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Nitrite Reductase Activity of Cytochrome c
Open accessAbstract
Small increases in physiological nitrite concentrations have now been shown to mediate a number of biological responses, including hypoxic vasodilation, cytoprotection after ischemia/reperfusion, and regulation of gene and protein expression. Thus, while nitrite was until recently believed to be biologically inert, it is now recognized as a potentially important hypoxic signaling molecule and therapeutic agent. Nitrite mediates signaling through its reduction to nitric oxide, via reactions with several heme-containing proteins. In this report, we show for the first time that the mitochondrial electron carrier cytochrome c can also effectively reduce nitrite to NO. This nitrite reductase activity is highly regulated as it is dependent on pentacoordination of the heme iron in the protein and occurs under anoxic and acidic conditions. Further, we demonstrate that in the presence of nitrite, pentacoordinate cytochrome c generates bioavailable NO that is able to inhibit mitochondrial respiration. These data suggest an additional role for cytochrome c as a nitrite reductase that may play an important role in regulating mitochondrial function and contributing to hypoxic, redox, and apoptotic signaling within the cell.
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In the citing paper
“We subsequently demonstrated that cytochrome-c gained ability to reduce nitrite in the presence of anionic phospholipids [73].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [73]
In the citing paper
“Under conditions where pentacoordination is favored, we previously calculated that cytochrome-c mediated NO production from nitrite could reach 14 nM/s [73].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [73]
In the citing paper
“the nitrite reductase activity of neuroglobin [63, 64, 70, 76] or cytochrome c [47] is negligible when the heme is hexacoordinated.”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [47]
In the citing paper
“exogenous administration of nitrite correlates with increased levels of S-nitrosothiols in red blood cells and other tissues both in vivo and in vitro [25, 43, 46-53].”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [47]
In the citing paper
“A potential mechanism by which nitrite could induce cGMP-independent effects is S-nitrosation of cysteine residues, which is being increasingly recognized as a potential nitrite-induced post-translational modification that can alter protein function[17, 43, 46, 47, 51, 96].”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [47]
In the citing paper
“Recent work from Basu and colleagues reported that liposomes containing cytochrome c also reduces nitrite to NO in a pH and nitrite concentration dependent manner [122].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [122]
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Metadata
- Authors
- Basu, S., Azarova, N. A., Font, M. D., King, S. B., Hogg, N., Gladwin, M. T., Shiva, S., & Kim-Shapiro, D. B.
- Affiliations
- Wake Forest University (US)
- Medical College of Wisconsin (US)
- University of Pittsburgh (US)
- Corresponding author
- Shiva, Sruti
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 283
- Issue
- 47
- Pages
- 32590-32597
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2583304
- OpenAlex
- W2078178926
- Cited by
- 214
- References
- 61
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 8 · 2020: 16 · 2019: 6 · 2018: 17 · 2017: 10 · 2016: 14 · 2015: 16 · 2014: 11 · 2013: 14 · 2012: 13
- FWCI
- 7.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HL058091)
- National Heart, Lung, and Blood Institute (HL058091, K02HL078706, R37HL058091, HL078706)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- cytochrome c, nitrite reductase activity, nitric oxide, hypoxia signaling, mitochondrial respiration inhibition, mitochondrial function, redox signaling, apoptosis
- MeSH terms
- Animals, Hypoxia, Cattle, Hydrogen-Ion Concentration, Kinetics, Mitochondria, Nitric Oxide, Nitrite Reductases, Oxygen, Oxygen Consumption, Phosphatidylcholines, Spectrophotometry, Signal Transduction, Apoptosis, Cytochromes c
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