SnapShot: Selective Autophagy

There are various types of autophagy, which can be categorized as nonselective or selective. Macroautophagy is an evolutionarily conserved process through which cells degrade and recycle cytoplasm. Nonselective macroautophagy randomly engulfs a portion of the cytoplasm into autophagosomes and then delivers them to the vacuole (in fungi or plants) or the lysosome (in other higher eukaryotes) for degradation. Selective macroautophagy, however, specifically recognizes and degrades a particular cargo, either a protein complex, an organelle, or an invading microbe. The morphological hallmark of macroautophagy is the formation of an initial sequestering compartment, the phagophore, which expands into the double-membrane autophagosome; the initial sequestration occurs in a compartment that is separate from the degradative organelle. Selective microautophagy utilizes the same cellular machinery, but in this case, the sequestration event takes place directly at the limiting membrane of the lysosome/vacuole. In higher eukaryotes, selective types of autophagy also include chaperone-mediated autophagy (CMA), and two similar processes, endosomal microautophagy (e-MI) and chaperone-assisted selective autophagy (CASA), each of which involves uptake at the limiting membrane of either the lysosome or endosome. In all cases, how a substrate is targeted for sequestration and segregated from other parts of the cell is one of the major questions in this research field. Nonselective autophagy is primarily a starvation response, whereas cells use selective autophagy for a variety of purposes, including remodeling to adapt to changing environmental/nutritional conditions and to eliminate damaged organelles. Accordingly, defects in selective autophagy are associated with a range of pathophysiologies in humans, including certain types of neurodegenerative diseases.