Myristic acid as a checkpoint to regulate STING-dependent autophagy and interferon responses by promoting N-myristoylation

Mutian Jia, Yuanyuan Wang, Jie Wang, Danhui Qin, Mengge Wang, Li Chai, Yue Fu, Chunyuan Zhao, Chengjiang Gao, Jihui Jia and Wei Zhao ()
Additional contact information
Mutian Jia: Shandong University
Yuanyuan Wang: Shandong University
Jie Wang: Shandong University
Danhui Qin: Shandong University
Mengge Wang: Shandong University
Li Chai: Shandong University
Yue Fu: Shandong University
Chunyuan Zhao: Shandong University
Chengjiang Gao: Shandong University
Jihui Jia: Shandong University
Wei Zhao: Shandong University

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36332-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36332-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36332-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().