title: The control of mitochondrial succinate-dependent H2O2 production.
abstract: In brain mitochondria succinate activates H(2)O(2) release, concentration dependently (starting at 15 μM), and in the presence of NAD dependent substrates (glutamate, pyruvate, β-hydroxybutyrate). We report that TCA cycle metabolites (citrate, isocitrate, α-ketoglutarate, fumarate, malate) individually and quickly inhibit H(2)O(2) release. When they are present together at physiological concentration (0.2, 0.01, 0.15, 0.12, 0.2 mM respectively) they decrease H(2)O(2) production by over 60% at 0.1-0.2 mM succinate. The degree of inhibition depends on the concentration of each metabolite. Acetoacetate is a strong inhibitor of H(2)O(2) release, starting at 10 μM and acting quickly. It potentiates the inhibition induced by TCA cycle metabolites. The action of acetoacetate is partially removed by β-hydroxybutyrate. Removal is minimal at 0.1 mM acetoacetate, and is higher at 0.5 mM acetoacetate. We conclude that several inhibitors of H(2)O(2) release act jointly and concentration dependently to rapidly set the required level of H(2)O(2) generation at each succinate concentration.
authors: Dipartimento di Chimica Biologica, Università di Padova, Padova, Italy.
authors: Franco
authors: F
authors: Zoccarato
authors: Claudio
authors: C
authors: Miotto
authors: Lucia
authors: L
authors: Cavallini
authors: Adolfo
authors: A
authors: Alexandre
mesh_terms: D000090:Acetoacetates / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002952:Citric Acid Cycle; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019802:Succinic Acid / Q000378:metabolism*
chemical_list: D000090:Acetoacetates; D019802:Succinic Acid; D006861:Hydrogen Peroxide