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dc.contributor.authorPreston, Sarah
dc.contributor.authorKorhonen, Pasi K
dc.contributor.authorMouchiroud, Laurent
dc.contributor.authorCornaglia, Matteo
dc.contributor.authorMcGee, Sean L
dc.contributor.authorYoung, Neil D
dc.contributor.authorDavis, Rohan A
dc.contributor.authorCrawford, Simon
dc.contributor.authorNowell, Cameron
dc.contributor.authorAnsell, Brendan RE
dc.contributor.authorFisher, Gillian M
dc.contributor.authorAndrews, Katherine T
dc.contributor.authorChang, Bill CH
dc.contributor.authorGijs, Martin AM
dc.contributor.authorSternberg, Paul W
dc.contributor.authorAuwerx, Johan
dc.contributor.authorBaell, Jonathan
dc.contributor.authorHofmann, Andreas
dc.contributor.authorJabbar, Abdul
dc.contributor.authorGasser, Robin B
dc.description.abstractAs 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 plantderived 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.
dc.publisherFederation of American Societies for Experimental Biology
dc.relation.ispartofjournalFASEB Journal
dc.subject.fieldofresearchBiochemistry and Cell Biology not elsewhere classified
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchMedical Physiology
dc.titleDeguelin exerts potent nematocidal activity via the mitochondrial respiratory chain
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorAndrews, Katherine T.
gro.griffith.authorDavis, Rohan A.
gro.griffith.authorFisher, Gill M.
gro.griffith.authorHofmann, Andreas

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