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

作者：Shi Sally Yu; Lu Shun Yan; Sivasubramaniyam Tharini; Revelo Xavier S; Cai Erica P; Luk Cynthia T; Schroer Stephanie A; Patel Prital; Kim Raymond H; Bombardier Eric; Quadrilatero Joe; Tupling A Russell; Mak Tak W; Winer Daniel A; Woo Minna^*

来源：Nature Communications, 2015, 6(1): 7415.

DOI：10.1038/ncomms8415

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.

• 出版日期2015-6
• 单位河北医科大学