UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells

Uncoupling proteins (UCPs) are a family of mitochondrial transporter protei ns that have been implicated in thermoregulatory heat production and mainte nance of the basal metabolic rate, We have identified and partially charact erized a novel member of the human uncoupling protein family termed uncoupl ing protein-4 (UCP4). Protein sequence analyses showed that UCP4 is most re lated to UCP3 and possesses features characteristic of mitochondrial transp orter proteins, Unlike other known UCPs, UCP3 transcripts are exclusively e xpressed in both fetal and adult brain tissues. UCP4 maps to human chromoso me 6p11.2-q12. Consistent with its potential role as an uncoupling protein, UCP4 is localized to the mitochondria and its ectopic expression in mammal ian cells reduces mitochondrial membrane potential. These findings suggest that UCP4 may be involved in thermoregulatory heat production and metabolis m in the brain. (C) 1999 Federation of European Biochemical Societies.