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IUBMB Life Dec 2018Mitochondria are the sandbox of evolution as exemplified most particularly by the diplonemids, a group of marine microeukaryotes. These protists are uniquely... (Review)
Review
Mitochondria are the sandbox of evolution as exemplified most particularly by the diplonemids, a group of marine microeukaryotes. These protists are uniquely characterized by their highly multipartite mitochondrial genome and systematically fragmented genes whose pieces are spread out over several dozens of chromosomes. The type species Diplonema papillatum was the first member of this group in which the expression of fragmented mitochondrial genes was investigated experimentally. We now know that gene expression involves separate transcription of gene pieces (modules), RNA editing of module transcripts, and module joining to mature mRNAs and rRNAs. The mechanism of cognate module recognition and ligation is distinct from known intron splicing and remains to be uncovered. Here, we review the current status of research on mitochondrial genome architecture, as well as gene complement, structure, and expression modes in diplonemids. Further, we discuss the potential molecular mechanisms of posttranscriptional processing, and finally reflect on the evolutionary trajectories and trends of mtDNA evolution as seen in this protist group. © 2018 IUBMB Life, 70(12):1197-1206, 2018.
Topics: Aquatic Organisms; DNA, Mitochondrial; Euglenozoa; Genes, Mitochondrial; Genome, Mitochondrial; Introns; Mitochondria
PubMed: 30304578
DOI: 10.1002/iub.1927 -
Biochemical Society Transactions Oct 2013The persistence of mtDNA to encode a small subset of mitochondrial proteins reflects the selective advantage of co-location of key respiratory chain subunit genes with...
The persistence of mtDNA to encode a small subset of mitochondrial proteins reflects the selective advantage of co-location of key respiratory chain subunit genes with their gene products. The disadvantage of this co-location is exposure of mtDNA to mutagenic ROS (reactive oxygen species), which are by-products of aerobic respiration. The resulting 'vicious circle' of mitochondrial mutation has been proposed to underlie aging and its associated degenerative diseases. Recent evidence is consistent with the hypothesis that oocyte mitochondria escape the aging process by acting as quiescent genetic templates, transcriptionally and bioenergetically repressed. Transmission of unexpressed mtDNA in the female germline is considered as a reason for the existence of separate sexes, i.e. male and female. Maternal inheritance then circumvents incremental accumulation of age-related disease in each new generation.
Topics: Aerobiosis; Aging; DNA Damage; Female; Genes, Mitochondrial; Genome, Mitochondrial; Germ Cells; Humans; Male; Mitochondria; Mutation; Oocytes; Oxidative Stress; Reactive Oxygen Species
PubMed: 24059523
DOI: 10.1042/BST20130106 -
Developmental Cell Dec 2016Inherited mtDNA mutations cause severe human disease. In most species, mitochondria are inherited maternally through mechanisms that are poorly understood. Genes that...
Inherited mtDNA mutations cause severe human disease. In most species, mitochondria are inherited maternally through mechanisms that are poorly understood. Genes that specifically control the inheritance of mitochondria in the germline are unknown. Here, we show that the long isoform of the protein Oskar regulates the maternal inheritance of mitochondria in Drosophila melanogaster. We show that, during oogenesis, mitochondria accumulate at the oocyte posterior, concurrent with the bulk streaming and churning of the oocyte cytoplasm. Long Oskar traps and maintains mitochondria at the posterior at the site of primordial germ cell (PGC) formation through an actin-dependent mechanism. Mutating long oskar strongly reduces the number of mtDNA molecules inherited by PGCs. Therefore, Long Oskar ensures germline transmission of mitochondria to the next generation. These results provide molecular insight into how mitochondria are passed from mother to offspring, as well as how they are positioned and asymmetrically partitioned within polarized cells.
Topics: Actins; Animals; DNA Copy Number Variations; DNA, Mitochondrial; Drosophila Proteins; Drosophila melanogaster; Embryonic Germ Cells; Female; Genes, Insect; Genes, Mitochondrial; Humans; Oogenesis; Protein Isoforms
PubMed: 27923120
DOI: 10.1016/j.devcel.2016.11.004 -
Proceedings of the National Academy of... Aug 2013In animals, mtDNA is always transmitted through the female and this is termed "maternal inheritance." Recently, autophagy was reported to be involved in maternal...
