Figure 2.

A simplified scheme of macro autophagy (further: autophagy). Mechanistic targets of rapamycin (mTOR) and AMP-activated kinase (AMPK) are the primary autophagy inhibitor and inducer, respectively. On autophagy initiation, the cytoplasmic material to be degraded (cargo) is gradually encapsulated by double membranes: phagophores to encapsulated vesicles (autophagosomes), which then fuse with lysosomes to form autolysosomes, where cargo is degraded and then released into cytoplasm to be used again (recycling). Autophagy is regulated by many proteins, the autophagy-related proteins (ATGs), and their complexes. The initiation process is led by the Unc − 51-like kinase 1 (ULK1) complex, the formation of the double membrane, provided by ATG − 9-containing vesicles, and autophagosome—by the class III PI3K (phosphatidylinositol 3-kinase) nucleation complex and the phosphatidylinositol 3-phosphate (PI3P)-binding complex, which includes ATG12, Beclin 1, and the microtubule-associated protein light chain 3/γ-aminobutyric acid receptor-associated proteins (LC3/GABARAPs), represented here only by LC3. ATG12 attaches to ATG5, which is then associated with ATG16L1. This complex stimulates the cleavage of LC3 by ATG4 to form LC3-I, which is then conjugated with phosphatidylethanolamine (PE) to form LC3-II. On the incorporation into autophagosomal membranes, LC3 interacts with cargo receptors, which have LC3-interacting motifs (LIRs).