Antagonistic controls of autophagy and glycogen accumulation by Snf1p, theyeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase Pho85p
Z. Wang et al., Antagonistic controls of autophagy and glycogen accumulation by Snf1p, theyeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase Pho85p, MOL CELL B, 21(17), 2001, pp. 5742-5752
In the yeast Saccharomyces cerevisiae, glycogen is accumulated as a carbohy
drate reserve when cells are deprived of nutrients. Yeast mutated in SNF1,
a gene encoding a protein kinase required for glucose derepression, has dim
inished glycogen accumulation and concomitant inactivation of glycogen synt
hase. Restoration of synthesis in an snf1 strain results only in transient
glycogen accumulation, implying the existence of other SNF1-dependent contr
ols of glycogen storage. A genetic screen revealed that two genes involved
in autophagy, APG1 and APG13, may be regulated by SNF1. Increased autophagi
c activity was observed in wild-type cells entering the stationary phase, b
ut this induction was impaired in an snf1 strain. Mutants defective for aut
ophagy were able to synthesize glycogen upon approaching the stationary pha
se, but were unable to maintain their glycogen stores, because subsequent s
ynthesis was impaired and degradation by phosphorylase, Gph1p, was enhanced
. Thus, deletion of GPH1 partially reversed the loss of glycogen accumulati
on in autophagy mutants. Loss of the vacuolar glucosidase, SGA1, also prote
cted 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 glyco
gen synthesis. Induction of autophagy in pho85 mutants entering the station
ary 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, respe
ctively, positive and negative regulators of autophagy, probably via Apg1 a
nd/or Apg13. Defective glycogen storage in snf1 cells can be attributed to
both defective synthesis upon entry into stationary phase and impaired main
tenance of glycogen levels caused by the lack of autophagy.