| 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 |
6.17
|
| Times Cited |
77
|
|
WOS Category
|
ENDOCRINOLOGY & METABOLISM
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| C.elegans |
tm358 |
