Cited by 137Cancer, Lipids, and MetabolismLipid metabolism and biosynthesisPeroxisome Proliferator-Activated Receptors

Induced polymerization of mammalian acetyl-CoA carboxylase by MIG12 provides a tertiary level of regulation of fatty acid synthesis

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Kim, Chai-Wan, Moon, Young-Ah, Park, Sahng Wook, Cheng, Dong, Kwon, Hyock Joo, Horton, Jay D.·2010·Proceedings of the National Academy of Sciences

Abstract

Acetyl-CoA carboxylase (ACC), the first committed enzyme in fatty acid (FA) synthesis, is regulated by phosphorylation/dephosphorylation, transcription, and an unusual mechanism of protein polymerization. Polymerization of ACC increases enzymatic activity and is induced in vitro by supraphysiological concentrations of citrate (> 5 mM). Here, we show that MIG12, a 22 kDa cytosolic protein of previously unknown function, binds to ACC and lowers the threshold for citrate activation into the physiological range (< 1 mM). In vitro, recombinant MIG12 induced polymerization of ACC (as determined by nondenaturing gels, FPLC, and electron microscopy) and increased ACC activity by > 50-fold in the presence of 1 mM citrate. In vivo, overexpression of MIG12 in liver induced ACC polymerization, increased FA synthesis, and produced triglyceride accumulation and fatty liver. Thus, in addition to its regulation by phosphorylation and transcription, ACC is regulated at a tertiary level by MIG12, which facilitates ACC polymerization and enhances enzymatic activity.

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Authors
Kim, C.-W., Moon, Y.-A., Park, S. W., Cheng, D., Kwon, H. J., & Horton, J. D.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • Bristol-Myers Squibb (United States) (US)
Venue
Proceedings of the National Academy of Sciences
Published
2010-05-08
Volume
107
Issue
21
Pages
9626-9631
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2023893231
Cited by
136
References
31
Citations by year
2026: 3 · 2025: 12 · 2024: 12 · 2023: 9 · 2022: 9 · 2021: 8 · 2020: 7 · 2019: 9 · 2018: 14 · 2017: 6 · 2016: 5 · 2015: 8 · 2014: 9 · 2013: 6 · 2012: 9
FWCI
2.52
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by)
Funders
  • National Institutes of Health (HL20948)
  • National Heart, Lung, and Blood Institute (HL 38049, HL-20948, R01HL038049, P01HL020948)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords
acetyl-CoA carboxylase, protein polymerization, fatty acid synthesis, citrate activation, enzyme regulation, triglyceride accumulation, hepatic steatosis, liver
MeSH terms
Acetyl-CoA Carboxylase, Animals, Cytosol, Fatty Acids, Male, Mice, Inbred C57BL, Microtubule-Associated Proteins, Phosphorylation, Protein Binding, Mice, Protein Multimerization

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