Mitochondrial respiratory mutants in yeast inhibit glycogen accumulation by blocking activation of glycogen synthase.
Control of glycogen synthase activity by protein phosphorylation is important for regulating the synthesis of glycogen. In this report, we describe a regulatory linkage between the ability of yeast cells to respire and activation of glycogen synthase. Strains containing respiration-deficient mutations in genes such as COQ3, required for the synthesis of coenzyme Q, were reduced in their ability to accumulate glycogen in response to limiting glucose. This lowered glycogen accumulation results from inactivation of the rate-determining enzyme, glycogen synthase (Gsy2p). Reduced glycogen synthase activity is coincident with lowered glucose 6-phosphate and ATP levels in the respiration-deficient cells deprived of glucose. Alanine substitutions of three previously characterized phosphorylation sites in Gsy2p, Ser-650, Ser-654, or Thr-667, each suppressed the glycogen defect in cells unable to respire, suggesting that inactivation of this enzyme is mediated by phosphorylation of these residues. Inactivation of glycogen synthase requires the RAS signaling pathway that controls cAMP-dependent protein kinase and is independent of Pho85p previously identified as a Gsy2p kinase. These results suggest that yeast cells unable to shift from a fermentative to a respiratory metabolic regimen block accumulation of glycogen by inactivating Gsy2p through protein phosphorylation.
Yang
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R
Department of Biochemistry and Molecular Biology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5122, USA.
Chun
K T
KT
Wek
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RC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation; D005656:Fungal Proteins; D005947:Glucose / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis*; D006006:Glycogen Synthase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010101:Oxygen Consumption / Q000235:genetics*; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D005656:Fungal Proteins; D007527:Isoenzymes; C028325:ubiquinone Q3; D014451:Ubiquinone; D013912:Threonine; D012694:Serine; D019298:Glucose-6-Phosphate; D000255:Adenosine Triphosphate; D006003:Glycogen; D006006:Glycogen Synthase; D017868:Cyclic AMP-Dependent Protein Kinases; D018631:ras Proteins; D005947:Glucose