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- Title
Myristic acid as a checkpoint to regulate STING-dependent autophagy and interferon responses by promoting N-myristoylation.
- Authors
Jia, Mutian; Wang, Yuanyuan; Wang, Jie; Qin, Danhui; Wang, Mengge; Chai, Li; Fu, Yue; Zhao, Chunyuan; Gao, Chengjiang; Jia, Jihui; Zhao, Wei
- Abstract
Stimulator of interferon gene (STING)-triggered autophagy is crucial for the host to eliminate invading pathogens and serves as a self-limiting mechanism of STING-induced interferon (IFN) responses. Thus, the mechanisms that ensure the beneficial effects of STING activation are of particular importance. Herein, we show that myristic acid, a type of long-chain saturated fatty acid (SFA), specifically attenuates cGAS-STING-induced IFN responses in macrophages, while enhancing STING-dependent autophagy. Myristic acid inhibits HSV-1 infection-induced innate antiviral immune responses and promotes HSV-1 replication in mice in vivo. Mechanistically, myristic acid enhances N-myristoylation of ARF1, a master regulator that controls STING membrane trafficking. Consequently, myristic acid facilitates STING activation-triggered autophagy degradation of the STING complex. Thus, our work identifies myristic acid as a metabolic checkpoint that contributes to immune homeostasis by balancing STING-dependent autophagy and IFN responses. This suggests that myristic acid and N-myristoylation are promising targets for the treatment of diseases caused by aberrant STING activation. Stimulator of interferon gene (STING) plays critical roles in the host response to infection and in the production of interferon. Here the authors suggests myristic acid is involved in the homeostatic balancing of STING dependent autophagy and the interferon response.
- Subjects
VENOM; AUTOPHAGY; INTERFERONS; SATURATED fatty acids; SCORPION venom
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-36332-3