Import of cytochrome c into mitochondria: reduction of heme, mediated by NADH and flavin nucleotides, is obligatory for its covalent linkage to apocytochrome c

The covalent attachment of heme to apocytochrome c, and therefore the import of cytochrome c into mitochondria, is dependent on both NADH plus a cytosolic cofactor that has been identified to be FMN or FAD. NADH in concert with flavin nucleotides mediates the reduction of heme. Heme in the reduced state is a prerequisite for its covalent attachment to apocytochrome c by the enzyme cytochrome c heme lyase and thus for subsequent translocation of cytochrome c across the outer mitochondrial membrane during import.