Skip to main content
Journal cover image

SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase.

Publication ,  Journal Article
Laurent, G; German, NJ; Saha, AK; de Boer, VCJ; Davies, M; Koves, TR; Dephoure, N; Fischer, F; Boanca, G; Vaitheesvaran, B; Lovitch, SB ...
Published in: Mol Cell
June 6, 2013

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

June 6, 2013

Volume

50

Issue

5

Start / End Page

686 / 698

Location

United States

Related Subject Headings

  • Sirtuins
  • Oxidation-Reduction
  • Obesity
  • Mitochondrial Proteins
  • Mice, Knockout
  • Mice
  • Male
  • Lipids
  • Lipid Metabolism
  • Fatty Acids
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Laurent, G., German, N. J., Saha, A. K., de Boer, V. C. J., Davies, M., Koves, T. R., … Haigis, M. C. (2013). SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol Cell, 50(5), 686–698. https://doi.org/10.1016/j.molcel.2013.05.012
Laurent, Gaëlle, Natalie J. German, Asish K. Saha, Vincent C. J. de Boer, Michael Davies, Timothy R. Koves, Noah Dephoure, et al. “SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase.Mol Cell 50, no. 5 (June 6, 2013): 686–98. https://doi.org/10.1016/j.molcel.2013.05.012.
Laurent G, German NJ, Saha AK, de Boer VCJ, Davies M, Koves TR, et al. SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol Cell. 2013 Jun 6;50(5):686–98.
Laurent, Gaëlle, et al. “SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase.Mol Cell, vol. 50, no. 5, June 2013, pp. 686–98. Pubmed, doi:10.1016/j.molcel.2013.05.012.
Laurent G, German NJ, Saha AK, de Boer VCJ, Davies M, Koves TR, Dephoure N, Fischer F, Boanca G, Vaitheesvaran B, Lovitch SB, Sharpe AH, Kurland IJ, Steegborn C, Gygi SP, Muoio DM, Ruderman NB, Haigis MC. SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol Cell. 2013 Jun 6;50(5):686–698.
Journal cover image

Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

June 6, 2013

Volume

50

Issue

5

Start / End Page

686 / 698

Location

United States

Related Subject Headings

  • Sirtuins
  • Oxidation-Reduction
  • Obesity
  • Mitochondrial Proteins
  • Mice, Knockout
  • Mice
  • Male
  • Lipids
  • Lipid Metabolism
  • Fatty Acids