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Repair of mitochondrial DNA in aging and carcinogenesis

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Abstract

Mitochondria are responsible for the generation of energy in the form of adenosine triphosphate. These organelles contain their own genetic material, mitochondrial (mt) DNA. This mtDNA has been hypothesized to play a role in the processes of aging and carcinogenesis. Initial reports have shown that there is no repair of cyclobutylpyrimidine dimers (CPD). More recent reports indicate however, that the mitochondrion contains several defence mechanisms against endogenous or exogenous damaging agents such as ultraviolet radiation or oxidative damage. The role of these defence mechanisms in the removal of mitochondrial DNA damage and the link to aging and carcinogenesis-associated processes are discussed in this review.

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Abbreviations

BER:

base excision repair

DSBR:

double strand break repair

HR:

homologous recombination

MMR:

mismatch repair

NHEJ:

non homologous end joining

References

  1. K. B. Beckman, B. N. Ames, Oxidative decay of DNA, J. Biol. Chem., 1997, 272, 19633–19636.

    Article  CAS  PubMed  Google Scholar 

  2. Y. H. Wei, H. C. Lee, Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging, Exp. Biol. Med., 2002, 227, 671–682.

    Article  CAS  Google Scholar 

  3. D. Kang, N. Hamasaki, Mitochondrial oxidative stress and mitochondrial DNA, Clin. Chem. Lab. Med., 2003, 41, 1281–1288.

    Article  CAS  PubMed  Google Scholar 

  4. D. F. Bogenhagen, Repair of mtDNA in vertebrates, Am. J. Hum. Genet., 1999, 64, 1276–1281.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. M. S. Cooke, M. D. Evans, M. Dizdaroglu, J. Lunec, Oxidative DNA damage: mechanisms, mutation, and disease, FASEB J., 2003, 17, 1195–1214.

    Article  CAS  PubMed  Google Scholar 

  6. S. Papa, Mitochondrial oxidative phosphorylation changes in the life span, Biochim. Biophys. Acta, 1996, 1276, 87–105.

    Article  PubMed  Google Scholar 

  7. I. Fridovich, Mitochondria: are they the seat of senescence?, Aging Cell, 2004, 3, 1, 13–16.

    Article  CAS  PubMed  Google Scholar 

  8. M. Valko, M. Izakovic, M. Mazur, C. J. Rhodes, J. Telser, Role of oxygen radicals in DNA damage and cancer incidence, Mol. Cell. Biochem., 2004, 266, 37–56.

    Article  CAS  PubMed  Google Scholar 

  9. A. P. Grollman, M. Moriya, Mutagenesis by 8-oxoguanine: an enemy within, Trends Genet., 1993, 9, 246–249.

    Article  CAS  PubMed  Google Scholar 

  10. S. S. Wallace, Biological consequences of free radical-damaged DNA bases, Free Radical Biol. Med., 2002, 33, 1–14.

    Article  CAS  Google Scholar 

  11. A. K. Basu, E. L. Loechler, S. A. Leadon, J. M. Essigmann, Genetic effects of thymine glycol: site-specific mutagenesis and molecular modeling studies, Proc. Natl. Acad. Sci. USA, 1989, 86, 7677–7681.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. N. B. Larsen, M. Rasmussen, L. J. Rasmussen, Nuclear and mitochondrial DNA repair: similar pathways?, Mitochondrion, 2005, 5, 89–108.

    Article  CAS  PubMed  Google Scholar 

  13. M. J. Jou, S. B. Jou, M. J. Guo, H. Y. Wu, T. I. Peng, Mitochondrial reactive oxygen species generation and calcium increase induced by visible light in astrocytes, Ann. N. Y. Acad. Sci., 2004, 1011, 45–56.

    Article  CAS  PubMed  Google Scholar 

  14. A. King, E. Gottlieb, D. G. Brooks, M. P. Murphy, J. L. Dunaief, Mitochondria-derived reactive oxygen species mediate if blue light-induced death of retinal pigment epithelial cells, Photochem. Photobiol., 2004, 79, 470–475.

    Article  CAS  PubMed  Google Scholar 

  15. U. K. Tirlapur, K. Konig, C. Peuckert, R. Krieg, K. J. Halbhuber, Femtosecond near-infrared laser pulses elicit generation of reactive oxygen species in mammalian cells leading to apoptosis-like death, Exp. Cell Res., 2001, 263, 88–97.

