High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal
<p>Abstract</p> <p>Background</p> <p>The activities of mitochondrial complex III (ubiquinol-cytochrome <it>c </it>reductase, EC 1.10.2.2) and complex IV (cytochrome <it>c </it>oxidase EC 1.9.3.1) are reduced by 30-70% in Huntington's disease...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-07-01
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| Series: | Molecular Neurodegeneration |
| Online Access: | http://www.molecularneurodegeneration.com/content/6/1/53 |
| _version_ | 1811277606295699456 |
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| author | Kilbride Seán M Gluchowska Sonia A Telford Jayne E O'Sullivan Catherine Davey Gavin P |
| author_facet | Kilbride Seán M Gluchowska Sonia A Telford Jayne E O'Sullivan Catherine Davey Gavin P |
| author_sort | Kilbride Seán M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The activities of mitochondrial complex III (ubiquinol-cytochrome <it>c </it>reductase, EC 1.10.2.2) and complex IV (cytochrome <it>c </it>oxidase EC 1.9.3.1) are reduced by 30-70% in Huntington's disease and Alzheimer's disease, respectively, and are associated with excitotoxic cell death in these disorders. In this study, we investigated the control that complexes III and complex IV exert on glutamate release from the isolated nerve terminal.</p> <p>Results</p> <p>Inhibition of complex III activity by 60-90% was necessary for a major increase in the rate of Ca<sup>2+</sup>-independent glutamate release to occur from isolated nerve terminals (synaptosomes) depolarized with 4-aminopyridine or KCl. Similarly, an 85-90% inhibition of complex IV activity was required before a major increase in the rate of Ca<sup>2+</sup>-independent glutamate release from depolarized synaptosomes was observed. Inhibition of complex III and IV activities by ~ 60% and above was required before rates of glutamate efflux from polarized synaptosomes were increased.</p> <p>Conclusions</p> <p>These results suggest that nerve terminal mitochondria possess high reserves of complex III and IV activity and that high inhibition thresholds must be reached before excess glutamate is released from the nerve terminal. The implications of the results in the context of the relationship between electron transport chain enzyme deficiencies and excitotoxicity in neurodegenerative disorders are discussed.</p> |
| first_indexed | 2024-04-13T00:19:46Z |
| format | Article |
| id | doaj.art-0ca9f55cba70498a97b1b807b5846a87 |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-04-13T00:19:46Z |
| publishDate | 2011-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-0ca9f55cba70498a97b1b807b5846a872022-12-22T03:10:49ZengBMCMolecular Neurodegeneration1750-13262011-07-01615310.1186/1750-1326-6-53High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminalKilbride Seán MGluchowska Sonia ATelford Jayne EO'Sullivan CatherineDavey Gavin P<p>Abstract</p> <p>Background</p> <p>The activities of mitochondrial complex III (ubiquinol-cytochrome <it>c </it>reductase, EC 1.10.2.2) and complex IV (cytochrome <it>c </it>oxidase EC 1.9.3.1) are reduced by 30-70% in Huntington's disease and Alzheimer's disease, respectively, and are associated with excitotoxic cell death in these disorders. In this study, we investigated the control that complexes III and complex IV exert on glutamate release from the isolated nerve terminal.</p> <p>Results</p> <p>Inhibition of complex III activity by 60-90% was necessary for a major increase in the rate of Ca<sup>2+</sup>-independent glutamate release to occur from isolated nerve terminals (synaptosomes) depolarized with 4-aminopyridine or KCl. Similarly, an 85-90% inhibition of complex IV activity was required before a major increase in the rate of Ca<sup>2+</sup>-independent glutamate release from depolarized synaptosomes was observed. Inhibition of complex III and IV activities by ~ 60% and above was required before rates of glutamate efflux from polarized synaptosomes were increased.</p> <p>Conclusions</p> <p>These results suggest that nerve terminal mitochondria possess high reserves of complex III and IV activity and that high inhibition thresholds must be reached before excess glutamate is released from the nerve terminal. The implications of the results in the context of the relationship between electron transport chain enzyme deficiencies and excitotoxicity in neurodegenerative disorders are discussed.</p>http://www.molecularneurodegeneration.com/content/6/1/53 |
| spellingShingle | Kilbride Seán M Gluchowska Sonia A Telford Jayne E O'Sullivan Catherine Davey Gavin P High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal Molecular Neurodegeneration |
| title | High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal |
| title_full | High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal |
| title_fullStr | High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal |
| title_full_unstemmed | High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal |
| title_short | High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal |
| title_sort | high level inhibition of mitochondrial complexes iii and iv is required to increase glutamate release from the nerve terminal |
| url | http://www.molecularneurodegeneration.com/content/6/1/53 |
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