Reduction of Hydrogen Peroxide by Human Mitochondrial Amidoxime Reducing Component Enzymes

The mitochondrial amidoxime reducing component (mARC) is a human molybdoenzyme known to catalyze the reduction of various N-oxygenated substrates. The physiological function of mARC enzymes, however, remains unknown. In this study, we examine the reduction of hydrogen peroxide (H₂O₂) by the human mARC1 and mARC2 enzymes. Furthermore, we demonstrate an increased sensitivity toward H₂O₂ for HEK-293T cells with an MTARC1 knockout, which implies a role of mARC enzymes in the cellular response to oxidative stress. H₂O₂ is a reactive oxygen species (ROS) formed in all living cells involved in many physiological processes. Furthermore, H₂O₂ constitutes the first mARC substrate without a nitrogen-oxygen bond, implying that mARC enzymes may have a substrate spectrum going beyond the previously examined N-oxygenated compounds.