Advertisement

Models of Mitochondrial Oxidative Stress

  • Enrique CadenasEmail author
  • Alberto Boveris
Chapter
  • 1.1k Downloads
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

Abstract

Mitochondria are sources of H2O2 under aerobic and physiological ­conditions; the mitochondrial H2O2 generation is conceived as a consequence of the univalent and nonenzymatic reduction of oxygen to superoxide anion followed by its disproportionation to H2O2. Recognized sites for the univalent reduction of ­oxygen to superoxide are the autoxidation of ubisemiquinone in complex I and complex III and probably the autoxidation of the flavin semiquinone in complex I. The formation of H2O2 by mitochondria acquires further significance when ­considering that it reports a high mitochondrial energy charge by its diffusion to the cytosol and that it may be involved in domain-specific signaling pathways or ­signaling in localized subcellular areas. H2O2 is considered a major player in the redox regulation of cell signaling by modulating the activity of glutathione-, ­thioredoxin-, and peroxiredoxin-supported systems. Although H2O2 is highly ­diffusible across biological membranes, significant gradients are established in the cells and the involvement of mitochondrial H2O2 in the regulation of specific signaling pathways requires careful consideration of its sources, of its removal by specific enzymic systems, and of the mechanism by which H2O2 modifies the signaling pathways.

Keywords

Coenzyme Q Complex I Hydrogen peroxide Mitochondria Oxidative stress Redox signaling ROS Superoxide anion 

References

  1. 1.
    Chance B and Oshino N (1971) Kinetics and mechanisms of catalase in peroxisomes of the mitochondrial fraction. Biochem. J. 122: 225–233.PubMedGoogle Scholar
  2. 2.
    Loschen G, Flohé L and Chance B (1971) Respiratory chain linked H2O2 production in pigeon heart mitochondria. FEBS Letter. 18: 261–264.CrossRefGoogle Scholar
  3. 3.
    Boveris A and Chance B (1973) The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem. J. 134: 707–716.Google Scholar
  4. 4.
    Loschen G, Azzi A and Flohé L (1973) Mitochondrial H2O2 formation: relationship with energy conservation. FEBS Lett. 33: 84–87.PubMedCrossRefGoogle Scholar
  5. 5.
    Loschen G, Azzi A, Richter C and Flohe L (1974) Superoxide radicals as precursors of mitochondrial hydrogen peroxide. FEBS Lett. 42: 68–72.PubMedCrossRefGoogle Scholar
  6. 6.
    Boveris A and Cadenas E (1975) Mitochondrial production of superoxide anions and its relationship to the antimycin-insensitive respiration. FEBS Lett. 54: 311–314.PubMedCrossRefGoogle Scholar
  7. 7.
    Dionisi O, Galeotti T, Terranova T, Azzi A (1975) Superoxide radicals and hydrogen peroxide formation in mitochondria from normal and neoplastic tissues. Biochim Biophys Acta 403: 292–300.PubMedCrossRefGoogle Scholar
  8. 8.
    Forman HJ and Boveris A. (1982) Superoxide radical and hydrogen peroxide in mitochondria. In Free Radicals in Biology (Pryor, W. A., ed.). pp. 65–90, Academic Press, San Diego.Google Scholar
  9. 9.
    Weisinger RA and Fridovich I (1973) Mitochondrial superoxide dismutase. Site of synthesis and intramitochondrial localization. J. Biol. Chem. 248: 4793–4796.Google Scholar
  10. 10.
    Cadenas E, Boveris A, Ragan CI and Stoppani AO (1977) Production of superoxide radicals and hydrogen peroxide by NADH- ubiquinone reductase and ubiquinol-cytochrome c reductase from beef- heart mitochondria. Arch. Biochem. Biophys. 180: 248–257.PubMedCrossRefGoogle Scholar
  11. 11.
    Hauptmann N, Grimsby J, Shih JC and Cadenas E (1996) The metabolism of tyramine by monoamine oxidase A/B causes oxidative damage to mitochondrial DNA. Arch. Biochem. Biophys. 335: 295–304.PubMedCrossRefGoogle Scholar
  12. 12.
