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Mitochondrial Reactive Oxygen Species Alicia Kowaltowski

Mitochondrial Reactive Oxygen Species Alicia Kowaltowski. Mitochondrial Structure. Oxidative Phosphorylation. Cytochrome c Oxidase. Mitochondrial Reactive Oxygen Species Formation. Loschen G, Flohe L, Chance B. Respiratory chain linked H 2 O 2 production in pigeon heart mitochondria.

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Mitochondrial Reactive Oxygen Species Alicia Kowaltowski

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  1. Mitochondrial Reactive Oxygen Species Alicia Kowaltowski

  2. Mitochondrial Structure

  3. Oxidative Phosphorylation

  4. Cytochrome c Oxidase

  5. Mitochondrial Reactive Oxygen Species Formation Loschen G, Flohe L, Chance B. Respiratory chain linked H2O2 production in pigeon heart mitochondria. FEBS Lett., 1971 18:261-264. (Effects of different respiratory states) Boveris A, Chance B. The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem. J., 1973 134:707-716. (Effects of respiratory inhibitors rotenone and antimycin) Dionisi O, Galeotti T, Terranova T, Azzi A. Superoxide radicals and hydrogen peroxide formation in mitochondria from normal and neoplastic tissues. Biochim. Biophys. Acta 1975 403:292-300. (Detection of superoxide radicals)

  6. Complex I Nicholls and Ferguson, Bioenergetics 3, Academic Press, 2004

  7. Reverse Electron Transfer Nicholls and Ferguson, Bioenergetics 3, Academic Press, 2004

  8. Complex III Nicholls and Ferguson, Bioenergetics 3, Academic Press, 2004

  9. Electron Leakage at the Respiratory Chain Turrens JF, J. Physiol. 2003, 552:335-344.

  10. Dehydrogenases and Electron Leakage Tretter and Adam-Vizi J. Neurosci. 2004, 24:7771-7778. Starkov et al. J. Neurosci. 2004, 24:7779-7788.

  11. catalase GPx TPx Fe3+ Fe2+ SOD O2.- H2O2 HO. O2 .- 2H+ ONOO- Cad. Resp. NO. Inner Membrane NOS Outer Membrane cat TPx ROS Detected in Mitochondria H2O

  12. Mitochondrial NOS - Alpha isoform of neuronal NOS - Constitutive - Regulates Complex IV L-arginine NOS L-citrulline NO. Haynes et al., J. Bioenerg. Biomembr. 2004, 36:341-346.

  13. Mitochondrial SODs - MnSOD in the matrix, CuZnSOD in the intermembrane space 2O2-. + 2H+ H2O2 + O2 - Mutant MnSOD (-/-) animals do not survive unless treated with MnTBAP Weisiger and Fridovich J. Biol. Chem. 1973, 248:4793-4796. Sturtz et al J. Biol. Chem. 2001, 276:38084-38089. Okado-Matsumoto and Fridovich J. Biol. Chem. 2001, 276:38388-383893

  14. Glutathione Peroxidase/Reductase System GPx H2O2 + 2GSH 2H2O + GSSG Glut red. 2GSH + NADP+ GSSG + NADPH Transhidr. NADPH + NAD+ NADP+ + NADH () Green and O'Brien Biochim. Biophys. Acta. 1970, 197:31-39. Levander et al. Biochem. Biophys. Res. Commun. 1974, 58:1047-1052.

  15. Thioredoxin Peroxidase/Reductase System TPx H2O2 + 2RSH 2H2O + RSSR TR RSSR + NADPH 2RSH + NADP+ Watabe et al. Eur. J. Biochem. 1997, 249:52-60. Catalase 2H2O2 2H2O + O2 Radi et al. J. Biol. Chem. 1991, 266:22028-22034.

  16. Cytochrome c 2Cyt c3+ + 2O2-. 2Cyt c2+ + 2O2 2Cyt c2+ + H2O2 + 2H+ 2Cyt c3+ + 2H2O Skulachev FEBS Lett. 1998, 423:275-280.

  17. Electron Transport, OxPhos and ROS Cyt c + + + + + + + + + + + I Inner Mitochondrial Membrane Q IV III II SUCC O2 + 4e- + 4H+ 2H2O NADH ADP ATP H+ O2 + e- O2-. H2O2

  18. Mild Uncoupling Decreases ROS Release Loschen et al. FEBS Lett. 1971, 18:261-264. Korshunov et al. FEBS Lett. 1997, 416:15-18.

  19. Electron Transport, OxPhos and ROS Cyt c + + + + + + + + + + + I Inner Mitochondrial Membrane Q IV III II SUCC O2 + 4e- + 4H+ 2H2O NADH ADP ATP H+ O2 + e- O2-. H2O2

  20. Uncoupling Proteins Regulate ROS Release Negre-Salvayre et al. FASEB J. 1997, 11:809-815.

  21. MitoKATP Regulates ROS Release - + K+ - + - + - + K+ H+ - + ATP - + K+ - + Ferranti et al., 2003, FEBS Letts 536:51-5

  22. Tissue Protection Through Uncoupling Mattiasson G, Shamloo M, Gido G, Mathi K, Tomasevic G, Yi S, Warden CH, Castilho RF, Melcher T, Gonzalez-Zulueta M, Nikolich K, Wieloch T. Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. Nat. Med. 2003, 9:1062-1068. Hoerter J, Gonzalez-Barroso MD, Couplan E, Mateo P, Gelly C, Cassard-Doulcier AM, Diolez P, Bouillaud F. Mitochondrial uncoupling protein 1 expressed in the heart of transgenic mice protects against ischemic-reperfusion damage. Circulation 2004, 110:528-533. Holmuhamedov EL, Jahangir A, Oberlin A, Komarov A, Colombini M, Terzic A. Potassium channel openers are uncoupling protonophores: implication in cardioprotection. FEBS Lett. 2004, 568:167-170. Barros MH, Bandy B, Tahara EB, Kowaltowski AJ. Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae. J Biol Chem. 2004, 279:49883-49888.

  23. 25 min 30 min 30 min wash ischemia reperfusion  damage  damage + antioxidants IP  damage  damage + antioxidants Preconditioning and Postconditioning

  24. Preconditioning and ROS Vanden Hoek et al. J. Biol. Chem. 1998 273:18092-18098.

  25. IP  Mitochondrial ROS mitoKATP UCP Mild Uncoupling  ROS Ischemic Protection

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