ABSTRACT
In the early years, autophagy was thought to be a nonselective bulk degradation pathway. However, later experiments demonstrated that some cytosolic proteins upon microinjection into cultured fibroblast cells underwent differential rates of degradation in the lysosomes. Basal CMA activity has been detected in most cell types for maintenance of cellular homeostasis. At the basal level, chaperone-mediated autophagy (CMA) plays an important role in protein quality control. Apart from being a stress response pathway, CMA also plays an imperative role in maintaining metabolic balance in more than one way. Besides alleviating proteotoxicity, CMA also protects against genotoxicity. CMA also performs specialized functions related to the client substrates it regulates in certain cell types. In order to ensure adequate protein quality control, recycling of raw materials, and maintenance of cellular homeostasis, coordination between the various proteolytic pathways is necessary, particularly in eliciting compensatory responses when one of the degradative pathways fails to work properly.
