MondoA deficiency enhances sprint performance in mice

Minako Imamura, Benny Hung Junn Chang, Motoyuki Kohjima, Ming Li, Byounghoon Hwang, Heinrich Taegtmeyer, Robert Harris, Lawrence Chan

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

MondoA is a basic helix-loop-helix (bHLH)/leucine zipper (ZIP) transcription factor that is expressed predominantly in skeletal muscle. Studies in vitro suggest that the Max-like protein X (MondoA:Mlx) heterodimer senses the intracellular energy status and directly targets the promoter region of thioredoxin interacting protein (Txnip) and possibly glycolytic enzymes. We generated MondoA-inactivated (MondoA-/-) mice by gene targeting. MondoA-/- mice had normal body weight at birth, exhibited normal growth and appeared to be healthy. However, they exhibited unique metabolic characteristics. MondoA-/- mice built up serum lactate and alanine levels and utilized fatty acids for fuel during exercise. Gene expression and promoter analysis suggested that MondoA functionally represses peroxisomeproliferatoractivated receptor γ co-activator-1α (PGC-1α)-mediated activation of pyruvate dehydrogenase kinase 4 (PDK-4) transcription. PDK4 normally down-regulates the activity of pyruvate dehydrogenase, an enzyme complex that catalyses the decarboxylation of pyruvate to acetyl-CoA for entry into the Krebs cycle; in the absence of MondoA, pyruvate is diverted towards lactate and alanine, both products of glycolysis. Dynamic testing revealed that MondoA-/- mice excel in sprinting as their skeletal muscles display an enhanced glycolytic capacity. Our studies uncover a hitherto unappreciated function of MondoA in fuel selection in vivo. Lack of MondoA results in enhanced exercise capacity with sprinting.

Original languageEnglish (US)
Pages (from-to)35-48
Number of pages14
JournalBiochemical Journal
Volume464
DOIs
StatePublished - Nov 15 2014
Externally publishedYes

Fingerprint

Pyruvic Acid
Alanine
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Muscle
Lactic Acid
Acetyl Coenzyme A
Skeletal Muscle
Thioredoxins
Enzymes
Transcription
Pyruvate Dehydrogenase Complex
Genetic Promoter Regions
Gene expression
Ideal Body Weight
Decarboxylation
Citric Acid Cycle
Gene Targeting
Oxidoreductases
Proteins
Glycolysis

Keywords

  • Energy metabolism
  • Exercise
  • Fuel selection
  • Glycolysis
  • MondoA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Imamura, M., Chang, B. H. J., Kohjima, M., Li, M., Hwang, B., Taegtmeyer, H., ... Chan, L. (2014). MondoA deficiency enhances sprint performance in mice. Biochemical Journal, 464, 35-48. https://doi.org/10.1042/BJ20140530

MondoA deficiency enhances sprint performance in mice. / Imamura, Minako; Chang, Benny Hung Junn; Kohjima, Motoyuki; Li, Ming; Hwang, Byounghoon; Taegtmeyer, Heinrich; Harris, Robert; Chan, Lawrence.

In: Biochemical Journal, Vol. 464, 15.11.2014, p. 35-48.

Research output: Contribution to journalArticle

Imamura, M, Chang, BHJ, Kohjima, M, Li, M, Hwang, B, Taegtmeyer, H, Harris, R & Chan, L 2014, 'MondoA deficiency enhances sprint performance in mice', Biochemical Journal, vol. 464, pp. 35-48. https://doi.org/10.1042/BJ20140530
Imamura M, Chang BHJ, Kohjima M, Li M, Hwang B, Taegtmeyer H et al. MondoA deficiency enhances sprint performance in mice. Biochemical Journal. 2014 Nov 15;464:35-48. https://doi.org/10.1042/BJ20140530
Imamura, Minako ; Chang, Benny Hung Junn ; Kohjima, Motoyuki ; Li, Ming ; Hwang, Byounghoon ; Taegtmeyer, Heinrich ; Harris, Robert ; Chan, Lawrence. / MondoA deficiency enhances sprint performance in mice. In: Biochemical Journal. 2014 ; Vol. 464. pp. 35-48.
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