Mitochondrial ATP Synthase and Mild Uncoupling by Butyl Ester of Rhodamine 19, C4R1

Zorova, L.D.; Pevzner, I.B.; Khailova, L.S.; Korshunova, G.A.; Kovaleva, M.A.; Kovalev, L.I.; Serebryakova, M.V.; Silachev, D.N.; Sudakov, R.V.; Zorov, S.D.; Rokitskaya, T.I.; Popkov, V.A.; Plotnikov, E.Y.; Antonenko, Y.N.; Zorov, D.B.

Авторы: Zorova Ljubava D., Pevzner Irina B., Khailova Ljudmila S., Korshunova Galina A., Kovaleva Marina A., Kovalev Leonid I., Serebryakova Marina V., Silachev Denis N., Sudakov Roman V., Zorov Savva D., Rokitskaya Tatyana I., Popkov Vasily A., Plotnikov Egor Y., Antonenko Yuri N., Zorov Dmitry B.
Журнал: ANTIOXIDANTS
Том: 12
Номер: 3
Год издания: 2023
Первая страница: 646
DOI: 10.3390/antiox12030646
Аннотация: The homeostasis of the transmembrane potential of hydrogen ions in mitochondria is a prerequisite for the normal mitochondrial functioning. However, in different pathological conditions it is advisable to slightly reduce the membrane potential, while maintaining it at levels sufficient to produce ATP that will ensure the normal functioning of the cell. A number of chemical agents have been found to provide mild uncoupling; however, natural proteins residing in mitochondrial membrane can carry this mission, such as proteins from the UCP family, an adenine nucleotide translocator and a dicarboxylate carrier. In this study, we demonstrated that the butyl ester of rhodamine 19, C4R1, binds to the components of the mitochondrial ATP synthase complex due to electrostatic interaction and has a good uncoupling effect. The more hydrophobic derivative C12R1 binds poorly to mitochondria with less uncoupling activity. Mass spectrometry confirmed that C4R1 binds to the β-subunit of mitochondrial ATP synthase and based on molecular docking, a C4R1 binding model was constructed suggesting the binding site on the interface between the α- and β-subunits, close to the anionic amino acid residues of the β-subunit. The association of the uncoupling effect with binding suggests that the ATP synthase complex can provide induced uncoupling.
Добавил в систему: Зорова Любава Дмитриевна

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Mitochondrial ATP Synthase and Mild Uncoupling by Butyl Ester of Rhodamine 19, C4R1статья