The effect of UCP3 overexpression on mitochondrial ROS production in skeletal muscle of young versus aged mice

Nabben, Miranda; Hoeks, Joris; Briedé, Jacob J.; Glatz, Jan F.C.; Moonen-Kornips, Esther; Hesselink, Matthijs K.C.; Schrauwen, Patrick

doi:10.1016/j.febslet.2008.11.016

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Volume 582, Issue 30 , Pages 4147-4152, 24 December 2008

The effect of UCP3 overexpression on mitochondrial ROS production in skeletal muscle of young versus aged mice

Edited by Vladimir Skulachev

Miranda Nabben
- Departments of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands
Joris Hoeks
- Departments of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands
Jacob J. Briedé
- Departments of Health Risk Analysis and Toxicology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, The Netherlands
Jan F.C. Glatz
- Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Netherlands
Esther Moonen-Kornips
- Departments of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands
Matthijs K.C. Hesselink
- Human Movement Sciences, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, The Netherlands
Patrick Schrauwen
- Departments of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands
- Corresponding author. Fax: +31 43 3670976.

Received 26 September 2008; received in revised form 4 November 2008; accepted 12 November 2008. published online 26 November 2008.

Abstract

Uncoupling protein 3 (UCP3) is suggested to protect mitochondria against aging and lipid-induced damage, possibly via modulation of reactive oxygen species (ROS) production. Here we show that mice overexpressing UCP3 (UCP3Tg) have a blunted age-induced increase in ROS production, assessed by electron spin resonance spectroscopy, but only after addition of 4-hydroxynonenal (4-HNE). Mitochondrial function, assessed by respirometry, on glycolytic substrate was lower in UCP3Tg mice compared to wild types, whereas this tended to be higher on fatty acids. State 4o respiration was higher in UCP3Tg animals. To conclude, UCP3 overexpression leads to increased state 4o respiration and, in presence of 4-HNE, blunts the age-induced increase in ROS production.

Abbreviations: ROS, reactive oxygen species, UCP, uncoupling protein, ESR, electron spin resonance, UCP3Tg, mice overexpressing human skeletal muscle UCP3, WT, wild type, BSA, bovine serum albumin, TA, tibialis anterior, 4-HNE, 4-hydroxynonenal, DMPO, 5,5-dimethyl-1-pyrolline N-oxide, FCCP, p-trifluoromethoxy carbonyl cyanide phenylhydrazone, SOD, superoxide dismutase