Mitochondria and neuronal survival
Abstract
Mitochondria play a central role in the survival and death of neurons. The detailed bioenergetic mechanisms by which isolated mitochondria generate ATP, sequester Ca 2+, generate reactive oxygen species, and undergo Ca 2+-dependent permeabilization of their inner membrane are currently being applied to the function of mitochondria in situ within neurons under physiological and pathophysiological conditions. Here we review the functional bioenergetics of isolated mitochondria, with emphasis on the chemiosmotic proton circuit and the application (and occasional misapplication) of these principles to intact neurons. Mitochondria play an integral role in both necrotic and apoptotic neuronal cell death, and the bioenergetic principles underlying current studies are reviewed.
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TMRM+ at low concentration (20 nM) provides a direct function of Δψm without complications from self-quenching.
“At equilibrium, the fluorescence produced by this low concentration of TMRM+ (excitation 543/emission red photomultiplier channel) is a direct function of Δψm, and complications attributable to self-quenching of the dye are eliminated (Nicholls and Budd, 2000; Nicholls and Ward, 2000; Nicholls and Ferguson, 2002).”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Nicholls and Budd, 2000
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- Authors
- Nicholls, D. G., & Budd, S. L.
- Affiliations
- Brigham and Women's Hospital (US)
- ORCID
- Nicholls, David G.
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2000-01-01
- Volume
- 80
- Issue
- 1
- Pages
- 315-360
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2112696881
- Cited by
- 1,243
- References
- 7
- Citations by year
- 2026: 32 · 2025: 30 · 2024: 26 · 2023: 26 · 2022: 30 · 2021: 43 · 2020: 38 · 2019: 26 · 2018: 43 · 2017: 39 · 2016: 41 · 2015: 33 · 2014: 46 · 2013: 48 · 2012: 50
- FWCI
- 3.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- 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
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mitochondria, neuronal survival, neuronal cell death, mitochondrial bioenergetics, ATP production, calcium sequestration, reactive oxygen species, mitochondrial membrane permeabilization, chemiosmotic theory, necrosis, apoptosis
- MeSH terms
- Animals, Calcium, Cell Survival, Humans, Intracellular Membranes, Mitochondria, Neurons, Apoptosis, Glutamic Acid
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