Parkin-mediated ubiquitylation redistributes MITOL/March5 from mitochondria to peroxisomes

EMBO Rep. 2019 Dec 5;20(12):e47728. doi: 10.15252/embr.201947728. Epub 2019 Oct 10.


Ubiquitylation of outer mitochondrial membrane (OMM) proteins is closely related to the onset of familial Parkinson's disease. Typically, a reduction in the mitochondrial membrane potential results in Parkin-mediated ubiquitylation of OMM proteins, which are then targeted for proteasomal and mitophagic degradation. The role of ubiquitylation of OMM proteins with non-degradative fates, however, remains poorly understood. In this study, we find that the mitochondrial E3 ubiquitin ligase MITOL/March5 translocates from depolarized mitochondria to peroxisomes following mitophagy stimulation. This unusual redistribution is mediated by peroxins (peroxisomal biogenesis factors) Pex3/16 and requires the E3 ligase activity of Parkin, which ubiquitylates K268 in the MITOL C-terminus, essential for p97/VCP-dependent mitochondrial extraction of MITOL. These findings imply that ubiquitylation directs peroxisomal translocation of MITOL upon mitophagy stimulation and reveal a novel role for ubiquitin as a sorting signal that allows certain specialized proteins to escape from damaged mitochondria.

Keywords: VCP; March5; PINK1- and Parkin-mediated mitophagy; peroxin; ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HCT116 Cells
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mitochondria / metabolism*
  • Mitophagy
  • Peroxins / metabolism
  • Peroxisomes / metabolism*
  • Protein Transport
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination
  • Valosin Containing Protein / metabolism


  • Membrane Proteins
  • Peroxins
  • MARCHF5 protein, human
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Valosin Containing Protein