Structural basis of translation termination, rescue, and recycling in mammalian mitochondria

Mol Cell. 2021 Jun 17;81(12):2566-2582.e6. doi: 10.1016/j.molcel.2021.03.042. Epub 2021 Apr 19.


The mitochondrial translation system originates from a bacterial ancestor but has substantially diverged in the course of evolution. Here, we use single-particle cryo-electron microscopy (cryo-EM) as a screening tool to identify mitochondrial translation termination mechanisms and to describe them in molecular detail. We show how mitochondrial release factor 1a releases the nascent chain from the ribosome when it encounters the canonical stop codons UAA and UAG. Furthermore, we define how the peptidyl-tRNA hydrolase ICT1 acts as a rescue factor on mitoribosomes that have stalled on truncated messages to recover them for protein synthesis. Finally, we present structural models detailing the process of mitochondrial ribosome recycling to explain how a dedicated elongation factor, mitochondrial EFG2 (mtEFG2), has specialized for cooperation with the mitochondrial ribosome recycling factor to dissociate the mitoribosomal subunits at the end of the translation process.

Keywords: ICT1; cryo-EM; mitochondria; mtEFG2; mtRF1a; mtRRF; recycling; ribosome; termination; translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carboxylic Ester Hydrolases
  • Codon, Terminator
  • Cryoelectron Microscopy / methods
  • Humans
  • Mitochondria / metabolism
  • Mitochondria / physiology*
  • Mitochondrial Proteins / metabolism
  • Mitochondrial Ribosomes / metabolism*
  • Peptide Chain Termination, Translational / genetics
  • Peptide Chain Termination, Translational / physiology*
  • Peptide Elongation Factor G / metabolism
  • Peptide Termination Factors / metabolism
  • Protein Biosynthesis
  • Ribosomal Proteins / metabolism
  • Ribosomal Proteins / physiology
  • Ribosomes / metabolism


  • Codon, Terminator
  • GFM2 protein, human
  • MRPL58 protein, human
  • MTRF1L protein, human
  • Mitochondrial Proteins
  • Peptide Elongation Factor G
  • Peptide Termination Factors
  • Ribosomal Proteins
  • Carboxylic Ester Hydrolases
  • aminoacyl-tRNA hydrolase