The Role of Chaperone-Mediated Autophagy in Tissue Homeostasis and Disease Pathogenesis

Abstract

Chaperone-mediated autophagy; Homeostasis; Pathogenesis

Autofagia mediada por chaperonas; Homeostasis; Patogénesis

Autofàgia mediada per xaperones; Homeòstasi; Patogènesi

Chaperone-mediated autophagy (CMA) is a selective proteolytic pathway in the lysosomes. Proteins are recognized one by one through the detection of a KFERQ motif or, at least, a KFERQ-like motif, by a heat shock cognate protein 70 (Hsc70), a molecular chaperone. CMA substrates are recognized and delivered to a lysosomal CMA receptor, lysosome-associated membrane protein 2A (LAMP-2A), the only limiting component of this pathway, and transported to the lysosomal lumen with the help of another resident chaperone HSp90. Since approximately 75% of proteins are reported to have canonical, phosphorylation-generated, or acetylation-generated KFERQ motifs, CMA maintains intracellular protein homeostasis and regulates specific functions in the cells in different tissues. CMA also regulates physiologic functions in different organs, and is then implicated in disease pathogenesis related to aging, cancer, and the central nervous and immune systems. In this minireview, we have summarized the most important findings on the role of CMA in tissue homeostasis and disease pathogenesis, updating the recent advances for this Special Issue.

This work was supported by PID2020-114010RB-I00 as “ERDF A way of making Europe” and RYC2019-027520-I as “ESF Investing in your future” funded by Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación, MCIN/AEI/10.13039/501100011033 (to RV) and the Fondo de Investigación Sanitaria-Instituto de Salud Carlos III (Spain)-FEDER (PI20/00728), the Fundación BBVA (NanoERT), and the Fundació La Caixa (HR22-00602) (to MMV).