Cited by 602Mitochondrial Function and PathologyNitric Oxide and Endothelin EffectsRedox biology and oxidative stress

Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase

Open access
Brown, Guy C.·2001·Biochimica et Biophysica Acta (BBA) - Bioenergetics

Abstract

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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Crossref · 10.1016/s0005-2728(00)00238-3

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Authors
Brown, G. C.
Affiliations
University of Cambridge (GB)
Corresponding author
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
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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