ToxSci Advance Access published online on November 12, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm278
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mitochondrial Modulation of Phosphine Toxicity and Resistance in Caenorhabditis elegans
,1
* School of Molecular and Microbial Sciences, University of Queensland, St. Lucia, Queensland 4072, Australia
School of Integrative Biology, University of Queensland, St. Lucia 4072, Brisbane, Australia
1 Corresponding author, email: p.ebert{at}uq.edu.au, phone: +617 336 52973; fax: +617 336 51655;, address: Goddard Building, School of Integrative Biology, University of Queensland, St Lucia, Queensland 4072, Australia
Received September 7, 2007; revision received November 6, 2007; accepted November 6, 2007
 |
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, C. 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 (
m) within 5 hours 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 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.
Key Words: Phosphine; mitochondria; Caenorhabditis elegans; pesticide; fumigant.