Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1 during mitophagy.
Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1 during mitophagy.
复制标题
DOI：
10.1083/jcb.201605093
复制
发表时间：
2016-12-05
期刊：
影响因子：
--
通讯作者：
Kanki T
中科院分区：
文献类型：
--
作者：
Yamashita SI;Jin X;Furukawa K;Hamasaki M;Nezu A;Otera H;Saigusa T;Yoshimori T;Sakai Y;Mihara K;Kanki T
Dnm 1/Drp 1介导的线粒体分裂是否是线粒体自噬所必需的仍有争议。Yamashita等人表明，Dnm 1/Drp 1非依赖性线粒体分裂发生在隔离膜形成后，并在线粒体自噬期间与自噬体形成合作。线粒体自噬被认为在线粒体质量控制中起重要作用。线粒体分裂被认为是首先发生的，并且自噬体形成随后发生以包裹线粒体作为线粒体自噬的过程。然而，还没有任何时间分析线粒体分裂和自噬体形成的线粒体自噬。因此，这些过程之间的关系仍然不清楚。我们发现，线粒体分裂因子Dnm 1在酵母或Drp 1在哺乳动物细胞中是不稳定的线粒体自噬。自噬体形成因子如FIP 200、ATG 14和WIPIs对线粒体自噬的线粒体分裂是必不可少的。活细胞成像显示线粒体上形成了隔离膜。一小部分线粒体从亲本线粒体中分离出来，同时伴随着分离膜的延伸和自噬体的形成。这些发现表明存在线粒体自噬过程，其中线粒体自噬的线粒体分裂与自噬体形成一起完成。
It remains controversial whether Dnm1/Drp1-mediated mitochondrial division is essential for mitophagy. Yamashita et al. show that Dnm1/Drp1-independent mitochondrial division occurs after formation of isolation membranes and in cooperation with autophagosome formation during mitophagy. Mitophagy is thought to play an important role in mitochondrial quality control. Mitochondrial division is believed to occur first, and autophagosome formation subsequently occurs to enwrap mitochondria as a process of mitophagy. However, there has not been any temporal analysis of mitochondrial division and autophagosome formation in mitophagy. Therefore, the relationships among these processes remain unclear. We show that the mitochondrial division factor Dnm1 in yeast or Drp1 in mammalian cells is dispensable for mitophagy. Autophagosome formation factors, such as FIP200, ATG14, and WIPIs, were essential for the mitochondrial division for mitophagy. Live-cell imaging showed that isolation membranes formed on the mitochondria. A small portion of the mitochondria then divided from parental mitochondria simultaneously with the extension of isolation membranes and autophagosome formation. These findings suggest the presence of a mitophagy process in which mitochondrial division for mitophagy is accomplished together with autophagosome formation.