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 peroxisome-proliferator-activated 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.
Skip Nav Destination
Follow us on Twitter @Biochem_Journal
Article navigation
November 2014
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
October 23 2014
MondoA deficiency enhances sprint performance in mice Available to Purchase
Minako Imamura;
Minako Imamura
1
*Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030, U.S.A.
†Diabetes Research Center, Baylor College of Medicine, Houston, TX 77030, U.S.A.
Search for other works by this author on:
Benny Hung-Junn Chang;
Benny Hung-Junn Chang
*Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030, U.S.A.
†Diabetes Research Center, Baylor College of Medicine, Houston, TX 77030, U.S.A.
Search for other works by this author on:
Motoyuki Kohjima;
Motoyuki Kohjima
*Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030, U.S.A.
†Diabetes Research Center, Baylor College of Medicine, Houston, TX 77030, U.S.A.
Search for other works by this author on:
Ming Li;
Ming Li
*Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030, U.S.A.
†Diabetes Research Center, Baylor College of Medicine, Houston, TX 77030, U.S.A.
Search for other works by this author on:
Byounghoon Hwang;
Byounghoon Hwang
‡Richard Roudebush VA Medical Center, 1481 West Tenth Street, Indianapolis, IN 46202, U.S.A.
Search for other works by this author on:
Heinrich Taegtmeyer;
Heinrich Taegtmeyer
§Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, U.S.A.
Search for other works by this author on:
Robert A. Harris;
Robert A. Harris
‡Richard Roudebush VA Medical Center, 1481 West Tenth Street, Indianapolis, IN 46202, U.S.A.
Search for other works by this author on:
Lawrence Chan
Lawrence Chan
2
*Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030, U.S.A.
†Diabetes Research Center, Baylor College of Medicine, Houston, TX 77030, U.S.A.
∥Department of Medicine, Baylor College of Medicine, Houston, TX 77030, U.S.A.
¶Baylor St. Luke's Medical Center, Houston, TX 77030, U.S.A.
2To whom correspondence should be addressed (email [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
April 24 2014
Revision Received:
August 19 2014
Accepted:
August 22 2014
Accepted Manuscript online:
August 22 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 464 (1): 35–48.
Article history
Received:
April 24 2014
Revision Received:
August 19 2014
Accepted:
August 22 2014
Accepted Manuscript online:
August 22 2014
Citation
Minako Imamura, Benny Hung-Junn Chang, Motoyuki Kohjima, Ming Li, Byounghoon Hwang, Heinrich Taegtmeyer, Robert A. Harris, Lawrence Chan; MondoA deficiency enhances sprint performance in mice. Biochem J 15 November 2014; 464 (1): 35–48. doi: https://doi.org/10.1042/BJ20140530
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |