata/*classification/*genetics ; Geography ; *Hybridization, Genetic ; Mitochondria/genetics ; Multigene Family ; *Phylogeny ; Principal Component Analysis ; Species Specificity ; Time Factors ; }, abstract = {Accurate species delimitation is essential to properly assess biodiversity, but also for management and conservation purposes. Yet, it is not always trivial to accurately define species boundaries in closely related species due to incomplete lineage sorting. Additional difficulties may be caused by hybridization, now evidenced as a frequent phenomenon. The brittle star cryptic species complex Ophioderma longicauda encompasses six mitochondrial lineages, including broadcast spawners and internal brooders, yet the actual species boundaries are unknown. Here, we combined three methods to delimit species in the Ophioderma longicauda complex and to infer its divergence history: (i) unsupervised species discovery based on multilocus genotypes; (ii) divergence time estimation using the multi-species coalescent; (iii) divergence scenario testing (including gene flow) using Approximate Bayesian Computation (ABC) methods. 30 sequence markers (transcriptome-based, mitochondrial or non-coding) for 89 O. longicauda and outgroup individuals were used. First, multivariate analyses revealed six genetic clusters, which globally corresponded to the mitochondrial lineages, yet with many exceptions, suggesting ancient hybridization events and challenging traditional mitochondrial barcoding approaches. Second, multi-species coalescent-based analyses confirmed the occurrence of six species and provided divergence time estimates, but the sole use of this method failed to accurately delimit species, highlighting the power of multilocus genotype clustering to delimit recently diverged species. Finally, Approximate Bayesian Computation showed that the most likely scenario involves hybridization between brooders and broadcasters. Our study shows that despite strong incomplete lineage sorting and past hybridization, accurate species delimitation in Ophioderma was possible using a combination of complementary methods. We propose that these methods, especially multilocus genotype clustering, may be useful to resolve other complex speciation histories.}, } @article {pmid30474737, year = {2019}, author = {Guo, J and Miao, X and He, P and Li, M and Wang, S and Cui, J and Huang, C and He, L and Zhao, J}, title = {Babesia gibsoni endemic to Wuhan, China: mitochondrial genome sequencing, annotation, and comparison with apicomplexan parasites.}, journal = {Parasitology research}, volume = {118}, number = {1}, pages = {235-243}, pmid = {30474737}, issn = {1432-1955}, support = {2017YFD0500402//National Key Research and Development Program of China/ ; 2015CB150300//National Basic Science Research Program (973 program) of China/ ; 31772729//National Natural Science Foundation of China/ ; 2017CFA020//Natural Science Foundation of Hubei Province/ ; }, mesh = {Amino Acid Sequence ; Animals ; Apicomplexa/classification/genetics/isolation & purification ; Babesia/classification/genetics/*isolation & purification ; Babesiosis/*parasitology ; China/epidemiology ; Cytochromes b/genetics ; DNA Primers/genetics ; Dog Diseases/*parasitology ; Dogs ; *Genome, Mitochondrial ; Molecular Sequence Annotation ; Phylogeny ; Protozoan Infections, Animal/epidemiology/*parasitology ; Sequence Analysis, DNA ; }, abstract = {Babesia gibsoni (B. gibsoni), an intracellular apicomplexan protozoan, poses great threat to canine health. Currently, little information is available about the B. gibsoni (WH58) endemic to Wuhan, China. Here, the mitochondrial (mt) genome of B. gibsoni (WH58) was amplified by five pairs of primers and sequenced and annotated by alignment with the reported mt genome sequences of Babesia canis (B. canis, KC207822), Babesia orientalis (KF218819), Babesia bovis (AB499088), and Theileria equi (AB499091). The evolutionary relationships were analyzed with the amino acid sequences of cytochrome c oxidase I (cox1) and cytochrome b (cob) genes in apicomplexan parasite species. Additionally, the mt genomes of Babesia, Theileria, and Plasmodium spp. were compared in size, host infection, form, distribution, and direction of the protein-coding genes. The full size of the mt genome of B. gibsoni (WH58) was 5865 bp with a linear form, containing terminal-inverted repeats on both ends, six large subunit ribosomal RNA fragments, and three protein-coding genes: cox1, cob, and cytochrome c oxidase III (cox3). Babesia, Theileria, and Plasmodium spp. had a similar mt genome size of about 6000 bp. The mt genomes of parasites that cause canine babesiosis showed a slightly smaller size than the other species. Moreover, Babesia microti (R1 strain) was about 11,100 bp in size, which was twice larger than that of the other species. The mt form was linear for Babesia and Theileria spp. but circular for Plasmodium falciparum and Plasmodium knowlesi. Additionally, all the species contained the three protein-coding genes of cox1, cox3, and cob except Toxoplasma gondii (RH strain) which only contained the cox1 and cob genes. The phylogenetic analysis indicated that B. gibsoni (WH58) was more identical to B. gibsoni (AB499087), B. canis (KC207822), and Babesia rossi (KC207823) and most divergent from Babesia conradae in Babesia spp. Despite the highest similarity to B. gibsoni (AB499087) reported in Japan, B. gibsoni (WH58) showed notable differences in the sequence of nucleotides and amino acids and the property in virulence to host and in vitro cultivation. This study compared the mt genomes of the two B. gibsoni isolates and other parasites in the phylum Apicomplexa and provided new insights into their differences and evolutionary relationships.