GPX4
细胞生物学
脂质过氧化
刺
内质网
先天免疫系统
化学
生物化学
生物
氧化应激
谷胱甘肽过氧化物酶
免疫系统
免疫学
工程类
超氧化物歧化酶
航空航天工程
作者
Mutian Jia,Danhui Qin,Chenyang Zhao,Li Chai,Zhongxia Yu,Wenwen Wang,Tong Li,Lin Lv,Yuanyuan Wang,Jan Rehwinkel,Jinming Yu,Wei Zhao
标识
DOI:10.1038/s41590-020-0699-0
摘要
Stimulator-of-interferon genes (STING) is vital for sensing cytosolic DNA and initiating innate immune responses against microbial infection and tumors. Redox homeostasis is the balance of oxidative and reducing reactions present in all living systems. Yet, how the intracellular redox state controls STING activation is unclear. Here, we show that cellular redox homeostasis maintained by glutathione peroxidase 4 (GPX4) is required for STING activation. GPX4 deficiency enhanced cellular lipid peroxidation and thus specifically inhibited the cGAS-STING pathway. Concordantly, GPX4 deficiency inhibited herpes simplex virus-1 (HSV-1)-induced innate antiviral immune responses and promoted HSV-1 replication in vivo. Mechanistically, GPX4 inactivation increased production of lipid peroxidation, which led to STING carbonylation at C88 and inhibited its trafficking from the endoplasmic reticulum (ER) to the Golgi complex. Thus, cellular stress-induced lipid peroxidation specifically attenuates the STING DNA-sensing pathway, suggesting that GPX4 facilitates STING activation by maintaining redox homeostasis of lipids.
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