Newly synthesized AIFM1 determines the hypersensitivity of T lymphocytes to STING activation-induced cell apoptosis
Wangsheng Ji,
Lianfei Zhang,
Chengxin Ma,
Xiaoyu Xu,
Shuai Li,
Huan Xia,
Weihong Zhou,
Xinqi Liu
Affiliations
Wangsheng Ji
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China; Joint National Laboratory for Antibody Drug Engineering, the First Affiliated Hospital of Henan University, Henan University, Kaifeng 475000, China
Lianfei Zhang
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Chengxin Ma
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Xiaoyu Xu
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Shuai Li
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Huan Xia
Department of Infectious Diseases, Nankai University Second People’s Hospital, Tianjin 300071, China
Weihong Zhou
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Xinqi Liu
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China; Corresponding author
Summary: STING is a well-known signaling adaptor essential for sensing cytosolic dsDNA to produce type I interferon. Although the detailed underlying mechanisms remain enigmatic, recent studies show that STING activation can lead to T lymphocyte apoptosis. Here, we report that AIFM1 facilitates STING activation-induced cell apoptosis in T lymphocytes. Mechanistically, AIFM1 is upregulated after STING activation in T cells but not in HEK293T-STING and THP-1 cells, rendering T cells more sensitive to apoptosis. In contrast to the canonical role of AIFM1 in the caspase-independent parthanatos, the function of AIFM1 is operated by the formation of an AIFM1/IRF3/BAX complex and mitochondrial outer membrane permeabilization, which cause cytochrome c release and caspase activation. Furthermore, supplementation with newly synthesized AIFM1 can reconstitute STING activation-induced cell apoptosis in HEK293T-STING and THP-1 cells. Our study identifies AIFM1 as a key regulating factor determining the hypersensitivity of T lymphocytes to STING activation-induced cell apoptosis.
