Mapping the interaction of Snf1 with TORC1 in
            <i>Saccharomyces cerevisiae</i>

Zhang, Jie; Vaga, Stefania; Chumnanpuen, Pramote; Kumar, Rahul; Vemuri, Goutham N.; Aebersold, Ruedi; Nielsen, Jens

doi:10.1038/msb.2011.80

Cited by 170 publications

(64 citation statements)

References 72 publications

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“…It is worth noting that our data for Snf1 stand in conflict with conclusions drawn in a previous study of TORC1-Snf1 signaling by Zhang et al (2011). Zhang et al (2011) compared the global transcription and phosphorylation changes that occur in tor1D and snf1D cells in several stress and starvation conditions, including glucose starvation.…”

Section: Discussioncontrasting

confidence: 55%

“…Zhang et al (2011) compared the global transcription and phosphorylation changes that occur in tor1D and snf1D cells in several stress and starvation conditions, including glucose starvation. They then argued that TORC1 and Snf1 must act independently since deletion of TOR1 has significantly less influence on transcription and protein phosphorylation than deletion of SNF1.…”

Section: Discussionmentioning

confidence: 99%

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State Transitions in the TORC1 Signaling Pathway and Information Processing in Saccharomyces cerevisiae

2014

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TOR kinase complex I (TORC1) is a key regulator of cell growth and metabolism in all eukaryotes. Previous studies in yeast have shown that three GTPases-Gtr1, Gtr2, and Rho1-bind to TORC1 in nitrogen and amino acid starvation conditions to block phosphorylation of the S6 kinase Sch9 and activate protein phosphatase 2A (PP2A). This leads to downregulation of 450 Sch9-dependent protein and ribosome synthesis genes and upregulation of 100 PP2A-dependent nitrogen assimilation and amino acid synthesis genes. Here, using bandshift assays and microarray measurements, we show that the TORC1 pathway also populates three other stress/starvation states. First, in glucose starvation conditions, the AMP-activated protein kinase (AMPK/Snf1) and at least one other factor push the TORC1 pathway into an off state, in which Sch9-branch signaling and PP2A-branch signaling are both inhibited. Remarkably, the TORC1 pathway remains in the glucose starvation (PP2A inhibited) state even when cells are simultaneously starved for nitrogen and glucose. Second, in osmotic stress, the MAPK Hog1/p38 drives the TORC1 pathway into a different state, in which Sch9 signaling and PP2A-branch signaling are inhibited, but PP2A-branch signaling can still be activated by nitrogen starvation. Third, in oxidative stress and heat stress, TORC1-Sch9 signaling is blocked while weak PP2A-branch signaling occurs. Together, our data show that the TORC1 pathway acts as an information-processing hub, activating different genes in different conditions to ensure that available energy is allocated to drive growth, amino acid synthesis, or a stress response, depending on the needs of the cell.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

State Transitions in the TORC1 Signaling Pathway and Information Processing in Saccharomyces cerevisiae

2014

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“…In yeast, such regulation is not yet well established. Evidence suggests that TORC1 and Snf1p/AMPK converge in the regulation of fatty acid metabolism and other outputs independently (57). A recent work provided strong evidence that Snf1p/AMPK participates as a possible upstream regulator of the TORC1 pathway under glucose-limiting conditions (58).…”

Section: Discussionmentioning

confidence: 99%

TORC1 Inhibition Induces Lipid Droplet Replenishment in Yeast

Madeira

Masuda

Maya‐Monteiro

et al. 2015

Molecular and Cellular Biology

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bLipid droplets (LDs) are intracellular structures that regulate neutral lipid homeostasis. In mammals, LD synthesis is inhibited by rapamycin, a known inhibitor of the mTORC1 pathway. In Saccharomyces cerevisiae, LD dynamics are modulated by the growth phase; however, the regulatory pathways involved are unknown. Therefore, we decided to study the role of the TORC1 pathway on LD metabolism in S. cerevisiae. Interestingly, rapamycin treatment resulted in a fast LD replenishment and growth inhibition. The discovery that osmotic stress (1 M sorbitol) also induced LD synthesis but not growth inhibition suggested that the induction of LDs in yeast is not a secondary response to reduced growth. The induction of LDs by rapamycin was due to increased triacylglycerol but not sterol ester synthesis. Induction was dependent on the TOR downstream effectors, the PP2A-related phosphatase Sit4p and the regulatory protein Tap42p. The TORC1-controlled transcriptional activators Gln3p, Gat1p, Rtg1p, and Rtg3p, but not Msn2p and Msn4p, were required for full induction of LDs by rapamycin. Furthermore, we show that the deletion of Gln3p and Gat1p transcription factors, which are activated in response to nitrogen availability, led to abnormal LD dynamics. These results reveal that the TORC1 pathway is involved in neutral lipid homeostasis in yeast. Lipid droplets (LDs) are intracellular structures formed by a core of neutral lipids, mainly triacylglycerols (TAG) and sterol esters (SE), which are delimited by a phospholipid monolayer embedded with proteins primarily related to lipid metabolism (1-3). At first, LDs were believed to be mere neutral lipid deposits, but later it became clear that LDs play other important roles in cellular physiology. The main function of LDs is to maintain cellular lipid homeostasis (4, 5), and it was shown that defects in the mobilization of neutral lipids from LDs are related to type 2 diabetes, inflammation, neurodegenerative disorders, and cancer (6-8). In addition to their importance in health, LDs also are studied in oleaginous yeast for their exploitation as cellular oil factories for biofuel production (9).Although the metabolic steps of LD biogenesis are well known, the signals that govern LD dynamics are not clear yet. Because the signaling pathways are well conserved between yeast and mammals, Saccharomyces cerevisiae has been a model for studying LD dynamics. In S. cerevisiae, LDs follow a particular dynamic tightly linked to the growth phase and to the nutritional status of the cell (10, 11). When quiescent yeast cells encounter a rich medium containing glucose, cells must exit G 0 in order to start duplication and cell growth (12). This start demands a large amount of sterols and fatty acids, leading to the strong mobilization of the neutral lipids stored in LDs. As a result, LDs are diminished in number and in size (10). After this strong lipolytic phase, yeast cells shift to a lipogenic phase to replenish the levels of LDs, reaching its maximum at early stationary phase (10, 11).The regu...

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“…However, the phosphorylation sites in Acc1 remain to be determined. snf1 mutant cells have a higher amount of fatty acids under glucose-limiting conditions (Usaite et al 2009;Zhang et al 2011). Thus, the role of AMPK in the regulation of lipogenesis seems to be evolutionarily conserved.…”

Section: Opposing Roles Of Torc1 and Ampk In Controlling Autophagymentioning

confidence: 99%

The Opposing Actions of Target of Rapamycin and AMP-Activated Protein Kinase in Cell Growth Control

Hindupur

González

Hall

2015

Cold Spring Harb Perspect Biol

121

107

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Mapping the interaction of Snf1 with TORC1 in Saccharomyces cerevisiae

Abstract: Nutrient sensing and coordination of metabolic pathways are crucial functions for living cells. A combined analysis of the yeast transcriptome, phosphoproteome and metabolome is used to investigate the interactions between the Snf1 and TORC1 pathways under nutrient-limited conditions.

Cited by 170 publications

References 72 publications

State Transitions in the TORC1 Signaling Pathway and Information Processing in Saccharomyces cerevisiae

State Transitions in the TORC1 Signaling Pathway and Information Processing in Saccharomyces cerevisiae

TORC1 Inhibition Induces Lipid Droplet Replenishment in Yeast

The Opposing Actions of Target of Rapamycin and AMP-Activated Protein Kinase in Cell Growth Control

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