Mitochondria-localized cGAS suppresses ferroptosis to promote cancer progression  

作　　者：Shiqiao Qiu Xiuying Zhong Xiang Meng Shiting Li Xiaoyu Qian Hui Lu Jin Cai Yi Zhang Mingjie Wang Zijian Ye Huafeng Zhang Ping Gao 

机构地区：[1]School of Medicine,South China University of Technology,Guangzhou,Guangdong,China [2]Medical Research Institute,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Southern Medical University,Guangzhou,Guangdong,China [3]The Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease,School of Basic Medical Sciences,Division of Life Science and Medicine,University of Science and Technology of China,Hefei,Anhui,China

出　　处：《Cell Research》2023年第4期299-311,共13页细胞研究（英文版）

基　　金：supported by the National Natural Science Foundation of China(91957203,81930083,82130087,82072656,82192893,81821001);the National Key R&D Program of China(2018YFA0800303,2022YFA1304504);the Chinese Academy of Sciences(XDB39000000);Hefei Comprehensive National Science Center Institute of Health and Medicine Project(DJK-LX-2022001).

摘　　要：A well-established role of cyclic GMP-AMP synthase(cGAS)is the recognition of cytosolic DNA,which is linked to the activation of host defense programs against pathogens via stimulator of interferon genes(STING)-dependent innate immune response.Recent advance has also revealed that cGAS may be involved in several noninfectious contexts by localizing to subcellular compartments other than the cytosol.However,the subcellular localization and function of cGAS in different biological conditions is unclear;in particular,its role in cancer progression remains poorly understood.Here we show that cGAS is localized to mitochondria and protects hepatocellular carcinoma cells from ferroptosis in vitro and in vivo.cGAS anchors to the outer mitochondrial membrane where it associates with dynamin-related protein 1(DRP1)to facilitate its oligomerization.In the absence of cGAS or DRP1 oligomerization,mitochondrial ROS accumulation and ferroptosis increase,inhibiting tumor growth.Collectively,this previously unrecognized role for cGAS in orchestrating mitochondrial function and cancer progression suggests that cGAS interactions in mitochondria can serve as potential targets for new cancer interventions.

关 键 词：INTERFERON STIMULATOR cGAS 

分 类 号：R730[医药卫生—肿瘤]