Frederic Bouillaud

Uncoupling Protein 2, in Vivo Distribution, Induction upon Oxidative Stress, and Evidence for Translational Regulation

Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family and partially uncouples respiration from ATP synthesis when expressed in recombinant yeast mitochondria. We generated a highly sensitive polyclonal antibody against human UCP2. Its reactivity toward mitochondrial proteins was compared between wild type and ucp2(−/−) mice, leading to non-ambiguous identification of UCP2. We detected UCP2 in spleen, lung, stomach, and white adipose tissue. No UCP2 was detected in heart, skeletal muscle, liver, and brown adipose tissue. The level of UCP2 in spleen mitochondria is less than 1% of the level of UCP1 in brown adipose tissue mitochondria. Starvation and LPS treatments increase UCP2 level up to 12 times in lung and stomach, which supports the hypothesis that UCP2 responds to oxidative stress situations. Stimulation of the UCP2 expression occurs without any change in UCP2 mRNA levels. This is explained by translational regulation of the UCP2 mRNA. We have shown that an upstream open reading frame located in exon two of theucp2 gene strongly inhibits the expression of the protein. This further level of regulation of the ucp2 gene provides a mechanism by which expression can be strongly and rapidly induced under stress conditions.

A Molecular Biology Study of the Uncoupling Protein of Brown Fat Mitochondria. A Contribution to the Analysis of Genes of Mitochondrial Carriers

The uncoupling protein (UCP) is a specialized mitochondrial carrier unique to brown adipose tissue mitochondria. It acts as a proton carrier able to dissipate the proton gradient, to bypass ATP synthesis and to dissipate energy as heat (Nicholls & Locke, 1984). The proton translocating activity of UCP is inhibited by di- and triphosphate purine nucleotides and activated by free fatty acids (Nicholls et al., 1986). Moreover, UCP can be used as a marker to identify thermogenic adipocytes.