Mammalian mitochondrial uncoupling proteins.
The mammalian uncoupling protein (UCP-1) from the gene family of mitochondrial carriers is a dimer of identical 33 kDa subunits, each containing six membrane-spanning alpha-helices. Its expression, restricted to brown fat, occurs upon birth, cold acclimation and overfeeding. UCP-1 dissipates redox energy and thereby provides heat to the animal. Two additional isoforms have recently been discovered, 59% homologous UCP-2, widely expressed (heart, kidney, lung, placenta, lymphocytes, white fat); and UCP-3 (57% homologous), found in brown fat and skeletal muscle. Their physiological roles are unknown, but may include the regulation of body weight and energy balance, muscle nonshivering thermogenesis, fever, and defense against generation of reactive oxygen species. Consequently, great pharmacological potential is expected in revealing their biochemical and hormonal regulators. UCP-1 mediates a purine-nucleotide-sensitive uniport of monovalent unipolar anions, including fatty acids, that lead to fatty acid cycling and uncoupling. UCP-2 and UCP-3 are expected to share a similar mechanism.
Jezek
P
P
Department of Membrane Transport Biophysics, Academy of Sciences of the Czech Republic, Prague, Czech Republic. jezek@sun1.biomed.cas.cz
Garlid
K D
KD
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1