Elongational stalling activates mitoribosome-associated quality control

Science. 2020 Nov 27;370(6520):1105-1110. doi: 10.1126/science.abc7782.


The human mitochondrial ribosome (mitoribosome) and associated proteins regulate the synthesis of 13 essential subunits of the oxidative phosphorylation complexes. We report the discovery of a mitoribosome-associated quality control pathway that responds to interruptions during elongation, and we present structures at 3.1- to 3.3-angstrom resolution of mitoribosomal large subunits trapped during ribosome rescue. Release factor homolog C12orf65 (mtRF-R) and RNA binding protein C6orf203 (MTRES1) eject the nascent chain and peptidyl transfer RNA (tRNA), respectively, from stalled ribosomes. Recruitment of mitoribosome biogenesis factors to these quality control intermediates suggests additional roles for these factors during mitoribosome rescue. We also report related cryo-electron microscopy structures (3.7 to 4.4 angstrom resolution) of elongating mitoribosomes bound to tRNAs, nascent polypeptides, the guanosine triphosphatase elongation factors mtEF-Tu and mtEF-G1, and the Oxa1L translocase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy
  • Electron Transport Complex IV / chemistry
  • Escherichia coli
  • Exoribonucleases / genetics
  • HEK293 Cells
  • Humans
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Ribosomes / chemistry*
  • Nuclear Proteins / chemistry
  • Peptide Termination Factors / chemistry
  • Protein Domains
  • RNA, Transfer / chemistry
  • RNA-Binding Proteins / chemistry
  • Ribosomal Proteins / chemistry
  • Transcription Elongation, Genetic*
  • Transcriptional Elongation Factors / chemistry


  • C12orf65 protein, human
  • MTRES1 protein, human
  • Mitochondrial Proteins
  • Nuclear Proteins
  • OXA1 protein
  • Peptide Termination Factors
  • RNA-Binding Proteins
  • Ribosomal Proteins
  • Transcriptional Elongation Factors
  • ribosomal protein S4
  • RNA, Transfer
  • Electron Transport Complex IV
  • Exoribonucleases
  • PDE12 protein, human