Mitochondrial uncoupling protein 3 and its role in cardiac- and skeletal muscle metabolism.
Uncoupling protein 3 (UCP3), is primarily expressed in skeletal muscle mitochondria and has been suggested to be involved in mediating energy expenditure via uncoupling, hereby dissipating the mitochondrial proton gradient necessary for adenosine triphosphate (ATP) synthesis. Although some studies support a role for UCP3 in energy metabolism, other studies pointed towards a function in fatty acid metabolism. Thus, the protein is up regulated or high when fatty acid supply to the mitochondria exceeds the capacity to oxidize fatty acids and down regulated or low when oxidative capacity is high or improved. Irrespective of the exact operating mechanism, UCP3 seems to protect mitochondria against lipid-induced oxidative stress, which makes this protein a potential player in the development of type 2 diabetes mellitus. Next to skeletal muscle, UCP3 is also expressed in cardiac muscle where its role is relatively unexplored. Interestingly, energy deficiency in cardiac muscle is associated to heart failure and UCP3 might contribute to this energy deficiency. It has been suggested that UCP3 decreases energy status via uncoupling of mitochondrial respiration, but the available data does not provide a unified answer. In fact, the results obtained regarding cardiac UCP3 are very similar as in skeletal muscle, implying that its physiological function can be extrapolated. Therefore, cardiac UCP3 can just as well serve to protect the heart against lipid-induced oxidative stress, similar to the function described for skeletal muscle UCP3. The present review will deal with the available literature on both skeletal muscle- and cardiac UCP3 to elucidate its physiological function in these tissues.
Nabben
Miranda
M
Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. m.nabben@hb.unimaas.nl
Hoeks
Joris
J
D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D005223:Fats / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D054792:Muscle, Striated / Q000502:physiology*; D000071247:Uncoupling Protein 3
D005223:Fats; D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3