}, } @article {pmid30477329, year = {2018}, author = {Smith, CF and McGlaughlin, ME and Mackessy, SP}, title = {DNA barcodes from snake venom: a broadly applicable method for extraction of DNA from snake venoms.}, journal = {BioTechniques}, volume = {65}, number = {6}, pages = {339-345}, doi = {10.2144/btn-2018-0096}, pmid = {30477329}, issn = {1940-9818}, mesh = {Alethinophidia/classification/*genetics ; Animals ; Cell Nucleus/genetics ; DNA/*genetics/*isolation & purification ; DNA Barcoding, Taxonomic/*methods ; Mitochondria/genetics ; Phylogeny ; Snake Venoms/classification/*genetics ; }, abstract = {DNA barcoding is a simple technique used to develop a large-scale system of classification that is broadly applicable across a wide variety of taxa. DNA-based analysis of snake venoms can provide a system of classification independent of currently accepted taxonomic relationships by generating DNA barcodes specific to each venom sample. DNA purification from dried snake venoms has previously required large amounts of starting material, has resulted in low yields and inconsistent amplification, and was possible with front-fanged snakes only. Here, we present a modified DNA extraction protocol applied to venoms of both front- and rear-fanged snakes that requires significantly less starting material (1 mg) and yields sufficient amounts of DNA for successful PCR amplification of regions commonly used for DNA barcoding. [Formula: see text].}, } @article {pmid30480548, year = {2018}, author = {Melvin, RG and Lamichane, N and Havula, E and Kokki, K and Soeder, C and Jones, CD and Hietakangas, V}, title = {Natural variation in sugar tolerance associates with changes in signaling and mitochondrial ribosome biogenesis.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {30480548}, issn = {2050-084X}, mesh = {Animals ; Cellular Reprogramming/genetics ; Diet/methods ; Dietary Sugars/administration & dosage/*metabolism ; Drosophila/drug effects/*genetics/metabolism ; Drosophila Proteins/genetics/metabolism ; Drosophila simulans/drug effects/*genetics/metabolism ; Drug Tolerance/*genetics ; Gene Expression Regulation ; Genetic Variation ; *Genome, Insect ; Larva/drug effects/genetics/metabolism ; Metabolic Networks and Pathways/genetics ; Mitochondria/metabolism ; Organelle Biogenesis ; Protein Phosphatase 1/genetics/metabolism ; Ribosomes/drug effects/metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics/metabolism ; *Signal Transduction ; Species Specificity ; }, abstract = {How dietary selection affects genome evolution to define the optimal range of nutrient intake is a poorly understood question with medical relevance. We have addressed this question by analyzing Drosophila simulans and sechellia, recently diverged species with differential diet choice. D. sechellia larvae, specialized to a nutrient scarce diet, did not survive on sugar-rich conditions, while the generalist species D. simulans was sugar tolerant. Sugar tolerance in D. simulans was a tradeoff for performance on low-energy diet and was associated with global reprogramming of metabolic gene expression. Hybridization and phenotype-based introgression revealed the genomic regions of D. simulans that were sufficient for sugar tolerance. These regions included genes that are involved in mitochondrial ribosome biogenesis and intracellular signaling, such as PPP1R15/Gadd34 and SERCA, which contributed to sugar tolerance. In conclusion, genomic variation affecting genes involved in global metabolic control defines the optimal range for dietary macronutrient composition.}, } @article {pmid30481564, year = {2019}, author = {Xie, B and Wang, S and Jiang, N and Li, JJ}, title = {Cyclin B1/CDK1-regulated mitochondrial bioenergetics in cell cycle progression and tumor resistance.}, journal = {Cancer letters}, volume = {443}, number = {}, pages = {56-66}, pmid = {30481564}, issn = {1872-7980}, support = {R01 CA213830/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; CDC2 Protein Kinase/*metabolism ; Cell Cycle ; Cell Nucleus/metabolism ; Cyclin B1/*metabolism ; *Drug Resistance, Neoplasm ; Energy Metabolism ; Humans ; Mitochondria/metabolism ; Neoplasms/*metabolism ; }, abstract = {A mammalian cell houses two genomes located separately in the nucleus and mitochondria. During evolution, communications and adaptations between these two genomes occur extensively to achieve and sustain homeostasis for cellular functions and regeneration. Mitochondria provide the major cellular energy and contribute to gene regulation in the nucleus, whereas more than 98% of mitochondrial proteins are encoded by the nuclear genome. Such two-way signaling traffic presents an orchestrated dynamic between energy metabolism and consumption in cells. Recent reports have elucidated the way how mitochondrial bioenergetics synchronizes with the energy consumption for cell cycle progression mediated by cyclin B1/CDK1 as the communicator. This review is to recapitulate cyclin B1/CDK1 mediated mitochondrial activities in cell cycle progression and stress response as well as its potential link to reprogram energy metabolism in tumor adaptive resistance. Cyclin B1/CDK1-mediated mitochondrial bioenergetics is applied as an example to show how mitochondria could timely sense the cellular fuel demand and then coordinate ATP output. Such nucleus-mitochondria oscillation may play key roles in the flexible bioenergetics required for tumor cell survival and compromising the efficacy of anti-cancer therapy. Further deciphering the cyclin B1/CDK1-controlled mitochondrial metabolism may invent effect targets to treat resistant cancers.