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TitleMembrane insertion of mitochondrial-encoded proteins regulates ribosome decoding speed.
Journal, issue, pagesNat Struct Mol Biol, Vol. 33, Issue 5, Page 853-867, Year 2026
Publish dateMay 7, 2026
AuthorsThomas Schöndorf / Valentyn Petrychenko / Ilgin Kotan / Drishan Dahal / Natalia Napieraj / Luis Daniel Cruz-Zaragoza / Cong Wang / Oliver Urbach / Tanja Gall / Sven Dennerlein / Günter Kramer / Niels Fischer / Peter Rehling /
PubMed AbstractThe human mitochondrial genome encodes 13 subunits of the oxidative phosphorylation system essential for energy metabolism to drive cellular activities. Translation of 11 mRNAs by membrane-bound ...The human mitochondrial genome encodes 13 subunits of the oxidative phosphorylation system essential for energy metabolism to drive cellular activities. Translation of 11 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 sufficiently understood. Here, we applied ribosome profiling to assess translation dynamics in combination with cryo-electron microscopy analysis of a COX1 ribosome-nascent chain complex to visualize cotranslational 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 pausing events. Thus, our findings reveal a link between translation process and folding and membrane insertion of nascent polypeptides at the inner mitochondrial membrane.
External linksNat Struct Mol Biol / PubMed:42098403 / PubMed Central
MethodsEM (single particle)
Resolution3.0 - 3.7 Å
Structure data

54637

9s7b

EMDB-54637, PDB-9s7b:
Structure of human mitochondrial COX1-translating ribosome nascent chain complex with tRNAs in intermediate state (AP*)
Method: EM (single particle) / Resolution: 3.7 Å

54638

9s7c

EMDB-54638, PDB-9s7c:
Structure of human mitochondrial COX1-translating ribosome nascent chain complex with tRNAs in initial hybrid state (H1)
Method: EM (single particle) / Resolution: 3.2 Å

54639

9s7d

EMDB-54639, PDB-9s7d:
Structure of human mitochondrial COX1-translating ribosome nascent chain-OXA1L/MITRAC complex in open state (open COX1-mtRNC-OXA1L/MITRAC)
Method: EM (single particle) / Resolution: 3.6 Å

54640

9s7e

EMDB-54640, PDB-9s7e:
Structure of human mitochondrial COX1-translating ribosome nascent chain-OXA1L/MITRAC complex in closed state (closed COX1-mtRNC-OXA1L/MITRAC)
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-55836: Structure of human mitochondrial COX1-translating ribosome nascent chain complex with peptidyl-tRNA (P)
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-55837: Structure of human mitochondrial COX1-translating ribosome nascent chain complex with tRNAs in classical pre-translocation state (AP)
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-55838: Structure of human mitochondrial COX1-translating ribosome nascent chain complex with tRNAs in late hybrid state (H2)
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-K:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-VAL:
VALINE

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER

ChemComp-ZN:
Unknown entry

ChemComp-NAD:
NICOTINAMIDE-ADENINE-DINUCLEOTIDE / NAD*YM

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
KeywordsRIBOSOME / mt55S / micochondria / COX1 / membrane / translation

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