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  • Title: Manganese ions induce H2O2 generation at the ubiquinone binding site of mitochondrial complex II.
    Author: Bonke E, Zwicker K, Dröse S.
    Journal: Arch Biochem Biophys; 2015 Aug 15; 580():75-83. PubMed ID: 26116786.
    Abstract:
    Manganese-induced toxicity has been recently associated with an increased ROS generation from mitochondrial complex II (succinate:ubiquinone oxidoreductase). To achieve a deeper mechanistic understanding how divalent manganese ions (Mn(2+)) could stimulate mitochondrial ROS production we performed investigations with bovine heart submitochondrial particles (SMP). In succinate fueled SMP, the Mn(2+) induced hydrogen peroxide (H2O2) production was blocked by the specific complex II ubiquinone binding site (IIQ) inhibitor atpenin A5 while a further downstream block at complex III increased the rate markedly. This suggests that site IIQ was the source of the reactive oxygen species. Moreover, Mn(2+) ions also accelerated the rate of superoxide dismutation, explaining the general increase in the measured rates of H2O2 production and an attenuation of direct superoxide detection.
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