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Nitrite: A physiological store of nitric oxide and modulator of mitochondrial function
Open accessAbstract
Nitrite, long considered a biologically inert metabolite of nitric oxide (NO) oxidation, is now accepted as a physiological storage pool of NO that can be reduced to bioactive NO in hypoxic conditions to mediate a spectrum of physiological responses in blood and tissue. This graphical review will provide a broad overview of the role of nitrite in physiology, focusing on its formation and reduction to NO as well as its regulation of the mitochondrion- an emerging subcellular target for its biological actions in tissues.
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“Emerging evidence suggests that NO deficiency is associated with impaired mitochondrial function”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [167]
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“and that restoration of NO bioavailability induces mitochondrial biogenesis (127, 135, 167, 168)”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [167]
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Cites
The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739 · cited 2×
“Nitrite reduction by these enzymes with differing oxygen affinities, tissue distribution and rates of reduction, ensures NO generation and nitrosative modification of target proteins over a wide range of physiological hypoxia in the cell [1].”
BackgroundNitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation
Cosby, K., Partovi, K. S., Crawford, J. H., Patel, R. P., Reiter, C. D., Martyr, S., Yang, B. K., Waclawiw, M. A., Zalos, G., Xu, X., et al. (2003) · Nature Medicine · doi:10.1038/nm954 · Cited by 1,807
Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury
Murphy, E., & Steenbergen, C. (2008) · Physiological Reviews · doi:10.1152/physrev.00024.2007 · Cited by 1,504 · cited 1×
“respiratory chain results in excessive reactive oxygen species generation at complexes I and III and oxidation of critical proteins leading to opening of the mitochondrial permeability transition pore (PTP) as well as release of cytochrome c to initiate apoptosis [30,31].”
BackgroundCleeter, M. W. J., Cooper, J. M., Darley-Usmar, V. M., Moncada, S., & Schapira, A. H. V. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00424-2 · Cited by 1,241
Dietary Inorganic Nitrate Improves Mitochondrial Efficiency in Humans
Larsen, F. J., Schiffer, T. A., Borniquel, S., Sahlin, K., Ekblom, B., Lundberg, J. O., & Weitzberg, E. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.004 · Cited by 689 · cited 3×
“Further, the authors reported a NO3 -induced decrease in the expression of uncoupling protein 3 (UCP-3) and the adenine nucleotide translocase (ANT), two proteins which facilitate proton leak [25].”
BackgroundCytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver
Duranski, M. R., Greer, J. J. M., Dejam, A., Jaganmohan, S., Hogg, N., Langston, W., Patel, R. P., Yet, S.-F., Wang, X., Kevil, C. G., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22493 · Cited by 674
Oxidation of nitrogen-oxides by bound dioxygen in hemoproteins
Doyle, M. P., & Hoekstra, J. W. (1981) · Journal of Inorganic Biochemistry · doi:10.1016/s0162-0134(00)80291-3 · Cited by 643
Effects of dietary nitrate on oxygen cost during exercise
Larsen, F. J., Weitzberg, E., Lundberg, J. O., & Ekblom, B. (2007) · Acta Physiologica · doi:10.1111/j.1748-1716.2007.01713.x · Cited by 637 · cited 2×
“This leads to downstream signaling to induce a wide spectrum of biological responses including hypoxic vasodilation [8], stimulation of angiogenesis [23], modulation of glucose metabolism [24], augmentation of exercise efficiency [20], regulation of mitochondrial function [9,25,26] and tolerance to I/R [22,27–29] (Fig.”
BackgroundWebb, A., Bond, R., McLean, P., Uppal, R., Benjamin, N., & Ahluwalia, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402927101 · Cited by 608
Shiva, S., Huang, Z., Grubina, R., Sun, J., Ringwood, L. A., MacArthur, P. H., Xu, X., Murphy, E., Darley-Usmar, V. M., & Gladwin, M. T. (2007) · Circulation Research · doi:10.1161/01.res.0000260171.52224.6b · Cited by 599
Self-citationShiva, S., Sack, M. N., Greer, J. J., Duranski, M., Ringwood, L. A., Burwell, L., Wang, X., MacArthur, P. H., Shoja, A., Raghavachari, N., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070198 · Cited by 555
Self-citationEnzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control
Huang, Z. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24650 · Cited by 520
Castello, P. R., David, P. S., McClure, T., Crook, Z., & Poyton, R. O. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.011 · Cited by 495 · cited 1×
“Nitrite reduction by the mitochondrial ETC has been shown to occur in near anoxic conditions, predominantly at pH less than 7 and with relatively high (millimolar) concentrations of NO2 [15].”
