Cardiolipin modulates allosterically peroxynitrite detoxification by horse heart cytochrome c.
Abstract: Upon interaction with bovine heart cardiolipin (CL), horse heart cytochrome c (cytc) changes its tertiary structure disrupting the heme-Fe-Met80 distal bond, reduces drastically the midpoint potential out of the range required for its physiological role, binds CO and NO with high affinity, and displays peroxidase activity. Here, the effect of CL on peroxynitrite isomerization by ferric cytc (cytc-Fe(III)) is reported. In the absence of CL, hexa-coordinated cytc does not catalyze peroxynitrite isomerization. In contrast, CL facilitates cytc-Fe(III)-mediated isomerization of peroxynitrite in a dose-dependent fashion inducing the penta-coordination of the heme-Fe(III)-atom. The value of the second order rate constant for CL-cytc-Fe(III)-mediated isomerization of peroxynitrite (k(on)) is (3.2±0.4)×10(5) M(-1) s(-1). The apparent dissociation equilibrium constant for CL binding to cytc-Fe(III) is (5.1±0.8)×10(-5) M. These results suggest that CL-cytc could play either pro-apoptotic or anti-apoptotic effects facilitating lipid peroxidation and scavenging of reactive nitrogen species, such as peroxynitrite, respectively.
Copyright © 2010 Elsevier Inc. All rights reserved.
Publication Date: 2010-11-24 PubMed ID: 21110943DOI: 10.1016/j.bbrc.2010.11.091Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study investigates how cardiolipin, a lipid molecule present in the heart, affects the detoxification of peroxynitrite by cytochrome c, a protein found in the heart of horses. The researchers found that cardiolipin assists this process, suggesting that such interaction could have potential applications in controlling cell death and lipid peroxidation.
Study Background
- The research focuses on the interaction between bovine cardiolipin (CL), a crucial lipid of the mitochondrial inner membrane primarily found in heart tissue, and horse heart cytochrome c (cytc), a small heme protein involved in cell apoptosis.
- The authors previously found that interaction with CL prompts cytc to change its tertiary structure, allowing it to bind with carbon monoxide (CO) and nitric oxide (NO), and exhibit peroxidase activity—oxidizing harmful substances.
Methodology and Results
- In this experiment, the researchers studied the effect of CL on the isomerization—structural reconfiguration—of peroxynitrite by ferric cytc (cytc-Fe(III)). Peroxynitrite is a potent oxidant and nitrating agent that can contribute to cell injury during stress or disease.
- It was found that in the absence of CL, cytc cannot catalyze the isomerization of peroxynitrite, but when CL is available, it encourages this isomerization process.
- This facilitation of peroxynitrite isomerization by cytc-Fe(III) was observed to occur in a dose-dependent manner, meaning the more CL present, the more isomerization took place.
- Quantitative results revealed the second order rate constant for the isomerization process (k(on)) as well as the apparent dissociation equilibrium constant for CL binding to cytc-Fe(III), important parameters in the understanding of this chemical process.
Conclusions
- The study suggested that the interaction between CL and cytc has potential pro-apoptotic or anti-apoptotic effects. This could facilitate lipid peroxidation—a process that leads to cell damage—and the scavenging or neutralizing of reactive nitrogen species like peroxynitrite, which are harmful to cells.
- The findings hence may have potential implications in understanding and controlling cell death processes and oxidative stress in heart tissues.
Cite This Article
APA
Ascenzi P, Ciaccio C, Sinibaldi F, Santucci R, Coletta M.
(2010).
Cardiolipin modulates allosterically peroxynitrite detoxification by horse heart cytochrome c.
