Uncoupling protein-3 (UCP3) gene is a member of the mitochondrial carrier superfamily preferentially expressed in skeletal muscle and up-regulated by fatty acids. Peroxisome proliferator-activated receptor (PPAR)alpha and PPARdelta (also known as PPARbeta) mediate human UCP3 gene regulation by fatty acids through a direct-repeat (DR-1) element in the promoter. DR-1 mutation renders UCP3 promote...

Glutathionylation has emerged as a key modification required for controlling protein function in response to changes in cell redox status. Recently, we showed that the glutathionylation state of uncoupling protein-3 (UCP3) modulates the leak of protons back into the mitochondrial matrix, thus controlling reactive oxygen species production. However, whether or not UCP3 glutathionylation is media...

Leak of protons into the mitochondrial matrix during substrate oxidation partially uncouples electron transport from phosphorylation of ADP, but the functions and source of basal and inducible proton leak in vivo remain controversial. In the present study we describe an endogenous activation of proton conductance in mitochondria isolated from rat and mouse skeletal muscle following addition of ...

The uncoupling protein UCP3 belongs to a family of mitochondrial carriers located in the inner mitochondrial membrane of certain cell types. It is expressed almost exclusively at high levels in skeletal muscle and its physiological role has not been fully determined in this tissue. In the present study we have addressed the possible interaction between a hypercaloric diet and thyroid hormone (T...

Uncoupling protein 1 (UCP1) is a proton transporter/channel residing on the inner mitochondrial membrane and is involved in cellular heat production. Using immunohistochemistry, we investigated the expression of UCP1 and UCP3 in a series of 98 patients with non-small cell lung cancer (NSCLC) treated with surgery. Expression patterns were correlated with histopathological variables, prognosis, a...

Oxidative capacity and uncoupling protein-3 (UCP3) content are reduced in limb muscles of patients with chronic obstructive pulmonary disease (COPD). It has been hypothesized that the physiological role of UCP3 is to protect mitochondria against lipotoxicity in cases where fatty acid influx exceeds the capacity to oxidize them. Exercise training improves oxidative capacity and reduces UCP3 prot...

Antibodies against Escherichia coli-expressed uncoupling protein-2 (UCP2) and uncoupling protein-3 (UCP3) were raised by operating the blotted proteins into the spleen of minipigs. The antisera reacted more intensively with the recombinant UCP2 and UCP3 than with uncoupling protein-1 (UCP1) isolated from brown adipose tissue. Moreover, anti-UCP2 and cross-reacting anti-UCP3 antibodies identifie...

Uncoupling protein-3 (UCP3), a mitochondrial membrane transporter, is a candidate effector of thermogenesis. Even though mice with targeted disruption of the UCP3 gene are not obese, indirect evidence suggests that this protein contributes to the control of energy expenditure in humans. We therefore characterized the human UCP3 gene and compared it with its rodent homologues with respect to tis...

Ischaemic heart disease limits oxygen and metabolic substrate availability to the heart, resulting in tissue death. Here, we demonstrate that the AMP-activated protein kinase (AMPK)-related protein Snf1-related kinase (SNRK) decreases cardiac metabolic substrate usage and mitochondrial uncoupling, and protects against ischaemia/reperfusion. Hearts from transgenic mice overexpressing SNRK have d...

Thyroid hormone (TH) plays a fundamental role in thermoregulation, yet the molecular mediators of its effects are not fully defined. Recently, skeletal muscle (SKM) uncoupling protein (UCP) 3 was shown to be an important mediator of the thermogenic effects of the widely abused sympathomimetic agents 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) and methamphetamine. Expression of UCP3 is reg...