a The State Key Laboratory of Membrane Biology , Tsinghua University-Peking University Joint Centre for Life Sciences, School of Life Sciences, Tsinghua University , Beijing , China.
b Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology , Zhejiang University School of Medicine , Hangzhou , China.
Autophagy. 2018;14(6):1084-1085. doi: 10.1080/15548627.2017.1382785. Epub 2017 Dec 24.
Macroautophagy/autophagy, a process that is highly conserved from yeast to mammals, delivers unwanted cellular contents to lysosomes or the vacuole for degradation. It has been reported that autophagy is crucial for maintaining glucose homeostasis. However, the mechanism by which energy deprivation induces autophagy is not well established. Recently, we found that Mec1/ATR, originally identified as a sensor of DNA damage, is essential for glucose starvation-induced autophagy. Mec1 is recruited to mitochondria where it is phosphorylated by activated Snf1 in response to glucose starvation. Phosphorylation of Mec1 leads to the assembly of a Snf1-Mec1-Atg1 module on mitochondria, which promotes the association of Atg1 with Atg13. Furthermore, we found that mitochondrial respiration is specifically required for glucose starvation-induced autophagy but not autophagy induced by canonical stimuli. The Snf1-Mec1-Atg1 module is essential for maintaining mitochondrial respiration and regulating glucose starvation-induced autophagy.
自噬/巨自噬是一种从酵母到哺乳动物高度保守的过程，它将不需要的细胞内容物输送到溶酶体或液泡中进行降解。已经报道自噬对于维持葡萄糖内稳态至关重要。然而，能量剥夺诱导自噬的机制尚不清楚。最近，我们发现最初被鉴定为 DNA 损伤传感器的 Mek1/ATR 对于葡萄糖饥饿诱导的自噬是必需的。Mek1 被招募到线粒体，在那里它被激活的 Snf1 磷酸化，作为对葡萄糖饥饿的响应。Mek1 的磷酸化导致 Snf1-Mek1-Atg1 模块在线粒体上的组装，这促进了 Atg1 与 Atg13 的结合。此外，我们发现线粒体呼吸对于葡萄糖饥饿诱导的自噬是特异性必需的，而不是经典刺激诱导的自噬。Snf1-Mek1-Atg1 模块对于维持线粒体呼吸和调节葡萄糖饥饿诱导的自噬是必需的。