BackgroundHendgen-Cotta, U. B., Merx, M. W., Shiva, S., Schmitz, J., Becher, S., Klare, J. P., Steinhoff, H.-J., Goedecke, A., Schrader, J., Gladwin, M. T., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801336105 · Cited by 418
Self-citationBryan, N. S., Rassaf, T., Maloney, R. E., Rodriguez, C. M., Saijo, F., Rodriguez, J. R., & Feelisch, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306706101 · Cited by 400
Carlström, M., Larsen, F. J., Nyström, T., Hezel, M., Borniquel, S., Weitzberg, E., & Lundberg, J. O. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008872107 · Cited by 382 · cited 1×
“This leads to downstream signaling to induce a wide spectrum of biological responses including hypoxic vasodilation [8], stimulation of angiogenesis [23], modulation of glucose metabolism [24], augmentation of exercise efficiency [20], regulation of mitochondrial function [9,25,26] and tolerance to I/R [22,27–29] (Fig.”
BackgroundCeruloplasmin is a NO oxidase and nitrite synthase that determines endocrine NO homeostasis
Shiva, S., Wang, X., Ringwood, L. A., Xu, X., Yuditskaya, S., Annavajjhala, V., Miyajima, H., Hogg, N., Harris, Z. L., & Gladwin, M. T. (2006) · Nature Chemical Biology · doi:10.1038/nchembio813 · Cited by 359
Self-citationA mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis
Jansson, E. Å., Huang, L., Malkey, R., Govoni, M., Nihlén, C., Olsson, A., Stensdotter, M., Petersson, J., Holm, L., Weitzberg, E., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.92 · Cited by 356
Erythrocytes are the major intravascular storage sites of nitrite in human blood
Dejam, A. (2005) · Blood · doi:10.1182/blood-2005-02-0567 · Cited by 350
Mitochondrial Oxygen Affinity, Respiratory Flux Control And Excess Capacity Of Cytochrome c Oxidase
Gnaiger, E., Lassnig, B., Kuznetsov, A. V., Rieger, G. E., & Margreiter, R. (1998) · Journal of Experimental Biology · doi:10.1242/jeb.201.8.1129 · Cited by 318
Human neuroglobin functions as a redox-regulated nitrite reductase
Tiso, M., Tejero, J., Basu, S., Azarov, I., Wang, X., Simplaceanu, V., Frizzell, S., Jayaraman, T., Geary, L., Shapiro, C., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.159541 · Cited by 287
Self-citationJung, K.-H., Chu, K., Ko, S.-Y., Lee, S.-T., Sinn, D.-I., Park, D.-K., Kim, J.-M., Song, E.-C., Kim, M., & Roh, J.-K. (2006) · Stroke · doi:10.1161/01.str.0000245116.40163.1c · Cited by 253
CONTROL OF ELECTRON FLUX THROUGH THE RESPIRATORY CHAIN IN MITOCHONDRIA AND CELLS
Brand, M. D., & Murphy, M. P. (1987) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.1987.tb01265.x · Cited by 240 · cited 6×
“Once formed, NO2 is reduced to bioactive NO through acidification or via reaction with a number of proteins possessing NO2 reductase activity, including heme globins [8–10], molybdenum-containing enzymes [11,12], NOS [13], and components of the mitochondrial electron transport chain (ETC) [14–16].”
BackgroundInfluentialNitrite reductase activity of cytochrome c
Basu, S., Azarova, N. A., Font, M. D., King, S. B., Hogg, N., Gladwin, M. T., Shiva, S., & Kim-Shapiro, D. B. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806934200 · Cited by 214
Self-citationNitrite regulates hypoxic vasodilation via myoglobin-dependent nitric oxide generation
Totzeck, M., Hendgen-Cotta, U. B., Luedike, P., Berenbrink, M., Klare, J. P., Steinhoff, H.-J., Semmler, D., Shiva, S., Williams, D., Kipar, A., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.087155 · Cited by 202
Self-citationRole of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics
DEZFULIAN, C., RAAT, N., SHIVA, S., & GLADWIN, M. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.05.001 · Cited by 198
Self-citationChronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis
Kumar, D., Branch, B. G., Pattillo, C. B., Hood, J., Thoma, S., Simpson, S., Illum, S., Arora, N., Chidlow, J. H., Langston, W., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711480105 · Cited by 187
Li, H., Samouilov, A., Liu, X., & Zweier, J. L. (2003) · Biochemistry · doi:10.1021/bi026385a · Cited by 180 · cited 2×
“While the exact reaction scheme underlying XOR-mediated NO2 reduction is unclear, it is known that this reaction occurs at the molybdenum cofactor of XOR and aldehyde oxidase [11,12].”
BackgroundBurwell, L. S., & Brookes, P. S. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1845 · Cited by 177 · cited 1×
“respiratory chain results in excessive reactive oxygen species generation at complexes I and III and oxidation of critical proteins leading to opening of the mitochondrial permeability transition pore (PTP) as well as release of cytochrome c to initiate apoptosis [30,31].”
