Molecular Wiring of a Mitochondrial Translational Feedback Loop

Mol Cell. 2020 Feb 20;77(4):887-900.e5. doi: 10.1016/j.molcel.2019.11.019. Epub 2019 Dec 26.


The mitochondrial oxidative phosphorylation system comprises complexes assembled from subunits derived from mitochondrial and nuclear gene expression. Both genetic systems are coordinated by feedback loops, which control the synthesis of specific mitochondrial encoded subunits. Here, we studied how this occurs in the case of cytochrome b, a key subunit of mitochondrial complex III. Our data suggest the presence of a molecular rheostat consisting of two translational activators, Cbp3-Cbp6 and Cbs1, which operates at the mitoribosomal tunnel exit to connect translational output with assembly efficiency. When Cbp3-Cbp6 is engaged in assembly of cytochrome b, Cbs1 binds to the tunnel exit to sequester the cytochrome b-encoding mRNA, repressing its translation. After mediating complex III assembly, binding of Cbp3-Cbp6 to the tunnel exit replaces Cbs1 and the bound mRNA to permit cytochrome b synthesis. Collectively, the data indicate the molecular wiring of a feedback loop to regulate synthesis of a mitochondrial encoded protein.

Keywords: Mitochondrial biogenesis; mitochondrial gene expression; mitochondrial ribosome; mitoribosome interactors; respiratory chain assembly; ribosomal tunnel exit; translation activation; translation regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytochromes b / biosynthesis
  • Cytochromes b / genetics
  • Gene Expression Regulation*
  • Membrane Proteins / metabolism
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Molecular Chaperones / metabolism
  • Protein Biosynthesis*
  • RNA, Messenger / analysis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Trans-Activators / metabolism


  • CBP3 protein, S cerevisiae
  • CBS1 protein, S cerevisiae
  • CBS2 protein, S cerevisiae
  • Cbp6 protein, S cerevisiae
  • Membrane Proteins
  • Mitochondrial Proteins
  • Molecular Chaperones
  • RNA, Messenger
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • cbp1 protein, S cerevisiae
  • Cytochromes b