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Updated: Jan 5, 2026

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy
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Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy

Published on: May 4, 2016

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

Fumika Koyano1, Koji Yamano1, Hidetaka Kosako2

  • 1Ubiquitin Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

EMBO Reports
|October 12, 2019
PubMed

Insights

Parkin-mediated ubiquitylation guides the outer mitochondrial membrane protein MITOL to peroxisomes during mitophagy. This ubiquitin sorting mechanism allows proteins to escape damaged mitochondria, revealing a novel non-degradative fate.

Area of Science:

  • Cell Biology
  • Mitochondrial Dynamics
  • Neurodegenerative Diseases

Background:

  • Ubiquitylation of outer mitochondrial membrane (OMM) proteins is linked to Parkinson's disease.
  • Parkin-mediated ubiquitylation typically targets OMM proteins for degradation during mitophagy.
  • The non-degradative roles of OMM protein ubiquitylation are not well understood.

Purpose of the Study:

  • To investigate the fate of OMM proteins ubiquitylated by Parkin beyond degradation.
  • To elucidate the mechanism of MITOL/March5 translocation during mitophagy.
  • To identify novel roles for ubiquitylation in protein trafficking.

Main Methods:

  • Mitochondrial isolation and fractionation.
  • Immunoblotting and immunoprecipitation assays.
  • Analysis of protein localization using microscopy.
  • Genetic manipulation of E3 ligase activity and peroxins.

Main Results:

  • MITOL/March5 translocates from depolarized mitochondria to peroxisomes upon mitophagy stimulation.
  • This translocation is dependent on peroxins Pex3/16 and Parkin's E3 ligase activity.
  • Parkin ubiquitylates MITOL at K268, facilitating its extraction via p97/VCP.

Conclusions:

  • Ubiquitylation acts as a sorting signal directing MITOL to peroxisomes during mitophagy.
  • This pathway represents a novel non-degradative fate for OMM proteins.
  • Findings shed light on Parkinson's disease mechanisms and protein trafficking.
Keywords:
VCPMarch5PINK1- and Parkin-mediated mitophagyperoxinubiquitin

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