Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator
Journal article, 2009

Highly conserved among eukaryotic cells, ghe 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, ∆snf1, ∆snf4, and ∆snf1∆snf4 knockout strains. Using four newly developed computional 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 that 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.

Author

Renata Usaite

Technical University of Denmark (DTU)

Scripps Research Institute

Michael C Jewett

Technical University of Denmark (DTU)

Harvard Medical School

Ana Paula Oliveira

Technical University of Denmark (DTU)

Swiss Federal Institute of Technology in Zürich (ETH)

John R. Yates

Scripps Research Institute

Lisbeth Olsson

Technical University of Denmark (DTU)

Chalmers

Jens B Nielsen

Chalmers

Technical University of Denmark (DTU)

Molecular Systems Biology

17444292 (eISSN)

Vol. 5 319 1-12 319

Subject Categories

Industrial Biotechnology

Biochemistry and Molecular Biology

DOI

10.1038/msb.2009.67

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4/5/2022 7