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MitoPedia: Uncouplers
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- » Definition: Uncoupler (U)
Term | Abbreviation | Description |
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BAM15 | BAM15 | 2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine (BAM15) is a protonophore or uncoupler of oxidative phosphorylation detected in a screen for uncoupling agents exerting less toxicity than commonly used uncouplers and first described by Kennwood et al. 2013. In their comparison of BAM15 with FCCP it was shown to increase oxygen flux to a similar extent as the classical uncoupler, to display a much broader range of concentrations inducing maximum respiration, to stimulate no formation of H2O2, to leave cellular membrane potential unaffected, and to ultimately exert less cytotoxicity. |
Carbonyl cyanide m-chlorophenyl hydrazone | CCCP | Carbonyl cyanide m-chlorophenyl hydrazone, CCCP (U; C9H5ClN4; FW = 204.62) is a protonophore (H+ ionophore) and is used as a potent chemical uncoupler of oxidative phosphorylation. Like all uncouplers, CCCP concentrations must be titrated carefully to evaluated the optimum concentration for maximum stimulation of mitochondrial respiration, particularly to avoid inhibition of respiration at higher CCCP concentrations. |
Dinitrophenole | DNP | 2,4-dinitrophenole (C6H4N2O5; M = 184.11 g·mol-1) is a protonophore acting as an uncoupler of oxidative phosphorylation. |
ET capacity | E | ![]() |
FCCP | FCCP | FCCP (Carbonyl cyanide p-trifluoro-methoxyphenyl hydrazone, C10H5F3N4O) is a protonophore or uncoupler: added at uncoupler concentration Uc; c is the optimum uncoupler concentration in titrations to obtain maximum mitochondrial respiration in the noncoupled state of ET capacity. |
Metabolic control variable | X | A metabolic control variable X causes the transition between a background state Y (background rate YX) and a reference state Z (reference rate ZX). X may be a stimulator or activator of flux, inducing the step change from background to reference steady state (Y to Z). Alternatively, X may be an inhibitor of flux, absent in the reference state but present in the background state (step change from Z to Y). |
Noncoupled respiration | E | ![]() Noncoupled respiration is maximum electron flow in an open-transmembrane proton circuit mode of operation (see ET capacity). » MiPNet article |
Perfluorooctanoic acid | PFOA | Perfluorooctanoic acid (PFOA) is a metabolically inert perfluorinated fatty acid which activates UCP1 in brown-fat mitochondria. UCP1-dependent respiration can be stimulated with 600 μM PFOA after inhibition of the phosphorylation system. |
Preparation of SUIT chemicals | Preparation of SUIT chemicals describes the preparation of chemicals used in Substrate-Uncoupler-Inhibitor Ttitration (SUIT) protocols. | |
Proton slip | Proton slip is a property of the proton pumps (Complexes CI, CIII, and CIV) when the proton slips back to the matrix side within the proton pumping process. Slip is different from the proton leak, which depends on Δp and is a property of the inner mt-membrane (including the boundaries between membrane-spanning proteins and the lipid phase). Slip is an uncoupling process that depends mainly on flux and contributes to a reduction in the biochemical coupling efficiency of ATP production and oxygen consumption. Together with proton leak and cation cycling, proton slip is compensated for by LEAK respiration or LEAK oxygen flux, L. Compare: Proton leak. | |
SF6847 | SF6847 | SF6847 (C18H22N2O), also known as tyrphostin A9 or malonoben, is a protonophore and a very potent uncoupler of oxidative phosphorylation, being used in the nM range. Like all uncouplers, SF6847 concentrations must be titrated carefully to evaluate the optimum concentration for maximum stimulation of mitochondrial respiration, particularly to avoid inhibition of respiration at higher concentrations. |
State 3u | E | ![]() |
Substrate-uncoupler-inhibitor titration | SUIT | Mitochondrial Substrate-uncoupler-inhibitor titration (SUIT) protocols are used with mitochondrial preparations to study respiratory control in a sequence of coupling and substrates states induced by multiple titrations within a single experimental assay. |
Tetrachloro-2-trifluoromethylbenzimidazole | TTFB | 4,5,6,7-Tetrachloro-2-trifluoromethylbenzimidazole is a protonophore or uncoupler of oxidative phosphorylation. |
Uncoupler | U | An uncoupler is a protonophore (CCCP, FCCP, DNP) which cycles across the inner mt-membrane with transport of protons and dissipation of the electrochemical proton gradient. Mild uncoupling may be induced at low uncoupler concentrations, the noncoupled state of ET capacity is obtained at optimum uncoupler concentration for maximum flux, whereas at higher concentrations an uncoupler-induced inhibition is observed. |
Uncoupler titrations | In uncoupler titrations various uncouplers, such as CCCP, FCCP or DNP are applied to uncouple mitochondrial electron transfer from phosphorylation (ATP synthase, ANT and phosphate carrier), particularly with the aim to measure ET capacity. ET capacity is maximum oxygen flux measured as noncoupled respiration with optimum uncoupler concentration. | |
Uncoupling protein 1 | UCP1 | Uncoupling protein 1 (UCP1) is also called thermogenin and is predominantly found in brown adipose tissue (BAT). UCP1 belongs to the gene family of uncoupling proteins. It is vital for the maintenance of body temperature, especially for small mammals. As the essential component of non-shivering thermogenesis, it possesses the ability to build and open a pore in the inner mitochondrial membrane through which protons may flow along their electrochemical gradient, generated by respiration, bypassing the ATP-producing re-entry site at the F1F0-ATP synthase. Thereby the energy stored in the electrochemical gradient is dissipated as heat. |
Uncoupling protein 2 | UCP2 | Uncoupling protein 2 (UCP2) belongs to the gene family of uncoupling proteins. Whereas UCP1 acts as an uncoupler, this may not be the case for UCP2. |
Uncoupling proteins | UCP | Uncoupling proteins (UCPs) are mitochondrial anion carrier proteins that can be found in the inner mitochondrial membranes of animals and plants. UCP1 acts as an uncoupler by dissipating the electrochemical proton gradient (mitochondrial membrane potential), generated by the electron transfer pathway by pumping protons from the mitochondrial matrix to the mitochondrial intermembrane space. |