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Bibliography on: Mitochondrial Evolution

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 22 Oct 2020 at 01:50 Created: 

Mitochondrial Evolution

The endosymbiotic hypothesis for the origin of mitochondria (and chloroplasts) suggests that mitochondria are descended from specialized bacteria (probably purple nonsulfur bacteria) that somehow survived endocytosis by another species of prokaryote or some other cell type, and became incorporated into the cytoplasm.

Created with PubMed® Query: mitochondria AND evolution NOT 26799652[PMID] NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2020-10-21
CmpDate: 2020-10-21

GÓmez-Zurita J, Platania L, A Cardoso (2020)

A new species of the genus Tricholapita nom. nov. and stat. nov. (Coleoptera: Chrysomelidae, Eumolpinae) from New Caledonia.

Zootaxa, 4858(1):zootaxa.4858.1.5 pii:zootaxa.4858.1.5.

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.

RevDate: 2020-10-20

Qu C, Wang L, Zhao Y, et al (2020)

Molecular Evolution of Maize Ascorbate Peroxidase Genes and Their Functional Divergence.

Genes, 11(10): pii:genes11101204.

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.

RevDate: 2020-10-20
CmpDate: 2020-10-20

Vargas-Ramírez M, Caballero S, Morales-Betancourt MA, et al (2020)

Genomic analyses reveal two species of the matamata (Testudines: Chelidae: Chelus spp.) and clarify their phylogeography.

Molecular phylogenetics and evolution, 148:106823.

The matamata is one of the most charismatic turtles on earth, widely distributed in northern South America. Debates have occurred over whether or not there should be two subspecies or species recognized due to its geographic variation in morphology. Even though the matamata is universally known, its natural history, conservation status and biogeography are largely unexplored. In this study we examined the phylogeographic differentiation of the matamata based on three mitochondrial DNA fragments (2168 bp of the control region, cytochrome oxidase subunit I, and the cytochrome b gene), one nuclear genomic DNA fragment (1068 bp of the R35 intron) and 1661 Single Nucleotide Polymorphisms (SNPs). Our molecular and morphological analyses revealed the existence of two distinct, genetically deeply divergent evolutionary lineages of matamatas that separated in the late Miocene (approximately 12.7 million years ago), corresponding well to the time when the Orinoco Basin was established. As a result of our analyses, we describe the genetically and morphologically highly distinct matamata from the Orinoco and Río Negro Basins and the Essequibo drainage as a species new to science (Chelus orinocensis sp. nov.). Chelus fimbriata sensu stricto is distributed in the Amazon Basin and the Mahury drainage. Additionally, the analyses revealed that each species displays phylogeographic differentiation. For C. orinocensis, there is moderate mitochondrial differentiation between the Orinoco and the Río Negro. For C. fimbriata, there is more pronounced differentiation matching different river systems. One mitochondrial clade was identified from the Amazon, Ucayali, and Mahury Rivers, and another one from the Madeira and Jaci Paraná Rivers. The C. orinocensis in the Essequibo and Branco Rivers have haplotypes that constitute a third clade clustering with C. fimbriata. Phylogenetic analyses of the R35 intron and SNP data link the matamatas from the Essequibo and Branco with the new species, suggesting past gene flow and old mitochondrial introgression. Chelus orinocensis is collected for the pet trade in Colombia and Venezuela. However, neither the extent of the harvest nor its impact are known. Hence, it is crucial to gather more information and to assess its exploitation throughout its distribution range to obtain a better understanding of its conservation status and to design appropriate conservation and management procedures. RESUMEN: La matamata es una de las tortugas más carismáticas del mundo, ampliamente distribuida en el norte de Sudamérica. Debido a su variación morfológica geográfica, se debate sobre el reconocimiento de dos subespecies o especies. A pesar de que la matamata es universalmente conocida, su historia natural, estado de conservación y biogeografía han sido muy poco estudiados. En este estudio examinamos la diferenciación filogeográfica de las matamatas en base ​​a tres fragmentos de ADN mitocondrial (2168 pb de la región de control, la subunidad I del citocromo oxidasa y el gen del citocromo b), un fragmento de ADN genómico nuclear (1068 pb del intrón R35) y 1661 polimorfismos de nucleótido único (SNPs). Nuestros análisis moleculares y morfológicos revelaron la existencia de dos linajes evolutivos distintos de matamatas, genéticamente divergentes que se separaron en el Mioceno tardio (hace aproximadamente 12.7 millones de años), correspondiendo al tiempo en que se estableció la cuenca del Orinoco. Como resultado de nuestros análisis, describimos las genéticamente y morfológicamente distintas matamatas de las cuencas del Orinoco, Río Negro y Essequibo como una especie nueva para la ciencia (Chelus orinocensis sp. nov.). Chelus fimbriata sensu stricto se distribuye en la cuenca del Amazonas y en el drenaje del Mahury. Adicionalmente, los análisis revelaron que cada especie muestra diferenciación filogeográfica. Para C. orinocensis, hay una moderada diferenciación mitocondrial entre el Orinoco y el Río Negro. Para C. fimbriata, hay una diferenciación más pronunciada, concordando con los diferentes sistemas fluviales. Se identificó un clado de los ríos Amazonas, Ucayali y Mahury y otro de los ríos Madeira y Jaci Paraná. Las C. orinocensis de los ríos Essequibo y Branco tienen haplotipos que constituyen un tercer clado que se agrupa con C. fimbriata. Los análisis filogenéticos del intrón R35 y los datos de SNP asocian las matamatas de Essequibo y Branco con la nueva especie, sugiriendo flujo de genes pasado ​​e introgresión mitocondrial antigua. Chelus orinocensis se colecta para el comercio de mascotas en Colombia y Venezuela. Sin embargo, ni se conoce el alcance de las colectas ni su impacto. Por lo tanto, es crucial recopilar más información y evaluar su explotación en todo su rango de distribución, comprender mejor su estado de conservación y para diseñar acciones apropiadas de conservación y manejo.

RevDate: 2020-10-19
CmpDate: 2020-10-19

Cinar HN, Gopinath G, Murphy HR, et al (2020)

Molecular typing of Cyclospora cayetanensis in produce and clinical samples using targeted enrichment of complete mitochondrial genomes and next-generation sequencing.

Parasites & vectors, 13(1):122.

BACKGROUND: Outbreaks of cyclosporiasis, a diarrheal illness caused by Cyclospora cayetanensis, have been a public health issue in the USA since the mid 1990's. In 2018, 2299 domestically acquired cases of cyclosporiasis were reported in the USA as a result of multiple large outbreaks linked to different fresh produce commodities. Outbreak investigations are hindered by the absence of standardized molecular epidemiological tools for C. cayetanensis. For other apicomplexan coccidian parasites, multicopy organellar DNA such as mitochondrial genomes have been used for detection and molecular typing.

METHODS: We developed a workflow to obtain complete mitochondrial genome sequences from cilantro samples and clinical samples for typing of C. cayetanensis isolates. The 6.3 kb long C. cayetanensis mitochondrial genome was amplified by PCR in four overlapping amplicons from genomic DNA extracted from cilantro, seeded with oocysts, and from stool samples positive for C. cayetanensis by diagnostic methods. DNA sequence libraries of pooled amplicons were prepared and sequenced via next-generation sequencing (NGS). Sequence reads were assembled using a custom bioinformatics pipeline.

RESULTS: This approach allowed us to sequence complete mitochondrial genomes from the samples studied. Sequence alterations, such as single nucleotide polymorphism (SNP) profiles and insertion and deletions (InDels), in mitochondrial genomes of 24 stool samples from patients with cyclosporiasis diagnosed in 2014, exhibited discriminatory power. The cluster dendrogram that was created based on distance matrices of the complete mitochondrial genome sequences, indicated distinct strain-level diversity among the 2014 C. cayetanensis outbreak isolates analyzed in this study.

CONCLUSIONS: Our results suggest that genomic analyses of mitochondrial genome sequences may help to link outbreak cases to the source.

RevDate: 2020-10-19
CmpDate: 2020-10-19

Dujon B (2020)

Mitochondrial genetics revisited.

Yeast (Chichester, England), 37(2):191-205.

Mitochondrial genetics started decades ago with the discovery of yeast mutants that ignored the Mendelian rules of inheritance. Today, the many known DNA sequences of this second eukaryotic genome illustrate its eccentricity in terms of informational content and functional organisation, suggesting a yet incomplete understanding of its evolution. The hereditary transmission of mitochondrial alleles relies on complex mixes of molecular and cellular mechanisms in which recombination and limited sampling, two sources of rapid genetic changes, play central roles. It is also under the influence of invasive genetic elements whose inconstant distribution in mitochondrial genomes suggests rapid turnovers in evolving populations. This susceptibility to changes contrasts with the development of specific functional interactions between the mitochondrial and nuclear genetic compartments, a trend that is prone to limit the genetic exchanges between distinct lineages. It is perhaps this opposition and the discordant inheritance between mitochondrial and nuclear genomes that best explain the maintenance of a second genome and a second independent protein synthesising machinery in eukaryotic cells.

RevDate: 2020-10-19
CmpDate: 2020-10-19

Huang G, Cong Z, Wang X, et al (2020)

Targeting HSP90 attenuates angiotensin II-induced adventitial remodelling via suppression of mitochondrial fission.

Cardiovascular research, 116(5):1071-1084.

AIMS: Adventitial remodelling presenting with the phenotypic switch of adventitial fibroblasts (AFs) to myofibroblasts is reportedly involved in the evolution of several vascular diseases, including hypertension. In our previous study, we reported that heat shock protein 90 (HSP90) inhibition by 17-dime-thylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) markedly attenuates angiotensin II (AngII)-induced abdominal aortic aneurysm formation by simultaneously inhibiting several key signalling and transcriptional pathways in vascular smooth muscle cells; however, little is known about its role on AFs. Given that the AF phenotypic switch is likely to be associated with mitochondrial function and calcineurin (CN), a client protein of HSP90 that mediates mitochondrial fission and function, the aim of this study was to investigate whether mitochondrial fission contributes to phenotypic switch of AF, and if it does, we further aimed to determine whether HSP90 inhibition attenuates mitochondrial fission and subsequently suppresses AF transformation and adventitial remodelling in AngII-induced hypertensive mice.

METHODS AND RESULTS: In primary mouse AFs, we found that CN-dependent dephosphorylation of Drp1 induced mitochondrial fission and regulated mitochondrial reactive oxygen species production, which stimulated AF proliferation, migration, and phenotypic switching in AngII-treated AFs. Moreover, AngII was found to increase the binding of HSP90 and CN in AFs, while HSP90 inhibition significantly reversed AngII-induced mitochondrial fission and AF phenotypic switching by modulating the CN-dependent dephosphorylation of Drp1. Consistent with the effects in AFs, in an animal model of AngII-induced adventitial remodelling, 17-DMAG markedly reduced mitochondrial fission, AF differentiation, vessel wall thickening, and fibrosis in the aortic adventitia, which were mediated by CN/Drp1 signalling pathways.

CONCLUSIONS: Our study suggests that CN/Drp1-dependent mitochondrial fission may be essential for understanding adventitial remodelling in hypertension and that HSP90 inhibition may serve as a novel approach for the treatment of adventitial remodelling-related diseases.

RevDate: 2020-10-20
CmpDate: 2020-10-20

Hirano T, Saito T, Tsunamoto Y, et al (2019)

Enigmatic incongruence between mtDNA and nDNA revealed by multi-locus phylogenomic analyses in freshwater snails.

Scientific reports, 9(1):6223 pii:10.1038/s41598-019-42682-0.

Phylogenetic incongruence has frequently been encountered among different molecular markers. Recent progress in molecular phylogenomics has provided detailed and important information for evolutionary biology and taxonomy. Here we focused on the freshwater viviparid snails (Cipangopaludina chinensis chinensis and C. c. laeta) of East Asia. We conducted phylogenetic analyses and divergence time estimation using two mitochondrial markers. We also performed population genetic analyses using genome-wide SNPs. We investigated how and which phylogenetic patterns reflect shell morphology. The results showed these two species could be separated into four major mitochondrial clades, whereas the nuclear clusters supported two groups. The phylogenetic patterns of both mtDNA and nDNA largely reflected the geographical distribution. Shell morphology reflected the phylogenetic clusters based on nDNA. The findings also showed these two species diversified in the Pliocene to early Pleistocene era, and occurred introgressive hybridisation. The results also raise the taxonomic issue of the two species.

RevDate: 2020-10-19

Kang JS, Zhang HR, Wang YR, et al (2020)

Distinctive evolutionary pattern of organelle genomes linked to the nuclear genome in Selaginellaceae.

The Plant journal : for cell and molecular biology [Epub ahead of print].

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-kb 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 (DNA-RRR) proteins indicated that, several single-targeted proteins, particularly plastid-targeted RecA1, have been lost in Selaginellaceae; conversely, the dual-targeted proteins remain intact. According to the reported function of RecA1, 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.

RevDate: 2020-10-19

Teulière J, Bernard G, E Bapteste (2020)

The Distribution of Genes Associated With Regulated Cell Death Is Decoupled From the Mitochondrial Phenotypes Within Unicellular Eukaryotic Hosts.

