Regulating mitochondrial outer membrane proteins by ubiquitination and proteasomal degradation

Curr Opin Cell Biol. 2011 Aug;23(4):476-82. doi: 10.1016/ Epub 2011 Jun 24.


Mitochondrial outer membrane proteins have been found to be ubiquitinated and degraded by the proteasome. This process shares at least one component of the ERAD pathway of ER membrane protein degradation, the AAA ATPase cdc48/p97/VCP, thought to extract integral membrane proteins from the lipid bilayer and chaperone them to the proteasome. Proteasomal degradation of the outer mitochondrial membrane (OMM) protein Mcl1 regulates apoptosis whereas Parkin-mediated ubiquitination and degradation of Mitofusins can inhibit mitochondrial fusion and promote mitophagy. The breadth of OMM ubiquitin/proteasome substrates and the physiological relevance of their turnover are only beginning to be understood.

Publication types

  • Review

MeSH terms

  • Animals
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism
  • Humans
  • Membrane Proteins / metabolism*
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Proteins / metabolism*
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Processing, Post-Translational
  • Ubiquitin / metabolism*
  • Ubiquitination
  • Yeasts / cytology
  • Yeasts / metabolism


  • Membrane Proteins
  • Mitochondrial Proteins
  • Ubiquitin
  • Proteasome Endopeptidase Complex