Fig. 2

Different types of autophagy [132]. Microautophagy refers to the sequestration of cytosolic components directly by lysosomes through invaginations in their limiting membrane. The function of this process in higher eukaryotes is not known, whereas microautophagy-like processes in fungi are involved in selective organelle degradation. In the case of macroautophagy, the cargoes are sequestered within a unique double-membrane cytosolic vesicle, an autophagosome. Sequestration can be either nonspecific, involving the engulfment of bulk cytoplasm, or selective, targeting specific cargoes such as organelles or invasive microbes. The autophagosome is formed by expansion of the phagophore, but the origin of the membrane is unknown. Fusion of the autophagosome with an endosome (not shown) or a lysosome provides hydrolases. Lysis of the autophagosome inner membrane and breakdown of the contents occurs in the autolysosome, and the resulting macromolecules are released back into the cytosol through membrane permeases. Chaperone-mediated autophagy (CMA) involves direct translocation of unfolded substrate proteins across the lysosome membrane through the action of a cytosolic and lysosomal chaperone hsc70, and the integral membrane receptor lysosome-associated membrane protein type 2A (LAMP-2A)