Frontiers in cell and developmental biology, 8:536389.

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.

RevDate: 2020-10-19

Friesen CR, Noble DWA, M Olsson (2020)

The role of oxidative stress in postcopulatory selection.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 375(1813):20200065.

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'.

RevDate: 2020-10-15

Lima-Posada I, NA Bobadilla (2020)

Understanding the opposite effects of sex hormones in mediating renal injury.

Nephrology (Carlton, Vic.) [Epub ahead of print].

According to epidemiological studies, chronic kidney disease (CKD) affects more women than men, but the incidence of end-stage renal disease (ESRD) is higher in men than in women. However, most of these studies have not considered the CKD incidence in women of reproductive or postmenopausal age, and even less 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, males of reproductive age exhibit more abnormalities in renal function and structure that lead to greater progression to CKD than females, which suggests that these differences are mediated by sex hormones rather other factors. This review intents to show the mechanisms regulated by estrogen or testosterone that may explain the different risk and evolution of the renal diseases between males and females. 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 AKI to CKD does not occur in female rats 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.

RevDate: 2020-10-14
CmpDate: 2020-10-14

Bolívar-Leguizamón SD, Silveira LF, Derryberry EP, et al (2020)

Phylogeography of the Variable Antshrike (Thamnophilus caerulescens), a South American passerine distributed along multiple environmental gradients.

Molecular phylogenetics and evolution, 148:106810.

The Neotropics show a wealth of distributional patterns shared by many co-distributed species. A distinctive pattern is the so-called "circum-Amazonian distribution," which is observed in species that do not occur in Amazonia but rather along a belt of forested habitats spanning south and east of Amazonia, the Andean foothills, and often into the Venezuelan Coastal Range and the Tepuis. Although this pattern is widespread across animals and plants, its underlying biogeographic mechanisms remain poorly understood. The Variable Antshrike (Thamnophilus caerulescens) is a sexually dimorphic suboscine passerine that exhibits extreme plumage variation and occurs along the southern portion of the circum-Amazonian belt. We describe broad-scale phylogeographic patterns of T. caerulescens and assess its demographic history using DNA sequences from the mitochondrion and ultraconserved elements (UCEs). We identified three genomic clusters: a) northern Atlantic Forest; b) southeastern Cerrado and central-southern Atlantic Forest, and c) Chaco and Andes. Our results were consistent with Pleistocene divergence followed by gene flow, mainly between the latter two clusters. There were no genetic signatures of rapid population expansions or bottlenecks. The population from the northern Atlantic Forest was the most genetically divergent group within the species. The demographic history of T. caerulescens was probably affected by series of humid and dry periods throughout the Quaternary that generated subtle population expansions and contractions allowing the intermittent connection of habitats along the circum-Amazonian belt. Recognizing the dynamic history of climate-mediated forest expansions, contractions, and connections during the South American Pleistocene is central toward a mechanistic understanding of circum-Amazonian distributions.

RevDate: 2020-10-14
CmpDate: 2020-10-14

Li JN, Liang D, Wang YY, et al (2020)

A large-scale systematic framework of Chinese snakes based on a unified multilocus marker system.

Molecular phylogenetics and evolution, 148:106807.

Snakes are one of the most diverse groups of terrestrial vertebrates, with approximately 3500 extant species. A robust phylogeny and taxonomy of snakes is crucial for us to know, study and protect them. For a large group such as snakes, broad-scale phylogenetic reconstructions largely rely on data integration. Increasing the compatibility of the data from different researches is thus important, which can be facilitated by standardization of the loci used in systematic analyses. In this study, we proposed a unified multilocus marker system for snake systematics by conflating 5 mitochondrial markers, 19 vertebrate-universal nuclear protein coding (NPC) markers and 72 snake-specific noncoding intron markers. This marker system is an addition to the large squamate conserved locus set (SqCL) for studies preferring a medium-scale data set. We applied this marker system to over 440 snake samples and constructed the currently most comprehensive systematic framework of the snakes in China. Robust snake phylogenetic relationships were recovered at both deep and shallow evolutionary depths, demonstrating the usefulness of this multilocus marker system. Discordance was revealed by a parallel comparison between the snake tree based on the multilocus marker system and that based on only the mitochondrial loci, highlighting the necessity of using multiple types of markers to better understand the snake evolutionary histories. The divergence times of different snake groups were estimated with the nuclear data set. Our comprehensive snake tree not only confirms many important nodes inferred in previous studies but also contributes new insights into many snake phylogenetic relationships. Suggestions are made for the current Chinese snake taxonomy.

RevDate: 2020-10-16
CmpDate: 2020-10-16

Eberle J, Ahrens D, Mayer C, et al (2020)

A Plea for Standardized Nuclear Markers in Metazoan DNA Taxonomy.

Trends in ecology & evolution, 35(4):336-345.

The ease of sequencing DNA barcodes promoted a species identification system universally applicable across animal phyla. However, relying on a single mitochondrial DNA fragment has a number of drawbacks that can mislead species delimitation and identification. Implementation of multiple nuclear markers would mitigate the limits of the current barcoding system if these markers are universally applicable across species, carry sufficient information to discriminate between closely related species, and if sequencing and analyzing these markers can be automatized. As sequencing costs continue to fall, we believe that the time is right to extend DNA barcoding. Here we argue that nearly universal single-copy nuclear protein-coding genes deliver the desired characteristics and could be used to reliably delimit and identify animal species.

RevDate: 2020-10-13

da Veiga Moreira J, Schwartz L, M Jolicoeur (2020)

Targeting Mitochondrial Singlet Oxygen Dynamics Offers New Perspectives for Effective Metabolic Therapies of Cancer.

Frontiers in oncology, 10:573399.

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 (1O2) dynamics may be an efficient target for metabolic therapy development.

RevDate: 2020-10-07

Bolmatov D, Carrillo JY, Sumpter BG, et al (2020)

Double membrane formation in heterogeneous vesicles.

Soft matter, 16(38):8806-8817.

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.

RevDate: 2020-10-05

Mayr SJ, Mendel RR, G Schwarz (2020)

Molybdenum cofactor biology, evolution and deficiency.

Biochimica et biophysica acta. Molecular cell research pii:S0167-4889(20)30241-X [Epub ahead of print].

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.

RevDate: 2020-10-02

Braymer JJ, Freibert SA, Rakwalska-Bange M, et al (2020)

Mechanistic concepts of iron-sulfur protein biogenesis in Biology.

Biochimica et biophysica acta. Molecular cell research pii:S0167-4889(20)30221-4 [Epub ahead of print].

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.

RevDate: 2020-09-30

Friedl J, Knopp MR, Groh C, et al (2020)

More than just a ticket canceller: The mitochondrial processing peptidase tailors complex precursor proteins at internal cleavage sites.

Molecular biology of the cell [Epub ahead of print].

Most mitochondrial proteins are synthesized as precursors that carry N-terminal presequences. After import into mitochondria, these targeting signals are cleaved off by the mitochondrial processing peptidase MPP. Using the mitochondrial tandem protein Arg5,6 as 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 "ticket canceller" for removal of presequences, MPP exhibits a second, conserved activity as internal processing peptidase for complex mitochondrial precursor proteins.

RevDate: 2020-10-02

Tan DX, R Hardeland (2020)

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.

Molecules (Basel, Switzerland), 25(19): pii:molecules25194410.

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.

RevDate: 2020-10-06

Cheong A, Lingutla R, J Mager (2020)

Expression analysis of mammalian mitochondrial ribosomal protein genes.

Gene expression patterns : GEP, 38:119147 pii:S1567-133X(20)30170-8 [Epub ahead of print].

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.

RevDate: 2020-10-08
CmpDate: 2020-10-08

Camus MF (2020)

The perils of cheating.

eLife, 9:.

Experiments on mitochondrial DNA in worms highlight that cheating does not always pay off.

RevDate: 2020-10-02

Yamada Y, Sato Y, Nakamura T, et al (2020)

Evolution of drug delivery system from viewpoint of controlled intracellular trafficking and selective tissue targeting toward future nanomedicine.

Journal of controlled release : official journal of the Controlled Release Society, 327:533-545 pii:S0168-3659(20)30514-9 [Epub ahead of print].

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.

RevDate: 2020-09-28

Mallard J, Hucteau E, Schott R, et al (2020)

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.

Frontiers in oncology, 10:1304.

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.

RevDate: 2020-09-08

Zhao D, Wang H, Chen S, et al (2020)

Phytomelatonin: An Emerging Regulator of Plant Biotic Stress Resistance.

Trends in plant science pii:S1360-1385(20)30256-9 [Epub ahead of print].

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.

RevDate: 2020-09-07

Royes J, Biou V, Dautin N, et al (2020)

Inducible intracellular membranes: molecular aspects and emerging applications.

Microbial cell factories, 19(1):176 pii:10.1186/s12934-020-01433-x.

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).

RevDate: 2020-09-28

Karakaidos P, T Rampias (2020)

Mitonuclear Interactions in the Maintenance of Mitochondrial Integrity.

Life (Basel, Switzerland), 10(9): pii:life10090173.

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.

RevDate: 2020-10-12
CmpDate: 2020-09-30

Yazaki E, Kume K, Shiratori T, et al (2020)

Barthelonids represent a deep-branching metamonad clade with mitochondrion-related organelles predicted to generate no ATP.

Proceedings. Biological sciences, 287(1934):20201538.

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.

RevDate: 2020-09-01

Seeliger B, Alesina PF, Walz MK, et al (2020)

Intraoperative imaging for remnant viability assessment in bilateral posterior retroperitoneoscopic partial adrenalectomy in an experimental model.

The British journal of surgery [Epub ahead of print].

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.

RevDate: 2020-09-03

Dawson ER, Patananan AN, Sercel AJ, et al (2020)

Stable retention of chloramphenicol-resistant mtDNA to rescue metabolically impaired cells.

Scientific reports, 10(1):14328.

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.

RevDate: 2020-08-28

Medini H, Cohen T, D Mishmar (2020)

Mitochondria Are Fundamental for the Emergence of Metazoans: On Metabolism, Genomic Regulation, and the Birth of Complex Organisms.

Annual review of genetics [Epub ahead of print].

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; (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. Expected final online publication date for the Annual Review of Genetics, Volume 54 is November 23, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

RevDate: 2020-08-27

Arakawa T, Kagami H, Katsuyama T, et al (2020)

A lineage-specific paralogue of Oma1 evolved into a gene family from which a suppressor of male sterility-inducing mitochondria emerged in plants.

Genome biology and evolution pii:5898194 [Epub ahead of print].

Cytoplasmic male sterility in plants is caused by male sterility-inducing mitochondria, which have emerged frequently during plant evolution. Nuclear Restorer-of-fertility (Rf) genes can suppress their cognate male sterility-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 homologues in plants. We analyzed 37 plant genomes and concluded that a single copy is the ancestral state in Caryophyllales. Among the sugar beet Oma1 homologues, 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 homologue 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 A. thaliana. This suggests a segmental duplication rather than a whole genome duplication as the mechanism of RF-Oma1 evolution. Among the positively selected codons in RF-Oma1, many 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 paralogue. 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.

RevDate: 2020-08-28

Pérez-Hernández CA, Kern CC, Butkeviciute E, et al (2020)

Mitochondrial Signature in Human Monocytes and Resistance to Infection in C. elegans During Fumarate-Induced Innate Immune Training.

Frontiers in immunology, 11:1715.

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 Ca2+ 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.

RevDate: 2020-09-28

Aguirre-López B, Escalera-Fanjul X, Hersch-González J, et al (2020)

In Kluyveromyces lactis a Pair of Paralogous Isozymes Catalyze the First Committed Step of Leucine Biosynthesis in Either the Mitochondria or the Cytosol.

Frontiers in microbiology, 11:1843.

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.

RevDate: 2020-09-28

Chen M, Chen N, Wu T, et al (2020)

Characterization of Two Mitochondrial Genomes and Gene Expression Analysis Reveal Clues for Variations, Evolution, and Large-Sclerotium Formation in Medical Fungus Wolfiporia cocos.

Frontiers in microbiology, 11:1804.

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-UUG2), 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.

RevDate: 2020-08-27

Krajnc E, Visentin M, Gai Z, et al (2020)

Untargeted metabolomics reveals anaerobic glycolysis as a novel target of the hepatotoxic antidepressant nefazodone.

The Journal of pharmacology and experimental therapeutics pii:jpet.120.000120 [Epub ahead of print].

