Mitochondrial Fusion Machinery Specifically Involved in Energy Deprivation-Induced Autophagy
Mitochondrial Fusion Machinery Specifically Involved in Energy Deprivation-Induced Autophagy
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DOI：
10.3389/fcell.2020.00221
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发表时间：
2020-04
影响因子：
5.5
通讯作者：
Choufei Wu;Weijing Yao;Wenwen Kai;Weikang Liu;Wenlve Wang;Shuzhen Li;Yingcong Chen;Xiaoyong Wu;Liefeng Wang;Ying Li;Jingjing Tong;Jing Qian;Liqin Zhang;Zhi Hong;Cong Yi
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文献类型：
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作者：
Choufei Wu;Weijing Yao;Wenwen Kai;Weikang Liu;Wenlve Wang;Shuzhen Li;Yingcong Chen;Xiaoyong Wu;Liefeng Wang;Ying Li;Jingjing Tong;Jing Qian;Liqin Zhang;Zhi Hong;Cong Yi
线粒体是高度动态的细胞器，可以通过融合、分裂和管状作用在细胞内形成网络。其形态与线粒体的功能密切相关。受损的线粒体可以通过有丝分裂被移除。然而，线粒体形态和非选择性自噬之间的关系还不完全清楚。我们发现，线粒体融合机制，而不是分裂或管状机制，在能量剥夺诱导的自噬中是必不可少的。作为对葡萄糖饥饿的响应，线粒体融合蛋白的缺失严重削弱了Atg1/ULK1与Atg13的结合，进而影响了Atg1和其他自噬蛋白向Pas(噬菌体组装位点)的募集。此外，融合蛋白的缺失阻止了线粒体的呼吸作用，阻止了Snf1与Mec1的结合，阻止了Snf1对Mec1的磷酸化，以及在长期饥饿下Mec1与线粒体的解离。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。
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.