Journal of Bioenergetics and Biomembranes

, Volume 43, Issue 1, pp 25–29 | Cite as

The role of mitochondrial DNA damage in the citotoxicity of reactive oxygen species

  • R. A. P. Costa
  • C. D. Romagna
  • J. L. Pereira
  • N. C. Souza-Pinto


Mitochondria contain their own genome, a small circular molecule of around 16.5 kbases. The mitochondrial DNA (mtDNA) encodes for only 13 polypeptides, but its integrity is essential for mitochondrial function, as all 13 proteins are regulatory subunits of the oxidative phosphorylation complexes. Nonetheless, the mtDNA is physically associated with the inner mitochondrial membrane, where the majority of the cellular reactive oxygen species are generated. In fact, the mitochondrial DNA accumulates high levels of oxidized lesions, which have been associated with several pathological and degenerative processes. The cellular responses to nuclear DNA damage have been extensively studied, but so far little is known about the functional outcome and cellular responses to mtDNA damage. In this review we will discuss the mechanisms that lead to damage accumulation and the in vitro models we are establishing to dissect the cellular responses to oxidative damage in the mtDNA and to sort out the differential cellular consequences of accumulation of damage in each cellular genome, the nuclear and the mitochondrial genome.


Mitochondrial DNA Reactive oxygen species Oxidative DNA damage Methylene blue Singlet oxygen 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alberici LC, Vercesi AE, Oliveira HCF (2011) J Bioenerg Biomembr. doi: 10.1007/s10863-011-9326-y
  2. Atamna H, Nguyen A, Schultz C, Boyle K, Newberry J, Kato H, Ames BN (2008) FASEB J 22:703–712CrossRefGoogle Scholar
  3. Batandier C, Leverve X, Fontaine E (2004) J Biol Chem 279:17197–17204CrossRefGoogle Scholar
  4. Blazquez-Castro A, Stockert JC, Sanz-Rodriguez F, Zamarron A, Juarranz A (2009) Photochem Photobiol Sci 8:371–376CrossRefGoogle Scholar
  5. Boveris A, Chance B (1973) Biochem J 134:707–716Google Scholar
  6. Boveris A, Cadenas E, Stoppani AO (1976) Biochem J 156:435–444Google Scholar
  7. Broekemeier KM, Dempsey ME, Pfeiffer DR (1989) J Biol Chem 264:7826–7830Google Scholar
  8. Butow RA, Avadhani NG (2004) Mol Cell 14:1–15CrossRefGoogle Scholar
  9. Cadenas E, Boveris A, Ragan CI, Stoppani AO (1977) Arch Biochem Biophys 180:248–257CrossRefGoogle Scholar
  10. Castilho RF, Kowaltowski AJ, Meinicke AR, Bechara EJ, Vercesi AE (1995) Free Radic Biol Med 18:479–486CrossRefGoogle Scholar
  11. Castilho RF, Kowaltowski AJ, Vercesi AE (1996) J Bioenerg Biomembr 28:523–529CrossRefGoogle Scholar
  12. Clayton DA, Doda JN, Friedberg EC (1974) Proc Natl Acad Sci USA 71(7):2777–2781CrossRefGoogle Scholar
  13. Connern CP, Halestrap AP (1994) Biochem J 302(Pt 2):321–324Google Scholar
  14. Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003) FASEB J 17:1195–1214CrossRefGoogle Scholar
  15. Crompton M, Ellinger H, Costi A (1988) Biochem J 255:357–360Google Scholar
  16. de Souza-Pinto NC, Vercesi AE, Hoffmann ME (1996) Free Radic Biol Med 20:657–666CrossRefGoogle Scholar
  17. Devasagayam TP, Steenken S, Obendorf MS, Schulz WA, Sies H (1991) Biochemistry 30:6283–6289CrossRefGoogle Scholar
  18. Di Mascio P, Menck CF, Nigro RG, Sarasin A, Sies H (1990) Photochem Photobiol 51:293–298CrossRefGoogle Scholar
  19. Doonan S, Barra D, Bossa F (1984) Int J Biochem 16:1193–1199CrossRefGoogle Scholar
  20. Ernster L, Forsmark P, Nordenbrand K (1992) J Nutr Sci Vitaminol (Tokyo) Spec No 548–551Google Scholar
  21. Evans MD, Dizdaroglu M, Cooke MS (2004) Mutat Res 567:1–61CrossRefGoogle Scholar
  22. Fagian MM, Pereira-da-Silva L, Martins IS, Vercesi AE (1990) J Biol Chem 265:19955–19960Google Scholar
  23. Gabrielli D, Belisle E, Severino D, Kowaltowski AJ, Baptista MS (2004) Photochem Photobiol 79:227–232CrossRefGoogle Scholar