}, } @article {pmid30484227, year = {2018}, author = {Trosko, JE}, title = {The Role of the Mitochondria in the Evolution of Stem Cells, Including MUSE Stem Cells and Their Biology.}, journal = {Advances in experimental medicine and biology}, volume = {1103}, number = {}, pages = {131-152}, doi = {10.1007/978-4-431-56847-6_7}, pmid = {30484227}, issn = {0065-2598}, mesh = {Adult Stem Cells/cytology ; *Biological Evolution ; Cell Differentiation ; Humans ; Induced Pluripotent Stem Cells/cytology ; Mitochondria/*physiology ; Pluripotent Stem Cells/*cytology ; }, abstract = {From the transition of single-cell organisms to multicellularity of metazoans, evolutionary pressures selected new genes and phenotypes to cope with the oxygenation of the Earth's environment, especially via the symbiotic acquisition of the mitochondrial organelle. There were many new genes and phenotypes that appeared, namely, stem cells, low-oxygen-micro-environments to house these genes ("niches"), new epigenetic mechanisms to regulate , selectively, the gene repertoire to control proliferation, differentiation, apoptosis, senescence and DNA protection mechanisms, including antioxidant genes and DNA repair. This transition required a critical regulation of the metabolism of glucose to produce energy for both the stem cell quiescent state and the energy-requiring differentiated state. While the totipotent-, embryonic-, pluripotent-, and a few adult organ-specific stem cells were recognized, only relatively recently, because of the isolation of somatic cell nuclear transfer (SCNT) stem cells and "induced pluripotent stem" cells, challenges to the origin of these "iPS" cells have been made. The isolation and characterization of human MUSE stem cells and more adult organ-specific adult stem cells have indicated that these MUSE cells have many shared characteristics of the "iPS" cells, yet they do not form teratomas but can give rise to the trigeminal cell layers. While the MUSE cells are a subset of human fibroblastic cells, they have not been characterized, yet, for the mitochondrial metabolic genes, either in the stem cell state or during their differentiation processes. A description of other human adult stem cells will be made to set future studies of how the MUSE stem cells compare to all other stem cells.}, } @article {pmid30486096, year = {2018}, author = {Agarwal, I and Mahony, S and Giri, VB and Chaitanya, R and Bauer, AM}, title = {Six new Cyrtodactylus (Squamata: Gekkonidae) from northeast India.}, journal = {Zootaxa}, volume = {4524}, number = {5}, pages = {501-535}, doi = {10.11646/zootaxa.4524.5.1}, pmid = {30486096}, issn = {1175-5334}, mesh = {Animals ; *Color ; India ; *Lizards ; Mitochondria ; Myanmar ; Phylogeny ; }, abstract = {We use mitochondrial sequence data to identify divergent lineages within the gekkonid genus Cyrtodactylus in northeast India and use morphological data to describe six new species from within the Indo-Burma clade of Cyrtodactylus. The new species share an irregular colour pattern but differ from described species from the region in morphology and mitochondrial sequence data (>11 % uncorrected pairwise sequence divergence). Three new species are from along the Brahmaputra River and three are from mountains south of the Brahmaputra, including the largest Cyrtodactylus from India and the fifth gecko to be described from a major Indian city, Guwahati.}, } @article {pmid30486780, year = {2018}, author = {Fletcher, K and Klosterman, SJ and Derevnina, L and Martin, F and Bertier, LD and Koike, S and Reyes-Chin-Wo, S and Mou, B and Michelmore, R}, title = {Comparative genomics of downy mildews reveals potential adaptations to biotrophy.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {851}, pmid = {30486780}, issn = {1471-2164}, support = {P30 CA093373/CA/NCI NIH HHS/United States ; S10 OD018223/OD/NIH HHS/United States ; S10 RR026825/RR/NCRR NIH HHS/United States ; Endowed Chair in Genomics//Novozymes Inc./ ; C06 RR012088/RR/NCRR NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; *Genomics ; Heterozygote ; Likelihood Functions ; Mitochondria/genetics ; Molecular Sequence Annotation ; Peronospora/*genetics/pathogenicity ; Phylogeny ; Plant Diseases/*microbiology ; Sequence Analysis, RNA ; Terminal Repeat Sequences/genetics ; }, abstract = {BACKGROUND: Spinach downy mildew caused by the oomycete Peronospora effusa is a significant burden on the expanding spinach production industry, especially for organic farms where synthetic fungicides cannot be deployed to control the pathogen. P. effusa is highly variable and 15 new races have been recognized in the past 30 years.

