Organotins as Mitochondrial Toxins
Pp. 112-124 (13)
Sabrina Manente, Alessandra Iero and Marcantonio Bragadin
In vitro toxicity, molecular study of the toxicity mechanisms, which should account for the observed in
vivo effects of toxic compounds, is a complicate issue. The study of organotin compounds is particularly
complicate, since organotins, being chemically versatile, are able to bind covalently and non-covalently to many
biomolecules; also organotins are soluble in lipophilic environments and can affect a wide variety of biological
functions. Therefore, it is difficult to identify the biological mechanism and the molecular target inhibited by the
lowest effective dose. In the interactions of organotin compounds with mitochondria, the problem is “simplified”
since many organotins cause in vivo acute toxicity. Being mitochondria the energy source of the cell,
mitochondrial impairment induces cell damage; therefore, in many cases, mitochondria are the molecular target
responsible for the in vivo acute toxicity. On these bases, ATP synthesis mechanism in mitochondria should be
carefully analysed, in order to individuate the step(s) inhibited by the toxic compounds. Many organotin effects
on the mitochondrial functions are correlated with the ATP synthesis inhibition. In isolated mitochondria, the
(alkyl)3-Sn- compounds inhibit all the steps involved in the ATP synthesis mechanism, but experiments
performed in isolated cells suggest that the mitochondrial ATP synthesis inhibition is probably related to the
opening of the membrane permeability transition pore. In addition, also triphenyltin opens the permeability
transition pore and triggers apoptosis. Other putative and proven mechanisms of organotin action in mitochondria
are considered in detail.
Organotin - mitochondria - membrane permeability transition pore (MPTP) - protonophores - ATP
synthesis inhibition - mitochondrial respiratory chain (MRC).
Department of Environmental Sciences, Ca Foscari University, Calle Larga S. Marta 2137, Dorsoduro 30123 Venice, Italy.