Artículos de revistas
Mitochondria And Reactive Oxygen Species
Registro en:
Free Radical Biology And Medicine. , v. 47, n. 4, p. 333 - 343, 2009.
10.1016/j.freeradbiomed.2009.05.004
2-s2.0-67649866121
Autor
Kowaltowski A.J.
de Souza-Pinto N.C.
Castilho R.F.
Vercesi A.E.
Institución
Resumen
Mitochondria are a quantitatively relevant source of reactive oxygen species (ROS) in the majority of cell types. Here we review the sources and metabolism of ROS in this organelle, including the conditions that regulate the production of these species, such as mild uncoupling, oxygen tension, respiratory inhibition, Ca2+ and K+ transport, and mitochondrial content and morphology. We discuss substrate-, tissue-, and organism-specific characteristics of mitochondrial oxidant generation. Several aspects of the physiological and pathological roles of mitochondrial ROS production are also addressed. © 2009 Elsevier Inc. All rights reserved. 47 4 333 343 Hinkle, P.C., Butow, R.A., Racker, E., Chance, B., Partial resolution of the enzymes catalyzing oxidative phosphorylation. XV. Reverse electron transfer in the flavin-cytochrome beta region of the respiratory chain of beef heart submitochondrial particles (1967) J. Biol. Chem., 242, pp. 5169-5173 Jensen, P.K., Antimycin-insensitive oxidation of succinate and reduced nicotinamide-adenine dinucleotide in electron-transport particles. I. pH dependency and hydrogen peroxide formation (1966) Biochim. Biophys. Acta, 122, pp. 157-166 Loschen, G., Azzi, A., Flohé, L., Mitochondrial H2O2 formation: relationship with energy conservation (1973) FEBS Lett., 33, pp. 84-87 Boveris, A., Cadenas, E., Mitochondrial production of superoxide anions and its relationship to the antimycin insensitive respiration (1975) FEBS Lett., 54, pp. 311-314 Forman, H.J., Kennedy, J.A., Role of superoxide radical in mitochondrial dehydrogenase reactions (1974) Biochem. Biophys. Res. Commun., 60, pp. 1044-1050 Loschen, G., Azzi, A., Richter, C., Flohé, L., Superoxide radicals as precursors of mitochondrial hydrogen peroxide (1974) FEBS Lett., 42, pp. 68-72 Weisiger, R.A., Fridovich, I., Superoxide dismutase: organelle specificity (1973) J. Biol. Chem., 248, pp. 3582-3592 Weisiger, R.A., Fridovich, I., Mitochondrial superoxide simutase: site of synthesis and intramitochondrial localization (1973) J. Biol. Chem., 248, pp. 4793-4796 Dröge, W., Free radicals in the physiological control of cell function (2002) Physiol. Rev., 82, pp. 47-95 Fridovich, I., Superoxide radical and superoxide dismutases (1995) Annu. Rev. Biochem., 64, pp. 97-112 Okado-Matsumoto, A., Fridovich, I., Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu,Zn-SOD in mitochondria (2001) J. Biol. Chem., 276, pp. 38388-38393 Liu, Y., Fiskum, G., Schubert, D., Generation of reactive oxygen species by the mitochondrial electron transport chain (2002) J. Neurochem., 80, pp. 780-787 Lambertucci, R.H., Hirabara, S.M., Silveira, L.D.R., Levada-Pires, A.C., Curi, R., Pithon-Curi, T.C., Palmitate increases superoxide production through mitochondrial electron transport chain and NADPH oxidase activity in skeletal muscle cells (2008) J. Cell. Physiol., 216, pp. 796-804 Tretter, L., Takacs, K., Hegedus, V., Adam-Vizi, V., Characteristics of alpha-glycerophosphate-evoked H2O2 generation in brain mitochondria (2007) J. Neurochem., 100, pp. 650-663 Tretter, L., Takacs, K., Kövér, K., Adam-Vizi, V., Stimulation of H2O2 generation by calcium in brain mitochondria respiring on alpha-glycerophosphate (2007) J. Neurosci. Res., 85, pp. 3471-3479 Lenaz, G., The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology (2001) IUBMB Life, 52, pp. 159-164 Starkov, A.A., Fiskum, G., Chinopoulos, C., Lorenzo, B.J., Browne, S.E., Patel, M.S., Beal, M.F., Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species (2004) J. Neurosci., 24, pp. 7779-7788 Tretter, L., Adam-Vizi, V., Generation of reactive oxygen species in the reaction catalyzed by alpha-ketoglutarate dehydrogenase (2004) J. Neurosci., 24, pp. 7771-7778 Tahara, E.B., Barros, M.H., Oliveira, G.A., Netto, L.E.S., Kowaltowski, A.J., Dihydrolipoyl