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Immunity. 2011 Dec 23;35(6):871-82. doi: 10.1016/j.immuni.2011.09.021.

The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation.

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1
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Abstract

To fulfill the bioenergetic and biosynthetic demand of proliferation, T cells reprogram their metabolic pathways from fatty acid β-oxidation and pyruvate oxidation via the TCA cycle to the glycolytic, pentose-phosphate, and glutaminolytic pathways. Two of the top-ranked candidate transcription factors potentially responsible for the activation-induced T cell metabolic transcriptome, HIF1α and Myc, were induced upon T cell activation, but only the acute deletion of Myc markedly inhibited activation-induced glycolysis and glutaminolysis in T cells. Glutamine deprivation compromised activation-induced T cell growth and proliferation, and this was partially replaced by nucleotides and polyamines, implicating glutamine as an important source for biosynthetic precursors in active T cells. Metabolic tracer analysis revealed a Myc-dependent metabolic pathway linking glutaminolysis to the biosynthesis of polyamines. Therefore, a Myc-dependent global metabolic transcriptome drives metabolic reprogramming in activated, primary T lymphocytes. This may represent a general mechanism for metabolic reprogramming under patho-physiological conditions.

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PMID:
22195744
PMCID:
PMC3248798
DOI:
10.1016/j.immuni.2011.09.021
[Indexed for MEDLINE]
Free PMC Article
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