    Article  CAS  PubMed  Google Scholar 

  16. A. A. Krasnovsky, N. N. Drozdova, A. V. Ivanov, R. V. Ambartsumian, Activation of molecular oxygen by infrared laser radiation in pigment-free aerobic systems, Biochemistry (Moscow), 2003, 68, 963–966.

    Article  CAS  Google Scholar 

  17. C. Richter, Oxidative damage to mitochondrial DNA and its relationship to ageing, Int. J. Biochem. Cell Biol., 1995, 27, 647–653.

    Article  CAS  PubMed  Google Scholar 

  18. R. M. Anson, E. Hudson, V. A. Bohr, Mitochondrial endogenous oxidative damage has been overestimated, FASEB J., 2000, 14, 355–360.

    Article  CAS  PubMed  Google Scholar 

  19. R. M. Anson, S. Senturker, M. Dizdaroglu, V. A. Bohr, Measurement of oxidatively induced base lesions in liver from Wistar rats of different ages, Free Radical Biol. Med., 1999, 27, 456–462.

    Article  CAS  Google Scholar 

  20. R. G. Boles, T. Roe, D. Senadheera, V. Mahnovski, L. J. C. Wong, Mitochondrial DNA deletion with Kearns Sayre syndrome in a child with Addison disease, Eur. J. Pediatrics, 1998, 157, 643–647.

    Article  CAS  Google Scholar 

  21. M. Berneburg, H. Plettenberg, J. Krutmann, Photoaging of human skin, Photodermatol. Photoimmunol. Photomed., 2000, 16, 239–244.

    Article  CAS  PubMed  Google Scholar 

  22. C. Y. Pang, H. C. Lee, J. H. Yang, Y. H. Wei, Human skin mitochondrial DNA deletions associated with light exposure, Arch. Biochem. Biophys., 1994, 312, 534–538.

    Article  CAS  PubMed  Google Scholar 

  23. M. Berneburg, N. Gattermann, H. Stege, M. Grewe, K. Vogelsang, T. Ruzicka, J. Krutmann, Chronically ultraviolet-exposed human skin shows a higher mutation frequency of mitochondrial DNA as compared to unexposed skin and the hematopoietic system, Photochem. Photobiol., 1997, 66, 271–275.

    Article  CAS  PubMed  Google Scholar 

  24. M. Berneburg, S. Grether-Beck, V. Kurten, T. Ruzicka, K. Briviba, H. Sies, J. Krutmann, Singlet oxygen mediates the UVA-induced generation of the photoaging-associated mitochondrial common deletion, J. Biol. Chem., 1999, 274, 15345–15349.

    Article  CAS  PubMed  Google Scholar 

  25. J. H. Yang, H. C. Lee, K. J. Lin, Y. H. Wei, A specific 4977-bp deletion of mitochondrial DNA in human ageing skin, Arch. Dermatol. Res., 1994, 286, 386–390.

    Article  CAS  PubMed  Google Scholar 

  26. D. A. Clayton, J. N. Doda, E. C. Friedberg, The absence of a pyrimidine dimer repair mechanism in mammalian mitochondria, Proc. Natl. Acad. Sci. USA, 1974, 71, 2777–2781.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. K. Nishioka, T. Ohtsubo, H. Oda, T. Fujiwara, D. Kang, K. Sugimachi, Y. Nakabeppu, Expression and differential intracellular localization of two major forms of human 8-oxoguanine DNA glycosylase encoded by alternatively spliced OGG1 mRNAs, Mol. Biol. Cell, 1999, 10, 1637–1652.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. D. Kang, J. Nishida, A. Iyama, Y. Nakabeppu, M. Furuichi, T. Fujiwara, M. Sekiguchi, K. Takeshige, Intracellular localization of 8-oxo-dGTPase in human cells, with special reference to the role of the enzyme in mitochondria, J. Biol. Chem., 1995, 270, 14659–14665.

    Article  CAS  PubMed  Google Scholar 

  29. G. Slupphaug, F. H. Markussen, L. C. Olsen, R. Aasland, N. Aarsaether, O. Bakke, H. E. Krokan, D. E. Helland, Nuclear and mitochondrial forms of human uracil-DNA glycosylase are encoded by the same gene, Nucleic Acids Res., 1993, 21, 2579–2584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. O. D. Schärer, Chemie und Biologie der DNA-Reparatur, Angewandte Chemie, 2003, 115, 3052–3082.

