The mitochondrial F1FO-ATPase desensitization to oligomycin by tributyltin is due to thiol oxidation

Add time:07/25/2019    Source:sciencedirect.com

The antibiotic oligomycin is known to inhibit mitochondrial F-type ATP synthases. The antibiotic inhibits both ATP synthesis and hydrolysis by blocking the H+ translocation through FO which is coupled to the catalytic activity of F1. The amphiphilic organotin tri-n-butyltin (TBT), a known mitochondrial poison, can penetrate into biological membranes and covalently bind to electron-donor atoms of biomolecules such as sulfur. This study aims at exploring the mechanism(s) involved in the enzyme desensitization to oligomycin which occurs at concentrations >1 μM TBT. This poorly known effect of TBT, which only appeared at temperatures above the break in the Arrhenius plot of the enzyme activity, was found to be accompanied by the oxidation of isolated thiol groups of the mitochondrial complex. The oligomycin sensitivity was restored by the reducing agents glutathione and dithioerythritol and not influenced by antioxidants. The whole of data is consistent with the hypothesis that thiol oxidation is caused by TBT covalent binding to cysteine residues in a low-affinity site on FO and not by other possible oxidative events. According to this putative model, the onset of tin–sulfur bonds would trigger conformational changes and weaken the oligomycin interaction with FO.

We also recommend Trading Suppliers and Manufacturers of DI-T-BUTYLTIN OXIDE (cas 19140-19-3). Pls Click Website Link as below: cas 19140-19-3 suppliers

Prev:Exposure of Jurkat cells to bis (tri-n-butyltin) oxide (TBTO) induces transcriptomics changes indicative for ER- and oxidative stress, T cell activation and apoptosis
Next:Facile reaction of bis(tri-n-butyltin) oxide with silica gel)