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Cleaved PGAM5 is released from mitochondria depending on proteasome-mediated rupture of the outer mitochondrial membrane during mitophagy


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タイトル: Cleaved PGAM5 is released from mitochondria depending on proteasome-mediated rupture of the outer mitochondrial membrane during mitophagy
著者: Yamaguchi, Ayane / Ishikawa, Hayate / Furuoka, Mana / Yokozeki, Masashi / Matsuda, Noriyuki / Tanimura, Susumu / Takeda, Kohsuke
発行日: 2018年 9月21日
出版者: Oxford University Press
引用: Journal of biochemistry, 165(1), pp.19-25; 2019
抄録: PGAM5 is a unique type of protein phosphatase that exists in mitochondria. It has been shown to exist in the inner mitochondrial membrane through its transmembrane domain and to be cleaved within the transmembrane domain upon mitochondrial dysfunction. However, its submitochondrial localization remains controversial; many researchers claim that PGAM5 localizes to the outer mitochondrial membrane based on the findings that PGAM5 associates with many cytoplasmic proteins. Here, we found that cleaved PGAM5 was released from mitochondria during mitophagy, a selective form of autophagy specific for mitochondria,and that the release was inhibited by proteasome inhibitors in HeLa cells stably expressing the E3 ubiquitin ligase Parkin.However, treatment of parental HeLa cells lacking Parkin with mitophagy-inducing agents caused PGAM5 cleavage but did not cause its release from mitochondria. Thus, cleaved PGAM5 appears to be released from mitochondria depending on proteasome-mediated rupture of the outer membrane during mitophagy, which has been previously shown to precede autophagy-mediated degradation of whole mitochondria. This study suggests that PGAM5 senses mitochondrial dysfunction in the inner mitochondrial membrane and serves as a signalling intermediate that regulates the cellular response to mitochondrial stress upon its cleavage and release from mitochondria.
キーワード: mitochondria / mitophagy / Parkin / PGAM5 / Proteasome
URI: http://hdl.handle.net/10069/38785
ISSN: 0021924X
DOI: 10.1093/jb/mvy077
権利: © The Author(s) 2018. Published by Oxford University Press on behalf of the Japanese Biochemical Society.
資料タイプ: Journal Article
原稿種類: author
出現コレクション:110 学術雑誌論文

引用URI : http://hdl.handle.net/10069/38785

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