Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis

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.PaperFlickeyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJhM2I5OTM1ZjBhZWZhYjM1MWY1MDZlZDlkYWVkNzg5YSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc5MTkwOTc1fQ.Rk968c2WBOuzrhkdbM7O8l0YMmSM6DWtCEBl8_Gr6cTQImoR1WcofYMdMe2Z_IzGn0nhT_SNEXWQuf41H-jChxIhXKX0_gypqx9auOj2f45anwLGJfht0iQw1YPjF_7lYQRiFPnyqai592ufqVyjbX43_5womu8j_YMZeCba8mgfmwmh8MbUiVhPkAVJ-fVMb3J2JS514In4JoKcuiqbeRv6GCSbyXDYXAupAZGppbnSTnbHXdCLvpWmmFG4wM9_kPt0GnQL8OY632KdvmPsso3JO5lNNbsQcoRmpki3EDBdPPPpsSQlpc9o-RN9zFHIEkY3tFP7Sh7JExPJYbcVjA(mp4, (70.66 MB) Download video