| First Author | Rong Y | Year | 2022 |
| Journal | J Cell Biol | Volume | 221 |
| Issue | 7 | PubMed ID | 35510944 |
| Mgi Jnum | J:345512 | Mgi Id | MGI:7579558 |
| Doi | 10.1083/jcb.202202060 | Citation | Rong Y, et al. (2022) STING controls energy stress-induced autophagy and energy metabolism via STX17. J Cell Biol 221(7) |
| abstractText | 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. |
