A protonophore, also known as a proton translocator, is an

ionophore In chemistry, an ionophore () is a chemical species that reversibly binds ions. Many ionophores are lipid-soluble entities that transport ions across the cell membrane. Ionophores catalyze ion transport across hydrophobic membranes, such as liq ...

that moves

proton A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron mass ...

s across

lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...

s or other type of membranes. This would otherwise not occur as protons cations (H⁺) have

positive charge Electric charge is the physical property of matter that causes charged matter to experience a force when placed in an electromagnetic field. Electric charge can be ''positive'' or ''negative'' (commonly carried by protons and electrons respectiv ...

and

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are no ...

properties, making them unable to cross without a

channel Channel, channels, channeling, etc., may refer to: Geography * Channel (geography), in physical geography, a landform consisting of the outline (banks) of the path of a narrow body of water. Australia * Channel Country, region of outback Austral ...

or transporter in the form of a protonophore. Protonophores are generally aromatic compounds with a negative charge, that are both

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, th ...

and capable of distributing the negative charge over a number of atoms by π- orbitals which delocalize a proton's charge when it attaches to the molecule. Both the neutral and the charged protonophore can diffuse across the lipid bilayer by passive diffusion and simultaneously facilitate proton transport. Protonophores uncouple oxidative phosphorylation via a decrease in the membrane potential of the inner membrane of mitochondria. They stimulate mitochondria respiration and heat production. Protonophores (uncouplers) are often used in biochemistry research to help explore the bioenergetics of chemiosmotic and other membrane transport processes. It has been reported that the protonophore has antibacterial activity by perturbing bacterial proton motive force. Representative anionic protonophores include: * 2,4-dinitrophenol *

Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone Carbonyl cyanide-''p''-trifluoromethoxyphenylhydrazone (FCCP) is an ionophore that is a mobile ion carrier. It is referred to as an uncoupling agent because it disrupts ATP synthesis by transporting hydrogen ions through the mitochondrial me ...

(FCCP) *

Carbonyl cyanide m-chlorophenyl hydrazone Carbonyl cyanide ''m''-chlorophenyl hydrazone (CCCP; also known as 3-chlorophenyl)hydrazonoalononitrile) is a chemical inhibitor of oxidative phosphorylation. It is a nitrile, hydrazone and protonophore. In general, CCCP causes the gradual de ...

(CCCP) Representative cationic protonophores include: * C4R1 (a short-chain alkyl derivative of rhodamine 19) * Ellipticine Representative zwitterionic protonophores include: * mitoFluo (10-

-(3-hydroxy-6-oxo-xanthen-9-yl)benzoyl The hyphen-minus is the most commonly used type of hyphen, widely used in digital documents. It is the only character that looks like a minus sign or a dash in many character sets such as ASCII or on most keyboards, so it is also used as such. ...

xydecyl-triphenyl-phosphonium bromide) * PP6 (2-(2-Hydroxyaryl)hexylphosphonium bromide)

Mechanism of action

The facilitated transport of protons across the biological membrane by anionic protonophore is achieved as follows.{{cite journal , vauthors=Ozaki S, Kano K, Shirai O , title=Electrochemical elucidation on the mechanism of uncoupling caused by hydrophobic weak acids , journal=Phys Chem Chem Phys , volume=10 , issue=30 , pages=4449–55 , date=August 2008 , pmid=18654685 , doi=10.1039/b803458c , bibcode=2008PCCP...10.4449O # The anionic form of the protonophore (P⁻) is adsorbed onto one side (Positive) of the biological membrane. # Protons (H⁺) from the aqueous solution combine with the anion (P⁻) to produce the neutral form (PH) # PH diffuses across the biological membrane and dissociates into H⁺ and P⁻ on the other side. # This H⁺ is released from the biological membrane into the other aqueous solution # P⁻ returns to the first side of the biological membrane by electrophoresis (its electrostatic attraction to the positive side of the membrane).

References

Ionophores Proton

Mechanism of action

See also

References