MitoCLox: A Novel Mitochondria-Targeted Fluorescent Probe for Tracing Lipid Peroxidation

Lyamzaev, K.G.; Sumbatyan, N.V.; Nesterenko, A.M.; Kholina, E.G.; Natalia, V.; Heinz-Jürgen, S.; Mulkidjanian, A.Y.; Chernyak, B.V.

Авторы: Lyamzaev Konstantin G., Sumbatyan Natalia V., Nesterenko Alexey M., Kholina Ekaterina G., Natalia Voskoboynikova, Heinz-Jürgen Steinhoff, Mulkidjanian Armen Y., Chernyak Boris V.
Журнал: Oxidative Medicine and Cellular Longevity
Том: 2019
Год издания: 2019
Издательство: Landes Bioscience
Местоположение издательства: United States
Первая страница: 9710208
DOI: 10.1155/2019/9710208
Аннотация: Peroxidation of cardiolipin (CL) in the inner mitochondrial membrane plays a key role in the development of various pathologies and, probably, aging. The four fatty acid tails of CL are usually polyunsaturated, which makes CL particularly sensitive to peroxidation. Peroxidation of CL is involved in the initiation of apoptosis, as well as in some other important cellular signaling chains. However, the studies of CL peroxidation are strongly limited by the lack of methods for its tracing in living cells. We have synthesized a new mitochondria-targeted fluorescent probe sensitive to lipid peroxidation (dubbed MitoCLox), where the BODIPY fluorophore, carrying a diene-containing moiety (as in the C11-BODIPY (581/591) probe), is conjugated with a triphenylphosphonium cation (TPP+) via a long flexible linker that contains two amide bonds. The oxidation of MitoCLox could be measured either as a decrease of absorbance at 588 nm or as an increase of fluorescence in the ratiometric mode at 520/590 nm (emission). In CL-containing liposomes, MitoCLox oxidation was induced by cytochrome c and developed in parallel with cardiolipin oxidation. TPP+-based mitochondria-targeted antioxidant SkQ1, in its reduced form, inhibited oxidation of MitoCLox concurrently with the peroxidation of cardiolipin. Molecular dynamic simulations of MitoCLox in a cardiolipin-containing membrane showed affinity of positively charged MitoCLox to negatively charged CL molecules; the oxidizable diene moiety of MitoCLox resided on the same depth as the cardiolipin lipid peroxides. We suggest that MitoCLox could be used for monitoring CL oxidation in vivo and, owing to its flexible linker, also serve as a platform for producing peroxidation sensors with affinity to particular lipids.
Добавил в систему: Лямзаев Константин Геннадьевич

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MitoCLox: A Novel Mitochondria-Targeted Fluorescent Probe for Tracing Lipid Peroxidationстатья

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