Figure 2.

Overview of the autophagic pathway. Autophagy is induced by different stress stimuli including nutritional status, hypoxia and ROS. The autophagic process is initiated by the activity of ULK1 complex, which is regulated negatively by mTORC1 and positively by AMPK. ULK1 complex initiates phagophore nucleation by phosphorylating components of the PI3KC3 complex that leads to the recruitment of several ATGs to assist autophagosome formation. The elongation step involves two ubiquitin-like conjugation complex, the ATG5-ATG12 complex and the LC3-PE complex, which are required for proper phagophore membrane expansion and subsequent closure of the autophagosome. Completed autophagosome fuses with the lysosome to form the autolysosome, where hydrolytic enzymes degrade the enclosed material. The degrading metabolites are transported back to the cytosol for macromolecule synthesis and energy production. In addition, the autophagic machinery is associated with unconventional secretory processes. See the text for additional information. AMPK, AMP-activated protein kinase; ATG, autophagy-related proteins; BafA1, bafilomycin A1; BECN1, Beclin-1; BCL-2, B Cell Lymphoma 2; CQ, chloroquine; ER, endoplasmic reticulum; FIP200, focal adhesion kinase family interacting protein of 200 kDa; JNK1, c-Jun N-terminal kinase 1; LC3, microtubule-associated protein 1A/1B-light chain 3; mTORC1, mammalian target of rapamycin complex 1; PE, phosphatidylethanolamine; PI3K, phosphatidylinositol 3-kinase; SNAREs, soluble N-ethylmaleimide-sensitive factor attachment protein receptors; ULK1, unc-51-like kinase; VPS, vacuolar protein sorting; vWF, von Willebrand factor; 3-MA, 3-methyladenine.