Superoxide activates mitochondrial uncoupling proteins

@article{Echtay2002SuperoxideAM,
  title={Superoxide activates mitochondrial uncoupling proteins},
  author={K. Echtay and D. Roussel and J. St-Pierre and M. Jekabsons and S. Cadenas and J. Stuart and J. Harper and Stephen J Roebuck and A. Morrison and S. Pickering and J. Clapham and M. Brand},
  journal={Nature},
  year={2002},
  volume={415},
  pages={96-99}
}
Uncoupling protein 1 (UCP1) diverts energy from ATP synthesis to thermogenesis in the mitochondria of brown adipose tissue by catalysing a regulated leak of protons across the inner membrane. The functions of its homologues, UCP2 and UCP3, in other tissues are debated. UCP2 and UCP3 are present at much lower abundance than UCP1, and the uncoupling with which they are associated is not significantly thermogenic. Mild uncoupling would, however, decrease the mitochondrial production of reactive… Expand
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It is found that native U CP3 actively lowers the rate of ROS production in isolated energized skeletal muscle mitochondria, in the absence of exogenous activators, suggesting that UCP3 can also affect ROS production through a membrane potential-independent mechanism. Expand
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TLDR
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Mitochondrial uncoupling proteins--what is their physiological role?
  • K. Echtay
  • Biology, Medicine
  • Free radical biology & medicine
  • 2007
TLDR
This review critically examines the evidence of the different proposed mechanisms for UCPs functions, namely (a) to export fatty acid anions from mitochondria, (b) to regulate insulin secretion in pancreatic beta-cells, and (c) to cause mild uncoupling and so diminish mitochondrial superoxide production, hence protecting against oxidative damage. Expand
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TLDR
The skeletal muscle isoform of the uncoupling protein family, UCP3, seems to be specifically active under conditions of high fatty acid availability and suggested to export fatty acid anions and/or peroxides from the mitochondrial matrix, thereby specifically protecting fatty acids from ROS-induced oxidative damage. Expand
Mitochondrial UCPs: new insights into regulation and impact.
TLDR
New information emerging from comparative proteomics about the impact of UCPs on mitochondrial physiology, when recombinant UCP1 is expressed in yeast and when UCP2 is over-expressed in hepatic mitochondria during steatosis is discussed. Expand
Uncoupling Protein 1 Decreases Superoxide Production in Brown Adipose Tissue Mitochondria*
TLDR
It is shown that UCP1 potently reduces mitochondrial superoxide production after cold acclimation and during fatty acid oxidation and suggests diminished probability of “reverse electron transport” facilitated by uncoupled respiration as the underlying mechanism of reactive oxygen species suppression in BAT. Expand
Respiratory uncoupling by UCP1 and UCP2 and superoxide generation in endothelial cell mitochondria.
TLDR
It is shown that UCPs do have uncoupled properties when expressed in BAE mitochondria but that uncoupling by UCP1 or UCP2 does not prevent acute substrate-driven endothelial cell superoxide as effluxed from mitochondria respiring in vitro. Expand
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Results strongly suggest that UCP2 is sensitive to GDP and that the UCPs, particularly U CP2, are able to modulate H2O2 mitochondrial generation, which supports a role for UCP1 in cellular (patho‐) physiological processes involving free radicals generated by mitochondria, such as oxidative damage, inflammation, or apoptosis. Expand
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TLDR
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TLDR
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TLDR
Results suggest either that Northern and Western blots do not reflect the levels of active protein or that these UCPs do not catalyse the basal proton conductance in skeletal muscle mitochondria. Expand
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