The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation
  • Glucose / metabolism
  • Glutamine / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Lymphocyte Activation* / genetics
  • Metabolic Networks and Pathways / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ornithine / metabolism
  • Polyamines / metabolism
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • TOR Serine-Threonine Kinases / metabolism
  • Transcriptome

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Polyamines
  • Proto-Oncogene Proteins c-myc
  • Glutamine
  • Ornithine
  • TOR Serine-Threonine Kinases
  • Glucose