Inhibition of Mitochondrial Electron Transport by Peroxynitrite
Abstract
Mammalian mitochondria are sensitive targets of the cytotoxic effects of superoxide (O.2-) and nitric oxide (.NO). In turn, when superoxide and nitric oxide are simultaneously produced, they rapidly react with each other yielding the highly oxidizing peroxynitrite anion (ONOO-) which may be also toxic to mammalian mitochondria. In this study we report that peroxynitrite exposure to rat heart mitochondria resulted in significant inactivation of electron carriers such as succinate dehydrogenase and NADH dehydrogenase as well as the mitochondrial ATPase. As a result of enzyme inactivation, peroxynitrite lead to a profound inhibition of glutamate/malate- and succinate-supported oxygen consumption but did not cause mitochondrial uncoupling. Secondary to inhibiting mitochondrial electron transport, peroxynitrite induced an enhanced succinate-stimulated hydrogen peroxide formation by heart mitochondria. Most of the damaging effects against mitochondria can be ascribed to peroxynitrite anion itself and not to hydroxyl radical-like oxidant yielded during the proton-catalyzed decomposition of peroxynitrite, as hydroxyl radical scavengers provided a rather modest protection. Our observations indicate that mitochondria may constitute a key intracellular loci for the toxic effects of peroxynitrite under the various pathological conditions in which peroxynitrite appears to play a contributory role.
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Tyrosine nitration is measured as the hallmark of peroxynitrite presence and is traditionally viewed as a sign of nitrative or oxidative stress.
“This modification is measured as the hallmark of peroxynitrite presence and is traditionally viewed as a sign of nitrative or oxidative stress (78, 765).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [765]
Superoxide reacts rapidly with nitric oxide, generating peroxynitrite, which can impair proteins involved in electron transport.
“Moreover, superoxide is known to react very rapidly with NO (107), generating a damaging peroxynitrite (ONOO−) radical (98, 144, 246), which can impair proteins involved in electron transport (261).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [261]
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- Authors
- Radi, R., Rodriguez, M., Castro, L., & Telleri, R.
- Affiliations
- Universidad de la República de Uruguay (UY)
- ORCID
- Castro, L.
- Venue
- Archives of Biochemistry and Biophysics
- Publisher
- Elsevier BV
- Published
- 1994-01
- Volume
- 308
- Issue
- 1
- Pages
- 89-95
- ISSN
- 0003-9861 (ISSN-L)
- OpenAlex
- W2085366528
- Cited by
- 693
- References
- 0
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 9 · 2023: 6 · 2022: 10 · 2021: 13 · 2020: 8 · 2019: 11 · 2018: 15 · 2017: 9 · 2016: 14 · 2015: 11 · 2014: 19 · 2013: 18 · 2012: 24
- FWCI
- 11.77
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- peroxynitrite, mitochondrial electron transport chain, heart mitochondria, superoxide, nitric oxide, succinate dehydrogenase, NADH dehydrogenase, mitochondrial ATPase, oxygen consumption, hydrogen peroxide production, hydroxyl radicals, hydroxyl radical scavengers, mitochondrial toxicity
- MeSH terms
- Animals, Electron Transport, Hydrogen Peroxide, Kinetics, Male, Mitochondria, Heart, Nitrates, Oxygen Consumption, Succinate Dehydrogenase, Rats
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