Newly synthesized AIFM1 determines the hypersensitivity of T lymphocytes to STING activation-induced cell apoptosis
- Cell Rep. 2023 Mar 30;42(4):112327. doi: 10.1016/j.celrep.2023.112327.
- 1. 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.
- 2. 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.
- 3. Department of Infectious Diseases, Nankai University Second People's Hospital, Tianjin 300071, China.
- 4. 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. Electronic address: [email protected].
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.