Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator

Renata Usaite, Michael C. Jewett, Ana Paula Oliveira, John R. Yates, Lisbeth Olsson, Jens Nielsen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

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, Δsnf1, Δsnf4, and Δsnf1Δsnf4 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.

Original languageEnglish (US)
Article number319
JournalMolecular Systems Biology
Volume5
DOIs
StatePublished - Jan 20 2009

Keywords

  • Catabolic repression
  • Metabolome
  • Proteome
  • Transcriptome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Fingerprint

Dive into the research topics of 'Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator'. Together they form a unique fingerprint.

Cite this