dehydrogenase as a source of reactive oxygen species inhibited by caloric restriction and involved in Saccharomyces cerevisiae aging (2007) FASEB J., 21, pp. 274-283 Johnson, D.T., Harris, R.A., French, S., Blair, P.V., You, J., Bemis, K.G., Wang, M., Balaban, R.S., Tissue heterogeneity of the mammalian mitochondrial proteome (2007) Am. J. Physiol. Cell Physiol., 292, pp. C689-697 Johnson, D.T., Harris, R.A., Blair, P.V., Balaban, R.S., Functional consequences of mitochondrial proteome heterogeneity (2007) Am. J. Physiol. Cell Physiol., 292, pp. C698-707 Sturtz, L.A., Diekert, K., Jensen, L.T., Lill, R., Culotta, V.C.A., fraction of yeast Cu,Zn-superoxide dismutase and its metallochaperone, CCS, localize to the intermembrane space of mitochondria: a physiological role for SOD1 in guarding against mitochondrial oxidative damage (2001) J. Biol. Chem., 276, pp. 38084-38089 Santiago, A.P.S.A., Chaves, E.A., Oliveira, M.F., Galina, A., Reactive oxygen species generation is modulated by mitochondrial kinases: correlation with mitochondrial antioxidant peroxidases in rat tissues (2008) Biochimie, 90, pp. 1566-1577 Tahara, E.B., Navarete, F.D., Kowaltowski, A.J., Tissue-, substrate-, and site-specific characteristics of mitochondrial reactive oxygen species generation (2009) Free Radic. Biol. Med., 46, pp. 1283-1297 Capel, F., Rimbert, V., Lioger, D., Diot, A., Rousset, P., Mirand, P.P., Boirie, Y., Mosoni, L., Due to reverse electron transfer, mitochondrial H2O2 release increases with age in human vastus lateralis muscle although oxidative capacity is preserved (2005) Mech. Ageing Dev., 126, pp. 505-511 Fornazari, M., de Paula, J.G., Castilho, R.F., Kowaltowski, A.J., Redox properties of the adenoside triphosphate-sensitive K+ channel in brain mitochondria (2008) J. Neurosci. Res., 86, pp. 1548-1556 Grivennikova, V.G., Vinogradov, A.D., Generation of superoxide by the mitochondrial complex I (2006) Biochim. Biophys. Acta, 1757, pp. 553-561 Barros, M.H., Bandy, B., Tahara, E.B., Kowaltowski, A.J., Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae (2004) J. Biol. Chem., 279, pp. 49883-49888 Oliveira, G.A., Tahara, E.B., Gombert, A.K., Barros, M.H., Kowaltowski, A.J., Increased aerobic metabolism is essential for the beneficial effects of caloric restriction on yeast life span (2008) J. Bioenerg. Biomembr., 40, pp. 381-388 Cavalheiro, R.A., Fortes, F., Borecký, J., Faustinoni, V.C., Schreiber, A.Z., Vercesi, A.E., Respiration, oxidative phosphorylation, and uncoupling protein in Candida albicans (2004) Braz. J. Med. Biol. Res., 37, pp. 1455-1461 Jarmuszkiewicz, W., Milani, G., Fortes, F., Schreiber, A.Z., Sluse, F.E., Vercesi, A.E., First evidence and characterization of an uncoupling protein in Fungi kingdom: cpUCP of Candida parapsilosis (2000) FEBS Lett., 467, pp. 145-149 Milani, G., Jarmuszkiewicz, W., Sluse-Goffart, C.M., Schreiber, A.Z., Vercesi, A.E., Sluse, F.E., Respiratory chain network in mitochondria of Candida parapsilosis: ADP/O appraisal of the multiple electron pathways (2001) FEBS Lett., 508, pp. 231-235 Lebovitz, R.M., Zhang, H., Vogel, H., Cartwright, J.J., Dionne, L., Lu, N., Huang, S., Matzuk, M.M., Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice (1996) Proc. Natl. Acad. Sci. USA, 93, pp. 9782-9787 Ruy, F., Vercesi, A.E., Kowaltowski, A.J., Inhibition of specific electron transport pathways leads to oxidative stress and decreased Candida albicans proliferation (2006) J. Bioenerg. Biomembr., 38, pp. 129-135 Affourtit, C., Krab, K., Moore, A.L., Control of plant mitochondrial respiration (2001) Biochim. Biophys. Acta, 1504, pp. 58-69 Almeida, A.M., Navet, R., Jarmuszkiewicz, W., Vercesi, A.E., Sluse-Goffart, C.M., Sluse, F.E., The energy-conserving and energy-dissipating processes in mitochondria isolated from wild type and nonripening tomato fruits during development on the plant (2002) J. Bioenerg. Biomembr., 34, pp. 487-498 Borecky, J., Nogueira, F.T.S., de Oliveira, K.A.P., Maia, I.G., Vercesi, A.E., Arruda, P., The plant energy-dissipating