Mitochondrial modulation of phosphine toxicity and resistance in Caenorhabditis elegans

Zuryn, Steven, Kuang, Jujiao and Ebert, Paul (2008) Mitochondrial modulation of phosphine toxicity and resistance in Caenorhabditis elegans. Toxicological Sciences, 102 1: 179-186. doi:10.1093/toxsci/kfm278


Author Zuryn, Steven
Kuang, Jujiao
Ebert, Paul
Title Mitochondrial modulation of phosphine toxicity and resistance in Caenorhabditis elegans
Formatted title
Mitochondrial Modulation of Phosphine Toxicity and Resistance in Caenorhabditis elegans
Journal name Toxicological Sciences   Check publisher's open access policy
ISSN 1096-0929
1096-6080
Publication date 2008-03-01
Sub-type Article (original research)
DOI 10.1093/toxsci/kfm278
Open Access Status Not Open Access
Volume 102
Issue 1
Start page 179
End page 186
Total pages 8
Publisher Oxford University Press
Language eng
Subject 1115 Pharmacology and Pharmaceutical Sciences
Formatted abstract
Phosphine is a fumigant used to protect stored commodities from infestation by pest insects, though high-level phosphine resistance in many insect species threatens the continued use of the fumigant. The mechanisms of toxicity and resistance are not clearly understood. In this study, the model organism, Caenorhabditis elegans, was employed to investigate the effects of phosphine on its proposed in vivo target, the mitochondrion. We found that phosphine rapidly perturbs mitochondrial morphology, inhibits oxidative respiration by 70%, and causes a severe drop in mitochondrial membrane potential ({Delta}{Psi}m) within 5 h of exposure. We then examined the phosphine-resistant strain of nematode, pre-33, to determine whether resistance was associated with any changes to mitochondrial physiology. Oxygen consumption was reduced by 70% in these mutant animals, which also had more mitochondrial genome copies than wild-type animals, a common response to reduced metabolic capacity. The mutant also had an unexpected increase in the basal {Delta}{Psi}m, which protected individuals from collapse of the membrane potential following phosphine treatment. We tested whether directly manipulating mitochondrial function could influence sensitivity toward phosphine and found that suppression of mitochondrial respiratory chain genes caused up to 10-fold increase in phosphine resistance. The current study confirms that phosphine targets the mitochondria and also indicates that direct alteration of mitochondrial function may be related to phosphine resistance.
Keyword phosphine
mitochondria
Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
 
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