Hypothesis: the mitochondrial NO(*) signaling pathway, and the transduction of nitrosative to oxidative cell signals: an alternative function for cytochrome c oxidase
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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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].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [33]
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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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