T Cell Activation Depends on Extracellular Alanine. Author Noga Ron-Harel, Jonathan Ghergurovich, Giulia Notarangelo, Martin LaFleur, Yoshiki Tsubosaka, Arlene Sharpe, Joshua Rabinowitz, Marcia Haigis Publication Year 2019 Type Journal Article Abstract T cell stimulation is metabolically demanding. To exit quiescence, T cells rely on environmental nutrients, including glucose and the amino acids glutamine, leucine, serine, and arginine. The expression of transporters for these nutrients is tightly regulated and required for T cell activation. In contrast to these amino acids, which are essential or require multi-step biosynthesis, alanine can be made from pyruvate by a single transamination. Here, we show that extracellular alanine is nevertheless required for efficient exit from quiescence during naive T cell activation and memory T cell restimulation. Alanine deprivation leads to metabolic and functional impairments. Mechanistically, this vulnerability reflects the low expression of alanine aminotransferase, the enzyme required for interconverting pyruvate and alanine, whereas activated T cells instead induce alanine transporters. Stable isotope tracing reveals that alanine is not catabolized but instead supports protein synthesis. Thus, T cells depend on exogenous alanine for protein synthesis and normal activation. Journal Cell Rep Volume 28 Issue 12 Pages 3011-3021.e4 Date Published 09/2019 ISSN Number 2211-1247 DOI 10.1016/j.celrep.2019.08.034 Alternate Journal Cell Rep PMID 31533027 PubMedGoogle ScholarBibTeXEndNote X3 XML