    Naoi M, Maruyama W, Akao Y, Yi H and Yamaoka Y (2006) Involvement of type A monoamine oxidase in neurodegeneration: regulation of mitochondrial signaling leading to cell death or neuroprotection. J. Neural Transm. Suppl. (71): 67–77.Google Scholar
  13. 13.
    Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 79: 527–605.Google Scholar
  14. 14.
    Boveris A and Cadenas E. (1997) Cellular sources and steady-state levels of reactive oxygen species. In Oxygen, gene expression, and cellular function (Clerch, L. B. and Massaro, D. J., eds.). pp. 1–25, Marcel Dekker, New York.Google Scholar
  15. 15.
    Boveris A, Valdez LB, Zaobornyj T and Bustamante J (2006) Mitochondrial metabolic states regulate nitric oxide and hydrogen peroxide diffusion to the cytosol. Biochim. Biophys. Acta. 1757: 535–542.PubMedCrossRefGoogle Scholar
  16. 16.
    Boveris A (1984) Determination of the production of superoxide radicals and hydrogen peroxide in mitochondria. Methods Enzymol. 105: 429–435.PubMedCrossRefGoogle Scholar
  17. 17.
    Turrens JF and Boveris A (1980) The generation of superoxide radicals by the NADH-dehydrogenase of bovine heart mammalian mitochondria. Biochem J 191: 421–427.PubMedGoogle Scholar
  18. 18.
    Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem. J. 417: 1–13.PubMedCrossRefGoogle Scholar
  19. 19.
    Gutteridge JM, Nagy I, Maidt L, Floyd RA (1990) ADP-iron as a Fenton reactant: radical reactions detected by spin trapping, hydrogen abstraction and aromatic hydroxylation. Arch Biochem Biophys 277: 422–428.PubMedCrossRefGoogle Scholar
  20. 20.
    Hink HU, Santanam N, Dikalov S, McCann L, Nguyen AD, Pathasarathy S, Harrison DG, Fukai T (2002). Peroxidase properties of extracellular superoxide dismutase: role of uric caid in modulating in vino activity. Arterioscler Thromb Vasc Biol 22: 1402–1408.PubMedCrossRefGoogle Scholar
  21. 21.
    Benov L, Sztejnberg L and Fridovich I (1998) Critical evaluation of the use of hydroethidine as a measure of superoxide anion radical. Free Radic. Biol. Med. 25: 826–831.PubMedCrossRefGoogle Scholar
  22. 22.
    Rota C, Chignell CF and Mason RP (1999) Evidence for free radical formation during the oxidation of 2′-7′-dichlorofluorescin to the fluorescent dye 2′-7′-dichlorofluorescein by horseradish peroxidase: possible implications for oxidative stress measurements. Free Radic. Biol. Med. 27: 873–881.PubMedCrossRefGoogle Scholar
  23. 23.
    Rota C, Fann YC and Mason RP (1999) Phenoxyl free radical formation during the oxidation of the fluorescent dye 2′-7′-dichlorofluorescein by horseradish peroxidase: possible consequences for oxidative stress measurements. J. Biol. Chem. 274: 28161–28168.PubMedCrossRefGoogle Scholar
  24. 24.
    Takeshige K and Minakami S (1979) NADH- and NADPH-dependent formation of superoxide anions by bovine heart submitochondrial particles and NADH-ubiquinone reductase preparation. Biochem. J. 180: 129–135.PubMedGoogle Scholar
  25. 25.
    Lambert AJ and Brand MD (2004) Inhibitors of the quinone-binding site allow rapid superoxide production from mitochondrial NADH:ubiquinone oxidoreductase (complex I). J. Biol. Chem. 279: 39414–39420.PubMedCrossRefGoogle Scholar
  26. 26.
    Gonzalez-Flecha B, Cutrin JC and Boveris A (1993). Time course and mechanism of oxidative stress in rat liver subjected to in vivo ischemis-reperfusion. J Clin Invest 91: 456–464.PubMedCrossRefGoogle Scholar
  27. 27.
    Hensley K, Kotake Y, Sang H, Pye QN, Wallis GL, Kolker LM, Tabatabaie T, Stewart Ca, Konishi Y, Nakae D and Floyd RA (2000) Dietary choline restriction causes complex I dysfunction and increased H2O2 generation in liver mitochondria. Carcinogenesis 21: 983–989.PubMedCrossRefGoogle Scholar
  28. 28.
