Wu Choufei, Yao Weijing, Kai Wenwen, Liu Weikang, Wang Wenlve, Li Shuzhen, Chen Yingcong, Wu Xiaoyong, Wang Liefeng, Li Ying, Tong Jingjing, Qian Jing, Zhang Liqin, Hong Zhi, Yi Cong
Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Life Sciences, Huzhou University, Huzhou, China.
Department of Biochemistry, Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Cell Dev Biol. 2020 Apr 7;8:221. doi: 10.3389/fcell.2020.00221. eCollection 2020.
Mitochondria are highly dynamic organelles, which can form a network in cells through fusion, fission, and tubulation. Its morphology is closely related to the function of mitochondria. The damaged mitochondria can be removed by mitophagy. However, the relationship between mitochondrial morphology and non-selective autophagy is not fully understood. We found that mitochondrial fusion machinery, not fission or tubulation machinery, is essential for energy deprivation-induced autophagy. In response to glucose starvation, deletion of mitochondrial fusion proteins severely impaired the association of Atg1/ULK1 with Atg13, and then affected the recruitment of Atg1 and other autophagic proteins to PAS (phagophore assembly site). Furthermore, the deletion of fusion proteins blocks mitochondrial respiration, the binding of Snf1-Mec1, the phosphorylation of Mec1 by Snf1, and the dissociation of Mec1 from mitochondria under prolonged starvation. We propose that mitochondrial fusion machinery regulates energy deprivation-induced autophagy through maintaining mitochondrial respiration.
线粒体是高度动态的细胞器，可通过融合、裂变和形成管状结构在细胞中形成网络。其形态与线粒体的功能密切相关。受损的线粒体可通过线粒体自噬被清除。然而，线粒体形态与非选择性自噬之间的关系尚未完全明确。我们发现，线粒体融合机制而非裂变或管状结构形成机制对于能量剥夺诱导的自噬至关重要。在葡萄糖饥饿状态下，线粒体融合蛋白的缺失严重损害了Atg1/ULK1与Atg13的结合，进而影响了Atg1和其他自噬蛋白向吞噬泡组装位点（PAS）的募集。此外，融合蛋白的缺失会阻断线粒体呼吸、Snf1-Mec1的结合、Snf1对Mec1的磷酸化以及在长期饥饿状态下Mec1从线粒体上的解离。我们认为，线粒体融合机制通过维持线粒体呼吸来调节能量剥夺诱导的自噬。
