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.