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  • Open Access

Uncoupling protein 3 attenuates generation of reactive oxygen species by interacting with thioredoxin 2 in the mitochondrial intermembrane space

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Arthritis Research & Therapy201214 (Suppl 1) :P24

  • Published:


  • Reactive Oxygen Species
  • Target Signaling
  • Uncouple Protein
  • Intermembrane Space
  • Complementation Analysis

Uncoupling protein 3 (UCP3) is primarily expressed in the inner membrane of skeletal muscle mitochondria. It has been proposed that UCP3 reduces production of reactive oxygen species (ROS) and oxidative damage. However, the mechanisms by which UCP3 attenuates ROS production are not well understood. Here we report that UCP3 interacts with the non-processed form of thioredoxin 2 (Trx2), a redox protein that is localized in mitochondria, but not processed Trx2, which is involved in cellular responses to ROS. The hydrophilic sequences within the N-terminal tail of UCP3, which faces the intermembrane space, are necessary for binding to Trx2. In addition, Trx2 directly associated with UCP3 through a mitochondrial targeting signaling sequence, was processed in the intermembrane space, and thereby allowing redox reactions. A bimolecular fluorescence complementation analysis demonstrated that the interaction of these proteins occurs in the mitochondrial intermembrane space. Furthermore, increased UCP3 expression significantly attenuated ROS production in isolated mitochondrial without effects on membrane potential, however this effect is lost by Trx2 knock down. These results suggest that UCP3 binds to Trx2 in the mitochondrial intermembrane space and attenuates ROS production.

Authors’ Affiliations

Department of Nutritional Physiology, Institute of Health Biosciences, University of Tokushima, Tokushima 770-8503, Japan
Division of Pharmacology/Toxicology, University of Texas at Austin, Austin, TX 78712, USA


© Hirasaka et al.; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.