A Caenorhabditis elegans mutant lacking functional nicotinamide nucleotide transhydrogenase displays increased sensitivity to oxidative stress
A Caenorhabditis elegans mutant lacking functional nicotinamide nucleotide transhydrogenase displays increased sensitivity to oxidative stress
复制标题
DOI：
10.1016/j.freeradbiomed.2005.02.012
复制
发表时间：
2005-06-01
影响因子：
7.4
通讯作者：
Rydström, J
中科院分区：
文献类型：
--
作者：
Arkblad, EL;Tuck, S;Rydström, J
研究了秀丽隐杆线虫线粒体质子转运型烟酰胺核苷酸转氢酶（NNT）的生理功能。NNT催化由电化学质子梯度Δ p驱动的NADH还原NADP+，因此是线粒体NADPH的潜在重要来源。谷胱甘肽依赖性过氧化物酶对活性氧（ROS）的线粒体解毒依赖于还原型谷胱甘肽再生的NADPH。因此转氢酶可能直接参与防御氧化应激。线虫nnt-1缺失突变体nnt-1（sv 34）在正常实验室条件下基本上与野生型一样生长，但GSH/GSSG比值显著降低。在由超氧化物生成剂甲基紫精引起的氧化应激条件下，缺乏nnt-1活性的蠕虫的生长严重受损。通过使用RNAi获得了类似的结果。在nnt-1（sv 34）敲除突变体中重新引入nnt-1导致在氧化应激条件下生长的部分拯救。这些结果第一次提供了nnt-1在抵抗线粒体氧化应激中重要的证据。(c)2005年爱思唯尔公司All rights reserved.
Proton-translocating mitochondrial nicotinamide nucleotide transhydrogenase (NNT) was investigated regarding its physiological role in Caenorhabditis elegans. NNT catalyzes the reduction of NADP+ by NADH driven by the electrochemical proton gradient, Delta p, and is thus a potentially important source of mitochondrial NADPH. Mitochondrial detoxification of reactive oxygen species (ROS) by glutathione-dependent peroxidases depends on NADPH for regeneration of reduced glutathione. Transhydrogenase may therefore be directly involved in the defense against oxidative stress. nnt-1 deletion mutants of C elegans, nnt-1(sv34), were isolated and shown to grow essentially as wild type under normal laboratory conditions, but with a strongly lowered GSH/GSSG ratio. Under conditions of oxidative stress, caused by the superoxide-generating agent methyl viologen, growth of worms lacking nnt-1 activity was severely impaired. A similar result was obtained by using RNAi. Reintroducing nnt-1 in the nnt-1(sv34) knockout mutant led to a partial rescue of growth under oxidative stress conditions. These results provide evidence for the first time that nnt-1 is important in the defense against mitochondrial oxidative stress. (c) 2005 Elsevier Inc. All rights reserved.