Abstract
In brain mitochondria succinate activates H2O2 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 H2O2 release. When they are present together at physiological concentration (0.2, 0.01, 0.15, 0.12, 0.2 mM respectively) they decrease H2O2 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 H2O2 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 H2O2 release act jointly and concentration dependently to rapidly set the required level of H2O2 generation at each succinate concentration.
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Zoccarato, F., Miotto, C., Cavallini, L. et al. The control of mitochondrial succinate-dependent H2O2 production. J Bioenerg Biomembr 43, 359–366 (2011). https://doi.org/10.1007/s10863-011-9363-6
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DOI: https://doi.org/10.1007/s10863-011-9363-6