title: Mitochondrial impacts of insecticidal formate esters in insecticide-resistant and insecticide-susceptible Drosophila melanogaster.
abstract: BACKGROUND
  Previous research on insecticidal formate esters in flies and mosquitoes has documented toxicity profiles, metabolism characteristics and neurological impacts. The research presented here investigated mitochondrial impacts of insecticidal formate esters and their hydrolyzed metabolite formic acid in the model dipteran insect Drosophila melanogaster Meig. These studies compared two Drosophila strains: an insecticide-susceptible strain (Canton-S) and a strain resistant by cytochrome P450 overexpression (Hikone-R).
  
  
  RESULTS
  In initial studies investigating inhibition of mitochondrial cytochrome c oxidase, two proven insecticidal materials (hydramethylnon and sodium cyanide) caused significant inhibition. However, for insecticidal formate esters and formic acid, no significant inhibition was identified in either fly strain. Mitochondrial impacts of formate esters were then investigated further by tracking toxicant-induced cytochrome c release from mitochondria into the cytoplasm, a biomarker of apoptosis and neurological dysfunction. Formic acid and three positive control treatments (rotenone, antimycin A and sodium cyanide) induced cytochrome c release, verifying that formic acid is capable of causing mitochondrial disruption. However, when comparing formate ester hydrolysis and cytochrome c release between Drosophila strains, formic acid liberation was only weakly correlated with cytochrome c release in the susceptible Canton-S strain (r(2) = 0.70). The resistant Hikone-R strain showed no correlation (r(2) < 0.0001) between formate ester hydrolysis and cytochrome c release.
  
  
  CONCLUSIONS
  The findings of this study provide confirmation of mitochondrial impacts by insecticidal formate esters and suggest links between mitochondrial disruption, respiratory inhibition, apoptosis and formate-ester-induced neurotoxicity.
authors.affiliation: Entomology and Nematology Department, University of Florida, Gainesville, FL 32611-0620, USA.
authors.forename: Cheol
authors.initials: C
authors.lastname: Song
authors.forename: Michael E
authors.initials: ME
authors.lastname: Scharf
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D004952:Esters / Q000494:pharmacology*; D005561:Formates / Q000494:pharmacology; D019476:Insect Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D004952:Esters; D005561:Formates; D019476:Insect Proteins; D007306:Insecticides; C030544:formic acid; D045304:Cytochromes c; D003576:Electron Transport Complex IV