Mitochondrial damage is considered a hallmark of drug-induced liver injury (DILI). However, despite the common molecular etiology, the evolution of the injury is usually unpredictable, with some cases that are mild and reversible upon discontinuation of the treatment and others characterized by irreversible acute liver failure. This suggests that additional mechanisms of damage play a role in determining the progression of the initial insult. To uncover novel pathways potentially involved in DILI, we investigated in vitro the metabolic perturbations associated with nefazodone, an antidepressant associated with acute liver failure. Several pathways associated with ATP production, including gluconeogenesis, anaerobic glycolysis and oxidative phosphorylation, were altered in human hepatocellular carcinoma-derived (Huh7) cells after two hour-exposure to a 50 μM extracellular concentration of nefazodone. In the presence or absence of glucose, ATP production of Huh7 cells was glycolysis- and oxidative phosphorylation-dependent, respectively. In glucose-containing medium, nefazodone-induced ATP depletion from Huh7 cells was biphasic. Huh7 cells in glucose-free medium were more sensitive to nefazodone than those in glucose-containing medium, losing the biphasic inhibition. Primary cultured mouse hepatocytes, mainly dependent on oxidative phosphorylation, were more sensitive than Huh7 cells to nefazodone exposure in glucose-containing medium. At lower extracellular concentrations, nefazodone inhibited the oxygen consumption of Huh7 cells, whereas, at higher extracellular concentrations, it also inhibited the extracellular acidification. ATP content was rescued by increasing the extracellular concentration of glucose. In conclusion, nefazodone has a dual inhibitory effect on mitochondrial-dependent and mitochondrial-independent ATP production. Significance Statement Mitochondrial damage is a hallmark of drug-induced liver injury, yet other collateral alterations might contribute to the severity and evolution of the injury. Our in vitro study supports previous results arguing that a deficit in hepatic glucose metabolism, concomitant to the mitochondrial injury, might be cardinal in the prognosis of the initial insult to the liver. From a drug development standpoint, coupling anaerobic glycolysis and mitochondrial function assessment might increase the drug-induced liver injury preclinical screening performance.

RevDate: 2020-08-27

Nunes-Nesi A, Cavalcanti JHF, AR Fernie (2020)

Characterization of In Vivo Function(s) of Members of the Plant Mitochondrial Carrier Family.

Biomolecules, 10(9): pii:biom10091226.

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.

RevDate: 2020-10-09

Esch T, Kream RM, GB Stefano (2020)

Emerging regulatory roles of opioid peptides, endogenous morphine, and opioid receptor subtypes in immunomodulatory processes: Metabolic, behavioral, and evolutionary perspectives.

Immunology letters, 227:28-33.

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.

RevDate: 2020-09-24

Shen H, Zheng X, Zhou Z, et al (2020)

Oriented immobilization of enzyme-DNA conjugates on magnetic Janus particles for constructing a multicompartment multienzyme system with high activity and stability.

Journal of materials chemistry. B, 8(36):8467-8475.

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.

RevDate: 2020-09-28

Santos HJ, Chiba Y, Makiuchi T, et al (2020)

Import of Entamoeba histolytica Mitosomal ATP Sulfurylase Relies on Internal Targeting Sequences.

Microorganisms, 8(8):.

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.

RevDate: 2020-09-28

N Miyata M, Nomura M, D Kageyama (2020)

Wolbachia have made it twice: Hybrid introgression between two sister species of Eurema butterflies.

Ecology and evolution, 10(15):8323-8330.

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.

RevDate: 2020-09-09
CmpDate: 2020-09-09

Pittis AA, Goh V, Cebrian-Serrano A, et al (2020)

Discovery of EMRE in fungi resolves the true evolutionary history of the mitochondrial calcium uniporter.

Nature communications, 11(1):4031.

Calcium (Ca2+) influx into mitochondria occurs through a Ca2+-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-Ca2+ uptake. Here, we trace the mt-Ca2+ 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-Ca2+ uptake when reconstituted in vivo in the yeast Saccharomyces cerevisiae. Our study represents the most comprehensive phylogenomic analysis of the mt-Ca2+ 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.

RevDate: 2020-09-07

Bennewitz B, Sharma M, Tannert F, et al (2020)

Dual targeting of TatA points to a chloroplast-like Tat pathway in plant mitochondria.

Biochimica et biophysica acta. Molecular cell research, 1867(11):118816.

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.

RevDate: 2020-09-07

Nechushtai R, Karmi O, Zuo K, et al (2020)

The balancing act of NEET proteins: Iron, ROS, calcium and metabolism.

Biochimica et biophysica acta. Molecular cell research, 1867(11):118805.

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.

RevDate: 2020-08-02

Smith SK, ES Musiek (2020)

Impact of circadian and diurnal rhythms on cellular metabolic function and neurodegenerative diseases.

International review of neurobiology, 154:393-412.

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.

RevDate: 2020-10-02

Williams R, Laskovs M, Williams RI, et al (2020)

A Mitochondrial Stress-Specific Form of HSF1 Protects against Age-Related Proteostasis Collapse.

Developmental cell, 54(6):758-772.e5.

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.

RevDate: 2020-09-29
CmpDate: 2020-09-29

Pelster B, Wood CM, Campos DF, et al (2020)

Cellular oxygen consumption, ROS production and ROS defense in two different size-classes of an Amazonian obligate air-breathing fish (Arapaima gigas).

PloS one, 15(7):e0236507.

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.

RevDate: 2020-08-05

Wang X, Wang J, Liu J, et al (2020)

Insights into the phylogenetic relationships and drug targets of Babesia isolates infective to small ruminants from the mitochondrial genomes.

Parasites & vectors, 13(1):378.

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.

RevDate: 2020-09-09
CmpDate: 2020-09-09

Fernando HSD, Hapugoda M, Perera R, et al (2020)

Mitochondrial metabolic genes provide phylogeographic relationships of global collections of Aedes aegypti (Diptera: Culicidae).

PloS one, 15(7):e0235430.

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.

RevDate: 2020-07-31

Flament-Simon SC, de Toro M, Chuprikova L, et al (2020)

High diversity and variability of pipolins among a wide range of pathogenic Escherichia coli strains.

Scientific reports, 10(1):12452.

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.

RevDate: 2020-08-28

Bertgen L, Mühlhaus T, JM Herrmann (2020)

Clingy genes: Why were genes for ribosomal proteins retained in many mitochondrial genomes?.

Biochimica et biophysica acta. Bioenergetics, 1861(11):148275.

Why mitochondria still retain their own genome is a puzzle given the enormous effort to maintain a mitochondrial translation machinery. Most mitochondrially encoded proteins are membrane-embedded subunits of the respiratory chain. Their hydrophobicity presumably impedes their import into mitochondria. However, many mitochondrial genomes also encode protein subunits of the mitochondrial ribosome. These proteins lack transmembrane domains and hydrophobicity cannot explain why their genes remained in mitochondria. In this review, we provide an overview about mitochondrially encoded subunits of mitochondrial ribosomes of fungi, plants and protists. Moreover, we discuss and evaluate different hypotheses which were put forward to explain why (ribosomal) proteins remained mitochondrially encoded. It seems likely that the synthesis of ribosomal proteins in the mitochondrial matrix is used to regulate the assembly of the mitochondrial ribosome within mitochondria and to avoid problems that mitochondrial proteins might pose for cytosolic proteostasis and for the assembly of cytosolic ribosomes.

RevDate: 2020-08-31

Cunnane SC, Trushina E, Morland C, et al (2020)

Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing.

Nature reviews. Drug discovery, 19(9):609-633.

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner - a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes.

RevDate: 2020-09-07

Žihala D, Salamonová J, M Eliáš (2020)

Evolution of the genetic code in the mitochondria of Labyrinthulea (Stramenopiles).

Molecular phylogenetics and evolution, 152:106908.

Mitochondrial translation often exhibits departures from the standard genetic code, but the full spectrum of these changes has certainly not yet been described and the molecular mechanisms behind the changes in codon meaning are rarely studied. Here we report a detailed analysis of the mitochondrial genetic code in the stramenopile group Labyrinthulea (Labyrinthulomycetes) and their relatives. In the genus Aplanochytrium, UAG is not a termination codon but encodes tyrosine, in contrast to the unaffected meaning of the UAA codon. This change is evolutionarily independent of the reassignment of both UAG and UAA as tyrosine codons recently reported from two uncultivated labyrinthuleans (S2 and S4), which we show are not thraustochytrids as proposed before, but represent the clade LAB14 previously recognised in environmental 18S rRNA gene surveys. We provide rigorous evidence that the UUA codon in the mitochondria of all labyrinthuleans serves as a termination codon instead of encoding leucine, and propose that a sense-to-stop reassignment has also affected the AGG and AGA codons in the LAB14 clade. The distribution of the different forms of sense-to-stop and stop-to-sense reassignments correlates with specific modifications of the mitochondrial release factor mtRF2a in different subsets of labyrinthuleans, and with the unprecedented loss of mtRF1a in Aplanochytrium and perhaps also in the LAB14 clade, pointing towards a possible mechanistic basis of the code changes observed. Curiously, we show that labyrinthulean mitochondria also exhibit a sense-to-sense codon reassignment, manifested as AUA encoding methionine instead of isoleucine. Furthermore, we show that this change evolved independently in the uncultivated stramenopile lineage MAST8b, together with the reassignment of the AGR codons from arginine to serine. Altogether, our study has uncovered novel variants of the mitochondrial genetic code and previously unknown modifications of the mitochondrial translation machinery, further enriching our understanding of the rules governing the evolution of one of the central molecular process in the cell.

RevDate: 2020-09-15
CmpDate: 2020-09-15

Codo AC, Davanzo GG, Monteiro LB, et al (2020)

Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis.

Cell metabolism, 32(3):437-446.e5.

COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19.

RevDate: 2020-08-12

Kami D, S Gojo (2020)

From Cell Entry to Engraftment of Exogenous Mitochondria.

International journal of molecular sciences, 21(14):.

Mitochondrial transfer has been recognized to play a role in a variety of processes, ranging from fertilization to cancer and neurodegenerative diseases as well as mammalian horizontal gene transfer. It is achieved through either exogeneous or intercellular mitochondrial transfer. From the viewpoint of evolution, exogeneous mitochondrial transfer is quite akin to the initial process of symbiosis between α-protobacterium and archaea, although the progeny have developed more sophisticated machinery to engulf environmental materials, including nutrients, bacteria, and viruses. A molecular-based knowledge of endocytosis, including macropinocytosis and endosomal escape involving bacteria and viruses, could provide mechanistic insights into exogeneous mitochondrial transfer. We focus on exogeneous mitochondrial transfer in this review to facilitate the clinical development of the use of isolated mitochondria to treat various pathological conditions. Several kinds of novel procedures to enhance exogeneous mitochondrial transfer have been developed and are summarized in this review.

RevDate: 2020-09-28

Praud C, Jimenez J, Pampouille E, et al (2020)

Molecular Phenotyping of White Striping and Wooden Breast Myopathies in Chicken.

Frontiers in physiology, 11:633.

The White Striping (WS) and Wooden Breast (WB) defects are two myopathic syndromes whose occurrence has recently increased in modern fast-growing broilers. The impact of these defects on the quality of breast meat is very important, as they greatly affect its visual aspect, nutritional value, and processing yields. The research conducted to date has improved our knowledge of the biological processes involved in their occurrence, but no solution has been identified so far to significantly reduce their incidence without affecting growing performance of broilers. This study aims to follow the evolution of molecular phenotypes in relation to both fast-growing rate and the occurrence of defects in order to identify potential biomarkers for diagnostic purposes, but also to improve our understanding of physiological dysregulation involved in the occurrence of WS and WB. This has been achieved through enzymatic, histological, and transcriptional approaches by considering breast muscles from a slow- and a fast-growing line, affected or not by WS and WB. Fast-growing muscles produced more reactive oxygen species (ROS) than slow-growing ones, independently of WS and WB occurrence. Within fast-growing muscles, despite higher mitochondria density, muscles affected by WS or WB defects did not show higher cytochrome oxidase activity (COX) activity, suggesting altered mitochondrial function. Among the markers related to muscle remodeling and regeneration, immunohistochemical staining of FN1, NCAM, and MYH15 was higher in fast- compared to slow-growing muscles, and their amount also increased linearly with the presence and severity of WS and WB defects, making them potential biomarkers to assess accurately their presence and severity. Thanks to an innovative histological technique based on fluorescence intensity measurement, they can be rapidly quantified to estimate the injuries induced in case of WS and WB. The muscular expression of several other genes correlates also positively to the presence and severity of the defects like TGFB1 and CTGF, both involved in the development of connective tissue, or Twist1, known as an inhibitor of myogenesis. Finally, our results suggested that a balance between TGFB1 and PPARG would be essential for fibrosis or adiposis induction and therefore for determining WS and WB phenotypes.

RevDate: 2020-08-24
CmpDate: 2020-08-24

Arbeithuber B, Hester J, Cremona MA, et al (2020)

Age-related accumulation of de novo mitochondrial mutations in mammalian oocytes and somatic tissues.

PLoS biology, 18(7):e3000745.

Mutations create genetic variation for other evolutionary forces to operate on and cause numerous genetic diseases. Nevertheless, how de novo mutations arise remains poorly understood. Progress in the area is hindered by the fact that error rates of conventional sequencing technologies (1 in 100 or 1,000 base pairs) are several orders of magnitude higher than de novo mutation rates (1 in 10,000,000 or 100,000,000 base pairs per generation). Moreover, previous analyses of germline de novo mutations examined pedigrees (and not germ cells) and thus were likely affected by selection. Here, we applied highly accurate duplex sequencing to detect low-frequency, de novo mutations in mitochondrial DNA (mtDNA) directly from oocytes and from somatic tissues (brain and muscle) of 36 mice from two independent pedigrees. We found mtDNA mutation frequencies 2- to 3-fold higher in 10-month-old than in 1-month-old mice, demonstrating mutation accumulation during the period of only 9 mo. Mutation frequencies and patterns differed between germline and somatic tissues and among mtDNA regions, suggestive of distinct mutagenesis mechanisms. Additionally, we discovered a more pronounced genetic drift of mitochondrial genetic variants in the germline of older versus younger mice, arguing for mtDNA turnover during oocyte meiotic arrest. Our study deciphered for the first time the intricacies of germline de novo mutagenesis using duplex sequencing directly in oocytes, which provided unprecedented resolution and minimized selection effects present in pedigree studies. Moreover, our work provides important information about the origins and accumulation of mutations with aging/maturation and has implications for delayed reproduction in modern human societies. Furthermore, the duplex sequencing method we optimized for single cells opens avenues for investigating low-frequency mutations in other studies.

