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Accession IconGSE49553

Trancriptome analysis in mice deficient for chaperone-mediated autophagy in liver

Organism Icon Mus musculus
Sample Icon 12 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

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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 this regulated degradation contributes to the metabolic abnormalities observed in CMA-defective animals. These findings highlight the involvement of CMA in regulating hepatic metabolism and suggest that the age-related decline in CMA may have a negative impact on the energetic balance of old organisms.
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