    Carreras MC, Converso DP, Lorenti AS, Barbich M, Levisman DM, Jaitovich A, Antico-Arciuch VG, Galli S and Poderoso JJ (2004) Mitochondrial nitric oxide synthase drives redox signals for proliferation and quiescence in rat liver development. Hepatology 40: 157–166.PubMedCrossRefGoogle Scholar
  29. 29.
    Boveris A and Stoppani AOM (1971). Inhibition of electron transport and energy transfer by 19-nor-ethinyl-testosterone acetate. Arch Biochem Biophys 141: 641–655.CrossRefGoogle Scholar
  30. 30.
    Gomez C, Bandez MJ and Navarro A (2007). Pesticides and impairment of mitochondrial function in relation with the parkinsonian syndrome. Front Biosci 12: 1079–1093.PubMedCrossRefGoogle Scholar
  31. 31.
    Shapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, and Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54: 823–827.CrossRefGoogle Scholar
  32. 32.
    Shapira AH (2008) Mitochondria in the aethiology of Parkinson’s disease. Lancet Neurol 7: 97–109.CrossRefGoogle Scholar
  33. 33.
    Carreras MC, Franco MC, Peralta JG and Poderoso JJ (2004) Mol Aspects Med 25: 125–139.PubMedCrossRefGoogle Scholar
  34. 34.
    Navarro A, Boveris A, Bandez MJ, Sanchez-Pino MJ, Gomez C, Muntane G and Ferrer 1 (2009) Human brain cortex: mitchondrial oxidative damage and adaptive response in Parkinson’s disease and in dementia with Lewy bodies. Free Radic Biol Med 46: 1574–1580.Google Scholar
  35. 35.
    Boveris A and Navarro A (2008) Brain mitochondrial dysfunction in aging. IUBMB Life 60: 308–314.PubMedCrossRefGoogle Scholar
  36. 36.
    Liu Q, Raina AK, Smith MA, Sayre LM and Perry G (2003) Hydroxynonenal, toxic carbonyls and Alzheimer disease. Mol Aspects Med 24: 305–313.PubMedCrossRefGoogle Scholar
  37. 37.
    Han D, Antunes F, Daneri F and Cadenas E (2002) Mitochondrial superoxide anion production and release into intermembrane space. Meth. Enzymol. 349: 271–280.PubMedCrossRefGoogle Scholar
  38. 38.
    Starkov AA and Fiskum G (2001) Myxothiazol induces H2O2 production from mitochondrial respiratory chain. Biochem. Biophys. Res. Commun. 281: 645–650.PubMedCrossRefGoogle Scholar
  39. 39.
    von Jagow G and Link TA (1986) Use of specific inhibitors on the mitochondrial bc1 complex. Methods Enzymol. 126: 253–271.CrossRefGoogle Scholar
  40. 40.
    Iñarrea P (2002) Purification and determination of activity of mitochondrial cyanide-sensitive superoxide dismutase in rat tissue extract. Methods Enzymol. 349: 106–114.PubMedCrossRefGoogle Scholar
  41. 41.
    Iñarrea P, Moini H, Han D, Rettori D, Aguilo I, Alava MA, Iturralde M and Cadenas E (2007) Mitochondrial respiratory chain and thioredoxin reductase regulate intermembrane Cu,Zn-superoxide dismutase activity: implications for mitochondrial energy metabolism and apoptosis. Biochem. J. 405: 173–179.Google Scholar
  42. 42.
    Iñarrea P, Moini H, Rettori D, Han D, Martinez J, Garcia I, Fernandez-Vizarra E, Iturralde M and Cadenas E (2005) Redox activation of mitochondrial intermembrane space Cu,Zn-superoxide dismutase. Biochem J. 387: 203–209.PubMedCrossRefGoogle Scholar
  43. 43.
    Muller FL, Liu Y and Van Remmen H (2004) Complex III releases superoxide to both sides of the inner mitochondrial membrane. J. Biol. Chem.. 279: 49064–49073.PubMedCrossRefGoogle Scholar
  44. 44.
    Poderoso JJ, Carreras MC, Lisdero C, Riobo N, Schopfer F and Boveris A (1996) Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch. Biochem. Biophys. 328: 85–92.PubMedCrossRefGoogle Scholar
  45. 45.