    Article  Google Scholar 

  31. H. Miller, A. S. Fernandes, E. Zaika, M. M. McTigue, M. C. Torres, M. Wente, C. R. Iden, A. P. Grollman, Stereoselective excision of thymine glycol from oxidatively damaged DNA, Nucleic Acids Res., 2004, 32, 338–345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. B. Karahalil, N. C. Souza-Pinto, J. L. Parsons, R. H. Elder, V. A. Bohr, Compromised incision of oxidized pyrimidines in liver mitochondria of mice deficient in NTH1 and OGG1 glycosylases, J. Biol. Chem., 2003, 278, 33701–33707.

    Article  CAS  PubMed  Google Scholar 

  33. K. G. Pinz, D. F. Bogenhagen, Efficient repair of abasic sites in DNA by mitochondrial enzymes, Mol. Cell. Biol., 1998, 18, 1257–1265.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. U. Lakshmipathy, C. Campbell, Mitochondrial DNA ligase III function is independent of Xrcc1, Nucleic Acids Res., 2000, 28, 3880–3886.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. U. Lakshmipathy, C. Campbell, The human DNA ligase III gene encodes nuclear and mitochondrial proteins, Mol. Cell. Biol., 1999, 19, 3869–3876.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. K. A. Myers, R. Saffhill, P. J. O℉Connor, Repair of alkylated purines in the hepatic DNA of mitochondria and nuclei in the rat, Carcinogenesis, 1988, 9, 285–292.

    Article  CAS  PubMed  Google Scholar 

  37. S. P. Ledoux, G. L. Wilson, E. J. Beecham, T. Stevnsner, K. Wassermann, V. A. Bohr, Repair of mitochondrial DNA after various types of DNA damage in Chinese hamster ovary cells, Carcinogenesis, 1992, 13, 1967–1973.

    Article  CAS  PubMed  Google Scholar 

  38. C. C. Pettepher, S. P. Ledoux, V. A. Bohr, G. L. Wilson, Repair of alkali-labile sites within the mitochondrial DNA of RINr 38 cells after exposure to the nitrosourea streptozotocin, J. Biol. Chem., 1991, 266, 3113–3117.

    Article  CAS  PubMed  Google Scholar 

  39. E. G. Snyderwine, V. A. Bohr, Gene- and strand-specific damage and repair in Chinese hamster ovary cells treated with 4-nitroquinoline 1-oxide, Cancer Res., 1992, 52, 4183–4189.

    CAS  PubMed  Google Scholar 

  40. M. S. Satoh, N. Huh, M. F. Rajewsky, T. Kuroki, Enzymatic removal of O6-ethylguanine from mitochondrial DNA in rat tissues exposed to N-ethyl-N-nitrosourea in vivo, J. Biol. Chem., 1988, 263, 6854–6856.

    Article  CAS  PubMed  Google Scholar 

  41. L. S. Kaguni, DNA polymerase gamma, the mitochondrial replicase, Annu. Rev. Biochem., 2004, 73, 293–320.

    Article  CAS  PubMed  Google Scholar 

  42. M. A. Graziewicz, B. J. Day, W. C. Copeland, The mitochondrial DNA polymerase as a target of oxidative damage, Nucleic Acids Res., 2002, 30, 2817–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. P. A. Mason, E. C. Matheson, A. G. Hall, R. N. Lightowlers, Mismatch repair activity in mammalian mitochondria, Nucleic Acids Res., 2003, 31, 1052–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Z. Chen, R. Felsheim, P. Wong, L. B. Augustin, R. Metz, B. T. Kren, C. J. Steer, Mitochondria isolated from liver contain the essential factors required for RNA/DNA oligonucleotide-targeted gene repair, Biochem. Biophys. Res. Commun., 2001, 285, 188–94.

    Article  CAS  PubMed  Google Scholar 

  45. S. J. Collis, T. L. DeWeese, P. A. Jeggo, A. R. Parker, The life and death of DNA-PK, Oncogene, 2005, 24, 949–961.

    Article  CAS  PubMed  Google Scholar 

  46. F. Ling, F. Makishima, N. Morishima, T. Shibata, A nuclear mutation defective in mitochondrial recombination in yeast, EMBO J., 1995, 14, 4090–4101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. W. Habano, T. Sugai, T. Yoshida, S. Nakamura, Mitochondrial gene mutation, but not large-scale deletion, is a feature of colorectal carcinomas with mitochondrial microsatellite instability, Int. J. Cancer, 1999, 83, 625–629.

