High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal

Hdl Handle:
http://hdl.handle.net/10147/142313
Title:
High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal
Authors:
Kilbride, Sean M; Gluchowska, Sonia A; Telford, Jayne E; O'Sullivan, Catherine; Davey, Gavin P
Citation:
Molecular Neurodegeneration. 2011 Jul 26;6(1):53
Issue Date:
26-Jul-2011
URI:
http://hdl.handle.net/10147/142313
Abstract:
Abstract Background The activities of mitochondrial complex III (ubiquinol-cytochrome c reductase, EC 1.10.2.2) and complex IV (cytochrome c 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. Results Inhibition of complex III activity by 60-90% was necessary for a major increase in the rate of Ca2+-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 Ca2+-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. Conclusions 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.
Item Type:
Journal Article

Full metadata record

DC FieldValue Language
dc.contributor.authorKilbride, Sean M-
dc.contributor.authorGluchowska, Sonia A-
dc.contributor.authorTelford, Jayne E-
dc.contributor.authorO'Sullivan, Catherine-
dc.contributor.authorDavey, Gavin P-
dc.date.accessioned2011-09-14T11:22:19Z-
dc.date.available2011-09-14T11:22:19Z-
dc.date.issued2011-07-26-
dc.identifierhttp://dx.doi.org/10.1186/1750-1326-6-53-
dc.identifier.citationMolecular Neurodegeneration. 2011 Jul 26;6(1):53-
dc.identifier.urihttp://hdl.handle.net/10147/142313-
dc.description.abstractAbstract Background The activities of mitochondrial complex III (ubiquinol-cytochrome c reductase, EC 1.10.2.2) and complex IV (cytochrome c 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. Results Inhibition of complex III activity by 60-90% was necessary for a major increase in the rate of Ca2+-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 Ca2+-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. Conclusions 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.-
dc.titleHigh-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderKilbride et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2011-09-12T15:33:29Z-
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