Importance of oxidative damage on the electron transport chain for the rational use of mitochondria-targeted antioxidants

Mini-Reviews in Medicinal Chemistry

Volumn 11, Issue 7, 2011, Pages 625-632

  Cortes Rojo C ^a   Rodriguez Orozco A R ^a,b  

^a UNIVERSIDAD MICHOACANA DE SAN NICOLÁS DE HIDALGO   (Mexico)

^b Instituto de Investigacion Cientifica en Temas de Familia   (Mexico)

Author keywords

Iron; Ischemia reperfusion; Lipid peroxidation; Liver diseases; Mitoq; Neurodegeneration; Respiratory chain; Thiol oxidation

Indexed keywords

ANTIOXIDANT; GLUTATHIONE; REACTIVE OXYGEN METABOLITE; THIOL;

ANTIOXIDANT ACTIVITY; ARTICLE; BRAIN MITOCHONDRION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG TARGETING; ELECTRON TRANSPORT; IRON OVERLOAD; LIPID PEROXIDATION; MITOCHONDRION DAMAGE; OXIDATION; OXIDATIVE STRESS;

ANIMALS; ANTIOXIDANTS; ELECTRON TRANSPORT; HUMANS; MITOCHONDRIA; OXIDATION-REDUCTION; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES;

EID: 79960027264     PISSN: 13895575     EISSN: 18755607     Source Type: Journal    
DOI: 10.2174/138955711795906879     Document Type: Article

References (89)

