Pyrophosphate Stimulates the Phosphate-Sodium Symporter ofTrypanosoma bruceiAcidocalcisomes andSaccharomyces cerevisiaeVacuoles
ABSTRACTInorganic pyrophosphate (PPi) is a by-product of biosynthetic reactions and has bioenergetic and regulatory roles in a variety of cells. Here we show that PPiand other pyrophosphate-containing compounds, including polyphosphate (polyP), can stimulate sodium-dependent depolarization of the membrane potential and Piconductance inXenopusoocytes expressing aSaccharomyces cerevisiaeorTrypanosoma bruceiNa+/Pisymporter. PPiis not taken up byXenopusoocytes, and deletion of the TbPho91 SPX domain abolished its depolarizing effect. PPigenerated outward currents in Na+/Pi-loaded giant vacuoles prepared from wild-type orpho91Δ yeast strains expressingTbPHO91but not from thepho91Δstrains. Our results suggest that PPi, at physiological concentrations, can function as a signaling molecule releasing PifromS. cerevisiaevacuoles andT. bruceiacidocalcisomes.IMPORTANCEAcidocalcisomes, first described in trypanosomes and known to be present in a variety of cells, have similarities withS. cerevisiaevacuoles in their structure and composition. Both organelles share a Na+/Pisymporter involved in Pirelease to the cytosol, where it is needed for biosynthetic reactions. Here we show that PPi, at physiological cytosolic concentrations, stimulates the symporter expressed in eitherXenopusoocytes or yeast vacuoles via its SPX domain, revealing a signaling role of this molecule.