Mitochondrial modulation of phosphine toxicity and resistance in Caenorhabditis elegans.
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 (DeltaPsim) 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 DeltaPsim, 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.
Zuryn
Steven
S
School of Molecular and Microbial Sciences, University of Queensland, St Lucia, Queensland 4072, Australia.
Kuang
Jujiao
J
Ebert
Paul
P
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D007306:Insecticides / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009154:Mutation; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010720:Phosphines / Q000633:toxicity*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors
D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins; D007306:Insecticides; D010720:Phosphines; D034741:RNA, Small Interfering; C044646:phosphine