The respiratory chain complex thresholds in mitochondria of a Drosophila subobscura mutant strain.
Analysis of a mutant strain of Drosophila subobscura revealed that most (80%) mitochondrial genomes have undergone a large scale deletion (5 kb) in the coding region. Compared with the wild-type strain, complex I and III activities are, respectively, reduced by 50% and 30% in the mutant. However, the ATP synthesis capacities remain unchanged. In order to elucidate how the ATP synthesis is maintained at a normal level, despite a significant decrease in complex I and III activities, we progressively inhibited respiratory chain complex activities, respiration rate and ATP synthesis. Complex I, III and IV activities were inhibited by rotenone, antimycin and KCN, respectively. Threshold curves were thus determined for each complex. Our results demonstrated that in the mutant strain, both mitochondrial respiration and ATP synthesis had decreased when complex I activity was inhibited by more than 20%, whereas 70% inhibition is required to induce similar changes in the wild-type. The complex I inhibition pattern of the wild-type was restored by a backcross (mutant female/wild-type male). The complex III activity threshold is below 20% in both strains, and we observed some difference in antimycin sensitivity, suggesting a modification of the complex enzymatic properties in the mutant. In contrast, threshold values of 70% were measured for complex IV inhibition. Our data suggest that the difference in the complex I threshold curves between the wild-type and mutant strains could partially account for the absence of pathological phenotype in the mutant.
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Equipe << Génome Mitochondrial >>, UMR CNRS 6547, Université Blaise-Pascal, Clermont II, 63177 Aubière, cedex, France.
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D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000968:Antimycin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D002950:Citrate (si)-Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D004579:Electron Transport / Q000502:physiology; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005994:Glycerophosphates / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism; D009154:Mutation; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption; D011190:Potassium Cyanide / Q000494:pharmacology; D012402:Rotenone / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005994:Glycerophosphates; D009097:Multienzyme Complexes; D012402:Rotenone; C032456:antimycin; D000968:Antimycin A; D000255:Adenosine Triphosphate; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D011190:Potassium Cyanide