Rong, Y., Zhang, S., Nandi, N., Wu, Z., Li, L., Liu, Y., Wei, Y., Zhao, Y., Yuan, W., Zhou, C., Xiao, G., Levine, B., Yan, N., Mou, S., Deng, L., Tang, Z., Liu, X., Kramer, H., Zhong, Q. (2022). STING controls energy stress-induced autophagy and energy metabolism via STX17.  J. Cell Biol. 221(7): e202202060.

FBrf0253398

Research paper

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.

PMC9082627 (PMC) (EuropePMC)