The School of Cardiovascular Medicine and Sciences, King's College London British Heart Foundation Centre of Excellence, London SE5 9NU, UK.
Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
Cell Rep. 2019 Jan 8;26(2):338-345.e6. doi: 10.1016/j.celrep.2018.12.050.
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.
线粒体通过选择性自噬（称为线粒体自噬）降解有助于控制线粒体质量。Bcl2-L-13 是酵母中 Atg32 的哺乳动物同源物，是必需的线粒体自噬受体。然而，Bcl2-L-13 介导的线粒体自噬所涉及的分子机制仍有待阐明。在这里，我们表明 ULK1（unc-51 样激酶）复合物是 Bcl2-L-13 处理线粒体自噬所必需的。对一系列酵母 Atg 突变体的筛选表明，在酵母中，Bcl2-L-13 和 Atg32 介导的线粒体自噬使用一组不同的 ATG 基因。在饥饿诱导的自噬中必需的 Atg1 复合物的组分对于 Bcl2-L-13-但不是 Atg32-介导的线粒体自噬是不可或缺的。ULK1 复合物是 Atg1 复合物的对应物，是哺乳动物细胞中 Bcl2-L-13 介导的线粒体自噬所必需的。我们提出了一个模型，即在诱导线粒体自噬时，Bcl2-L-13 招募 ULK1 复合物来处理线粒体自噬，并且 LC3B 与 ULK1 的相互作用以及 Bcl2-L-13 对于线粒体自噬很重要。