In animals, mtDNA is always transmitted through the female and this is termed "maternal inheritance." Recently, autophagy was reported to be involved in maternal inheritance by elimination of paternal mitochondria and mtDNA in Caenorhabditis elegans; moreover, by immunofluorescence, P62 and LC3 proteins were also found to colocalize to sperm mitochondria after fertilization in mice. Thus, it has been speculated that autophagy may be an evolutionary conserved mechanism for paternal mitochondrial elimination. However, by using two transgenic mouse strains, one bearing GFP-labeled autophagosomes and the other bearing red fluorescent protein-labeled mitochondria, we demonstrated that autophagy did not participate in the postfertilization elimination of sperm mitochondria in mice. Although P62 and LC3 proteins congregated to sperm mitochondria immediately after fertilization, sperm mitochondria were not engulfed and ultimately degraded in lysosomes until P62 and LC3 proteins disengaged from sperm mitochondria. Instead, sperm mitochondria unevenly distributed in blastomeres during cleavage and persisted in several cells until the morula stages. Furthermore, by using single sperm mtDNA PCR, we observed that most motile sperm that had reached the oviduct for fertilization had eliminated their mtDNA, leaving only vacuolar mitochondria. However, if sperm with remaining mtDNA entered the zygote, mtDNA was not eliminated and could be detected in newborn mice. Based on these results, we conclude that, in mice, maternal inheritance of mtDNA is not an active process of sperm mitochondrial and mtDNA elimination achieved through autophagy in early embryos, but may be a passive process as a result of prefertilization sperm mtDNA elimination and uneven mitochondrial distribution in embryos.
Topics: Animals; Autophagy; Base Sequence; DNA, Mitochondrial; Embryo, Mammalian; Female; Genes, Mitochondrial; Inheritance Patterns; Luminescent Proteins; Lysosomes; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microscopy, Confocal; Microtubule-Associated Proteins; Mitochondria; Molecular Sequence Data; Phagosomes; Sequence Homology, Nucleic Acid; Spermatozoa; Transcription Factor TFIIH; Transcription Factors
PubMed: 23878233
DOI: 10.1073/pnas.1303231110 -
Nature Reviews. Molecular Cell Biology Dec 2010Mitochondria are dynamic organelles that constantly fuse and divide. These processes (collectively termed mitochondrial dynamics) are important for mitochondrial... (Review)
Review
Mitochondria are dynamic organelles that constantly fuse and divide. These processes (collectively termed mitochondrial dynamics) are important for mitochondrial inheritance and for the maintenance of mitochondrial functions. The core components of the evolutionarily conserved fusion and fission machineries have now been identified, and mechanistic studies have revealed the first secrets of the complex processes that govern fusion and fission of a double membrane-bound organelle. Mitochondrial dynamics was recently recognized as an important constituent of cellular quality control. Defects have detrimental consequences on bioenergetic supply and contribute to the pathogenesis of neurodegenerative diseases. These findings open exciting new directions to explore mitochondrial biology.
Topics: Animals; Cell Death; Cell Proliferation; Cytokinesis; Genes, Mitochondrial; Humans; Membrane Fusion; Mitochondria; Mitochondrial Membranes; Models, Biological
PubMed: 21102612
DOI: 10.1038/nrm3013 -
Mitochondrial DNA. Part A, DNA Mapping,... Nov 2016In this study, we cloned and sequenced the complete mitochondrial DNA (mtDNA) of Oncorhynchus mykiss triploid to characterize and compare their mitochondrial genomes....
In this study, we cloned and sequenced the complete mitochondrial DNA (mtDNA) of Oncorhynchus mykiss triploid to characterize and compare their mitochondrial genomes. The total length of the mitochondrial genome is 16,656 bp with an accession number KP085590. The organization of the mitochondrial genomes was similar to those reported from other fish mitochondrial genomes containing 37 genes (13 protein-coding genes, 2 ribosomal RNA, and 22 transfer RNAs) and a major non-coding control region. Except for ND6 and 8 tRNAs, all other genes are encoded on the heavy strand. The nucleotide skewness for the coding strands of O. mykiss triploid (AT-skew = -0.41, GC-skew = 0.34) is biased toward T and G. The complete mitogenome may provide important date set for the study of genetic mechanism of O. mykiss.