mitochondrial systems: depicting the genomic structure and the expression profiles of the gene families of uncoupling protein and alternative oxidase in monocots and dicots (2006) J. Exp. Bot., 57, pp. 849-864 Borecký, J., Vercesi, A.E., Plant uncoupling mitochondrial protein and alternative oxidase: energy metabolism and stress (2005) Biosci. Rep., 25, pp. 271-286 Brandalise, M., Maia, I.G., Borecký, J., Vercesi, A.E., Arruda, P., Overexpression of plant uncoupling mitochondrial protein in transgenic tobacco increases tolerance to oxidative stress (2003) J. Bioenerg. Biomembr., 35, pp. 203-209 Clifton, R., Millar, A.H., Whelan, J., Alternative oxidases in Arabidopsis: a comparative analysis of differential expression in the gene family provides new insights into function of non-phosphorylating bypasses (2006) Biochim. Biophys. Acta, 1757, pp. 730-741 Costa, A.D., Nantes, I.L., Jezek, P., Leite, A., Arruda, P., Vercesi, A.E., Plant uncoupling mitochondrial protein activity in mitochondria isolated from tomatoes at different stages of ripening (1999) J. Bioenerg. Biomembr., 31, pp. 527-533 Vercesi, A., Martins, I., Silva, M., Leite, H., Cuccovia, I., Chalmovich, H., Pumping plants (1995) Nature, 375, p. 24 Vercesi, A.E., Borecký, J., Maia, I.D.G., Arruda, P., Cuccovia, I.M., Chaimovich, H., Plant uncoupling mitochondrial proteins (2006) Annu. Rev. Plant Biol., 57, pp. 383-404 Li, Y., Huang, T.T., Carlson, E.J., Melov, S., Ursell, P.C., Olson, J.L., Noble, L.J., Epstein, C.J., Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase (1995) Nat. Genet., 11, pp. 376-381 Sluse, F.E., Jarmuszkiewicz, W., Uncoupling proteins outside the Animal and Plant kingdoms: functional and evolutionary aspects (2002) FEBS Lett., 510, pp. 117-120 Brookes, P.S., Mitochondrial H+ leak and ROS generation: an odd couple (2005) Free Radic. Biol. Med., 38, pp. 12-23 Caldeira da Silva, C.C., Cerqueira, F.M., Barbosa, L.F., Medeiros, M.H.G., Kowaltowski, A.J., Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity (2008) Aging Cell, 7, pp. 552-560 Korshunov, S.S., Skulachev, V.P., Starkov, A.A., High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria (1997) FEBS Lett., 416, pp. 15-18 Kowaltowski, A.J., Costa, A.D., Vercesi, A.E., Activation of the potato plant uncoupling mitochondrial protein inhibits reactive oxygen species generation by the respiratory chain (1998) FEBS Lett., 425, pp. 213-216 Popov, V.N., Simonian, R.A., Skulachev, V.P., Starkov, A.A., Inhibition of the alternative oxidase stimulates H2O2 production in plant mitochondria (1997) FEBS Lett., 415, pp. 87-90 Skulachev, V.P., Uncoupling: new approaches to an old problem of bioenergetics (1998) Biochim. Biophys. Acta, 1363, pp. 100-124 Czarna, M., Jarmuszkiewicz, W., Activation of alternative oxidase and uncoupling protein lowers hydrogen peroxide formation in amoeba Acanthamoeba castellanii mitochondria (2005) FEBS Lett., 579, pp. 3136-3140 Ferranti, R., da Silva, M.M., Kowaltowski, A.J., Mitochondrial ATP-sensitive K+ channel opening decreases reactive oxygen species generation (2003) FEBS Lett., 536, pp. 51-55 Nègre-Salvayre, A., Hirtz, C., Carrera, G., Cazenave, R., Troly, M., Salvayre, R., Pénicaud, L., Casteilla, L., A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation (1997) FASEB J., 11, pp. 809-815 Melov, S., Doctrow, S.R., Schneider, J.A., Haberson, J., Patel, M., Coskun, P.E., Huffman, K., Malfroy, B., Lifespan extension and rescue of spongiform encephalopathy in superoxide dismutase 2 nullizygous mice treated with superoxide dismutase-catalase mimetics (2001) J. Neurosci., 21, pp. 8348-8353 Facundo, H.T.F., Carreira, R.S., de Paula, J.G., Santos, C.C.X., Ferranti, R., Laurindo, F.R.M., Kowaltowski, A.J., Ischemic preconditioning requires increases in reactive oxygen release independent of mitochondrial K+ channel activity (2006) Free Radic. Biol. Med., 40, pp. 469-479 Vanden Hoek, T., Becker, L.B., Shao, Z.H., Li, C.Q., Schumacker, P.T., Preconditioning in cardiomyocytes protects by attenuating oxidant stress at reperfusion (2000) Circ. Res., 