Antagonistic controls of autophagy and glycogen accumulation by snf1p, the yeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase pho85p

Z. Wang, W. A. Wilson, M. A. Fujino, Peter Roach

Research output: Contribution to journalArticle

198 Citations (Scopus)

Abstract

In the yeast Saccharomyces cerevisiae, glycogen is accumulated as a carbohydrate reserve when cells are deprived of nutrients. Yeast mutated in SNF1, a gene encoding a protein kinase required for glucose derepression, has diminished glycogen accumulation and concomitant inactivation of glycogen synthase. Restoration of synthesis in an snf1 strain results only in transient glycogen accumulation, implying the existence of other SNF1-dependent controls of glycogen storage. A genetic screen revealed that two genes involved in autophagy, APG1 and APG13, may be regulated by SNF1. Increased autophagic activity was observed in wild-type cells entering the stationary phase, but this induction was impaired in an snf1 strain. Mutants defective for autophagy were able to synthesize glycogen upon approaching the stationary phase, but were unable to maintain their glycogen stores, because subsequent synthesis was impaired and degradation by phosphorylase, Gph1p, was enhanced. Thus, deletion of GPH1 partially reversed the loss of glycogen accumulation in autophagy mutants. Loss of the vacuolar glucosidase, SGA1, also protected glycogen stores, but only very late in the stationary phase. Gph1p and Sga1p may therefore degrade physically distinct pools of glycogen. Pho85p is a cyclin-dependent protein kinase that antagonizes SNF1 control of glycogen synthesis. Induction of autophagy in pho85 mutants entering the stationary phase was exaggerated compared to the level in wild-type cells, but was blocked in apg1 pho85 mutants. We propose that Snf1p and Pho85p are, respectively, positive and negative regulators of autophagy, probably via Apg1 and/or Apg13. Defective glycogen storage in snf1 cells can be attributed to both defective synthesis upon entry into stationary phase and impaired maintenance of glycogen levels caused by the lack of autophagy.

Original languageEnglish
Pages (from-to)5742-5752
Number of pages11
JournalMolecular and Cellular Biology
Volume21
Issue number17
DOIs
StatePublished - 2001

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AMP-Activated Protein Kinases
Cyclin-Dependent Kinases
Autophagy
Glycogen
Yeasts
Glucosidases
Glycogen Synthase
Phosphorylases
Protein Kinases
Genes
Saccharomyces cerevisiae
Maintenance
Carbohydrates

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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Antagonistic controls of autophagy and glycogen accumulation by snf1p, the yeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase pho85p. / Wang, Z.; Wilson, W. A.; Fujino, M. A.; Roach, Peter.

In: Molecular and Cellular Biology, Vol. 21, No. 17, 2001, p. 5742-5752.

Research output: Contribution to journalArticle

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