Topics: Animals; DNA, Mitochondrial; Genes, Mitochondrial; Genome, Mitochondrial; Mitochondria; Oncorhynchus mykiss; RNA, Ribosomal; RNA, Transfer; Sequence Analysis, DNA; Triploidy
PubMed: 25629478
DOI: 10.3109/19401736.2014.1003859 -
Reproduction, Fertility, and Development Jan 2017Preformationist William Harvey's proclamation of everything live coming from an egg still holds true for mammalian mitochondria and mitochondrial genes. At... (Review)
Review
Preformationist William Harvey's proclamation of everything live coming from an egg still holds true for mammalian mitochondria and mitochondrial genes. At fertilisation, mitochondria carried into the oocyte cytoplasm by the spermatozoon are sought out and destroyed, leaving only oocyte mitochondria to propagate their mitochondrial (mt) DNA to offspring. This clonal inheritance mode, the 'mitochondrial Eve' paradigm, is mediated by oocytes' resident proteolytic, organelle-targeting mechanisms, including the substrate-specific ubiquitin proteasome system and the autophagic machinery for bulk protein and organelle degradation. Ubiquitination of sperm mitochondria within the cytoplasm of the fertilised oocyte was initially discovered in mammals. More recent studies in Drosophila and Caenorhabditis elegans implicated the ubiquitin-binding autophagy protein sequestosome 1 (SQSTM1) as the early adaptor channelling ubiquitinated sperm mitochondria towards the autophagic machinery. Downstream receptors include microtubule-associated protein 1 light chain 3α (LC3) and GABA type A receptor-associated protein (GABARAP). Among mammals, the domestic pig is the ideal mammalian model of mitochondrial inheritance because of rapid sperm mitophagy at the 1-cell stage of embryo development. Primary recognition of sperm mitochondria by SQSTM1 inside the porcine zygote is followed by GABARAP-containing autophagophore formation, and contributed to by valosin-containing protein (VCP), a 26S proteasome-presenting protein dislocase. Consequently, coinhibition of SQSTM1-GABARAP and VCP activities in the porcine zygotes, resulting in 2- to 4-cell embryos carrying intact sperm mitochondrial sheaths, revived the moniker of 'Mitochondrial Steve'. Further work will identify the determinants of species specificity of sperm mitophagy and explain the interplay and possible consequences of a mismatch between clonal mitochondrial genome and biparentally inherited chromosomal genes encoding for structural mitochondrial proteins and transcription factors. By better understanding sperm mitophagy and its potential failure, we may be able to alleviate mitochondrial disease and early pregnancy loss in livestock and improve their fitness, reproduction and ability to pass favourable production traits to offspring.
Topics: Animals; DNA, Mitochondrial; Female; Fertilization; Genes, Mitochondrial; Humans; Male; Maternal Inheritance; Mitophagy; Pregnancy; Spermatozoa
PubMed: 29539303
DOI: 10.1071/RD17364 -
MBio Apr 2013Uniparental inheritance of mitochondrial DNA is pervasive in nonisogamic higher eukaryotes during sexual reproduction, and postzygotic and/or prezygotic factors are...
UNLABELLED
Uniparental inheritance of mitochondrial DNA is pervasive in nonisogamic higher eukaryotes during sexual reproduction, and postzygotic and/or prezygotic factors are shown to be important in ensuring such an inheritance pattern. Although the fungus Cryptococcus neoformans undergoes sexual production with isogamic partners of opposite mating types a and α, most progeny derived from such mating events inherit the mitochondrial DNA (mtDNA) from the a parent. The homeodomain protein complex Sxi1α/Sxi2a, formed in the zygote after a-α cell fusion, was previously shown to play a role in this uniparental mtDNA inheritance. Here, we defined the timing of the establishment of the mtDNA inheritance pattern during the mating process and demonstrated a critical role in determining the mtDNA inheritance pattern by a prezygotic factor, Mat2. Mat2 is the key transcription factor that governs the pheromone sensing and response pathway, and it is critical for the early mating events that lead to cell fusion and zygote formation. We show that Mat2 governs mtDNA inheritance independently of the postzygotic factors Sxi1α/Sxi2a, and the cooperation between these prezygotic and postzygotic factors helps to achieve stricter uniparental mitochondrial inheritance in this eukaryotic microbe.
IMPORTANCE
Mitochondrial DNA is inherited uniparentally from the maternal parent in the majority of eukaryotes. Studies done on higher eukaryotes such as mammals have shown that the transmission of parental mitochondrial DNA is controlled at both the prefertilization and postfertilization stages to achieve strict uniparental inheritance. However, the molecular mechanisms underlying such uniparental mitochondrial inheritance have been investigated in detail mostly in anisogamic multicellular eukaryotes. Here, we show that in a simple isogamic microbe, Cryptococcus neoformans, the mitochondrial inheritance is controlled at the prezygotic level as well as the postzygotic level by regulators that are critical for sexual development. Furthermore, the cooperation between these two levels of control ensures stricter uniparental mitochondrial inheritance, echoing what has been observed in higher eukaryotes. Thus, the investigation of uniparental mitochondrial inheritance in this eukaryotic microbe could help advance our understanding of the convergent evolution of this widespread phenomenon in the eukaryotic domain.
