Chaperone-mediated autophagy: mechanisms and physiological relevance

A fraction of the cellular proteome can be selectively targeted to lysosomes for degradation within this organelle by a process known as chaperone-mediated autophagy (CMA). A dedicated network of genes and their protein products contribute to CMA execution and regulation. Here, we describe the most recent advances on the molecular dissection of CMA and on the understanding of the lysosomal and cellular components that contribute to its regulation, both under physiological conditions and in response to different stressors. The recent development of experimental mouse models to track, upregulate, or downregulate CMA in vivo has helped identify that, besides the role of CMA in cellular protein quality control, this type of autophagy also contributes to timely remodeling of the cellular functional proteome to modulate a variety of cellular processes. We review some of the novel regulatory roles of CMA and the consequences of CMA failure on physiology and cellular functioning.