1. Nicholls, D.G. Mitochondria and cell signalling. Cell Calcium, 2005, 38, 311-7.
2. Kwok, E.; Kosman, D. In: Molecular Biology of Metal Homeostasis and Detoxification. From Microbes to Man, Tamàs, M.J.; Martinoia, E., Eds.; Springer: Berlin, 2006; pp. 59-100.
3. Giannattasio, S.; Liu, Z.; Thornton, J.; Butow, R.A. Retrograde response to mitochondrial dysfunction is separable from TOR1/2 regulation of retrograde gene expression. J. Biol. Chem., 2005, 280, 42528-35.
4. Chelstowska, A.; Liu, Z.; Jia, Y.; Amberg, D.; Butow, R.A. Signalling between mitochondria and the nucleus regulates the expression of a new D-lactate dehydrogenase activity in yeast. Yeast, 1999, 15, 1377-91.
5. Sugiyama, K.; Izawa, S.; Inoue, Y. The Yap1p-dependent inductionof glutathione synthesis in heat shock response of Saccharomyces cerevisiae. J. Biol. Chem., 2000, 275, 15535-40.
6. Mandal, S.; Guptan, P.; Owusu-Ansah, E.; Banerjee, U. Mitochondrial regulation of cell cycle progression during development as revealed by the tenured mutation in Drosophila. Dev. Cell., 2005, 9, 843-54.
7. Byun, H.O.; Kim, H.Y.; Lim, J.J.; Seo, Y.H.; Yoon, G. Mitochondrial dysfunction by complex II inhibition delays overall cell cycle progression via reactive oxygen species production. J. Cell Biochem., 2008, 104, 1747-59.
8. Kroemer, G.; Reed, J.C. Mitochondrial control of cell death. Nat. Med., 2000, 6, 513-9.
9. Nicholls, D.G.; Ferguson, S.J. Bioenergetics 3; Academic Press: London, 2002.
10. Seppet, E.; Gruno, M.; Peetsalu, A.; Gizatullina, Z.; Nguyen, H.P.; Vielhaber, S.; Wussling, M.H.; Trumbeckaite, S.; Arandarcikaite, O.; Jerzembeck, D.; Sonnabend, M.; Jegorov, K.; Zierz, S.; Striggow, F.; Gellerich, F.N. Mitochondria and energetic depression in cell pathophysiology. Int. J. Mol. Sci., 2009, 10, 2252-303.
11. Do, T.Q.; Schultz, J.R.; Clarke, C.F. Enhanced sensitivity of ubiquinone-deficient mutants of Saccharomyces cerevisiae to products of autoxidized polyunsaturated fatty acids. Proc. Natl. Acad. Sci. USA, 1996, 93, 7534-39.
12. Paravicini, T.M.; Touyz, R.M. NADPH oxidases; reactive oxygen species, and hypertension. Diabetes care, 2008, 31, S170-80.
13. Rojas, A.; Figueroa, H.; Morales, M.A.; Re, L. Facing up the ROS labyrinth -Where to go? Curr. Vasc. Pharmacol., 2006, 4, 277-89.
14. Lambert, A.J.; Brand, M.D. Reactive oxygen species production by mitochondria. Methods. Mol. Biol., 2009, 554, 165-81.
15. Czarna, M.; Jarmuszkiewicz, W. Role of mitochondria in reactive oxygen species generation and removal; relevance to signaling and programmed cell death. Postepy. Biochem., 2006, 52, 145-56.
16. Krause, K.H. Aging: a revisited theory based on free radicals generated by NOX family NADPH oxidases. Exp. Gerontol., 2007, 42, 256-62.
17. Block, K.; Gorin, Y.; Abboud, H.E. Subcellular localization of Nox4 and regulation in diabetes. Proc. Natl. Acad. Sci. U S A., 2009, 106, 14385-90.
18. Ago, T.; Kuroda, J.; Pain, J.; Fu, C.; Li, H.; Sadoshima, J. Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ. Res., 2010, 106, 1253-64.
19. Graham, K.A.; Kulawiec, M.; Owens, K.M.; Li, X.; Desouki, M.M.; Chandra, D.; Singh, K.K. NADPH oxidase 4 is an oncoprotein localized to mitochondria. Cancer Biol. Ther., 2010, 10, 223-31.
20. Doughan, A.K.; Harrison, D.G.; Dikalov, S.I. Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ. Res., 2008, 102, 488-96.
21. Dikalova, A.E.; Bikineyeva, A.T.; Budzyn, K.; Nazarewicz, R.R.; McCann, L.; Lewis, W.; Harrison, D.G.; Dikalov, S.I. Therapeutic targeting of mitochondrial superoxide in hypertension. Circ. Res., 2010, 107, 106-16.
22. Boldogh, I.; Bacsi, A.; Choudhury, B.K.; Dharajiya, N.; Alam, R.; Hazra, T.K.; Mitra, S.; Goldblum, R.M.; Sur, S. ROS generated by pollen NADPH oxidase provide a signal that augments antigeninduced allergic airway inflammation. J. Clin. Invest., 2005, 115, 2169-179.
