BIOMAT Database Logo BIOMAT Database Logo

A mutation in mitochondrial complex I increases ethanol sensitivity in Caenorhabditis elegans. 2003

Ernst-Bernhard Kayser, and Charles L Hoppel, and Phil G Morgan, and Margaret M Sedensky
Department of Anesthesiology, University Hospitals, Cleveland, Ohio 44106, USA.

BACKGROUND The gene gas-1 encodes the 49-kDa subunit of complex I of the mitochondrial electron transport chain in Caenorhabditis elegans. A mutation in gas-1 profoundly increases sensitivity to ethanol and decreases complex I-dependent metabolism in mitochondria. METHODS Mitochondria were isolated from wild-type and gas-1 strains of C. elegans. The effects of ethanol on complex I-, II-, and III-dependent oxidative phosphorylation were measured for mitochondria from each strain. Reversibility of the effects of ethanol was determined by measuring oxidative phosphorylation after removal of mitochondria from 1.5 M ethanol. The effects of ethanol on mitochondrial structure were visualized with electron microscopy. RESULTS We found that ethanol inhibited complex I-, II-, and III-dependent oxidative phosphorylation in isolated wild-type mitochondria at concentrations that immobilize intact worms. It is important to note that the inhibitory effects of ethanol on mitochondria from either C. elegans or rat skeletal muscle were reversible even at molar concentrations. Complex I activity was lower in mitochondria from gas-1 animals than in mitochondria from wild-type animals at equal ethanol concentrations. Complex II activity was higher in gas-1 than in wild-type mitochondria at all concentrations of ethanol. No difference was seen between the strains in the sensitivity of complex III to ethanol. CONCLUSIONS The difference in ethanol sensitivities between gas-1 and wild-type nematodes results solely from altered complex I function. At the respective concentrations of ethanol that immobilize whole animals, mitochondria from each strain of worms displayed identical rates of complex I-dependent state 3 respiration. We conclude that a threshold value of complex I activity controls the transition from mobility to immobility of C. elegans.

UI MeSH Term Description Entries
D007103 Immobilization The restriction of the MOVEMENT of whole or part of the body by physical means (RESTRAINT, PHYSICAL) or chemically by ANALGESIA, or the use of TRANQUILIZING AGENTS or NEUROMUSCULAR NONDEPOLARIZING AGENTS. It includes experimental protocols used to evaluate the physiologic effects of immobility. Hypokinesia, Experimental,Experimental Hypokinesia,Experimental Hypokinesias,Hypokinesias, Experimental
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017173 Caenorhabditis elegans A species of nematode that is widely used in biological, biochemical, and genetic studies. Caenorhabditis elegan,elegan, Caenorhabditis
D042967 Electron Transport Complex I A flavoprotein and iron sulfur-containing oxidoreductase complex that catalyzes the conversion of UBIQUINONE to ubiquinol. In MITOCHONDRIA the complex also couples its reaction to the transport of PROTONS across the internal mitochondrial membrane. The NADH DEHYDROGENASE component of the complex can be isolated and is listed as EC 1.6.99.3. NADH Dehydrogenase (Ubiquinone),Complex I Dehydrogenase,NADH DH I,NADH Dehydrogenase Complex 1,NADH Dehydrogenase I,NADH Q1 Oxidoreductase,NADH-CoQ Reductase,NADH-Coenzyme Q Reductase,NADH-Ubiquinone Oxidoreductase,NADH-Ubiquinone Reductase,Respiratory Complex I,Rotenone-Sensitive Mitochondrial NADH-Ubiquinone Oxidoreductase,Ubiquinone Reductase,Dehydrogenase, Complex I,NADH CoQ Reductase,NADH Coenzyme Q Reductase,NADH Ubiquinone Oxidoreductase,NADH Ubiquinone Reductase,Oxidoreductase, NADH Q1,Oxidoreductase, NADH-Ubiquinone,Reductase, NADH-Ubiquinone,Rotenone Sensitive Mitochondrial NADH Ubiquinone Oxidoreductase

Related Publications

Ernst-Bernhard Kayser, and Charles L Hoppel, and Phil G Morgan, and Margaret M Sedensky
Mitochondrial complex I function affects halothane sensitivity in Caenorhabditis elegans.
August 2004, Anesthesiology,
Ernst-Bernhard Kayser, and Charles L Hoppel, and Phil G Morgan, and Margaret M Sedensky
Isoflurane selectively inhibits distal mitochondrial complex I in Caenorhabditis elegans.
June 2011, Anesthesia and analgesia,
Ernst-Bernhard Kayser, and Charles L Hoppel, and Phil G Morgan, and Margaret M Sedensky
Mutations in mitochondrial complex III uniquely affect complex I in Caenorhabditis elegans.
December 2010, The Journal of biological chemistry,
Ernst-Bernhard Kayser, and Charles L Hoppel, and Phil G Morgan, and Margaret M Sedensky
UNC-18 modulates ethanol sensitivity in Caenorhabditis elegans.
January 2009, Molecular biology of the cell,
Ernst-Bernhard Kayser, and Charles L Hoppel, and Phil G Morgan, and Margaret M Sedensky
Reduction of Caenorhabditis elegans frataxin increases sensitivity to oxidative stress, reduces lifespan, and causes lethality in a mitochondrial complex II mutant.
January 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology,
Ernst-Bernhard Kayser, and Charles L Hoppel, and Phil G Morgan, and Margaret M Sedensky
Identification of a novel mitochondrial complex I assembly factor ACDH-12 in Caenorhabditis elegans.
May 2019, Mitochondrion,
Ernst-Bernhard Kayser, and Charles L Hoppel, and Phil G Morgan, and Margaret M Sedensky
Mutations affecting sensitivity to ethanol in the nematode, Caenorhabditis elegans.
December 1995, Alcoholism, clinical and experimental research,
Ernst-Bernhard Kayser, and Charles L Hoppel, and Phil G Morgan, and Margaret M Sedensky
Mitochondrial complex I function modulates volatile anesthetic sensitivity in C. elegans.
August 2006, Current biology : CB,
Ernst-Bernhard Kayser, and Charles L Hoppel, and Phil G Morgan, and Margaret M Sedensky
A mutation in Caenorhabditis elegans that increases recombination frequency more than threefold.
October 1979, Nature,
Ernst-Bernhard Kayser, and Charles L Hoppel, and Phil G Morgan, and Margaret M Sedensky
Mitochondrial respiratory chain dysfunction variably increases oxidant stress in Caenorhabditis elegans.
March 2010, Mitochondrion,
Copied contents to your clipboard!