期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 38, 期 11, 页码 1518-1525出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2005.02.012
关键词
transhydrogenase; oxidative stress; Caenorhabditis elegans; paraquat; free radical; NADPH
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.
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