SUMMARY PARAGRAPH for COX15
The COX15 gene encodes a mitochondrial inner membrane protein (2) involved in the synthesis of heme A (1). In this pathway, protoheme IX is converted to heme O by the action of Cox10p (3). The methyl group at C8 of heme O is then hydroxylated in a process requiring Cox15p, Yah1p (adrenodoxin), and possibly also Arh1p (adrenodoxin reductase) (4). This produces an intermediate that is further converted to heme A in an additional step catalyzed by an unidentified enzyme (5). Two heme A molecules generated by this pathway are incorporated into the Cox1p subunit of cytochrome c oxidase, which is the terminal member of the mitochondrial electron transport chain involved in cellular respiration.
Because the heme A cofactor is essential to cytochrome c oxidase and Cox15p is required for its synthesis, cox15 mutations lead to a deficiency in respiratory growth. Cytochrome c oxidase subunits are present in the cox15 mutant but are not assembled into a functional enzyme (2). The mutant accumulates heme O but lacks heme A (1).
Cox15p is well-conserved, with similarity to bacterial, fungal, and human predicted proteins (5, 1, 6). In Schizosaccharomyces pombe, one gene contains similarity to both COX15 and YAH1; its expression complements the S. cerevisiae cox15 yah1 double mutation (1).
Last updated: 2006-07-20