Consequences of the selective blockage of chaperone-mediated autophagy.
Chaperone-mediated autophagy (CMA) is a selective pathway for the degradation of cytosolic proteins in lysosomes. CMA declines with age because of a decrease in the levels of lysosome-associated membrane protein (LAMP) type 2A, a lysosomal receptor for this pathway. We have selectively blocked the expression of LAMP-2A in mouse fibroblasts in culture and analyzed the cellular consequences of reduced CMA activity. CMA-defective cells maintain normal rates of long-lived protein degradation by up-regulating macroautophagy, the major form of autophagy. Constitutive up-regulation of macroautophagy is unable, however, to compensate for all CMA functions. Thus, CMA-defective cells are more sensitive to stressors, suggesting that, although protein turnover is maintained, the selectivity of CMA is necessary as part of the cellular response to stress. Our results also denote the existence of cross-talk among different forms of autophagy.
Massey
Ashish C
AC
Department of Anatomy and Structural Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Ullmann Building, Room 611, Bronx, NY 10461, USA.
Kaushik
Susmita
S
Sovak
Guy
G
Kiffin
Roberta
R
Cuervo
Ana Maria
AM
D016475:3T3 Cells; D000818:Animals; D001343:Autophagy; D002478:Cells, Cultured; D018833:Chaperonins / Q000037:antagonists & inhibitors / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D007700:Kinetics; D051907:Lysosomal Membrane Proteins / Q000502:physiology; D008247:Lysosomes / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D034622:RNA Interference
D051907:Lysosomal Membrane Proteins; D018833:Chaperonins