Quiescent CD4 T cells have a metabolism dominated by oxidative phosphorylation (OXPHOS) in mitochondria. OXPHOS is fueled by pyruvate from glycolysis and by β oxidation of lipids. This metabolic program is enforced by the activity of NAD-dependent Sirtuins (Sirt). Nuclear Sirtuin 1 induces PGC-1, which increases mitochondrial biogenesis. Sirtuin 6 suppresses HIF-1 α and NFκB, decreasing glycolytic metabolism and effector functions. Mitochondrial Sirt 3 promotes OXPHOS, and Sirt 4 lowers the production of reactive oxygen species (ROS). ER, endoplasmic reticulum. NAD, nicotinamide-adenine dinucleotide. Glut1, glucose transporter 1.