Schematic model of the major pathways of the autophagic mechanisms. (A) Macroautophagy of intracellular substances includes initiation, elongation, closure, maturation, and degradation. The endoplasmic reticulum, Golgi apparatus, mitochondria, and plasma membranes are membrane sources of autophagic vesicles. The Ulk macromolecular complex promotes the initiation of the phagophore, thereby regulating PI3P formation to control nascent autophagosomes. Varieties of autophagy-related proteins are involved in this process. The autophagosome sequesters proteins, both misfolded and unfolded, and defective mitochondria. After maturation, autophagosomes fuse with lysosomes to form the autolysosome where the contents are degraded by acid hydrolases. (B) In microautophagy, lysosomes directly engulf cellular components. (C) In CMA, Hsc70 transports the target protein to the lysosome for degradation. ULK (UNC51-like) enzymes are a family of mammalian kinases that have critical roles in autophagy and development. PI3P, phosphatidyl inositol triphosphate; Atg, autophagy related gene; LC3, microtuble-associated protein light chain 3; ER, endoplasmic reticulum; Hsc, heat-shock cognate protein; LAMP, lysosome-associated membrane glycoprotein; CMA, chaperone-mediated autophagy; Hsc70, heat shock cognate 70.