Chaperone-mediated autophagy in the kidney: the road more traveled.
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.
Research Service, Atlanta Veterans Affairs Medical Center, Decatur, GA; and Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, GA. Electronic address: hfranch@emory.edu.
Harold A
HA
Franch
D000375:Aging; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D003920:Diabetes Mellitus / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology; D052119:Lysosomal-Associated Membrane Protein 2 / Q000502:physiology; D018832:Molecular Chaperones / Q000502:physiology*; D009369:Neoplasms / Q000473:pathology; D018384:Oxidative Stress
D052119:Lysosomal-Associated Membrane Protein 2; D018832:Molecular Chaperones
Hypertrophy; cancer; diabetes; starvation