Deakin University

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Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain

journal contribution
posted on 2017-10-01, 00:00 authored by S Preston, P K Korhonen, L Mouchiroud, M Cornaglia, Sean McgeeSean Mcgee, N D Young, R A Davis, S Crawford, C Nowell, B R E Ansell, G M Fisher, K T Andrews, B C H Chang, M A M Gijs, P W Sternberg, J Auwerx, J Baell, A Hofmann, A Jabbar, R B Gasser
As a result of limited classes of anthelmintics and an over-reliance on chemical control, there is a great need to discover new compounds to combat drug resistance in parasitic nematodes. Here, we show that deguelin, a plant-derived rotenoid, selectively and potently inhibits the motility and development of nematodes, which supports its potential as a lead candidate for drug development. Furthermore, we demonstrate that deguelin treatment significantly increases gene transcription that is associated with energy metabolism, particularly oxidative phosphorylation and mitoribosomal protein production before inhibiting motility. Mitochondrial tracking confirmed enhanced oxidative phosphorylation. In accordance, real-time measurements of oxidative phosphorylation in response to deguelin treatment demonstrated an immediate decrease in oxygen consumption in both parasitic (Haemonchus contortus) and free-living (Caenorhabditis elegans) nematodes. Consequently, we hypothesize that deguelin is exerting its toxic effect on nematodes as a modulator of oxidative phosphorylation. This study highlights the dynamic biologic response of multicellular organisms to deguelin perturbation.-Preston, S., Korhonen, P. K., Mouchiroud, L., Cornaglia, M., McGee, S. L., Young, N. D., Davis, R. A., Crawford, S., Nowell, C., Ansell, B. R. E., Fisher, G. M., Andrews, K. T., Chang, B. C. H., Gijs, M. A. M., Sternberg, P. W., Auwerx, J., Baell, J., Hofmann, A., Jabbar, A., Gasser, R. B. Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain.



The FASEB Journal : official publication of the Federation of American Societies for Experimental Biology






4515 - 4532


Federation of American Societies for Experimental Biology


Bethesda, Md.







Publication classification

C Journal article; C1 Refereed article in a scholarly journal

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2017, FASEB