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. Author manuscript; available in PMC: 2014 Apr 1.
Published in final edited form as: Annu Rev Pathol. 2012 Oct 31;8:105–137. doi: 10.1146/annurev-pathol-020712-163918

Figure 3. Major stress pathways that induce autophagy.

Figure 3

(A) As part of the mTORC1 complex, active mTOR phosphorylates and inactivates Ulk1. Starvation inactivates mTOR, leading to formation of an active Ulk1 complex in which Ulk1 phosphorylates Atg13 and FIP200. During conditions of low cellular energy, AMPK is activated by high AMP:ATP and induces autophagy both by phosphorylation and activation of Ulk1 and by inhibition of mTORC1 via phosphorylation of Raptor. (B) HIF-1 and BNIP3 induce autophagy following hypoxia. HIF-1 is stabilized under hypoxic conditions, leading to increased BNIP3 transcription. BNIP3 binds Bcl-2 and disrupts its inhibitory interaction with Beclin 1, leading to autophagy induction. (C) Following infection, activation of toll-like receptors (TLRs) by pathogen-associated molecular patterns (PAMPs) leads to autophagy induction. Induction downstream of TLR1/2 stimulation depends on AMPK signaling. The downstream TLR signaling molecules MyD88 and TRIF interact with Beclin 1 following TLR activation and disrupt the inhibitory Bcl-2/Beclin 1 complex. Abbreviations: PAMP, pathogen-associated molecular pattern.