Klingenspor Martin, Fromme Tobias, Hughes David A, Manzke Lars, Polymeropoulos Elias, Riemann Tobias, Trzcionka Magdalene, Hirschberg Verena, Jastroch Martin
Technische Universität München, Molecular Nutritional Medicine, Else Kröner-Fresenius Center, Freising-Weihenstephan, Germany.
Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):637-41. doi: 10.1016/j.bbabio.2008.03.006. Epub 2008 Mar 18.
Brown adipose tissue serves as a thermogenic organ in placental mammals to defend body temperature in the cold by nonshivering thermogenesis. The thermogenic function of brown adipose tissue is enabled by several specialised features on the organ as well as on the cellular level, including dense sympathetic innervation and vascularisation, high lipolytic capacity and mitochondrial density and the unique expression of uncoupling protein 1 (UCP1). This mitochondrial carrier protein is inserted into the inner mitochondrial membrane and stimulates maximum mitochondrial respiration by dissipating proton-motive force as heat. Studies in knockout mice have clearly demonstrated that UCP1 is essential for nonshivering thermogenesis in brown adipose tissue. For a long time it had been presumed that brown adipose tissue and UCP1 emerged in placental mammals providing them with a unique advantage to survive in the cold. Our subsequent discoveries of UCP1 orthologues in ectotherm vertebrates and marsupials clearly refute this presumption. We can now initiate comparative studies on the structure-function relationships in UCP1 orthologues from different vertebrates to elucidate when during vertebrate evolution UCP1 gained the biochemical properties required for nonshivering thermogenesis.
在胎盘哺乳动物中，棕色脂肪组织作为一个产热器官，通过非颤抖性产热来在寒冷环境中维持体温。棕色脂肪组织的产热功能得益于该器官以及细胞水平上的几个特殊特征，包括密集的交感神经支配和血管化、高脂肪分解能力和线粒体密度以及解偶联蛋白1（UCP1）的独特表达。这种线粒体载体蛋白插入线粒体内膜，并通过将质子动力以热量形式耗散来刺激最大程度的线粒体呼吸。对基因敲除小鼠的研究清楚地表明，UCP1对于棕色脂肪组织中的非颤抖性产热至关重要。长期以来，人们一直认为棕色脂肪组织和UCP1出现在胎盘哺乳动物中，使它们在寒冷环境中生存具有独特优势。我们随后在外温脊椎动物和有袋动物中发现UCP1直系同源物，这清楚地反驳了这一推测。我们现在可以对来自不同脊椎动物的UCP1直系同源物的结构-功能关系展开比较研究，以阐明在脊椎动物进化过程中，UCP1何时获得了非颤抖性产热所需的生化特性。
