Staniek Katrin, Gille Lars, Kozlov Andrey V, Nohl Hans
Institute of Pharmacology and Toxicology, Veterinary University Vienna, Austria.
Free Radic Res. 2002 Apr;36(4):381-7. doi: 10.1080/10715760290021225.
The generation of oxygen radicals in biological systems and their sites of intracellular release have been subject of numerous studies in the last decades. Based on these studies mitochondria are considered to be the major source of intracellular oxygen radicals. Although this finding is more or less accepted, the mechanism of univalent oxygen reduction in mitochondria is still obscure. One of the most critical electron transfer steps in the respiratory chain is the electron bifurcation at the cytochrome bc1 complex. Recent studies with genetically mutated mitochondria have made it clear that electron bifurcation from ubiquinol to the cytochrome bc1 complex requires the free mobility of the head domain of the Rieske iron-sulfur protein. On the other hand, it has been long known that inhibition of electron bifurcation by antimycin A causes leakage of single electrons to dioxygen, which results in the release of superoxide radicals. These findings lead us to study whether hindrance of the interaction of ubiquinol with the cytochrome bc1 complex is the regulator of single electron diversion to oxygen. Hindrance of electron bifurcation was observed following alterations of the physical state of membrane phospholipids in which the cytochrome bc1 complex is inserted. Irrespective of whether the fluidity of the membrane lipids was elevated or decreased, electron flow rates to the Rieske iron-sulfur protein were drastically reduced. Concomitantly superoxide radicals were released from these mitochondria, strongly suggesting an effect on the mobility of the head domain of the Rieske iron-sulfur protein. This revealed the involvement of the ubiquinol cytochrome bc1 redox couple in mitochondrial superoxide formation. The regulator, which controls leakage of electrons to oxygen, appears to be the electron-branching activity of the cytochrome bc1 complex.
在过去几十年中，生物系统中氧自由基的产生及其细胞内释放位点一直是众多研究的主题。基于这些研究，线粒体被认为是细胞内氧自由基的主要来源。尽管这一发现或多或少已被接受，但线粒体中单价氧还原的机制仍然不清楚。呼吸链中最关键的电子传递步骤之一是细胞色素bc1复合物处的电子分叉。最近对基因变异线粒体的研究表明，从泛醇到细胞色素bc1复合物的电子分叉需要 Rieske 铁硫蛋白头部结构域的自由移动性。另一方面，长期以来人们已知抗霉素A对电子分叉的抑制会导致单电子泄漏到双氧，从而导致超氧自由基的释放。这些发现促使我们研究泛醇与细胞色素bc1复合物相互作用的阻碍是否是单电子向氧转移的调节因子。在插入细胞色素bc1复合物的膜磷脂物理状态改变后，观察到了电子分叉的阻碍。无论膜脂的流动性是升高还是降低，流向 Rieske 铁硫蛋白的电子流速都急剧降低。与此同时，超氧自由基从这些线粒体中释放出来，强烈表明对 Rieske 铁硫蛋白头部结构域的移动性有影响。这揭示了泛醇-细胞色素bc1氧化还原对参与线粒体超氧的形成。控制电子向氧泄漏的调节因子似乎是细胞色素bc1复合物的电子分支活性。
