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Tissue-, substrate-, and site-specific characteristics of mitochondrial reactive oxygen species generation
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Reactive oxygen species are a by-product of mitochondrial oxidative phosphorylation, derived from a small quantity of superoxide radicals generated during electron transport. We conducted a comprehensive and quantitative study of oxygen consumption, inner membrane potentials, and H(2)O(2) release in mitochondria isolated from rat brain, heart, kidney, liver, and skeletal muscle, using various respiratory substrates (alpha-ketoglutarate, glutamate, succinate, glycerol phosphate, and palmitoyl carnitine). The locations and properties of reactive oxygen species formation were determined using oxidative phosphorylation and the respiratory chain modulators oligomycin, rotenone, myxothiazol, and antimycin A and the uncoupler CCCP. We found that in mitochondria isolated from most tissues incubated under physiologically relevant conditions, reactive oxygen release accounts for 0.1-0.2% of O(2) consumed. Our findings support an important participation of flavoenzymes and complex III and a substantial role for reverse electron transport to complex I as reactive oxygen species sources. Our results also indicate that succinate is an important substrate for isolated mitochondrial reactive oxygen production in brain, heart, kidney, and skeletal muscle, whereas fatty acids generate significant quantities of oxidants in kidney and liver. Finally, we found that increasing respiratory rates is an effective way to prevent mitochondrial oxidant release under many, but not all, conditions. Altogether, our data uncover and quantify many tissue-, substrate-, and site-specific characteristics of mitochondrial ROS release.
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“Complex III has been labeled as a higher contributor of ROS in SM mitochondria (14).”
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“This hypothesis was confirmed in many models, including, for example, isolated rat and pigeon liver mitochondria (decrease in H2O2) [143], human monoblastic ML-1 cells (decrease in O2•(−) and ONOO−), and rat brains, hearts, kidneys, livers, and skeletal muscles [137].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [137]
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Self-citation
Metadata
- Authors
- Tahara, E. B., Navarete, F. D. T., & Kowaltowski, A. J.
- Affiliations
- Universidade de São Paulo (BR)
- Corresponding author
- Kowaltowski, Alicia J.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 46
- Issue
- 9
- Pages
- 1283-1297
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2079100436
- Cited by
- 479
- References
- 83
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 34 · 2023: 19 · 2022: 28 · 2021: 33 · 2020: 27 · 2019: 23 · 2018: 27 · 2017: 28 · 2016: 31 · 2015: 45 · 2014: 25 · 2013: 28 · 2012: 34
- FWCI
- 12.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- 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 (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- mitochondrial reactive oxygen species, superoxide, oxidative phosphorylation, respiratory substrates, succinic acid, fatty acids, palmitoylcarnitine, flavoenzyme, cytochrome bc1 complex, reverse electron transfer, complex I, mitochondrial membrane potential, hydrogen peroxide release, oxygen consumption, tissue-specific differences, brain, heart, kidney, liver, skeletal muscle
- MeSH terms
- Animals, Brain, Kidney, Liver, Male, Mitochondria, Myocardium, Organ Specificity, Oxidative Phosphorylation, Oxygen Consumption, Substrate Specificity, Rats, Sprague-Dawley, Reactive Oxygen Species, Oxidative Stress, Muscle, Skeletal, Electron Transport Chain Complex Proteins, Membrane Transport Modulators, Rats, Membrane Potential, Mitochondrial
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