Choline and dimethylglycine produce superoxide/hydrogen peroxide from the electron transport chain in liver mitochondria

Here, we report that choline and dimethylglycine can stimulate reactive oxygen species (ROS) production in liver mitochondria. Choline stimulated O2˙−/H2O2formation at a concentration of 5 μm. We also observed that ComplexIIandIIIinhibitors, atpenin A5 and myxothiazol, collectively induced a 95% decrease in O2˙−/H2O2production indicating both sites serve as the main sources ofROSduring choline oxidation. Dimethylglycine, an intermediate of choline oxidation, was a more effectiveROSgenerator. Rates of production were ~ 43% higher than choline‐mediated O2˙−/H2O2production. The main site for dimethylglycine‐mediatedROSproduction was via reverse electron transfer to Complex I. Our results demonstrate that metabolism of essential metabolites involved in methionine and folic acid biosynthesis can stimulate mitochondrialROSproduction.