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Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain.
Journal article

Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain.

  • Preston S Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia.
  • Korhonen PK Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia.
  • Mouchiroud L Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Cornaglia M Laboratory of Microsystems, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • McGee SL Metabolic Research Unit, Metabolic Reprogramming Laboratory, School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, Victoria, Australia.
  • Young ND Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia.
  • Davis RA Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia.
  • Crawford S School of Biosciences, University of Melbourne, Parkville, Victoria, Australia.
  • Nowell C Drug Discovery Biology, Monash University Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
  • Ansell BRE Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia.
  • Fisher GM Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia.
  • Andrews KT Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia.
  • Chang BCH Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia.
  • Gijs MAM Laboratory of Microsystems, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Sternberg PW Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
  • Auwerx J Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Baell J Medicinal Chemistry, Monash University Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
  • Hofmann A Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia.
  • Jabbar A Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia.
  • Gasser RB Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia; robinbg@unimelb.edu.au.
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  • 2017-07-09
Published in:
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - 2017
anthelmintic activity
natural product
nematode
oxidative phosphorylation
transcriptomics
Animals
Anthelmintics
Caenorhabditis elegans
Drug Resistance
Electron Transport
Energy Metabolism
Mitochondria
Mitochondrial Membranes
Rotenone
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/163096
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