UCPs are transmembrane proteins that decrease the proton gradient generated in oxidative phosphorylation.
They do this by increasing the permeability of the inner mitochondrial membrane, allowing protons that have been pumped into the intermembrane space to return to the mitochondrial matrix.
UCP1-mediated heat generation in brown fat uncouples the respiratory chain, allowing for fast substrate oxidation with a low rate of ATP production.
UCP1 is related to other mitochondrial metabolite transporters such as the adenine nucleotide translocator, a proton channel in the mitochondrial inner membrane that permits the translocation of protons from the mitochondrial intermembrane space to the mitochondrial matrix.
UCP1 is restricted to brown adipose tissue, where it provides a mechanism for the enormous heat-generating capacity of the tissue.

UCP1 is activated in the brown fat cell by fatty acids and inhibited by nucleotides.
Fatty acids are released by the following signaling cascade: Sympathetic nervous system terminals release Norepinephrine onto a Beta-3 adrenergic receptor on the plasma membrane.
This activates adenylyl cyclase, which catalyses the conversion of ATP to cyclic AMP (cAMP).
cAMP activates protein kinase A, causing its active C subunits to be freed from its regulatory R subunits.
Active protein kinase A, in turn, phosphorylates triacylglycerol lipase, thereby activating it.
The lipase converts triacylglycerols into free fatty acids, which activate UCP1, overriding the inhibition caused by purine nucleotides (GDP and ADP).
During the termination of thermogenesis, thermogenin is inactivated and residual fatty acids are disposed of through oxidation, allowing the cell to resume its normal energy-conserving state.

UCP1 is very similar to the ATP/ADP Carrier protein, or Adenine Nucleotide Translocator (ANT).
The proposed alternating access model for UCP1 is based on the similar ANT mechanism.
The substrate comes in to the half open UCP1 protein from the cytoplasmic side of the membrane, the protein closes the cytoplasmic side so the substrate is enclosed in the protein, and then the matrix side of the protein opens, allowing the substrate to be released into the mitochondrial matrix.
The opening and closing of the protein is accomplished by the tightening and loosening of salt bridges at the membrane surface of the protein.
Substantiation for this modelling of UCP1 on ANT is found in the many conserved residues between the two proteins that are actively involved in the transportation of substrate across the membrane.
Both proteins are integral membrane proteins, localized to the inner mitochondrial membrane, and they have a similar pattern of salt bridges, proline residues, and hydrophobic or aromatic amino acids that can close or open when in the cytoplasmic or matrix state.
UCPs are transmembrane proteins that decrease the proton gradient generated in oxidative phosphorylation. They do this by increasing the permeability of the inner mitochondrial membrane, allowing protons that have been pumped into the intermembrane space to return to the mitochondrial matrix. UCP1-mediated heat generation in brown fat uncouples the respiratory chain, allowing for fast substrate oxidation with a low rate of ATP production. UCP1 is related to other mitochondrial metabolite transporters such as the adenine nucleotide translocator, a proton channel in the mitochondrial inner membrane that permits the translocation of protons from the mitochondrial intermembrane space to the mitochondrial matrix. UCP1 is restricted to brown adipose tissue, where it provides a mechanism for the enormous heat-generating capacity of the tissue.
UCP1 is activated in the brown fat cell by fatty acids and inhibited by nucleotides. Fatty acids are released by the following signaling cascade: Sympathetic nervous system terminals release Norepinephrine onto a Beta-3 adrenergic receptor on the plasma membrane. This activates adenylyl cyclase, which catalyses the conversion of ATP to cyclic AMP (cAMP). cAMP activates protein kinase A, causing its active C subunits to be freed from its regulatory R subunits. Active protein kinase A, in turn, phosphorylates triacylglycerol lipase, thereby activating it. The lipase converts triacylglycerols into free fatty acids, which activate UCP1, overriding the inhibition caused by purine nucleotides (GDP and ADP). During the termination of thermogenesis, thermogenin is inactivated and residual fatty acids are disposed of through oxidation, allowing the cell to resume its normal energy-conserving state.
UCP1 is very similar to the ATP/ADP Carrier protein, or Adenine Nucleotide Translocator (ANT). The proposed alternating access model for UCP1 is based on the similar ANT mechanism. The substrate comes in to the half open UCP1 protein from the cytoplasmic side of the membrane, the protein closes the cytoplasmic side so the substrate is enclosed in the protein, and then the matrix side of the protein opens, allowing the substrate to be released into the mitochondrial matrix. The opening and closing of the protein is accomplished by the tightening and loosening of salt bridges at the membrane surface of the protein. Substantiation for this modelling of UCP1 on ANT is found in the many conserved residues between the two proteins that are actively involved in the transportation of substrate across the membrane. Both proteins are integral membrane proteins, localized to the inner mitochondrial membrane, and they have a similar pattern of salt bridges, proline residues, and hydrophobic or aromatic amino acids that can close or open when in the cytoplasmic or matrix state.
Thermogenin