A quest for the origin of mammal uncoupling proteins

Nonshivering thermogenesis is dependent on the presence of UCP1 in brown adipose tissue. The function of UCP2 and UCP3 is most likely related to mitochondrial superoxide metabolism and/or fatty acid oxidation. These three members of the core UCP family are known in eutherians but had not been found in marsupials and monotremes so far. The objective of our search is to determine the origin of UCP1 and classical nonshivering thermogenesis. Furthermore, our approach to characterize UCP2/UCP3 in distantly related animal species will assist in the functional annotation of these proteins. We recently reported on the molecular identifi cation, tissue-distribution, and physiological regulation of UCP2 and UCP3 mRNA in the marsupial Antechinus fl avipes (yellow-footed Antechinus). Despite separate evolution of the marsupial lineage since 130 million years, our data suggest a conserved physiological role of these UCPs. Here, we present the immunological detection of marsupial UCP3 in skeletal muscle using antibodies raised against mouse/rat UCP3. A comprehensive phylogenetic analysis led us to hypothesize that all uncoupling proteins were already present at the evolutionary stage of modern teleost fi shes and questions the unique presence of UCP1 in placental mammals. However, the search for UCP1 in nonplacental mammals has been unsuccessful so far and is most likely hampered by the more rapid evolution of UCP1 as compared to other UCPs.