Journal
CELL METABOLISM
Volume 20, Issue 3, Pages 417-432Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2014.06.009
Keywords
-
Categories
Funding
- National Institutes of Health [AG021904, AG031782, AG038072, DK098408, AG024391, GM104459, DK20541]
- NIH/NIA [T32-GM007288, F30AG046109]
Ask authors/readers for more resources
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. 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 in old organisms.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available