The CoQ biosynthetic di-iron carboxylate hydroxylase COQ7 is inhibited by in vivo metalation with manganese but remains functional by metalation with cobalt

Coenzyme Q (CoQ; ubiquinone) is an obligate component of the mitochondrial electron transport chain. COQ7 is a mitochondrial hydroxylase that is required for CoQ biosynthesis. COQ7 belongs to di-iron carboxylate enzymes, a rare type of enzyme that carries out a wide range of reactions. We found that manganese exposure of mouse cells leads to decreased COQ7 activity, but that pre-treatment with cobalt interferes with the inhibition by manganese. Our findings suggest that cobalt has greater affinity for the active site of COQ7 than both iron and manganese and that replacement of iron by cobalt at the active site preserves catalytic activity.