23. Aguilera-Aguirre, L.; Bacsi, A.; Saavedra-Molina, A.; Kurosky, A.; Sur, S.; Boldogh, I. Mitochondrial dysfunction increases allergic airway inflammation. J. Immunol., 2009, 183, 5379-387.
24. Soberanes, S.; Urich, D.; Baker, C.M.; Burgess, Z.; Chiarella, S.E.; Bell, E.L.; Ghio, A.J.; De Vizcaya-Ruiz, A.; Liu, J.; Ridge, K.M.; Kamp, D.W.; Chandel, N.S.; Schumacker, P.T.; Mutlu, G.M.; Budinger, G.R. Mitochondrial complex III-generated oxidants activate ASK1 and JNK to induce alveolar epithelial cell death following exposure to particulate matter air pollution. J. Biol. Chem., 2009, 284, 2176-186.
25. Ambrosio, G.; Zweier, J.L.; Duilio, C.; Kuppusamy, P.; Santoro, G.; Elia, P.P.; Tritto, I.; Cirillo, P.; Condorelli, M.; Chiariello, M.; Flaherty, J.T. Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow. J. Biol. Chem., 1993, 268, 18532-41.
26. Paradies, G.; Petrosillo, G.; Pistolese, M.; Di Venosa, N.; Federici, A.; Ruggiero, F.M. Decrease in mitochondrial complex I activity in ischemic/reperfused rat heart: involvement of reactive oxygen species and cardiolipin. Circ. Res., 2004, 94, 53-59
27. Petrosillo, G.; Ruggiero, F.M.; Di Vennosa, N.; Paradies, G. Decreased complex III activity in mitochondria isolated from rat heart subjected to ischemia and reperfusion: role of reactive oxygen species and cardiolipin. FASEB J., 2003, 17, 714-6.
28. Paradies, G.; Petrosillo, G.; Pistolese, M.; Di Venosa, N.; Serena, D.; Ruggiero, F.M. Lipid peroxidation and alterations to oxidative metabolism in mitochondria isolated from rat heart subjected to ischemia and reperfusion. Free. Rad. Biol. Med., 1999, 27, 42-50.
29. Camara, A.K.; Lesnefsky, E.J.; Stowe, D.F. Potential therapeutic benefits of strategies directed to mitochondria. Antioxid. Redox. Signal., 2010, 13, 279-347.
30. Korenaga, M.; Wang, T.; Li, Y.; Showalter, L.A.; Chan, T.; Sun, J.; Weinman, S.A. Hepatitis C virus core protein inhibits mitochondrial electron transport and increases reactive oxygen species (ROS) production. J. Biol. Chem., 2005, 280, 37481-8.
31. Graf, E.; Mahone, J.R.; Bryant, R.G.; Eaton, J.W. Iron-catalyzed hydroxyl radical formation. Stringent requirement for free iron coordination site. J. Biol. Chem., 1984, 259, 3620-4.
32. Luo, Y.; Han, Z.; Chin, S.M.; Linn, S. Three chemically distinct types of oxidants formed by iron-mediated Fenton reactions in the presence of DNA. Proc. Natl. Acad. Sci. U S A, 1994, 191, 12438-42.
33. Faucheux, B.A.; Martin, M.E.; Beaumont, C.; Hauw, J.J.; Agid, Y.; Hirsch, E.C. Neuromelanin associated redox-active iron is increased in the substantia nigra of patients with Parkinson's disease. J. Neurochem., 2003, 86, 1142-8.
34. Bharath, S.; Hsu, M.; Kaur, D.; Rajagopalan, S.; Andersen, J.K. Glutathione, iron and Parkinson's disease. Biochem. Pharmacol., 2002, 64, 1037-48.
35. Keeney, P.M.; Xie, J.; Capaldi, R.A.; Bennett, J.P. Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J. Neurosci., 2006, 26, 5256-64.
36. Casadesus, G.; Smith, M.A.; Zhu, X.; Aliev, G.; Cash, A.D.; Honda, K.; Petersen, R.B.; Perry, G. Alzheimer disease: evidence for a central pathogenic role of iron-mediated reactive oxygen species. J. Alzheimers Dis., 2004, 6, 165-9.
37. Castellani, R.; Hirai, K.; Aliev, G.; Drew, K.L.; Nunomura, A.; Takeda, A.; Cash, A.D.; Obrenovich, M.E.; Perry, G.; Smith, M.A. Role of mitochondrial dysfunction in Alzheimer's disease. J. Neurosci. Res., 2002, 70, 357-360.
38. Sen, T.; Sen, N.; Tripathi, G.; Chatterjee, U.; Chakrabarti, S. Lipid peroxidation associated cardiolipin loss and membrane depolarization in rat brain mitochondria. Neurochem. Int., 2006, 49, 20-27.
