Mitochondrial DNA: Consensuses and Controversies

In the course of its short history, mitochondrial DNA (mtDNA) has made a long journey from obscurity to the forefront of research on major biological processes. mtDNA alterations have been found in all major disease groups, and their significance remains the subject of intense research. Despite remarkable progress, our understanding of the major aspects of mtDNA biology, such as its replication, damage, repair, transcription, maintenance, etc., is frustratingly limited. The path to better understanding mtDNA and its role in cells, however, remains torturous and not without errors, which sometimes leave a long trail of controversy behind them. This review aims to provide a brief summary of our current knowledge of mtDNA and highlight some of the controversies that require attention from the mitochondrial research community.

[1]  Su-Jeong Kim,et al.  Mitochondria-derived peptides in aging and healthspan , 2022, The Journal of clinical investigation.

[2]  Swagat Ray,et al.  Mitochondrial DNA replication and repair defects: Clinical phenotypes and therapeutic interventions. , 2022, Biochimica et biophysica acta. Bioenergetics.

[3]  A. Toscano,et al.  Molecular Genetics Overview of Primary Mitochondrial Myopathies , 2022, Journal of clinical medicine.

[4]  Elizabeth K. Schmidt,et al.  A replication-linked mutational gradient drives somatic mutation accumulation and influences germline polymorphisms and genome composition in mitochondrial DNA , 2021, Nucleic acids research.

[5]  M. Alexeyev,et al.  Quantification of mtDNA content in cultured cells by direct droplet digital PCR. , 2021, Mitochondrion.

[6]  A. Rodríguez-Luis,et al.  Controlling the topology of mammalian mitochondrial DNA , 2021, Open Biology.

[7]  G. Shan,et al.  Mitochondria Encoded Non-coding RNAs in Cell Physiology , 2021, Frontiers in Cell and Developmental Biology.

[8]  Aaron M. Streets,et al.  The complete sequence of a human genome , 2021, bioRxiv.

[9]  J. Enríquez,et al.  Mitochondrial DNA impact on joint damaged process in a conplastic mouse model after being surgically induced with osteoarthritis , 2021, Scientific Reports.

[10]  P. Reynier,et al.  Mitochondria: their role in spermatozoa and in male infertility. , 2021, Human reproduction update.

[11]  V. Bohr,et al.  Skin Abnormalities in Disorders with DNA Repair Defects, Premature Aging, and Mitochondrial Dysfunction. , 2020, The Journal of investigative dermatology.

[12]  M. Camargo,et al.  Mechanisms for sperm mitochondrial removal in embryos. , 2020, Biochimica et biophysica acta. Molecular cell research.

[13]  L. P. Van den Heuvel,et al.  Mitochondrial Disease and the Kidney With a Special Focus on CoQ10 Deficiency , 2020, Kidney international reports.

[14]  Wei Zhang,et al.  Mitochondrial dysfunction in fibrotic diseases , 2020, Cell death discovery.

[15]  Laura C. Greaves,et al.  Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss , 2020, Scientific Reports.

[16]  A. Need,et al.  Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans , 2020, Nature Communications.

[17]  B. Bax,et al.  Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and treatment , 2020, Journal of translational genetics and genomics.

[18]  K. Ray Mitochondrial dysfunction in Crohn’s disease , 2020, Nature Reviews Gastroenterology & Hepatology.

[19]  H. Bandelt,et al.  Extraordinary claims require extraordinary evidence in asserted mtDNA biparental inheritance , 2020, Forensic Science International: Genetics.

[20]  H. Prokisch,et al.  ncRNAs: New Players in Mitochondrial Health and Disease? , 2020, Frontiers in Genetics.

[21]  James H. Joly,et al.  Mitochondrial-Encoded Peptide MOTS-c is an Exercise-Induced Regulator of Aging Metabolic Homeostasis and Physical Capacity , 2019, bioRxiv.

[22]  M. Alexeyev,et al.  Limited predictive value of TFAM in mitochondrial biogenesis. , 2019, Mitochondrion.

[23]  I. H. Hamzah,et al.  Polycystic ovary syndrome dependency on mtDNA mutation; copy Number and its association with insulin resistance , 2019, BMC research notes.

