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, th...

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Veröffentlicht in:Biochimie 2002-12, Vol.84 (12), p.1189-1197
Hauptverfasser: Farge, G., Touraille, S., Debise, R., Alziari, S.
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creator Farge, G.
Touraille, S.
Debise, R.
Alziari, S.
description 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.
doi_str_mv 10.1016/S0300-9084(02)00038-X
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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. 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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. 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inhibitors</subject><subject>Electron Transport Complex IV - metabolism</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Female</subject><subject>Glycerophosphates - metabolism</subject><subject>Heteroplasmy</subject><subject>Kinetics</subject><subject>Male</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - enzymology</subject><subject>Multienzyme Complexes - metabolism</subject><subject>Mutation</subject><subject>NADH, NADPH Oxidoreductases - antagonists &amp; inhibitors</subject><subject>NADH, NADPH Oxidoreductases - metabolism</subject><subject>Oxidation-Reduction - drug effects</subject><subject>Oxygen Consumption</subject><subject>Potassium Cyanide - pharmacology</subject><subject>Respiratory chain complexes</subject><subject>Rotenone - pharmacology</subject><subject>Threshold curves</subject><issn>0300-9084</issn><issn>1638-6183</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQQC1ERZfCT6DyCcEh7dhZJ_GpqvoBSJU4tEi9WY49VlwlcWo7iP573O6qHDnNaObNjP0I-cTghAFrTm-hBqgkdNsvwL8CQN1V92_IhjUlaVhXvyWbV-SQvE_poUACuHxHDhlveMel2BB9NyCNmBYfdQ7xiZpB-5maMC0j_qF5KL0hjDbRUp18DmYIs41e0-CoppcxpLAMftQ0rX3ok1mjptOa9ZxpyrHs-kAOnB4TftzHI_Lr-uru4nt18_Pbj4vzm8rUkudKyBKZto4J53q0bQNOdK5F2DpkAh1rZcPl1rS2d1xAb8GVnq1lt211Y-sj8nm3d4nhccWU1eSTwXHUM4Y1KSZbUTeSFVDsQFMenyI6tUQ_6fikGKhnt-rFrXoWp4CrF7fqvswd7w-s_YT239ReZgHOdgCWb_72GFUyHmeD1kc0Wdng_3PiLyVci4Q</recordid><startdate>20021201</startdate><enddate>20021201</enddate><creator>Farge, G.</creator><creator>Touraille, S.</creator><creator>Debise, R.</creator><creator>Alziari, S.</creator><general>Elsevier Masson SAS</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SS</scope></search><sort><creationdate>20021201</creationdate><title>The respiratory chain complex thresholds in mitochondria of a Drosophila subobscura mutant strain</title><author>Farge, G. ; 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inhibitors</topic><topic>Electron Transport Complex IV - metabolism</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Female</topic><topic>Glycerophosphates - metabolism</topic><topic>Heteroplasmy</topic><topic>Kinetics</topic><topic>Male</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - enzymology</topic><topic>Multienzyme Complexes - metabolism</topic><topic>Mutation</topic><topic>NADH, NADPH Oxidoreductases - antagonists &amp; inhibitors</topic><topic>NADH, NADPH Oxidoreductases - metabolism</topic><topic>Oxidation-Reduction - drug effects</topic><topic>Oxygen Consumption</topic><topic>Potassium Cyanide - pharmacology</topic><topic>Respiratory chain complexes</topic><topic>Rotenone - pharmacology</topic><topic>Threshold curves</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Farge, G.</creatorcontrib><creatorcontrib>Touraille, S.</creatorcontrib><creatorcontrib>Debise, R.</creatorcontrib><creatorcontrib>Alziari, S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><jtitle>Biochimie</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Farge, G.</au><au>Touraille, S.</au><au>Debise, R.</au><au>Alziari, S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The respiratory chain complex thresholds in mitochondria of a Drosophila subobscura mutant strain</atitle><jtitle>Biochimie</jtitle><addtitle>Biochimie</addtitle><date>2002-12-01</date><risdate>2002</risdate><volume>84</volume><issue>12</issue><spage>1189</spage><epage>1197</epage><pages>1189-1197</pages><issn>0300-9084</issn><eissn>1638-6183</eissn><abstract>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.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>12628295</pmid><doi>10.1016/S0300-9084(02)00038-X</doi><tpages>9</tpages></addata></record>
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subjects Adenosine Triphosphate - biosynthesis
Animals
Antimycin A - analogs & derivatives
Antimycin A - pharmacology
ATP synthesis
Citrate (si)-Synthase - antagonists & inhibitors
Citrate (si)-Synthase - metabolism
Dose-Response Relationship, Drug
Drosophila - genetics
Drosophila - metabolism
Drosophila subobscura
Electron Transport - physiology
Electron Transport Complex I - metabolism
Electron Transport Complex III - antagonists & inhibitors
Electron Transport Complex III - metabolism
Electron Transport Complex IV - antagonists & inhibitors
Electron Transport Complex IV - metabolism
Enzyme Inhibitors - pharmacology
Female
Glycerophosphates - metabolism
Heteroplasmy
Kinetics
Male
Mitochondria - drug effects
Mitochondria - enzymology
Multienzyme Complexes - metabolism
Mutation
NADH, NADPH Oxidoreductases - antagonists & inhibitors
NADH, NADPH Oxidoreductases - metabolism
Oxidation-Reduction - drug effects
Oxygen Consumption
Potassium Cyanide - pharmacology
Respiratory chain complexes
Rotenone - pharmacology
Threshold curves
title The respiratory chain complex thresholds in mitochondria of a Drosophila subobscura mutant strain
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