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

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

EMBO reports (2019-10-12)
Fumika Koyano, Koji Yamano, Hidetaka Kosako, Yoko Kimura, Mayumi Kimura, Yukio Fujiki, Keiji Tanaka, Noriyuki Matsuda
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-PMP70 antibody, Mouse monoclonal, clone 70-18, purified from hybridoma cell culture
Sigma-Aldrich
Oligomycin, A mixture of A, B, and C isomers.
Sigma-Aldrich
Carbonyl cyanide 3-chlorophenylhydrazone, ≥97% (TLC), powder
Sigma-Aldrich
G 418 disulfate salt solution, 50 mg/mL in H2O, 0.1 μm filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Anti-Pex14 (peroxisomal membrane marker) Antibody, serum, from rabbit
Sigma-Aldrich
Antimycin A from Streptomyces sp.