    Article  CAS  PubMed  Google Scholar 

  48. A. Sancar, L. A. Lindsey-Boltz, K. Unsal-Kacmaz, S. Linn, Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints, Annu. Rev. Biochem., 2004, 73, 39–85.

    Article  CAS  PubMed  Google Scholar 

  49. B. Thyagarajan, R. A. Padua, C. Campbell, Mammalian mitochondria possess homologous DNA recombination activity, J. Biol. Chem., 1996, 271, 27536–27543.

    Article  CAS  PubMed  Google Scholar 

  50. G. Coffey, U. Lakshmipathy, C. Campbell, Mammalian mitochondrial extracts possess DNA end-binding activity, Nucleic Acids Res., 1999, 27, 3348–3354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. M. Berneburg, A. R. Lehmann, Xeroderma pigmentosum and related disorders: defects in DNA repair and transcription, Adv. Genet., 2001, 43, 71–102.

    Article  CAS  PubMed  Google Scholar 

  52. K. Y. Loke, Cockayne syndrome-a case report, and a review of the premature aging syndromes in paediatrics, J. Singapore Paediatr. Soc., 1991, 33, 49–54.

    CAS  PubMed  Google Scholar 

  53. S. Beauregard, B. A. Gilchrest, Syndromes of premature aging, Dermatol. Clin., 1987, 5, 109–121.

    Article  CAS  PubMed  Google Scholar 

  54. C. L. Licht, T. Stevnsner, V. A. Bohr, Cockayne syndrome group B cellular and biochemical functions, Am. J. Hum. Genet., 2003, 73, 1217–1239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. A. S. Balajee, I. Dianova, V. A. Bohr, Oxidative damage-induced PCNA complex formation is efficient in xeroderma pigmentosum group A but reduced in Cockayne syndrome group B cells, Nucleic Acids Res., 1999, 27, 4476–4482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. G. Dianov, C. Bischoff, M. Sunesen, V. A. Bohr, Repair of 8-oxoguanine in DNA is deficient in Cockayne syndrome group B cells, Nucleic Acids Res., 1999, 27, 1365–1368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. R. R. Selzer, S. Nyaga, J. Tuo, A. May, M. Muftuoglu, M. Christiansen, E. Citterio, R. M. Brosh, Jr., V. A. Bohr, Differential requirement for the ATPase domain of the Cockayne syndrome group B gene in the processing of UV-induced DNA damage and 8-oxoguanine lesions in human cells, Nucleic Acids Res., 2002, 30, 782–793.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. F. Le Page, E. E. Kwoh, A. Avrutskaya, A. Gentil, S. A. Leadon, A. Sarasin, P. K. Cooper, Transcription-coupled repair of 8-oxoguanine: requirement for XPG, TFIIH, and CSB and implications for Cockayne syndrome, Cell, 2000, 101, 159–171.

    Article  PubMed  Google Scholar 

  59. J. Tuo, C. Chen, X. Zeng, M. Christiansen, V. A. Bohr, Functional crosstalk between hOgg1 and the helicase domain of Cockayne syndrome group B protein, DNA Repair, 2002, 1, 913–927.

    Article  CAS  PubMed  Google Scholar 

  60. J. Tuo, M. Muftuoglu, C. Chen, P. Jaruga, R. R. Selzer, R. M. Brosh, Jr., H. Rodriguez, M. Dizdaroglu, V. A. Bohr, The Cockayne Syndrome group B gene product is involved in general genome base excision repair of 8-hydroxyguanine in DNA, J. Biol. Chem., 2001, 276, 45772–45779.

    Article  CAS  PubMed  Google Scholar 

  61. J. Tuo, P. Jaruga, H. Rodriguez, M. Dizdaroglu, V. A. Bohr, The cockayne syndrome group B gene product is involved in cellular repair of 8-hydroxyadenine in DNA, J. Biol. Chem., 2002, 277, 30832–30837.

    Article  CAS  PubMed  Google Scholar 

  62. D. Harman, Aging: Overview, in Healthy Aging for Functional Longevity, Ann. N. Y. Acad. Sci., 2001, vol. 928, pp. 1–21.

