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Nat Commun. 2015 Jul 6;6:7527. doi: 10.1038/ncomms8527.

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

Author information

1
Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
2
Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
3
Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
4
Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, 125 Coldharbour Lane, London SE5 9NU, UK.
5
Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-Cho, Nagahama, Shiga 526-0829, Japan.
6
Frontier Research Center, Tokyo Institute of Technology, 4259-S2-12 Nagatsuta-cho, Midori-Ku, Yokohama, Kanagawa 226-8503, Japan.

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.

PMID:
26146385
PMCID:
PMC4501433
DOI:
10.1038/ncomms8527
[Indexed for MEDLINE]
Free PMC Article

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