86, pp. 541-548 Echtay, K.S., Brand, M., D. 4-Hydroxy-2-nonenal and uncoupling proteins: an approach for regulation of mitochondrial ROS production (2007) Redox Rep., 12, pp. 26-29 Echtay, K.S., Roussel, D., St-Pierre, J., Jekabsons, M.B., Cadenas, S., Stuart, J.A., Harper, J.A., Brand, M.D., Superoxide activates mitochondrial uncoupling proteins (2002) Nature, 415, pp. 96-99 Echtay, K.S., Murphy, M.P., Smith, R.A.J., Talbot, D.A., Brand, M.D., Superoxide activates mitochondrial uncoupling protein 2 from the matrix side: studies using targeted antioxidants (2002) J. Biol. Chem., 277, pp. 47129-47135 Costa, A.D.T., Garlid, K.D., Intramitochondrial signaling: interactions among mitoKATP, PKCepsilon, ROS, and MPT (2008) Am. J. Physiol. Heart Circ. Physiol., 295, pp. H874-H882 Zhang, D.X., Chen, Y.F., Campbell, W.B., Zou, A.P., Gross, G.J., Li, P.L., Characteristics and superoxide-induced activation of reconstituted myocardial mitochondrial ATP-sensitive potassium channels (2001) Circ. Res., 89, pp. 1177-1183 Rhoads, D.M., Umbach, A.L., Sweet, C.R., Lennon, A.M., Rauch, G.S., Siedow, J.N., Regulation of the cyanide-resistant alternative oxidase of plant mitochondria: identification of the cysteine residue involved in alpha-keto acid stimulation and intersubunit disulfide bond formation (1998) J. Biol. Chem., 273, pp. 30750-30756 Jezek, P., Engstová, H., Zácková, M., Vercesi, A.E., Costa, A.D., Arruda, P., Garlid, K.D., Fatty acid cycling mechanism and mitochondrial uncoupling proteins (1998) Biochim. Biophys. Acta, 1365, pp. 319-327 Alberici, L.C., Oliveira, H.C.F., Patrício, P.R., Kowaltowski, A.J., Vercesi, A.E., Hyperlipidemic mice present enhanced catabolism and higher mitochondrial ATP-sensitive K+ channel activity (2006) Gastroenterology, 131, pp. 1228-1234 Bienert, G.P., Schjoerring, J.K., Jahn, T.P., Membrane transport of hydrogen peroxide (2006) Biochim. Biophys. Acta, 1758, pp. 994-1003 Paucek, P., Yarov-Yarovoy, V., Sun, X., Garlid, K.D., Inhibition of the mitochondrial KATP channel by long-chain acyl-CoA esters and activation by guanine nucleotides (1996) J. Biol. Chem., 271, pp. 32084-32088 Meyer, L.E., Machado, L.B., Santiago, A.P.S.A., da-Silva, W.S., De Felice, F.G., Holub, O., Oliveira, M.F., Galina, A., Mitochondrial creatine kinase activity prevents reactive oxygen species generation: antioxidant role of mitochondrial kinase-dependent ADP re-cycling activity (2006) J. Biol. Chem., 281, pp. 37361-37371 da-Silva, W.S., Gómez-Puyou, A., de Gómez-Puyou, M.T., Moreno-Sanchez, R., De Felice, F.G., de Meis, L., Oliveira, M.F., Galina, A., Mitochondrial bound hexokinase activity as a preventive antioxidant defense: steady-state ADP formation as a regulatory mechanism of membrane potential and reactive oxygen species generation in mitochondria (2004) J. Biol. Chem., 279, pp. 39846-39855 Andersen, J.K., Oxidative stress in neurodegeneration: cause or consequence? (2004) Nat. Med., 10, pp. S18-25 Calabrese, V., Lodi, R., Tonon, C., D'Agata, V., Sapienza, M., Scapagnini, G., Mangiameli, A., Butterfield, D.A., Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia (2005) J. Neurol. Sci., 233, pp. 145-162 Fiskum, G., Mitochondrial participation in ischemic and traumatic neural cell death (2000) J. Neurotrauma, 17, pp. 843-855 Fukui, H., Moraes, C.T., The mitochondrial impairment, oxidative stress and neurodegeneration connection: reality or just an attractive hypothesis? (2008) Trends Neurosci., 31, pp. 251-256 Geromel, V., Kadhom, N., Cebalos-Picot, I., Ouari, O., Polidori, A., Munnich, A., Rötig, A., Rustin, P., Superoxide-induced massive apoptosis in cultured skin fibroblasts harboring the neurogenic ataxia retinitis pigmentosa (NARP) mutation in the ATPase-6 gene of the mitochondrial DNA (2001) Hum. Mol. Genet., 10, pp. 1221-1228 Sousa, S.C., Castilho, R.F., Protective effect of melatonin on rotenone plus Ca2+-induced mitochondrial oxidative stress and PC12 cell death (2005) Antioxid. Redox Signaling, 7, pp. 1110-1116 Kowaltowski, A.J., Vercesi, A.E., Mitochondrial damage induced by conditions