Cloning and characterization of an uncoupling protein homolog: a potential molecular mediator of human thermogenesis.
We have identified a novel cDNA encoding a protein highly homologous to the mammalian brown fat uncoupling protein (UCP). Unlike the known UCP, which is expressed specifically in brown adipose tissue, the UCP homolog (UCPH) mRNA is expressed in a variety of tissues, with predominant expression in human white adipose tissue and skeletal muscle. In the white adipose tissue of ob/ob and db/db mice, the UCPH transcript is induced approximately fivefold relative to lean littermate controls. Expression of murine UCPH in yeast results in growth inhibition under conditions that require aerobic respiration, but does not affect growth under anaerobic conditions. Furthermore, UCPH expression in yeast causes a decrease in the mitochondrial membrane potential, as judged by staining with the potential-sensitive dye DiOC6. These observations suggest that UCPH, like UCP, uncouples oxidative phosphorylation. The possibility that the UCPH protein is an important mediator of human thermogenesis is discussed.
Gimeno
R E
RE
Millennium Pharmaceuticals, Cambridge, Massachusetts 02139, USA.
Dembski
M
M
Weng
X
X
Deng
N
N
Shyjan
A W
AW
Gimeno
C J
CJ
Iris
F
F
Ellis
S J
SJ
Woolf
E A
EA
Tartaglia
L A
LA
D000595:Amino Acid Sequence; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics* / Q000494:pharmacology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D006801:Humans; D007473:Ion Channels; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D010085:Oxidative Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014475:Uncoupling Agents / Q000737:chemistry / Q000494:pharmacology; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D018076:DNA, Complementary; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1