    CAS  Google Scholar 

  63. K. D. Munkres, R. S. Rana, E. Goldstein, Genetically determined conidial longevity is positively correlated with superoxide dismutase, catalase, glutathione peroxidase, cytochrome c peroxidase, and ascorbate free radical reductase activities in Neurospora crassa, Mech. Ageing Dev., 1984, 24, 83–100.

    Article  CAS  PubMed  Google Scholar 

  64. T. E. Johnson, G. J. Lithgow, The search for the genetic basis of aging: the identification of gerontogenes in the nematode Caenorhabditis elegans, J. Am. Geriatr. Soc, 1992, 40, 936–945.

    Article  CAS  PubMed  Google Scholar 

  65. M. K. Shigenaga, T. M. Hagen, B. N. Ames Oxidative, damage and mitochondrial decay in aging, Proc. Natl. Acad. Sci. USA, 1994, 91, 10771–10778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. S. Hekimi, L. Guarente, Genetics and the specificity of the aging process, Science, 2003, 299, 1351–1354.

    Article  CAS  PubMed  Google Scholar 

  67. R. Weindruch, P. H. Naylor, A. L. Goldstein, R. L. Walford, Influences of aging and dietary restriction on serum thymosin alpha 1 levels in mice, J. Gerontol., 1988, 43, 40–42.

    Article  Google Scholar 

  68. G. A. Cortopassi, E. Wang, There is substantial agreement among interspecies estimates of DNA repair activity, Mech. Ageing Dev., 1996, 91, 211–218.

    Article  CAS  PubMed  Google Scholar 

  69. R. W. Hart, R. B. Setlow, Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species, Proc. Natl. Acad. Sci. USA, 1974, 71, 2169–2173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. J. de Boer, J. O. Andressoo, J. de Wit, J. Huijmans, R. B. Beems, H. van Steeg, G. Weeda, G. T. J. van der Horst, W. van Leeuwen, A. P. N. Themmen, M. Meradji, J. H. J. Hoeijmakers, Premature aging in mice deficient in DNA repair and transcription, Science, 2002, 296, 1276–1279.

    Article  PubMed  Google Scholar 

  71. N. C. Souza-Pinto, D. L. Croteau, E. K. Hudson, R. G. Hansford, V. A. Bohr, Age-associated increase in 8-oxo-deoxyguanosine glycosylase/AP lyase activity in rat mitochondria, Nucleic Acids Res., 1999, 27, 1935–1942.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. B. Szczesny, K. K. Bhakat, S. Mitra, I. Boldogh, Age-dependent modulation of DNA repair enzymes by covalent modification and subcellular distribution, Mech. Ageing Dev., 2004, 125, 755–65.

    Article  CAS  PubMed  Google Scholar 

  73. N. Weraarchakul, R. Strong, W. G. Wood, A. Richardson, The effect of aging and dietary restriction on DNA repair, Exp. Cell Res., 1989, 181, 197–204.

    Article  CAS  PubMed  Google Scholar 

  74. J. A. Stuart, B. Karahalil, B. A. Hogue, N. C. Souza-Pinto, V. A. Bohr, Mitochondrial and nuclear DNA base excision repair are affected differently by caloric restriction, FASEB J., 2004, 18, 595–597.

    Article  CAS  PubMed  Google Scholar 

  75. A. Trifunovic, A. Wredenberg, M. Falkenberg, J. N. Spelbrink, A. T. Rovio, C. E. Bruder, Y. Bohlooly, S. Gidlof, A. Oldfors, R. Wibom, J. Tornell, H. T. Jacobs, N. G. Larsson, Premature ageing in mice expressing defective mitochondrial DNA polymerase, Nature, 2004, 429, 417–423.

    Article  CAS  PubMed  Google Scholar 

  76. M. Berneburg, H. Plettenberg Medve-König, A. Pfahlberg, H. Gers-Barlag, O. Gefeller, J. Krutmann, Induction of the Photoaging-Associated Mitochondrial Common Deletion In Vivo in Normal Human Skin, J. Invest. Dermatol., 2004, 122, 1277–1283.

    Article  CAS  PubMed  Google Scholar 

  77. V. Koivukangas, M. Kallioinen, H. Autio-Harmainen, A. Oikarinen, UV irradiation induces the expression of gelatinases in human skin in vivo, Acta Dermatol. Venereol., 1994, 74, 279–282.

    CAS  Google Scholar 

  78. G. J. Fisher, S. C. Datta, H. S. Talwar, Z. Q. Wang, J. Varani, S. Kang, J. J. Voorhees, Molecular basis of sun-induced premature skin ageing and retinoid antagonism, Nature, 1996, 379, 335–339.

