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.
STING controls energy stress-induced autophagy and energy metabolism via STX17
Beth Levine died on June 16, 2020.
- Award Id(s): 91754205,91957204,31771529,31771523,31801170,31870830,91854116
- Award Id(s): 20JC1410100,20JC1411100
- Award Id(s): 2019YFA0508602
- Award Id(s): 19XD1402200
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Yueguang Rong, Shen Zhang, Nilay Nandi, Zhe Wu, Linsen Li, Yang Liu, Yuehan Wei, Yuan Zhao, Weigang Yuan, Chuchu Zhou, Guanghua Xiao, Beth Levine, Nan Yan, Shan Mou, Liufu Deng, Zaiming Tang, Xiaoxia Liu, Helmut Kramer, Qing Zhong; STING controls energy stress-induced autophagy and energy metabolism via STX17. J Cell Biol 4 July 2022; 221 (7): e202202060. doi: https://doi.org/10.1083/jcb.202202060
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