of oxidative stress (1999) Free Radic. Biol. Med., 26, pp. 463-471 Lee, W.K., Thévenod, F., A role for mitochondrial aquaporins in cellular life-and-death decisions? (2006) Am. J. Physiol. Cell Physiol., 291, pp. 195-202 Birket, M.J., Passos, J.F., von Zglinicki, T., Birch-Machin, M.A., The relationship between the aging- and photo-dependent T414G mitochondrial DNA mutation with cellular senescence and reactive oxygen species production in cultured skin fibroblasts (2009) J. Invest. Dermatol., 129, pp. 1361-1366 Gonzalo, R., Garcia-Arumi, E., Llige, D., Marti, R., Solano, A., Montoya, J., Arenas, J., Andreu, A.L., Free radicals-mediated damage in transmitochondrial cells harboring the T14487C mutation in the ND6 gene of mtDNA (2005) FEBS Lett., 579, pp. 6909-6913 Li, J., Zhou, K., Meng, X., Wu, Q., Li, S., Liu, Y., Wang, J., Increased ROS generation and SOD activity in heteroplasmic tissues of transmitochondrial mice with A3243G mitochondrial DNA mutation (2008) Genet. Mol. Res., 7, pp. 1054-1062 Menzies, K.J., Robinson, B.H., Hood, D.A., Effect of thyroid hormone on mitochondrial properties and oxidative stress in cells from pa Holmgren, A., Antioxidant function of thioredoxin and glutaredoxin systems (2000) Antioxid. Redox Signaling, 2, pp. 811-820 Nordberg, J., Arnér, E.S., Reactive oxygen species, antioxidants, and the mammalian thioredoxin system (2001) Free Radic. Biol. Med., 31, pp. 1287-1312 Dalton, T.P., Shertzer, H.G., Puga, A., Regulation of gene expression by reactive oxygen (1999) Annu. Rev. Pharmacol. Toxicol., 39, pp. 67-101 Carreira, R.S., Miyamoto, S., Di Mascio, P., Gonçalves, L.M., Monteiro, P., Providência, L.A., Kowaltowski, A.J., Ischemic preconditioning enhances fatty acid-dependent mitochondrial uncoupling (2007) J. Bioenerg. Biomembr., 39, pp. 313-320 Facundo, H.T.F., de Paula, J.G., Kowaltowski, A.J., Mitochondrial ATP-sensitive K+ channels are redox-sensitive pathways that control reactive oxygen species production (2007) Free Radic. Biol. Med., 42, pp. 1039-1048 Talbot, D.A., Hanuise, N., Rey, B., Rouanet, J., Duchamp, C., Brand, M.D., Superoxide activates a GDP-sensitive proton conductance in skeletal muscle mitochondria from king penguin (Aptenodytes patagonicus) (2003) Biochem. Biophys. Res. Commun., 312, pp. 983-988 Talbot, D.A., Lambert, A.J., Brand, M.D., Production of endogenous matrix superoxide from mitochondrial complex I leads to activation of uncoupling protein 3 (2004) FEBS Lett., 556, pp. 111-115 Radi, R., Turrens, J.F., Chang, L.Y., Bush, K.M., Crapo, J.D., Freeman, B.A., Detection of catalase in rat heart mitochondria (1991) J. Biol. Chem., 266, pp. 22028-22034 Salvi, M., Battaglia, V., Brunati, A.M., La Rocca, N., Tibaldi, E., Pietrangeli, P., Marcocci, L., Toninello, A., Catalase takes part in rat liver mitochondria oxidative stress defense (2007) J. Biol. Chem., 282, pp. 24407-24415 Petrova, V.Y., Drescher, D., Kujumdzieva, A.V., Schmitt, M.J., Dual targeting of yeast catalase A to peroxisomes and mitochondria (2004) Biochem. J., 380, pp. 393-400 Arnér, E.S., Holmgren, A., Physiological functions of thioredoxin and thioredoxin reductase (2000) Eur. J. Biochem., 267, pp. 6102-6109 Hofmann, B., Hecht, H., Flohé, L., Peroxiredoxins (2002) Biol. Chem., 383, pp. 347-364 Pedrajas, J.R., Miranda-Vizuete, A., Javanmardy, N., Gustafsson, J.A., Spyrou, G., Mitochondria of Saccharomyces cerevisiae contain one-conserved cysteine type peroxiredoxin with thioredoxin peroxidase activity (2000) J. Biol. Chem., 275, pp. 16296-16301 Monteiro, G., Horta, B.B., Pimenta, D.C., Augusto, O., Netto, L.E.S., Reduction of 1-Cys peroxiredoxins by ascorbate changes the thiol-specific antioxidant paradigm, revealing another function of vitamin C (2007) Proc. Natl. Acad. Sci. USA, 104, pp. 4886-4891 Rydström, J., Mitochondrial NADPH, transhydrogenase and disease (2006) Biochim. Biophys. Acta, 1757, pp. 721-726 Castilho, R.F., Kowaltowski, A.J., Meinicke, A.R., Bechara, E.J., Vercesi, A.E., Permeabilization of the inner mitochondrial membrane by Ca2+ ions is stimulated by t-butyl