BackgroundDezfulian, C., Shiva, S., Alekseyenko, A., Pendyal, A., Beiser, D. G., Munasinghe, J. P., Anderson, S. A., Chesley, C. F., Vanden Hoek, T. L., & Gladwin, M. T. (2009) · Circulation · doi:10.1161/circulationaha.109.853267 · Cited by 174
Self-citationNitric oxide synthase reduces nitrite to NO under anoxia
Vanin, A. F., Bevers, L. M., Slama-Schwok, A., & van Faassen, E. E. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6374-2 · Cited by 151
Cardioprotection by metabolic shut-down and gradual wake-up
Burwell, L. S., Nadtochiy, S. M., & Brookes, P. S. (2009) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2009.02.026 · Cited by 146 · cited 1×
“Inhibitors of complex I have been demonstrated to attenuate I/R injury by limiting electron flow through the ETC at reperfusion, thereby limiting ROS generation [32].”
BackgroundLi, H., Kundu, T. K., & Zweier, J. L. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.019125 · Cited by 126 · cited 2×
“While the exact reaction scheme underlying XOR-mediated NO2 reduction is unclear, it is known that this reaction occurs at the molybdenum cofactor of XOR and aldehyde oxidase [11,12].”
BackgroundMitochondria recycle nitrite back to the bioregulator nitric monoxide.
Nohl, H., Staniek, K., Sobhian, B., Bahrami, S., Redl, H., & Kozlov, A. V. (2000) · Acta Biochimica Polonica · doi:10.18388/abp.2000_3946 · Cited by 116 · cited 1×
“Contents lists available at SciVerse ScienceDirect Redox Biology 2213-23 http://d $This Commo reprodu n Corr Pittsbur E-m journal homepage: www.elsevier.com/locate/redox Graphical Review Nitrite: A physiological store of nitric oxide and modulator of mitochondrial function$ Sruti Shiva n”
Control of cytochrome c oxidase activity by nitric oxide
Brunori, M., Giuffrè, A., Forte, E., Mastronicola, D., Barone, M. C., & Sarti, P. (2003) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2003.06.008 · Cited by 103
Alef, M. J., Vallabhaneni, R., Carchman, E., Morris, S. M., Shiva, S., Wang, Y., Kelley, E. E., Tarpey, M. M., Gladwin, M. T., Tzeng, E., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44079 · Cited by 101
Self-citationRaat, N. J. H., Noguchi, A. C., Liu, V. B., Raghavachari, N., Liu, D., Xu, X., Shiva, S., Munson, P. J., & Gladwin, M. T. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.05.015 · Cited by 97
Mo, L., Wang, Y., Geary, L., Corey, C., Alef, M. J., Beer-Stolz, D., Zuckerbraun, B. S., & Shiva, S. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.07.080 · Cited by 62
Self-citation
Cited by
Sorted by citations
The role of the nitric oxide pathway in brain injury and its treatment — From bench to bedside
Garry, P. S., Ezra, M., Rowland, M. J., Westbrook, J., & Pattinson, K. T. S. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2014.10.017 · Cited by 380
“NOdonorsmay be neuroprotective by preventingNOdepletion, helping to normalize capillary blood flow and improve oxygen delivery to the tissue (Shiva, 2013).”
BackgroundLiquid Chromatography Analysis of Common Nutritional Components, in Feed and Food
Cortés-Herrera, C., Artavia, G., Leiva, A., & Granados-Chinchilla, F. (2018) · Foods · doi:10.3390/foods8010001 · Cited by 275
Kumar, M., Sahu, S. K., Kumar, R., Subuddhi, A., Maji, R. K., Jana, K., Gupta, P., Raffetseder, J., Lerm, M., Ghosh, Z., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.01.007 · Cited by 259
“Nitrite also serves as a physiological storage pool of NO that can be reduced to bioactive NO under hypoxic conditions (Shiva, 2013).”
BackgroundRemote ischaemic conditioning—a new paradigm of self-protection in the brain
Hess, D. C., Blauenfeldt, R. A., Andersen, G., Hougaard, K. D., Hoda, M. N., Ding, Y., & Ji, X. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.223 · Cited by 234
Antioxidative nanomaterials and biomedical applications
Liu, Y., & Shi, J. (2019) · Nano Today · doi:10.1016/j.nantod.2019.05.008 · Cited by 174
Metadata
- Authors
- Shiva, S.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Shiva, Sruti
- ORCID
- Shiva, Sruti
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2013
- Volume
- 1
- Issue
- 1
- Pages
- 40-44
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC3661298
- OpenAlex
- W2059688150
- Cited by
- 207
- References
- 38
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 18 · 2023: 7 · 2022: 20 · 2021: 18 · 2020: 16 · 2019: 14 · 2018: 18 · 2017: 17 · 2016: 21 · 2015: 20 · 2014: 8 · 2013: 3
- FWCI
- 12.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- NIH (1R01HL096973)
- AHA (09SDG2150066)
- Institution of Transfusion Medicine
- Hemophilia Center of Western Pennsylvania
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- nitrite, nitric oxide, nitric oxide storage, hypoxia, mitochondrial function, nitrite reduction, nitric oxide signaling, redox regulation
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