Spot14/Mig12 heterocomplex sequesters polymerization and restrains catalytic function of human acetyl-CoA carboxylase 2

Authors

  • Sungjo Park,

    1. Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, USA
    2. Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN, USA
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  • In-Wook Hwang,

    1. Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, USA
    2. Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN, USA
    3. Laboratory of Biotechnology, Graduate School of Science and Technology, Shizuoka University, Shizuoka, Japan
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  • Yu Makishima,

    1. Laboratory of Biotechnology, Graduate School of Science and Technology, Shizuoka University, Shizuoka, Japan
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  • Ester Perales-Clemente,

    1. Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, USA
    2. Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN, USA
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  • Tatsuya Kato,

    1. Laboratory of Biotechnology, Graduate School of Science and Technology, Shizuoka University, Shizuoka, Japan
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  • Nicolas J. Niederländer,

    1. Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, USA
    2. Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN, USA
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  • Enoch Y. Park,

    1. Laboratory of Biotechnology, Graduate School of Science and Technology, Shizuoka University, Shizuoka, Japan
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  • Andre Terzic

    Corresponding author
    1. Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, USA
    2. Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN, USA
    • Correspondence to: A. Terzic, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

      E-mail: terzic.andre@mayo.edu

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  • This article is published in Journal of Molecular Recognition as part of the virtual Special Issue ‘AFM BioMed Shanghai 2013, edited by Jun Hu, SINAP, China and Pierre Parot and Jean-Luc Pellequer, CEA, France’.

Abstract

Acetyl-CoA carboxylase 2 (ACC2) is an isoform of ACC functioning as a negative regulator of fatty acid β-oxidation. Spot14, a thyroid hormone responsive protein, and Mig12, a Spot14 paralog, have recently been identified as regulators of fatty acid synthesis targeting ACC1, a distinctive subtype of ACC. Here, we examined whether Spot14/Mig12 modulates ACC2. Nanoscale protein topography mapped putative protein–protein interactions between purified human Spot14/Mig12 and ACC2, validated by functional assays. Human ACC2 displayed consistent enzymatic activity, and homogeneous particle distribution was probed by atomic force microscopy. Citrate-induced polymerization and enzymatic activity of ACC2 were restrained by the addition of the recombinant Spot14/Mig12 heterocomplex but only partially by the oligo-heterocomplex, demonstrating that the heterocomplex is a designated metabolic inhibitor of human ACC2. Moreover, Spot14/Mig12 demonstrated a sequestering role preventing an initial ACC2 nucleation step during filamentous polymer formation. Thus, the Spot14/Mig12 heterocomplex controls human ACC2 polymerization and catalytic function, emerging as a previously unrecognized molecular regulator in catalytic lipid metabolism. © 2013 The Authors. Journal of Molecular Recognition published by John Wiley & Sons, Ltd.

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