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. 2023 Jan 23;14:1094020. doi: 10.3389/fphar.2023.1094020

FIGURE 3.

FIGURE 3

Primary mechanism of autophagy. The autophagic signaling pathway. Under metabolic stress, AMPK activation and/or mTORC1 inhibition lead to the activation of the preinitiation complex (ULK1, FIP200, and ATG13). The latter activates the initiation complex (beclin 1, VPS15, and VPS34) that generates PI3P and recruits ATG7 to the phagophore. ATG7 initiates two conjugation pathways necessary for membrane elongation and closure of the autophagosome. In the ATG5-ATG12 conjugation pathway, ATG12 is sequentially transferred to ATG7, ATG10, and ATG12. The ATG5-12 conjugate recruits ATG16L and forms a complex necessary to stabilize the phagophore and to complete the second conjugation pathway. In the LC3-PE pathway, LC3 is cleaved by ATG4 and sequentially conjugated to ATG7 and ATG3. The ATG5-ATG12-ATG16 L complex carries out the final step by transferring LC3 to PE to form an LC3-PE conjugate (also called LC3-II). LC3-II binds to the autophagosomal membrane, and form autolysosome. AMPK, AMP-activated protein kinase; Atg, autophagy related gene; Bcl2, antiapoptotic protein; Beclin1, myosin-like BCL2 interacting protein; LC3 (MAP1LC3), microtubule-associated proteins light chain three; mTORC1, mammalian target of rapamycin complex one; p62, p62 protein; PIP, polyphosphoinositides; Rag, Rag proteins (RagA–D); TFEB, transcription factor EB; ULK, Unc-51-like kinase; vATPases, vacuolar-type adenosine triphosphatases.