Autophagy
-
Chaperone-mediated autophagy (CMA) is a lysosomal pathway of proteolysis that is responsible for the degradation of 30% of cytosolic proteins under conditions of prolonged nutrient deprivation. Molecular chaperones in the cytosol and in the lysosomal lumen stimulate this proteolytic pathway. The molecular chaperones in the cytosol unfold substrate proteins prior to their translocation across the lysosomal membrane, while the chaperone in the lysosomal lumen is probably required to pull the substrate protein across the lysosomal membrane. ⋯ The reduced CMA in aging is due to reduced LAMP-2A in the lysosomal membrane. This reduction is caused by an age-related increased degradation of LAMP-2A and an age-related reduced ability of LAMP-2A to reinsert into the lysosomal membrane. These findings reveal a rich complexity of mechanisms to control CMA activity.