title: Chaperone-mediated autophagy: roles in disease and aging.
abstract: This review focuses on chaperone-mediated autophagy (CMA), one of the proteolytic systems that contributes to degradation of intracellular proteins in lysosomes. CMA substrate proteins are selectively targeted to lysosomes and translocated into the lysosomal lumen through the coordinated action of chaperones located at both sides of the membrane and a dedicated protein translocation complex. The selectivity of CMA permits timed degradation of specific proteins with regulatory purposes supporting a modulatory role for CMA in enzymatic metabolic processes and subsets of the cellular transcriptional program. In addition, CMA contributes to cellular quality control through the removal of damaged or malfunctioning proteins. Here, we describe recent advances in the understanding of the molecular dynamics, regulation and physiology of CMA, and discuss the evidence in support of the contribution of CMA dysfunction to severe human disorders such as neurodegeneration and cancer.
authors.affiliation: Department of Developmental and Molecular Biology, Institute for Aging Studies, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Chanin Building 504, Bronx, NY 10461, USA.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Cuervo
authors.affiliation: School of Biological Sciences, Nanyang Technological University, SBS-03n-05, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Esther
authors.initials: E
authors.lastname: Wong
mesh_terms: D000375:Aging; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics; D018832:Molecular Chaperones / Q000378:metabolism / Q000502:physiology*; D009369:Neoplasms / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology*
chemical_list: C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D035683:MicroRNAs; D018832:Molecular Chaperones