RevDate: 2020-08-08

Pedriali G, Morciano G, Patergnani S, et al (2020)

Aortic Valve Stenosis and Mitochondrial Dysfunctions: Clinical and Molecular Perspectives.

International journal of molecular sciences, 21(14):.

Calcific aortic stenosis is a disorder that impacts the physiology of heart valves. Fibrocalcific events progress in conjunction with thickening of the valve leaflets. Over the years, these events promote stenosis and obstruction of blood flow. Known and common risk factors are congenital defects, aging and metabolic syndromes linked to high plasma levels of lipoproteins. Inflammation and oxidative stress are the main molecular mediators of the evolution of aortic stenosis in patients and these mediators regulate both the degradation and remodeling processes. Mitochondrial dysfunction and dysregulation of autophagy also contribute to the disease. A better understanding of these cellular impairments might help to develop new ways to treat patients since, at the moment, there is no effective medical treatment to diminish neither the advancement of valve stenosis nor the left ventricular function impairments, and the current approaches are surgical treatment or transcatheter aortic valve replacement with prosthesis.

RevDate: 2020-08-31

Fan L, Wu D, Goremykin V, et al (2020)

Phylogenetic analyses with systematic taxon sampling show that mitochondria branch within Alphaproteobacteria.

Nature ecology & evolution, 4(9):1213-1219.

Though it is well accepted that mitochondria originated from an alphaproteobacteria-like ancestor, the phylogenetic relationship of the mitochondrial endosymbiont to extant Alphaproteobacteria is yet unresolved. The focus of much debate is whether the affinity between mitochondria and fast-evolving alphaproteobacterial lineages reflects true homology or artefacts. Approaches such as site exclusion have been claimed to mitigate compositional heterogeneity between taxa, but this comes at the cost of information loss, and the reliability of such methods is so far unproven. Here we demonstrate that site-exclusion methods produce erratic phylogenetic estimates of mitochondrial origin. Thus, previous phylogenetic hypotheses on the origin of mitochondria based on pretreated datasets should be re-evaluated. We applied alternative strategies to reduce phylogenetic noise by systematic taxon sampling while keeping site substitution information intact. Cross-validation based on a series of trees placed mitochondria robustly within Alphaproteobacteria, sharing an ancient common ancestor with Rickettsiales and currently unclassified marine lineages.

RevDate: 2020-08-02

Fang Y, Zhao C, Xiang H, et al (2020)

Melatonin improves cryopreservation of ram sperm by inhibiting mitochondrial permeability transition pore opening.

Reproduction in domestic animals = Zuchthygiene [Epub ahead of print].

Cryopreservation damages permeability of sperm mitochondrial membranes, with formation of a mitochondrial permeability transition pore (mPTP). Mitochondria are both a primary synthesis site and principle target for melatonin, which can directly inhibit mPTP formation. The objective was to determine effects of melatonin on mPTP opening of frozen-thawed ram sperm and elucidate underlying pathways by antagonist and agonists of melatonin receptors (MTs), and antagonists of PI3K and GSK 3β treatments; furthermore, plasma membrane integrity, mitochondrial membrane potential (ΔΨm), mitochondrial cytochrome c (Cyt c) release and fertilization were analysed to assess the effect of mPTP status mediated by melatonin on quality of frozen-thawed sperm. Fresh ram semen was diluted in glucose-egg yolk buffer with 0 or 10-7 M melatonin (frozen and frozen + melatonin groups, respectively) and slow-frozen. In frozen-thawed sperm, melatonin added at initiation of 4°C equilibration was most effective for inhibiting mPTP opening, decreasing peptidyl-prolyl-cis/trans isomerase activity of cyclophilin D and increasing plasma membrane integrity, ΔΨm, mitochondrial Cyt c concentration and fertilizing ability (p < .05). In a mechanistic study, the melatonin receptor (MT)1 antagonist eliminated inhibition of melatonin on mPTP opening, whereas MT1 agonist had opposite effects (p < .05). Neither MT2 antagonist nor agonist had significant effect, but PI3K and/or GSK 3β antagonist decreased inhibition of MT1 agonist on mPTP opening (p < .05). In conclusion, melatonin improved sperm cryopreservation, perhaps by acting on MT1 via the PI3K-Akt-GSK 3β pathway to inhibit mPTP opening.

RevDate: 2020-09-14
CmpDate: 2020-09-14

de Oliveira VC, Gomes Mariano Junior C, Belizário JE, et al (2020)

Characterization of post-edited cells modified in the TFAM gene by CRISPR/Cas9 technology in the bovine model.

PloS one, 15(7):e0235856.

Gene editing in large animal models for future applications in translational medicine and food production must be deeply investigated for an increase of knowledge. The mitochondrial transcription factor A (TFAM) is a member of the HMGB subfamily that binds to mtDNA promoters. This gene maintains mtDNA, and it is essential for the initiation of mtDNA transcription. Lately, we generated a new cell line through the disruption of the TFAM gene in bovine fibroblast cells by CRISPR/Cas 9 technology. We showed that the CRISPR/Cas9 design was efficient through the generation of heterozygous mutant clones. In this context, once this gene regulates the mtDNA replication specificity, the study aimed to determine if the post-edited cells are capable of in vitro maintenance and assess if they present changes in mtDNA copies and mitochondrial membrane potential after successive passages in culture. The post-edited cells were expanded in culture, and we performed a growth curve, doubling time, cell viability, mitochondrial DNA copy number, and mitochondrial membrane potential assays. The editing process did not make cell culture unfeasible, even though cell growth rate and viability were decreased compared to control since we observed the cells grow well when cultured in a medium supplemented with uridine and pyruvate. They also exhibited a classical fibroblastoid appearance. The RT-qPCR to determine the mtDNA copy number showed a decrease in the edited clones compared to the non-edited ones (control) in different cell passages. Cell staining with Mitotracker Green and red suggests a reduction in red fluorescence in the edited cells compared to the non-edited cells. Thus, through characterization, we demonstrated that the TFAM gene is critical to mitochondrial maintenance due to its interference in the stability of the mitochondrial DNA copy number in different cell passages and membrane potential confirming the decrease in mitochondrial activity in cells edited in heterozygosis.

RevDate: 2020-09-28

Porter SM (2020)

Insights into eukaryogenesis from the fossil record.

Interface focus, 10(4):20190105.

Eukaryogenesis-the process by which the eukaryotic cell emerged-has long puzzled scientists. It has been assumed that the fossil record has little to say about this process, in part because important characters such as the nucleus and mitochondria are rarely preserved, and in part because the prevailing model of early eukaryotes implies that eukaryogenesis occurred before the appearance of the first eukaryotes recognized in the fossil record. Here, I propose a different scenario for early eukaryote evolution than is widely assumed. Rather than crown group eukaryotes originating in the late Paleoproterozoic and remaining ecologically minor components for more than half a billion years in a prokaryote-dominated world, I argue for a late Mesoproterozoic origin of the eukaryotic crown group, implying that eukaryogenesis can be studied using the fossil record. I review the proxy records of four crown group characters: the capacity to form cysts as evidenced by the presence of excystment structures; a complex cytoskeleton as evidenced by spines or pylomes; sterol synthesis as evidenced by steranes; and aerobic respiration-and therefore mitochondria-as evidenced by eukaryotes living in oxic environments, and argue that it might be possible to use these proxy records to infer the order in which these characters evolved. The records indicate that both cyst formation and a complex cytoskeleton appeared by late Paleoproterozoic time, and sterol synthesis appeared in the late Mesoproterozioc or early Neoproterozoic. The origin of aerobic respiration cannot as easily be pinned down, but current evidence permits the possibility that it evolved sometime in the Mesoproterozoic.

RevDate: 2020-09-28

Long X, Xue H, JT Wong (2020)

Descent of Bacteria and Eukarya From an Archaeal Root of Life.

Evolutionary bioinformatics online, 16:1176934320908267.

The 3 biological domains delineated based on small subunit ribosomal RNAs (SSU rRNAs) are confronted by uncertainties regarding the relationship between Archaea and Bacteria, and the origin of Eukarya. The similarities between the paralogous valyl-tRNA and isoleucyl-tRNA synthetases in 5398 species estimated by BLASTP, which decreased from Archaea to Bacteria and further to Eukarya, were consistent with vertical gene transmission from an archaeal root of life close to Methanopyrus kandleri through a Primitive Archaea Cluster to an Ancestral Bacteria Cluster, and to Eukarya. The predominant similarities of the ribosomal proteins (rProts) of eukaryotes toward archaeal rProts relative to bacterial rProts established that an archaeal parent rather than a bacterial parent underwent genome merger with bacteria to generate eukaryotes with mitochondria. Eukaryogenesis benefited from the predominantly archaeal accelerated gene adoption (AGA) phenotype pertaining to horizontally transferred genes from other prokaryotes and expedited genome evolution via both gene-content mutations and nucleotidyl mutations. Archaeons endowed with substantial AGA activity were accordingly favored as candidate archaeal parents. Based on the top similarity bitscores displayed by their proteomes toward the eukaryotic proteomes of Giardia and Trichomonas, and high AGA activity, the Aciduliprofundum archaea were identified as leading candidates of the archaeal parent. The Asgard archaeons and a number of bacterial species were among the foremost potential contributors of eukaryotic-like proteins to Eukarya.

RevDate: 2020-08-11

Gonçalves DJP, Jansen RK, Ruhlman TA, et al (2020)

Under the rug: Abandoning persistent misconceptions that obfuscate organelle evolution.

Molecular phylogenetics and evolution, 151:106903.

The advent and advance of next generation sequencing over the past two decades made it possible to accumulate large quantities of sequence reads that could be used to assemble complete or nearly complete organelle genomes (plastome or mitogenome). The result has been an explosive increase in the availability of organelle genome sequences with over 4000 different species of green plants currently available on GenBank. During the same time period, plant molecular biologists greatly enhanced the understanding of the structure, repair, replication, recombination, transcription and translation, and inheritance of organelle DNA. Unfortunately many plant evolutionary biologists are unaware of or have overlooked this knowledge, resulting in misrepresentation of several phenomena that are critical for phylogenetic and evolutionary studies using organelle genomes. We believe that confronting these misconceptions about organelle genome organization, composition, and inheritance will improve our understanding of the evolutionary processes that underly organelle evolution. Here we discuss four misconceptions that can limit evolutionary biology studies and lead to inaccurate phylogenies and incorrect structure of the organellar DNA used to infer organelle evolution.

RevDate: 2020-09-07

Zhu X, Liu G, Bu Y, et al (2020)

In Situ Monitoring of Mitochondria Regulating Cell Viability by the RNA-Specific Fluorescent Photosensitizer.

Analytical chemistry, 92(15):10815-10821.

Cell viability is greatly affected by external stimulus eliciting correlated dynamical physiological processes for cells to choose survival or death. A few fluorescent probes have been designed to detect whether the cell is in survival state or apoptotic state, but monitoring the regulation process of the cell undergoing survival to death remains a long-standing challenge. Herein, we highlight the in situ monitor of mitochondria regulating the cell viability by the RNA-specific fluorescent photosensitizer L. At normal conditions, L anchored mitochondria and interacted with mito-RNA to light up the mitochondria with red fluorescence. With external light stimulus, L generated reactive oxide species (ROS) and cause damage to mitochondria, which activated mitochondrial autophagy to prevent death, during which the red fluorescence of L witnessed dynamical distribution in accordance with the evolution of vacuole structures containing damaged mitochondria into autophagosomes. However, with ROS continuously increasing, the mitochondrial apoptosis was eventually commenced and L with red fluorescent was gradually accumulated in the nucleoli, indicating the programmed cell death. This work demonstrated how the delicate balance between survival and death are regulated by mitochondria.

RevDate: 2020-09-09
CmpDate: 2020-09-09

Rossi NA, Menchaca-Rodriguez A, Antelo R, et al (2020)

High levels of population genetic differentiation in the American crocodile (Crocodylus acutus).

PloS one, 15(7):e0235288.

