期刊
CELL REPORTS
卷 28, 期 12, 页码 3011-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.08.034
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资金
- Ludwig Center at Harvard Medical School
- NIH [U54-CA225088, R01CA213062]
- NSF Graduate Research Fellowship Program
- European Molecular Biology Organization long-term postdoctoral fellowship
- Israeli National Postdoctoral Award Program for Advancing Women In Science
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 multistep 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.
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