39. Batts, K.P. Iron overload syndromes and the liver. Mod. Pathol., 2007, 20, S31-9.
40. Masini, A.; Ceccarelli, D.; Giovannini, F.; Montosi, G.; Garuti, C.; Pietrangelo, A. Iron-induced oxidant stress leads to irreversible mitochondrial dysfunctions and fibrosis in the liver of chronic irondosed gerbils. The effect of silybin. J. Bioenerg. Biomembr., 2000, 32, 175-82.
41. Halliwell, B.; Gutteridge, J.M.C. Free radicals in biology and medicine, Oxford University Press: Oxford, 1999.
42. Rice-Evans, C.A.; Burdon, R.H. Free radical damage and its control, Elsevier Science BV: Amsterdam, 1994.
43. Chicco, A.J.; Sparagna, G.C. Role of cardiolipin alterations in mitochondrial dysfunction and disease. Am. J. Physiol. Cell Physiol., 2007, 292, 33-44.
44. Lange, C.; Nett, J.H.; Trumpower, B.L.; Hunte, C. Specific roles of protein-phospholipid interactions in the yeast cytochrome bc1 complex structure. EMBO J., 2001, 20, 6591-600.
45. Tsai, A.; Palmer, G. The role of phospholipids in the binding of antimycin to yeast complex III. Biochim. Biophys. Acta, 1986, 852, 100-5.
46. Forsmark-Andreé, P.; Lee, C.P.; Dallner, G.; Ernster, L. Lipid peroxidation and changes in the ubiquinone content and the respiratory chain enzymes of submitochondrial particles. Free Radic. Biol. Med., 1997, 22, 391-400.
47. Cortés-Rojo, C.; Calderón-Cortés, E.; Clemente-Guerrero, M.; Estrada-Villagómez, M.; Manzo-Avalos, S.; Mejía-Zepeda, R.; Boldogh, I.; Saavedra-Molina, A. Elucidation of the effects of lipoperoxidation on the mitochondrial electron transport chain using yeast mitochondria with manipulated fatty acid content. J. Bioenerg. Biomembr., 2009, 41, 15-28.
48. Cardoso, S.M.; Pereira, C.; Oliveira, C.R. Mitochondrial function is differentially affected upon oxidative stress. Free Radic. Biol. Med., 1999, 26, 3-13.
49. Winterbourn, C.C. Superoxide as an intracellular radical sink. Free Radic. Biol. Med., 1993, 14, 85-90.
50. Lin, T.K.; Hughes, G.; Muratovska, A; Blaikie, F.H.; Brookes, P.S.; Darley-Usmar, V.; Smith, R.A.; Murphy, M.P. Specific modification of mitochondrial protein thiols in response to oxidative stress: a proteomics approach. J. Biol. Chem., 2002, 277, 17048-56.
51. Hurd, T.R.; Prime, T.A.; Harbour, M.E.; Lilley, K.S.; Murphy, M.P. Detection of reactive oxygen species-sensitive thioproteins by redox difference gel electrophoresis: implications for mitochondrial redox signaling. J. Biol. Chem., 2007, 282, 22040-51.
52. Cortés-Rojo, C.; Calderón-Cortés, E.; Clemente-Guerrero, M.; Manzo-Avalos, S.; Uribe, S.; Boldogh, I.; Saavedra-Molina, A. Electron transport chain of Saccharomyces cerevisiae mitochondria is inhibited by H2O2 at succinate-cytochrome c oxidoreductase level without lipid peroxidation involvement. Free Radic. Res., 2007, 41, 1212-23.
53. Zhang, Y.; Marcillat, O.; Giulivi, C.; Ernster, L.; Davies, K.J. The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J. Biol. Chem., 1990, 265, 16330-6.
54. Hurd, T.R.; Requejo, R.; Filipovska, A.; Brown, S.; Prime, T.A.; Robinson, A.J.; Fearnley, I.M.; Murphy, M.P. Complex I within oxidatively stressed bovine heart mitochondria is glutathionylated on Cys-531 and Cys-704 of the 75-kDa subunit: potential role of Cys residues in decreasing oxidative damage. J. Biol. Chem., 2008, 283, 24801-15.
55. Nulton-Persson, A.C.; Szweda, L.I. Modulation of mitochondrial function by hydrogen peroxide. J. Biol. Chem., 2001, 276, 23357-61.
56. Zini, R.; Berdeaux, A.; Morin, D. The differential effects of superoxide anion, hydrogen peroxide and hydroxyl radical on cardiac mitochondrial oxidative phosphorylation. Free Radic. Res. 2007, 41, 1159-66.
57. Forman, H.J.J.; Fukuto, M.; Torres, M. Redox signaling: thiol chemistry defines which reactive oxygen and nitrogen species can act as second messengers. Am. J. Physiol. Cell Physiol., 2004, 287, C246-56.
