Molecular Dynamics Modeling of the Interaction of Cationic Fluorescent Lipid Peroxidation-Sensitive Probes with the Mitochondrial Membrane

Cardiolipin (CL) plays a central role in lipid peroxidation (LPO) of the mitochondrial inner membrane due to higher content of unsaturated fatty acids in CL in comparison with the other phospholipids. CL oxidation plays an important role in the regulation of various intracellular signaling pathways...

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Bibliographic Details
Published in:Doklady. Biochemistry and biophysics 2019-05, Vol.486 (1), p.220-223
Main Authors: Nesterenko, A. M., Kholina, E. G., Lyamzaev, K. G., Mulkidjanian, A. Ya, Chernyak, B. V.
Format: Article
Language:English
Subjects:
Aging
Antioxidants
Biochemistry
Biological and Medical Physics
Biomedical and Life Sciences
Biophysics
Cardiolipin
Fatty acids
Fluorescent indicators
Intracellular signalling
Life Sciences
Lipid peroxidation
Mitochondria
Molecular Biology
Oxidation
Peroxidation
Phospholipids
Probes
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Summary:Cardiolipin (CL) plays a central role in lipid peroxidation (LPO) of the mitochondrial inner membrane due to higher content of unsaturated fatty acids in CL in comparison with the other phospholipids. CL oxidation plays an important role in the regulation of various intracellular signaling pathways and its excessive oxidation contributes to the development of various pathologies and, possibly, participates in the aging process. Mitochondria-targeted antioxidants containing triphenylphosphonium (TPP + ) effectively protect CL from oxidation. It is assumed that fluorescent probes on the basis of the C11-BODIPY fluorophore sensitive to LPO and containing TPP + can selectively register CL oxidation. To test this possibility, we carried out a molecular dynamic simulation of such probes in a model mitochondrial membrane. It is shown that the probes are located in the membrane at the same depth as the unsaturated bonds in CL molecules sensitive to oxidation. Increasing the length of the linker that binds the fluorophore and TPP + residue ha little effect on the position of the probe in the membrane. This indicates the possibility of modifying the linker to increase the selectivity of the probes to CL.
ISSN:1607-6729
1608-3091
DOI:10.1134/S1607672919030153