Pyrophosphate Stimulates the Phosphate-Sodium Symporter of Trypanosoma brucei Acidocalcisomes and Saccharomyces cerevisiae Vacuoles

Inorganic pyrophosphate (PP(i)) is a by-product of biosynthetic reactions and has bioenergetic and regulatory roles in a variety of cells. Here we show that PP(i) and other pyrophosphate-containing compounds, including polyphosphate (polyP), can stimulate sodium-dependent depolarization of the membrane potential and P(i) conductance in Xenopus oocytes expressing a Saccharomyces cerevisiae or Trypanosoma brucei Na(+)/P(i) symporter. PP(i) is not taken up by Xenopus oocytes, and deletion of the TbPho91 SPX domain abolished its depolarizing effect. PP(i) generated outward currents in Na(+)/P(i)-loaded giant vacuoles prepared from wild-type or pho91Δ yeast strains expressing TbPHO91 but not from the pho91Δ strains. Our results suggest that PP(i), at physiological concentrations, can function as a signaling molecule releasing P(i) from S. cerevisiae vacuoles and T. brucei acidocalcisomes. IMPORTANCE Acidocalcisomes, first described in trypanosomes and known to be present in a variety of cells, have similarities with S. cerevisiae vacuoles in their structure and composition. Both organelles share a Na(+)/P(i) symporter involved in P(i) release to the cytosol, where it is needed for biosynthetic reactions. Here we show that PP(i), at physiological cytosolic concentrations, stimulates the symporter expressed in either Xenopus oocytes or yeast vacuoles via its SPX domain, revealing a signaling role of this molecule.