The American crocodile (Crocodylus acutus) is a widely distributed species across coastal and brackish areas of the Neotropical region of the Americas and the Greater Antilles. Available information on patterns of genetic differentiation in C. acutus shows a complex structuring influenced by interspecific interactions (mainly hybridization) and anthropogenic actions (mostly historical hunting, recent poaching, habitat loss and fragmentation, and unintentional translocation of individuals). In this study, we used data on mitochondrial DNA control region and 11 nuclear polymorphic microsatellite loci to assess the degree of population structure of C. acutus in South America, North America, Central America and the Greater Antilles. We used traditional genetic differentiation indices, Bayesian clustering and multivariate methods to create a more comprehensive picture of the genetic relationships within the species across its range. Analyses of mtDNA and microsatellite loci show evidence of a strong population genetic structure in the American crocodile, with unique populations in each sampling locality. Our results support previous findings showing large degrees of genetic differentiation between the continental and the Greater Antillean C. acutus. We report three new haplotypes unique to Venezuela, which are considerably less distant from the Central and North American haplotypes than to the Greater Antillean ones. Our findings reveal genetic population differentiation between Cuban and Jamaican C. acutus and offer the first evidence of strong genetic differentiation among the populations of Greater Antillean C. acutus.

RevDate: 2020-09-28

Noiret A, Puch L, Riffaud C, et al (2020)

Sex-Specific Response to Caloric Restriction After Reproductive Investment in Microcebus murinus: An Integrative Approach.

Frontiers in physiology, 11:506.

In seasonal environments, males and females usually maintain high metabolic activity during the whole summer season, exhausting their energy reserves. In the global warming context, unpredictability of food availability during summer could dramatically challenge the energy budget of individuals. Therefore, one can predict that resilience to environmental stress would be dramatically endangered during summer. Here, we hypothesized that females could have greater capacity to survive harsh conditions than males, considering the temporal shift in their respective reproductive energy investment, which can challenge them differently, as well as enhanced flexibility in females' physiological regulation. We tackled this question on the gray mouse lemur (Microcebus murinus), focusing on the late summer period, after the reproductive effort. We monitored six males and six females before and after a 2-weeks 60% caloric restriction (CR), measuring different physiological and cellular parameters in an integrative and comparative multiscale approach. Before CR, females were heavier than males and mostly characterized by high levels of energy expenditure, a more energetic mitochondrial profile and a downregulation of blood antioxidants. We observed a similar energy balance between sexes due to CR, with a decrease in metabolic activity over time only in males. Oxidative damage to DNA was also reduced by different pathways between sexes, which may reflect variability in their physiological status and life-history traits at the end of summer. Finally, females' mitochondria seemed to exhibit greater flexibility and greater metabolic potential than males in response to CR. Our results showed strong differences between males and females in response to food shortage during late summer, underlining the necessity to consider sex as a factor for population dynamics in climate change models.

RevDate: 2020-08-27
CmpDate: 2020-08-25

Keaney TA, Wong HWS, Dowling DK, et al (2020)

Sibling rivalry versus mother's curse: can kin competition facilitate a response to selection on male mitochondria?.

Proceedings. Biological sciences, 287(1930):20200575.

Assuming that fathers never transmit mitochondrial DNA (mtDNA) to their offspring, mitochondrial mutations that affect male fitness are invisible to direct selection on males, leading to an accumulation of male-harming alleles in the mitochondrial genome (mother's curse). However, male phenotypes encoded by mtDNA can still undergo adaptation via kin selection provided that males interact with females carrying related mtDNA, such as their sisters. Here, using experiments with Drosophila melanogaster carrying standardized nuclear DNA but distinct mitochondrial DNA, we test whether the mitochondrial haplotype carried by interacting pairs of larvae affects survival to adulthood, as well as the fitness of the adults. Although mtDNA had no detectable direct or indirect genetic effect on larva-to-adult survival, the fitness of male and female adults was significantly affected by their own mtDNA and the mtDNA carried by their social partner in the larval stage. Thus, mtDNA mutations that alter the effect of male larvae on nearby female larvae (which often carry the same mutation, due to kinship) could theoretically respond to kin selection. We discuss the implications of our findings for the evolution of mitochondria and other maternally inherited endosymbionts.

RevDate: 2020-09-21
CmpDate: 2020-09-21

Wu Z, Waneka G, Broz AK, et al (2020)

MSH1 is required for maintenance of the low mutation rates in plant mitochondrial and plastid genomes.

Proceedings of the National Academy of Sciences of the United States of America, 117(28):16448-16455.

Mitochondrial and plastid genomes in land plants exhibit some of the slowest rates of sequence evolution observed in any eukaryotic genome, suggesting an exceptional ability to prevent or correct mutations. However, the mechanisms responsible for this extreme fidelity remain unclear. We tested seven candidate genes involved in cytoplasmic DNA replication, recombination, and repair (POLIA, POLIB, MSH1, RECA3, UNG, FPG, and OGG1) for effects on mutation rates in the model angiosperm Arabidopsis thaliana by applying a highly accurate DNA sequencing technique (duplex sequencing) that can detect newly arisen mitochondrial and plastid mutations even at low heteroplasmic frequencies. We find that disrupting MSH1 (but not the other candidate genes) leads to massive increases in the frequency of point mutations and small indels and changes to the mutation spectrum in mitochondrial and plastid DNA. We also used droplet digital PCR to show transmission of de novo heteroplasmies across generations in msh1 mutants, confirming a contribution to heritable mutation rates. This dual-targeted gene is part of an enigmatic lineage within the mutS mismatch repair family that we find is also present outside of green plants in multiple eukaryotic groups (stramenopiles, alveolates, haptophytes, and cryptomonads), as well as certain bacteria and viruses. MSH1 has previously been shown to limit ectopic recombination in plant cytoplasmic genomes. Our results point to a broader role in recognition and correction of errors in plant mitochondrial and plastid DNA sequence, leading to greatly suppressed mutation rates perhaps via initiation of double-stranded breaks and repair pathways based on faithful homologous recombination.

RevDate: 2020-09-21
CmpDate: 2020-09-21

Greenway R, Barts N, Henpita C, et al (2020)

Convergent evolution of conserved mitochondrial pathways underlies repeated adaptation to extreme environments.

Proceedings of the National Academy of Sciences of the United States of America, 117(28):16424-16430.

Extreme environments test the limits of life; yet, some organisms thrive in harsh conditions. Extremophile lineages inspire questions about how organisms can tolerate physiochemical stressors and whether the repeated colonization of extreme environments is facilitated by predictable and repeatable evolutionary innovations. We identified the mechanistic basis underlying convergent evolution of tolerance to hydrogen sulfide (H2S)-a toxicant that impairs mitochondrial function-across evolutionarily independent lineages of a fish (Poecilia mexicana, Poeciliidae) from H2S-rich springs. Using comparative biochemical and physiological analyses, we found that mitochondrial function is maintained in the presence of H2S in sulfide spring P. mexicana but not ancestral lineages from nonsulfidic habitats due to convergent adaptations in the primary toxicity target and a major detoxification enzyme. Genome-wide local ancestry analyses indicated that convergent evolution of increased H2S tolerance in different populations is likely caused by a combination of selection on standing genetic variation and de novo mutations. On a macroevolutionary scale, H2S tolerance in 10 independent lineages of sulfide spring fishes across multiple genera of Poeciliidae is correlated with the convergent modification and expression changes in genes associated with H2S toxicity and detoxification. Our results demonstrate that the modification of highly conserved physiological pathways associated with essential mitochondrial processes mediates tolerance to physiochemical stress. In addition, the same pathways, genes, and-in some instances-codons are implicated in H2S adaptation in lineages that span 40 million years of evolution.

RevDate: 2020-09-28

Mannella CA (2020)

Consequences of Folding the Mitochondrial Inner Membrane.

Frontiers in physiology, 11:536.

A fundamental first step in the evolution of eukaryotes was infolding of the chemiosmotic membrane of the endosymbiont. This allowed the proto-eukaryote to amplify ATP generation while constraining the volume dedicated to energy production. In mitochondria, folding of the inner membrane has evolved into a highly regulated process that creates specialized compartments (cristae) tuned to optimize function. Internalizing the inner membrane also presents complications in terms of generating the folds and maintaining mitochondrial integrity in response to stresses. This review describes mechanisms that have evolved to regulate inner membrane topology and either preserve or (when appropriate) rupture the outer membrane.

RevDate: 2020-09-02

Nesci S, Pagliarani A, Algieri C, et al (2020)

Mitochondrial F-type ATP synthase: multiple enzyme functions revealed by the membrane-embedded FO structure.

Critical reviews in biochemistry and molecular biology, 55(4):309-321.

Of the two main sectors of the F-type ATP synthase, the membrane-intrinsic FO domain is the one which, during evolution, has undergone the highest structural variations and changes in subunit composition. The FO complexity in mitochondria is apparently related to additional enzyme functions that lack in bacterial and thylakoid complexes. Indeed, the F-type ATP synthase has the main bioenergetic role to synthesize ATP by exploiting the electrochemical gradient built by respiratory complexes. The FO membrane domain, essential in the enzyme machinery, also participates in the bioenergetic cost of synthesizing ATP and in the formation of the cristae, thus contributing to mitochondrial morphology. The recent enzyme involvement in a high-conductance channel, which forms in the inner mitochondrial membrane and promotes the mitochondrial permeability transition, highlights a new F-type ATP synthase role. Point mutations which cause amino acid substitutions in FO subunits produce mitochondrial dysfunctions and lead to severe pathologies. The FO variability in different species, pointed out by cryo-EM analysis, mirrors the multiple enzyme functions and opens a new scenario in mitochondrial biology.

RevDate: 2020-09-02
CmpDate: 2020-09-02

Pyrih J, Rašková V, Škodová-Sveráková I, et al (2020)

ZapE/Afg1 interacts with Oxa1 and its depletion causes a multifaceted phenotype.

PloS one, 15(6):e0234918.

ZapE/Afg1 is a component of the inner cell membrane of some eubacteria and the inner mitochondrial membrane of eukaryotes. This protein is involved in FtsZ-dependent division of eubacteria. In the yeast and human mitochondrion, ZapE/Afg1 likely interacts with Oxa1 and facilitates the degradation of mitochondrion-encoded subunits of respiratory complexes. Furthermore, the depletion of ZapE increases resistance to apoptosis, decreases oxidative stress tolerance, and impacts mitochondrial protein homeostasis. It remains unclear whether ZapE is a multifunctional protein, or whether some of the described effects are just secondary phenotypes. Here, we have analyzed the functions of ZapE in Trypanosoma brucei, a parasitic protist, and an important model organism. Using a newly developed proximity-dependent biotinylation approach (BioID2), we have identified the inner mitochondrial membrane insertase Oxa1 among three putative interacting partners of ZapE, which is present in two paralogs. RNAi-mediated depletion of both ZapE paralogs likely affected the function of respiratory complexes I and IV. Consistently, we show that the distribution of mitochondrial ZapE is restricted only to organisms with Oxa1, respiratory complexes, and a mitochondrial genome. We propose that the evolutionarily conserved interaction of ZapE with Oxa1, which is required for proper insertion of many inner mitochondrial membrane proteins, is behind the multifaceted phenotype caused by the ablation of ZapE.

RevDate: 2020-06-22

Levitskii SA, Baleva MV, Chicherin IV, et al (2020)

Protein Biosynthesis in Mitochondria: Past Simple, Present Perfect, Future Indefinite.

Biochemistry. Biokhimiia, 85(3):257-263.

Mitochondria are obligate organelles of most eukaryotic cells that perform many different functions important for cellular homeostasis. The main role of mitochondria is supplying cells with energy in a form of ATP, which is synthesized in a chain of oxidative phosphorylation reactions on the organelle inner membrane. It is commonly believed now that mitochondria have the endosymbiotic origin. In the course of evolution, they have lost most of their genetic material as a result of genome reduction and gene transfer to the nucleus. The majority of mitochondrial proteins are synthesized in the cytosol and then imported to the mitochondria. However, almost all known mitochondria still contain genomes that are maintained and expressed. The processes of protein biosynthesis in the mitochondria - mitochondrial translation - substantially differs from the analogous processes in bacteria and the cytosol of eukaryotic cells. Mitochondrial translation is characterized by a high degree of specialization and specific regulatory mechanisms. In this review, we analyze available information on the common principles of mitochondrial translation with emphasis on the molecular mechanisms of translation initiation in the mitochondria of yeast and mammalian cells.

RevDate: 2020-08-24
CmpDate: 2020-08-24

Nong W, Cao J, Li Y, et al (2020)

Jellyfish genomes reveal distinct homeobox gene clusters and conservation of small RNA processing.

Nature communications, 11(1):3051 pii:10.1038/s41467-020-16801-9.

The phylum Cnidaria represents a close outgroup to Bilateria and includes familiar animals including sea anemones, corals, hydroids, and jellyfish. Here we report genome sequencing and assembly for true jellyfish Sanderia malayensis and Rhopilema esculentum. The homeobox gene clusters are characterised by interdigitation of Hox, NK, and Hox-like genes revealing an alternate pathway of ANTP class gene dispersal and an intact three gene ParaHox cluster. The mitochondrial genomes are linear but, unlike in Hydra, we do not detect nuclear copies, suggesting that linear plastid genomes are not necessarily prone to integration. Genes for sesquiterpenoid hormone production, typical for arthropods, are also now found in cnidarians. Somatic and germline cells both express piwi-interacting RNAs in jellyfish revealing a conserved cnidarian feature, and evidence for tissue-specific microRNA arm switching as found in Bilateria is detected. Jellyfish genomes reveal a mosaic of conserved and divergent genomic characters evolved from a shared ancestral genetic architecture.