    Brown GC and Copper CE (1994) Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett. 356: 295–298.PubMedCrossRefGoogle Scholar
  46. 46.
    Cleeter MW, Cooper JM, Darley-Usmar VM, Moncada S and Schapira AH (1994) Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases. FEBS Lett. 345: 50–54.Google Scholar
  47. 47.
    Cooper CE and Giulivi C (2007) Nitric oxide regulation of mitochondrial oxygen consumption II: molecular mechanism and tissue physiology. Am. J. Physiol. Cell Physiol. 292: C1993–C2003.PubMedCrossRefGoogle Scholar
  48. 48.
    Brown GC (1995) Nitric oxide regulates mitochondrial respiration and cell functions by inhibiting cytochrome oxidase. FEBS Lett. 369: 136–139.PubMedCrossRefGoogle Scholar
  49. 49.
    Antunes F, Boveris A and Cadenas E (2004) On the mechanism and biology of cytochrome oxidase inhibition by nitric oxide. Proc. Natl. Acad. Sci. USA. 101: 16774–16779.PubMedCrossRefGoogle Scholar
  50. 50.
    Antunes F, Boveris A and Cadenas E (2007) On the biologic role of the reaction of NO with oxidized cytochrome c oxidase. Antioxid. Redox Signal. 9: 1569–1579.PubMedCrossRefGoogle Scholar
  51. 51.
    Han D, Antunes F, Canali R, Rettori D and Cadenas E (2003) Voltage-dependent anion channels control the release of the superoxide anion from mitochondria to cytosol. J. Biol. Chem. 278: 5557–5563.PubMedCrossRefGoogle Scholar
  52. 52.
    Skulachev VP (1996) Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants. Q. Rev. Biophys. 29: 169–202.PubMedCrossRefGoogle Scholar
  53. 53.
    Korshunov SS, Skulachev VP and Starkov AA (1997) High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett. 416: 15–18.PubMedCrossRefGoogle Scholar
  54. 54.
    Starkov AA and Fiskum G (2003) Regulation of brain mitochondrial H2O2 production by membrane potential and NAD(P)H redox state. J. Neurochem. 86: 1101–1107.PubMedCrossRefGoogle Scholar
  55. 55.
    Boveris A (1977) Mitochondrial production of superoxide radical and hydrogen peroxide. Adv. Exp. Med. Biol. 78: 67–82.PubMedCrossRefGoogle Scholar
  56. 56.
    Boveris A, Cadenas E and Stoppani AOM (1976) Role of ubiquinone in the mitochondrial generation of hydrogen peroxide. Biochem. J. 156: 435–444.PubMedGoogle Scholar
  57. 57.
    Guzy RD, Sharma B, Bell E, Chandel NS and Schumacker PT (2008) Loss of the SdhB, but not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-induced factor activation and tumorigenesis. Mol. Cell. Biol. 28: 718–731.PubMedCrossRefGoogle Scholar
  58. 58.
    Yankovskaya V, Horsefield R, Törnroth S, Luna-Chavez C, Miyoshi H, Léger C, Byrne B, Cecchini G and Iwata S (2003) Architecture of succinate dehydrogenase and reactive oxygen species generation. Science. 299: 700–704.PubMedCrossRefGoogle Scholar
  59. 59.
    Bacsi A, Woodberry M, Widger W, Papaconstantinou J, Mitra S, Peterson JW and Boldogh I (2006) Localization of superoxide anion production to mitochondrial electron transport chain in 3-NPA-treated cells. Mitochondrion. 6: 235–244.PubMedCrossRefGoogle Scholar
  60. 60.
    Forman HJ and Kennedy J (1976) Dihydroorotate-dependent superoxide production in rat brain and liver. A function of the primary dehydrogenase. Arch. Biochem. Biophys. 173: 219–224.CrossRefGoogle Scholar
  61. 61.
    Tretter L and Adam-Vizi V (2005) Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress. Philosophical transactions of the Royal Society of London. 360: 2335–2345.PubMedCrossRefGoogle Scholar
  62. 62.