RESULTS: We virulence phenotyped, sequenced, and assembled two isolates of P. effusa from the Salinas Valley, California, U.S.A. that were identified as race 13 and 14. These assemblies are high quality in comparison to assemblies of other downy mildews having low total scaffold count (784 & 880), high contig N50s (48 kb & 52 kb), high BUSCO completion and low BUSCO duplication scores and share many syntenic blocks with Phytophthora species. Comparative analysis of four downy mildew and three Phytophthora species revealed parallel absences of genes encoding conserved domains linked to transporters, pathogenesis, and carbohydrate activity in the biotrophic species. Downy mildews surveyed that have lost the ability to produce zoospores have a common loss of flagella/motor and calcium domain encoding genes. Our phylogenomic data support multiple origins of downy mildews from hemibiotrophic progenitors and suggest that common gene losses in these downy mildews may be of genes involved in the necrotrophic stages of Phytophthora spp.

CONCLUSIONS: We present a high-quality draft genome of Peronospora effusa that will serve as a reference for Peronospora spp. We identified several Pfam domains as under-represented in the downy mildews consistent with the loss of zoosporegenesis and necrotrophy. Phylogenomics provides further support for a polyphyletic origin of downy mildews.}, } @article {pmid30487140, year = {2019}, author = {Kolli, R and Soll, J and Carrie, C}, title = {OXA2b is Crucial for Proper Membrane Insertion of COX2 during Biogenesis of Complex IV in Plant Mitochondria.}, journal = {Plant physiology}, volume = {179}, number = {2}, pages = {601-615}, pmid = {30487140}, issn = {1532-2548}, mesh = {Arabidopsis/cytology/*physiology ; Arabidopsis Proteins/genetics/*metabolism ; Electron Transport Complex IV/genetics/*metabolism ; Genetic Complementation Test ; Membrane Proteins/genetics/*metabolism ; Mitochondria/*metabolism ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Mutation ; Organelle Biogenesis ; Phylogeny ; Plant Cells/metabolism ; Protein Domains ; Seeds/genetics/metabolism ; }, abstract = {The evolutionarily conserved YidC/Oxa1/Alb3 proteins are involved in the insertion of membrane proteins in all domains of life. In plant mitochondria, individual knockouts of OXA1a, OXA2a, and OXA2b are embryo-lethal. In contrast to other members of the protein family, OXA2a and OXA2b contain a tetratricopeptide repeat (TPR) domain at the C-terminus. Here, the role of Arabidopsis (Arabidopsis thaliana) OXA2b was determined by using viable mutant plants that were generated by complementing homozygous lethal OXA2b T-DNA insertional mutants with a C-terminally truncated OXA2b lacking the TPR domain. The truncated-OXA2b-complemented plants displayed severe growth retardation due to a strong reduction in the steady-state abundance and enzyme activity of the mitochondrial respiratory chain complex IV. The TPR domain of OXA2b directly interacts with cytochrome c oxidase subunit 2, aiding in efficient membrane insertion and translocation of its C-terminus. Thus, OXA2b is crucial for the biogenesis of complex IV in plant mitochondria.}, } @article {pmid30496844, year = {2019}, author = {Boubli, JP and Byrne, H and da Silva, MNF and Silva-Júnior, J and Costa Araújo, R and Bertuol, F and Gonçalves, J and de Melo, FR and Rylands, AB and Mittermeier, RA and Silva, FE and Nash, SD and Canale, G and Alencar, RM and Rossi, RV and Carneiro, J and Sampaio, I and Farias, IP and Schneider, H and Hrbek, T}, title = {On a new species of titi monkey (Primates: Plecturocebus Byrne et al., 2016), from Alta Floresta, southern Amazon, Brazil.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {117-137}, doi = {10.1016/j.ympev.2018.11.012}, pmid = {30496844}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Brazil ; Cytochromes b/genetics ; Ecosystem ; Endangered Species ; Genome ; Mitochondria/genetics ; Phylogeny ; Pitheciidae/anatomy & histology/*classification/genetics ; Polymorphism, Single Nucleotide ; }, abstract = {The taxonomy of the titi monkeys (Callicebinae) has recently received considerable attention. It is now recognised that this subfamily is composed of three genera with 33 species, seven of them described since 2002. Here, we describe a new species of titi, Plecturocebus, from the municipality of Alta Floresta, Mato Grosso, Brazil. We adopt an integrative taxonomic approach that includes phylogenomic analyses, pelage characters, and locality records. A reduced representation genome-wide approach was employed to assess phylogenetic relationships among species of the eastern Amazonian clade of the Plecturocebus moloch group. Using existing records, we calculated the Extent of Occurrence (EOO) of the new species and estimated future habitat loss for the region based on predictive models. We then evaluated the species' conservation status using the IUCN Red list categories and criteria. The new species presents a unique combination of morphological characters: (1) grey agouti colouration on the crown and dorsal parts; (2) entirely bright red-brown venter; (3) an almost entirely black tail with a pale tip; and (4) light yellow colouration of the hair on the cheeks contrasting with bright red-brown hair on the sides of the face. Our phylogenetic reconstructions based on maximum-likelihood and Bayesian methods revealed well-supported species relationships, with the Alta Floresta taxon as sister to P. moloch + P. vieirai. The species EOO is 10,166,653 ha and we predict a total habitat loss of 86% of its original forest habitat under a "business as usual" scenario in the next 24 years, making the newly discovered titi monkey a Critically Endangered species under the IUCN A3c criterion. We give the new titi monkey a specific epithet based on: (1) clear monophyly of this lineage revealed by robust genomic and mitochondrial data; (2) distinct and diagnosable pelage morphology; and (3) a well-defined geographical distribution with clear separation from other closely related taxa. Urgent conservation measures are needed to safeguard the future of this newly discovered and already critically endangered primate.