Myoglobin promotes nitrite-dependent mitochondrial S-nitrosation to mediate cytoprotection after hypoxia/reoxygenation
- PMID: 32891753
- PMCID: PMC7606822
- DOI: 10.1016/j.niox.2020.08.005
Myoglobin promotes nitrite-dependent mitochondrial S-nitrosation to mediate cytoprotection after hypoxia/reoxygenation
Abstract
It is well established that myoglobin supports mitochondrial respiration through the storage and transport of oxygen as well as through the scavenging of nitric oxide. However, during ischemia/reperfusion (I/R), myoglobin and mitochondria both propagate myocardial injury through the production of oxidants. Nitrite, an endogenous signaling molecule and dietary constituent, mediates potent cardioprotection after I/R and this effect relies on its interaction with both myoglobin and mitochondria. While independent mechanistic studies have demonstrated that nitrite-mediated cardioprotection requires the presence of myoglobin and the post-translational S-nitrosation of critical cysteine residues on mitochondrial complex I, it is unclear whether myoglobin directly catalyzes the S-nitrosation of complex I or whether mitochondrial-dependent nitrite reductase activity contributes to S-nitrosation. Herein, using purified myoglobin and isolated mitochondria, we characterize and directly compare the nitrite reductase activities of mitochondria and myoglobin and assess their contribution to mitochondrial S-nitrosation. We demonstrate that myoglobin is a significantly more efficient nitrite reductase than isolated mitochondria. Further, deoxygenated myoglobin catalyzes the nitrite-dependent S-nitrosation of mitochondrial proteins. This reaction is enhanced in the presence of oxidized (Fe3+) myoglobin and not significantly affected by inhibitors of mitochondrial respiration. Using a Chinese Hamster Ovary cell model stably transfected with human myoglobin, we show that both myoglobin and mitochondrial complex I expression are required for nitrite-dependent attenuation of cell death after anoxia/reoxygenation. These data expand the understanding of myoglobin's role both as a nitrite reductase to a mediator of S-nitrosation and as a regulator of mitochondrial function, and have implications for nitrite-mediated cardioprotection after I/R.
Keywords: Complex I; Ischemia; Mitochondria; Myoglobin; Nitrite; S-nitrosothiol.
Copyright © 2020 Elsevier Inc. All rights reserved.
Figures
![Figure 1:](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7606822/bin/nihms-1628096-f0001.gif)
![Figure 2:](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7606822/bin/nihms-1628096-f0002.gif)
![Figure 3:](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7606822/bin/nihms-1628096-f0003.gif)
![Figure 4:](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7606822/bin/nihms-1628096-f0004.gif)
![Figure 5:](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7606822/bin/nihms-1628096-f0005.gif)
Similar articles
-
S-nitrosation of calpains is associated with cardioprotection in myocardial I/R injury.Nitric Oxide. 2017 Jul 1;67:68-74. doi: 10.1016/j.niox.2017.04.003. Epub 2017 Apr 6. Nitric Oxide. 2017. PMID: 28392447
-
A highlight of myoglobin diversity: the nitrite reductase activity during myocardial ischemia-reperfusion.Nitric Oxide. 2010 Feb 15;22(2):75-82. doi: 10.1016/j.niox.2009.10.003. Epub 2009 Oct 29. Nitric Oxide. 2010. PMID: 19836457 Review.
-
Nitrite mediates cytoprotection after ischemia/reperfusion by modulating mitochondrial function.Basic Res Cardiol. 2009 Mar;104(2):113-9. doi: 10.1007/s00395-009-0009-3. Epub 2009 Feb 26. Basic Res Cardiol. 2009. PMID: 19242636 Review.
-
Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury.Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10256-61. doi: 10.1073/pnas.0801336105. Epub 2008 Jul 16. Proc Natl Acad Sci U S A. 2008. PMID: 18632562 Free PMC article.
-
Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration.Circ Res. 2007 Mar 16;100(5):654-61. doi: 10.1161/01.RES.0000260171.52224.6b. Epub 2007 Feb 9. Circ Res. 2007. PMID: 17293481
Cited by
-
Nitrite Concentration in the Striated Muscles Is Reversely Related to Myoglobin and Mitochondrial Proteins Content in Rats.Int J Mol Sci. 2022 Feb 28;23(5):2686. doi: 10.3390/ijms23052686. Int J Mol Sci. 2022. PMID: 35269826 Free PMC article.
References
-
- Brunori M, Nitric oxide, cytochrome-c oxidase and myoglobin, Trends Biochem Sci 26 (2001) 21–3. - PubMed
-
- Wittenberg JB, Wittenberg BA, Myoglobin-enhanced oxygen delivery to isolated cardiac mitochondria, J Exp Biol 210 (2007) 2082–90. - PubMed
-
- Garry DJ, Kanatous SB, Mammen PP, Emerging roles for myoglobin in the heart, Trends Cardiovasc Med 13 (2003) 111–6. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources