The Transcription Factor Myc Controls Metabolic Reprogramming upon T Lymphocyte Activation

Academic Article

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. © 2011 Elsevier Inc.
  • Published In

  • Immunity  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 27884544
  • Author List

  • Wang R; Dillon CP; Shi LZ; Milasta S; Carter R; Finkelstein D; McCormick LL; Fitzgerald P; Chi H; Munger J
  • Start Page

  • 871
  • End Page

  • 882
  • Volume

  • 35
  • Issue

  • 6