Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation.

ABSTRACT: The activity of chaperone-mediated autophagy (CMA), a catabolic pathway for selective degradation of cytosolic proteins in lysosomes, decreases with age, but the consequences of this functional decline in vivo remain unknown. In this work, we have generated a conditional knockout mouse to selectively block CMA in liver. We have found that blockage of CMA causes hepatic glycogen depletion and hepatosteatosis. The liver phenotype is accompanied by reduced peripheral adiposity, increased energy expenditure, and altered glucose homeostasis. Comparative lysosomal proteomics revealed that key enzymes in carbohydrate and lipid metabolism are normally degraded by CMA and that impairment of their regulated degradation contributes to the metabolic abnormalities observed in CMA-defective animals. The

SUBMITTER: Schneider JL 

PROVIDER: S-EPMC4156578 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature