TY - JOUR
T1 - STING controls energy stress-induced autophagy and energy metabolism via STX17
AU - Rong, Yueguang
AU - Zhang, Shen
AU - Nandi, Nilay
AU - Wu, Zhe
AU - Li, Linsen
AU - Liu, Yang
AU - Wei, Yuehan
AU - Zhao, Yuan
AU - Yuan, Weigang
AU - Zhou, Chuchu
AU - Xiao, Guanghua
AU - Levine, Beth
AU - Yan, Nan
AU - Mou, Shan
AU - Deng, Liufu
AU - Tang, Zaiming
AU - Liu, Xiaoxia
AU - Kramer, Helmut
AU - Zhong, Qing
N1 - Publisher Copyright:
© 2022 Rong et al.
PY - 2022/7/4
Y1 - 2022/7/4
N2 - 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.
AB - 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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U2 - 10.1083/jcb.202202060
DO - 10.1083/jcb.202202060
M3 - Article
C2 - 35510944
AN - SCOPUS:85129998063
SN - 0021-9525
VL - 221
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 7
M1 - e202202060
ER -