BMCP1, a novel mitochondrial carrier with high expression in the central nervous system of humans and rodents, and respiration uncoupling activity inrecombinant yeast

We report here the cloning and functional analysis of a novel homologue of the mitochondrial carriers predominantly expressed in the central nervous s ystem and referred to as BMCP1 ((b) under bar rain (m) under bar itochondri al (c) under bar arrier (p) under bar rotein-(1) under bar). The predicted amino acid sequence of this novel mitochondrial carrier indicates a level o f identity of 39, 31, or 30%, toward the mitochondrial oxoglutarate carrier , phosphate carrier, or adenine nucleotide translocator, respectively, and a level of identity of 34, 38, or 39% with the mitochondrial uncoupling pro teins UCP1, UCP2, or UCP3, respectively. Northern analysis of mouse, rat, o r human tissues demonstrated that mRNA of this novel gene is mainly express ed in brain, although it is 10-30-fold less expressed in other tissues. In situ hybridization analysis of brain showed it is particularly abundant in cortex, hippocampus, thalamus, amygdala, and hypothalamus. Chromosomal mapp ing indicates that BMCP1 is located on chromosome X off mice and at Xq24 in man. Expression of the protein in yeast strongly impaired growth rate. Ana lysis of respiration of total recombinant yeast or yeast spheroplasts and i n particular of the relationship between respiratory rate and membrane pote ntial of yeast spheroplasts revealed a marked uncoupling activity of respir ation, suggesting that although BMCP1 sequence is more distant from the unc oupling proteins (UCPs), this protein could be a fourth member of the UCP f amily.