  24. Giulivi C (1998) Biochem J 332(Pt 3):673–679Google Scholar
  25. Gredilla R, Bohr VA, Stevnsner T (2010) Exp Gerontol 45:478–488CrossRefGoogle Scholar
  26. Hoek JB, Rydstrom J (1988) Biochem J 254:1–10Google Scholar
  27. Huang Y, Zhang F, Gong Y (2005) Tetrahedron Lett 46:7217–7219CrossRefGoogle Scholar
  28. Huen MS, Chen J (2010) Trends Biochem Sci 35(2):101–108CrossRefGoogle Scholar
  29. Hunter DR, Haworth RA (1979) Arch Biochem Biophys 195:453–459CrossRefGoogle Scholar
  30. Indig GL, Anderson GS, Nichols MG, Bartlett JA, Mellon WS, Sieber F (2000) J Pharm Sci 89:88–99CrossRefGoogle Scholar
  31. Jones G, Oh C, Goswami K (1991) J Photochem Photobiol, A 57:65–80CrossRefGoogle Scholar
  32. Kowaltowski AJ, Castilho RF, Grijalba MT, Bechara EJ, Vercesi AE (1996a) J Biol Chem 271:2929–2934CrossRefGoogle Scholar
  33. Kowaltowski AJ, Castilho RF, Vercesi AE (1996b) FEBS Lett 378:150–152CrossRefGoogle Scholar
  34. Kowaltowski AJ, Netto LE, Vercesi AE (1998) J Biol Chem 273:12766–12769CrossRefGoogle Scholar
  35. Kowaltowski AJ, de Souza-Pinto NC, Castilho RF, Vercesi AE (2009) Free Radic Biol Med 47:333–343CrossRefGoogle Scholar
  36. Liu SS (1997) Biosci Rep 17:259–272CrossRefGoogle Scholar
  37. Maciel EN, Vercesi AE, Castilho RF (2001) J Neurochem 79:1237–1245CrossRefGoogle Scholar
  38. Maynard S, Schurman SH, Harboe C, de Souza-Pinto NC, Bohr VA (2009) Carcinogenesis 30(1):2–10CrossRefGoogle Scholar
  39. Mellish KJ, Cox RD, Vernon DI, Griffiths J, Brown SB (2002) Photochem Photobiol 75:392–397CrossRefGoogle Scholar
  40. Mitchell P (1966) Biol Rev Camb Philos Soc 41:445–502CrossRefGoogle Scholar
  41. Moore C, Wallis C, Melnick JL, Kuns MD (1972) Infect Immun 5:169–171Google Scholar
  42. Murphy MP (1997) Trends Biotechnol 15:326–330CrossRefGoogle Scholar
  43. Nicolli A, Basso E, Petronilli V, Wenger RM, Bernardi P (1996) J Biol Chem 271:2185–2192CrossRefGoogle Scholar
  44. Ross MF, Kelso GF, Blaikie FH, James AM, Cocheme HM, Filipovska A, Da RT, Hurd TR, Smith RA (2005) Murphy MP. Biochem Mosc 70:222–230CrossRefGoogle Scholar
  45. Severino D, Junqueira HC, Gugliotti M, Gabrielli DS, Baptista MS (2003) Photochem Photobiol 77:459–468CrossRefGoogle Scholar
  46. Sies H, Moss KM (1978) Eur J Biochem 84:377–383CrossRefGoogle Scholar
  47. Skulachev VP (1998) FEBS Lett 423:275–280CrossRefGoogle Scholar
  48. Spelbrink JN (2010) IUBMB Life 62:19–32Google Scholar
  49. Thorslund T, Sunesen M, Bohr VA (2002) Stevnsner T. DNA Repair Amst 1:261–273CrossRefGoogle Scholar
  50. Turrens JF (1997) Biosci Rep 17:3–8CrossRefGoogle Scholar
  51. Turrens JF, Boveris A (1980) Biochem J 191:421–427Google Scholar
  52. Turrens JF, Alexandre A, Lehninger AL (1985) Arch Biochem Biophys 237:408–414CrossRefGoogle Scholar
  53. Valle VG, Fagian MM, Parentoni LS, Meinicke AR, Vercesi AE (1993) Arch Biochem Biophys 307:1–7CrossRefGoogle Scholar
  54. Vercesi AE, Kowaltowski AJ, Grijalba MT, Meinicke AR, Castilho RF (1997) Biosci Rep 17:43–52CrossRefGoogle Scholar
  55. Wallace DC (2010) Environ Mol Mutagen 51(5):440–450Google Scholar
  56. Will O, Gocke E, Eckert I, Schulz I, Pflaum M, Mahler HC, Epe B (1999) Mutat Res 435:89–101Google Scholar
  57. Zakowski JJ, Tappel AL (1978) Biochim Biophys Acta 526:65–76Google Scholar
  58. Zhu TC, Finlay JC (2008) Med Phys 35:3127–3136CrossRefGoogle Scholar
  59. Zoratti M, Szabo I (1995) Biochim Biophys Acta 1241:139–176Google Scholar
  60. Zorov DB, Filburn CR, Klotz LO, Zweier JL, Sollott SJ (2000) J Exp Med 192:1001–1014CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • R. A. P. Costa
    • 1
  • C. D. Romagna
    • 2
  • J. L. Pereira
    • 2
  • N. C. Souza-Pinto
    • 2
  1. 1.Depto. de Patologia Clinica, Faculdade de Ciências MedicasUNICAMPCampinasBrazil
  2. 2.Depto. de BioquímicaInstituto de Química, USPSão PauloBrazil

Personalised recommendations