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Here, we show that deguelin, a plant\u2010derived 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\u2010time measurements of oxidative phosphorylation in response to deguelin treatment demonstrated an immediate decrease in oxygen consumption in both parasitic (\n                    <jats:italic>Haemonchus contortus<\/jats:italic>\n                    ) and free\u2010living (\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    ) 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.\u2014Preston, 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\n                    <jats:italic>via<\/jats:italic>\n                    the mitochondrial respiratory chain. FASEB J. 31, 4515\u20134532 (2017).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700288r","type":"journal-article","created":{"date-parts":[[2017,7,7]],"date-time":"2017-07-07T20:10:17Z","timestamp":1499458217000},"page":"4515-4532","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Deguelin exerts potent nematocidal activity\n                    <i>via<\/i>\n                    the mitochondrial respiratory chain"],"prefix":"10.1096","volume":"31","author":[{"given":"Sarah","family":"Preston","sequence":"first","affiliation":[{"name":"Faculty of Veterinary and Agricultural Sciences University of Melbourne Parkville Victoria Australia"},{"name":"Faculty of Science and Technology Federation University Ballarat Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasi K.","family":"Korhonen","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary and Agricultural Sciences University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Mouchiroud","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative and Systems Physiology \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Cornaglia","sequence":"additional","affiliation":[{"name":"Laboratory of Microsystems \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean L.","family":"McGee","sequence":"additional","affiliation":[{"name":"Metabolic Research Unit Metabolic Reprogramming Laboratory School of Medicine, Faculty of Health, Deakin University Waurn Ponds Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil D.","family":"Young","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary and Agricultural Sciences University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan A.","family":"Davis","sequence":"additional","affiliation":[{"name":"Griffith Institute for Drug Discovery Griffith University Nathan Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Crawford","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Nowell","sequence":"additional","affiliation":[{"name":"Drug Discovery Biology Monash University Institute of Pharmaceutical Sciences Monash University Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan R. 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