Succinate modulation of H2O2 release at NADH: ubiquinone oxidoreductase (Complex I) in brain mitochondria

International audienceComplex I is responsible for most of the mitochondrial H 2}O 2} release, both during the oxidation of NAD-linked substrates and during succinate oxidation. The much faster succinate-dependent H 2}O 2} production is ascribed to Complex I, being rotenone sensitive. We report high affinity succinate - supported H 2}O 2} generation in the absence as well as in the presence of glutamate/malate ( G/M) 1 or 2 mM each. In brain mitochondria, their only effect was to increase from 0.35 to 0.5 or to 0.65 mM the succinate concentration evoking the semi-maximal H 2}O 2} release. G/M are still oxidized in the presence of succinate, as indicated by the oxygen consumption rates, which are intermediate between those of G/M and of succinate alone when all substrates are present together. This effect is removed by rotenone, showing that it is not due to inhibition of succinate influx. Moreover, α-ketoglutarate production from G/M, a measure of the activity of Complex I, is decreased but not stopped by succinate. It is concluded that succinate-induced H 2}O 2} production occurs in conditions of regular downward electron flow in Complex I. Succinate concentration appears to modulate the rate of H 2}O 2} release probably by controlling the QH 2}-Q ratio