Sestrins control metabolism through AMPK and mTORC1. Sestrins potentiate AMPK activation and thereby suppress mTORC1 activity, leading to inhibition of cellular anabolism and augmentation of catabolic processes such as beta-oxidation and autophagy. Abbreviations: TBC1D1, TBC1 domain family member 1; GS, glycogen synthase; CRTC2, CREB regulated transcription coactivator 2; PKFB, fructose-6-phosphate kinase; ACC2, acetyl-coA carboxylase 2; HMGCR, HMG-CoA reductase; CAD, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase.