title: Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation.
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.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Murakawa
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
authors.affiliation: Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Hashimoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Shungo
authors.initials: S
authors.lastname: Hikoso
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takeda
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Oka
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ueda
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Akazawa
authors.affiliation: Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, 125 Coldharbour Lane, London SE5 9NU, UK.
authors.forename: Manabu
authors.initials: M
authors.lastname: Taneike
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, 125 Coldharbour Lane, London SE5 9NU, UK.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Misaka
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, 125 Coldharbour Lane, London SE5 9NU, UK.
authors.forename: Shigemiki
authors.initials: S
authors.lastname: Omiya
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, 125 Coldharbour Lane, London SE5 9NU, UK.
authors.forename: Ajay M
authors.initials: AM
authors.lastname: Shah
authors.affiliation: Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-Cho, Nagahama, Shiga 526-0829, Japan.
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, 125 Coldharbour Lane, London SE5 9NU, UK.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishida
authors.affiliation: Frontier Research Center, Tokyo Institute of Technology, 4259-S2-12 Nagatsuta-cho, Midori-Ku, Yokohama, Kanagawa 226-8503, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ohsumi
authors.affiliation: Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sakata
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, 125 Coldharbour Lane, London SE5 9NU, UK.
authors.forename: Kinya
authors.initials: K
authors.lastname: Otsu
mesh_terms: D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D063306:Mitophagy / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C431152:BCL2L13 protein, human; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins