Cardiolipin Switch in Mitochondria: Shutting off the Reduction of Cytochrome c and Turning on the Peroxidase Activity
Open accessAbstract
Upon interaction with anionic phospholipids, particularly mitochondria-specific cardiolipin (CL), cytochrome c (cyt c) loses its tertiary structure and its peroxidase activity dramatically increases. CL-induced peroxidase activity of cyt c has been found to be important for selective CL oxidation in cells undergoing programmed death. During apoptosis, the peroxidase activity and the fraction of CL-bound cyt c markedly increase, suggesting that CL may act as a switch to regulate cyt c's mitochondrial functions. Using cyclic voltammetry and equilibrium redox titrations, we show that the redox potential of cyt c shifts negatively by 350-400 mV upon binding to CL-containing membranes. Consequently, functions of cyt c as an electron transporter and cyt c reduction by Complex III are strongly inhibited. Further, CL/cyt c complexes are not effective in scavenging superoxide anions and are not effectively reduced by ascorbate. Thus, both redox properties and functions of cyt c change upon interaction with CL in the mitochondrial membrane, diminishing cyt c's electron donor/acceptor role and stimulating its peroxidase activity.
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In cytochrome c, transition from hexa- to pentacoordination is induced by Met-80 oxidation, Tyr-67 nitration, and interaction with anionic lipids such as cardiolipin.
“In the case of cytochrome c, transition from hexa- to pentacoordination has been shown to be induced by Met-80 oxidation [77], Tyr-67 nitration [78] and by interaction with anionic lipids such as cardiolipin [79].”
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 [79]
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Flagged first, then by citations
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- Authors
- Basova, L. V., Kurnikov, I. V., Wang, L., Ritov, V. B., Belikova, N. A., Vlasova, I. I., Pacheco, A. A., Winnica, D. E., Peterson, J., Bayir, H., Waldeck, D. H., & Kagan, V. E.
- Affiliations
- University of Pittsburgh (US)
- Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, Department of Chemistry, and Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, and Department of Chemistry, University of WisconsinMilwaukee, Milwaukee, Wisconsin 53211
- Corresponding author
- Kagan, Valerian E.
- ORCID
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2007-02-24
- Volume
- 46
- Issue
- 11
- Pages
- 3423-3434
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- PMC
- PMC3356783
- OpenAlex
- W1970607230
- Cited by
- 212
- References
- 64
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 8 · 2023: 7 · 2022: 8 · 2021: 7 · 2020: 5 · 2019: 11 · 2018: 11 · 2017: 13 · 2016: 14 · 2015: 16 · 2014: 15 · 2013: 17 · 2012: 7
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-70755, HL-61411, R01HL061411, R01HL070755)
- National Institute of Allergy and Infectious Diseases (U19AI068021)
- National Institute for Occupational Safety and Health (R01 OH008282, OH008282)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- cardiolipin, cytochrome c, peroxidase activity, redox potential, mitochondrial membrane, apoptosis, cytochrome bc1 complex, electron transport, superoxide radical scavenging, anionic phospholipids, protein-lipid interactions, programmed cell death
- MeSH terms
- Animals, Ascorbic Acid, Cardiolipins, Electron Transport Complex IV, Electrochemistry, Electron Spin Resonance Spectroscopy, Liposomes, Male, Mitochondria, Liver, Oxidation-Reduction, Peroxidases, Rats, Sprague-Dawley, Cytochromes c, Rats
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