1. HarmanD (1956) Aging: A theory based on free radical and radiation chemistry. J Gerontol 11: 298–300.
2. HarmanD (1972) The biological clock: The mitochondria? J Am Geriatr Soc 20: 145–147.
3. WallaceDC (1999) Mitochondrial diseases in man and mouse. Science 283: 1482–1488.
4. TaylorRW, TurnbullDM (2005) Mitochondrial DNA mutations in human disease. Nat Rev Genet 6: 389–402.
5. ShortKR, BigelowML, KahlJ, SinghR, Coenen-SchimkeJ, et al. (2005) Decline in skeletal muscle mitochondrial function with aging in humans. Proc Nat Acad Sci U S A 102: 5618–5623.
6. GreavesLC, BarronMJ, Campbell-ShielG, KirkwoodTBL, TurnbullDM (2011) Differences in the accumulation of mitochondrial defects with age in mice and humans. Mech Ageing Devel 132: 588–591.
7. CaoZ, WanagatJ, McKiernanSH, AikenJM (2001) Mitochondrial DNA deletion mutations are concomitant with ragged red regions of individual, aged muscle fibers: analysis by laser-capture microdissection. Nuc Acid Res 29: 4502–4508.
8. HsiehR, HouJ, HsuH, WeiW (1994) Age-dependent respiratory function decline and DNA deletions in human muscle mitochondria. Biochem Mol Biol Int 32: 1009–1022.
9. KraytsbergY, KudryavtsevaE, McKeeAC, GeulaC, KowallNW, et al. (2006) Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat Genetics 38: 518–520.
10. LezzaA, BoffoliD, CantatoreP, GadaletaM (1994) Correlation between mitochondrial DNA 4977-bp deletion and respiratory chain enzyme activities in aging human skeletal muscles. Biochem Bioph Res Co 205: 772–779.
11. Corral-DebrinskiM, HortonT, LottMT, ShoffnerJM, BealMF, et al. (1992) Mitochondrial DNA deletions in human brain: Regional variability and increase with advanced age. Nat Genetics 2: 324–329.
12. MohamedSA, HankeT, ErasmiAW, BechtelMJF, ScharfschwerdtM, et al. (2006) Mitochondrial DNA deletions and the aging heart. Exp Gerontol 41: 508–517.
13. BenderA, KrishnanKJ, MorrisCM, TaylorGA, ReeveAK, et al. (2006) High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genetics 38: 515–517.
14. GuG, ReyesPF, GoldenGT, WoltjerRL, HuletteC, et al. (2002) Mitochondrial DNA deletions/rearrangements in parkinson disease and related neurodegenerative disorders. J Neuropath Exp Neurol 61: 634–639.
15. Corral-DebrinskiM, HortonT, LottMT, ShoffnerJM, McKeeAC, et al. (1994) Marked changes in mitochondrial DNA deletion levels in Alzheimer brains. Genomics 23: 471–476.
16. KasaiH, NishimuraS (1984) Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents. Nuc Acid Res 12: 2137–2145.
17. FragaCG, ShigenagaMK, ParkJ-W, DeganP, AmesBN (1990) Oxidative damage to DNA during aging: 8-Hydroxy-2′-deoxyguanosine in rat organ DNA and urine. Proc Nat Acad Sci U S A 87: 4533–4537.
18. MecocciP, MacGarveyU, KaufmanAE, KoontzD, ShoffnerJM, et al. (1993) Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann Neurol 34: 609–616.
19. AsuncionJGdl, MillanA, PlaR, BruseghiniL, EsterasA, et al. (1996) Mitochondrial glutathione oxidation correlates with age-associated oxidative damage to mitochondrial DNA. FASEB J 10: 333–338.
20. BarjaG, HerreroA (2000) Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals. FASEB J 14: 312–318.
21. EdgarD, ShabalinaI, CamaraY, WredenbergA, CalvarusoMA, et al. (2009) Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice. Cell Metab 10: 131–138.
22. VermulstM, BielasJH, KujothGC, LadigesWC, RabinovitchPS, et al. (2007) Mitochondrial point mutations do not limit the natural lifespan of mice. Nat Genetics 39: 540–543.
23. LinMT, Cantuti-CastelvetriI, ZhengK, JacksonKE, TanYB, et al. (2012) Somatic mitochondrial DNA mutations in early Parkinson and incidental Lewy Body Disease. Ann Neurol 71: 850–854.
