Different types of autophagy coexist in most mammalian cells, and each of them fulfills very specific tasks in intracellular degradation. Some of these autophagic pathways contribute to cellular metabolism by directly hydrolyzing intracellular lipid stores and glycogen. Chaperone-mediated autophagy (CMA), in contrast, is a selective form of autophagy that can only target proteins for lysosomal degradation. Consequently, it was expected that the only possible contribution of this pathway to cellular metabolism would be by providing free amino acids resulting from protein breakdown. However, recent studies have demonstrated that disturbance in CMA leads to important alterations in glucose and lipid metabolism and in overall organism energetics. Here, we describe the unique mechanisms by which CMA contributes to the regulation of cellular metabolism and discuss the possible implications of these previously unknown functions of CMA for the pathogenesis of common metabolic diseases.
Chaperone-mediated autophagy (CMA) contributes to metabolic regulation through selective and timely degradation of key metabolic enzymes that participate in glycolysis and lipogenesis. This autophagic pathway also regulates lipolysis by selectively removing perilipins from the surface of lipid droplets. Loss of CMA activity with age and in different pathologies may underlie the basis of the metabolic syndrome associated to these conditions.