An uncoupler or uncoupling agent is a molecule that disrupts

oxidative phosphorylation Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine tri ...

prokaryotes A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...

and

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

or photophosphorylation in chloroplasts and

cyanobacteria Cyanobacteria (), also known as Cyanophyta, are a phylum of gram-negative bacteria that obtain energy via photosynthesis. The name ''cyanobacteria'' refers to their color (), which similarly forms the basis of cyanobacteria's common name, blu ...

by dissociating the reactions of ATP synthesis from the

electron transport chain An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...

. 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 ATP synthase is a protein that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). It is classified under ligases as it changes ADP by the formation ...

can recapture this energy and use it to make

ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals, men's professional tennis governing body * American Technical Publishers, employee-owned publishing company * ', a Danish pension * Armenia Tree Project, non ...

. 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 ( ATP synthesis, transhydrogenation, reverse electron flow, active transport of cations, etc.) 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 Pseudo-uncouplers show one or more of these properties, but not all, and thus must be combined with one or more other pseudo-uncouplers to achieve full uncoupling.

Classical uncouplers

The following compounds are known to be classical uncouplers: *

2,4-dinitrophenol 2,4-Dinitrophenol (2,4-DNP or simply DNP) is an organic compound with the formula HOC6H3(NO2)2. It is a yellow, crystalline solid that has a sweet, musty odor. It sublimates, is volatile with steam, and is soluble in most organic solvents as well ...

(DNP) * 2,5-di nitrophenol * 1799 (α,α′-bis(hexafluoracetonyl)acetone) *

BAM15 BAM15 is a novel mitochondrial protonophore uncoupler capable of protecting mammals from acute renal ischemic-reperfusion injury and cold-induced microtubule damage. References {{reflist External links Fat-fighting molecule sees the body burn ...

, ''N''⁵,''N''⁶-bis(2-fluorophenyl)-

,2,5 The comma is a punctuation mark that appears in several variants in different languages. It has the same shape as an apostrophe or single closing quotation mark () in many typefaces, but it differs from them in being placed on the baseline o ...

xadiazolo ,4-''b''yrazine-5,6-diamine * 2-''tert''-butyl-4,6-dinitrophenol (Dinoterb) * 6-''sec''-butyl-2,4-dinitrophenol (Dinoseb) * C₄R1 (a short-chain alkyl derivative of rhodamine 19) * Carbonyl cyanide phenylhydrazone (CCP) * Carbonyl cyanide ''m''-chlorophenyl hydrazone (CCCP) * Carbonyl cyanide-''p''-trifluoromethoxyphenyl hydrazone (FCCP) * CDE () (produced by Verbesina) * CZ5 * Desaspidin * Dicoumarol * Dinitro-''ortho''-cresol (DNOC) * Ellipticine * Endosidin 9 (ES9) * Flufenamic acid * Niclosamide ethanolamine (NEN) * Ppc-1 (a secondary metabolite produced by '' Polysphondylium pseudocandidum'') *

Pentachlorophenol Pentachlorophenol (PCP) is an organochlorine compound used as a pesticide and a disinfectant. First produced in the 1930s, it is marketed under many trade names. It can be found as pure PCP, or as the sodium salt of PCP, the latter of which diss ...

(PCP) *

Perfluorotriethylcarbinol Perfluorotriethylcarbinol is a perfluorinated alcohol. It is a powerful uncoupling agent and is toxic by inhalation. See also *Perfluorinated compound *Uncoupling agent An uncoupler or uncoupling agent is a molecule that disrupts oxidative phos ...

* S-13 (5-chloro-3-''t''-butyl-2′-chloro-4′-nitro salicylanilide) * SF 6847 (3,5-di-''t''-butyl-4-hydroxybenzylidine malononitrile) * TTFB (4,5,6,7-tetrachloro-2-trifluoromethyl benzimidazole) * Tyrphostin A9 (SF-6847) (AG17) * (+)-

usnic acid Usnic acid is a naturally occurring dibenzofuran derivative found in several lichen species with the formula C18H16O7. It was first isolated by German scientist W. Knop in 1844 and first synthesized between 1933-1937 by Curd and Robertson. Usnic a ...

XCT-790 XCT-790 is a potent and selective inverse agonist ligand of the estrogen-related receptor alpha (ERRα). Independent of its inhibition of ERRα, XCT-790 is a potent mitochondrial electron transport chain uncoupler. Mitochondrial electron transpo ...

* mitoFluo (10- -(3-hydroxy-6-oxo-xanthen-9-yl)benzoylxydecyl-triphenyl-phosphonium bromide) * Triclosan (Trichloro-2'-hydroxydiphenyl ether) * Pyrrolomycin C (produced by Genus Streptomyces) *

Salicylic acid Salicylic acid is an organic compound with the formula HOC6H4CO2H. A colorless, bitter-tasting solid, it is a precursor to and a metabolite of aspirin (acetylsalicylic acid). It is a plant hormone, and has been listed by the EPA Toxic Substance ...

(if taken in extreme excess)

Pseudo-uncouplers

The following compounds are known to be pseudo-uncouplers: *

Azide In chemistry, azide is a linear, polyatomic anion with the formula and structure . It is the conjugate base of hydrazoic acid . Organic azides are organic compounds with the formula , containing the azide functional group. The dominant applic ...

* Biguanides * Bupivacaine * Calcimycin ( A23187) * Dodecyltriphenyl phosphonium (C₁₂TPP) * Lasalocid (X537A) * Long-chain fatty acids, such as linoleic acid * MitoQ10 * Nigericin *

Picric acid Picric acid is an organic compound with the formula (O2N)3C6H2OH. Its IUPAC name is 2,4,6-trinitrophenol (TNP). The name "picric" comes from el, πικρός (''pikros''), meaning "bitter", due to its bitter taste. It is one of the most acidic ...

(2,4,6-trinitrophenol) * Sodium tetraphenylborate * SR4 (1,3-bis(dichlorophenyl)urea 13) * Tetraphenylphosphonium chloride * Valinomycin * Arsenate

Notes

References

External links

* Uncoupling agents Ionophores Respiratory toxins {{molecular-cell-biology-stub