Biochem Biophys Res Commun, 404(1), 190-194.
https://doi.org/10.1016/j.bbrc.2010.11.091 Publication
Researcher Affiliations
- Department of Biology and Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, I-00146 Roma, Italy. ascenzi@uniroma3.it
MeSH Terms
- Allosteric Regulation
- Animals
- Cardiolipins / metabolism
- Cytochromes c / chemistry
- Cytochromes c / metabolism
- Horses
- Inactivation, Metabolic
- Myocardium / enzymology
- Peroxynitrous Acid / metabolism
- Protein Conformation
Citations
This article has been cited 14 times.- Turilli-Ghisolfi ES, Lualdi M, Fasano M. Ligand-Based Regulation of Dynamics and Reactivity of Hemoproteins. Biomolecules 2023 Apr 17;13(4).
- De Simone G, Coletta A, di Masi A, Coletta M, Ascenzi P. The Balancing of Peroxynitrite Detoxification between Ferric Heme-Proteins and CO(2): The Case of Zebrafish Nitrobindin. Antioxidants (Basel) 2022 Sep 28;11(10).
- Giordano D, Pesce A, Vermeylen S, Abbruzzetti S, Nardini M, Marchesani F, Berghmans H, Seira C, Bruno S, Javier Luque F, di Prisco G, Ascenzi P, Dewilde S, Bolognesi M, Viappiani C, Verde C. Structural and functional properties of Antarctic fish cytoglobins-1: Cold-reactivity in multi-ligand reactions. Comput Struct Biotechnol J 2020;18:2132-2144.
- Ascenzi P, De Simone G, Tundo GR, Platas-Iglesias C, Coletta M. Ferric nitrosylated myoglobin catalyzes peroxynitrite scavenging. J Biol Inorg Chem 2020 May;25(3):361-370.
- De Simone G, di Masi A, Polticelli F, Ascenzi P. Human nitrobindin: the first example of an all-β-barrel ferric heme-protein that catalyzes peroxynitrite detoxification. FEBS Open Bio 2018 Dec;8(12):2002-2010.
- Capdevila DA, Marmisollé WA, Tomasina F, Demicheli V, Portela M, Radi R, Murgida DH. Specific methionine oxidation of cytochrome c in complexes with zwitterionic lipids by hydrogen peroxide: potential implications for apoptosis. Chem Sci 2015 Jan 1;6(1):705-713.
- Ascenzi P, Pesce A. Peroxynitrite scavenging by Campylobacter jejuni truncated hemoglobin P. J Biol Inorg Chem 2017 Dec;22(8):1141-1150.
- Ascenzi P, di Masi A, Fanali G, Fasano M. Heme-based catalytic properties of human serum albumin. Cell Death Discov 2015;1:15025.
- Ascenzi P, Sbardella D, Santucci R, Coletta M. Cyanide binding to ferrous and ferric microperoxidase-11. J Biol Inorg Chem 2016 Jul;21(4):511-22.
- Ascenzi P, Sbardella D, Sinibaldi F, Santucci R, Coletta M. The nitrite reductase activity of horse heart carboxymethylated-cytochrome c is modulated by cardiolipin. J Biol Inorg Chem 2016 Jun;21(3):421-32.
- Ascenzi P, Marino M, Polticelli F, Santucci R, Coletta M. Cardiolipin modulates allosterically the nitrite reductase activity of horse heart cytochrome c. J Biol Inorg Chem 2014 Oct;19(7):1195-201.
- Ascenzi P, Coletta A, Cao Y, Trezza V, Leboffe L, Fanali G, Fasano M, Pesce A, Ciaccio C, Marini S, Coletta M. Isoniazid inhibits the heme-based reactivity of Mycobacterium tuberculosis truncated hemoglobin N. PLoS One 2013;8(8):e69762.
- Balakrishnan G, Hu Y, Spiro TG. His26 protonation in cytochrome c triggers microsecond β-sheet formation and heme exposure: implications for apoptosis. J Am Chem Soc 2012 Nov 21;134(46):19061-9.
- Kulikov AV, Shilov ES, Mufazalov IA, Gogvadze V, Nedospasov SA, Zhivotovsky B. Cytochrome c: the Achilles' heel in apoptosis. Cell Mol Life Sci 2012 Jun;69(11):1787-97.
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