Fig. 1

Overview of three types of autophagy in mammalian cells. During macroautophagy, cytosolic materials are first sequestered into a cup-shaped double-membrane structure, called phagophore, which elongates and matures into the double-membrane vesicle known as an autophagosome. The autophagosome fuses with the lysosome to form an autolysosome. Alternatively, the autophagosome fuses with the late endosome to form amphisome, which then fuses with the lysosome to form autolysosome. Gray arrows show mechanisms of autophagy. Autophagy is initiated by stresses (such as the mechanistic target of rapamycin kinase complex 1 (mTORC1)), followed by activation of the unc-51 like autophagy activating kinase 1 (ULK1) complex and phosphatidylinositol 3-kinase catalytic subunit type 3 complex I (PI3KC3-C1), which generates phosphatidylinositol-3-phosphate (PI3P). PI3P further recruits the ATG12-ATG5-ATG16L1 complex, which enhances the ubiquitin-like microtubule associated protein 1 light chain 3 (LC3)-I conjugates with PE to become the lipidated form LC3-II, contributing to autophagosome formation. Then a series of tethering related components are involved in the formation of autolysosome. Microautophagy involves the direct uptake of cytoplasmic materials through the invagination of the lysosomal membrane. Chaperone-mediated autophagy (CMA) can only degrade soluble proteins containing the KFERQ-like motif, which are recognized by the chaperone heat shock protein family A (Hsp70) member 8 (HSPA8), and directly across the lysosomal membrane by a receptor or translocon containing lysosomal associated membrane protein 2 (LAMP2) in the cytoplasm. During all three types of autophagy, the sequestered cargos are degraded by lysosomal hydrolases and recycled for the maintenance of cellular homeostasis