Enhancement of hydrogen peroxide formation by protophores and ionophores in antimycin-supplemented mitochondria
Open accessAbstract
Rat and pigeon heart mitochondria supplemented with antimycin produce 0.3–1.0nmol of H2O2/min per mg of protein. These rates are stimulated up to 13-fold by addition of protophores (carbonyl cyanide p-trifluoromethoxyphenylhydrazone, carbonyl cyanide m-chloromethoxyphenylhydrazone and pentachlorophenol). Ionophores, such as valinomycin and gramicidin, and Ca2+ also markedly stimulated H2O2 production by rat heart mitochondria. The enhancement of H2O2 generation in antimycin-supplemented mitochondria and the increased O2 uptake of the State 4-to-State 3 transition showed similar protophore, ionophore and Ca2+ concentration dependencies. Thenoyltrifluoroacetone and N-bromosuccinimide, which inhibit succinate–ubiquinone reductase activity, also decreased mitochondrial H2O2 production. Addition of cyanide to antimycin-supplemented beef heart submitochondrial particles inhibited the generation of O2−, the precursor of mitochondrial H2O2. This effect was parallel to the increase in cytochrome c reduction and it is interpreted as indicating the necessity of cytochrome c13+ to oxidize ubiquinol to ubisemiquinone, whose autoxidation yields O2−. The effect of protophores, ionophores and Ca2+ is analysed in relation to the propositions of a cyclic mechanism for the interaction of ubiquinone with succinate dehydrogenase and cytochromes b and c1 [Wikstrom & Berden (1972) Biochim. Biophys. Acta283, 403–420; Mitchell (1976) J. Theor. Biol.62, 337–367]. A collapse in membrane potential, increasing the rate of ubisemiquinone formation and O2− production, is proposed as the molecular mechanism for the enhancement of H2O2 formation rates observed on addition of protophores, ionophores and Ca2+.
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Much less is known about the specific molecular sites and conditions for electron leak and O2•− generation along the electron-transport pathway under pathophysiologic conditions.
“Although much is known of the chemistry of ROS (151), much less is known about the specific molecular sites and conditions for electron leak and O2•− generation along the electron-transport pathway under pathophysiologic conditions (32, 61).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [61]
These studies point to H2O2 (and other peroxides), rather than O2•− per se, as the transduction factor in physiologic regulation by ROS.
“These studies again point to H2O2 (and other peroxides), rather than O2•− per se, as the transduction factor in physiologic regulation by ROS (61).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [61]
Support for a role of ROS in HIF-1α stabilization derives from studies showing that the absence of cytochrome c or blocked Rieske Fe-S proteins under hypoxic conditions blocks HIF-1α stabilization.
“Support for a role of ROS in HIF-1α stabilization derives from studies showing that the absence of cytochrome c or blocked Rieske Fe-S proteins under hypoxic conditions blocks HIF-1α stabilization (61, 221).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [61]
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- Authors
- Cadenas, E., & Boveris, A.
- Affiliations
- Universidad de Buenos Aires (AR)
- ORCID
- Cadenas, Enrique
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1980-04-15
- Volume
- 188
- Issue
- 1
- Pages
- 31-37
- ISSN
- 0264-6021 (ISSN-L)
- PMC
- PMC1162533
- OpenAlex
- W1850791929
- Cited by
- 275
- References
- 23
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 8 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 6 · 2012: 9
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fogarty International Center
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- hydrogen peroxide production, heart mitochondria, antimycin, ionophores, valinomycin, gramicidin, calcium, cytochrome c1, superoxide, succinate-ubiquinone reductase, succinate dehydrogenase, mitochondrial respiration, cytochrome c reduction
- MeSH terms
- Adenosine Triphosphate, Animals, Antimycin A, Bromosuccinimide, Calcium, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Hydrogen Peroxide, Ionophores, Mitochondria, Heart, Nitriles, Columbidae, Potassium Cyanide, Thenoyltrifluoroacetone, Rats, In Vitro Techniques
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