[24]  K. Khrapko,et al.  Quasi-Mendelian paternal inheritance of mitochondrial DNA: A notorious artifact, or anticipated behavior? , 2019, Proceedings of the National Academy of Sciences.

[25]  Xiawei Wei,et al.  Mitochondrial dysfunction and chronic lung disease , 2019, Cell Biology and Toxicology.

[26]  D. Mari,et al.  Quantitative mitochondrial DNA copy number determination using droplet digital PCR with single-cell resolution , 2019, Genome Research.

[27]  W. Parson,et al.  No further evidence for paternal leakage of mitochondrial DNA in humans yet , 2019, Proceedings of the National Academy of Sciences.

[28]  Y. Chien,et al.  Reply to Lutz-Bonengel et al.: Biparental mtDNA transmission is unlikely to be the result of nuclear mitochondrial DNA segments , 2019, Proceedings of the National Academy of Sciences.

[29]  Y. Chien,et al.  Biparental Inheritance of Mitochondrial DNA in Humans , 2018, Proceedings of the National Academy of Sciences.

[30]  R. Youle,et al.  Molecular and topological reorganizations in mitochondrial architecture interplay during Bax-mediated steps of apoptosis , 2018, bioRxiv.

[31]  A. Oberst,et al.  Mitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis , 2018, The EMBO journal.

[32]  C. Moraes,et al.  The mitochondrial DNA polymerase gamma degrades linear DNA fragments precluding the formation of deletions , 2018, Nature Communications.

[33]  Pedro Rebelo-Guiomar,et al.  Linear mitochondrial DNA is rapidly degraded by components of the replication machinery , 2018, Nature Communications.

[34]  M. Alexeyev,et al.  Elimination of Mitochondrial DNA from Mammalian Cells , 2018, Current protocols in cell biology.

[35]  K. Rogers,et al.  BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis , 2018, Science.

[36]  A. Orekhov,et al.  The role of mitochondrial dysfunction in cardiovascular disease: a brief review , 2018, Annals of medicine.

[37]  F. Prosdocimi,et al.  The heavy strand dilemma of vertebrate mitochondria on genome sequencing age: number of encoded genes or G + T content? , 2018, Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis.

[38]  T. Shioda,et al.  Technical adequacy of bisulfite sequencing and pyrosequencing for detection of mitochondrial DNA methylation: Sources and avoidance of false-positive detection , 2018, PloS one.

[39]  G. Sieck,et al.  Mitochondrial Dysfunction in Airway Disease , 2017, Chest.

[40]  J. Kleinjans,et al.  Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes , 2017, Chemical research in toxicology.

[41]  Jinhang Gao,et al.  Methylation of mitochondrial DNA displacement loop region regulates mitochondrial copy number in colorectal cancer , 2017, Molecular medicine reports.

[42]  Jin Han,et al.  Mitochondrial Nucleoid: Shield and Switch of the Mitochondrial Genome , 2017, Oxidative medicine and cellular longevity.

[43]  S. Saini,et al.  DNA Methyltransferase1 (DNMT1) Isoform3 methylates mitochondrial genome and modulates its biology , 2017, Scientific Reports.

[44]  P. O’Farrell,et al.  The Mitochondrial DNA Polymerase Promotes Elimination of Paternal Mitochondrial Genomes , 2017, Current Biology.

[45]  Rebecca Rojansky,et al.  Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1 , 2016, eLife.

[46]  P. Barboni,et al.  A neurodegenerative perspective on mitochondrial optic neuropathies , 2016, Acta Neuropathologica.

[47]  Stefan J. Siira,et al.  POLRMT regulates the switch between replication primer formation and gene expression of mammalian mtDNA , 2016, Science Advances.

[48]  C. Gustafsson,et al.  Maintenance and Expression of Mammalian Mitochondrial DNA. , 2016, Annual review of biochemistry.

[49]  N. Lax,et al.  Review: Central nervous system involvement in mitochondrial disease , 2016, Neuropathology and applied neurobiology.

[50]  M. Alexeyev,et al.  Correction: Presequence-Independent Mitochondrial Import of DNA Ligase Facilitates Establishment of Cell Lines with Reduced mtDNA Copy Number , 2016, PloS one.

