Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase
Open accessAbstract
Nitric oxide (NO) and its derivatives inhibit mitochondrial respiration by a variety of means. Nanomolar concentrations of NO immediately, specifically and reversibly inhibit cytochrome oxidase in competition with oxygen, in isolated cytochrome oxidase, mitochondria, nerve terminals, cultured cells and tissues. Higher concentrations of NO and its derivatives (peroxynitrite, nitrogen dioxide or nitrosothiols) can cause irreversible inhibition of the respiratory chain, uncoupling, permeability transition, and/or cell death. Isolated mitochondria, cultured cells, isolated tissues and animals in vivo display respiratory inhibition by endogenously produced NO from constitutive isoforms of NO synthase (NOS), which may be largely mediated by NO inhibition of cytochrome oxidase. Cultured cells expressing the inducible isoform of NOS (iNOS) can acutely and reversibly inhibit their own cellular respiration and that of co-incubated cells due to NO inhibition of cytochrome oxidase, but after longer-term incubation result in irreversible inhibition of cellular respiration due to NO or its derivatives. Thus the NO inhibition of cytochrome oxidase may be involved in the physiological and/or pathological regulation of respiration rate, and its affinity for oxygen.
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The high affinity and rapid binding of NO to ferrous heme are important biologically for regulation of mitochondrial respiration at CcOx.
“The high affinity and rapid binding to ferrous heme are important biologically for the activation of sGC to generate the second messenger cGMP and the regulation of mitochondrial respiration at CcOx (9–16).”
From What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology (2010) · cites this paper as [10]
The high affinity and rapid binding of NO to ferrous heme are important biologically for activation of sGC to generate cGMP.
“The high affinity and rapid binding to ferrous heme are important biologically for the activation of sGC to generate the second messenger cGMP and the regulation of mitochondrial respiration at CcOx (9–16).”
From What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology (2010) · cites this paper as [10]
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Nitric oxide inhibition of mitochondrial respiration and its role in cell death
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- Authors
- Brown, G. C.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Brown, Guy C.
- ORCID
- Brown, Guy C.
- Venue
- Biochimica et Biophysica Acta (BBA) - Bioenergetics
- Publisher
- Elsevier BV
- Published
- 2001-03
- Volume
- 1504
- Issue
- 1
- Pages
- 46-57
- ISSN
- 0005-2728 (ISSN-L)
- OpenAlex
- W1976995270
- Cited by
- 602
- References
- 97
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 15 · 2023: 17 · 2022: 18 · 2021: 20 · 2020: 23 · 2019: 31 · 2018: 26 · 2017: 24 · 2016: 23 · 2015: 18 · 2014: 24 · 2013: 22 · 2012: 32
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Bioenergetics (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, cytochrome c oxidase, mitochondrial respiration, nitric oxide synthase, inducible nitric oxide synthase, peroxynitrite, S-nitrosothiols, electron transport inhibition, uncoupling, permeability transition, cell death, oxygen affinity
- MeSH terms
- Animals, Cells, Cultured, Electron Transport Complex IV, Enzyme Inhibitors, Humans, Mitochondria, Nitric Oxide, Oxygen Consumption, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type I
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