RevDate: 2020-07-14

Tobiasson V, A Amunts (2020)

Ciliate mitoribosome illuminates evolutionary steps of mitochondrial translation.

eLife, 9:.

To understand the steps involved in the evolution of translation, we used Tetrahymena thermophila, a ciliate with high coding capacity of the mitochondrial genome, as the model organism and characterized its mitochondrial ribosome (mitoribosome) using cryo-EM. The structure of the mitoribosome reveals an assembly of 94-ribosomal proteins and four-rRNAs with an additional protein mass of ~700 kDa on the small subunit, while the large subunit lacks 5S rRNA. The structure also shows that the small subunit head is constrained, tRNA binding sites are formed by mitochondria-specific protein elements, conserved protein bS1 is excluded, and bacterial RNA polymerase binding site is blocked. We provide evidence for anintrinsic protein targeting system through visualization of mitochondria-specific mL105 by the exit tunnel that would facilitate the recruitment of a nascent polypeptide. Functional protein uS3m is encoded by three complementary genes from the nucleus and mitochondrion, establishing a link between genetic drift and mitochondrial translation. Finally, we reannotated nine open reading frames in the mitochondrial genome that code for mitoribosomal proteins.

RevDate: 2020-09-28

Timón-Gómez A, A Barrientos (2020)

Mitochondrial respiratory chain composition and organization in response to changing oxygen levels.

Journal of life sciences (Westlake Village, Calif.), 2(2):.

Mitochondria are the major consumer of oxygen in eukaryotic cells, owing to the requirement of oxygen to generate ATP through the mitochondrial respiratory chain (MRC) and the oxidative phosphorylation system (OXPHOS). This aerobic energy transduction is more efficient than anaerobic processes such as glycolysis. Hypoxia, a condition in which environmental or intracellular oxygen levels are below the standard range, triggers an adaptive signaling pathway within the cell. When oxygen concentrations are low, hypoxia-inducible factors (HIFs) become stabilized and activated to mount a transcriptional response that triggers modulation of cellular metabolism to adjust to hypoxic conditions. Mitochondrial aerobic metabolism is one of the main targets of the hypoxic response to regulate its functioning and efficiency in the presence of decreased oxygen levels. During evolution, eukaryotic cells and tissues have increased the plasticity of their mitochondrial OXPHOS system to cope with metabolic needs in different oxygen contexts. In mammalian mitochondria, two factors contribute to this plasticity. First, several subunits of the multimeric MRC complexes I and IV exist in multiple tissue-specific and condition-specific isoforms. Second, the MRC enzymes can coexist organized as individual entities or forming supramolecular structures known as supercomplexes, perhaps in a dynamic manner to respond to environmental conditions and cellular metabolic demands. In this review, we will summarize the information currently available on oxygen-related changes in MRC composition and organization and will discuss gaps of knowledge and research opportunities in the field.

RevDate: 2020-09-28

Monteiro LB, Davanzo GG, de Aguiar CF, et al (2020)

Using flow cytometry for mitochondrial assays.

MethodsX, 7:100938.

The understanding of how different cell types adapt their metabolism in the face of challenges has been attracting the attention of researchers for many years. Recently, immunologists also started to focus on how the metabolism of immune cells can impact the way that immunity drives its responses. The presence of a pathogen or damage in a tissue changes severely the way that the immune cells need to respond. When activated, immune cells usually shift their metabolism from a high energy demanding status using mitochondria respiration to a glycolytic based rapid ATP production. The diminished amount of respiration leads to changes in the mitochondrial membrane potential and, consequently, generation of reactive oxygen species. Here, we show how flow cytometry can be used to track changes in mitochondrial mass, membrane potential and superoxide (ROS) production in live immune cells. ● This protocol suggests a quick way of evaluating mitochondrial fitness using flow cytometry. We propose using the probes MitoTraker Green and MitoTracker Red/ MitoSOX at the same time. This way, it is possible to evaluate different parameters of mitochondrial biology in living cells. ● Flow cytometry is a highly used tool by immunologists. With the advances of studies focusing on the metabolism of immune cells, a simplified application of flow cytometry for mitochondrial studies and screenings is a helpful clarifying method for immunology.

RevDate: 2020-07-23

Valero C, Colabardini AC, Chiaratto J, et al (2020)

Aspergillus fumigatus Transcription Factors Involved in the Caspofungin Paradoxical Effect.

mBio, 11(3):.

Aspergillus fumigatus is the leading cause of pulmonary fungal diseases. Azoles have been used for many years as the main antifungal agents to treat and prevent invasive aspergillosis. However, in the last 10 years there have been several reports of azole resistance in A. fumigatus and new strategies are needed to combat invasive aspergillosis. Caspofungin is effective against other human-pathogenic fungal species, but it is fungistatic only against A. fumigatus Resistance to caspofungin in A. fumigatus has been linked to mutations in the fksA gene that encodes the target enzyme of the drug β-1,3-glucan synthase. However, tolerance of high caspofungin concentrations, a phenomenon known as the caspofungin paradoxical effect (CPE), is also important for subsequent adaptation and drug resistance evolution. Here, we identified and characterized the transcription factors involved in the response to CPE by screening an A. fumigatus library of 484 null transcription factors (TFs) in CPE drug concentrations. We identified 11 TFs that had reduced CPE and that encoded proteins involved in the basal modulation of the RNA polymerase II initiation sites, calcium metabolism, and cell wall remodeling. One of these TFs, FhdA, was important for mitochondrial respiratory function and iron metabolism. The ΔfhdA mutant showed decreased growth when exposed to Congo red or to high temperature. Transcriptome sequencing (RNA-seq) analysis and further experimental validation indicated that the ΔfhdA mutant showed diminished respiratory capacity, probably affecting several pathways related to the caspofungin tolerance and resistance. Our results provide the foundation to understand signaling pathways that are important for caspofungin tolerance and resistance.IMPORTANCEAspergillus fumigatus, one of the most important human-pathogenic fungal species, is able to cause aspergillosis, a heterogeneous group of diseases that presents a wide range of clinical manifestations. Invasive pulmonary aspergillosis is the most serious pathology in terms of patient outcome and treatment, with a high mortality rate ranging from 50% to 95% primarily affecting immunocompromised patients. Azoles have been used for many years as the main antifungal agents to treat and prevent invasive aspergillosis. However, there were several reports of evolution of clinical azole resistance in the last decade. Caspofungin, a noncompetitive β-1,3-glucan synthase inhibitor, has been used against A. fumigatus, but it is fungistatic and is recommended as second-line therapy for invasive aspergillosis. More information about caspofungin tolerance and resistance is necessary in order to refine antifungal strategies that target the fungal cell wall. Here, we screened a transcription factor (TF) deletion library for TFs that can mediate caspofungin tolerance and resistance. We have identified 11 TFs that are important for caspofungin sensitivity and/or for the caspofungin paradoxical effect (CPE). These TFs encode proteins involved in the basal modulation of the RNA polymerase II initiation sites, calcium metabolism or cell wall remodeling, and mitochondrial respiratory function. The study of those genes regulated by TFs identified in this work will provide a better understanding of the signaling pathways that are important for caspofungin tolerance and resistance.

RevDate: 2020-10-06
CmpDate: 2020-10-06

Li Y, Nourbakhsh N, Pham H, et al (2020)

Evolution of altered tubular metabolism and mitochondrial function in sepsis-associated acute kidney injury.

American journal of physiology. Renal physiology, 319(2):F229-F244.

Sepsis-associated acute kidney injury (s-AKI) has a staggering impact in patients and lacks any treatment. Incomplete understanding of the pathogenesis of s-AKI is a major barrier to the development of effective therapies. We address the gaps in knowledge regarding renal oxygenation, tubular metabolism, and mitochondrial function in the pathogenesis of s-AKI using the cecal ligation and puncture (CLP) model in mice. At 24 h after CLP, renal oxygen delivery was reduced; however, fractional oxygen extraction was unchanged, suggesting inefficient renal oxygen utilization despite decreased glomerular filtration rate and filtered load. To investigate the underlying mechanisms, we examined temporal changes in mitochondrial function and metabolism at 4 and 24 h after CLP. At 4 h after CLP, markers of mitochondrial content and biogenesis were increased in CLP kidneys, but mitochondrial oxygen consumption rates were suppressed in proximal tubules. Interestingly, at 24 h, proximal tubular mitochondria displayed high respiratory capacity, but with decreased mitochondrial content, biogenesis, fusion, and ATP levels in CLP kidneys, suggesting decreased ATP synthesis efficiency. We further investigated metabolic reprogramming after CLP and observed reduced expression of fatty acid oxidation enzymes but increased expression of glycolytic enzymes at 24 h. However, assessment of functional glycolysis revealed lower glycolytic capacity, glycolytic reserve, and compensatory glycolysis in CLP proximal tubules, which may explain their susceptibility to injury. In conclusion, we demonstrated significant alterations in renal oxygenation, tubular mitochondrial function, and metabolic reprogramming in s-AKI, which may play an important role in the progression of injury and recovery from AKI in sepsis.

RevDate: 2020-09-21

Vertika S, Singh KK, S Rajender (2020)

Mitochondria, spermatogenesis, and male infertility - An update.

Mitochondrion, 54:26-40.

The incorporation of mitochondria in the eukaryotic cell is one of the most enigmatic events in the course of evolution. This important organelle was thought to be only the powerhouse of the cell, but was later learnt to perform many other indispensable functions in the cell. Two major contributions of mitochondria in spermatogenesis concern energy production and apoptosis. Apart from this, mitochondria also participate in a number of other processes affecting spermatogenesis and fertility. Mitochondria in sperm are arranged in the periphery of the tail microtubules to serve to energy demand for motility. Apart from this, the role of mitochondria in germ cell proliferation, mitotic regulation, and the elimination of germ cells by apoptosis are now well recognized. Eventually, mutations in the mitochondrial genome have been reported in male infertility, particularly in sluggish sperm (asthenozoospermia); however, heteroplasmy in the mtDNA and a complex interplay between the nucleus and mitochondria affect their penetrance. In this article, we have provided an update on the role of mitochondria in various events of spermatogenesis and male fertility and on the correlation of mitochondrial DNA mutations with male infertility.

RevDate: 2020-06-10

Enomoto H, Mittal N, Inomata T, et al (2020)

Dilated Cardiomyopathy (DCM)-linked Heat shock protein Family D Member 1 (HSPD1) mutations cause upregulation of ROS and autophagy through mitochondrial dysfunction.

Cardiovascular research pii:5855671 [Epub ahead of print].

BACKGROUND: During heart failure, the levels of circulatory HSPD1 (HSP60) increase. However, its underlying mechanism is still unknown. The apical domain of HSPD1 is conserved throughout evolution. We found a point mutation in HSPD1 in a familial dilated cardiomyopathy (DCM) patient. A similar point mutation in HSPD1 in the zebrafish mutant, nbl, led to loss of its regenerative capacity and development of pericardial edema under heat stress condition. In this study, we aimed to determine the direct involvement of HSPD1 in the development of DCM.

METHODS AND RESULTS: By Sanger method, we found a point mutation (Thr320Ala) in the apical domain of HSPD1, in one familial DCM patient, which was four amino acids away from the point mutation (Val324Glu) in the nbl mutant zebrafish. The nbl mutants showed atrioventricular block and sudden death at eight months post-fertilization. Histological and microscopic analysis of the nbl mutant hearts showed decreased ventricular wall thickness, elevated level of reactive oxygen species (ROS), increased fibrosis, mitochondrial damage, and increased autophagosomes. mRNA and protein expression of autophagy-related genes significantly increased in nbl mutants. We established HEK293 stable cell lines of WT, nbl-type, and DCM-type HSPD1, with tetracycline-dependent expression. Compared to WT, both nbl- and DCM-type cells showed decreased cell growth, increased expression of ROS and autophagy-related genes, inhibition of the activity of mitochondrial electron transport chain complexes III and IV, and decreased mitochondrial fission and fusion.

CONCLUSIONS: Mutations in HSPD1 caused mitochondrial dysfunction and induced mitophagy. Mitochondrial dysfunction caused increased ROS and cardiac atrophy.

TRANSLATIONAL PERSPECTIVE: The aged heart is more susceptible to stress despite the increased compensatory chaperones/co-chaperones activity. Here, we identified a point mutation in HSPD1 in a human DCM family. Using zebrafish, we demonstrated that functional inactivation of HSPD1 resulted in increased ROS level and mitophagy, thereby resulting in heart failure at a relatively early age. Inhibition of ROS activity by antioxidants decreased cell death and mitophagy. This work identifies the key role of HSPD1 in cardiac muscle protection and suggests the supplementation of antioxidants may improve the cardiac function through the mitochondrial ROS pathway in patients with chronic heart failure.

RevDate: 2020-08-03

Shah SI, Ong HL, Demuro A, et al (2020)

PunctaSpecks: A tool for automated detection, tracking, and analysis of multiple types of fluorescently labeled biomolecules.

Cell calcium, 89:102224.

