at Google ScholarTitle data
Laurent, Gaëlle ; German, Natalie J. ; Saha, Asish K. ; de Boer, Vincent C. J. ; Davies, Michael ; Koves, Timothy R. ; Dephoure, Noah ; Fischer, Frank ; Boanca, Gina ; Vaitheesvaran, Bhavapriya ; Lovitch, Scott B. ; Sharpe, Arlene H. ; Kurland, Irwin J. ; Steegborn, Clemens ; Gygi, Steven P. ; Muoio, Deborah M. ; Ruderman, Neil B. ; Haigis, Marcia C.:
SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase.
In: Molecular Cell.
Vol. 50
(2013)
Issue 5
.
- pp. 686-698.
ISSN 1097-4164
DOI: https://doi.org/10.1016/j.molcel.2013.05.012
Abstract in another language
Lipid metabolism is tightly controlled by the nutritional state of the organism. Nutrient-rich conditions increase lipogenesis, whereas nutrient deprivation promotes fat oxidation. In this study, we identify the mitochondrial sirtuin, SIRT4, as a regulator of lipid homeostasis. SIRT4 is active in nutrient-replete conditions to repress fatty acid oxidation while promoting lipid anabolism. SIRT4 deacetylates and inhibits malonyl CoA decarboxylase (MCD), an enzyme that produces acetyl CoA from malonyl CoA. Malonyl CoA provides the carbon skeleton for lipogenesis and also inhibits fat oxidation. Mice lacking SIRT4 display elevated MCD activity and decreased malonyl CoA in skeletal muscle and white adipose tissue. Consequently, SIRT4 KO mice display deregulated lipid metabolism, leading to increased exercise tolerance and protection against diet-induced obesity. In sum, this work elucidates SIRT4 as an important regulator of lipid homeostasis, identifies MCD as a SIRT4 target, and deepens our understanding of the malonyl CoA regulatory axis.
Further data
| Item Type: | Article in a journal |
|---|---|
| Refereed: | Yes |
| Additional notes: | PubMed-ID: 23077570 |
| Institutions of the University: | Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry I - Proteinbiochemie der Signaltransduktion > Chair Biochemistry - Univ.-Prof. Dr. Clemens Steegborn Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry I - Proteinbiochemie der Signaltransduktion |
| Result of work at the UBT: | Yes |
| DDC Subjects: | 500 Science > 540 Chemistry |
| Date Deposited: | 20 Apr 2015 12:22 |
| Last Modified: | 10 Dec 2024 12:53 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/10421 |