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The AMP activated kinase (AMPK) and the mammalian target of rapamycin (mTOR) are key intracellular signaling molecules that are regulated by nutrient status.AMPK is activated by nutrient limitation whereas mTORC1 is inhibited.They display opposite effects on cellular metabolism and growth.AMPK promotes autophagy while mTORC1 inhibits autophagy.We investigated the mechanism of mTOR regulation by amino acids and discovered that different amino acids use different mechanisms to activate mTOR.Leucine and glutamine act through Rag GTPases and Arf1 GTPase, respectively, to activate mTOR.We show that AMPK and mTORC1 regulate the autophagy initiating protein kinase ULK1 and the autophagy machinery VPS34, which is a lipid kinase critically important for intracellular vesicle trafficking and autophagosome formation.Our study reveals a molecular link from nutrient status, to intracellular nutrient sensor/integrator, eventually to regulation of autophagy.