[51]  V. Chouljenko,et al.  Methods for Efficient Elimination of Mitochondrial DNA from Cultured Cells , 2016, PloS one.

[52]  Yu Ding,et al.  Point mutation in mitochondrial tRNA gene is associated with polycystic ovary syndrome and insulin resistance. , 2016, Molecular medicine reports.

[53]  M. Alexeyev,et al.  Presequence-Independent Mitochondrial Import of DNA Ligase Facilitates Establishment of Cell Lines with Reduced mtDNA Copy Number , 2016, PloS one.

[54]  Chunling Ma,et al.  CpG methylation patterns of human mitochondrial DNA , 2016, Scientific Reports.

[55]  G. Wilson,et al.  The “fast” and the “slow” modes of mitochondrial DNA degradation , 2016, Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis.

[56]  A. Picca,et al.  Regulation of mitochondrial biogenesis through TFAM-mitochondrial DNA interactions: Useful insights from aging and calorie restriction studies. , 2015, Mitochondrion.

[57]  M. Alexeyev,et al.  Mitochondrial DNA: A disposable genome? , 2015, Biochimica et biophysica acta.

[58]  Yukichi Tanaka,et al.  Clinical manifestations and enzymatic activities of mitochondrial respiratory chain complexes in Pearson marrow-pancreas syndrome with 3-methylglutaconic aciduria: a case report and literature review , 2015, European Journal of Pediatrics.

[59]  M. Herbert,et al.  Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans , 2015, PLoS genetics.

[60]  Changhan Lee,et al.  The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. , 2015, Cell metabolism.

[61]  William Lee,et al.  Mitochondrial DNA copy number is regulated by DNA methylation and demethylation of POLGA in stem and cancer cells and their differentiated progeny , 2015, Cell Death and Disease.

[62]  D. Temiakov,et al.  Replication-transcription switch in human mitochondria , 2015, Science.

[63]  R. Means,et al.  Mitochondrial DNA Stress Primes the Antiviral Innate Immune Response , 2014, Nature.

[64]  Matthew E. Ritchie,et al.  Apoptotic Caspases Suppress mtDNA-Induced STING-Mediated Type I IFN Production , 2014, Cell.

[65]  T. Taniguchi,et al.  Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA , 2014, Cell.

[66]  X. Cui,et al.  Autophagy and ubiquitin-mediated proteolysis may not be involved in the degradation of spermatozoon mitochondria in mouse and porcine early embryos , 2014, Zygote.

[67]  C. Fabian,et al.  Mitochondrial DNA Aberrations and Pathophysiological Implications in Hematopoietic Diseases, Chronic Inflammatory Diseases, and Cancers , 2014, Annals of laboratory medicine.

[68]  C. Gustafsson,et al.  In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication , 2014, PLoS genetics.

[69]  G. Wilson,et al.  Aging: A mitochondrial DNA perspective, critical analysis and an update. , 2014, World journal of experimental medicine.

[70]  Bin Tean Teh,et al.  Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer , 2014, eLife.

[71]  C. Dalgård,et al.  Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly , 2014, Human Genetics.

[72]  C. Dalgård,et al.  Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly , 2014, Human Genetics.

[73]  G. Lemesle,et al.  Circulating Long Noncoding RNA, LIPCAR, Predicts Survival in Patients With Heart Failure , 2014, Circulation research.

[74]  F. Santorelli,et al.  Syndromes associated with mitochondrial DNA depletion , 2014, Italian Journal of Pediatrics.

[75]  M. Beekman,et al.  Low mitochondrial DNA content associates with familial longevity: the Leiden Longevity Study , 2014, AGE.

[76]  Scott R. Kennedy,et al.  Oxidative Stress Is Not a Major Contributor to Somatic Mitochondrial DNA Mutations , 2014, PLoS genetics.

[77]  R. Phillips,et al.  Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation , 2014, Nature Communications.

[78]  Scott R. Kennedy,et al.  Ultra-Sensitive Sequencing Reveals an Age-Related Increase in Somatic Mitochondrial Mutations That Are Inconsistent with Oxidative Damage , 2013, PLoS genetics.

