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Tri‐ n ‐butyltin binding to a low‐affinity site decreases the F 1 F O ‐ATPase sensitivity to oligomycin in mussel mitochondria
Author(s) -
Nesci Salvatore,
Ventrella Vittoria,
Trombetti Fabiana,
Pirini Maurizio,
Pagliarani Alessandra
Publication year - 2012
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/aoc.2904
Subject(s) - oligomycin , chemistry , submitochondrial particle , atpase , enzyme , binding site , stereochemistry , biophysics , biochemistry , biology
In mussel digestive gland mitochondria the environmental pollutant tri‐ n ‐butyltin (TBT), other than strongly inhibiting ATPase activity at <1.0 μ m , at ≥1.0 μ m concentration was previously found to desensitize F 1 F O ‐ATPase to the antibiotic oligomycin. While F 1 F O ‐ATPase inhibition is widely known as one of the main mitochondrial damages caused by TBT, the enzyme's desensitization to oligomycin was quite unexpected. The possible mechanisms involved are here stepwise approached, aiming at enlightening the molecular mechanism(s) of TBT toxicity and the still poorly investigated oligomycin interaction with F O . The findings strongly suggest that the oligomycin desensitization directly stems from the covalent binding of TBT to monothiols of the F 1 F O ‐ATPase. This binding implies sulfur oxidation , irrespective of the possible formation of radical species in mitochondria, a mechanism which does not seem to be involved here. It is hypothesized that TBT interacts with the enzyme complex in at least two sites distinguished by different affinities: TBT binding to the high‐affinity site would lead to ATPase inhibition, while TBT binding to monothiols in the low‐affinity site could mirror the decrease in F 1 F O ‐ATPase oligomycin sensitivity at ≥1.0 μ m TBT. Experiments carried out on inside‐out submitochondrial particles hint that TBT binding destabilizes the oligomycin‐blocked F O conformation, allowing proton flux recovery within F O , without uncoupling the catalytic function from proton channeling. Copyright © 2012 John Wiley & Sons, Ltd.