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A Caenorhabditis el...
A Caenorhabditis elegans mutant lacking functional nicotinamide nucleotide transhydrogenase displays increased sensitivity to oxidative stress.
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Arkblad, Eva L (author)
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- Tuck, Simon (author)
- Umeå universitet,Umeå centrum för molekylär patogenes (UCMP)
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Pestov, Nikolay B (author)
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Dmitriev, Ruslan I (author)
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Kostina, Maria B (author)
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Stenvall, Jörgen (author)
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- Tranberg, Mattias, 1977 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi,Department of Chemistry
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- Rydström, Jan, 1943 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi,Department of Chemistry
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(creator_code:org_t)
- Elsevier BV, 2005
- 2005
- English.
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In: Free radical biology & medicine. - : Elsevier BV. - 0891-5849. ; 38:11, s. 1518-25
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http://www.ncbi.nlm....
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- 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 Transhydrogenase
- genetics
- physiology
- Oxidative Stress
- Paraquat
- pharmacology
- Phenotype
- Plasmids
- metabolism
- Protons
- RNA Interference
- RNA
- Double-Stranded
- chemistry
- Time Factors
- Animals
Publication and Content Type
- ref (subject category)
- art (subject category)
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