58. Requejo, R.; Hurd, T.R.; Costa, N.J.; Murphy, M.P. Cysteine residues exposed on protein surfaces are the dominant and mitochondrial dysfunction in cardiac myocytes. Circ. Res., 2010, 106, 1253-64.
59. Song, Y.; Cook, N.R.; Albert, C.M.; Van Denburgh, M.; Manson, J.E. Effects of vitamins C and E and beta-carotene on the risk of type 2 diabetes in women at high risk of cardiovascular disease: a randomized controlled trial. Am. J. Clin. Nutr., 2009, 90, 429-37.
60. Sesso, H.D.; Buring, J.E.; Christen, W.G.; Kurth, T.; Belanger, C.; MacFadyen, J.; Bubes, V.; Manson, J.E.; Glynn, R.J.; Gaziano, J.M. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA, 2008, 300, 2123-33.
61. Smith, R.A.J.; Porteous, C.M.; Gane, A.M.; Murphy, M.P. Delivery of bioactive molecules to mitochondria in vivo. Proc. Natl. Acad. Sci. U S A, 2003, 100, 5407-12.
62. Dhanasekaran, A.; Kotamraju, S.; Kalivendi, S.V.; Matsunaga, T.; Shang, T.; Keszler, A.; Joseph, J.; Kalyanaraman, B. Supplementation of endothelial cells with mitochondria-targeted antioxidants inhibit peroxide-induced mitochondrial iron uptake, oxidative damage, and apoptosis. J. Biol. Chem., 2004, 279, 37575-87.
63. Adlam, V.J.; Harrison, J.C.; Porteous, C.M.; James, A.M.; Smith, R.A.; Murphy, M.P.; Sammut, I.A. Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury. FASEB J., 2005, 19, 1088-95.
64. Jauslin, M.L.; Meier, T.; Smith, R.A.J.; Murphy, M.P. Mitochondria-targeted antioxidants protect Friedreich ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants. FASEB J., 2003, 17, 1972-4.
65. Heidari, M.M.; Houshmand, M.; Hosseinkhani, S.; Nafissi, S.; Khatami, M. Complex I and ATP content deficiency in lymphocytes from Friedreich's ataxia. Can. J. Neurol. Sci., 2009, 36, 26-31.
66. James, A.M.; Cochemé, H.M.; Smith, R.A.J.; Murphy, M.P. Interactions of mitochondria-targeted and untargeted ubiquinones with the mitochondrial respiratory chain and reactive oxygen species. J. Biol. Chem., 2005, 280, 21295-312.
67. Snow, B.J.; Rolfe, F.L.; Lockhart, M.M.; Frampton, C.M.; O'Sullivan, J.D.; Fung, V.; Smith, R.A.; Murphy, M.P.; Taylor, K.M.; Protect Study Group. A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease. Mov. Disord., 2010, 25, 1670-4.
68. Smith, R.A.; Murphy, M.P. Animal and human studies with the mitochondria-targeted antioxidant MitoQ. Ann. N Y Acad. Sci., 2010, 1201, 96-103.
69. Jha, N.; Jurma, O.; Lalli, G.; Liu, Y.; Pettus, E.H.; Greenamyre, J.T.; Liu, R.M.; Forman, H.J.; Andersen, J.K. Glutathione depletion in PC12 results in selective inhibition of mitochondrial complex I activity. Implications for Parkinson_s disease. J. Biol. Chem., 2000, 275, 26096-101.
70. Sheu, S.S.; Nauduri, D.; Anders, M.W. Targeting antioxidants to mitochondria: a new therapeutic direction. Biochim. Biophys. Acta, 2006, 1762, 256-65.
71. Doughan, A.K.; Dikalov, S.I. Mitochondrial redox cycling of mitoquinone leads to superoxide production and cellular apoptosis. Antioxid. Redox Signal., 2007, 9, 1825-36.
72. Kelso, G.F.; Porteous, C.M.; Coulter, C.V.; Hughes, G.; Porteous, W.K.; Ledgerwood, E.C.; Smith, R.A.; Murphy, M.P. Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J. Biol. Chem., 2001, 276,4588-4596.
73. Skulachev, V.P.; Anisimov, V.N.; Antonenko, Y.N.; Bakeeva, L.E.; Chernyak, B.V.; Erichev, V.P.; Filenko, O.F.; Kalinina, N.I.; Kapelko, V.I.; Kolosova, N.G.; Kopnin, B.P.; Korshunova, G.A.; Lichinitser, M.R.; Obukhova, L.A.; Pasyukova, E.G.; Pisarenko, O.I.; Roginsky, V.A.; Ruuge, E.K.; Senin, I.I.; Severina, I.I.; Skulachev, M.V.; Spivak, I.M.; Tashlitsky, V.N.; Tkachuk, V.A.; Vyssokikh, M.Y.; Yaguzhinsky, L.S.; Zorov, D.B. An attempt to prevent senescence: a mitochondrial approach. Biochim Biophys Acta, 2009, 1787, 437-61.