    Article  CAS  PubMed  Google Scholar 

  79. K. Scharffetter, M. Wlaschek, A. Hogg, K. Bolsen, A. Schothorst, G. Goerz, T. Krieg, G. Plewig, UVA irradiation induces collagenase in human dermal fibroblasts in vitro and in vivo, Arch. Dermatol. Res., 1991, 283, 506–511.

    Article  CAS  PubMed  Google Scholar 

  80. G. J. Fisher, S. C. Datta, H. S. Talwar, Z. Q. Wang, J. Varani, S. Kang, J. J. Voorhees, Molecular basis of sun-induced premature skin ageing and retinoid antagonism, Nature, 1996, 379, 335–339.

    Article  CAS  PubMed  Google Scholar 

  81. J. A. Stuart, B. M. Bourque, N. C. de Souza-Pinto, V. A. Bohr, No evidence of mitochondrial respiratory dysfunction in OGG1-null mice deficient in removal of 8-oxodeoxyguanine from mitochondrial DNA, Free Radical Biol. Med., 2005, 38, 737–45.

    Article  CAS  Google Scholar 

  82. A. D. de Grey, The reductive hotspot hypothesis of mammalian aging: membrane metabolism magnifies mutant mitochondrial mischief, Eur. J. Biochem., 2002, 269, 2003–9.

    Article  PubMed  CAS  Google Scholar 

  83. P. S. Brookes, Mitochondrial H(+) leak and ROS generation: an odd couple, Free Radical Biol. Med., 2005, 38, 12–23.

    Article  CAS  Google Scholar 

  84. O. Warburg, On the origin of cancer cells, Science, 1956, 123, 309–314.

    Article  CAS  PubMed  Google Scholar 

  85. D. R. Green, G. Kroemer, The pathophysiology of mitochondrial cell death, Science, 2004, 305, 626–629.

    Article  CAS  PubMed  Google Scholar 

  86. J. S. Carew, P. Huang, Mitochondrial defects in cancer, Mol. Cancer, 2002, 1, 1–9.

    Article  Google Scholar 

  87. H. Okada, T. W. Mak, Pathways of apoptotic and non-apoptotic death in tumour cells, Nat. Rev. Cancer, 2004, 4, 592–603.

    Article  CAS  PubMed  Google Scholar 

  88. B. Joshi, L. Li, B. G. Taffe, Z. Zhu, S. Wahl, H. Tian, E. Ben Josef, J. D. Taylor, A. T. Porter, D. G. Tang, Apoptosis induction by a novel anti-prostate cancer compound, BMD188 (a fatty acid-containing hydroxamic acid), requires the mitochondrial respiratory chain, Cancer Res., 1999, 59, 4343–4355.

    CAS  PubMed  Google Scholar 

  89. S. Cai, Y. Xu, R. J. Cooper, M. J. Ferkowicz, J. R. Hartwell, K. E. Pollok, M. R. Kelley, Mitochondrial targeting of human O6-methylguanine DNA methyltransferase protects against cell killing by chemotherapeutic alkylating agents, Cancer Res., 2005, 65, 3319–3327.

    Article  CAS  PubMed  Google Scholar 

  90. G. Amuthan, G. Biswas, S. Y. Zhang, A. Klein-Szanto, C. Vijayasarathy, N. G. Avadhani, Mitochondria-to-nucleus stress signaling induces phenotypic changes, tumor progression and cell invasion, EMBO J., 2001, 20, 1910–1920.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Q. Felty, W. C. Xiong, D. Sun, S. Sarkar, K. P. Singh, J. Parkash, D. Roy, Estrogen-Induced Mitochondrial Reactive Oxygen Species as Signal-Transducing Messengers, Biochemistry, 2005, 44, 6900–6909.

    Article  CAS  PubMed  Google Scholar 

  92. S. L. Liu, X. Lin, D. Y. Shi, J. Cheng, C. Q. Wu, Y. D. Zhang, Reactive oxygen species stimulated human hepatoma cell proliferation via cross-talk between PI3-K/PKB and JNK signaling pathways, Arch. Biochem. Biophys., 2002, 406, 173–182.

