Cited by 137Mitochondrial Function and PathologyRedox biology and oxidative stressNitric Oxide and Endothelin Effects

Hypothesis: the mitochondrial NO(*) signaling pathway, and the transduction of nitrosative to oxidative cell signals: an alternative function for cytochrome c oxidase

Brookes, Paul, Darley-Usmar, Victor M.·2002·Free Radical Biology and Medicine

Abstract

Nitric oxide (NO(*)) signaling is diverse, and involves reaction with free radicals, metalloproteins, and specific protein amino acid residues. Prominent among these interactions are the heme protein soluble guanylate cyclase and cysteine residues within several proteins such as caspases, the executors of apoptosis. Another well characterized site of NO(*) binding is the terminal complex of the mitochondrial respiratory chain, cytochrome c oxidase, although the downstream signaling effects of this interaction remain unclear. Recently, it has been recognized that the intracellular formation of hydrogen peroxide (H(2)O(2)) by controlled mechanisms contributes to what we term "redox tone," and so controls the activity and activation thresholds of redox-sensitive signaling pathways. In this hypothesis paper, it is proposed that NO(*)-dependent modulation of the respiratory chain can control the mitochondrial generation of H(2)O(2) for cell signaling purposes without affecting ATP synthesis.

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Crossref · 10.1016/s0891-5849(01)00805-x

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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].”

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Authors
Brookes, P., & Darley-Usmar, V. M.
Affiliations
University of Alabama at Birmingham (US)
Corresponding author
Darley-Usmar, Victor M.
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2002-02
Volume
32
Issue
4
Pages
370-374
ISSN
0891-5849 (ISSN-L)
OpenAlex
W2011779329
Cited by
137
References
44
Citations by year
2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 2 · 2014: 9 · 2013: 4 · 2012: 8
FWCI
3.82
Type
journal article
Language
en
Open access
closed
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Heart Association
  • National Institutes of Health (1r03aa012613-01)
  • National Institute on Alcohol Abuse and Alcoholism (AA 12613)
  • National Heart, Lung, and Blood Institute (R01HL058031, HL-58031)
  • National Institute of Environmental Health Sciences (R01ES010167, ES-10167)
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
nitric oxide signaling, cytochrome c oxidase, mitochondrial respiratory chain, hydrogen peroxide, redox signaling, oxidative stress, soluble guanylate cyclase, caspases, apoptosis
MeSH terms
Adenosine Triphosphate, Electron Transport Complex IV, Dose-Response Relationship, Drug, Free Radicals, Hydrogen Peroxide, Membrane Potentials, Mitochondria, Models, Biological, Nitric Oxide, Oxidation-Reduction, Oxygen, Signal Transduction

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