Mitochondria and neuronal glutamate excitotoxicity
Open accessAbstract
The role of mitochondria in the control of glutamate excitotoxicity is investigated. The response of cultured cerebellar granule cells to continuous glutamate exposure is characterised by a transient elevation in cytoplasmic free calcium concentration followed by decay to a plateau as NMDA receptors partially inactivate. After a variable latent period, a secondary, irreversible increase in calcium occurs (delayed calcium deregulation, DCD) which precedes and predicts subsequent cell death. DCD is not controlled by mitochondrial ATP synthesis since it is unchanged in the presence of the ATP synthase inhibitor oligomycin in cells with active glycolysis. However, mitochondrial depolarisation (and hence inhibition of mitochondrial calcium accumulation) without parallel ATP depletion (oligomycin plus either rotenone or antimycin A) strongly protects the cells against DCD. Glutamate exposure is associated with an increase in the generation of superoxide anion by the cells, but superoxide generation in the absence of mitochondrial calcium accumulation is not neurotoxic. While it is concluded that mitochondrial calcium accumulation plays a critical role in the induction of DCD we can find no evidence for the involvement of the mitochondrial permeability transition.
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Mitochondrial dysfunction is characteristic of the excitotoxic pathway.
“This aligns with the knowledge that mitochondrial dysfunction is characteristic of the excitotoxic pathway (Nicholls and Budd, 1998; Votyakova and Reynolds, 2005), whereas ferroptosis may operate through damage other than (Wang et al., 2015) mitochondrial cellular membranes, such as the cytoplasmic membrane (Vaglio-Garro et al., 2024b).”
From Toxic Concentrations of Glutamate Induce Ferroptosis without Affecting Mitochondrial Respiration in Rodent Brain Slice Cultures (2026) · cites this paper as Nicholls and Budd, 1998
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Research works printed but not linked: 8
- M.F. Beal, N. Howell, I. Bodis-Wollner, Mitochondria and Free Radicals in Neurodegenerative Disease, Wiley-Liss, New York, 1997.
- D.G. Nicholls, S.J. Ferguson, Bioenergetics, Vol. 2, Academ- ic Press, London, 1992.
- L.M. Loew, W. Carrington, R.A. Tuft, F.S. Fay, Proc. Natl. Acad. Sci. U.S.A. 91 (1994) 12579^12583.
- E. Bonfoco, D. Krainc, M. Ankarcrona, P. Nicotera, S.A. Lipton, Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 7162^7166.
- H. Hara, R.M. Friedlander, V. Gagliardini, C. Ayata, K. Fink, Z.H. Huang, M. Shimizu-Sasamata, J.Y. Yuan, M.A. Moskowitz, Proc. Natl. Acad. Sci. U.S.A. 94 (1997) 2007^2012.
- R.C. Henneberry, in: M.F. Beal, N. Howell, I. Bodis-Woll- ner (Eds.), Mitochondria and Free Radicals in Neurodegen- erative Disease, Wiley-Liss, New York, 1997, pp. 111^143.
- E. Brouillet, P. Hantraye, R.J. Ferrante, R. Dolan, A. Leroy Willig, N.W. Kowall, M.F. Beal, Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 7105^7109.
- R.G. Victor, G.D. Thomas, E. Marban, B. O'Rourke, Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 6269^6273.
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Vaglio-Garro, A., Theuermann, M., Sweis, K. E., Zavadskis, S., Kokas, M., Környei, Z., Karas, M., Tretter, L., Komlódi, T., Weidinger, A., et al. (2026) · eneuro · doi:10.1523/eneuro.0439-25.2026
- Authors
- Nicholls, D. G., & Budd, S. L.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- Nicholls, David G
- ORCID
- Nicholls, David G
- Venue
- Biochimica et Biophysica Acta (BBA) - Bioenergetics
- Publisher
- Elsevier BV
- Published
- 1998-08
- Volume
- 1366
- Issue
- 1-2
- Pages
- 97-112
- ISSN
- 0005-2728 (ISSN-L)
- OpenAlex
- W2096426937
- Cited by
- 171
- References
- 0
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 1 · 2014: 5 · 2013: 3 · 2012: 8
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Bioenergetics (publishedVersion)
- Funders
- Wellcome Trust
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- mitochondrial calcium accumulation, glutamate excitotoxicity, cerebellar granule cells, mitochondrial depolarization, superoxide, mitochondrial permeability transition, oligomycin, rotenone, antimycin A, ATP synthase, cell death, neurotoxicity
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