Overexpression of the UCP3 gene in both murine and human myotube cell Cultures leads to a significant activation of the different proteolytic systems involved in muscle myofibrillar protein breakdown. Thus, lysosomal (cathepsin 13) and non-lysosomal (m-calpain and ubiquitin-proteasome) mRNA content was significantly increased in the different cell Culture systems used. Interestingly, the overexpression of the UCP3 gene was not associated with any changes in apoptosis. Although the function of the UCP3 protein is not completely understood (uncoupling, oxidative stress), these results suggest a possible relation between these main mechanisms involved in muscle wasting during cancer. (c) 2005 Elsevier B.V. All rights reserved.