    Starkov AA, Fiskum G, Chinopoulos C, Lorenzo BJ, Browne SE, Patel MS and Beal MF (2004) Mitochondrial a-ketoglutarate dehydrogenase complex generates reactive oxygen species. J. Neurosci. 24: 7779–7788.PubMedCrossRefGoogle Scholar
  63. 63.
    Tretter L, Takacs K, Hegedus V and Adam-Vizi V (2007) Characteristics of alpha-glycerophosphate-evoked H2O2 generation in brain mitochondria. J. Neurochem.. 100: 650–663.PubMedCrossRefGoogle Scholar
  64. 64.
    Suzuki YJ, Forman HJ and Sevanian A (1997) Oxidants as stimulators of signal transduction. Free Radic. Biol. Med. 22: 269–285.PubMedCrossRefGoogle Scholar
  65. 65.
    Aslund F and Beckwith J (1999) Bridge over troubled waters: sensing stress by disulfide bond formation. Cell. 96: 751–753.PubMedCrossRefGoogle Scholar
  66. 66.
    Rhee SG (2006) Hydrogen peroxide. A necessary evil for cell signaling. Science. 312: 1882–1883.Google Scholar
  67. 67.
    Janssen-Heininger YM, Mossman BT, Heintz NH, Forman HJ, Kalyanaraman B, Finkel T, Stamler JS, Rhee SG and van der Vliet A (2008) Redox-based regulation of signal transduction: principles, pitfalls, and promises. Free Radic. Biol. Med. 45: 1–17.PubMedCrossRefGoogle Scholar
  68. 68.
    Oshino N, Chance B, Sies H and Bucher T (1973) The role of hydrogen peroxide generation in perfused rat liver and the reaction of catalase compound I and hydrogen donors. Arch. Biochem. Biophys. 154: 117–131.PubMedCrossRefGoogle Scholar
  69. 69.
    Boveris A, Oshino N, Chance B (1972) The cellular production of hydrogen peroxide. Biocehm J. 128: 617–630.Google Scholar
  70. 70.
    Watabe S, Hiroi T, Yamamoto Y, Fujioka Y, Hasegawa H, Yago N and Takahashi SY (1997) SP-22 is a thioredoxin-dependent peroxide reductase in mitochondria. Eur. J. Biochem. 249: 52–60.PubMedCrossRefGoogle Scholar
  71. 71.
    Rhee SG, Chae HZ and Kim K (2005) Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radic. Biol. Med. 38: 1543–1552.PubMedCrossRefGoogle Scholar
  72. 72.
    Noh YH, Baek JY, Jeong W, Rhee SG and Chang TS (2009) Sulfiredoxin Translocation into Mitochondria Plays a Crucial Role in Reducing Hyperoxidized Peroxiredoxin III. J. Biol. Chem.. 284: 8470–8477.PubMedCrossRefGoogle Scholar
  73. 73.
    Lambeth JD (2004) NOX enzymes and the biology of reactive oxygen. Nat. Rev. Immunol. 4: 181–189.PubMedCrossRefGoogle Scholar
  74. 74.
    Terada LS (2006) Specificity in reactive oxidant signaling: think globally, act locally. J. Cell. Biol. 174: 615–623.PubMedCrossRefGoogle Scholar
  75. 75.
    Zou MH, Kirkpatrick SS, Davis BJ, Nelson JS, Wiles WG, Schlattner U, Neumann D, Brownlee M, Freeman MB and Goldman MH (2004) Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin in vivo. Role of mitochondrial reactive nitrogen species. J. Biol. Chem.. 279: 43940–43951.Google Scholar
  76. 76.
    Nemoto S, Takeda K, Yu ZX, Ferrans VJ and Finkel T (2000) Role for mitochondrial oxidants as regulators of cellular metabolism. Mol. Cell Biol. 20: 7311–7318.PubMedCrossRefGoogle Scholar
  77. 77.
    Zhou Q, Lam PY, Han D and Cadenas E (2008) c-Jun N-terminal kinase regulates mitochondrial bioenergetics by modulating pyruvate dehydrogenase activity in primary cortical neurons. J. Neurochem. 104: 325–335.PubMedGoogle Scholar
  78. 78.
