Structural transformations of cytochrome c upon interaction with cardiolipin
Open accessAbstract
Interactions of cytochrome c (cyt c) with cardiolipin (CL) play a critical role in early stages of apoptosis. Upon binding to CL, cyt c undergoes changes in secondary and tertiary structure that lead to a dramatic increase in its peroxidase activity. Insertion of the protein into membranes, insertion of CL acyl chains into the protein interior, and extensive unfolding of cyt c after adsorption to the membrane have been proposed as possible modes for interaction of cyt c with CL. Dissociation of Met80 is accompanied by opening of the heme crevice and binding of another heme ligand. Fluorescence studies have revealed conformational heterogeneity of the lipid-bound protein ensemble with distinct polypeptide conformations that vary in the degree of protein unfolding. We correlate these recent findings to other biophysical observations and rationalize the role of experimental conditions in defining conformational properties and peroxidase activity of the cyt c ensemble. Latest time-resolved studies propose the trigger and the sequence of cardiolipin-induced structural transitions of cyt c.
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During early apoptosis, cytochrome c changes conformation through interactions with cardiolipin, contributing to cytosolic cytochrome c release and caspase activation.
“Furthermore, during early apoptosis, cytochrome c undergoes conformational changes owing to interactions with cardiolipin, contributing to the subsequent cytosolic release of cytochrome c and caspase activation194.”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [194]
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Investigation of the Lipid Dependence of Respiratory Complex IV Activation Using Nanoscale Bilayers
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- Authors
- Muenzner, J., & Pletneva, E. V.
- Affiliations
- Dartmouth College (US)
- Corresponding author
- Pletneva, Ekaterina V.
- Venue
- Chemistry and Physics of Lipids
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 179
- Pages
- 57-63
- ISSN
- 0009-3084 (ISSN-L)
- PMC
- PMC3979421
- OpenAlex
- W2049774523
- Cited by
- 74
- References
- 105
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 6 · 2018: 5 · 2017: 13 · 2016: 5 · 2015: 9 · 2014: 3 · 2013: 1
- FWCI
- 0.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Chemistry and Physics of Lipids (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (RO1 - GM098502)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- cytochrome c, cardiolipin, protein-lipid interactions, apoptosis, peroxidase activity, protein unfolding, conformational heterogeneity, heme crevice, membrane insertion, time-resolved spectroscopy
- MeSH terms
- Animals, Cardiolipins, Cell Membrane Permeability, Free Radicals, Heme, Humans, Protein Binding, Cytochromes c
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