Lw. Fu et al., Loss of the major isoform of phosphoglucomutase results in altered calciumhomeostasis in Saccharomyces cerevisiae, J BIOL CHEM, 275(8), 2000, pp. 5431-5440
Phosphoglucomutase (PGM) is a key enzyme in glucose metabolism, where it ca
talyzes the interconversion of glucose 1-phosphate (Glc-1-P) and glucose 6-
phosphate (Glc-6-P), In this study, we make the novel observation that PGM
is also involved in the regulation of cellular Ca2+ homeostasis in Saccharo
myces cerevisiae. When a strain lacking the major isoform of PGM (pgm2 Delt
a) was grown on media containing galactose as sole carbon source, its rate
of Ca2+ uptake was 5-fold higher than an isogenic wild-type strain. This in
creased rate of Ca2+ uptake resulted in a 9-fold increase in the steady-sta
te total cellular Ca2+ level. The fraction of cellular Ca2+ located in the
exchangeable pool in the pgm2 Delta strain was found to be as large as the
exchangeable fraction observed in wild-type cells, suggesting that the depl
etion of Golgi Ca2+ stores is not responsible for the increased rate of Ca2
+ uptake. We also found that growth of the pgm2 Delta strain on galactose m
edia is inhibited by 10 mu M cyclosporin A, suggesting that activation of t
he calmodulin/calcineurin signaling pathway is required to activate the Ca2
+ transporters that sequester the increased cytosolic Ca2+ load caused by t
his high rate of Ca2+ uptake. We propose that these Ca2+-related alteration
s are attributable to a reduced metabolic flux between Glc-1-P and Glc-6-P
due to a limitation of PGM enzymatic activity in the pgm2 Delta strain. Con
sistent with this hypothesis, we found that this "metabolic bottleneck" res
ulted in an 8-fold increase in the Glc-1-P level compared with the wild-typ
e strain, while the Glc-6-P and ATP levels were normal. These results sugge
st that Glc-1-P (or a related metabolite) may participate in the control of
Ca2+ uptake from the environment.