In particular, the recoupling effect of 6-ketocholestanol (kCh) found earlier by Starkov and colleagues was tentatively considered as an evidence in favor of involvement of proteins in mitochondrial uncoupling mediated by such agents as carbonyl cyanide- m-chlorophenylhydrazone (CCCP), carbonyl cyanide p-trifluoromethoxy phenylhydrazone (FCCP) and tyrphostin A9 (SF6847). There is so far no consensus whether the uncoupling action occurs with or without the aid of membrane proteins, despite the general confidence in the protonophoric nature of this action. Although the experiments with uncouplers on artificial membranes, mitochondria and bacteria have played a crucial role in the validation of Mitchell’s chemiosmotic theory, the mechanism of uncoupling remains not fully understood. Compounds that compromise the coupling between respiration and phosphorylation called uncouplers have recently received strong interest as promising anti-cancer, antibacterial, anti-obesity, antidiabetic, neuroprotective and cardioprotective agents. It is now generally accepted that electron transfer via a chain of proton pumps in the inner mitochondrial or bacterial membrane results in the formation of a transmembrane difference of electrochemical potentials of hydrogen ions that couples the oxidation of respiratory substrates to ATP synthesis.
N5,N6-bis(2-fluorophenyl)oxadiazolopyrazine-5,6-diamine mitoCCCP,ġ0-(oxy)decyl(triphenyl)phosphonium bromide TPP,ġ-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine POPG,ġ-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol EggPC, This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the manuscript and its Supporting Information files.įunding: This work was financially supported by the Russian Science Foundation, grant number 16-14-10025.Ĭompeting interests: The authors have declared that no competing interests exist.Ĭarbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone CCCP,Ĭarbonyl cyanide 3-chlorophenylhydrazone SF6847 tyrphostin A9,ģ,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile DNP,
Received: JAccepted: DecemPublished: December 30, 2020Ĭopyright: © 2020 Iaubasarova et al. Dmitriev, University of Saskatchewan, CANADA (2020) The mitochondria-targeted derivative of the classical uncoupler of oxidative phosphorylation carbonyl cyanide m-chlorophenylhydrazone is an effective mitochondrial recoupler. Citation: Iaubasarova IR, Khailova LS, Firsov AM, Grivennikova VG, Kirsanov RS, Korshunova GA, et al.
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