Modification of the transport of protons and Ca2+ ions across mitochondrial coupling membrane by N-(phosphonomethyl)glycine.

The proton permeability of mitochondrial membranes suspended in 0.15 N NH4Cl was enhanced by N-(phosphonomethyl)glycine (PMG), a broad-spectrum and a non-selective herbicide, in a concentration-dependent manner. Significant decreases in light scattering by these membranes were observed at concentrations greater than or equal to 600 microM PMG. The effect of PMG is therefore several times lower than that of FCCP, a classical uncoupler of oxidative phosphorylation. Using a sensitive pH-glass electrode, PMG significantly enhanced the movement of protons into mitochondrial matrix. Furthermore, the rate of PMG-induced release of Ca2+ ions following its accumulation by energized mitochondria was only slightly over one-half that induced by FCCP (1 microM). Whereas Ca2+ or Mg2+ only marginally reduced the effect induced by PMG, inclusion of glycine into the reaction media did not have any influence whatsoever on the effect induced by PMG. These results indicate that, although PMG increases the permeability of the mitochondrial membrane to protons and to Ca2+, the herbicide does not seem to act like a true protonophore. Its uncoupling effect may, therefore, be due to its ability to act both as a chelator and a mild protonophore.