A proposal for a new mechanism of interaction of trialkyltin (TAT) compounds with mitochondria

The interactions of trialkyltin (TAT) compounds with the mitochondria were largely studied The current view of this phenomenon is that these compounds, by exploiting the Cl- and OH- gradient in energised mitochondria, behave as electroneutral OH-/Cl- exchangers. Experiments performed with triethyltin-, tripropyltin-, and tributyltin-chloride, allow as to propose an alternative mechanism. The crucial point of this new mechanism is that TATs enter the mitochondria as lipophilic cations (alkyl)(3)Sn+ and not as electroneutral compounds. The influx is followed by extrusion of the trialkyltin compounds as electroneutral hydroxi compounds (alkyl)(3)Sn-OH. Measurements of membrane potential show that the uptake of the TAT cation (alkyl)(3)Sn+ is followed by membrane depolarisation measured as the release of the trimethylphenylphosphonium probe. The depolarization occurs in the order: (Et)(3)Sn-Cl < (Pro)(3)Sn-Cl < (Bu)(3)Sn-Cl in agreement with the increasing lipophilicity of the tested compounds from ethyltin toward butyltin derivative. The uptake of TAT induces the opening of a selective anionic channel which could explain the swelling of mitochondria observed in a chloride medium