Dissection of the Rhodoquinone synthesis pathway in C.elegans
Mark Spensley, Djina Pajkic, Sam Del Borello, Margot Lautens, Amy Caudy, Andrew Fraser Donnelly Centre, University of Toronto, Canada
Parasitic Helminths infect around a quarter of all humans — they are one of the major human pathogens. Most parasitic helminths (PHs) undergo major shifts in their metabolism following host infection. While PHs use standard aerobic metabolism during their free-living stages, many PHs live in hypoxic conditions in their host — to survive they use unusual metabolic pathways to make ATP. In particular they rely on Rhodoquinone (RQ) as a key electron carrier. While RQ is very similar to Ubiquinone, humans do not make RQ — RQ-utilizing anaerobic pathways are thus a perfect drug target but (a) no commercial drugs exist that target RQ synthesis (b) the key enzymes required for RQ synthesis are unknown. One key difficulty in studying RQ synthesis is the lack of a tractable genetic system — one cannot study this in yeast/mammals since they lack this pathway. C.elegans however does make RQ. I will present the work we have done to establish C.elegans as a powerful model for studying RQ synthesis and for identifying new drugs that target this pathway. We will also present a new pathway for RQ synthesis along with both genetic and biochemical data to support our model.
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