STING controls energy stress-induced autophagy and energy metabolism via STX17.
STING controls energy stress-induced autophagy and energy metabolism via STX17.
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STING 通过 STX17 控制能量应激诱导的自噬和能量代谢
DOI：
10.1083/jcb.202202060
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发表时间：
2022-07-04
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作者在果蝇、小鼠运动模型和培养细胞中鉴定了STING在能量应激诱导的自噬中的负调节功能。从机制上讲，STING通过在ER上隔离自噬陷阱蛋白STX 17来下调自噬融合过程，并抑制其向完全自噬体的易位。干扰素基因刺激因子（STING）在先天免疫中起着关键作用。新出现的证据表明，STING对于DNA或cGAMP诱导的非经典自噬是重要的，这与大部分经典自噬机制无关。在这里，我们报告说，在没有STING的情况下，能量应激诱导的自噬是上调而不是下调。果蝇脂肪细胞中STING的耗尽增强了基础和饥饿诱导的自噬通量。在急性运动期间，STING敲除小鼠显示出增加的自噬通量、运动耐力和改变的葡萄糖代谢。从机制上讲，这些观察结果可以通过STING-STX 17相互作用来解释。STING与STX 17物理相互作用，STX 17是自噬体生物发生和自噬体-溶酶体融合所必需的陷阱。能量危机和TBK 1介导的磷酸化都破坏了STING-STX 17的相互作用，允许不同的STX 17库易位到吞噬细胞和成熟的自噬体，并促进自噬通量。总之，我们证明了迄今为止意想不到的功能STING在能量应激诱导的自噬通过空间调节自噬陷阱STX 17。
The authors identify the negative regulating function of STING in energy stress-induced autophagy in Drosophila, mice exercising model, and cultured cells. Mechanistically, STING downregulates the autophagic fusion process by sequestering autophagic SNARE protein STX17 on ER and inhibits its translocation toward complete autophagosome. The stimulator of interferon genes (STING) plays a critical role in innate immunity. Emerging evidence suggests that STING is important for DNA or cGAMP-induced non-canonical autophagy, which is independent of a large part of canonical autophagy machineries. Here, we report that, in the absence of STING, energy stress-induced autophagy is upregulated rather than downregulated. Depletion of STING in Drosophila fat cells enhances basal- and starvation-induced autophagic flux. During acute exercise, STING knockout mice show increased autophagy flux, exercise endurance, and altered glucose metabolism. Mechanistically, these observations could be explained by the STING–STX17 interaction. STING physically interacts with STX17, a SNARE that is essential for autophagosome biogenesis and autophagosome–lysosome fusion. Energy crisis and TBK1-mediated phosphorylation both disrupt the STING–STX17 interaction, allow different pools of STX17 to translocate to phagophores and mature autophagosomes, and promote autophagic flux. Taken together, we demonstrate a heretofore unexpected function of STING in energy stress-induced autophagy through spatial regulation of autophagic SNARE STX17.
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影响因子：
64.8
作者：
Diao, Jiajie;Liu, Rong;Rong, Yueguang;Zhao, Minglei;Zhang, Jing;Lai, Ying;Zhou, Qiangjun;Wilz, Livia M.;Li, Jianxu;Vivona, Sandro;Pfuetzner, Richard A.;Brunger, Axel T.;Zhong, Qing
通讯作者：
Zhong, Qing
影响因子：
64.8
作者：
Chu TT;Tu X;Yang K;Wu J;Repa JJ;Yan N
通讯作者：
Yan N
DOI：
10.1083/jcb.201804028
发表时间：
2018-10-01
期刊：
The Journal of cell biology
影响因子：
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作者：
Bas L;Papinski D;Licheva M;Torggler R;Rohringer S;Schuschnig M;Kraft C
通讯作者：
Kraft C
影响因子：
15.9
作者：
Jeremiah, Nadia;Neven, Benedicte;Rieux-Laucat, Frederic
通讯作者：
Rieux-Laucat, Frederic
影响因子：
64.8
作者：
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