    Zhou Q, Lam PY, Han D and Cadenas E (2009) Activation of c-Jun-N-terminal kinase and decline of mitochondrial pyruvate dehydrogenase activity during brain aging. FEBS Lett. 583: 1132–1140.PubMedCrossRefGoogle Scholar
  79. 79.
    Forman HJ, Fukuto JM and Torres M (2004) Redox signaling: thiol chemistry defines which reactive oxygen and nitrogen species can act as second messengers. Am. J. Physiol., Cell Physiol. 287: C246–C256.CrossRefGoogle Scholar
  80. 80.
    Paget MS and Buttner MJ (2003) Thiol-based regulatory switches. Annu. Rev. Genet. 37: 91–121.PubMedCrossRefGoogle Scholar
  81. 81.
    Adler V, Funchs SY, Benezra M, Rosario L, Tew KD, Pincus MR, Sardana M, Henderson CJ, Wolf CR, Davis RJ and Ronai Z (1999) Regulation of JNK signaling by GSTp. EMBO J. 18: 1321–1234.PubMedCrossRefGoogle Scholar
  82. 82.
    Antunes F and Cadenas E (2000) Estimation of H2O2 gradients across biomembranes. FEBS Lett. 475: 121–126.PubMedCrossRefGoogle Scholar
  83. 83.
    Antunes F and Cadenas E (2001) Cellular titration of apoptosis with steady state concentrations of H(2)O(2): submicromolar levels of H(2)O(2) induce apoptosis through Fenton chemistry independent of the cellular thiol state. Free Radic. Biol. Med. 30: 1008–1018.PubMedCrossRefGoogle Scholar
  84. 84.
    Antunes F, Cadenas E and Brunk UT (2001) Apoptosis induced by exposure to a low ­steady-state concentration of H2O2 is a consequence of lysosomal rupture. Biochem. J. 356: 549–555.PubMedCrossRefGoogle Scholar
  85. 85.
    Pletjushkina OY, Fetisova EK, Lyamzaev KG, Ivanova OY, Domnina LV, Vyssokikh MY, Pustovidko AV, Alexeevski AV, Alexeevski DA, Vasiliev JM, Murphy MP, Chernyak BV and Skulachev VP (2006) Hydrogen peroxide produced inside mitochondria takes part in cell-to-cell transmission of apoptotic signal. Biochemistry (Mosc). 71: 60–67.CrossRefGoogle Scholar
  86. 86.
    Bao L, Avshalumov MV, Patel JC, Lee CR, Miller EW, Chang CJ and Rice ME (2009) Mitochondria are the source of hydrogen peroxide for dynamic brain cell signaling. J. Neurosci. 29: 9002–9010.PubMedCrossRefGoogle Scholar
  87. 87.
    Cerioni L and Cantoni O (2008) Mitochondrial H2O2 limits U937 cell survival to peroxynitrite by promoting ERK1/2 phosphorylation. Biochim. Biophys. Acta. 1783: 492–502.PubMedCrossRefGoogle Scholar
  88. 88.
    Cantoni O and Guidarelli A (2008) Peroxynitrite damages U937 cell DNA via the intermediate formation of mitochondrial oxidants. IUBMB Life. 60: 753–756.PubMedCrossRefGoogle Scholar
  89. 89.
    Schöpfer F, Riobó NA, Carreras MC, Alvarez B, Radi R, Boveris A, Cadenas E and Poderoso JJ (2000) Oxidation of ubiquinol by peroxynitrite: implications for protection of mitochondria against nitrosative damage. Biochem. J. 349: 35–42.PubMedCrossRefGoogle Scholar
  90. 90.
    Lam PY, Yin F, Hamilton RT, Boveris A and Cadenas E (2009) Elevated neuronal nitric oxide synthase expression during ageing and mitochondrial energy production. Free Radic. Res. 43: 431–439.PubMedCrossRefGoogle Scholar
  91. 91.
    Galli S, Antico Arciuch VG, Poderoso C, Converso DP, Zhou Q, Bal de Kier Joffé E, Cadenas E, Boczkowski J, Carreras MC and Poderoso JJ (2008) Tumor cell phenotype is sustained by selective MAPK oxidation in mitochondria. PLoS One. 3: e2379.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Pharmacology and Pharmaceutical Sciences, School of PharmacyUniversity of Southern CaliforniaLos AngelesUSA

Personalised recommendations