Apart from the symptoms of
poisoning which the fluorinated arylalkylsulphonamides share with the classical protonphore and uncoupler of oxidative phosphorylation,
carbonylcyanide p-trifluoromethoxyphenylhydrazone (
FCCP), the direct correlation between the lipophilic weak
acid properties of these chemicals and their
biological activity suggests that permeation of the inner mitochondrial membrane could be the initial step in the molecular mechanism of their
biological activity. Mitochondria isolated from the livers of rats intraperitoneally exposed to varying doses (0-80 mg/kg body wt.) of
perfluidone (1,1,1-trifluoro-N-(2 methyl-4-(phenylsulphonyl)phenyl methanesulphonamide), a fluorinated arylalkylsulphonamide
pesticide, exhibit the following dose-dependent features: (i) increased state-4 respiration: stimulation being maximal (greater than or equal to 400%) at 80 mg
perfluidone per kg body wt.), (ii) release of respiratory control by
ADP: least respiratory control ratios (RCRs) (less than or equal to 1.2) were obtained at 80 mg
perfluidone per kg body wt., (iii) reduced
ADP/O ratios, (iv) increased mitochondrial passive swelling, (vi) reduced rates of mitochondrial
proton ejection during
succinate oxidation, (vi) reduced rates of respiration-dependent Ca2+ accumulation and (vii) an enhanced
oligomycin-sensitive ATPase action. These features which are qualitatively identical to those of the classical protonophore
FCCP, suggest that permeation of the inner mitochondrial membrane by
perfluidone is accompanied by a movement of
protons into the matrix such that the proton motive force required for
ATP synthesis and ion transport becomes small or not formed at all.