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.

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Journal Article | Research Support, N.I.H., Extramural

Authors

Potapenko E, Cordeiro CD, Huang G, Docampo R

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