Co-translational membrane insertion of mitochondrially encoded proteins

The components of the mitochondrial proteome represent a mosaic of dual genetic origin: while most mitochondrial proteins are encoded by nuclear genes and imported into the organelle following synthesis in the cytosol, a small number of proteins is encoded by the mitochondrial genome. Though small in number, mitochondrial translation products are vital for cellular functionality as these proteins represent the core subunits of the respiratory chain and the ATPase which produce the vast majority of the cellular ATP. Mitochondrial translation products are almost exclusively highly hydrophobic polypeptides which are inserted into the inner membrane in the course of their synthesis. The machinery that mediates membrane insertion in mitochondria is deduced from that of their bacterial ancestors and hence shows profound similarities to the insertion machinery of prokaryotes. However, the specialization on the production of a very small set of translation products drove a severe reduction in the complexity of this system. The insertase Oxa1 forms the central component of the insertion machinery. Oxa1 directly binds to mitochondrial ribosomes and, together with the inner membrane protein Mba1, aligns the polypeptide exit tunnel of the ribosome with the insertion site at the inner membrane. The specific hallmarks and the critical components of this machinery are discussed in this review article.