The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Reactive Oxygen and Targeted Antioxidant Administration in Endothelial Cell Mitochondria
Open accessAbstract
We used fluorescent probes and EPR to study the mechanism(s) underlying reactive oxygen species (ROS) production by endothelial cell mitochondria and the action of mitoquinol, a mitochondria-targeted antioxidant. ROS measured by fluorescence resulted from complex I superoxide released to the matrix and converted to H(2)O(2). In contrast, EPR largely detected superoxide generated at complex III and effluxed outward. ROS fluorescence by mitochondria fueled by the complex II substrate, succinate, was substantial but markedly inhibited by rotenone. Superoxide, detected by EPR, in succinate-fueled mitochondria was not inhibited by rotenone and likely derived from semiquinone formation at complex III. Mitoquinol decreased H(2)O(2) fluorescence by succinate-fueled mitochondria but had little effect on the EPR signal for superoxide. This was not associated with a detectable decrease in membrane potential. Mitoquinol markedly enhanced ROS fluorescence in mitochondria fueled by the complex I substrates, glutamate and malate. Inhibitor studies suggested that this occurred in complex I, at one or more Q binding pockets. The above effects of mitoquinol were determined in mitochondria isolated and subsequently exposed to the targeted antioxidant. However, similar effects were observed in mitochondria after antecedent exposure to mitoquinol/mitoquinone in culture, suggesting that the agent is retained after isolation of the organelles. In conclusion, ROS production in bovine aortic endothelial cell mitochondria results largely from reverse transport to complex I and through the Q cycle in complex III. Mitoquinol blocks ROS from reverse electron transport but increases superoxide production derived from forward transport. These effects likely occur at one or more Q binding sites in complex I.
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“Further, stigmatellin, which blocks electron entry to the complex III Q-cycle, markedly reduced the EPR signal.”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [241]
In the citing paper
“These compounds markedly increased or decreased superoxide production, when assayed as DHPA fluorescence, depending on substrate provided for fuel (241).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [241]
In the citing paper
“During respiration on complex I substrates, superoxide appears to result from redox cycling of endogenous CoQ10 or exogenous analogues at Q-binding sites within complex I (84, 185, 241).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [241]
In the citing paper
“As opposed to DHPA fluorescence, we found that mitoquinone had essentially no effect on superoxide production with EPR spectroscopy (241).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [241]
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Metadata
- Authors
- O'Malley, Y., Fink, B. D., Ross, N. C., Prisinzano, T. E., & Sivitz, W. I.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Sivitz, William I.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 281
- Issue
- 52
- Pages
- 39766-39775
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1971215002
- Cited by
- 123
- References
- 50
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 7 · 2016: 4 · 2015: 7 · 2014: 7 · 2013: 5 · 2012: 12
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-25295, P30DK025295)
- 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 › Coenzyme Q10 studies and effects
- Keywords
- reactive oxygen species, mitochondria-targeted antioxidants, superoxide, complex I, cytochrome bc1 complex, Q-cycle, reverse electron transfer, semiquinone, rotenone, succinic acid, glutamate, malate, hydrogen peroxide, mitochondrial membrane potential
- MeSH terms
- Animals, Antioxidants, Cattle, Cells, Cultured, Electron Spin Resonance Spectroscopy, Endothelium, Vascular, Female, Male, Membrane Potentials, Mice, Inbred C57BL, Mitochondria, Muscle, Organophosphorus Compounds, Ubiquinone, Reactive Oxygen Species, Oxidative Stress, Mitochondrial Membranes, Mice
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