Disulfiram Inhibition of the Alternative Respiratory Pathway in Plant Mitochondria

Abstract

Disulfiram (tetraethylthiuram disulfide) was found to be a potent and selective inhibitor of the alternative respiratory path of plant mitochondria. The onset of inhibition by disulfiram takes several minutes and the inhibition is not readily reversed by washing, nor by metal ions. By contrast, thiols such as dithiothreitol not only reverse, but also prevent, disulfiram inhibition. Inhibition by disulfiram and by hydroxamic acids are not mutually exclusive. Structural analogs of disulfiram are far less potent inhibitors, with the exception of bisethyl xanthogen. Inhibition is due to disulfiram, per se, and not to its reduction product, diethyldithiocarbamate, a powerful chelator. Accordingly, the inhibitory effect of disulfiram is considered to involve the formation of mixed disulfides with one or more sulfhydryl groups in the alternative path. Disulfiram does not act as an electron sink diverting electron flow from oxygen.