FIGURE 2: Autophagy regulation by nutrient-sensing pathways.

Tor1 is the main negative regulator of autophagy. Tor1 can directly exert its negative regulation through phosphorylation of Atg13 and Atg1 or through its downstream target, PP2A (serine/threonine protein phosphatase 2A), a negative regulator of autophagy. Atg1 and Atg13 could also be phosphorylated by PKA, at residues distinct from those targeted by Tor1. PKA and Sch9 pathways are also negative regulators of autophagy. Apparently, TOR and PKA pathways operate in parallel, whereas Sch9 acts in parallel with PKA and partially dependent on TOR. Regulation of autophagy by Sch9 and PKA can be mediated by the inhibition of Rim15 and the Msn2/4 transcription factors. Tor1 is also able to inhibit the activity of the metabolic sensor Snf1, which is a positive regulator of autophagy by still unknown mechanisms. Green arrows indicate interactions that induce autophagy, red bars indicate inhibition. See the text for details.