Inhibition of phosphoglucomutase activity by lithium alters cellular calcium homeostasis and signaling in Saccharomyces cerevisiae

Academic Article


  • Phosphoglucomutase is a key enzyme of glucose metabolism that interconverts glucose-1-phosphate and glucose-6-phosphate. Loss of the major isoform of phosphoglucomutase in Saccharomyces cerevisiae results in a significant increase in the cellular glucose-1-phosphate-to-glucose-6-phosphate ratio when cells are grown in medium containing galactose as carbon source. This imbalance in glucose metabolites was recently shown to also cause a six- to ninefold increase in cellular Ca2+ accumulation. We found that Li+ inhibition of phosphoglucomutase causes a similar elevation of total cellular Ca2+ and an increase in 45Ca2+ uptake in a wild-type yeast strain grown in medium containing galactose, but not glucose, as sole carbon source. Li+ treatment also reduced the transient elevation of cytosolic Ca2+ response that is triggered by exposure to external CaCl2 or by the addition of galactose to yeast cells starved of a carbon source. Finally, we found that the Ca2+ overaccumulation induced by Li+ exposure was significantly reduced in a strain lacking the vacuolar Ca2+-ATPase Pmc1p. These observations suggest that Li+ inhibition of phosphoglucomutase results in an increased glucose-1-phosphate-to-glucose-6-phosphate ratio, which results in an accelerated rate of vacuolar Ca2+ uptake via the Ca 2+-ATPase Pmc1p. Copyright © 2005 the American Physiological Society.
  • Digital Object Identifier (doi)

    Author List

  • Csutora P; Strassz A; Boldizsár F; Németh P; Sipos K; Aiello DP; Bedwell DM; Miseta A
  • Volume

  • 289
  • Issue

  • 1 58-1