Intracellular glucose 1-phosphate and glucose 6-phosphate levels modulate Ca2+ homeostasis in Saccharomyces cerevisiae

David P. Aiello, Lianwu Fu, Attila Miseta, David M. Bedwell

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31 Citations (Scopus)

Abstract

The enzyme phosphoglucomutase plays a key role in cellular metabolism by virtue of its ability to interconvert Glc-1-P and Glc-6-P. It was recently shown that a yeast strain lacking the major isoform of phosphoglucomutase (pgm2Δ) accumulates a high level of Glc-1-P and exhibits several phenotypes related to altered Ca2+ homeostasis when D-galactose is utilized as the carbon source (Fu, L., Miseta, A., Hunton, D., Marchase, R. B., and Bedwell, D. M. (2000) J. Biol. Chem. 275, 5431-5440). These phenotypes include increased Ca2+ uptake and accumulation and sensitivity to high environmental Ca2+ levels. In the present study, we overproduced the enzyme UDP-Glc pyrophosphorylase to test whether the overproduction of a downstream metabolite produced from Glc-1-P can also mediate changes in Ca2+ homeostasis. We found that overproduction of UDP-Glc did not cause any alterations in Ca2+ uptake or accumulation. We also examined whether Glc-6-P can influence cellular Ca2+ homeostasis. A yeast strain lacking the β-sub unit of phosphofructokinase (pfk2Δ) accumulates a high level of Glc-6-P (Huang, D., Wilson, W. A., and Roach, P. J. (1997) J. Biol. Chem. 272, 22495-22501). We found that this increase in Glc-6-P led to a 1.5-2-fold increase in total cellular Ca2+. We also found that the pgm2Δ/ pfk2Δ strain, which accumulated high levels of both Glc-6-P and Glc-1-P, no longer exhibited the Ca2+-related phenotypes associated with high Glc-1-P levels in the pgm2Δ mutant. These results provide strong evidence that cellular Ca2+ homeostasis is coupled to the relative levels of Glc-6-P and Glc-1-P in yeast.

Original languageEnglish
Pages (from-to)45751-45758
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number48
DOIs
Publication statusPublished - Nov 29 2002

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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