24. LinMT, SimonDK, AhnCH, KimLM, BealMF (2002) High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain. Hum Mol Genet 11: 133–145.
25. NekhaevaE, BodyakND, KraytsbergY, McGrathSB, OrsouwNJV, et al. (2002) Clonally expanded mtDNA point mutations are abundant in individual cells of human tissues. Proc Nat Acad Sci U S A 99: 5521–5526.
26. MichikawaY, MazzucchelliF, BresolinN, ScarlatoG, AttardiG (1999) Mutations in the human mtDNA control region for replication. Science 286: 774–779.
27. LoebLA (2011) Human cancers express mutator phenotypes: Origin, consequences and targeting. Nat Rev Cancer 11: 450–457.
28. SalkJJ, FoxEJ, LoebLA (2010) Mutational heterogeneity in human cancers: Origin and consequences. Annu Rev Pathol-Mech 5: 51–75.
29. VermulstM, BielasJH, LoebLA (2008) Quantification of random mutations in the mitochondrial genome. Methods 46: 263–268.
30. MarcelinoLA, ThillyWG (1999) Mitochondrial mutagenesis in human cells and tissues. Mutat Res 434: 177–203.
31. HarismendyO, NgPC, StrausbergRL, WangX, StockwellTB, et al. (2009) Evaluation of next generation sequencing platforms for population targeted sequencing studies. Genome Biol 10: R32.
32. SchmittMW, KennedySR, SalkJJ, FoxEJ, HiattJB, et al. (2012) Detection of ultra-rare mutations by next-generation sequencing. Proc Nat Acad Sci U S A 109: 14508–14513.
33. MarinhoANdR, MoraesMRd, SantosS, Ribeiro-dos-SantosÂ (2011) Human aging and somatic point mutations in mtDNA: A comparative study of generational differences (grandparents and grandchildren). Genet Mol Biol 34: 31–34.
34. HeY, WuJ, DressmanDC, Iacobuzio-DonahueC, MarkowitzSD, et al. (2010) Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature 464: 610–614.
35. DuncanBK, MillerJH (1980) Mutagenic deamination of cytosine residues in DNA. Nature 287: 560–561.
36. SpelbrinkJN, ToivonenJM, HakkaartGAJ, KurkelaJM, CooperHM, et al. (2000) In vivo functional analysis of the human mitochondrial DNA polymerase POLG expressed in cultured human cells. J Biol Chem 275: 24818–24828.
37. NordmannPL, MakrisJC, ReznikoffWS (1988) Inosine induced mutations. Mol Gen Genet 214: 62–67.
38. SongS, PursellZF, CopelandWC, LongleyMJ, KunkelTA, et al. (2005) DNA precursor asymmetries in mammalian tissue mitochondria and possible contribution to mutagenesis through reduced replication fidelity. Proc Nat Acad Sci U S A 102: 4990–4995.
39. LongleyMJ, NguyenD, KunkelTA, CopelandWC (2001) The fidelity of human DNA polymerase γ with and without exonucleolytic proofreading and the p55 accessory subunit. J Biol Chem 276: 38555–38562.
40. ZhengW, KhrapkoK, CollerHA, ThillyWG, CopelandWC (2006) Origins of human mitochondrial point mutations as DNA polymerase γ-mediated errors. Mutat Res-Fundamental and Molecular Mechanisms of Mutagenesis 599: 11–20.
41. MecocciP, MacGarveyU, BealMF (1994) Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease. Ann Neurol 36: 747–751.
42. ChengKC, CahillDS, KasaisH, NishimurasS, LoebLA (1992) 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G→T and A→C substitutions. J Biol Chem 267: 166–172.
43. BeckmanKB, AmesBN (1998) The free radical theory of aging matures. Physiol Rev 78: 547–581.
44. KirkwoodTBL, KowaldA (2012) The free-radical theory of ageing-older, wiser and still alive. Bioessays 34: 692–700.
45. LiB, KrishnanVG, MortME, XinF, KamatiKK, et al. (2009) Automated inference of molecular mechanisms of disease from amino acid substitutions. Bioinformatics 25: 2744–2750.
46. GreavesLC, ElsonJL, NooteboomM, GradyJP, TaylorGA, et al. (2012) Comparison of mitochondrial mutation spectra in ageing human colonic epithelium and disease: Absence of evidence for purifying selection in somatic mitochondrial DNA point mutations. Plos Genet 8: e10003082.
47. GaltierN, EnardD, RadondyY, BazinE, BelkhirK (2006) Mutation hot spots in mammalian mitochondrial DNA. Genome Res 16: 215–222.
