[PDF][PDF] The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation

R Wang, CP Dillon, LZ Shi, S Milasta, R Carter… - Immunity, 2011 - cell.com
R Wang, CP Dillon, LZ Shi, S Milasta, R Carter, D Finkelstein, LL McCormick, P Fitzgerald…
Immunity, 2011cell.com
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 …
Summary
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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