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dc.contributor.authorPreston, Sarahen_US
dc.contributor.authorKorhonen, Pasi K.en_US
dc.contributor.authorMouchiroud, Laurenten_US
dc.contributor.authorCornaglia, Matteoen_US
dc.contributor.authorMcGee, Sean L.en_US
dc.contributor.authorYoung, Neil D.en_US
dc.contributor.authorDavis, Rohanen_US
dc.contributor.authorCrawford, Simonen_US
dc.contributor.authorNowell, Cameronen_US
dc.contributor.authorAnsell, Brendan R. E.en_US
dc.contributor.authorFisher, Gillen_US
dc.contributor.authorAndrews, Katherineen_US
dc.contributor.authorChang, Bill C. H.en_US
dc.contributor.authorGijs, Martin A. M.en_US
dc.contributor.authorSternberg, Paul W.en_US
dc.contributor.authorAuwerx, Johanen_US
dc.contributor.authorBaell, Jonathanen_US
dc.contributor.authorHofmann, Andreasen_US
dc.contributor.authorJabbar, Abdulen_US
dc.contributor.authorGasser, Robin B.en_US
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.en_US
dc.publisherFederation of American Societies for Experimental Biologyen_US
dc.relation.ispartofjournalFASEB Journalen_US
dc.subject.fieldofresearchBiochemistry and Cell Biology not elsewhere classifieden_US
dc.titleDeguelin exerts potent nematocidal activity via the mitochondrial respiratory chainen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.hasfulltextNo Full Text

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