2. Academic Validation
  3. Newly synthesized AIFM1 determines the hypersensitivity of T lymphocytes to STING activation-induced cell apoptosis

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.
Wangsheng Ji 1,  Lianfei Zhang 2,  Chengxin Ma 2,  Xiaoyu Xu 2,  Shuai Li 2,  Huan Xia 3,  Weihong Zhou 2,  Xinqi Liu 4
Affiliations

Affiliations

  • 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: liu2008@nankai.edu.cn.
PMID: 37000625 DOI: 10.1016/j.celrep.2023.112327
Abstract

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.

Keywords

AIFM1; CP: Immunology; STING; T lymphocytes; apoptosis; mitochondria.

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