Transport into mitochondria and intramitochondrial sorting of the Fe/S protein of ubiquinol-cytochrome c reductase

The Fe/S protein of complex III is encoded by a nuclear gene,
synthesized in the cytoplasm as a precursor with a 32 residue
amino-terminal extension, and transported to the outer surface of
the inner mitochondrial membrane. Our data suggest the following
transport pathway. First, the precursor is translocated via
translocation contact sites into the matrix. There, cleavage to an
intermediate containing an eight residue extension occurs. The
intermediate is then redirected across the inner membrane,
processed to the mature subunit, and assembled into complex III. We
suggest that the folding and membrane-translocation pathway in the
endosymbiotic ancestor of mitochondria has been conserved during
evolution of eukaryotic cells; transfer of the gene for Fe/S
protein to the nucleus has led to addition of the presequence,
which routes the precursor back to its “ancestral” assembly
pathway.