The potential toxicity of the herbicide paraquat (1,1-dimethyl-4,4'-bipyridylium dichloride) was tested in bioenergetic functions of
isolated rat liver mitochondria. Paraquat increases the rate of State 4 respiration, doubling at 10 mM, indicating uncoupling effects.
Additionally, State 3 respiration is depressed by about 15%, at 10 mM paraquat, whereas uncoupled respiration in the presence of CCCP
is depressed by about 30%. Furthermore, paraquat partially inhibits the ATPase activity through a direct effect on this enzyme complex.
However, at high concentrations (5-10 mM), the ATPase activity is stimulated, probably as consequence of the described uncoupling
effect. Depression of respiratory activity is mediated through partial inhibitions of mitochondrial complexes III and IV. Paraquat
depresses A~ as a function of herbicide concentration. In addition, the depolarization induced by ADP is decreased and repolarization is
biphasic suggesting a double effect. Repolarization resumes at a level consistently higher than the initial level before ADP addition, for
paraquat concentrations up to 10 mM. This particular effect is clear at 1 mM paraquat and tends to fade out with increasing concentrations
of the herbicide.