Schematic depiction of the three types of autophagy. (a) Chaperone-mediated autophagy. The cytosolic chaperone protein HSC 70 binds to the substrate protein; the consensus sequence LysPheGluArgGln of the substrate-chaperone complex is recognized by LAMP-2A, a lysosomal membrane receptor. The protein substrate is then unfolded and translocated across the lysosomal membrane to be degraded inside the lysosome. (b) Macroautophagy. Cytosolic material is sequestered by an expanding membrane sac (phagophore) forming a double-membrane vesicle, an autophagosome. Fusion of the autophagosome to the lysosome will expose the content of the autophagosome to lysosomal hydrolases. (c) Microautophagy. Small proteins can be engulfed directly by the lysosome without intermediate vesicles.
