- Title
- Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain
- Creator
- Preston, Sarah; Korhonen, Pasi; Mouchiroud, Laurent; Cornaglia, Matteo; McGee, Sean; Young, Neil; Davis, Rohan; Crawford, Simon; Nowell, Cameron; Ansell, Brendan; Fisher, Gillian; Andrews, Katherine; Chang, Bill; Gijs, Martin; Sternberg, Paul; Auwerx, Johan; Baell, Jonathan; Hofmann, Andreas; Jabbar, Abdul; Gasser, Robin
- Date
- 2017
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/164176
- Identifier
- vital:13022
- Identifier
-
https://doi.org/10.1096/fj.201700288R
- Identifier
- ISBN:0892-6638
- Abstract
- 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. © FASEB.
- Publisher
- FASEB
- Relation
- FASEB Journal Vol. 31, no. 10 (2017), p. 4515-4532
- Rights
- Copyright © FASEB.
- Rights
- This metadata is freely available under a CCO license
- Subject
- 0601 Biochemistry and Cell Biology; 0606 Physiology; 1116 Medical Physiology; Anthelmintic activity; Natural product; Nematode; Oxidative phosphorylation; Transcriptomics
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