气候变化领域集成服务门户(CCPortal): Redox homeostasis maintained by GPX4 facilitates STING activation

CCPortal

DOI	10.1038/s41590-020-0699-0
	Redox homeostasis maintained by GPX4 facilitates STING activation
	Jia, Mutian; Qin, Danhui; Zhao, Chunyuan; Chai, Li; Yu, Zhongxia; Wang, Wenwen; Tong, Li; Lv, Lin; Wang, Yuanyuan; Rehwinkel, Jan; Yu, Jinming; Zhao, Wei
发表日期	2020
ISSN	1529-2908
起始页码	727
结束页码	+
卷号	21 期号:7
英文摘要	Zhao and colleagues show that STING activation is sensitive to membrane lipid peroxidation that occurs upon reactive oxygen species (ROS) production. The lipid hydroperoxidase glutathione peroxidase 4 (GPX4) reduces such oxidized lipids. Lack of GPX4 leads to STING protein carbonylation, which impedes its trafficking from the ER to the Golgi. 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.
WOS研究方向	Immunology
WOS类目	Immunology
来源期刊	NATURE IMMUNOLOGY
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/158825
作者单位	Zhao, W (corresponding author), Shandong Univ, Sch Basic Med Sci, Dept Immunol, Cheeloo Coll Med,Chinese Minist Educ, Jinan, Shandong, Peoples R China.; Zhao, W (corresponding author), Shandong Univ, Sch Basic Med Sci, Key Lab Expt Teratol, Cheeloo Coll Med,Chinese Minist Educ, Jinan, Shandong, Peoples R China.; Zhao, W (corresponding author), Shandong Univ, State Key Lab Microbial Technol, Jinan, Shandong, Peoples R China.
推荐引用方式 GB/T 7714	Jia, Mutian,Qin, Danhui,Zhao, Chunyuan,et al. Redox homeostasis maintained by GPX4 facilitates STING activation[J],2020,21(7).
APA	Jia, Mutian.,Qin, Danhui.,Zhao, Chunyuan.,Chai, Li.,Yu, Zhongxia.,...&Zhao, Wei.(2020).Redox homeostasis maintained by GPX4 facilitates STING activation.NATURE IMMUNOLOGY,21(7).
MLA	Jia, Mutian,et al."Redox homeostasis maintained by GPX4 facilitates STING activation".NATURE IMMUNOLOGY 21.7(2020).