Inhibition of phosphoglucomutase activity by lithium alters cellular calcium homeostasis and signaling in Saccharomyces cerevisiae.
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+ over-accumulation 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 Ca2+-ATPase Pmc1p.
Csutora
Péter
P
Department of Laboratory Medicine, Faculty of Medicine, Pécs University, Ifjúság u. 13, 7624 Pécs, Hungary.
Strassz
András
A
Boldizsár
Ferenc
F
Németh
Péter
P
Sipos
Katalin
K
Aiello
David P
DP
Bedwell
David M
DM
Miseta
Attila
A
D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005690:Galactose / Q000008:administration & dosage; D019298:Glucose-6-Phosphate / Q000378:metabolism; D005958:Glucosephosphates / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D007425:Intracellular Membranes / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D010733:Phosphoglucomutase / Q000037:antagonists & inhibitors*; D053499:Plasma Membrane Calcium-Transporting ATPases; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014018:Tissue Distribution; D014617:Vacuoles / Q000378:metabolism
D003470:Culture Media; D005958:Glucosephosphates; C085484:PMC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D019298:Glucose-6-Phosphate; D008094:Lithium; C031590:glucose-1-phosphate; D053499:Plasma Membrane Calcium-Transporting ATPases; D010733:Phosphoglucomutase; D000252:Calcium-Transporting ATPases; D008274:Magnesium; D002118:Calcium; D005690:Galactose