Sites of generation of reactive oxygen species in homogenates of brain tissue determined with the use of respiratory substrates and inhibitors
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Reactive oxygen species (ROS) have been widely implicated in the pathogenesis of various neurological diseases and aging. But the exact sites of ROS generation in brain tissue remained so far elusive. Here, we provide direct experimental evidence that at least 50% of total ROS generation in succinate-oxidizing homogenates of brain tissue can be attributed to complex I of mitochondrial respiratory chain. Applying quantitative methods for ROS detection we observed in different preparations from human, rat and mouse brain (digitonin-permeabilized tissue homogenates and isolated mitochondria) a linear relationship between rate of oxygen consumption and ROS generation with succinate as mitochondrial substrate. This quantitative relationship indicates, that under the particular conditions of oxygen saturation about 1% of the corresponding respiratory chain electron flow is redirected to form superoxide. Since we observed in mouse and rat brain mitochondria a unique dependency of both forward and reverse electron flow-dependent mitochondrial H(2)O(2) production on NAD redox state, we substantiated previous evidence that the FMN moiety of complex I is the major donor of electrons for the single electron reduction of molecular oxygen.
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Some authors pointed to complex I as the most relevant site for single electron reduction in brain mitochondria.
“Concretely, some authors pointed to complex I as the most relevant site for single electron reduction in brain mitochondria ([90](#B90)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [90]
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- Authors
- Kudin, A. P., Malinska, D., & Kunz, W. S.
- Affiliations
- University of Bonn (DE)
- Corresponding author
- Kunz, Wolfram S.
- ORCID
- Kunz, Wolfram S.
- Venue
- Biochimica et Biophysica Acta (BBA) - Bioenergetics
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 1777
- Issue
- 7-8
- Pages
- 689-695
- ISSN
- 0005-2728 (ISSN-L)
- OpenAlex
- W2070048444
- Cited by
- 84
- References
- 37
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 7 · 2018: 6 · 2017: 2 · 2016: 5 · 2015: 6 · 2014: 5 · 2013: 7 · 2012: 7
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Bioenergetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB TR 3, Ku 911/15)
- Bundesministerium für Bildung und Forschung (01GZ0704)
- Rheinische Friedrich-Wilhelms-Universität Bonn
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- reactive oxygen species, superoxide, hydrogen peroxide, complex I, mitochondrial respiratory chain, brain mitochondria, succinate oxidation, NAD redox state, flavin mononucleotide, electron flow, oxygen consumption, respiratory substrates, respiratory inhibitors
- MeSH terms
- Animals, Brain, Hydrogen Peroxide, Kinetics, Mice, Inbred C57BL, Mitochondria, NAD, Oxygen Consumption, Submitochondrial Particles, Superoxides, Rats, Wistar, Reactive Oxygen Species, Electron Transport Complex I, Mice, Rats
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