MITOCHONDRIAL BIOENERGETICS IS AFFECTED BY THE HERBICIDE PARAQUAT

The potential toxicity of the herbicide paraquat (1,1-dimethyl-4,4'-bi pyridylium dichloride) was tested in bioenergetic functions of isolate d rat liver mitochondria. Paraquat increases the rate of State 4 respi ration, doubling at 10 mM, indicating uncoupling effects. Additionally , State 3 respiration is depressed by about 15%, at 10 mM paraquat, wh ereas uncoupled respiration in the presence of CCCP is depressed by ab out 30%. Furthermore, paraquat partially inhibits the ATPase activity through a direct effect on this enzyme complex. However, at high conce ntrations (5-10 mM), the ATPase activity is stimulated, probably as co nsequence of the described uncoupling effect. Depression of respirator y activity is mediated through partial inhibitions of mitochondrial co mplexes III and IV. Paraquat depresses Delta Psi as a function of herb icide 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. T his particular effect is clear at 1 mM paraquat and tends to fade out with increasing concentrations of the herbicide.