The COX10 gene encodes the mitochondrial enzyme hemeA:farnesyltransferase, also known as heme O synthase or protoheme IX farnesyltransferase (3, 4). It catalyzes the transfer of a farnesyl group to protoheme IX, forming heme O. Heme O is then converted to heme A, probably by the action of a monooxygenase composed of Cox15p, Yah1p, and Arh1p (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 Cox10p is required for its synthesis, cox10 mutations lead to a deficiency in respiratory growth. Cytochrome c oxidase subunits are present in the cox10 mutant but are not assembled into a functional enzyme (6).

Homologs of Cox10p are found in various organisms from prokaryotes to humans (6, 7, 8, 9, 2). The human homolog functionally complements the yeast cox10 mutation (2). Mutations in the human homolog lead to cytochrome c oxidase deficiency, which may manifest itself as tubulopathy, leukodystrophy, Leigh syndrome, or infantile hypertrophic cardiomyopathy (1, 10).

Last updated: 2006-07-20