[79]  Marcos T. Oliveira,et al.  Replicating animal mitochondrial DNA , 2013, Genetics and molecular biology.

[80]  B. Wold,et al.  Genome-Wide Analysis Reveals Coating of the Mitochondrial Genome by TFAM , 2013, PloS one.

[81]  G. Wilson,et al.  Mitochondrial DNA Ligase Is Dispensable for the Viability of Cultured Cells but Essential for mtDNA Maintenance* , 2013, The Journal of Biological Chemistry.

[82]  Zhenbo Wang,et al.  Unique insights into maternal mitochondrial inheritance in mice , 2013, Proceedings of the National Academy of Sciences.

[83]  G. Wilson,et al.  Persistent damage induces mitochondrial DNA degradation. , 2013, DNA repair.

[84]  Vincenzo Riso,et al.  The Control Region of Mitochondrial DNA Shows an Unusual CpG and Non-CpG Methylation Pattern , 2013, DNA research : an international journal for rapid publication of reports on genes and genomes.

[85]  J. Finsterer,et al.  Adult Mitochondrial DNA Depletion Syndrome with Mild Manifestations , 2013, Neurology international.

[86]  S. Ledoux,et al.  The maintenance of mitochondrial DNA integrity--critical analysis and update. , 2013, Cold Spring Harbor perspectives in biology.

[87]  Marcela Dávila López,et al.  MTERF1 binds mtDNA to prevent transcriptional interference at the light-strand promoter but is dispensable for rRNA gene transcription regulation. , 2013, Cell metabolism.

[88]  H. Côté,et al.  Decreased skeletal muscle mitochondrial DNA in patients with statin-induced myopathy , 2013, Journal of the Neurological Sciences.

[89]  K. Kollewe,et al.  Mitofusin 2 mutations affect mitochondrial function by mitochondrial DNA depletion , 2013, Acta Neuropathologica.

[90]  T. Tanimura,et al.  Effects of overexpression of mitochondrial transcription factor A on lifespan and oxidative stress response in Drosophila melanogaster. , 2013, Biochemical and biophysical research communications.

[91]  D. Temiakov,et al.  Phosphorylation of human TFAM in mitochondria impairs DNA binding and promotes degradation by the AAA+ Lon protease. , 2013, Molecular cell.

[92]  Inn-Chi Lee,et al.  Mitochondrial Depletion Causes Neonatal-Onset Leigh Syndrome, Myopathy, and Renal Tubulopathy , 2013, Journal of child neurology.

[93]  H. Manev,et al.  Effect of aging on 5-hydroxymethylcytosine in brain mitochondria , 2012, Neurobiology of Aging.

[94]  F. Tort,et al.  Mitochondrial DNA depletion syndrome: new descriptions and the use of citrate synthase as a helpful tool to better characterise the patients. , 2012, Molecular genetics and metabolism.

[95]  D. Bogenhagen Mitochondrial DNA nucleoid structure. , 2012, Biochimica et biophysica acta.

[96]  R. Kasiviswanathan,et al.  The interface of transcription and DNA replication in the mitochondria. , 2012, Biochimica et biophysica acta.

[97]  J. Kolesar,et al.  Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number. , 2012, Biochimica et biophysica acta.

[98]  L. Almasy,et al.  Sex-Specific Regulation of Mitochondrial DNA Levels: Genome-Wide Linkage Analysis to Identify Quantitative Trait Loci , 2012, PloS one.

[99]  B. Van Houten,et al.  Oxidants and not alkylating agents induce rapid mtDNA loss and mitochondrial dysfunction. , 2012, DNA repair.

[100]  E. López-Collazo,et al.  Circulating cell-free mitochondrial DNA: a better early prognostic marker in patients with out-of-hospital cardiac arrest. , 2012, Resuscitation.

[101]  Cheng-Hsien Lu,et al.  Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room , 2012, Journal of Translational Medicine.

[102]  M. S. Gabriel,et al.  Influence of microsurgical varicocelectomy on human sperm mitochondrial DNA copy number: a pilot study , 2012, Journal of Assisted Reproduction and Genetics.

[103]  J. Arnold,et al.  Transcription from the second heavy-strand promoter of human mtDNA is repressed by transcription factor A in vitro , 2012, Proceedings of the National Academy of Sciences.

