Open AccessMolecular dynamics modeling of the interaction of cationic fluorescent lipid peroxidation-sensitive probes with the mitochondrial membrane
Author(s) -
Alexey M. Nesterenko,
Ekaterina G. Kholina,
Konstantin G. Lyamzaev,
A. Y. Mulkidzhanyan,
Boris V. Chernyak
Publication year - 2019
Publication title -
doklady akademii nauk. rossijskaâ akademiâ nauk
Language(s) - English
Resource type - Journals
ISSN - 0869-5652
DOI - 10.31857/s0869-56524864509-513
Subject(s) - fluorophore , cardiolipin , chemistry , membrane , inner mitochondrial membrane , biophysics , linker , mitochondrion , fluorescence , lipid peroxidation , intracellular , biochemistry , phospholipid , biology , oxidative stress , quantum mechanics , computer science , physics , operating system
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 cation (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 has 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.