74. Antonenko, Y.N.; Avetisyan, A.V.; Bakeeva, L.E.; Chernyak, B.V.; Chertkov, V.A.; Domnina, L.V.; Ivanova, O.Y.; Izyumov, D.S.; Khailova, L.S.; Klishin, S.S.; Korshunova, G.A.; Lyamzaev, K.G.; Muntyan, M.S.; Nepryakhina, O.K.; Pashkovskaya, A.A.; Pletjushkina, O.Y.; Pustovidko, A.V.; Roginsky, V.A.; Rokitskaya, T.I.; Ruuge, E.K.; Saprunova, V.B.; Severina, I.I.; Simonyan, R.A.; Skulachev, I.V.: Skulachev, M.V.; Sumbatyan, N.V.; Sviryaeva, I.V.; Tashlitsky, V.N.; Vassiliev, J.M.; Vyssokikh, M.Y.; Yaguzhinsky, L.S.; Zamyatnin, A.A. Jr,; Skulachev, V.P. Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in vitro studies. Biochemistry (Mosc), 2008, 73, 1273-87.
75. Rodríguez-Cuenca, S.; Cochemé, H.M.; Logan, A.; Abakumova, I.; Prime, T.A.; Rose, C.; Vidal-Puig, A.; Smith, A.C.; Rubinsztein, D.C.; Fearnley, I.M.; Jones, B.A.; Pope, S.; Heales, S.J.; Lam, B.Y.; Neogi, S.G.; McFarlane, I.; James, A.M.; Smith, R.A.; Murphy, M.P. Consequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type mice. Free Radic. Biol. Med., 2010, 48, 161-72.
76. Augustin, W.; Wiswedel, I.; Noack, H.; Reinheckel, T.; Reichelt, O. Role of endogenous and exogenous antioxidants in the defence against functional damage and lipid peroxidation in rat liver mitochondria. Mol. Cell Biochem., 1997, 174, 199-205.
77. Lambeth, J.D. Nox enzymes, ROS, and chronic disease: an example of antagonistic pleiotropy. Free Rad. Biol. Med., 2007, 43, 332-47.
78. Ng, Y.; Barhoumi, R.; Tjalkens, R.B.; Fan, Y.Y.; Kolar, S.; Wang, N.; Lupton, J.R.; Chapkin, R.S. The role of docosahexaenoic acid in mediating mitochondrial membrane lipid oxidation and apoptosis in colonocytes. Carcinogenesis, 2005, 26, 1914-21.
79. Smith, R.A.J.; Porteous, C.M.; Coulter, C.V.; Murphy, M.P. Selective targeting of an antioxidant to mitochondria. Eur. J. Biochem., 1999, 263, 709-16
80. Rokitskaya, T.I.; Klishin, S.S.; Severina, I.I.; Skulachev, V.P.; Antonenko, Y.N. Kinetic analysis of permeation of mitochondriatargeted antioxidants across bilayer lipid membranes. J. Membr. Biol., 2008, 224(1-3), 9-19.
81. Szeto, H.H. Mitochondria-targeted peptide antioxidants: novel neuroprotective agents. AAPS J., 2006, 8, E521-31.
82. Covey, M.V.; Murphy, M.P.; Hobbs, C.E.; Smith, R.A.; Oorschot, D.E. Effect of the mitochondrial antioxidant, Mito Vitamin E, on hypoxic-ischemic striatal injury in neonatal rats: a dose-response and stereological study. Exp. Neurol., 2006, 199, 513-19.
83. Li, Y.; Zhang, H.; Fawcett, J.P.; Tucker, I.G. Quantitation and metabolism of mitoquinone, a mitochondria-targeted antioxidant, in rat by liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom., 2007, 21, 1958-64.
84. Gane, E.J.; Weilert, F.; Orr, D.W.; Keogh, G.F.; Gibson, M.; Lockhart, M.M.; Frampton, C.M.; Taylor, K.M.; Smith, R.A.; Murphy, M.P. The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients. Liver Int., 2010, 30, 1019-26.
85. Armstrong, J.S. Mitochondrial medicine: pharmacological targeting of mitochondria in disease. Br. J. Pharmacol., 2007, 151, 1154-65.
86. Okuda, M.; Li, K.; Beard, M.R.; Showalter, L.A.; Scholle, F.; Lemon, S.M.; Weinman, S.A. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology, 2002, 122, 366-75.
87. Beal, M.F. Mitochondria, oxidative damage, and inflammation in Parkinson's disease. Ann. N Y Acad. Sci., 2003, 991, 120-31
88. Emond, M.; Lepage, G.; Vanasse, M.; Pandolfo, M. Increased levels of plasma malondialdehyde in Friedreich ataxia. Neurology, 2000, 55, 1752-3.
89. Bradley, J.L.; Blake, J.C.; Chamberlain, S.; Thomas, P.K.; Cooper, J.M.; Schapira, A.H. Clinical, biochemical and molecular genetic correlations in Friedreich's ataxia. Hum. Mol. Genet., 2000, 9, 275-82.