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Macroautophagy (hereafter referred as autophagy) is a highly conserved degradation pathway by which the cytoplasmic materials are sequestered by the double-membrane vesicles named autophagosomes, and delivered to lysosomes for degradation and recycling (Nakatogawa et al., 2009). Autophagy is initiated by the de novo formation of a double membrane phagophore (also known as isolation membrane) around intracellular substrates, the phagophore grows into an intact autophagosome, and the autophagosome fuses with lysosome. Autophagy is tightly controlled by diverse signaling molecules. Dysfunction of autophagy is often linked to a variety of diseases, including neurodegenerative diseases, cancer, metabolic disorders, and inflammation (Levine and Kroemer, 2019).

The hallmark of autophagy is autophagosome formation, which involves nucleation, expansion, and closure of the phagophore (Melia et al., 2020; Nakatogawa, 2020). A number of autophagy related proteins (ATG) cooperate to mediate autophagosome biogenesis. In mammalian cells, autophagosome nucleation is typically driven by the ULK1 (unc-51-like kinase 1) complex, the counterpart of the Atg1 complex in yeast. The class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) is activated to generate phosphatidylinositol-3-phosphate (PI (3) P), which recruits the downstream effector WIPIs (WD-repeat protein interacting with phosphoinositides). WIPIs in turn recruit and activate the conjugation machinery to mediate the lipidation of ATG8 family proteins. The lipid transporter ATG2, the scramblase ATG9 and lipidated ATG8 proteins contribute to phagophore …