The glycolytic enzyme PFKFB3/phosphofructokinase regulates autophagy

T lymphocytes, the master regulators of immunity, have an unusual lifestyle. Equipped with a clonally distributed receptor they remain resting for long periods of time but go into overdrive when encountering antigen. Antigen recognition triggers an activation program that results in massive proliferation, differentiation into effector/memory cells, egress from lymphoid storage sites, and production of an array of cytokines. To adapt to the sudden demand for energy and biosynthetic macromolecules, T cells resort to aerobic glycolysis, relying on the Warburg effect to provide sufficient ATP and precursor molecules. Metabolic adaptation to the biosynthetic needs includes upregulation of autophagy, a catabolic process resulting in the degradation of cytoplasmic contents. The close connection between a metabolic switch, proliferative expansion, and functional differentiation connects the metabolic conditions in the cell to normal and pathogenic immunity.