Organotin Effects on Membrane-Bound ATPase Activities

The structural properties of organotins, mainly consisting of an electrophilic tin core and from one-to four lipophilic organic arms, make these synthetic compounds chemically versatile. By binding both covalently and non-covalently to biomolecules, organotins affect a wide variety of biological functions, according to their structure. Such properties justified their wide exploitation as biocides and drugs. Unfortunately, after less than one century from organotin synthesis and subsequent diffusion, unexpected events came out. The high organotin toxicity to non-target species and the environmental persistency caused worldwide pollution and concern in spite of restrictions and bans. The organic moiety lipophilicity facilitates contaminant incorporation in biological membranes, in turn triggering changes in membrane chemical-physical state and function. Literature and research data on organotin effects on membrane-bound ATPase activities, including P-type, F-type and V-type ATPases are here reviewed. The involvement in crucial cell functions such as membrane transport and ionic regulation as well as energy metabolism make ATPase complexes an intriguing model to approach organotin effects from a molecular point of view. Their interaction with organotins may represent one of the molecular mechanisms of the widespread perturbations in contaminated animals. Among ATPases, the ubiquitous plasma membrane Na,K-ATPase, the coexistent stepsister ouabain-insensitive Na-ATPase and finally FOF1 complexes in eucaryotes and prokaryotes are considered in detail. Special attention is paid to trisubstituted alkyltins and aryltins, highly toxic to living systems and especially to mitochondria. Trisubstituted derivatives are enclosed among mitochondrial poisons as they act as uncouplers and also directly inhibit the ATPase/synthase. Most studies were carried out on mammals, yeasts and bacteria. Recent research data from our laboratory exploring the effect of tributyltin (TBT) on molluscan Na,K-ATPase, Na-ATPase and mitochondrial ATPase activities are reported. Kinetic studies suggest that the mechanism of TBT interaction may differ according to the ATPase under study. TBT binding to enzyme proteins may involve multiple sites, electrostatic interactions as well as dative bonds to sulphydrylic or other electron donor groups. Even if conformational changes in the ATPase structure driven by TBT interaction with surrounding lipids cannot be neglected, the observed similarities in the enzyme inhibition in different Phyla suggest a prevailing involvement of highly conserved domains in protein structures.