Autophagy describes a process where eukaryotic cells degrade cytoplasmic material in the lysosomal compartment.
The term “autophagy”, literally meaning “self-eating” when translated from Greek, was coined by Christian de Duve in 1963.
Autophagy is an essential cytoprotective process that provides various opportunities for adaptive responses to cellular insults, such as starvation. As such, autophagy is a survival mechanism and fulfills important roles in development, differentiation, immunity and pathogen defense. Autophagy is further considered to contribute to life-span extension, and autophagy dysregulation has been found to foster the pathogenesis of many human diseases.
Three major forms of autophagy have been recognized:
- Macroautophagy, characterized by the formation of autophagosomes that deliver cytoplasmic material to the lysosomes,
- Microautophagy, characterized by direct engulfment of cytoplasmic material through lysosomal membrane invagination,
- Chaperone-mediated autophagy, characterized by the degradation of proteins in lysosomes mediated by the chaperone Hsc70, co-chaperones and the lysosomal receptor LAMP2A.
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The process of macroautophagy
During the process of macroautophagy (herafter: autophagy), cytoplasmic material, including organelles, proteins, lipids and membranes, becomes sequestered in unique double-membrane vesicles, called autophagosomes. The sequestration of cytoplasmic material occurs either stochastically or due to specific cargo recognition. Autophagosomes are formed by the elongation and closure of a membrane template, referred to as isolation membrane or phagophore. Subsequently, autophagosomes acquire acidic hydrolases from the fusion with lysosomes, thereby forming the so-called autolysosome. Monomers of the degraded cargo are finally shuttled to the cytoplasm for recycling or storage. Autophagy is active on a constitutive low basal level, but rapidly elevated upon a great variety of cellular insults.