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FAD 和醌结合位点对猪蛔虫线粒体复合物 II 产生活性氧的贡献。

Contribution of the FAD and quinone binding sites to the production of reactive oxygen species from Ascaris suum mitochondrial complex II.

机构信息

Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

出版信息

Mitochondrion. 2010 Mar;10(2):158-65. doi: 10.1016/j.mito.2009.12.145. Epub 2009 Dec 16.

DOI:10.1016/j.mito.2009.12.145
PMID:20006739
Abstract

Reactive oxygen species (ROS) production from mitochondrial complex II (succinate-quinone reductase, SQR) has become a focus of research recently since it is implicated in carcinogenesis. To date, the FAD site is proposed as the ROS producing site in complex II, based on studies done on Escherichia coli, whereas the quinone binding site is proposed as the site of ROS production based on studies in Saccharomyces cerevisiae. Using the submitochondrial particles from the adult worms and L(3) larvae of the parasitic nematode Ascaris suum, we found that ROS are produced from more than one site in the mitochondrial complex II. Moreover, the succinate-dependent ROS production from the complex II of the A. suum adult worm was significantly higher than that from the complex II of the L(3) larvae. Considering the conservation of amino acids crucial for the SQR activity and the high levels of ROS production from the mitochondrial complex II of the A. suum adult worm together with the absence of complexes III and IV activities in its respiratory chain, it is a good model to examine the reactive oxygen species production from the mitochondrial complex II.

摘要

活性氧(ROS)产生于线粒体复合物 II(琥珀酸-醌还原酶,SQR),这一现象最近成为了研究的焦点,因为它与致癌作用有关。迄今为止,基于对大肠杆菌的研究,FAD 位点被提出是复合物 II 中 ROS 的产生位点,而基于对酿酒酵母的研究,醌结合位点被提出是 ROS 产生的位点。利用寄生线虫猪蛔虫的成虫和 L(3)幼虫的亚线粒体颗粒,我们发现 ROS 是从线粒体复合物 II 的多个部位产生的。此外,猪蛔虫成虫复合物 II 依赖琥珀酸盐的 ROS 产生量明显高于 L(3)幼虫复合物 II。考虑到对于 SQR 活性至关重要的氨基酸的保守性以及猪蛔虫成虫线粒体复合物 II 产生的高水平 ROS,再加上其呼吸链中不存在复合物 III 和 IV 的活性,它是一个很好的模型,可以用来研究线粒体复合物 II 中的活性氧产生。

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