Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator.
Highly conserved among eukaryotic cells, the AMP-activated kinase (AMPK) is a central regulator of carbon metabolism. To map the complete network of interactions around AMPK in yeast (Snf1) and to evaluate the role of its regulatory subunit Snf4, we measured global mRNA, protein and metabolite levels in wild type, Deltasnf1, Deltasnf4, and Deltasnf1Deltasnf4 knockout strains. Using four newly developed computational tools, including novel DOGMA sub-network analysis, we showed the benefits of three-level ome-data integration to uncover the global Snf1 kinase role in yeast. We for the first time identified Snf1's global regulation on gene and protein expression levels, and showed that yeast Snf1 has a far more extensive function in controlling energy metabolism than reported earlier. Additionally, we identified complementary roles of Snf1 and Snf4. Similar to the function of AMPK in humans, our findings showed that Snf1 is a low-energy checkpoint and that yeast can be used more extensively as a model system for studying the molecular mechanisms underlying the global regulation of AMPK in mammals, failure of which leads to metabolic diseases.
Usaite
Renata
R
Department of Systems Biology, Center for Microbial Biotechnology, BioCentrum-DTU, Technical University of Denmark, Lyngby, Denmark.
Jewett
Michael C
MC
Oliveira
Ana Paula
AP
Yates
John R
JR
Olsson
Lisbeth
L
Nielsen
Jens
J
D002244:Carbon / Q000378:metabolism; D002331:Carnitine / Q000378:metabolism; D030541:Databases, Genetic; D004734:Energy Metabolism / Q000235:genetics*; D005227:Fatty Acids / Q000096:biosynthesis; D053263:Gene Regulatory Networks / Q000235:genetics*; D017930:Genes, Reporter; D050356:Lipid Metabolism; D055442:Metabolome / Q000235:genetics; D010084:Oxidation-Reduction; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins
D005227:Fatty Acids; D029701:Saccharomyces cerevisiae Proteins; D002244:Carbon; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D002331:Carnitine