Chaperone-mediated autophagy at a glance

Chaperone-mediated autophagy (CMA) is an intracellular catabolic pathway that mediates the degradation of a selective subset of cytosolic proteins in lysosomes (Dice, 2007; Cuervo, 2010; Kon and Cuervo, 2010; Orenstein and Cuervo, 2010). The term autophagy (or self-eating) is broadly used to designate the lysosomal delivery and degradation of intracellular components (Mizushima et al., 2008; Mizushima and Levine, 2010; Yang and Klionsky, 2010). Various types of autophagy co-exist in almost all cells, and they can be differentiated by the mechanisms that mediate the delivery of cargo (the substrates to be degraded) to lysosomes. Macroautophagy and microautophagy are variants of the autophagic process, in which entire regions of cytosol (in 'bulk' autophagy) or selective cytosolic components (organelles, protein complexes, protein aggregates, pathogens, etc.) are sequestered in vesicular compartments. Lysosomal enzymes can gain access to the enclosed cargo through direct fusion of the vesicles with lysosomes (in macroautophagy), or by internalization of cargo-containing vesicles that form at the lysosomal membrane (in microautophagy). A third form of autophagy, solely dedicated to degradation of soluble proteins can also be detected in most cell types in mammals. This autophagic process, known as chaperone-mediated autophagy, differs from the other forms of autophagy in both the way in which cargo proteins are recognized for lysosomal delivery and the way in which these proteins reach the lysosomal lumen (Dice, 2007; Cuervo, 2010). In this article and the accompanying poster, we summarize the main steps involved in degradation of cytosolic proteins by CMA, the essential components of this pathway both in the cytosol and at the lysosomal membrane and the basis for the regulation of this autophagic process. We also include a synopsis of the described physiological functions of CMA and some (See poster insert)