Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator
Artikel i vetenskaplig tidskrift, 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.

Författare

Renata Usaite

Danmarks Tekniske Universitet

Scripps Research Institute

Michael C Jewett

Harvard Medical School

Danmarks Tekniske Universitet

Ana Paula Oliveira

ETH Zurich

Danmarks Tekniske Universitet

John R. Yates

Scripps Research Institute

Lisbeth Olsson

Danmarks Tekniske Universitet

Chalmers University of Technology

Jens B Nielsen

Chalmers University of Technology

Danmarks Tekniske Universitet

Molecular Systems Biology

1744-4292 (ISSN)

Vol. 5 1-12

Ämneskategorier

Industriell bioteknik

Biokemi och molekylärbiologi

DOI

10.1038/msb.2009.67