}, } @article {pmid30508570, year = {2019}, author = {Hiltunen, JK and Kastaniotis, AJ and Autio, KJ and Jiang, G and Chen, Z and Glumoff, T}, title = {17B-hydroxysteroid dehydrogenases as acyl thioester metabolizing enzymes.}, journal = {Molecular and cellular endocrinology}, volume = {489}, number = {}, pages = {107-118}, doi = {10.1016/j.mce.2018.11.012}, pmid = {30508570}, issn = {1872-8057}, mesh = {17-Hydroxysteroid Dehydrogenases/chemistry/*metabolism ; Animals ; Disease ; Esters/*metabolism ; Fatty Acids, Unsaturated/metabolism ; Humans ; Mitochondria/metabolism ; RNA/metabolism ; }, abstract = {17β-Hydroxysteroid dehydrogenases (HSD17B) catalyze the oxidation/reduction of 17β-hydroxy/keto group in position C17 in C18- and C19 steroids. Most HSD17Bs are also catalytically active with substrates other than steroids. A subset of these enzymes is able to process thioesters of carboxylic acids. This group of enzymes includes HSD17B4, HSD17B8, HSD17B10 and HSD17B12, which execute reactions in intermediary metabolism, participating in peroxisomal β-oxidation of fatty acids, mitochondrial oxidation of 3R-hydroxyacyl-groups, breakdown of isoleucine and fatty acid chain elongation in endoplasmic reticulum. Divergent substrate acceptance capabilities exemplify acquirement of catalytic site adaptiveness during evolution. As an additional common feature these HSD17Bs are multifunctional enzymes that arose either via gene fusions (HSD17B4) or are incorporated as subunits into multifunctional protein complexes (HSD17B8 and HSD17B10). Crystal structures of HSD17B4, HSD17B8 and HSD17B10 give insight into their structure-function relationships. Thus far, deficiencies of HSD17B4 and HSD17B10 have been assigned to inborn errors in humans, underlining their significance as enzymes of metabolism.}, } @article {pmid30512221, year = {2019}, author = {Speijer, D}, title = {Can All Major ROS Forming Sites of the Respiratory Chain Be Activated By High FADH2 /NADH Ratios?: Ancient evolutionary constraints determine mitochondrial ROS formation.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {41}, number = {1}, pages = {e1800180}, doi = {10.1002/bies.201800180}, pmid = {30512221}, issn = {1521-1878}, mesh = {Animals ; *Electron Transport ; Eukaryota/metabolism ; Flavin-Adenine Dinucleotide/*metabolism ; Humans ; Mitochondria/*metabolism ; Models, Biological ; NAD/*metabolism ; Oxidation-Reduction ; Reactive Oxygen Species/*metabolism ; }, abstract = {Aspects of peroxisome evolution, uncoupling, carnitine shuttles, supercomplex formation, and missing neuronal fatty acid oxidation (FAO) are linked to reactive oxygen species (ROS) formation in respiratory chains. Oxidation of substrates with high FADH2 /NADH (F/N) ratios (e.g., FAs) initiate ROS formation in Complex I due to insufficient availability of its electron acceptor (Q) and reverse electron transport from QH2 , e.g., during FAO or glycerol-3-phosphate shuttle use. Here it is proposed that the Q-cycle of Complex III contributes to enhanced ROS formation going from low F/N ratio substrates (glucose) to high F/N substrates. This contribution is twofold: 1) Complex III uses Q as substrate, thus also competing with Complex I; 2) Complex III itself will produce more ROS under these conditions. I link this scenario to the universally observed Complex III dimerization. The Q-cycle of Complex III thus again illustrates the tension between efficient ATP generation and endogenous ROS formation. This model can explain recent findings concerning succinate and ROS-induced uncoupling.}, } @article {pmid30517696, year = {2019}, author = {Ilhan, J and Kupczok, A and Woehle, C and Wein, T and Hülter, NF and Rosenstiel, P and Landan, G and Mizrahi, I and Dagan, T}, title = {Segregational Drift and the Interplay between Plasmid Copy Number and Evolvability.}, journal = {Molecular biology and evolution}, volume = {36}, number = {3}, pages = {472-486}, pmid = {30517696}, issn = {1537-1719}, support = {281357/ERC_/European Research Council/International ; }, mesh = {*Biological Evolution ; Chromosomes, Bacterial ; Escherichia coli ; Gene Frequency ; *Genetic Drift ; *Models, Genetic ; Plasmids/*genetics ; }, abstract = {The ubiquity of plasmids in all prokaryotic phyla and habitats and their ability to transfer between cells marks them as prominent constituents of prokaryotic genomes. Many plasmids are found in their host cell in multiple copies. This leads to an increased mutational supply of plasmid-encoded genes and genetically heterogeneous plasmid genomes. Nonetheless, the segregation of plasmid copies into daughter cells during cell division is considered to occur in the