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.