Recent advances in imaging technology and fluorescent probes have made it possible to gain information about the dynamics of subcellular processes at unprecedented spatiotemporal scales. Unfortunately, a lack of automated tools to efficiently process the resulting imaging data encoding fine details of the biological processes remains a major bottleneck in utilizing the full potential of these powerful experimental techniques. Here we present a computational tool, called PunctaSpecks, that can characterize fluorescence signals arising from a wide range of biological molecules under normal and pathological conditions. Among other things, the program can calculate the number, areas, life-times, and amplitudes of fluorescence signals arising from multiple sources, track diffusing fluorescence sources like moving mitochondria, and determine the overlap probability of two processes or organelles imaged using indicator dyes of different colors. We have tested PunctaSpecks on synthetic time-lapse movies containing mobile fluorescence objects of various sizes, mimicking the activity of biomolecules. The robustness of the software is tested by varying the level of noise along with random but known pattern of appearing, disappearing, and movement of these objects. Next, we use PunctaSpecks to characterize protein-protein interaction involved in store-operated Ca2+ entry through the formation and activation of plasma membrane-bound ORAI1 channel and endoplasmic reticulum membrane-bound stromal interaction molecule (STIM), the evolution of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ signals from sub-micrometer size local events into global waves in human cortical neurons, and the activity of Alzheimer's disease-associated β amyloid pores in the plasma membrane. The tool can also be used to study other dynamical processes imaged through fluorescence molecules. The open source algorithm allows for extending the program to analyze more than two types of biomolecules visualized using markers of different colors.

RevDate: 2020-06-29

Diederich NJ, Uchihara T, Grillner S, et al (2020)

The Evolution-Driven Signature of Parkinson's Disease.

Trends in neurosciences, 43(7):475-492.

In this review, we approach Parkinson's disease (PD) in the context of an evolutionary mismatch of central nervous system functions. The neurons at risk have hyperbranched axons, extensive transmitter release sites, display spontaneous spiking, and elevated mitochondrial stress. They function in networks largely unchanged throughout vertebrate evolution, but now connecting to the expanded human cortex. Their breakdown is favoured by longevity. At the cellular level, mitochondrial dysfunction starts at the synapses, then involves axons and cell bodies. At the behavioural level, network dysfunctions provoke the core motor syndrome of parkinsonism including freezing and failed gait automatization, and non-motor deficits including inactive blindsight and autonomic dysregulation. The proposed evolutionary re-interpretation of PD-prone cellular phenotypes and of prototypical clinical symptoms allows a new conceptual framework for future research.

RevDate: 2020-08-05
CmpDate: 2020-08-05

Allen R, Ryan H, Davis BW, et al (2020)

A mitochondrial genetic divergence proxy predicts the reproductive compatibility of mammalian hybrids.

Proceedings. Biological sciences, 287(1928):20200690.

Numerous pairs of evolutionarily divergent mammalian species have been shown to produce hybrid offspring. In some cases, F1 hybrids are able to produce F2s through matings with F1s. In other instances, the hybrids are only able to produce offspring themselves through backcrosses with a parent species owing to unisexual sterility (Haldane's Rule). Here, we explicitly tested whether genetic distance, computed from mitochondrial and nuclear genes, can be used as a proxy to predict the relative fertility of the hybrid offspring resulting from matings between species of terrestrial mammals. We assessed the proxy's predictive power using a well-characterized felid hybrid system, and applied it to modern and ancient hominins. Our results revealed a small overlap in mitochondrial genetic distance values that distinguish species pairs whose calculated distances fall within two categories: those whose hybrid offspring follow Haldane's Rule, and those whose hybrid F1 offspring can produce F2s. The strong correlation between genetic distance and hybrid fertility demonstrated here suggests that this proxy can be employed to predict whether the hybrid offspring of two mammalian species will follow Haldane's Rule.

RevDate: 2020-07-17

Tan M, Tol HTAV, Rosenkranz D, et al (2020)

PIWIL3 Forms a Complex with TDRKH in Mammalian Oocytes.

Cells, 9(6):.

P-element induced wimpy testis (PIWIs) are crucial guardians of genome integrity, particularly in germ cells. While mammalian PIWIs have been primarily studied in mouse and rat, a homologue for the human PIWIL3 gene is absent in the Muridae family, and hence the unique function of PIWIL3 in germ cells cannot be effectively modeled by mouse knockouts. Herein, we investigated the expression, distribution, and interaction of PIWIL3 in bovine oocytes. We localized PIWIL3 to mitochondria, and demonstrated that PIWIL3 expression is stringently controlled both spatially and temporally before and after fertilization. Moreover, we identified PIWIL3 in a mitochondrial-recruited three-membered complex with Tudor and KH domain-containing protein (TDRKH) and poly(A)-specific ribonuclease-like domain containing 1 (PNLDC1), and demonstrated by mutagenesis that PIWIL3 N-terminal arginines are required for complex assembly. Finally, we sequenced the piRNAs bound to PIWIL3-TDRKH-PNLDC1 and report here that about 50% of these piRNAs map to transposable elements, recapitulating the important role of PIWIL3 in maintaining genome integrity in mammalian oocytes.

RevDate: 2020-06-30

Mendoza H, Perlin MH, J Schirawski (2020)

Mitochondrial Inheritance in Phytopathogenic Fungi-Everything Is Known, or Is It?.

International journal of molecular sciences, 21(11):.

Mitochondria are important organelles in eukaryotes that provide energy for cellular processes. Their function is highly conserved and depends on the expression of nuclear encoded genes and genes encoded in the organellar genome. Mitochondrial DNA replication is independent of the replication control of nuclear DNA and as such, mitochondria may behave as selfish elements, so they need to be controlled, maintained and reliably inherited to progeny. Phytopathogenic fungi meet with special environmental challenges within the plant host that might depend on and influence mitochondrial functions and services. We find that this topic is basically unexplored in the literature, so this review largely depends on work published in other systems. In trying to answer elemental questions on mitochondrial functioning, we aim to introduce the aspect of mitochondrial functions and services to the study of plant-microbe-interactions and stimulate phytopathologists to consider research on this important organelle in their future projects.

RevDate: 2020-09-02

Gibellini L, De Gaetano A, Mandrioli M, et al (2020)

The biology of Lonp1: More than a mitochondrial protease.

International review of cell and molecular biology, 354:1-61.

Initially discovered as a protease responsible for degradation of misfolded or damaged proteins, the mitochondrial Lon protease (Lonp1) turned out to be a multifaceted enzyme, that displays at least three different functions (proteolysis, chaperone activity, binding of mtDNA) and that finely regulates several cellular processes, within and without mitochondria. Indeed, LONP1 in humans is ubiquitously expressed, and is involved in regulation of response to oxidative stress and, heat shock, in the maintenance of mtDNA, in the regulation of mitophagy. Furthermore, its proteolytic activity can regulate several biochemical pathways occurring totally or partially within mitochondria, such as TCA cycle, oxidative phosphorylation, steroid and heme biosynthesis and glutamine production. Because of these multiple activities, Lon protease is highly conserved throughout evolution, and mutations occurring in its gene determines severe diseases in humans, including a rare syndrome characterized by Cerebral, Ocular, Dental, Auricular and Skeletal anomalies (CODAS). Finally, alterations of LONP1 regulation in humans can favor tumor progression and aggressiveness, further highlighting the crucial role of this enzyme in mitochondrial and cellular homeostasis.

RevDate: 2020-07-08

Neveu E, Khalifeh D, Salamin N, et al (2020)

Prototypic SNARE Proteins Are Encoded in the Genomes of Heimdallarchaeota, Potentially Bridging the Gap between the Prokaryotes and Eukaryotes.

Current biology : CB, 30(13):2468-2480.e5.

A defining feature of eukaryotic cells is the presence of numerous membrane-bound organelles that subdivide the intracellular space into distinct compartments. How the eukaryotic cell acquired its internal complexity is still poorly understood. Material exchange among most organelles occurs via vesicles that bud off from a source and specifically fuse with a target compartment. Central players in the vesicle fusion process are the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. These small tail-anchored (TA) membrane proteins zipper into elongated four-helix bundles that pull membranes together. SNARE proteins are highly conserved among eukaryotes but are thought to be absent in prokaryotes. Here, we identified SNARE-like factors in the genomes of uncultured organisms of Asgard archaea of the Heimdallarchaeota clade, which are thought to be the closest living relatives of eukaryotes. Biochemical experiments show that the archaeal SNARE-like proteins can interact with eukaryotic SNARE proteins. We did not detect SNAREs in α-proteobacteria, the closest relatives of mitochondria, but identified several genes encoding for SNARE proteins in γ-proteobacteria of the order Legionellales, pathogens that live inside eukaryotic cells. Very probably, their SNAREs stem from lateral gene transfer from eukaryotes. Together, this suggests that the diverse set of eukaryotic SNAREs evolved from an archaeal precursor. However, whether Heimdallarchaeota actually have a simplified endomembrane system will only be seen when we succeed studying these organisms under the microscope.

RevDate: 2020-08-17
CmpDate: 2020-08-17

Roulet ME, Garcia LE, Gandini CL, et al (2020)

Multichromosomal structure and foreign tracts in the Ombrophytum subterraneum (Balanophoraceae) mitochondrial genome.

Plant molecular biology, 103(6):623-638.

Horizontal gene transfer (HGT) is frequent in parasitic plant mitochondria as a result of vascular connections established in host-parasite relationships. Recent studies of the holoparasitic plant Lophophytum mirabile (Balanophoraceae) revealed the unprecedented acquisition of a large amount of mitochondrial sequences from its legume host. We focused on a close relative, the generalist holoparasite Ombrophytum subterraneum, to examine the incidence of HGT events in the mitochondrial genome (mtDNA). The mtDNA of O. subterraneum assembles into 54 circular chromosomes, only 34 of which contain the 51 full-length coding regions. Numerous foreign tracts (totaling almost 100 kb, ~ 14% of the mtDNA), including 12 intact genes, were acquired by HGT from the Asteraceae hosts. Nine chromosomes concentrate most of those regions and eight are almost entirely foreign. Native homologs of each foreign gene coexist in the mtDNA and are potentially functional. A large proportion of shorter regions were related to the Fabaceae (a total of ~ 110 kb, 15.4%), some of which were shared with L. mirabile. We also found evidence of foreign sequences donated by angiosperm lineages not reported as hosts (Apocynaceae, Euphorbiaceae, Lamiaceae, and Malvales). We propose an evolutionary hypothesis that involves ancient transfers from legume hosts in the common ancestor of Ombrophytum and Lophophytum followed by more recent transfer events in L. mirabile. Besides, the O. subterraneum mtDNA was also subjected to additional HGT events from diverse angiosperm lineages, including large and recent transfers from the Asteraceae, and also from Lamiaceae.

RevDate: 2020-07-21

Speijer D, Hammond M, J Lukeš (2020)

Comparing Early Eukaryotic Integration of Mitochondria and Chloroplasts in the Light of Internal ROS Challenges: Timing is of the Essence.

mBio, 11(3):.

When trying to reconstruct the evolutionary trajectories during early eukaryogenesis, one is struck by clear differences in the developments of two organelles of endosymbiotic origin: the mitochondrion and the chloroplast. From a symbiogenic perspective, eukaryotic development can be interpreted as a process in which many of the defining eukaryotic characteristics arose as a result of mutual adaptions of both prokaryotes (an archaeon and a bacterium) involved. This implies that many steps during the bacterium-to-mitochondrion transition trajectory occurred in an intense period of dramatic and rapid changes. In contrast, the subsequent cyanobacterium-to-chloroplast development in a specific eukaryotic subgroup, leading to the photosynthetic lineages, occurred in a full-fledged eukaryote. The commonalities and differences in the two trajectories shed an interesting light on early, and ongoing, eukaryotic evolutionary driving forces, especially endogenous reactive oxygen species (ROS) formation. Differences between organellar ribosomes, changes to the electron transport chain (ETC) components, and mitochondrial codon reassignments in nonplant mitochondria can be understood when mitochondrial ROS formation, e.g., during high energy consumption in heterotrophs, is taken into account.IMPORTANCE The early eukaryotic evolution was deeply influenced by the acquisition of two endosymbiotic organelles - the mitochondrion and the chloroplast. Here we discuss the possibly important role of reactive oxygen species in these processes.

RevDate: 2020-09-21
CmpDate: 2020-09-21

Vecoli C, Borghini A, MG Andreassi (2020)

The molecular biomarkers of vascular aging and atherosclerosis: telomere length and mitochondrial DNA4977 common deletion.

Mutation research, 784:108309.

Age is the dominant risk factor for the most prevalent atherosclerotic vascular diseases, including coronary artery disease, myocardial infarction, cerebrovascular disease and stroke. In human, telomere erosion and mitochondrial DNA (mtDNA) damage play a central role in the mechanisms leading to cellular aging decline. This review summarizes the most relevant findings on the role of telomere shortening and the common mtDNA4977 deletion in the progression and evolution of atherosclerosis by combining insight from experimental models and human clinical studies. The current evidence shows a link between telomere erosion and compromised mitochondrial function and provides a new perspective regarding their potential role as clinical biomarkers and therapeutic targets.

RevDate: 2020-09-22
CmpDate: 2020-09-22

Chang H, Nie Y, Zhang N, et al (2020)

MtOrt: an empirical mitochondrial amino acid substitution model for evolutionary studies of Orthoptera insects.

