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

Sungjo Park, In Wook Hwang, Yu Makishima, Ester Perales-Clemente, Tatsuya Kato, Nicolas J. Niederländer, Enoch Y. Park, Andre Terzic

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)679-688
Number of pages10
JournalJournal of Molecular Recognition
Volume26
Issue number12
DOIs
StatePublished - Dec 2013

Keywords

  • Mig12
  • Spot14
  • Thrsp
  • acetyl-CoA carboxylase
  • atomic force microscopy
  • fatty acid oxidation
  • protein-protein interactions
  • silkworm Bombyx mori

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Park, S., Hwang, I. W., Makishima, Y., Perales-Clemente, E., Kato, T., Niederländer, N. J., Park, E. Y., & Terzic, A. (2013). Spot14/Mig12 heterocomplex sequesters polymerization and restrains catalytic function of human acetyl-CoA carboxylase 2. Journal of Molecular Recognition, 26(12), 679-688. https://doi.org/10.1002/jmr.2313