@article {1527658,
	title = {T Cell Activation Depends on Extracellular Alanine},
	journal = {Cell Reports},
	volume = {28},
	number = {12},
	year = {2019},
	pages = {3011-3021},
	abstract = {
	T cell stimulation is metabolically demanding. To exit quiescence, T\&nbsp;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\&nbsp;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\&nbsp;cell activation and memory T\&nbsp;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\&nbsp;cells instead induce alanine transporters. Stable isotope tracing reveals that alanine is not catabolized but instead supports protein synthesis. Thus, T\&nbsp;cells depend on exogenous alanine for protein synthesis and normal activation.



	PubMed\&nbsp;DOI

},
	author = {Ron-Harel, N and Ghergurovich, JM and Notarangelo, G and LaFleur, MW and Tsubosaka, Y and Sharpe, A. H. and Rabinowitz, JD and Haigis, MC}
}
