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

1 Department of Laboratory Medicine, 2 Department of Immunology and Biotechnology, and 3 Department of Biochemistry, Faculty of Medicine, Pécs University, Pécs, Hungary; and 4 Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama Submitted 21 September 2004 ; accepted in final form 8 February 2005 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 Ca 2+ accumulation. We found that Li + inhibition of phosphoglucomutase causes a similar elevation of total cellular Ca 2+ and an increase in 45 Ca 2+ 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 Ca 2+ response that is triggered by exposure to external CaCl 2 or by the addition of galactose to yeast cells starved of a carbon source. Finally, we found that the Ca 2+ overaccumulation induced by Li + exposure was significantly reduced in a strain lacking the vacuolar Ca 2+ -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 Ca 2+ uptake via the Ca 2+ -ATPase Pmc1p. calcium influx; calcium signal; galactose; glucose phosphate Address for reprint requests and other correspondence: A. Miseta, Pécs Univ., Faculty of Medicine, Dept. of Laboratory Medicine, Ifjúság u. 13, 7624 Pécs, Hungary (e-mail: attila.miseta{at}aok.pte.hu )