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SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
- Hirschey, Matthew D;
- Shimazu, Tadahiro;
- Goetzman, Eric;
- Jing, Enxuan;
- Schwer, Bjoern;
- Lombard, David B;
- Grueter, Carrie A;
- Harris, Charles;
- Biddinger, Sudha;
- Ilkayeva, Olga R;
- Stevens, Robert D;
- Li, Yu;
- Saha, Asish K;
- Ruderman, Neil B;
- Bain, James R;
- Newgard, Christopher B;
- Farese Jr, Robert V;
- Alt, Frederick W;
- Kahn, C Ronald;
- Verdin, Eric
Published Web Location
https://doi.org/10.1038/nature08778Abstract
SIRT3 regulation of fatty acid oxidationThe sirtuin family of regulatory proteins has been implicated in various biological pathways including responses to calorie restriction and metabolic stress. Work in mice now shows that sirtuin 3 (SIRT3), which mediates deacetylation of several mitochondrial proteins, is induced in liver and brown adipose tissue during fasting. One of SIRT3's substrates is shown to be long-chain acyl co-enzyme A dehydrogenase (LCAD). Without SIRT3, LCAD becomes hyperacetylated, which diminishes its activity, and reduces fatty acid oxidation. Mice without SIRT3 have all the hallmarks of fatty acid oxidation disorders during fasting, including reduced ATP levels and intolerance to cold. These findings suggest that acetylation is a novel regulatory mechanism for fatty acid oxidation.
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