Cited by 726Mitochondrial Function and PathologyNitric Oxide and Endothelin EffectsRedox biology and oxidative stress

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Nitric Oxide Inhibits Electron Transfer and Increases Superoxide Radical Production in Rat Heart Mitochondria and Submitochondrial Particles

Poderoso, Juan José, Carreras, Marı́a Cecilia, Lisdero, Constanza, Riobó, Natalia, Schöpfer, Francisco, Boveris, Alberto·1996·Archives of Biochemistry and Biophysics

DOI 10.1006/abbi.1996.0146

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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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Free Radicals in Biology
Pryor, W. A. (1976) · Cited by 1,876

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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)
DOI: 10.1006/abbi.1996.0146
OpenAlex: W2070235240
Cited by: 726
References: 1
Citations by year: 2026: 1 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 11 · 2021: 14 · 2020: 16 · 2019: 23 · 2018: 18 · 2017: 18 · 2016: 23 · 2015: 20 · 2014: 20 · 2013: 27 · 2012: 45
FWCI: 7.83
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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 (medical) › 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

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Nitric Oxide Inhibits Electron Transfer and Increases Superoxide Radical Production in Rat Heart Mitochondria and Submitochondrial Particles

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