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Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation

Tomokazu Murakawa, Osamu Yamaguchi, Ayako Hashimoto, Shungo Hikoso, Toshihiro Takeda, Takafumi Oka, Hiroki Yasui, Hiromichi Ueda, Yasuhiro Akazawa, Hiroyuki Nakayama, Manabu Taneike, Tomofumi Misaka, Shigemiki Omiya, Ajay M. Shah, Akitsugu Yamamoto, Kazuhiko Nishida, Yoshinori Ohsumi, Koji Okamoto, Yasushi Sakata and Kinya Otsu ()
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Tomokazu Murakawa: Graduate School of Medicine, Osaka University
Osamu Yamaguchi: Graduate School of Medicine, Osaka University
Ayako Hashimoto: Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University
Shungo Hikoso: Graduate School of Medicine, Osaka University
Toshihiro Takeda: Graduate School of Medicine, Osaka University
Takafumi Oka: Graduate School of Medicine, Osaka University
Hiroki Yasui: Graduate School of Medicine, Osaka University
Hiromichi Ueda: Graduate School of Medicine, Osaka University
Yasuhiro Akazawa: Graduate School of Medicine, Osaka University
Hiroyuki Nakayama: Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University
Manabu Taneike: King's College London British Heart Foundation Centre of Excellence
Tomofumi Misaka: King's College London British Heart Foundation Centre of Excellence
Shigemiki Omiya: King's College London British Heart Foundation Centre of Excellence
Ajay M. Shah: King's College London British Heart Foundation Centre of Excellence
Akitsugu Yamamoto: Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology
Kazuhiko Nishida: King's College London British Heart Foundation Centre of Excellence
Yoshinori Ohsumi: Frontier Research Center, Tokyo Institute of Technology
Koji Okamoto: Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University
Yasushi Sakata: Graduate School of Medicine, Osaka University
Kinya Otsu: King's College London British Heart Foundation Centre of Excellence

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: Abstract Damaged mitochondria are removed by mitophagy. Although Atg32 is essential for mitophagy in yeast, no Atg32 homologue has been identified in mammalian cells. Here, we show that Bcl-2-like protein 13 (Bcl2-L-13) induces mitochondrial fragmentation and mitophagy in mammalian cells. First, we hypothesized that unidentified mammalian mitophagy receptors would share molecular features of Atg32. By screening the public protein database for Atg32 homologues, we identify Bcl2-L-13. Bcl2-L-13 binds to LC3 through the WXXI motif and induces mitochondrial fragmentation and mitophagy in HEK293 cells. In Bcl2-L-13, the BH domains are important for the fragmentation, while the WXXI motif facilitates mitophagy. Bcl2-L-13 induces mitochondrial fragmentation in the absence of Drp1, while it induces mitophagy in Parkin-deficient cells. Knockdown of Bcl2-L-13 attenuates mitochondrial damage-induced fragmentation and mitophagy. Bcl2-L-13 induces mitophagy in Atg32-deficient yeast cells. Induction and/or phosphorylation of Bcl2-L-13 may regulate its activity. Our findings offer insights into mitochondrial quality control in mammalian cells.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8527

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DOI: 10.1038/ncomms8527

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