[104]  P. Chinnery,et al.  MFN2 mutations cause compensatory mitochondrial DNA proliferation , 2012, Brain : a journal of neurology.

[105]  V. Tiranti,et al.  Transcriptional requirements of the distal heavy-strand promoter of mtDNA , 2012, Proceedings of the National Academy of Sciences.

[106]  P. O’Farrell,et al.  Barriers to male transmission of mitochondrial DNA in sperm development. , 2012, Developmental cell.

[107]  E. Peterman,et al.  Protein sliding and DNA denaturation are essential for DNA organization by human mitochondrial transcription factor A , 2012, Nature Communications.

[108]  J. Mattick,et al.  Long noncoding RNAs are generated from the mitochondrial genome and regulated by nuclear-encoded proteins. , 2011, RNA.

[109]  E. Culetto,et al.  Postfertilization Autophagy of Sperm Organelles Prevents Paternal Mitochondrial DNA Transmission , 2011, Science.

[110]  Harald F Hess,et al.  Superresolution Fluorescence Imaging of Mitochondrial Nucleoids Reveals Their Spatial Range, Limits, and Membrane Interaction , 2011, Molecular and Cellular Biology.

[111]  Tim R. Mercer,et al.  The Human Mitochondrial Transcriptome , 2011, Cell.

[112]  S. Jakobs,et al.  Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA , 2011, Proceedings of the National Academy of Sciences.

[113]  A. Ohtake,et al.  Fatal case of mitochondrial DNA depletion with severe asphyxia in a newborn , 2011, Pediatrics international : official journal of the Japan Pediatric Society.

[114]  Shirley M. Taylor,et al.  DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria , 2011, Proceedings of the National Academy of Sciences.

[115]  M. Schuelke,et al.  Regionalized Pathology Correlates with Augmentation of mtDNA Copy Numbers in a Patient with Myoclonic Epilepsy with Ragged-Red Fibers (MERRF-Syndrome) , 2010, PloS one.

[116]  W. Junger,et al.  Circulating Mitochondrial DAMPs Cause Inflammatory Responses to Injury , 2009, Nature.

[117]  H. Erdjument-Bromage,et al.  MTERF2 is a nucleoid component in mammalian mitochondria. , 2009, Biochimica et biophysica acta.

[118]  N. Venediktova,et al.  Oxidative stress induces degradation of mitochondrial DNA , 2009, Nucleic acids research.

[119]  E. Schon,et al.  Mitochondrial nucleoids maintain genetic autonomy but allow for functional complementation , 2008, The Journal of cell biology.

[120]  Justin L Cotney,et al.  Relative abundance of the human mitochondrial transcription system and distinct roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expression , 2007, Nucleic acids research.

[121]  H. Jacobs,et al.  Replication of vertebrate mitochondrial DNA entails transient ribonucleotide incorporation throughout the lagging strand , 2006, The EMBO journal.

[122]  Hirohisa Tajima,et al.  Neuronal cell death in Alzheimer's disease and a neuroprotective factor, humanin. , 2006, Current neuropharmacology.

[123]  J. Griffith,et al.  Termination Factor-Mediated DNA Loop between Termination and Initiation Sites Drives Mitochondrial rRNA Synthesis , 2005, Cell.

[124]  H. Jacobs,et al.  Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[125]  T. D. Pugh,et al.  Mitochondrial DNA Mutations, Oxidative Stress, and Apoptosis in Mammalian Aging , 2005, Science.

[126]  N. Hamasaki,et al.  Architectural Role of Mitochondrial Transcription Factor A in Maintenance of Human Mitochondrial DNA , 2004, Molecular and Cellular Biology.

[127]  Xiaoxiang Hu,et al.  Further evidence for paternal inheritance of mitochondrial DNA in the sheep (Ovis aries) , 2004, Heredity.

[128]  Y. Matsushima,et al.  Drosophila Mitochondrial Transcription Factor B2 Regulates Mitochondrial DNA Copy Number and Transcription in Schneider Cells* , 2004, Journal of Biological Chemistry.

[129]  Kjell Hultenby,et al.  Mitochondrial transcription factor A regulates mtDNA copy number in mammals. , 2004, Human molecular genetics.

