FIG. 12.

Schematic representation of polygodial treatment on yeast. Polygodial inhibits mitochondrial ATPase, eliminating a major source of ATP (shading represents proteins with impaired functions). It also causes plasma membrane disruption, which leads to an influx of protons (wavy lines). This influx results in a collapse of the proton motive force and inhibition of nutrient uptake coupled to this gradient, followed by a decrease in internal pH, which inhibits enzymes as they are shifted off of their pH optima. Cells can recover by pumping protons out of the cell via the plasma membrane ATPase, Pma1p, which consumes large amounts of ATP. The combination of ATP consumption stimulated by proton permeability and ATP synthase inhibition contributes to a decrease in ATP to levels below those necessary for normal metabolic functions, resulting in nonviable yeast.