• Chih-Hao Chang, Jonathan D Curtis, Leonard B Maggi, Brandon Faubert, Alejandro V Villarino, David O'Sullivan, Stanley Ching-Cheng Huang, Gerritje J W van der Windt, Julianna Blagih, Jing Qiu, Jason D Weber, Edward J Pearce, Russell G Jones, and Erika L Pearce.
• Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
• Cell. 2013 Jun 6;153(6):1239-51.

AbstractA "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.Copyright © 2013 Elsevier Inc. All rights reserved.

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