Uncoupler
An uncoupler or uncoupling agent is a molecule that disrupts oxidative phosphorylation in prokaryotes and mitochondria or photophosphorylation in chloroplasts and cyanobacteria by dissociating the reactions of ATP synthesis from the electron transport chain. The result is that the cell or mitochondrion expends energy to generate a proton-motive force, but the proton-motive force is dissipated before the ATP synthase can recapture this energy and use it to make ATP. Because the intracellular supply of protons is replenished, uncouplers actually stimulate cellular metabolism and oxygen consumption and increase the energy cost of generating ATP. Uncouplers are capable of transporting protons through mitochondrial and lipid membranes.
Description
Classical uncouplers have five properties:- the complete release of respiratory control
- the substitution of all coupled processes by a cyclic proton transport mediated by the uncoupler
- the elimination of all protonic and cationic gradients generated across the mitochondrial or prokaryotic membrane
- no discrimination in these actions between one coupling site and another
- no discrimination between coupled processes driven by electron transfer and coupled processes driven by ATP hydrolysis
Classical uncouplers
The following compounds are known to be classical uncouplers:- 2,4-dinitrophenol
- 2,5-dinitrophenol
- 1799
- BAM15, N5,N6-bis-oxadiazolopyrazine-5,6-diamine
- 2-tert-butyl-4,6-dinitrophenol
- 6-sec-butyl-2,4-dinitrophenol
- C4R1
- Carbonyl cyanide phenylhydrazone
- Carbonyl cyanide m-chlorophenyl hydrazone
- Carbonyl cyanide-p-trifluoromethoxyphenyl hydrazone
- CDE
- Chlorfenapyr
- CZ5
- Desaspidin
- Dicoumarol
- Dinitro-ortho-cresol
- Ellipticine
- Endosidin 9
- Flufenamic acid
- Niclosamide ethanolamine
- Ppc-1
- Pentachlorophenol
- Perfluorotriethylcarbinol
- S-13
- TTFB
- Malonoben
- -usnic acid
- XCT-790
- mitoFluo
- Triclosan
- Pyrrolomycin C
- Salicylic acid
Pseudo-uncouplers
- Azide
- Biguanides
- Bupivacaine
- Calcimycin
- Dodecyltriphenylphosphonium
- Lasalocid
- Long-chain fatty acids, such as linoleic acid
- MitoQ10
- Nigericin
- Picric acid
- Sodium tetraphenylborate
- SR4
- Tetraphenylphosphonium chloride
- Valinomycin
- Arsenate