Figure 3

Control of autophagy. Autophagy is a major housekeeping pathway and under the control of many different signaling cascades. Mammalian Target of rapamycin (mTOR) plays a central role in the regulation of autophagic activity as it integrates signaling from different sensors of cellular homeostasis. When mTOR is active in yeast it keeps an important ULK1 binding partner (ATG13) phosphorylated, thus inhibiting the induction of autophagy. While signals indicating abundant nutritional and trophic support activate mTOR (and deactivate autophagy), signals of starvation or other stressors inhibit mTOR (and activate autophagy). Autophagy can be directly stimulated by intracellular debris (such as unfolded proteins and damaged organelles) or by indicators of an overwhelmed ubiquitin-proteasome system (UPS). Also certain pathogens activate autophagy. Autophagy can be directly inhibited by genetic ablation of important Atg genes, inhibitors of the class III PI3K-complex (WM, 3-MA), high nutrient levels, and inositol signaling. More recently screenings of small compound libraries have yielded inducers and inhibitors of autophagy, both mTOR dependent and independent. And last, transcriptional regulators, such as p53, eIF2α, E2F4, or FOXO3 regulate autophagy by controlling the expression levels of many Atg genes. For further details, please refer to the text.