The interactions of cetyltrimethylammonium with mitochondria: an uncoupler or a detergent?

Abstract

The interactions of cetyltrimethylammonium (CTA) with mitochondria have been investigated. We con®rm, as already observed in a previous paper, that this compound behaves as proton carrier (or uncoupler) of the oxidative phosphorylation, but evidences suggest that this compound enhances the membrane permeability to many other compounds such as sucrose. We conclude therefore that CTA as a detergent enhances membrane permeability to all ions including protons. Some evidences are also given that the inhibitory e ect of CTA on the mitochondrial respiratory chain is a consequence of the swelling induced. Ó

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

“…Assuming equal diffusion coefficients for C 12 TPP and C 16 TMA in the membrane core, it means that the rate constant for the transmembrane transfer of C 12 TPP is about 50 times higher than that for C 16 TMA. Such difference might, in principle, explain much lower activity of C 16 TMA than C 12 TPP in decreasing mitochondrial ΔΨ, if one assumes that C 16 TMA possesses some uncoupling effect (for discussion, see Bragadin et al, 2002). However, it seems more probable that the C 16 TMA-induced ΔΨ decrease is due to its inhibiting effect on the respiratory chain (Fig.…”

Prescription drugs and mitochondrial metabolism

“…rhodamine 19 derivatives), or may be due to induced permeability of the inner mitochondrial membrane to ions and polar uncharged solutes by molecules that lack dissociable protons such as quaternary amines (e.g. cetyltrimethylammonium) [ 66 , 67 ]. The inhibitory actions of organic cations may be due to competitive or non-competitive interactions with specific enzymes, which are potentiated by the high concentrations of compound that accumulate in the matrix [ 28 , 68 ].…”

Methylation of Phenyl Rings in Ester‐Stabilized Phosphorus Ylides Vastly Enhances Their Protonophoric Activity

“…The uncoupling of electron transfer from ATP synthesis in mitochondria may result from both protonophoric [36] and detergent effects of compounds. [37,38] The first is due to the cyclic movement of different forms of a protonophore in the inner mitochondrial membrane (Scheme 2), whereas the second is associated with disturbance of the barrier properties of the lipid membrane. Since the detergent effect of lipophilic ions increases with increasing lipophilicity, [37,[39][40][41] it is reasonable to expect an increase in their toxic effects.…”