CLONING OF A HUMAN GENE INVOLVED IN CYTOCHROME-OXIDASE ASSEMBLY BY FUNCTIONAL COMPLEMENTATION OF AN OXA1(-) MUTATION IN SACCHAROMYCES-CEREVISIAE

The yeast nuclear gene OXA1 is essential for cytochrome oxidase assemb ly, so that a null mutation in the OXA1 gene leads to complete respira tory deficiency. We have cloned by genetic selection a human OXA1 (OXA 1Hs) cDNA that complements the respiratory defect of yeast oxa1 mutant s. The deduced sequence of the human protein shares 33% identity with the yeast OXA1 protein. The OXA1Hs cDNA corresponds to a single and re latively highly expressed gene. Oxygen consumption measurements and cy tochrome absorption spectra show that replacement of the yeast protein with the human homolog leads to the correct assembly of cytochrome ox idase, suggesting that the proteins play essentially the same role in both organisms.