On the mode of action of bifenazate: New evidence for a mitochondrial target-site

Bifenazate is one the most frequently used acaricides to control spider mites. Although first thought to be a neurotoxin, genetic evidence has pointed towards a mitochondrial target site, in particular the Qo site of mitochondrially encoded cytochrome b. In this study, we present the first biochemical evidence for a physical interaction between [14C] bifenazate and mitochondrial complex III of Tetranychus urticae. We further show that bifenazate is differentially metabolized in insects and mites, possibly underlying the high selectivity of the compound. In contrast to the proposed mitochondrial mode of action, it was recently shown that bifenazate can act as a synergist or allosteric modulator of functionally expressed T. urticae GABA receptor homologues. We therefore sequenced and determined the expression level of all three T. urticae GABA receptors in bifenazate susceptible and highly resistant strains. We found no mutations linked with resistance in these receptors, and their expression level was not overall changed between strains. We finally summarize all available evidence and argue for a mitochondrial mode of action via inhibition of complex III at the cytochrome b Qo site.