摘要 : Mitochondrial production of H2O2 is low with NAD substrates (glutamate/pyruvate, 3 and 2 mM) (G/P) and increases over ten times upon further addition of succinate, with the formation of a sigmoidal curve (semimaximal value at 290 ... 展开 Mitochondrial production of H2O2 is low with NAD substrates (glutamate/pyruvate, 3 and 2 mM) (G/P) and increases over ten times upon further addition of succinate, with the formation of a sigmoidal curve (semimaximal value at 290 A mu M, maximal H2O2 production at 600 A mu M succinate). Malate counteracts rapidly the succinate induced increased H2O2 release and moves the succinate dependent H2O2 production curve to the right. Nitric oxide (NO) and carbon monoxide (CO) are cytochrome c oxidase inhibitors which increase mitochondrial ROS production. Cyanide (CN-) was used to mimic NO and CO. In the presence of G/P and succinate (300 A mu M), CN- progressively increased the H2O2 release rate, starting at 1.5 A mu M. The succinate dependent H2O2 production curve was moved to the left by 30 A mu M CN-. The V-max was little modified. We conclude that succinate is the controller of mitochondrial H2O2 production, modulated by malate and CN-. We propose that succinate promotes an interaction between Complex II and Complex I, which activates O (2) (-) production. 收起