Partial suppression of Oxa1 mutants by mitochondria‐targeted signal recognition particle provides insights into the evolution of the cotranslational insertion systems

The biogenesis of hydrophobic membrane proteins involves their cotranslational membrane integration in order to prevent their unproductive aggregation. In the cytosol of bacteria and eukaryotes, membrane targeting of ribosomes that synthesize membrane proteins is achieved by signal recognition particles (SRPs) and their cognate membrane‐bound receptors. As is evident from the genomes of fully sequenced eukaryotes, mitochondria generally lack an SRP system. Instead, mitochondrial ribosomes are physically associated with the protein insertion machinery in the inner membrane. Accordingly, deletion of ribosome‐binding sites on the Oxa1 insertase and the Mba1 ribosome receptor in yeast leads to severe defects in cotranslational protein insertion and results in respiration‐deficient mutants. In this study, we expressed mitochondria‐targeted versions of the bacterial SRP protein Ffh and its receptor FtsY in these yeast mutants. Interestingly, Ffh was found to bind to the large subunit of mitochondrial ribosomes, and could relieve, to some degree, the defect of these insertion mutants. Although FtsY could also bind to mitochondrial membranes, it did not improve membrane protein biogenesis in this strain, presumably because of its inability to interact with Ffh. Hence, mitochondrial ribosomes are still able to interact physically and functionally with the bacterial SRP system. Our observations are consistent with a model according to which the protein insertion system in mitochondria evolved in three steps. The loss of genes for hydrophilic polypeptides (step 1) allowed the development of ribosome‐binding sites on membrane proteins (step 2), which finally made the existence of an SRP‐mediated system dispensable (step 3).

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