Disease relevance of UCP1

• The failure of UCP1 expressed in Escherichia coli inclusion bodies to carry out fatty-acid-dependent H+ transport activity inclusion bodies made us seek a native UCP cofactor [1].

High impact information on UCP1

• An uncoupling protein (UCP) has been identified in mitochondria from Acanthamoeba castellanii, a nonphotosynthetic soil amoeboid protozoon that, in molecular phylogenesis, appears on a branch basal to the divergence points of plants, animals, and fungi [2].
• AcUCP was only weakly inhibited by purine nucleotides like UCP in plants [2].
• This is in line with the very strong pH dependence of nucleoside triphosphate affinity above pH 7 with a delta pKD/delta pH = -2 as an important regulatory mechanism for the H+ transport activity of UCP [3].
• It was demonstrated that UCP mRNA reached its highest level at birth in all bovine adipose tissues studied, except subcutaneous tissue [4].
• However, despite uncoupling, neither UCP1 nor UCP2 altered superoxide formation [5].

Biological context of UCP1

• UCP1 and UCP2 overexpression both increased the proton conductance of endothelial cell mitochondria, as rigorously determined by the kinetic relationship of respiration to inner membrane potential [5].
• Mapping of the UCP1 locus to bovine chromosome 17 [6].
• 5; n = 6 per group) was depleted of lipid in response to cold exposure, although UCP1 gene expression persisted [7].
• In both breed types, a marked decrease in BAT UCP1 mRNA between 24 and 14 d prepartum was associated with a similar reduction in lipogenesis from palmitate and a noticeable change in BAT mitochondrial morphology, as the mitochondria became more elongated and the cristae became more elaborate [8].
• Uncoupling protein-1 (UCP1) mRNA tripled during gestation in both breed types (P = 0.002), whereas mitochondrial cross-sectional area did not change (P = 0.14) during gestation [8].

Anatomical context of UCP1

• Respiratory uncoupling by UCP1 and UCP2 and superoxide generation in endothelial cell mitochondria [5].
• On addition of CoQ10 to reconstituted UCP1 from inclusion bodies, fatty-acid-dependent H+ transport reached the same rate as with native UCP1 [1].
• In intact parasites, expression of UCP1 induced a slight increase in respiratory rate and a modest decrease in mitochondrial membrane potential (delta psi(m)) [9].
• UCP mRNA was characterized for the first time in foetal bovine and ovine adipose tissue [4].
• The results indicate that thermogenin seems to be exclusively localised in brown fat mitochondria (as compared to white fat, liver or heart muscle mitochondria), and thermogenin antigen could only be found in brown adipocytes (as compared to white adipocytes) [10].

Associations of UCP1 with chemical compounds

• Therefore, a fully functional UCP1 was present and only partially inhibited in vivo by endogenous purine nucleotides [9].
• Neither the breed nor the age x breed effect was significant (P > or = 0.24) for UCP1 mRNA concentration or mitochondrial cross-sectional area [8].
• Lipogenesis from acetate and glucose in vitro decreased 97% during the last 96 d of gestation in both breed types, whereas the UCP1 gene expression tripled during gestation in both breed types [7].
• Interval to the first increase in progesterone (ovulation) was less (P < .05) in OCW (14.7 +/- 3.4 d) and OCR (19.9 +/- 3.4 d) than in the OCP (35.0 +/- 2.9 d), UCP (38.0 +/- 3.4 d), and OCR + UCP (37.6 +/- 3.4 d) treatments [11].
• Brown fat cells incubated for 24 h with or without NE showed no significant change in succinate dehydrogenase activity or uncoupling protein (UCP) content [12].

Regulatory relationships of UCP1

• Finally, the level of uncoupling protein-1 (UCP1) RNA was found to be higher in dwarf mice and lower in giant animals relative to controls, suggesting that GH-mediated signaling may negatively regulate UCP1 gene expression in BAT [13].

Analytical, diagnostic and therapeutic context of UCP1

• We used long-range PCR and genome walking to determine the complete genome sequence of pig UCP1 [14].
• The recombinant-tagged UCP1 was purified by immobilized metal-ion affinity chromatography to homogeneity (>95%) [15].
• An enzyme-linked immunosorbent assay (ELISA) has been developed to demonstrate and quantitate the occurrence of thermogenin antigen in small amounts of tissue, and thus to characterize different depots of fat tissue as white or brown [10].

References