A Mammalian Mitophagy Receptor, Bcl2-L-13, Recruits the ULK1 Complex to Induce Mitophagy
A Mammalian Mitophagy Receptor, Bcl2-L-13, Recruits the ULK1 Complex to Induce Mitophagy
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DOI：
10.1016/j.celrep.2018.12.050
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发表时间：
2019-01-08
期刊：
影响因子：
8.8
通讯作者：
Otsu, Kinya
中科院分区：
文献类型：
--
作者：
Murakawa, Tomokazu;Okamoto, Koji;Otsu, Kinya
通过选择性自噬来降解线粒体，称为有丝分裂吞噬，有助于控制线粒体的质量。Bcl2-L-13是酵母中一种重要的有丝分裂受体Atg32在哺乳动物中的同源物。然而，参与bcl2-L-13介导的有丝分裂吞噬的分子机制仍有待阐明。在这里，我们证明了ULK1(UNC-51样激酶)复合体是Bcl2-L-13进行有丝分裂过程所必需的。对一系列酵母atg突变体的筛选表明，一组不同的atg基因用于酵母中bcl2-L-13和atg32介导的有丝分裂噬菌体。在bcl2-L-13-中，Atg1复合体对于饥饿诱导的自噬是必不可少的，但不是Atg32介导的有丝分裂吞噬。ULK1复合体是ATG1复合体的对应物，是Bcl2-L-13介导的哺乳动物细胞有丝分裂吞噬所必需的。我们提出了一个模型，在这个模型中，在诱导有丝分裂时，Bcl2-L-13招募ULK1复合体进行有丝分裂，并且Lc3B与ULK1以及Bcl2-L-13的相互作用对有丝分裂是重要的。
Degradation of mitochondria by selective autophagy, termed mitophagy, contributes to the control of mitochondrial quality. Bcl2-L-13 is a mammalian homolog of Atg32, which is an essential mitophagy receptor in yeast. However, the molecular machinery involved in Bcl2-L-13-mediated mitophagy remains to be elucidated. Here, we show that the ULK1 (unc-51-like kinase) complex is required for Bcl2-L-13 to process mitophagy. Screening of a series of yeast Atg mutants revealed that a different set of ATG genes is used for Bcl2-L-13- and Atg32-mediated mitophagy in yeast. The components of the Atg1 complex essential for starvation-induced autophagy were indispensable in Bcl2-L-13-, but not Atg32-mediated, mitophagy. The ULK1 complex, a counterpart of the Atg1 complex, is necessary for Bcl2-L-13-mediated mitophagy in mammalian cells. We propose a model where, upon mitophagy induction, Bcl2-L-13 recruits the ULK1 complex to process mitophagy and the interaction of LC3B with ULK1, as well as Bcl2-L-13, is important for the mitophagy.