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

Fumika Koyano, Koji Yamano, Hidetaka Kosako, Yoko Kimura, Mayumi Kimura, Yukio Fujiki, Keiji Tanaka, Noriyuki Matsuda

EMBO reports 2019 Dec 05

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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. © 2019 The Authors. Published under the terms of the CC BY 4.0 license.

Citation

Fumika Koyano, Koji Yamano, Hidetaka Kosako, Yoko Kimura, Mayumi Kimura, Yukio Fujiki, Keiji Tanaka, Noriyuki Matsuda. Parkin-mediated ubiquitylation redistributes MITOL/March5 from mitochondria to peroxisomes. EMBO reports. 2019 Dec 05;20(12):e47728