| Title: |
STING controls energy stress-induced autophagy and energy metabolism via STX17 |
| Authors: |
Rong, Yueguang; Zhang, Shen; Nandi, Nilay; Wu, Zhe; Li, Linsen; Liu, Yang; Wei, Yuehan; Zhao, Yuan; Yuan, Weigang; Zhou, Chuchu; Xiao, Guanghua; Levine, Beth; Yan, Nan; Mou, Shan; Deng, Liufu; Tang, Zaiming; Liu, Xiaoxia; Kramer, Helmut; Zhong, Qing |
| Contributors: |
National Natural Science Foundation of China; Shanghai Science and Technology Commission; Ministry of Science and Technology; Shanghai Collaborative Innovation Center of Cellular Homeostasis Regulation and Human Diseases; Program of Shanghai Subject Chief Scientist |
| Source: |
Journal of Cell Biology ; volume 221, issue 7 ; ISSN 0021-9525 1540-8140 |
| Publisher Information: |
Rockefeller University Press |
| Publication Year: |
2022 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1083/jcb.202202060 |
| DOI: |
10.1083/jcb.202202060/1837908/jcb_202202060.pdf |
| Availability: |
https://doi.org/10.1083/jcb.202202060; https://rupress.org/jcb/article-pdf/doi/10.1083/jcb.202202060/1837908/jcb_202202060.pdf |
| Rights: |
http://www.rupress.org/terms/ ; https://creativecommons.org/licenses/by-nc-sa/4.0/ |
| Accession Number: |
edsbas.384409AA |
| Database: |
BASE |