A mutation in mitochondrial complex I increases ethanol sensitivity in Caenorhabditis elegans.
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.
Kayser
Ernst-Bernhard
EB
Department of Anesthesiology, University Hospitals, Cleveland, Ohio 44106, USA.
Hoppel
Charles L
CL
Morgan
Phil G
PG
Sedensky
Margaret M
MM
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D042967:Electron Transport Complex I / Q000235:genetics* / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D007103:Immobilization / Q000502:physiology; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics*; D009154:Mutation / Q000187:drug effects*
D000431:Ethanol; D042967:Electron Transport Complex I