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. Author manuscript; available in PMC: 2017 May 1.
Published in final edited form as: Metabolism. 2016 Jan 14;65(5):634–645. doi: 10.1016/j.metabol.2016.01.005

Figure 2. AMPK Signaling During Fed and Fasted States.

Figure 2

(A) In the fed state, insulin receptor signaling activates Akt which phosphorylates and inhibits the tuberous sclerosis complex (TSC1/TSC2). Inhibition of TSC1/TSC2 converts Ras homolog enriched in brain (Rheb) into its GTP-bound state, thus activating mTORC1. Akt can also directly phosphorylate and activate the mTORC1 complex and directly phosphorylate and inhibit AMPK (Fig. 1). Active mTORC1 inhibits autophagy by phosphorylating ULK1 at Ser757. (B) During starvation, increased levels of AMP activate AMPK which phosphorylates and activates TSC2. This promotes the formation of Rheb-GDP, thus decreasing mTORC1 activation and releasing its inhibition of ULK1. AMPK can directly inhibit mTORC1 activity by phosphorylating one of its components, Raptor. This, in conjunction with AMPK-induced phosphorylation (e.g. Ser555) of ULK1 activates ULK1 and stimulates autophagy.