absence of selection on the plasmid alleles. We investigate the implications of random genetic drift of multicopy plasmids during cell division-termed here "segregational drift"-to plasmid evolution. Performing experimental evolution of low- and high-copy non-mobile plasmids in Escherichia coli, we find that the evolutionary rate of multicopy plasmids does not reflect the increased mutational supply expected according to their copy number. In addition, simulated evolution of multicopy plasmid alleles demonstrates that segregational drift leads to increased loss frequency and extended fixation time of plasmid mutations in comparison to haploid chromosomes. Furthermore, an examination of the experimentally evolved hosts reveals a significant impact of the plasmid type on the host chromosome evolution. Our study demonstrates that segregational drift of multicopy plasmids interferes with the retention and fixation of novel plasmid variants. Depending on the selection pressure on newly emerging variants, plasmid genomes may evolve slower than haploid chromosomes, regardless of their higher mutational supply. We suggest that plasmid copy number is an important determinant of plasmid evolvability due to the manifestation of segregational drift.}, } @article {pmid30517740, year = {2019}, author = {Petrov, AS and Wood, EC and Bernier, CR and Norris, AM and Brown, A and Amunts, A}, title = {Structural Patching Fosters Divergence of Mitochondrial Ribosomes.}, journal = {Molecular biology and evolution}, volume = {36}, number = {2}, pages = {207-219}, pmid = {30517740}, issn = {1537-1719}, mesh = {Animals ; *Biological Evolution ; Humans ; *Mitochondrial Ribosomes ; Molecular Conformation ; Proteome ; }, abstract = {Mitochondrial ribosomes (mitoribosomes) are essential components of all mitochondria that synthesize proteins encoded by the mitochondrial genome. Unlike other ribosomes, mitoribosomes are highly variable across species. The basis for this diversity is not known. Here, we examine the composition and evolutionary history of mitoribosomes across the phylogenetic tree by combining three-dimensional structural information with a comparative analysis of the secondary structures of mitochondrial rRNAs (mt-rRNAs) and available proteomic data. We generate a map of the acquisition of structural variation and reconstruct the fundamental stages that shaped the evolution of the mitoribosomal large subunit and led to this diversity. Our analysis suggests a critical role for ablation and expansion of rapidly evolving mt-rRNA. These changes cause structural instabilities that are "patched" by the acquisition of pre-existing compensatory elements, thus providing opportunities for rapid evolution. This mechanism underlies the incorporation of mt-tRNA into the central protuberance of the mammalian mitoribosome, and the altered path of the polypeptide exit tunnel of the yeast mitoribosome. We propose that since the toolkits of elements utilized for structural patching differ between mitochondria of different species, it fosters the growing divergence of mitoribosomes.}, } @article {pmid30518034, year = {2018}, author = {Derbikova, K and Kuzmenko, A and Levitskii, S and Klimontova, M and Chicherin, I and Baleva, MV and Krasheninnikov, IA and Kamenski, P}, title = {Biological and Evolutionary Significance of Terminal Extensions of Mitochondrial Translation Initiation Factor 3.}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, pmid = {30518034}, issn = {1422-0067}, support = {17-14-01005//Russian Science Foundation/ ; 17-54-16005//Russian Foundation for Basic Research/ ; State Assignment AAAA_A16_116021660073_5//Russian Federation Government/ ; }, mesh = {Escherichia coli/metabolism ; *Evolution, Molecular ; Humans ; Mitochondria/*metabolism ; Prokaryotic Initiation Factor-3/*chemistry/*metabolism ; Protein Domains ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/metabolism ; }, abstract = {Protein biosynthesis in mitochondria is organized in a bacterial manner. However, during evolution, mitochondrial translation mechanisms underwent many organelle-specific changes. In particular, almost all mitochondrial translation factors, being orthologous to bacterial proteins, are characterized by some unique elements of primary or secondary structure. In the case of the organellar initiation factor 3 (IF3), these elements are several dozen amino acids long N- and C-terminal extensions. This study focused on the terminal extensions of baker's yeast mitochondrial IF3, Aim23p. By in vivo deletion and complementation analysis, we show that at least one extension is necessary for Aim23p function. At the same time, human mitochondrial IF3 is fully functional in yeast mitochondria even without both terminal extensions. While Escherichia coli IF3 itself is poorly active in yeast mitochondria, adding Aim23p terminal extensions makes the resulting chimeric protein as functional as the cognate factor. Our results show that the terminal extensions of IF3 have evolved as the "adaptors" that accommodate the translation factor of bacterial origin to the evolutionary changed protein biosynthesis system in mitochondria.}, } @article {pmid30523084, year = {2018}, author = {Antonova-Koch, Y and Meister, S and Abraham, M and Luth, MR and Ottilie, S and Lukens, AK and Sakata-Kato, T and Vanaerschot, M and Owen, E and Jado, JC and Maher, SP and Calla, J and Plouffe, D and Zhong, Y and Chen, K and Chaumeau, V and Conway, AJ and McNamara, CW and Ibanez, M and Gagaring, K and Serrano, FN and Eribez, K and Taggard, CM and Cheung, AL and Lincoln, C and Ambachew, B and Rouillier, M and Siegel, D and Nosten, F and Kyle, DE and Gamo, FJ and Zhou, Y and Llinás, M and Fidock, DA and Wirth, DF and Burrows, J and Campo, B and Winzeler, EA}, title = {Open-source discovery of chemical leads for next-generation chemoprotective antimalarials.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {}, pmid = {30523084}, issn = {1095-9203}, support = {P50 GM085764/GM/NIGMS NIH HHS/United States ; R01 AI090141/AI/NIAID NIH HHS/United States ; R01 AI093716/AI/NIAID NIH HHS/United States ; R01 AI103058/AI/NIAID NIH HHS/United States ; }, mesh = {Antimalarials/chemistry/isolation & purification/*pharmacology/therapeutic use ; *Chemoprevention ; *Drug Discovery ; Drug Evaluation, Preclinical ; Humans ; Malaria/*prevention & control ; Mitochondria/drug effects ; Plasmodium/*drug effects/growth & development ; }, abstract = {To discover leads for next-generation chemoprotective antimalarial drugs, we tested more than 500,000 compounds for their ability to inhibit liver-stage development of luciferase-expressing Plasmodium spp. parasites (681 compounds showed a half-maximal inhibitory concentration of less than 1 micromolar). Cluster analysis identified potent and previously unreported scaffold families as well as other series previously associated with chemoprophylaxis. Further testing through multiple phenotypic assays that predict stage-specific and multispecies antimalarial activity distinguished compound classes that are likely to provide symptomatic relief by reducing asexual blood-stage parasitemia from those which are likely to only prevent malaria. Target identification by using functional assays, in vitro evolution, or metabolic profiling revealed 58 mitochondrial inhibitors but also many chemotypes possibly with previously unidentified mechanisms of action.}, } @article {pmid30526820, year = {2018}, author = {Ndiaye, PI and Marchand, B and Bâ, CT and Justine, JL and Bray, RA and Quilichini, Y}, title = {Ultrastructure of mature spermatozoa of three Bucephalidae (Prosorhynchus longisaccatus, Rhipidocotyle khalili and Bucephalus margaritae) and phylogenetic implications.}, journal = {Parasite (Paris, France)}, volume = {25}, number = {}, pages = {65}, pmid = {30526820}, issn = {1776-1042}, mesh = {Animals ; Axoneme/ultrastructure ; Cell Nucleus/ultrastructure ; Fish Diseases/parasitology ; Fishes ; Male ; Microscopy, Electron, Transmission ; Microtubules/ultrastructure ; Mitochondria/ultrastructure ; New Caledonia ; Pacific Ocean ; *Phylogeny ; Spermatozoa/classification/*ultrastructure ; Trematoda/classification/*ultrastructure ; Trematode Infections/parasitology/veterinary ; }, abstract = {We describe here the mature spermatozoa of three species of bucephalids, namely Bucephalus margaritae, Rhipidocotyle khalili and Prosorhynchus longisaccatus. This study provides the first ultrastructural data on the genera Bucephalus and Rhipidocotyle and enabled us to confirm the model of the mature spermatozoon in the Bucephalinae. The spermatozoon exhibits two axonemes with the 9 + "1" pattern of the Trepaxonemata, one of which is very short, lateral expansion, external ornamentation of the plasma membrane located in the anterior extremity of the spermatozoon and associated with cortical microtubules, spine-like bodies, a mitochondrion, and a nucleus. The maximum number of cortical microtubules is located in the anterior part of the spermatozoon. However, more studies are needed to elucidate if spine-like bodies are present in all the Bucephalinae or not. In the Prosorhynchinae, the mature spermatozoon exhibits a similar ultrastructural pattern. Some differences are observed, particularly the axoneme lengths and the arrangement of the spine-like bodies. The posterior extremity of the spermatozoon in the Bucephalinae exhibits only the nucleus, but prosorhynchines have microtubules.}, } @article {pmid30527196, year = {2018}, author = {Kazdal, D and Harms, A and Endris, V and Penzel, R and Oliveira, C and Kriegsmann, M and Longuespée, R and Winter, H and Schneider, MA and Muley, T and Pfarr, N and Weichert, W and Stenzinger, A and Warth, A}, title = {Subclonal evolution of pulmonary adenocarcinomas delineated by spatially distributed somatic mitochondrial mutations.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {126}, number = {}, pages = {80-88}, doi = {10.1016/j.lungcan.2018.10.024}, pmid = {30527196}, issn = {1872-8332}, mesh = {Adenocarcinoma/*genetics/pathology ; Aged ; Clonal Evolution ; DNA, Mitochondrial/classification/*genetics ; Disease-Free Survival ; Female ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Middle Aged ; *Mutation ; Mutation Rate ; Phylogeny ; Prognosis ; }, abstract = {OBJECTIVES: The potential role of cancer associated somatic mutations of the mitochondrial genome (mtDNA) is controversial and still poorly understood. Our group and others recently challenged a direct tumorigenic impact and suggested a passenger-like character. In combination with the known increased mutation rate, somatic mtDNA mutations account for an interesting tool to delineate tumor evolution. Here, we comprehensively analyzed the spatial distribution of somatic mtDNA mutations throughout whole tumor sections of pulmonary adenocarcinoma (ADC).

