Posttranscriptional control of T cell effector function by aerobic glycolysis

Cell. 2013 Jun 6;153(6):1239-51. doi: 10.1016/j.cell.2013.05.016.


A "switch" from oxidative phosphorylation (OXPHOS) to aerobic glycolysis is a hallmark of T cell activation and is thought to be required to meet the metabolic demands of proliferation. However, why proliferating cells adopt this less efficient metabolism, especially in an oxygen-replete environment, remains incompletely understood. We show here that aerobic glycolysis is specifically required for effector function in T cells but that this pathway is not necessary for proliferation or survival. When activated T cells are provided with costimulation and growth factors but are blocked from engaging glycolysis, their ability to produce IFN-γ is markedly compromised. This defect is translational and is regulated by the binding of the glycolysis enzyme GAPDH to AU-rich elements within the 3' UTR of IFN-γ mRNA. GAPDH, by engaging/disengaging glycolysis and through fluctuations in its expression, controls effector cytokine production. Thus, aerobic glycolysis is a metabolically regulated signaling mechanism needed to control cellular function.

Publication types

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

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Proliferation
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Glycolysis*
  • Interferon-gamma / genetics
  • Listeria monocytogenes
  • Listeriosis / immunology
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Phosphorylation*
  • Protein Biosynthesis
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*


  • 3' Untranslated Regions
  • Interferon-gamma
  • Glyceraldehyde-3-Phosphate Dehydrogenases