Abstract
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.
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Dates
Type | When |
---|---|
Created | 19 years, 4 months ago (April 3, 2006, 8:35 p.m.) |
Deposited | 3 years, 4 months ago (April 12, 2022, 10:06 a.m.) |
Indexed | 2 days, 12 hours ago (Aug. 27, 2025, 12:36 p.m.) |
Issued | 19 years, 4 months ago (April 11, 2006) |
Published | 19 years, 4 months ago (April 11, 2006) |
Published Online | 19 years, 4 months ago (April 11, 2006) |
Published Print | 19 years, 4 months ago (April 11, 2006) |
@article{Massey_2006, title={Consequences of the selective blockage of chaperone-mediated autophagy}, volume={103}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0507436103}, DOI={10.1073/pnas.0507436103}, number={15}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Massey, Ashish C. and Kaushik, Susmita and Sovak, Guy and Kiffin, Roberta and Cuervo, Ana Maria}, year={2006}, month=apr, pages={5805–5810} }