A Caenorhabditis elegans mutant lacking functional nicotinamide nucleotide transhydrogenase displays increased sensitivity to oxidative stress.

• 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.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)