Mitochondrial uncoupling prevents cold-induced oxidative stress: a case study using UCP1 knockout mice

Antoine Stier*, Pierre Bize, Caroline Habold, Frederic Bouillaud, Sylvie Massemin, Franois Criscuolo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)


The relationship between metabolism and reactive oxygen species (ROS) production by the mitochondria has often been (wrongly) viewed as straightforward, with increased metabolism leading to higher generation of pro-oxidants. Insights into mitochondrial functioning show that oxygen consumption is principally coupled with either energy conversion as ATP or as heat, depending on whether the ATP-synthase or the mitochondrial uncoupling protein 1 (UCP1) is driving respiration. However, these two processes might greatly differ in terms of oxidative costs. We used a cold challenge to investigate the oxidative stress consequences of an increased metabolism achieved either by the activation of an uncoupled mechanism (i.e. UCP1 activity) in the brown adipose tissue (BAT) of wild-type mice or by ATP-dependent muscular shivering thermogenesis in mice deficient for UCP1. Although both mouse strains increased their metabolism by more than twofold when acclimatised for 4 weeks to moderate cold (12 C), only mice deficient for UCP1 suffered from elevated levels of oxidative stress. When exposed to cold, mice deficient for UCP1 showed an increase of 20.2% in plasmatic reactive oxygen metabolites, 81.8% in muscular oxidized glutathione and 47.1% in muscular protein carbonyls. In contrast, there was no evidence of elevated levels of oxidative stress in the plasma, muscles or BAT of wild-type mice exposed to cold despite a drastic increase in BAT activity. Our study demonstrates differing oxidative costs linked to the functioning of two highly metabolically active organs during thermogenesis, and advises careful consideration of mitochondrial functioning when investigating the links between metabolism and oxidative stress.

Original languageEnglish
Pages (from-to)624-630
Number of pages7
JournalJournal of Experimental Biology
Issue number4
Early online date12 Feb 2014
Publication statusPublished - Feb 2014

Bibliographical note

We are grateful to two anonymous reviewers for providing interesting and
constructive comments on a previous draft of the paper.

Competing interests
The authors declare no competing financial interests.

Author contributions
A.S. designed the study. A.S. and C.H. collected the data. A.S., F.C., P.B., S.M.
and F.B. took part in data analyses and interpretations. A.S., P.B. and F.C. wrote
the paper. All authors have read and approved the final version of the manuscript.

This work was supported by the CNRS (PICS, grant no. 5296 to F.C.), the French
Ministry of Research and the University of Strasbourg. P.B. is funded by the Swiss
National Research Foundation (grant no. 31003A_124988).


  • Uncoupling protein
  • Oxidative stress
  • Reactive oxygen species
  • Cold
  • Nonshivering thermogenesis
  • Mitochondria


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