ArticleMolecular neurodegeneration2011
High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal.
Article in Molecular neurodegeneration, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
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- The Power Struggle: Kynurenine Pathway Enzyme Knockouts and Brain Mitochondrial Respiration.Journal of neurochemistry · 2025Article
- Key genes of electron transfer, the nitrogen cycle and tetracycline removal in bioelectrochemical systems.Biotechnology for biofuels and bioproducts · 2023Article
- Expression of actin- and oxidative phosphorylation-related transcripts across the cortical visuospatial working memory network in unaffected comparison and schizophrenia subjects.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants.Cell stem cell · 2022Article
- Mitochondrial dysfunction in microglia: a novel perspective for pathogenesis of Alzheimer's disease.Journal of neuroinflammation · 2022Review
- Molecular Signatures of Mitochondrial Complexes Involved in Alzheimer's Disease via Oxidative Phosphorylation and Retrograde Endocannabinoid Signaling Pathways.Oxidative medicine and cellular longevity · 2022Article
- The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction.Biomedicines · 2021Review
- PPARγ/PGC1α signaling as a potential therapeutic target for mitochondrial biogenesis in neurodegenerative disorders.Pharmacology & therapeutics · 2021Review
- Complex I Controls Mitochondrial and Plasma Membrane Potentials in Nerve Terminals.Neurochemical research · 2021Article
- Mitochondrial biogenesis as a therapeutic target for traumatic and neurodegenerative CNS diseases.Experimental neurology · 2020Review
- Lidocaine Attenuates Cognitive Impairment After Isoflurane Anesthesia by Reducing Mitochondrial Damage.Neurochemical research · 2019Article
- Dichloroacetate Stabilizes Mitochondrial Fusion Dynamics in Models of Neurodegeneration.Frontiers in molecular neuroscience · 2019Article
- Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases: Pathogenesis and Treatment.CNS neuroscience & therapeutics · 2017Review
- Quantitative Proteome Profiling of Street Rabies Virus-Infected Mouse Hippocampal Synaptosomes.Current microbiology · 2016Article
- Roles of Neuroglobin Binding to Mitochondrial Complex III Subunit Cytochrome c1 in Oxygen-Glucose Deprivation-Induced Neurotoxicity in Primary Neurons.Molecular neurobiology · 2016Article
- Brain diabetic neurodegeneration segregates with low intrinsic aerobic capacity.Annals of clinical and translational neurology · 2014Article
- Mitochondrial dysfunctions in neurodegenerative diseases: relevance to Alzheimer's disease.BioMed research international · 2014Review
- A melatonin-based fluorescence method for the measurement of mitochondrial complex III function in intact cells.Journal of pineal research · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe 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.
resultsInhibition 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.
conclusionsThese 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.
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Registered trials
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