Pyrophosphate Stimulates the Phosphate-Sodium Symporter of Acidocalcisomes and Vacuoles.

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