Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation

Mitochondrial uncoupling proteins have been implicated in the maintenance o f metabolic rate and adaptational thermoregulation, We recently reported th e identification of a brain-specific mitochondrial uncoupling protein homol ogue, UCP4, Here we; characterized another newly described member of the un coupling protein family, termed UCP5 (also called BMCP1). UCP5 transcripts are present in multiple human and mouse tissues, with an especially high ab undance in the brain and testis, Expression of UCP5 in mammalian cells redu ces the mitochondrial membrane potential, Multiple isoforms of UCP5 were id entified and exhibited tissue-specific distribution and different potency i n reduction of membrane potential. Furthermore, the mRNA abundance of both UCP4 and UCP5 is modulated by nutritional status or temperature in a tissue -specific manner in mice. Brain UCP4 and UCP5 mRNA transcripts rose by 1.5- and 1.7-fold, respectively, and liver UCP5 expression increased by 1.8-fol d in response to acute cold exposure. A high-fat diet increased UCP5 mRNA i n liver by 1.6-fold selectively in the obesity-resistant A/J but not in the obesity-prone C57BL/6J mouse strain, Liver UCP5 expression decreased signi ficantly with a 24 h fast and was restored to the normal level after refeed ing. In contrast, brain transcripts for both genes were not significantly a ltered by fasting or high-fat diet. These findings are consistent with the notion that UCP4 and UCP5 may be involved in tissue-specific thermoregulati on and metabolic changes associated with nutritional status.