Journal
NATURE COMMUNICATIONS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms8415
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Funding
- Canadian Institute of Health Research (CIHR) [MOP-81148, MOP-93707]
- Canadian Diabetes Association (CDA)
- Canada Research Chair in Signal Transduction in Diabetes Pathogenesis
- CIHR Doctoral Research Award
- CDA Doctoral Student Research Award
- Canadian Liver Foundation Graduate Studentship
- Banting and Best Diabetes Centre (BBDC) Fellowship in Diabetes Care (Eli Lilly Canada)
- Eliot Phillipson Clinician Scientist Training Program
- CDA Postdoctoral Fellowship
- Canadian Society of Endocrinology and Metabolism
- BBDC
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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.
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