48. MeyerS, WeissG, HaeselerAv (1999) Pattern of nucleotide substitution and rate heterogeneity in the hypervariable regions I and II of human mtDNA. Genetics 152: 1103–1110.
49. WakeleyJ (1993) Substitution rate variation among sites in hypervariable region 1 of human mitochondrial DNA. J Mol Evol 37: 613–623.
50. ReyesA, GissiC, PesoleG, SacconeC (1998) Asymmetrical directional mutation pressure in the mitochondrial genome of mammals. Mol Biol Evol 15: 957–966.
51. BelleEMS, PiganeauG, GardnerM, Eyre-WalkerA (2005) An investigation of the variation in the transition bias among various animal mitochondrial DNA. Gene 355: 58–66.
52. TanakaM, OzawaT (1994) Strand asymmetry in human mitochondrial DNA mutations. Genomics 22: 327–335.
53. XiaX (2012) DNA replication and strand asymmetry in prokaryotic and mitochondrial genomes. Curr Genomics 13: 16–27.
54. KennedySR, LoebLA, HerrAJ (2012) Somatic mutations in aging, cancer and neurodegeneration. Mech Ageing Dev 133: 118–126.
55. CookeMS, EvansMD, DizdarogluM, LunecJ (2003) Oxidative DNA damage: mechanisms, mutation, and disease. FaSEB J 17: 1195–1214.
56. MarnettLJ (2000) Oxyradicals and DNA damage. Carcinogenesis 21: 361–370.
57. AmeurA, StewartJB, FreyerC, HagströmE, IngmanM, et al. (2011) Ultra-deep sequencing of mouse mitochondrial DNA: Mutational patterns and their origins. Plos Genet 7: e1002028.
58. HalsneR, EsbensenY, WangW, SchefflerK, SuganthanR, et al. (2012) Lack of the DNA glycosylases MYH and OGG1 in the cancer prone double mutant mouse does not increase mitochondrial DNA mutagenesis. DNA Repair 11: 278–285.
59. Ruiz-PesiniE, LottMT, ProcaccioV, PooleJC, BrandonMC, et al. (2007) An enhanced MITOMAP with a global mtDNA mutational phylogeny. Nuc Acids Res 35: D823–D828.
60. KocherTD, ThomasWK, MeyerA, EdwardsSV, PååboS, et al. (1989) Dynamics of mitochondrial DNA evolution in animals: amplification and sequencing with conserved primers. Proc Nat Acad Sci U S A 86: 6196–6200.
61. BasuAK, LoechlerEL, LeadonSA, EssigmannJM (1989) Genetic effects of thymine glycol: Site-specific mutagenesis and molecular modeling studies. Proc Nat Acad Sci U S A 86: 7677–7681.
62. KreutzerDA, EssigmannJM (1998) Oxidized, deaminated cytosines are a source of C→T transitions in vivo. Proc Nat Acad Sci U S A 95: 3578–3582.
63. Souz-PintoNC, CroteauDL, HudsonEK, HansfordRG, BohrVA (1999) Age-associated increase in 8-oxo-deoxyguanosine glycosylase/AP lyase activity in rat mitochondria. Nuc Acid Res 27: 1935–1942.
64. FurdaAM, MarrangoniAM, LokshinA, HoutenBV (2012) Oxidants and not alkylating agents induce rapid mtDNA loss and mitochondrial dysfunction. DNA Repair 11: 684–692.
65. YangYX, MuqitMMK, LatchmanDS (2006) Induction of parkin expression in the presence of oxidative stress. Eur J Neurosci 24: 1366–1372.
66. HanesJW, ThalDM, JohnsonKA (2006) Incorporation and replication of 8-oxo-deoxyguanosine by the human mitochondrial DNA polymerase. J Biol Chem 281: 36241–36248.
67. BrownTA, CecconiC, TkachukAN, BustamanteC, ClaytonDA (2005) Replication of mitochondrial DNA occurs by strand displacement with alternative light-strand origins, not via a strand-coupled mechanism. Genes Dev 19: 2466–2476.
68. ClaytonDA (1982) Replication of animal mitochondrial DNA. Cell 28: 693–705.
69. FredericoLA, KunkelTA, ShawBR (1990) A sensitive genetic assay for the detection of cytosine deamination: Determination of rate constants and the activation energy. Biochemistry 29: 2532–2537.
70. LiH, DurbinR (2009) Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25: 1754–1760.