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Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation.

Publication ,  Journal Article
Still, AJ; Floyd, BJ; Hebert, AS; Bingman, CA; Carson, JJ; Gunderson, DR; Dolan, BK; Grimsrud, PA; Dittenhafer-Reed, KE; Stapleton, DS ...
Published in: J Biol Chem
September 6, 2013

Lysine acetylation is rapidly becoming established as a key post-translational modification for regulating mitochondrial metabolism. Nonetheless, distinguishing regulatory sites from among the thousands identified by mass spectrometry and elucidating how these modifications alter enzyme function remain primary challenges. Here, we performed multiplexed quantitative mass spectrometry to measure changes in the mouse liver mitochondrial acetylproteome in response to acute and chronic alterations in nutritional status, and integrated these data sets with our compendium of predicted Sirt3 targets. These analyses highlight a subset of mitochondrial proteins with dynamic acetylation sites, including acetyl-CoA acetyltransferase 1 (Acat1), an enzyme central to multiple metabolic pathways. We performed in vitro biochemistry and molecular modeling to demonstrate that acetylation of Acat1 decreases its activity by disrupting the binding of coenzyme A. Collectively, our data reveal an important new target of regulatory acetylation and provide a foundation for investigating the role of select mitochondrial protein acetylation sites in mediating acute and chronic metabolic transitions.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

September 6, 2013

Volume

288

Issue

36

Start / End Page

26209 / 26219

Location

United States

Related Subject Headings

  • Sirtuin 3
  • Proteome
  • Mitochondria, Liver
  • Mice, Obese
  • Mice
  • Biochemistry & Molecular Biology
  • Animals
  • Acetylation
  • Acetyl-CoA C-Acetyltransferase
  • Acetyl Coenzyme A
 

Citation

APA
Chicago
ICMJE
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Still, A. J., Floyd, B. J., Hebert, A. S., Bingman, C. A., Carson, J. J., Gunderson, D. R., … Pagliarini, D. J. (2013). Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation. J Biol Chem, 288(36), 26209–26219. https://doi.org/10.1074/jbc.M113.483396
Still, Amelia J., Brendan J. Floyd, Alexander S. Hebert, Craig A. Bingman, Joshua J. Carson, Drew R. Gunderson, Brendan K. Dolan, et al. “Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation.J Biol Chem 288, no. 36 (September 6, 2013): 26209–19. https://doi.org/10.1074/jbc.M113.483396.
Still AJ, Floyd BJ, Hebert AS, Bingman CA, Carson JJ, Gunderson DR, et al. Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation. J Biol Chem. 2013 Sep 6;288(36):26209–19.
Still, Amelia J., et al. “Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation.J Biol Chem, vol. 288, no. 36, Sept. 2013, pp. 26209–19. Pubmed, doi:10.1074/jbc.M113.483396.
Still AJ, Floyd BJ, Hebert AS, Bingman CA, Carson JJ, Gunderson DR, Dolan BK, Grimsrud PA, Dittenhafer-Reed KE, Stapleton DS, Keller MP, Westphall MS, Denu JM, Attie AD, Coon JJ, Pagliarini DJ. Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation. J Biol Chem. 2013 Sep 6;288(36):26209–26219.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

September 6, 2013

Volume

288

Issue

36

Start / End Page

26209 / 26219

Location

United States

Related Subject Headings

  • Sirtuin 3
  • Proteome
  • Mitochondria, Liver
  • Mice, Obese
  • Mice
  • Biochemistry & Molecular Biology
  • Animals
  • Acetylation
  • Acetyl-CoA C-Acetyltransferase
  • Acetyl Coenzyme A