[130]  M. Schwartz,et al.  New patterns of inheritance in mitochondrial disease. , 2003, Biochemical and biophysical research communications.

[131]  Pinchas Cohen,et al.  Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[132]  Y. Matsuda,et al.  Functional Domains of Chicken Mitochondrial Transcription Factor A for the Maintenance of Mitochondrial DNA Copy Number in Lymphoma Cell Line DT40* , 2003, Journal of Biological Chemistry.

[133]  N. Hamasaki,et al.  Human mitochondrial DNA is packaged with TFAM. , 2003, Nucleic acids research.

[134]  A. Hall,et al.  Mismatch repair activity in mammalian mitochondria. , 2003, Nucleic acids research.

[135]  P. Heckerling Paternal inheritance of mitochondrial DNA. , 2002 .

[136]  M. Brand,et al.  Topology of Superoxide Production from Different Sites in the Mitochondrial Electron Transport Chain* , 2002, The Journal of Biological Chemistry.

[137]  G. Shadel,et al.  Modulation of mitochondrial transcription in response to mtDNA depletion and repletion in HeLa cells. , 2002, Nucleic acids research.

[138]  V. Bohr,et al.  Repair of 8-oxoG is slower in endogenous nuclear genes than in mitochondrial DNA and is without strand bias. , 2002, DNA repair.

[139]  G. Sobue,et al.  A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[140]  P Barrière,et al.  Mitochondrial DNA content affects the fertilizability of human oocytes. , 2001, Molecular human reproduction.

[141]  P. Dedon,et al.  Cu(II)/H2O2-induced DNA damage is enhanced by packaging of DNA as a nucleosome. , 2001, Chemical research in toxicology.

[142]  J. Mott,et al.  Oxidative stress is not an obligate mediator of disease provoked by mitochondrial DNA mutations. , 2001, Mutation research.

[143]  H. Nohl,et al.  Are mitochondria a permanent source of reactive oxygen species? , 2000, Biochimica et biophysica acta.

[144]  D. Clayton Transcription and replication of mitochondrial DNA. , 2000, Human reproduction.

[145]  M. Ng,et al.  Presence of mitochondrial tRNA Leu(UUR) A to G 3243 mutation in DNA extracted from serum and plasma of patients with type 2 diabetes mellitus , 2000, Journal of clinical pathology.

[146]  H. Nohl,et al.  H(2)O(2) detection from intact mitochondria as a measure for one-electron reduction of dioxygen requires a non-invasive assay system. , 1999, Biochimica et biophysica acta.

[147]  X. Shi,et al.  Effects of Ni(II) and Cu(II) on DNA interaction with the N-terminal sequence of human protamine P2: enhancement of binding and mediation of oxidative DNA strand scission and base damage. , 1999, Carcinogenesis.

[148]  J. Boore Animal mitochondrial genomes. , 1999, Nucleic acids research.

[149]  U. Lakshmipathy,et al.  Double strand break rejoining by mammalian mitochondrial extracts. , 1999, Nucleic acids research.

[150]  S. Dimauro,et al.  Mitochondrial DNA depletion in a patient with long survival , 1998, Neurology.

[151]  V. Mildažienė,et al.  Dependence of H2O2 Formation by Rat Heart Mitochondria on Substrate Availability and Donor Age , 1997, Journal of bioenergetics and biomembranes.

[152]  R. Floyd,et al.  Preferential targeting of oxidative base damage to internucleosomal DNA. , 1996, Carcinogenesis.

[153]  D. Wallace,et al.  Mitochondrial DNA sequence variation in human evolution and disease. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[154]  D. Wallace,et al.  Mitochondrial genetics: principles and practice. , 1992, American journal of human genetics.

[155]  Robert P. Hebbel,et al.  Nucleosomal histone protein protects DNA from iron-mediated damage , 1992, Nucleic Acids Res..

[156]  J. Schaper,et al.  Ultrastructural quantitation of mitochondria and myofilaments in cardiac muscle from 10 different animal species including man. , 1992, Journal of molecular and cellular cardiology.

[157]  A. Wilson,et al.  Paternal inheritance of mitochondrial DNA in mice , 1991, Nature.