MATERIALS AND METHODS: Central sections of 19 ADC were analyzed in a segmented manner (11-34 segments/tumor) together with non-neoplastic tissue samples and lymph node metastasis, if present. We performed whole mtDNA sequencing and real-time PCR based quantification of mtDNA copy numbers for all samples. Further, histological growth patterns were determined on H&E sections and the tumor cell content was quantified by digital pathology analyses.

RESULTS: Somatic mtDNA mutations were present in 96% (18/19) of the analyzed tumors, either ubiquitously or restricted to specific tumor regions. Spatial and histological mapping of the mutations enabled the identification of subclonal structures and phylogenetic relations within a tumor section indicating different progression levels. In this regard, lymph node metastases seem to be related to early events in ADC development. There was no concurrence between histological and mtDNA mutation based clusters. However, micropapillary patterns occurred only in tumors with ubiquitous mutations. ADC with more than two ubiquitous mutations were associated with shorter disease-free survival (p < 0.01).

CONCLUSION: Cancer related mtDNA mutations are interesting candidates for the understanding of subclonal ADC evolution and perspectively for monitoring tumor progression. Our data reveal a potential prognostic relevance of somatic mtDNA mutations.}, } @article {pmid30528084, year = {2019}, author = {Przyboś, E and Rautian, M and Beliavskaia, A and Tarcz, S}, title = {Evaluation of the molecular variability and characteristics of Paramecium polycaryum and Paramecium nephridiatum, within subgenus Cypriostomum (Ciliophora, Protista).}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {296-306}, doi = {10.1016/j.ympev.2018.12.003}, pmid = {30528084}, issn = {1095-9513}, mesh = {Bayes Theorem ; DNA, Mitochondrial/genetics/metabolism ; Electron Transport Complex IV/classification/genetics ; Haplotypes ; Likelihood Functions ; Mitochondria/genetics ; Paramecium/*classification ; Phylogeny ; }, abstract = {Although some Paramecium species are suitable research objects in many areas of life sciences, the biodiversity structure of other species is almost unknown. In the current survey, we present a molecular analysis of 60 Cypriostomum strains, which for the first time allows for the study of intra- and interspecific relationships within that subgenus, as well as the assessment of the biogeography patterns of its morphospecies. Analysis of COI mtDNA variation revealed three main clades (separated from each other by approximately 130 nucleotide substitutions), each one with internal sub-clusters (differing by 30 to 70 substitutions - a similar range found between P. aurelia cryptic species and P. bursaria syngens). The first clade is represented exclusively by P. polycaryum; the second one includes only four strains identified as P. calkinsi. The third cluster seems to be paraphyletic, as it includes P. nephridiatum, P. woodruffi, and Eucandidatus P. hungarianum. Some strains, previously identified as P. calkinsi, had COI sequences identical or very similar to P. nephridiatum ones. Morphological reinvestigation of several such strains revealed common morphological features with P. nephridiatum. The paper contains new information concerning speciation within particular species, i.e. existence of cryptic species within P. polycaryum (three) and in P. nephridiatum (six).}, } @article {pmid30529551, year = {2019}, author = {Liu, J and Yu, J and Zhou, M and Yang, J}, title = {Complete mitochondrial genome of Japalura flaviceps: Deep insights into the phylogeny and gene rearrangements of Agamidae species.}, journal = {International journal of biological macromolecules}, volume = {125}, number = {}, pages = {423-431}, doi = {10.1016/j.ijbiomac.2018.12.068}, pmid = {30529551}, issn = {1879-0003}, mesh = {Animals ; DNA, Mitochondrial/genetics ; Gene Rearrangement/*genetics ; Genome, Mitochondrial/*genetics ; Lizards/*genetics ; Mitochondria/*genetics ; Phylogeny ; RNA, Transfer/genetics ; Reptiles/*genetics ; }, abstract = {Japalura flaviceps is a subarboreal species, which is endemically distributed in China. Here, we determined the complete mitogenome of J. flaviceps. This mitogenome was a typical circular molecule of 17,140 bp in size, containing 13 protein-coding genes, 22 transfer-RNA-coding genes, two ribosomal-RNA-coding genes, and one control region. Our phylogenetic result using 15 genes divided all Agamidae lizards into six subfamilies and showed (((((Agaminae, Draconinae), Amphibolurinae), Hydrosaurinae), Uromastycinae), Leiolepinae), which was different from the previous studies. J. flaviceps had a closer relationship to Pseudocalotes species than Acanthosaura species, and they formed a well-supported lineage of Draconinae subfamily. There were nine mitochondrial gene rearrangement types among the 27 Agamidae species, and six of them were found in the Agaminae group. The trnP gene of J. flaviceps mitogenome was encoded on the heavy strand instead of its typical light strand position, providing an example of gene inversion in vertebrate mitogenomes. J. flaviceps shared the same gene arrangement type (inverted trnP gene) with other Draconinae species, strongly implying a single occurrence of the trnP inversion in the ancestral draconine lineage. Our study helps to understand mitogenome evolution and phylogenetic relations