RRC ID 3373
Author Arkblad EL, Tuck S, Pestov NB, Dmitriev RI, Kostina MB, Stenvall J, Tranberg M, Rydström J.
Title A Caenorhabditis elegans mutant lacking functional nicotinamide nucleotide transhydrogenase displays increased sensitivity to oxidative stress.
Journal Free Radic Biol Med
Abstract 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, Deltap, 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.
Volume 38(11)
Pages 1518-25
Published 2005-6-1
DOI 10.1016/j.freeradbiomed.2005.02.012
PII S0891-5849(05)00084-5
PMID 15890626
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / physiology Cell Proliferation Electrochemistry Gene Deletion Glutathione Green Fluorescent Proteins / metabolism Immunoblotting Mitochondria / metabolism Models, Chemical Models, Genetic Mutation* NADP / chemistry NADP Transhydrogenases / genetics* NADP Transhydrogenases / physiology Oxidative Stress Paraquat / pharmacology Phenotype Plasmids / metabolism Protons RNA Interference RNA, Double-Stranded / chemistry Time Factors
IF 5.657
Times Cited 77
C.elegans tm358