A protonophore, also known as a proton translocator, is an ionophore that moves protons across lipid bilayers. This would otherwise not occur as protons cations (H+) have positive charge and hydrophilic properties, making them unable to cross without a channel or transporter in the form of a protonophore. Protonophores are generally aromatic compounds with a negative charge, that are both hydrophobic 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.[1][2] Both the neutral and the charged protonophore can diffuse across the lipid bilayer by passive diffusion and simultaneously facilitate proton transport.[3] 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.[4]

Representative protonophores include:

Mechanism of action

The facilitated transport of protons across the biological membrane by protonophore is achieved as follows.[5]

  1. The anionic form of the protonophore (P) is adsorbed onto one side (Positive) of the biological membrane.
  2. Protons (H+) from the aqueous solution combine with the anion (P) to produce the neutral form (PH)
  3. PH diffuses across the biological membrane and dissociates into H+ and P on the other side.
  4. This H+ is released from the biological membrane into the other aqueous solution
  5. P returns to the first side of the biological membrane by electrophoresis (its electrostatic attraction to the positive side of the membrane).

See also


  1. (accessed 19th Nov 2008)
  2. Nicholls, David G. & Ferguson, Stuart J. (2002). Bioenergetics 3. London: Academic Press. ISBN 978-0-12-518121-1.
  3. Chopineaux-Courtois V, Reymond F, Bouchard G, Carrupt PA, Testa B, Girault HH (February 1999). "Effects of Charge and Intramolecular Structure on the Lipophilicity of Nitrophenols". J. Am. Chem. Soc. 121 (8): 1743–1747. doi:10.1021/ja9836139.
  4. Tharmalingam N, Jayamani E, Rajamuthiah R, Castillo D, Fuchs BB, Kelso MJ, Mylonakis E (2017). "Activity of a novel protonophore against methicillin-resistant Staphylococcus aureus". Future Med. Chem. 9 (12): 1401–1411. doi:10.4155/fmc-2017-0047. PMC 5941710. PMID 28771026.
  5. Ozaki S, Kano K, Shirai O (August 2008). "Electrochemical elucidation on the mechanism of uncoupling caused by hydrophobic weak acids". Phys Chem Chem Phys. 10 (30): 4449–55. Bibcode:2008PCCP...10.4449O. doi:10.1039/b803458c. PMID 18654685.
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