GOT1 regulates CD8+ effector and memory T cell generation

Cell Rep. 2023 Jan 31;42(1):111987. doi: 10.1016/j.celrep.2022.111987. Epub 2023 Jan 12.

Abstract

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.

Keywords: CP: Metabolism; GOT1; HIF; NADH/NAD; effector and memory CD8(+) T cell; glucose; glutamate; serine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes* / metabolism
  • Cell Differentiation / genetics
  • Glucose / metabolism
  • Immunologic Memory / genetics
  • Memory T Cells*
  • T-Lymphocytes, Cytotoxic

Substances

  • Glucose