Superoxide activates mitochondrial uncoupling proteins
Superoxide activates mitochondrial uncoupling proteins
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DOI：
10.1038/415096a
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发表时间：
2002-01-03
期刊：
影响因子：
64.8
通讯作者：
Brand, MD
中科院分区：
文献类型：
--
作者：
Echtay, KS;Roussel, D;Brand, MD
解偶联蛋白1（UCP1）通过催化质子穿过内膜的调节性泄漏，将能量从ATP合成转移到棕色脂肪组织线粒体中的产热作用（1，2）。其同系物UCP2和UCP3在其他组织中的功能存在争议（3，4）。UCP2和UCP3的丰度比UCP1低得多，并且与它们相关的解偶联不显著产热（5，6）。然而，轻度解偶联会减少线粒体产生的活性氧，这是氧化损伤的重要介质（7，8）。在这里，我们表明，超氧化物通过对UCP1，UCP2和UCP3的影响增加线粒体质子电导。超氧化物诱导的解偶联需要脂肪酸，并被嘌呤核苷酸抑制。它与UCPs的组织表达相关，出现在表达UCP1的酵母的线粒体中，而在UCP3敲除小鼠的骨骼肌线粒体中不存在。我们的研究结果表明，超氧化物与UCPs的相互作用可能是降低线粒体内活性氧浓度的一种机制。
Uncoupling protein 1 (UCP1) diverts energy from ATP synthesis to thermogenesis in the mitochondria of brown adipose tissue by catalysing a regulated leak of protons across the inner membrane(1,2). The functions of its homologues, UCP2 and UCP3, in other tissues are debated(3,4). UCP2 and UCP3 are present at much lower abundance than UCP1, and the uncoupling with which they are associated is not significantly thermogenic(5,6). Mild uncoupling would, however, decrease the mitochondrial production of reactive oxygen species, which are important mediators of oxidative damage(7,8). Here we show that superoxide increases mitochondrial proton conductance through effects on UCP1, UCP2 and UCP3. Superoxide-induced uncoupling requires fatty acids and is inhibited by purine nucleotides. It correlates with the tissue expression of UCPs, appears in mitochondria from yeast expressing UCP1, and is absent in skeletal muscle mitochondria from UCP3 knockout mice. Our findings indicate that the interaction of superoxide with UCPs may be a mechanism for decreasing the concentrations of reactive oxygen species inside mitochondria.