Absence of the mitochondrial AAA protease Yme1p restores F-0-ATPase subunit accumulation in an oxa1 deletion mutant of Saccharomyces cerevisiae

The nuclear gene OXA1 encodes a protein located within the mitochondrial in ner membrane that is required for the biogenesis of both cytochrome c oxida se (Cox) and ATPase, In the absence of Oxa1p, the translocation of the mito chondrially encoded subunit Cox2p to the intermembrane space (also referred to as export) is prevented, and it has been proposed that Oxa1p could be a component of a general mitochondrial export machinery. We have examined th e role of Oxa1p in light of its relationships with two mitochondrial protea ses, the matrix protease Afg3p-Rca1p and the intermembrane space protease Y me1p, by analyzing the assembly and activity of the Cox and ATPase complexe s in Delta oxa1, Delta oxa1 Delta afg3, and Delta oxa1 Delta yme1 mutants. We show that membrane subunits of both complexes are specifically degraded in the absence of Oxa1p, Neither Afg3p nor Yme1p is responsible for the deg radation of Cox subunits, However, the F-0 subunits Atp4p, Atp6p, and Atp17 p are stabilized in the Delta oxa1 Delta yme1 double mutant, and oligomycin -sensitive ATPase activity is restored, showing that the increased stabilit y of the ATPase subunits allows significant translocation and assembly to o ccur even in the absence of Oxa1p, These results suggest that Oxa1p is not essential for the export of ATPase subunits, In addition, although respirat ory function is dispensable in Saccharomyces cerevisiae, we show that the s imultaneous inactivation of AFG3 and YME1 is lethal and that the essential function does not reside in their protease activity.