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. Author manuscript; available in PMC: 2012 Feb 1.
Published in final edited form as: Curr Opin Genet Dev. 2011 Jan 20;21(1):113–119. doi: 10.1016/j.gde.2010.12.008

Figure 1. Regulation of autophagy under nutrient deprivation and its interaction with central carbon metabolism.

Figure 1

The major extra-cellular nutrient sensing pathways, controlled by PI3K-I and adenosine monophosphate activated kinase (AMPK) tightly regulate autophagy through mTOR signaling, although other mTOR independent mechanisms exist [9–11]. Under nutrient-replete conditions, autophagy is inhibited by mTOR and inactivation of the ULK1 complex. Metabolic stress relieves this inhibition to activate autophagy, and activates AMPK. AMPK inhibits mTOR by activating its negative regulator, the tuberous sclerosis protein 2 (TSC2) and inhibiting its positive-regulatory subunit, Raptor. The ULK1 complex activates the vacuolar sorting protein 34 (hVPS34)- and Beclin1-containing complexes (complex I and complex II), to initiate phagophore formation (Figure 1) [9]. Phagophores nucleate and expand around the cargo encapsulating it and targeting it to lysosomes for degradation. Degradation products of autophagy substrates may re-enter glycolysis and the TCA cycle for anabolic as well as catabolic processes leading to generation of energy and biomass production. For an extensive review of other forms of autophagy regulation, please see [11,12,55].