Role of charge screening and delocalization for lipophilic cation permeability of model and mitochondrial membranes

Mitochondrion. 2013 Sep;13(5):500-6. doi: 10.1016/j.mito.2012.10.006. Epub 2012 Oct 17.


The effects of the mitochondria-targeted lipophilic cation dodecyltriphenylphosphonium (C12TPP, the charge is delocalized and screened by bulky hydrophobic residues) and those of lipophilic cations decyltriethylammonium bromide and cetyltrimethylammonium bromide (C10TEA and C16TMA, the charges are localized and screened by less bulky residues) on bilayer planar phospholipid membranes and tightly-coupled mitochondria from the yeast Yarrowia lipolytica have been compared. In planar membranes, C12TPP was found to generate a diffusion potential as if it easily penetrates these membranes. In the presence of palmitate, C12TPP induced H(+) permeability like plastoquinonyl decyltriphenilphosphonium that facilitates transfer of fatty acid anions (Severin et al., PNAS, 2010, 107, 663-668). C12TPP was shown to stimulate State 4 respiration of mitochondria and caused a mitochondrial membrane depolarization with a half-maximal effect at 6μM. Besides, C12TPP profoundly potentiated the uncoupling effect of endogenous or added fatty acids. C10TEA and C16TMA inhibited State 4 respiration and decreased the membrane potential, though at much higher concentrations than C12TPP, and they did not promote the uncoupling action of fatty acids. These relationships were modeled by molecular dynamics. They can be explained by different membrane permeabilities for studied cations, which in turn are due to different availabilities of the positive charge in these cations to water dipoles.

Keywords: 10-(6′-plastoquinonyl)decyl triphenylphosphonium; ANT; BLM; BSA; C(10)TEA; C(12)TPP; C(16)TMA; CCCP; Mitochondria; Mitochondria-targeted antioxidants; Molecular dynamics; Penetrating ions; SkQ1; TPB; TPP; Yeast; adenine nucleotide translocase; bilayer planar phospholipid membrane; bovine serum albumin; carbonyl cyanide 3-chlorophenylhydrazone; cetyltrimethylammonium; decyltriethylammonium; dodecyltriphenylphosphonium; tetraphenylborate; tetraphenylphosphonium; transmembrane electric potential difference; ΔΨ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cations / chemistry
  • Cations / metabolism*
  • Cell Respiration / drug effects
  • Cetrimonium
  • Cetrimonium Compounds / chemistry
  • Cetrimonium Compounds / metabolism*
  • Fatty Acids / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Membranes / metabolism*
  • Mitochondrial Membranes / metabolism*
  • Models, Chemical
  • Organophosphorus Compounds / chemistry
  • Organophosphorus Compounds / metabolism*
  • Permeability*
  • Quaternary Ammonium Compounds / chemistry
  • Quaternary Ammonium Compounds / metabolism*
  • Yarrowia


  • Cations
  • Cetrimonium Compounds
  • Fatty Acids
  • Organophosphorus Compounds
  • Quaternary Ammonium Compounds
  • dodecyltriphenylphosphonium
  • N,N,N-triethyl-1-dodecylammonium
  • Cetrimonium