UCP2
MIM.601693 11q13 HGNC:12518 Entrez:7351
Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP).
UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak.
UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane.
They also reduce the mitochondrial membrane potential in mammalian cells. Tissue specificity occurs for the different UCPs and the exact methods of how UCPs transfer H+/OH- are not known.
UCPs contain the three homologous protein domains of MACPs. This gene is expressed in many tissues, with the greatest expression in skeletal muscle. It is thought to play a role in nonshivering thermogenesis, obesity and diabetes.
Chromosomal order is 5’-UCP3-UCP2-3’.
Although the most common mechanism underlying congenital hyperinsulinism is dysfunction of the pancreatic ATP-sensitive potassium channel, the pathogenesis and genetic origins of this disease remains largely unexplained in more than half of all patients.
UCP2 knockout mice exhibit an hyperinsulinemic hypoglycemia, suggesting an involvement of UCP2 in insulin secretion.
Parental-inherited heterozygous UCP2 variants encoding amino-acid changes were found in two unrelated children with congenital hyperinsulinism.
Functional assays in yeast and in insulin-secreting cells revealed an impaired activity of UCP2 mutants.
UCP2 coding variants in human congenital hyperinsulinism reveals a role for this gene in the regulation of insulin secretion and glucose metabolism in humans.
There is a direct association between UCP2 amino acid alteration and human disease and highlight a role for mitochondria in hormone secretion.
Pathology
UCP2-associated hyperinsulinism
References
UCP2, a metabolic sensor coupling glucose oxidation to mitochondrial metabolism? Pecqueur C, Alves-Guerra C, Ricquier D, Bouillaud F. IUBMB Life. 2009 Jul;61(7):762-7. PMID: #19514063#
Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion. González-Barroso MM, Giurgea I, Bouillaud F, Anedda A, Bellanné-Chantelot C, Hubert L, de Keyzer Y, de Lonlay P, Ricquier D. PLoS One. 2008;3(12):e3850. PMID: #19065272#
Paradis E, Clavel S, Bouillaud F, Ricquier D, Richard D. Uncoupling protein 2: a novel player in neuroprotection. Trends Mol Med. 2003 Dec;9(12):522-5. PMID: #14659466#