Disorders of Autophagy

The term autophagy derives from the Greek word autóphagos, which means “self-eating” or “self-digestion.” Autophagy is a fundamental and highly conserved intracellular pathway that in its most basic sense involves the delivery of cytoplasmic cargo to the lysosome for degradation. The Nobel Laureate in Physiology and Medicine in 1974, Christian de Duve, introduced this term to describe the self-eating function of lysosomes in degrading intracellular debris, including damaged organelles (mitochondria, endoplasmic reticulum membranes, ribosomes), and other cellular components such as larger protein aggregates (Harnett et al. 2017). Based on different modes of cargo delivery to lysosomes, three subtypes of autophagy have been defined: macro-autophagy, micro-autophagy, and chaperone-mediated autophagy. In macro-autophagy, cargo is transported inside double-membrane vesicles (or autophagosomes) which are delivered to and fused with lysosomes to form the autolysosome. In micro-autophagy, the cytosolic cargo is trapped in small vesicles formed by invagination of the lysosomal membrane. In chaperone-mediated autophagy, substrates are selectively targeted by hsp70 to the microvesicles and delivered by the receptor protein LAMP2 for lysosomal degradation.