FIGURE 1 Overview of the autophagy process. The autophagy process is initiated by activation of the Unc-51-like kinase 1 (ULK1) complex consisting of ULK1, autophagy-related protein 13 (ATG13), RB1-inducible coiled-coil protein 1 (FIP200) and ATG101. The ULK1 complex induces nucleation of the phagophore by phosphorylating components of the PI3KC3 complex consisting of Beclin 1, vacuolar protein sorting 34 (VPS34), vacuolar protein sorting 15 (VPS15) and ATG14. The PI3KC3 complex mediates the production of phosphatidylinositol-3-phosphate (PI3P) at the ER to mediate the formation of the omegasome. Then, zinc- fi nger FYVE domain-containing protein 1 (DFCP1) and WD repeat domain phosphoinositide- interacting protein 2 (WIPI2) containing PI3P-interacting regions are recruited to the omegasome, which are required for the recruitment of lipidation machinery consisting of ATG12-ATG5-ATG16L1 by binding to ATG16L1. The stepwise process of ATG8 lipidation is depicted in the lower box,exempli fi edwithLC3andresultinginLC3conjugationtophosphatidylethanolamine(PE)(depictedin fi gureasLC3-II)whichdriveselongationof phagophore. Cargos including protein aggregates, organelles or ribosomes are typically marked by ubiquitin eat-me signal (black dot) leading to their sequestration by autophagy receptors such as P62 that mediates their recruitment to the phagophore. The ATG8 proteins mediate closure of the autophagosome by recruiting Syntaxin17. Further, Rab7 is recruited to autophagosomes and facilitates the fusion process. During the fusion process ATG4 de-lipidates ATG8 on the outer membrane of the autophagosome and the inner membrane is degraded within the lysosome. The process of autophagosome and lysosome fusion is mediated by SNAREs, HOPS and small GTPases (Rab7). Finally lysosomal hydrolases degrade the autophagic