Fig. 1.

Two primary complexes are involved in autophagosome formation, the first include of III PI3K Vps34, Atg6/Beclin1, Atg14, and Vps15/p150.73, whereas the second include the serine/threonine kinase Atg1 signaling axis. Furthermore, autophagy is done in two phases; the first phase includes the formation of phagophores and the second phase includes elongation that involved ubiquitin-like conjugation pathways; Atg8/MAP-LC3/GABAP/GATE-16 and Atg12 systems, in the center of the figure. Inducing autophagy can be done in various ways, indicated by a plus sign. During the second phase, Atg8 protein undergoes cleavage for its carboxyl-terminal by cysteine protease Atg4. Then, Atg4 undergoes a long complexed signaling cascade involved activation of Atg4 by Atg7 and Atg3 that culminate in activation of Atg8 and it is binding with the LC3–II of the lysosome and formation of Atg8/LC3–II complex. The Atg8/LC3–II complex bind with autophagosome in a covalent bound unless Atg4 cleaves it to be recycled and degraded by the phagolysosome. Not necessarily, the presented modulators can target all these pathways and signaling steps.