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

• Koyano, Fumika

• Yamano, Koji

• Kosako, Hidetaka

• Kimura, Yoko

• Kimura, Mayumi

• Fujiki, Yukio

• Tanaka, Keiji

• Matsuda, Noriyuki

Abstract

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.

Journal

• EMBO Reports

  EMBO Reports 20 (12), e47728-, 2019-10-10

  EMBO Press

Keywords

• March5
• peroxin
• PINK1- and Parkin-mediated mitophagy
• ubiquitin
• VCP

Details

• CRID: 1050850569120445440
• NII Article ID: 120006942558
• ISSN: 14693178
• ISSN: 1469221X
• DOI: 10.15252/embr.201947728
• Web Site: http://repo.lib.tokushima-u.ac.jp/115092
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.15252/embr.201947728
• Web Site: https://onlinelibrary.wiley.com/doi/full-xml/10.15252/embr.201947728
• Web Site: https://www.embopress.org/doi/pdf/10.15252/embr.201947728
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN