Chaperone-mediated autophagy: a unique way to enter the lysosome world

All cellular proteins undergo continuous synthesis and degradation. This permanent renewal is necessary to maintain a functional proteome and to allow rapid changes in levels of specific proteins with regulatory purposes. Although for a long time lysosomes were considered unable to contribute to the selective degradation of individual proteins, the discovery of chaperone-mediated autophagy (CMA) changed this notion. Here, we review the characteristics that set CMA apart from other types of lysosomal degradation and the subset of molecules that confer cells the capability to identify individual cytosolic proteins and direct them across the lysosomal membrane for degradation. All cellular proteins undergo continuous synthesis and degradation. This permanent renewal is necessary to maintain a functional proteome and to allow rapid changes in levels of specific proteins with regulatory purposes. Although for a long time lysosomes were considered unable to contribute to the selective degradation of individual proteins, the discovery of chaperone-mediated autophagy (CMA) changed this notion. Here, we review the characteristics that set CMA apart from other types of lysosomal degradation and the subset of molecules that confer cells the capability to identify individual cytosolic proteins and direct them across the lysosomal membrane for degradation. degradation of intracellular proteins and organelles in lysosomes. proteases located inside lysosomes that reach maximal activity at acidic pH. protein that assists other proteins in their folding, unfolding, and intracellular trafficking by preventing non-specific interactions with other surrounding proteins. autophagic pathway in which cytosolic proteins are targeted one-by-one to the surface of the lysosome from where they reach the lumen by crossing the lysosomal membrane. degradation of cytosolic proteins in late endosomes after internalization by mechanisms that resemble those of microautophagy. single-membrane-enclosed vesicles dedicated to the breakdown of cellular structures for recycling. They are characterized by their luminal acidic pH and their high abundance of hydrolases. a family of single-span membrane proteins preferentially located in lysosomes that display a short C-terminus (10–12 amino acids) at the cytosolic side of the lysosomal membrane. The luminal part of these proteins is heavily glycosylated to protect them from degradation. autophagic pathway in which cytosolic proteins and organelles are sequestered into a double-membrane vesicle and then fuse with lysosomes to assure their degradation. internalization of cytosolic proteins and organelles into lysosomes through invaginations of the lysosomal membrane that then pinch off as single-membrane vesicles into the lysosomal lumen.