Pharmacological targeting of the helminth complex II: are there any rhodoquinone-driven adaptations?

Based on a particular biochemical model, the use of rhodoquinone (RQ) under hypoxic conditions has been linked to an alternative complex II in the electron transport chain in helminths. This model was derived from detailed studies on Ascaris suum and generalized for helminths. However, accumulated evidence warrants a critical model re-examination. RQ facilitates complex II to operate in reverse as a fumarate reductase when oxygen is unavailable, but this biochemical adaptation typically does not involve a dedicated alternative complex II. Based on recent genomic, biochemical, and pharmacological data, we argue that the Ascaris scenario cannot be extrapolated to other helminths. Complex II is a promising pharmacological target for helminths; thus, the revision of the model also has practical consequences.