Sensitivity of oligomycin-inhibited respiration of isolated rat liver mitochondria to perfluidone, a fluorinated arylalkylsulfonamide

Oxygen electrode polarographic measurements of the rate of oxygen consumption by isolated rat liver mitochondria revealed that oligomycin inhibition of respiration was offset to different degress by varying concentrations of perfluidone (1,1,1-trifluoro- N-(2 methyl-4-phenylsulfonyl) methane-sulfonamide). Using any of pyruvate-malate, succinate or ascorbate-TMPD ( N, N, N′, N′-tetramethyl- p-phenylenediamine) as substrate, this herbicidal and anti-inflammatory agent at 100 μM concentration caused a 5-fold stimulation of oligomycin-inhibited respiration. Higher concentrations of the herbicide (⩾ 120 μM) gave lower stimulatory effects. Similar stimulatory effects were obtained with 1 μM FCCP (carbonylcyanide p-trifluoromethyoxyphenyl- hydrazone), a classical protonophore. Our results also show an enhanced oligomycin-sensitive ATPase action in intact mitochondria incubated with ATP and varying concentrations of perfluidone. Maximum enhancement effect (111.3%) was obtained at 120 μM perfluidone. FCCP (1 μM) stimulated this ATPase action by 130%. An inhibition of respiration by oligomycin is due to an interaction with the proton well of F 0F 1-ATP synthetase (Lardy, H.A. et al., Arch. Biochem. Biophys., 78 (1953) 587). Perfluidone probably increases the proton conductance of mitochondrial inner membrane in the same manner as FCCP and thus causes an increase in mitochondrial respiratory rate. As protons move into the matrix, ΔμH +, the proton electrochemical potential gradient becomes very small and the F 0F 1-ATP synthetase functions in the direction of hydrolysis of ATP rather than its shnthesis (Mitchell, P., Eur. J. Biochem., 95 (1979) 1). These findings therefore indicate that perfluidone acts in a way similar to FCCP, a classical uncoupler and protonophore.