Ribosomal protein-Mdm2-p53 pathway coordinates nutrient stress with lipid metabolism by regulating MCD and promoting fatty acid oxidation
Abstract
Although progress has been made in the characterization of p53 in regulating metabolism, very little is known about the signaling pathways involved in this regulation in response to stress in vivo. Here we show that p53 controls hepatic fatty acid oxidation in mice in response to fasting. Disruption of ribosome protein (RP)-mouse double minute (Mdm)2 binding in Mdm2C305F mice results in fasting-induced hepatosteatosis. A full-dosage of p53 and an intact RP-Mdm2-p53 pathway are required for the induction of malonyl coA decarboxylase (MCD), a critical regulator of fatty acid oxidation. Thus, the RP-Mdm2-p53 pathway functions as a key regulator of hepatic lipid homeostasis in response to nutrient deprivation stress, a function that has implications in organismal survival and tumor suppression.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- June 2014
- DOI:
- 10.1073/pnas.1315605111
- Bibcode:
- 2014PNAS..111E2414L