COMPARATIVE EFFECTS OF THE HERBICIDE DINITRO-O-CRESOL ON MITOCHONDRIAL BIOENERGETICS

The herbicide dinitro-o-cresol (DNOC) was evaluated for its effects on bioenergetic activities of potato tuber mitochondria to elucidate its mechanism of action and to compare its toxicological properties with those of the chemically related uncoupler dinitrophenol (DNP). DNOC ac ts as a typical uncoupler, similarly to the classical uncouplers DNP a nd carbonylcyanide p-trifluoromethoxyphenyl-hydrazone (FCCP). Low conc entrations of DNOC (<l00 mu M) maximally stimulate succinate-supported respiration of plant mitochondria, with simultaneous collapse of tran s-membrane electrical potential, more efficiently than DNP. The herbic ide makes the plant mitochondrial membrane more permeable to protons, acting as a protonophore even in nonenergized mitochondria. High conce ntrations of DNOC (>100 mu M) act also more efficiently than DNP simul taneously as a protonophore and inhibitor of respiration, especially w hen respiration is supported by substrates that are transported to the matrix. The efficiency of DNOC is decreased with increase of mitochon drial protein, BSA and exogenous orthophosphate. Although similar effe cts were observed for animal and plant mitochondria, rat-liver mitocho ndrial respiration was more sensitive to DNOC than plant mitochondria. Furthermore, in the presence of DNOC, liver mitochondria exhibited a higher state 3 respiratory coupling level than potato tuber mitochondr ia, as a result of a considerable stimulation (60%) of state 3 respira tion. In conclusion, DNOC is a more potent mitochondrial uncoupler and respiratory chain inhibitor than DNP, although their chemical structu res are very similar. Apparently, the additional methyl group of DNOC increases its efficiency as an uncoupler and as an inhibitor, as compa red to DNP. Plant mitochondria were shown to be as useful as animal mi tochondria in evaluating the toxicity of these xenobiotics. (C) 1998 S ociety of Chemical Industry.