hydroperoxide and mediated by reactive oxygen species generated by mitochondria (1995) Free Radic. Biol. Med., 18, pp. 479-486 Kowaltowski, A.J., Castilho, R.F., Vercesi, A.E., Mitochondrial permeability transition and oxidative stress (2001) FEBS Lett., 495, pp. 12-15 Lehninger, A.L., Vercesi, A., Bababunmi, E.A., Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides (1978) Proc. Natl. Acad. Sci. USA, 75, pp. 1690-1694 Lemasters, J.J., Nieminen, A.L., Qian, T., Trost, L.C., Herman, B., The mitochondrial permeability transition in toxic, hypoxic and reperfusion injury (1997) Mol. Cell. Biochem., 174, pp. 159-165 Vercesi, A.E., Pereira-da-Silva, L., NADP redox state and mitochondrial Ca2+ efflux: a controversial issue (1984) Braz. J. Med. Biol. Res., 17, pp. 353-356 Zoratti, M., Szabò, I., The mitochondrial permeability transition (1995) Biochim. Biophys. Acta, 1241, pp. 139-176 Sazanov, L.A., Jackson, J.B., Proton-translocating transhydrogenase and NAD- and NADP-linked isocitrate dehydrogenases operate in a substrate cycle which contributes to fine regulation of the tricarboxylic acid cycle activity in mitochondria (1994) FEBS Lett., 344, pp. 109-116 Jo, S.H., Son, M.K., Koh, H.J., Lee, S.M., Song, I.H., Kim, Y.O., Lee, Y.S., Huh, T.L., Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenase (2001) J. Biol. Chem., 276, pp. 16168-16176 Paim, B.A., Velho, J.A., Castilho, R.F., Oliveira, H.C.F., Vercesi, A.E., Oxidative stress in hypercholesterolemic LDL (low-density lipoprotein) receptor knockout mice is associated with low content of mitochondrial NADPH-linked substrates and is partially reversed by citrate replacement (2008) Free Radic. Biol. Med., 44, pp. 444-451 Oliveira, H.C.F., Cosso, R.G., Alberici, L.C., Maciel, E.N., Salerno, A.G., Dorighello, G.G., Velho, J.A., Vercesi, A.E., Oxidative stress in atherosclerosis-prone mouse is due to low antioxidant capacity of mitochondria (2005) FASEB J., 19, pp. 278-280 Halliwell, B., Gutteridge, J.M., Role of free radicals and catalytic metal ions in human disease: an overview (1990) Methods Enzymol., 186, pp. 1-85 Kakhlon, O., Manning, H., Breuer, W., Melamed-Book, N., Lu, C., Cortopassi, G., Munnich, A., Cabantchik, Z.I., Cell functions impaired by frataxin deficiency are restored by drug-mediated iron relocation (2008) Blood, 112, pp. 5219-5227 Moncada, S., Higgs, A., The l-arginine-nitric oxide pathway (1993) N. Engl. J. Med., 329, pp. 2002-2012 Radi, R., Cassina, A., Hodara, R., Nitric oxide and peroxynitrite interactions with mitochondria (2002) Biol. Chem., 383, pp. 401-409 Bates, T.E., Loesch, A., Burnstock, G., Clark, J.B., Mitochondrial nitric oxide synthase: a ubiquitous regulator of oxidative phosphorylation? (1996) Biochem. Biophys. Res. Commun., 218, pp. 40-44 Frandsen, U., Lopez-Figueroa, M., Hellsten, Y., Localization of nitric oxide synthase in human skeletal muscle (1996) Biochem. Biophys. Res. Commun., 227, pp. 88-93 Kobzik, L., Stringer, B., Balligand, J.L., Reid, M.B., Stamler, J.S., Endothelial type nitric oxide synthase in skeletal muscle fibers: mitochondrial relationships (1995) Biochem. Biophys. Res. Commun., 211, pp. 375-381 Ghafourifar, P., Richter, C., Nitric oxide synthase activity in mitochondria (1997) FEBS Lett., 418, pp. 291-296 Giulivi, C., Poderoso, J.J., Boveris, A., Production of nitric oxide by mitochondria (1998) J. Biol. Chem., 273, pp. 11038-11043 Giulivi, C., Characterization and function of mitochondrial nitric-oxide synthase (2003) Free Radic. Biol. Med., 34, pp. 397-408 Brookes, P.S., Mitochondrial nitric oxide synthase (2004) Mitochondrion, 3, pp. 187-204 Navarro, A., Boveris, A., Mitochondrial nitric oxide synthase, mitochondrial brain dysfunction in aging, and mitochondria-targeted antioxidants (2008) Adv. Drug Delivery Rev., 60, pp. 1534-1544 Basu, S., Azarova, N.A., Font, M.D., King, S.B., Hogg, N., Gladwin, M.T., Shiva, S., Kim-Shapiro, D.B., Nitrite reductase activity of cytochrome c (2008) J. Biol. Chem., 283, pp. 32590-32597 Castello, P.R., David, P.S., McClure, T., Crook, Z., Poyton, R.O., Mitochondrial