[158]  D. Wallace,et al.  Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. , 1988, Science.

[159]  D. A. Clayton,et al.  Purification and characterization of human mitochondrial transcription factor 1 , 1988, Molecular and cellular biology.

[160]  G. Ponsot,et al.  KEARNS-SAYRE SYNDROME WITH MUSCLE MITOCHONDRIAL DNA DELETION , 1988, The Lancet.

[161]  A. Harding,et al.  Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies , 1988, Nature.

[162]  P. Cullis,et al.  Electron transfer from protein to DNA in irradiated chromatin , 1987, Nature.

[163]  D. A. Clayton,et al.  Precise assignment of the light-strand promoter of mouse mitochondrial DNA: a functional promoter consists of multiple upstream domains , 1986, Molecular and cellular biology.

[164]  M. Szyf,et al.  Methylation pattern of mouse mitochondrial DNA. , 1984, Nucleic acids research.

[165]  J. Miquel,et al.  Role of metabolic rate and DNA-repair in Drosophila aging: Implications for the Mitochondrial Mutation Theory of Aging , 1983, Experimental Gerontology.

[166]  J. Montoya,et al.  The pattern of transcription of the human mitochondrial rRNA genes reveals two overlapping transcription units , 1983, Cell.

[167]  M. Rabinowitz,et al.  Identification of initiation sites for heavy-strand and light-strand transcription in human mitochondrial DNA. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[168]  D. A. Clayton,et al.  Replication of animal mitochondrial DNA , 1982, Cell.

[169]  D. A. Clayton,et al.  Sequence and gene organization of mouse mitochondrial DNA , 1981, Cell.

[170]  G. Attardi,et al.  Synthesis and turnover of mitochondrial ribonucleic acid in HeLa cells: the mature ribosomal and messenger ribonucleic acid species are metabolically unstable , 1981, Molecular and cellular biology.

[171]  F. Sanger,et al.  Sequence and organization of the human mitochondrial genome , 1981, Nature.

[172]  Julio Montoya,et al.  tRNA punctuation model of RNA processing in human mitochondria , 1981, Nature.

[173]  J. Johnson,et al.  Mitochondrial role in cell aging , 1980, Experimental Gerontology.

[174]  B Chance,et al.  The cellular production of hydrogen peroxide. , 1972, The Biochemical journal.

[175]  R. Wells,et al.  Buoyant density studies on natural and synthetic deoxyribonucleic acids in neutral and alkaline solutions. , 1972, The Journal of biological chemistry.

[176]  Denham Harman,et al.  The Biologic Clock: The Mitochondria? , 1972, Journal of the American Geriatrics Society.

[177]  M. M. Nass,et al.  INTRAMITOCHONDRIAL FIBERS WITH DNA CHARACTERISTICS: I. Fixation and Electron Staining Reactions , 1963 .

[178]  D. Harman Aging: a theory based on free radical and radiation chemistry. , 1956, Journal of gerontology.

[179]  Denham. Harraan AGING: A THEORY BASED ON FREE RADICAL AND RADIATION CHEMISTRY , 1955 .

[180]  W. Copeland,et al.  DNA polymerases in the mitochondria: A critical review of the evidence. , 2017, Frontiers in bioscience.

[181]  M. Koenig,et al.  Mitochondrial cardiomyopathy: pathophysiology, diagnosis, and management. , 2013, Texas Heart Institute journal.

[182]  R. Wiesner,et al.  Transient overexpression of mitochondrial transcription factor A (TFAM) is sufficient to stimulate mitochondrial DNA transcription, but not sufficient to increase mtDNA copy number in cultured cells. , 2004, Nucleic acids research.

[183]  D. George Approaches to diagnosis and treatment. , 2001, The Veterinary record.

[184]  P. Hanawalt,et al.  Efficient protection against oxidative DNA damage in chromatin , 1992, Molecular carcinogenesis.

[185]  D. Clayton Transcription of the mammalian mitochondrial genome. , 1984, Annual review of biochemistry.

[186]  J. Miquel,et al.  Is cell aging caused by respiration-dependent injury to the mitochondrial genome? , 1982, Gerontology.