    Article  CAS  PubMed  Google Scholar 

  93. R. L. Delsite, L. J. Rasmussen, A. K. Rasmussen, A. Kalen, P. C. Goswami, K. K. Singh, Mitochondrial impairment is accompanied by impaired oxidative DNA repair in the nucleus, Mutagenesis, 2003, 18, 497–503.

    Article  CAS  PubMed  Google Scholar 

  94. E. Mambo, A. Chatterjee, N. C. Souza-Pinto, S. Mayard, B. A. Hogue, M. O. Hoque, M. Dizdaroglu, V. A. Bohr, D. Sidransky, Oxidized guanine lesions and hOgg1 activity in lung cancer, Oncogene, 2005, 24, 4496–5008.

    Article  CAS  PubMed  Google Scholar 

  95. S. Choudhury, R. Zhang, K. Frenkel, T. Kawamori, F. L. Chung, R. Roy, Evidence of alterations in base excision repair of oxidative DNA damage during spontaneous hepatocarcinogenesis in Long Evans Cinnamon rats, Cancer Res., 2003, 63, 7704–7707.

    CAS  PubMed  Google Scholar 

  96. W. Habano, S. Nakamura, T. Sugai, Microsatellite instability in the mitochondrial DNA of colorectal carcinomas: evidence for mismatch repair systems in mitochondrial genome, Oncogene, 1998, 17, 1931–1937.

    Article  CAS  PubMed  Google Scholar 

  97. K. Polyak, Y. Li, H. Zhu, C. Lengauer, J. K. Willson, S. D. Markowitz, M. A. Trush, K. W. Kinzler, B. Vogelstein, Somatic mutations of the mitochondrial genome in human colorectal tumours, Nat. Genet., 1998, 20, 291–293.

    Article  CAS  PubMed  Google Scholar 

  98. P. Parrella, Y. Xiao, M. Fliss, M. Sanchez-Cespedes, P. Mazzarelli, M. Rinaldi, T. Nicol, E. Gabrielson, C. Cuomo, D. Cohen, S. Pandit, M. Spencer, C. Rabitti, V. M. Fazio, D. Sidransky, Detection of mitochondrial DNA mutations in primary breast cancer and fine-needle aspirates, Cancer Res., 2001, 61, 7623–7626.

    CAS  PubMed  Google Scholar 

  99. W. Zhu, W. Qin, P. Bradley, A. Wessel, C. L. Puckett, E. R. Sauter, Mitochondrial DNA mutations in breast cancer tissue and in matched nipple aspirate fluid, Carcinogenesis, 2005, 26, 145–152.

    Article  PubMed  CAS  Google Scholar 

  100. J. M. Cuezva, G. Chen, A. M. Alonso, A. Isidoro, D. E. Misek, S. M. Hanash, D. G. Beer, The bioenergetic signature of lung adenocarcinomas is a molecular marker of cancer diagnosis and prognosis, Carcinogenesis, 2004, 25, 1157–1163.

    Article  CAS  PubMed  Google Scholar 

  101. S. E. Durham, K. J. Krishnan, J. Betts, M. A. Birch-Machin, Mitochondrial DNA damage in non-melanoma skin cancer, Br. J. Cancer, 2003, 88, 90–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. W. C. Copeland, J. T. Wachsman, F. M. Johnson, J. S. Penta Mitochondrial, DNA alterations in cancer, Cancer Invest., 2002, 20, 557–569.

    Article  CAS  PubMed  Google Scholar 

  103. M. Suzuki, S. Toyooka, K. Miyajima, T. Iizasa, T. Fujisawa, N. B. Bekele, A. F. Gazdar, Alterations in the mitochondrial displacement loop in lung cancers, Clin. Cancer Res., 2003, 9, 5636–5641.

    CAS  PubMed  Google Scholar 

  104. S. Nomoto, K. Yamashita, K. Koshikawa, A. Nakao, D. Sidransky, Mitochondrial D-loop mutations as clonal markers in multicentric hepatocellular carcinoma and plasma, Clin. Cancer Res., 2002, 8, 481–487.

    CAS  PubMed  Google Scholar 

  105. V. Maximo, P. Soares, R. Seruca, A. S. Rocha, P. Castro, M. Sobrinho-Simoes, Microsatellite instability, mitochondrial DNA large deletions, and mitochondrial DNA mutations in gastric carcinoma, Genes Chromosom. Cancer, 2001, 32, 136–143.

