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      Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression

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          Abstract

          Brown adipose tissue (BAT) and skeletal muscle are important sites of nonshivering thermogenesis. The uncoupling protein-1 (UCP1) is the main effector of nonshivering thermogenesis in BAT and the recently described ubiquitous UCP2 [1] has been implicated in energy balance. In an attempt to better understand the biochemical events underlying nonshivering thermogenesis in muscle, we screened a human skeletal muscle cDNA library and isolated three clones: UCP2, UCP3L and UCP3S. The novel UCP3 was 57% and 73% identical to human UCP1 and UCP2, respectively, highly skeletal muscle-specific and its expression was unaffected by cold acclimation. This new member of the UCP family is a candidate protein for the modulation of the respiratory control in skeletal muscle.

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          Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia.

          C Fleury, M Neverova, S. Collins … (1997)
          A mitochondrial protein called uncoupling protein (UCP1) plays an important role in generating heat and burning calories by creating a pathway that allows dissipation of the proton electrochemical gradient across the inner mitochondrial membrane in brown adipose tissue, without coupling to any other energy-consuming process. This pathway has been implicated in the regulation of body temperature, body composition and glucose metabolism. However, UCP1-containing brown adipose tissue is unlikely to be involved in weight regulation in adult large-size animals and humans living in a thermoneutral environment (one where an animal does not have to increase oxygen consumption or energy expenditure to lose or gain heat to maintain body temperature), as there is little brown adipose tissue present. We now report the discovery of a gene that codes for a novel uncoupling protein, designated UCP2, which has 59% amino-acid identity to UCP1, and describe properties consistent with a role in diabetes and obesity. In comparison with UCP1, UCP2 has a greater effect on mitochondrial membrane potential when expressed in yeast. Compared to UCP1, the gene is widely expressed in adult human tissues, including tissues rich in macrophages, and it is upregulated in white fat in response to fat feeding. Finally, UCP2 maps to regions of human chromosome 11 and mouse chromosome 7 that have been linked to hyperinsulinaemia and obesity. Our findings suggest that UCP2 has a unique role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli.
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            RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination

            Hans Lehrach, Helga Boedtker, John Wozney … (2002)
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              Mitochondrial carrier proteins.

              F Palmieri (1994)
              Ten mitochondrial carriers have been purified from animal mitochondria. They are small proteins with a molecular mass ranging from 28 to 34 kDa on SDS-PAGE. So far, five of these proteins have been sequenced. Their polypeptide chain consists of three tandemly related sequences of about 100 amino acids. The repeats of the different proteins are related and probably fold into two transmembrane alpha-helices linked by an extra-membrane loop. The features of this family are also present in several proteins of unknown function characterized by DNA sequencing. Isoforms of some carriers have been found. All mitochondrial carriers investigated in proteoliposomes function according to a simultaneous (sequential) mechanism of transport. The only exception is the carnitine carrier that proceeds via a ping-pong mechanism. Three mitochondrial carriers have been expressed in yeast and two overexpressed in E. coli and refolded in active form.
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                Author and article information

                Journal
                Title: FEBS Letters
                Publisher: Elsevier BV
                ISSN: 00145793
                Publication date Created: May 12 1997
                Publication date (Print): May 12 1997
                Publication date (Electronic): November 03 1997
                Volume: 408
                Issue: 1
                Pages: 39-42
                Article
                DOI: 10.1016/S0014-5793(97)00384-0
                PubMed ID: 9180264
                SO-VID: fcd5453a-ce17-49c0-a4ae-5b207f97411d
                Copyright © © 1997
                License:

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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