biostudies-literatureXu WNIBIB NIH HHSNIAID NIH HHSNCI NIH HHS111987https://www.ebi.ac.uk/biostudies/studies/S-EPMC9943022biostudies-literatureUnknown42(1)T cell activation, proliferation, function, and differentiation are tightly linked to proper metabolic reprogramming and regulation. By using [U-¹³C]glucose tracing, we reveal a critical role for GOT1 in promoting CD8⁺ T cell effector differentiation and function. Mechanistically, GOT1 enhances proliferation by maintaining intracellular redox balance and serine-mediated purine nucleotide biosynthesis. Further, GOT1 promotes the glycolytic programming and cytotoxic function of cytotoxic T lymphocytes via posttranslational regulation of HIF protein, potentially by regulating the levels of α-ketoglutarate. Conversely, genetic deletion of GOT1 promotes the generation of memory CD8⁺ T cells.Cell reportsGOT1 regulates CD8⁺ effector and memory T cell generation.PMC9943022R01 CA229451R01 AI155602P41 EB028239R01 AI077610R01 CA226765Zhao LWen JPatel CHSun IHHelms RSPowell JDOh MHXu WSun IMfalseGOT1 regulates CD8⁺ effector and memory T cell generation.T cell activation, proliferation, function, and differentiation are tightly linked to proper metabolic reprogramming and regulation. By using [U-¹³C]glucose tracing, we reveal a critical role for GOT1 in promoting CD8⁺ T cell effector differentiation and function. Mechanistically, GOT1 enhances proliferation by maintaining intracellular redox balance and serine-mediated purine nucleotide biosynthesis. Further, GOT1 promotes the glycolytic programming and cytotoxic function of cytotoxic T lymphocytes via posttranslational regulation of HIF protein, potentially by regulating the levels of α-ketoglutarate. Conversely, genetic deletion of GOT1 promotes the generation of memory CD8⁺ T cells.2023-01-01T00:00:00Z2023 Jan2025-04-22T09:57:41.308Z2025-02-18T22:57:31.034ZS-EPMC99430223664030910.1016/j.celrep.2022.111987