Topics: Cryptococcus neoformans; DNA, Mitochondrial; Genes, Mating Type, Fungal; Genes, Mitochondrial; Time Factors
PubMed: 23611907
DOI: 10.1128/mBio.00112-13 -
Wiley Interdisciplinary Reviews. RNA 2010Mitochondrial (mt-) tRNA (MTT) gene mutations are an important cause of human morbidity and are associated with a wide range of pathology, from isolated organ-specific... (Review)
Review
Mitochondrial (mt-) tRNA (MTT) gene mutations are an important cause of human morbidity and are associated with a wide range of pathology, from isolated organ-specific diseases such as myopathy or hearing loss, through to multisystem disorders with encephalopathy, gastrointestinal dysmotility, and life-threatening cardiomyopathy. Our understanding of how MTT mutations cause disease remains poor and progress has been hampered by the complex interaction of genotype with phenotype that can result in patients who harbor the same mutation exhibiting starkly contrasting phenotypes, whereas other (genetically heterogeneous) patients manifest clinically identical syndromes. A further complexity is the highly polymorphic nature of mitochondrial DNA (mtDNA), which must temper any reflex assumptions of pathogenicity for novel MTT substitutions. Nevertheless significant progress is being made and we shall review the methods employed to identify and characterize MTT mutations as pathogenic. Also important is our understanding of the molecular processes involved and we shall discuss the data available on two of the most studied MTT mutations (m.8344A > G and m.3243A > G) as well as other potential pathogenic mechanisms. Knowledge of factors influencing the inheritance of MTT mutations, and therefore the likelihood of disease transmission, is of particular importance to female patients. At present, the factors determining transmission remain elusive, but we shall examine several possible mechanisms and discuss the evidence for each. Finally, a number of different yeast and mouse models are currently used to investigate mitochondrial disease and we will assess the importance of and difficulties associated with each model as well as the future of possible therapies for patients with mitochondrial disease.
Topics: Animals; Base Sequence; Female; Genes, Mitochondrial; Humans; Mice; Mitochondria; Mitochondrial Diseases; Models, Biological; Molecular Sequence Data; Mutation; Nucleic Acid Conformation; RNA, Transfer
PubMed: 21935892
DOI: 10.1002/wrna.27 -
Proceedings. Biological Sciences Oct 2013The uniparental inheritance (UPI) of mitochondria is thought to explain the evolution of two mating types or even true sexes with anisogametes. However, the exact role...
The uniparental inheritance (UPI) of mitochondria is thought to explain the evolution of two mating types or even true sexes with anisogametes. However, the exact role of UPI is not clearly understood. Here, we develop a new model, which considers the spread of UPI mutants within a biparental inheritance (BPI) population. Our model explicitly considers mitochondrial mutation and selection in parallel with the spread of UPI mutants and self-incompatible mating types. In line with earlier work, we find that UPI improves fitness under mitochondrial mutation accumulation, selfish conflict and mitonuclear coadaptation. However, we find that as UPI increases in the population its relative fitness advantage diminishes in a frequency-dependent manner. The fitness benefits of UPI 'leak' into the biparentally reproducing part of the population through successive matings, limiting the spread of UPI. Critically, while this process favours some degree of UPI, it neither leads to the establishment of linked mating types nor the collapse of multiple mating types to two. Only when two mating types exist beforehand can associated UPI mutants spread to fixation under the pressure of high mitochondrial mutation rate, large mitochondrial population size and selfish mutants. Variation in these parameters could account for the range of UPI actually observed in nature, from strict UPI in some Chlamydomonas species to BPI in yeast. We conclude that UPI of mitochondria alone is unlikely to have driven the evolution of two mating types in unicellular eukaryotes.
Topics: Biological Evolution; Cell Nucleus; Eukaryota; Genes, Mitochondrial; Genetic Fitness; Heredity; Models, Genetic; Mutation; Reproduction; Selection, Genetic
PubMed: 23986113
DOI: 10.1098/rspb.2013.1920