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Membrane insertion of mitochondrial-encoded proteins regulates ribosome decoding speed

ABSTRACT: The human mitochondrial genome encodes thirteen subunits of the oxidative phosphorylation system essential for energy metabolism to drive cellular activities. 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. Thus, our findings reveal a tight link between translation process and folding and membrane insertion of nascent polypeptides at the inner mitochondrial membrane.

ORGANISM(S): Homo sapiens

PROVIDER: GSE303205 | GEO | 2026/03/27

REPOSITORIES: GEO

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