cytochrome oxidase produces nitric oxide under hypoxic conditions: implications for oxygen sensing and hypoxic signaling in eukaryotes (2006) Cell Metab., 3, pp. 277-287 Modolo, L.V., Augusto, O., Almeida, I.M.G., Magalhaes, J.R., Salgado, I., Nitrite as the major source of nitric oxide production by Arabidopsis thaliana in response to Pseudomonas syringae (2005) FEBS Lett., 579, pp. 3814-3820 Brown, G.C., Cooper, C.E., Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase (1994) FEBS Lett., 356, pp. 295-298 Cleeter, M.W., Cooper, J.M., Darley-Usmar, V.M., Moncada, S., Schapira, A.H., Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide: implications for neurodegenerative diseases (1994) FEBS Lett., 345, pp. 50-54 Bolli, R., Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of a decade of research (2001) J. Mol. Cell. Cardiol., 33, pp. 1897-1918 Ferdinandy, P., Schulz, R., Nitric oxide, superoxide, and peroxynitrite in myocardial ischaemia-reperfusion injury and preconditioning (2003) Br. J. Pharmacol., 138, pp. 532-543 Radi, R., Beckman, J.S., Bush, K.M., Freeman, B.A., Peroxynitrite oxidation of sulfhydryls. the cytotoxic potential of superoxide and nitric oxide (1991) J. Biol. Chem., 266, pp. 4244-4250 Landino, L.M., Iwig, J.S., Kennett, K.L., Moynihan, K.L., Repair of peroxynitrite damage to tubulin by the thioredoxin reductase system (2004) Free Radic. Biol. Med., 36, pp. 497-506 Brown, G.C., Borutaite, V., Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols (2004) Biochim. Biophys. Acta, 1658, pp. 44-49 Gadelha, F.R., Thomson, L., Fagian, M.M., Costa, A.D., Radi, R., Vercesi, A.E., Ca2+-independent permeabilization of the inner mitochondrial membrane by peroxynitrite is mediated by membrane protein thiol cross-linking and lipid peroxidation (1997) Arch. Biochem. Biophys., 345, pp. 243-250 Bonini, M.G., Radi, R., Ferrer-Sueta, G., Ferreira, A.M., Augusto, O., Direct EPR detection of the carbonate radical anion produced from peroxynitrite and carbon dioxide (1999) J. Biol. Chem., 274, pp. 10802-10806 Medinas, D.B., Cerchiaro, G., Trindade, D.F., Augusto, O., The carbonate radical and related oxidants derived from bicarbonate buffer (2007) IUBMB Life, 59, pp. 255-262 Berneburg, M., Grether-Beck, S., Kürten, V., Ruzicka, T., Briviba, K., Sies, H., Krutmann, J., Singlet oxygen mediates the UVA-induced generation of the photoaging-associated mitochondrial common deletion (1999) J. Biol. Chem., 274, pp. 15345-15349 Cosso, R.G., Turim, J., Nantes, I.L., Almeida, A.M., Di Mascio, P., Vercesi, A.E., Mitochondrial permeability transition induced by chemically generated singlet oxygen (2002) J. Bioenerg. Biomembr., 34, pp. 157-163 Almeida, R.D., Manadas, B.J., Carvalho, A.P., Duarte, C.B., Intracellular signaling mechanisms in photodynamic therapy (2004) Biochim. Biophys. Acta, 1704, pp. 59-86 Engelmann, F.M., Mayer, I., Gabrielli, D.S., Toma, H.E., Kowaltowski, A.J., Araki, K., Baptista, M.S., Interaction of cationic meso-porphyrins with liposomes, mitochondria and erythrocytes (2007) J. Bioenerg. Biomembr., 39, pp. 175-185 Gabrielli, D., Belisle, E., Severino, D., Kowaltowski, A.J., Baptista, M.S., Binding, aggregation and photochemical properties of methylene blue in mitochondrial suspensions (2004) Photochem. Photobiol., 79, pp. 227-232 Inada, N.M., da Silva, A.R., Jorge, R.A., Borecký, J., Vercesi, A.E., Irradiated cationic mesoporphyrin induces larger damage to isolated rat liver mitochondria than the anionic form (2007) Arch. Biochem. Biophys., 457, pp. 217-224 Ochsner, M., Photophysical and photobiological processes in the photodynamic therapy of tumours (1997) J. Photochem. Photobiol. B Biol., 39, pp. 1-18 Danial, N.N., Korsmeyer, S.J., Cell death: critical control points (2004) Cell, 116, pp. 205-219 Nantes, I.L., Faljoni-Alario, A., Vercesi, A.E., Santos, K.E., Bechara, E.J., Liposome effect on the cytochrome c-catalyzed peroxidation of carbonyl substrates to triplet species (1998) Free Radic. Biol. Med., 25, pp. 546-553 Kenten, R.H., The oxidation of phenyl-acetaldehyde by plant saps (1953) Biochem. J., 55, pp. 350-360 Knudsen, F.D., Campa, A., Stefani, H.A., Cilento, G., Plant hormone ethylene is a norrish type II product from enzymically generated triplet 1-butanal (1994) Proc. Natl. Acad. Sci. USA, 91, pp. 410-412 Nantes, I.L., Cilento, G., Bechara, E.J., Vercesi, A.E., Chemiluminescent diphenylacetaldehyde oxidation by mitochondria is promoted by cytochromes and leads to oxidative injury of the organelle (1995) Photochem. Photobiol., 62, pp. 522-527 Winterbourn, C.C., Hampton, M.B., Thiol chemistry and specificity in redox signaling (2008) Free Radic. Biol. Med., 45, pp. 549-561 Cadenas, E., Davies, K.J., Mitochondrial free radical generation, oxidative stress, and aging (2000) Free Radic. Biol. Med., 29, pp. 222-230 Murphy, M.P., How mitochondria produce reactive oxygen species (2009) Biochem. J., 417, pp. 1-13 Turrens, J.F., Mitochondrial formation of reactive oxygen species (2003) J. Physiol. (London), 552, pp. 335-344 Wosniak, J.J., Santos, C.X.C., Kowaltowski, A.J., Laurindo, F., Cross-talk between mitochondria and NADPH oxidase: effects of mild mitochondrial dysfunction on angiotensin II mediated increase in NOX isoform expression and activity in vascular smooth muscle cells (2009) Antioxid. Redox Signaling, 11, pp. 1265-1278 Boveris, A., Cadenas, E., Stoppani, A.O., Role of ubiquinone in the mitochondrial generation of hydrogen peroxide (1976) Biochem. J., 156, pp. 435-444 Cadenas, E., Boveris, A., Ragan, C.I., Stoppani, A.O., Production of superoxide radicals and hydrogen peroxide by NADH-ubiquinone reductase and ubiquinol-cytochrome c reductase from beef-heart mitochondria (1977) Arch. Biochem. Biophys., 180, pp. 248-257 Loschen, G., Azzi, A., On the formation of hydrogen peroxide and oxygen radicals in heart mitochondria (1975) Recent Adv. Stud. Cardiac Struct. Metab., 7, pp. 3-12 Nicholls, D., Fergusson, S., (2001) Bioenergetics 3, , Academic Press, San Diego Barros, M.H., Netto, L.E.S., Kowaltowski, A.J., H2O2 generation in Saccharomyces cerevisiae respiratory PET mutants: effect of cytochrome c (2003) Free Radic. Biol. Med., 35, pp. 179-188 Giannattasio, S., Atlante, A., Antonacci, L., Guaragnella, N., Lattanzio, P., Passarella, S., Marra, E., Cytochrome c is released from coupled mitochondria of yeast en route to acetic acid-induced programmed cell death and can work as an electron donor and a ROS scavenger (2008) FEBS Lett., 582, pp. 1519-1525 Pereverzev, M.O., Vygodina, T.V., Konstantinov, A.A., Skulachev, V.P., Cytochrome c, an ideal antioxidant (2003) Biochem. Soc. Trans., 31, pp. 1312-1315 Skulachev, V.P., Cytochrome c in the apoptotic and antioxidant cascades (1998) FEBS Lett., 423, pp. 275-280 Dröse, S., Brandt, U., The mechanism of mitochondrial superoxide production by the cytochrome bc1 complex (2008) J. Biol. Chem., 283, pp. 21649-21654 Kwong, L.K., Sohal, R.S., Substrate and site specificity of hydrogen peroxide generation in mouse mitochondria (1998) Arch. Biochem. Biophys., 350, pp. 118-126 Turrens, J.F., Alexandre, A., Lehninger, A.L., Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria (1985) Arch. Biochem. Biophys., 237, pp. 408-414 Han, D., Williams, E., Cadenas, E., Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space (2001) Biochem. J., 353, pp. 411-416 St-Pierre, J., Buckingham, J.A., Roebuck, S.J., Brand, M.D., Topology of superoxide production from different sites in the mitochondrial electron transport chain (2002) J. Biol. Chem., 277, pp. 44784-44790 Muller, F.L., Liu, Y., Van Remmen, H., Complex III releases superoxide to both sides of the inner mitochondrial membrane (2004) J. Biol. Chem., 279, pp. 49064-49073 Lambert, A.J., Brand, M.D., Inhibitors of the quinone-binding site allow rapid superoxide production from mitochondrial NADH:ubiquinone oxidoreductase (complex I) (2004) J. Biol. Chem., 279, pp. 39414-39420 Yankovskaya, V., Horsefield, R., Törnroth, S., Luna-Chavez, C., Miyoshi, H., Léger, C., Byrne, B., Iwata, S., Architecture of succinate dehydrogenase and reactive oxygen species generation (2003) Science, 299, pp. 700-704