Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation.
Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation.
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DOI：
10.1038/ncomms8527
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发表时间：
2015-07-06
影响因子：
16.6
通讯作者：
Otsu K
中科院分区：
文献类型：
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作者：
Murakawa T;Yamaguchi O;Hashimoto A;Hikoso S;Takeda T;Oka T;Yasui H;Ueda H;Akazawa Y;Nakayama H;Taneike M;Misaka T;Omiya S;Shah AM;Yamamoto A;Nishida K;Ohsumi Y;Okamoto K;Sakata Y;Otsu K
受损的线粒体通过线粒体自噬去除。尽管Atg 32对于酵母中的线粒体自噬至关重要，但在哺乳动物细胞中尚未发现Atg 32同源物。在这里，我们表明，Bcl-2样蛋白13（Bcl-2-L-13）诱导哺乳动物细胞的线粒体片段化和线粒体自噬。首先，我们假设未鉴定的哺乳动物线粒体自噬受体将共享Atg 32的分子特征。通过在公共蛋白质数据库中筛选Atg 32同源物，我们鉴定了Bcl 2-L-13。Bcl 2-L-13通过WXXI基序与LC 3结合，并诱导HEK 293细胞中的线粒体片段化和线粒体自噬。在Bcl 2-L-13中，BH结构域对于片段化是重要的，而WXXI基序促进线粒体自噬。Bcl 2-L-13在缺乏Drp 1的情况下诱导线粒体片段化，而在Parkin缺陷细胞中诱导线粒体自噬。Bcl 2-L-13基因敲低可减弱线粒体损伤诱导的碎裂和线粒体自噬。Bcl 2-L-13诱导Atg 32缺陷型酵母细胞的线粒体自噬。Bcl 2-L-13的诱导和/或磷酸化可调节其活性。我们的研究结果为哺乳动物细胞中的线粒体质量控制提供了见解。Atg 32是酵母线粒体自噬所必需的，然而，尚未鉴定出该蛋白质的哺乳动物同源物。Murakawa等人鉴定Bcl-2样蛋白13为哺乳动物细胞中Atg 32的功能同源物，并表明该蛋白可以拯救Atg 32缺陷型酵母细胞中的线粒体自噬。
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. Atg32 is required for mitophagy in yeast, however, a mammalian homologue of this protein has not been identified. Murakawa et al. identify Bcl-2-like protein 13 as a functional homologue of Atg32 in mammalian cells, and show that this protein can rescue mitophagy in Atg32-deficient yeast cells.