Chaperone-Mediated Autophagy in the Kidney: The Road More Traveled

• Type of Material: Article
• Authors: Harold Franch, Emory University
• Language: English
• Date: 2014-01-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.semnephrol.2013.11.010
• Title of Journal or Parent Work: Seminars in Nephrology
• ISSN: 0270-9295
• Volume: 34
• Issue: 1
• Start Page: 72
• End Page: 83
• Grant/Funding Information: Supported by the National Institute for Diabetes and Digestive and Kidney Diseases (R01 DK 073476).
• Keywords: MAMMALIAN TARGET; starvation; REGULATORS; Hypertrophy; Urology & Nephrology; LYSOSOMAL MEMBRANE; Life Sciences & Biomedicine; PROTEIN-DEGRADATION; Science & Technology; DISEASE; diabetes; RENAL HYPERTROPHY; CYTOSOLIC PROTEINS; SELECTIVE UPTAKE; PATHWAYS; cancer; PROTEOLYSIS
• Research Categories: Chemistry, Biochemistry; Health Sciences, Medicine and Surgery

Abstract

Chaperone-mediated autophagy (CMA) is a lysosomal proteolytic pathway in which cytosolic substrate proteins contain specific chaperone recognition sequences required for degradation and are translocated directly across the lysosomal membrane for destruction. CMA proteolytic activity has a reciprocal relationship with macroautophagy: CMA is most active in cells in which macroautophagy is least active. Normal renal proximal tubular cells have low levels of macroautophagy, but high basal levels of CMA activity. CMA activity is regulated by starvation, growth factors, oxidative stress, lipids, aging, and retinoic acid signaling. The physiological consequences of changes in CMA activity depend on the substrate proteins present in a given cell type. In the proximal tubule, increased CMA results from protein or calorie starvation and from oxidative stress. Overactivity of CMA can be associated with tubular lysosomal pathology and certain cancers. Reduced CMA activity contributes to protein accumulation in renal tubular hypertrophy, but may contribute to oxidative tissue damage in diabetes and aging. Although there are more questions than answers about the role of high basal CMA activity, this remarkable feature of tubular protein metabolism appears to influence a variety of chronic diseases.