The membrane insertase Oxa1 is required for efficient import of carrier proteins into mitochondria.
Hildenbeutel M, Theis M, Geier M, Haferkamp I, Neuhaus HE, Herrmann JM, Ott M
J Mol Biol (2012)
Category: mitochondria-biogenesis, mitochondria-transport, protein-membrane, protein transport, yeast ¤ Added: Aug 02, 2012 ¤ Rating: ◊◊
¤ PubMed
Oxa1 serves as a protein insertase of the mitochondrial inner membrane that is evolutionary related to the bacterial YidC insertase. Its activity is critical for membrane integration of mitochondrial translation products as well as for conservatively sorted inner membrane proteins after their passage through the matrix. All Oxa1 substrates identified thus far have bacterial homologs and are of endosymbiotic origin. Here we show that Oxa1 is critical for the biogenesis of members of the mitochondrial carrier proteins. Deletion mutants lacking Oxa1 show reduced steady state levels and activities of the mitochondrial ATP/ADP carrier protein Aac2. To reduce the risk of indirect effects, we generated a novel temperature-sensitive oxa1 mutant that allows rapid depletion of a mutated Oxa1 variant in situ by mitochondrial proteolysis. Oxa1-depleted mitochondria isolated from this mutant still contain normal levels of the membrane potential and of respiratory chain complexes. Nevertheless, in vitro import experiments showed severely reduced import rates of Aac2 and other members of the carrier family whereas the import of matrix proteins was unaffected. From this we conclude that Oxa1 is directly or indirectly required for efficient biogenesis of carrier proteins. This was unexpected, since carrier proteins are inserted into the inner membrane from the intermembrane space side and lack bacterial homologs. Our observations suggest that the function of Oxa1 is not only relevant for the biogenesis of conserved mitochondrial components like respiratory chain complexes or ABC transporters but also for mitochondria-specific membrane proteins of eukaryotic origin.