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DJ-1 links muscle ROS production with metabolic reprogramming and systemic energy homeostasis in mice

Author

Listed:
  • Sally Yu Shi

    (Toronto General Research Institute, University Health Network
    Institute of Medical Science, University of Toronto)

  • Shun-Yan Lu

    (Toronto General Research Institute, University Health Network)

  • Tharini Sivasubramaniyam

    (Toronto General Research Institute, University Health Network
    Institute of Medical Science, University of Toronto)

  • Xavier S. Revelo

    (Toronto General Research Institute, University Health Network)

  • Erica P. Cai

    (Toronto General Research Institute, University Health Network
    Institute of Medical Science, University of Toronto)

  • Cynthia T. Luk

    (Toronto General Research Institute, University Health Network
    Institute of Medical Science, University of Toronto)

  • Stephanie A. Schroer

    (Toronto General Research Institute, University Health Network)

  • Prital Patel

    (Toronto General Research Institute, University Health Network
    Present address: Lunenfeld–Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada)

  • Raymond H. Kim

    (The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network)

  • Eric Bombardier

    (University of Waterloo)

  • Joe Quadrilatero

    (University of Waterloo)

  • A. Russell Tupling

    (University of Waterloo)

  • Tak W. Mak

    (The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network)

  • Daniel A. Winer

    (Toronto General Research Institute, University Health Network)

  • Minna Woo

    (Toronto General Research Institute, University Health Network
    Institute of Medical Science, University of Toronto
    University Health Network, University of Toronto)

Abstract

Reactive oxygen species (ROS) have been linked to a wide variety of pathologies, including obesity and diabetes, but ROS also act as endogenous signalling molecules, regulating numerous biological processes. DJ-1 is one of the most evolutionarily conserved proteins across species, and mutations in DJ-1 have been linked to some cases of Parkinson’s disease. Here we show that DJ-1 maintains cellular metabolic homeostasis via modulating ROS levels in murine skeletal muscles, revealing a role of DJ-1 in maintaining efficient fuel utilization. We demonstrate that, in the absence of DJ-1, ROS uncouple mitochondrial respiration and activate AMP-activated protein kinase, which triggers Warburg-like metabolic reprogramming in muscle cells. Accordingly, DJ-1 knockout mice exhibit higher energy expenditure and are protected from obesity, insulin resistance and diabetes in the setting of fuel surplus. Our data suggest that promoting mitochondrial uncoupling may be a potential strategy for the treatment of obesity-associated metabolic disorders.

Suggested Citation

  • Sally Yu Shi & Shun-Yan Lu & Tharini Sivasubramaniyam & Xavier S. Revelo & Erica P. Cai & Cynthia T. Luk & Stephanie A. Schroer & Prital Patel & Raymond H. Kim & Eric Bombardier & Joe Quadrilatero & A, 2015. "DJ-1 links muscle ROS production with metabolic reprogramming and systemic energy homeostasis in mice," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8415
    DOI: 10.1038/ncomms8415
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