Cited by 480Mitochondrial Function and PathologyRedox biology and oxidative stressNitric Oxide and Endothelin Effects

Tissue-, substrate-, and site-specific characteristics of mitochondrial reactive oxygen species generation

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Tahara, Erich B., Navarete, Felipe D.T., Kowaltowski, Alicia J.·2009·Free Radical Biology and Medicine

Abstract

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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Crossref · 10.1016/j.freeradbiomed.2009.02.008

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  1. Nicholls, D.; Fergusson, S. Bioenergetics 3. Academic Press, San Diego; 2001.

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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
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 › 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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