Coenzyme Q is an obligatory cofactor for uncoupling protein function
Coenzyme Q is an obligatory cofactor for uncoupling protein function
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DOI：
10.1038/35046114
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发表时间：
2000-11-30
期刊：
影响因子：
64.8
通讯作者：
Klingenberg, M
中科院分区：
文献类型：
--
作者：
Echtay, KS;Winkler, E;Klingenberg, M
解偶联蛋白（UCP）被认为是复杂控制的解偶联物（1-3），负责线粒体化学渗透梯度的无效耗散，产生热量而不是ATP。它们存在于许多动物和植物细胞中（4-9），并形成线粒体载体家族的亚家族（10）。氧化磷酸化的生理解偶联必须受到强烈的调节，以避免由有毒解偶联剂引起的能量供应恶化和细胞死亡。然而，仅对来自棕色脂肪组织的UCP 1充分确立了H+转运解偶联功能（2，8，9，11），并且脂肪酸、核苷酸和pH对UCP 1的调节仍然存在争议（2，12 -14）。在大肠杆菌包涵体中表达的UCP 1不能进行脂肪酸依赖性H+转运活性包涵体（15），这使我们寻求天然UCP辅因子。在这里，我们报告的辅酶Q（泛醌）作为这样的辅因子的鉴定。在将辅酶Q（10）添加到来自包涵体的重组UCP 1中时，脂肪酸依赖性H+转运达到与天然UCP 1相同的速率。H+转运对嘌呤核苷酸高度敏感，仅被氧化而非还原CoQ激活。天然UCP 1的H+转运与内源性辅酶Q含量相关。
Uncoupling proteins (UCPs) are thought to be intricately controlled uncouplers(1-3) that are responsible for the futile dissipation of mitochondrial chemiosmotic gradients, producing heat rather than ATP. They occur in many animal and plant cells(4-9) and forma subfamily of the mitochondrial carrier family(10). Physiological uncoupling of oxidative phosphorylation must be strongly regulated to avoid deterioration of the energy supply and cell death, which is caused by toxic uncouplers. However, an H+ transporting uncoupling function is well established only for UCP1 from brown adipose tissue(2,8,9,11), and the regulation of UCP1 by fatty acids, nucleotides and pH remains controversial(2,12-14). The failure of UCP1 expressed in Escherichia coli inclusion bodies to carry out fatty-acid-dependent H+ transport activity inclusion bodies(15) made us seek a native UCP cofactor. Here we report the identification of coenzyme Q (ubiquinone) as such a cofactor. On addition of CoQ(10) to reconstituted UCP1 from inclusion bodies, fatty-acid-dependent H+ transport reached the same rate as with native UCP1. The H+ transport was highly sensitive to purine nucleotides, and activated only by oxidized but not reduced CoQ. H+ transport of native UCP1 correlated with the endogenous CoQ content.