    Article  CAS  PubMed  Google Scholar 

  106. S. R. McWhinney, R. T. Pilarski, S. R. Forrester, M. C. Schneider, M. M. Sarquis, E. P. Dias, C. Eng, Large germline deletions of mitochondrial complex II subunits SDHB and SDHD in hereditary paraganglioma, J. Clin. Endocrinol. Metab., 2004, 89, 5694–5699.

    Article  CAS  PubMed  Google Scholar 

  107. J. Z. Chen, N. Gokden, G. F. Greene, B. Green, F. F. Kadlubar, Simultaneous generation of multiple mitochondrial DNA mutations in human prostate tumors suggests mitochondrial hyper-mutagenesis, Carcinogenesis, 2003, 24, 1481–1487.

    Article  CAS  PubMed  Google Scholar 

  108. M. S. Fliss, H. Usadel, O. L. Caballero, L. Wu, M. R. Buta, S. M. Eleff, J. Jen, D. Sidransky, Facile detection of mitochondrial DNA mutations in tumors and bodily fluids, Science, 2000, 287, 2017–2019.

    Article  CAS  PubMed  Google Scholar 

  109. V. W. Liu, H. H. Shi, A. N. Cheung, P. M. Chiu, T. W. Leung, P. Nagley, L. C. Wong, H. Y. Ngan, High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas, Cancer Res., 2001, 61, 5998–6001.

    CAS  PubMed  Google Scholar 

  110. S. R. McWhinney, R. T. Pilarski, S. R. Forrester, M. C. Schneider, M. M. Sarquis, E. P. Dias, C. Eng, Large germline deletions of mitochondrial complex II subunits SDHB and SDHD in hereditary paraganglioma, J. Clin. Endocrinol. Metab., 2004, 89, 5694–5699.

    Article  CAS  PubMed  Google Scholar 

  111. Y. Shidara, K. Yamagata, T. Kanamori, K. Nakano, J. Q. Kwong, G. Manfredi, H. Oda, S. Ohta, Positive contribution of pathogenic mutations in the mitochondrial genome to the promotion of cancer by prevention from apoptosis, Cancer Res., 2005, 65, 1655–1663.

    Article  CAS  PubMed  Google Scholar 

  112. V. Maximo, P. Soares, J. Lima, J. Cameselle-Teijeiro, M. Sobrinho-Simoes, Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology: a study with emphasis on Hurthle cell tumors, Am. J. Pathol., 2002, 160, 1857–1865.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. J. J. Yeh, K. L. Lunetta, N. J. van Orsouw, F. D. Moore, Jr., G. L. Mutter, J. Vijg, P. L. Dahia, C. Eng, Somatic mitochondrial DNA (mtDNA) mutations in papillary thyroid carcinomas and differential mtDNA sequence variants in cases with thyroid tumours, Oncogene, 2000, 19, 2060–2066.

    Article  CAS  PubMed  Google Scholar 

  114. D. J. Tan, R. K. Bai, L. J. Wong, Comprehensive scanning of somatic mitochondrial DNA mutations in breast cancer, Cancer Res., 2002, 62, 972–976.

    CAS  PubMed  Google Scholar 

  115. K. Kotake, T. Nonami, T. Kurokawa, A. Nakao, T. Murakami, Y. Shimomura, Human livers with cirrhosis and hepatocellular carcinoma have less mitochondrial DNA deletion than normal human livers, Life Sci., 1999, 64, 1785–1791.

    Article  CAS  PubMed  Google Scholar 

  116. D. B. Shieh, W. P. Chou, Y. H. Wei, T. Y. Wong, Y. T. Jin, Mitochondrial DNA 4,977-bp deletion in paired oral cancer and precancerous lesions revealed by laser microdissection and real-time quantitative PCR, Ann. N. Y. Acad. Sci., 2004, 1011, 154–167.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Molecular Oncology and Aging, Department of Dermatology, Eberhard Karls University, Liebermeisterstrasse 25, D-72076, Tübingen, Germany

    Mark Berneburg & York Kamenisch

  2. Institut für Umweltmedizinische Forschung gGmbH at the Heinrich-Heine-University, Auf m Hennekamp 50, D-40225, Düsseldorf, Germany

    Jean Krutmann

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  1. Mark Berneburg
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Correspondence to Mark Berneburg.

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Berneburg, M., Kamenisch, Y. & Krutmann, J. Repair of mitochondrial DNA in aging and carcinogenesis. Photochem Photobiol Sci 5, 190–198 (2006). https://doi.org/10.1039/b507380d

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