Fig. 1. Schematic representation of autophagy progression in metazoans. (A) In response to starvation or other inductive cues, a membranous sac referred to as the phagophore or isolation membrane is nucleated from a poorly characterized structure known as the pre-autophagosomal structure or phagophore assembly site (PAS). (B) Expansion and curvature of the isolation membrane leads to engulfment of cytosolic material within the double membrane-bound autophagosome. The source of lipid contributing to this membrane growth has not been established. (C) Fusion of the autophagosomal outer membrane with lysosomes results in hydrolytic digestion of the inner membrane and the sequestered material, and export of the breakdown products into the cytoplasm. The prior fusion of autophagosomes with early or late endosomes (forming a structure known as an amphisome, not shown) may be required for autophagosome-lysosome fusion. (D,E) Electron micrographs of corresponding structures, including (D) a nearly completed autophagosome engulfing a mitochondrion, and (E) an auto-lysosome containing several degraded organelles and an intact mitochondrion.