Interaction of Tetraphenylphosphonium and Dodecyltriphenylphosphonium with Lipid Membranes and Mitochondria

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T. A. Trendeleva¹, A. G. Rogov¹, D. A. Cherepanov², E. I. Sukhanova¹, T. M. Il’yasova³, I. I. Severina³, and R. A. Zvyagilskaya^1*

¹Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky pr. 33, 119071 Moscow, Russia; fax: (495) 954-2732; E-mail: renata_z@inbi.ras.ru

²Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninsky pr. 31, 119991 Moscow, Russia; fax: (495) 952-5308

³Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia; fax: (495) 939-0338

^* To whom correspondence should be addressed.

Received May 28, 2012

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The permeability of a planar lipid membrane (composed of diphytanoylphosphatidylcholine) for tetraphenylphosphonium (TPP) was investigated. The observed level of the diffusion potential generated as a function of the TPP concentration gradient differed from the theoretically expected value, possibly due to proton leakage of the membrane mediated by the traces of fatty acids in the phospholipid forming the membrane. Using the molecular dynamics approach to study movement of TPP and dodecyltriphenylphosphonium (C₁₂TPP) with different affinity to the lipid bilayer through a bilayer lipid membrane, it was found that C₁₂TPP has a greater affinity to the membrane surface than TPP. However, the two cations have the same activation energy for transmembrane transfer. Interaction of TPP and C₁₂TPP with tightly-coupled mitochondria from the yeast Yarrowia lipolytica was also investigated. At low, micromolar concentrations, both cations are “relatively weak, mild uncouplers”, do not shunt electron transfer along the respiratory chain, do not disturb (damage) the inner mitochondrial membrane, and profoundly promote the uncoupling effect of fatty acids. At higher concentrations they inhibit respiration in state 3, and at much higher concentrations they induce swelling of mitochondria, possibly due to their detergent action.

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KEY WORDS: TPP, C₁₂TPP, diffusion potential, movement through lipid bilayer, yeast, Yarrowia lipolytica, mitochondria, fatty acids

DOI: 10.1134/S000629791209009X

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