BMC evolutionary biology, 20(1):57.

BACKGROUND: Amino acid substitution models play an important role in inferring phylogenies from proteins. Although different amino acid substitution models have been proposed, only a few were estimated from mitochondrial protein sequences for specific taxa such as the mtArt model for Arthropoda. The increasing of mitochondrial genome data from broad Orthoptera taxa provides an opportunity to estimate the Orthoptera-specific mitochondrial amino acid empirical model.

RESULTS: We sequenced complete mitochondrial genomes of 54 Orthoptera species, and estimated an amino acid substitution model (named mtOrt) by maximum likelihood method based on the 283 complete mitochondrial genomes available currently. The results indicated that there are obvious differences between mtOrt and the existing models, and the new model can better fit the Orthoptera mitochondrial protein datasets. Moreover, topologies of trees constructed using mtOrt and existing models are frequently different. MtOrt does indeed have an impact on likelihood improvement as well as tree topologies. The comparisons between the topologies of trees constructed using mtOrt and existing models show that the new model outperforms the existing models in inferring phylogenies from Orthoptera mitochondrial protein data.

CONCLUSIONS: The new mitochondrial amino acid substitution model of Orthoptera shows obvious differences from the existing models, and outperforms the existing models in inferring phylogenies from Orthoptera mitochondrial protein sequences.

RevDate: 2020-05-19

Pánek T, Eliáš M, Vancová M, et al (2020)

Returning to the Fold for Lessons in Mitochondrial Crista Diversity and Evolution.

Current biology : CB, 30(10):R575-R588.

Cristae are infoldings of the mitochondrial inner membrane jutting into the organelle's innermost compartment from narrow stems at their base called crista junctions. They are emblematic of aerobic mitochondria, being the fabric for the molecular machinery driving cellular respiration. Electron microscopy revealed that diverse eukaryotes possess cristae of different shapes. Yet, crista diversity has not been systematically examined in light of our current knowledge about eukaryotic evolution. Since crista form and function are intricately linked, we take a holistic view of factors that may underlie both crista diversity and the adherence of cristae to a recognizable form. Based on electron micrographs of 226 species from all major lineages, we propose a rational crista classification system that postulates cristae as variations of two general morphotypes: flat and tubulo-vesicular. The latter is most prevalent and likely ancestral, but both morphotypes are found interspersed throughout the eukaryotic tree. In contrast, crista junctions are remarkably conserved, supporting their proposed role as diffusion barriers that sequester cristae contents. Since cardiolipin, ATP synthase dimers, the MICOS complex, and dynamin-like Opa1/Mgm1 are known to be involved in shaping cristae, we examined their variation in the context of crista diversity. Moreover, we have identified both commonalities and differences that may collectively be manifested as diverse variations of crista form and function.

RevDate: 2020-05-19

Lane N (2020)

How energy flow shapes cell evolution.

Current biology : CB, 30(10):R471-R476.

How mitochondria shaped the evolution of eukaryotic complexity has been controversial for decades. The discovery of the Asgard archaea, which harbor close phylogenetic ties to the eukaryotes, supports the idea that a critical endosymbiosis between an archaeal host and a bacterial endosymbiont transformed the selective constraints present at the origin of eukaryotes. Cultured Asgard archaea are typically prokaryotic in both size and internal morphology, albeit featuring extensive protrusions. The acquisition of the mitochondrial predecessor by an archaeal host cell fundamentally altered the topology of genes in relation to bioenergetic membranes. Mitochondria internalised not only the bioenergetic membranes but also the genetic machinery needed for local control of oxidative phosphorylation. Gene loss from mitochondria enabled expansion of the nuclear genome, giving rise to an extreme genomic asymmetry that is ancestral to all extant eukaryotes. This genomic restructuring gave eukaryotes thousands of fold more energy availability per gene. In principle, that difference can support more and larger genes, far more non-coding DNA, greater regulatory complexity, and thousands of fold more protein synthesis per gene. These changes released eukaryotes from the bioenergetic constraints on prokaryotes, facilitating the evolution of morphological complexity.

RevDate: 2020-07-27

He Q, Luo J, Xu JZ, et al (2020)

Characterization of Hsp70 gene family provides insight into its functions related to microsporidian proliferation.

Journal of invertebrate pathology, 174:107394.

Heat shock protein 70 (Hsp70), a highly conserved protein family, is widely distributed in organisms and plays fundamental roles in biotic and abiotic stress responses. However, reports on Hsp70 genes are scarce in microsporidia, a very large group of obligate intracellular parasites that can infect nearly all animals, including humans. In this study, we identified 37 Hsp70 proteins from eight microsporidian genomes and classified them into four subfamilies (A-D). The number of Hsp70 genes in these microsporidia was significantly fewer than in Rozella allomycis and yeast. All microsporidian species contained genes from each subfamily and similar subcellular locations (mitochondria, endoplasmic reticulum, cytosol, and cytosol and/or nucleus), indicating that each Hsp70 member may fulfil distinct functions. The conserved structures and motifs of the Hsp70 proteins in the same subfamily were highly similar. Expression analysis indicated that the subfamily C cytosol (cyto)-associated Hsp70s is functional during microsporidia development. Immunofluorescence assays revealed that Cyto-NbHsp70 was cytoplasmically located in the proliferation-stage of Nosema bombycis. Cyto-NbHsp70 antiserum also labeled Encephalitozoon hellem within infected cells, suggesting that this antiserum is a potential molecular marker for labeling the proliferative phases of different microsporidian species. The propagation of N. bombycis was significantly inhibited following RNAi of Cyto-NbHsp70, indicating that Cyto-NbHsp70 is important for pathogen proliferation. Our phylogenetic data suggest that Hsp70 proteins evolved during microsporidia adaption to intracellular parasitism, and they play important roles in pathogen development.

RevDate: 2020-10-07

Arad M, Waldman M, Abraham NG, et al (2020)

Therapeutic approaches to diabetic cardiomyopathy: Targeting the antioxidant pathway.

Prostaglandins & other lipid mediators, 150:106454.

The global epidemic of cardiovascular disease continues unabated and remains the leading cause of death both in the US and worldwide. We hereby summarize the available therapies for diabetes and cardiovascular disease in diabetics. Clearly, the current approaches to diabetic heart disease often target the manifestations and certain mediators but not the specific pathways leading to myocardial injury, remodeling and dysfunction. Better understanding of the molecular events determining the evolution of diabetic cardiomyopathy will provide insight into the development of specific and targeted therapies. Recent studies largely increased our understanding of the role of enhanced inflammatory response, ROS production, as well as the contribution of Cyp-P450-epoxygenase-derived epoxyeicosatrienoic acid (EET), Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α (PGC-1α), Heme Oxygenase (HO)-1 and 20-HETE in pathophysiology and therapy of cardiovascular disease. PGC-1α increases production of the HO-1 which has a major role in protecting the heart against oxidative stress, microcirculation and mitochondrial dysfunction. This review describes the potential drugs and their downstream targets, PGC-1α and HO-1, as major loci for developing therapeutic approaches beside diet and lifestyle modification for the treatment and prevention of heart disease associated with obesity and diabetes.

RevDate: 2020-09-28

Fonseca PLC, Badotti F, De-Paula RB, et al (2020)

Exploring the Relationship Among Divergence Time and Coding and Non-coding Elements in the Shaping of Fungal Mitochondrial Genomes.

Frontiers in microbiology, 11:765.

The order Hypocreales (Ascomycota) is composed of ubiquitous and ecologically diverse fungi such as saprobes, biotrophs, and pathogens. Despite their phylogenetic relationship, these species exhibit high variability in biomolecules production, lifestyle, and fitness. The mitochondria play an important role in the fungal biology, providing energy to the cells and regulating diverse processes, such as immune response. In spite of its importance, the mechanisms that shape fungal mitogenomes are still poorly understood. Herein, we investigated the variability and evolution of mitogenomes and its relationship with the divergence time using the order Hypocreales as a study model. We sequenced and annotated for the first time Trichoderma harzianum mitochondrial genome (mtDNA), which was compared to other 34 mtDNAs species that were publicly available. Comparative analysis revealed a substantial structural and size variation on non-coding mtDNA regions, despite the conservation of copy number, length, and structure of protein-coding elements. Interestingly, we observed a highly significant correlation between mitogenome length, and the number and size of non-coding sequences in mitochondrial genome. Among the non-coding elements, group I and II introns and homing endonucleases genes (HEGs) were the main contributors to discrepancies in mitogenomes structure and length. Several intronic sequences displayed sequence similarity among species, and some of them are conserved even at gene position, and were present in the majority of mitogenomes, indicating its origin in a common ancestor. On the other hand, we also identified species-specific introns that advocate for the origin by different mechanisms. Investigation of mitochondrial gene transfer to the nuclear genome revealed that nuclear copies of the nad5 are the most frequent while atp8, atp9, and cox3 could not be identified in any of the nuclear genomes analyzed. Moreover, we also estimated the divergence time of each species and investigated its relationship with coding and non-coding elements as well as with the length of mitogenomes. Altogether, our results demonstrated that introns and HEGs are key elements on mitogenome shaping and its presence on fast-evolving mtDNAs could be mostly explained by its divergence time, although the intron sharing profile suggests the involvement of other mechanisms on the mitochondrial genome evolution, such as horizontal transference.

RevDate: 2020-07-28
CmpDate: 2020-07-28

Han X, He H, Shen H, et al (2020)

Comparative mitochondrial genome analysis of Dendrolimus houi (Lepidoptera: Lasiocampidae) and phylogenetic relationship among Lasiocampidae species.

PloS one, 15(5):e0232527.

Dendrolimus houi is one of the most common caterpillars infesting Gymnosperm trees, and widely distributed in several countries in Southeast Asia, and exists soley or coexists with several congeners and some Lasiocampidae species in various forest habitats. However, natural hybrids occasionally occur among some closely related species in the same habitat, and host preference, extreme climate stress, and geographic isolation probably lead to their uncertain taxonomic consensus. The mitochondrial DNA (mtDNA) of D. houi was extracted and sequenced by using high-throughput technology, and the mitogenome composition and characteristics were compared and analyzed of these species, then the phylogenetic relationship was constructed using the maximum likelihood method (ML) and the Bayesian method (BI) based on their 13 protein-coding genes (PCGs) dataset, which were combined and made available to download which were combined and made available to download among global Lasiocampidae species data. Mitogenome of D. houi was 15,373 bp in length, with 37 genes, including 13 PCGs, 22 tRNA genes (tRNAs) and 2 rRNA genes (rRNAs). The positions and sequences of genes were consistent with those of most known Lasiocampidae species. The nucleotide composition was highly A+T biased, accounting for ~80% of the whole mitogenome. All start codons of PCGs belonged to typical start codons ATN except for COI which used CGA, and most stop codons ended with standard TAA or TAG, while COI, COII, ND4 ended with incomplete T. Only tRNASer (AGN) lacked DHU arm, while the remainder formed a typical "clover-shaped" secondary structure. For Lasiocampidae species, their complete mitochondrial genomes ranged from 15,281 to 15,570 bp in length, and all first genes started from trnM in the same direction. And base composition was biased toward A and T. Finally, both two methods (ML and BI) separately revealed that the same phylogenetic relationship of D. spp. as ((((D. punctatus + D. tabulaeformis) + D. spectabilis) + D. superans) + (D. kikuchii of Hunan population + D. houi) as in previous research, but results were different in that D. kikuchii from a Yunnan population was included, indicating that different geographical populations of insects have differentiated. And the phylogenetic relationship among Lasiocampidae species was ((((Dendrolimus) + Kunugia) + Euthrix) + Trabala). This provides a better theoretical basis for Lasiocampidae evolution and classification for future research directions.

RevDate: 2020-07-27
CmpDate: 2020-07-27

Cai G, SR Scofield (2020)

Mitochondrial genome sequence of Phytophthora sansomeana and comparative analysis of Phytophthora mitochondrial genomes.

PloS one, 15(5):e0231296.

Phytophthora sansomeana infects soybean and causes root rot. It was recently separated from the species complex P. megasperma sensu lato. In this study, we sequenced and annotated its complete mitochondrial genome and compared it to that of nine other Phytophthora species. The genome was assembled into a circular molecule of 39,618 bp with a 22.03% G+C content. Forty-two protein coding genes, 25 tRNA genes and two rRNA genes were annotated in this genome. The protein coding genes include 14 genes in the respiratory complexes, four ATP synthase genes, 16 ribosomal proteins genes, a tatC translocase gene, six conserved ORFs and a unique orf402. The tRNA genes encode tRNAs for 19 amino acids. Comparison among mitochondrial genomes of 10 Phytophthora species revealed three inversions, each covering multiple genes. These genomes were conserved in gene content with few exceptions. A 3' truncated atp9 gene was found in P. nicotianae. All 10 Phytophthora species, as well as other oomycetes and stramenopiles, lacked tRNA genes for threonine in their mitochondria. Phylogenomic analysis using the mitochondrial genomes supported or enhanced previous findings of the phylogeny of Phytophthora spp.

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RJR Experience and Expertise

Researcher

Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.

Educator

Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.

Administrator

Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.

Technologist

Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.

Publisher

While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.

Speaker

Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.

Facilitator

Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.

Designer

Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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