Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles
Abstract
Nitric oxide (.NO) released by S-nitrosoglutathione (GSNO) inhibited enzymatic activities of rat heart mitochondrial membranes. Cytochrome oxidase activity was inhibited to one-half at an effective .NO concentration of 0.1 microM, while succinate- and NADH-cytochrome-c reductase activities were half-maximally inhibited at 0.3 microM .NO. Submitochondrial particles treated with .NO (either from GSNO or from a pure solution) showed increased O(-)(2) and H202 production when supplemented with succinate alone, at rates that were comparable to those of control particles with added succinate and antimycin. Rat heart mitochondria treated with .NO also showed increased H2O2 production. Cytochrome spectra and decreased enzymatic activities in the presence of .NO are consistent with a multiple inhibition of mitochondrial electron transfer at cytochrome oxidase and at the ubiquinone-cytochrome b region of the respiratory chain, the latter leading to the increased O2- production. Electrochemical detection showed that the buildup of a .NO concentration from GSNO was interrupted by submitochondrial particles supplemented with succinate and antimycin and was restored by addition of superoxide dismutase. The inhibitory effect of .NO on cytochrome oxidase was also prevented under the same conditions. Apparently, mitochondrial O2- reacts with .NO to form peroxynitrate and, by removing .NO, reactivates the previously inhibited cytochrome oxidase. It is suggested that, at physiological concentrations of .NO, inhibition of electron transfer, .NO-induced O2- production, and ONOO- formation participate in the regulatory control of mitochondrial oxygen uptake.
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NO inhibits cytochrome c oxidase, decreases mitochondrial ROS formation, and limits apoptotic cytochrome c release.
“NO is a well-characterized regulator of mitochondrial function that inhibits cytochrome c oxidase, decreases mitochondrial ROS formation, and limits apoptotic cytochrome c release [32–36].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [32]
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- Authors
- Poderoso, J. J., Carreras, M. C., Lisdero, C., Riobó, N., Schöpfer, F., & Boveris, A.
- Affiliations
- Universidad de Buenos Aires (AR)
- Venue
- Archives of Biochemistry and Biophysics
- Publisher
- Elsevier BV
- Published
- 1996-04
- Volume
- 328
- Issue
- 1
- Pages
- 85-92
- ISSN
- 0003-9861 (ISSN-L)
- OpenAlex
- W2070235240
- Cited by
- 726
- References
- 1
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- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Biochemistry and Biophysics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- nitric oxide, S-nitrosoglutathione, heart mitochondria, submitochondrial particles, cytochrome c oxidase inhibition, electron transfer inhibition, hydrogen peroxide production, peroxynitrite, superoxide dismutase, electron transport chain
- MeSH terms
- Animals, Electron Transport Complex IV, Electron Transport, Female, Mitochondria, Heart, NAD, NADH Dehydrogenase, Nitric Oxide, Submitochondrial Particles, Succinates, Superoxides, Rats, Sprague-Dawley, Ion-Selective Electrodes, Succinic Acid, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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