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Early Tcr Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions, Ashley V. Menk, Nicole E. Scharping, Rebecca S. Moreci, Xue Zeng, Cliff Guy, Sonia Salvatore, Heekyong Bae, Jianxin Xie, Howard A. Young, Stacy Gelhaus Wendell, Greg M. Delgoffe

Public Health Resources

To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, translation, CD28, and Akt and not involving increased glucose uptake or activity of glycolytic enzymes. Rather, TCR signaling promotes activation of pyruvate dehydrogenase kinase 1 (PDHK1), inhibiting mitochondrial import of pyruvate and facilitating breakdown into lactate. Inhibition of PDHK1 reveals this switch is required acutely for …