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. 2021 Jan 12;12:330. doi: 10.1038/s41467-020-20123-1

Fig. 3. Autophagosome formation is highly regulated and involves many proteins.

Fig. 3

Assembly of the ULK1-FIP200-Atg13-Atg101 complex primes the induction of Beclin1-VPS34-VPS15 complex to generate phosphatidylinositol-3-phosphate (PIP3) lipids in membranes of different organelles (e.g., endoplasmic reticulum). The ULK1 and the Beclin1 complexes are negatively or positively modulated by mTOR and AMPK, respectively. The PIP3 signal recruits the conjugation systems (LC3/GABARAP and Atg5/Atg12/Atg16) of autophagy that induces the covalent linking of phospholipids with LC3-GABARAP proteins for membrane’s commitment to becoming autophagosomes. Then the committed membrane (phagophore assembly site or isolation membrane) elongates and closes to form a double-layered vesicle (autophagosome) that is docked to the lysosome (Ly) for cargo destruction. The endoplasmic reticulum site where autophagosomes are formed, which is revealed by DFCP1 protein, is named omegasome.