Oxa1p acts as a general membrane insertion machinery for proteins encoded by mitochondrial DNA

Oxa1p is a member of the conserved Oxa1/YidC/Alb3 protein family involved i n the membrane insertion of proteins. Oxa1p has been shown previously to di rectly facilitate the export of the N-terminal domains of membrane proteins across the inner membrane to the intermembrane space of mitochondria. Here we report on a general role of Oxa1p in the membrane insertion of proteins , (i) The function of Oxa1p is not limited to the insertion of membrane pro teins that undergo N-terminal tail export; rather, it also extends to the i nsertion of other polytopic proteins such as the mitochondrially encoded Co x1p and Cox3p proteins. These are proteins whose N-terminal are retained in the mitochondrial matrix, (ii) Oxa1p interacts directly with these substra tes prior to completion of their synthesis. (iii) The interaction of Oxa1p with its substrates is particularly strong when nascent polypeptide chains are inserted into the inner membrane, suggesting a direct function of Oxa1p in co-translational insertion from the matrix. Taken together, we conclude that the Oxa1 complex represents a general membrane protein insertion mach inery in the inner membrane of mitochondria.