Membrane insertion of mitochondrial-encoded proteins regulates ribosome decoding speed

Translation of eleven mRNAs by membrane-bound ribosomes is coupled to insertion of the nascent polypeptides into the inner membrane aided by the OXA1L insertase. To this end, the mechanism of membrane insertion of nascent polypeptides and the functional link to the translation process are not understood.

Here we applied ribosome profiling to assess translation dynamics in combination with cryo-EM analyses of a COX1 ribosome nascent chain complex to visualize co-translational folding of the nascent chain. We find that the membrane topology of the translation product impacts translation speed and that positioning of amphipathic helices in the ribosome vestibule induces structural changes, correlating with translation stalling events.