title: Enhanced amino acid utilization sustains growth of cells lacking Snf1/AMPK.
abstract: The metabolism of proliferating cells shows common features even in evolutionary distant organisms such as mammals and yeasts, for example the requirement for anabolic processes under tight control of signaling pathways. Analysis of the rewiring of metabolism, which occurs following the dysregulation of signaling pathways, provides new knowledge about the mechanisms underlying cell proliferation. The key energy regulator in yeast Snf1 and its mammalian ortholog AMPK have earlier been shown to have similar functions at glucose limited conditions and here we show that they also have analogies when grown with glucose excess. We show that loss of Snf1 in cells growing in 2% glucose induces an extensive transcriptional reprogramming, enhances glycolytic activity, fatty acid accumulation and reliance on amino acid utilization for growth. Strikingly, we demonstrate that Snf1/AMPK-deficient cells remodel their metabolism fueling mitochondria and show glucose and amino acids addiction, a typical hallmark of cancer cells.
authors.affiliation: SYSBIO, Centre of Systems Biology, Milan, Italy; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Nicastro
authors.affiliation: SYSBIO, Centre of Systems Biology, Milan, Italy; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Farida
authors.initials: F
authors.lastname: Tripodi
authors.affiliation: SYSBIO, Centre of Systems Biology, Milan, Italy; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Guzzi
authors.affiliation: SYSBIO, Centre of Systems Biology, Milan, Italy; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Reghellin
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Sakda
authors.initials: S
authors.lastname: Khoomrung
authors.affiliation: Department of Food, Environmental and Nutritional Sciences, University of Milan, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Capusoni
authors.affiliation: Department of Food, Environmental and Nutritional Sciences, University of Milan, Milan, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Compagno
authors.affiliation: SYSBIO, Centre of Systems Biology, Milan, Italy; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Airoldi
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
authors.affiliation: SYSBIO, Centre of Systems Biology, Milan, Italy; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Lilia
authors.initials: L
authors.lastname: Alberghina
authors.affiliation: SYSBIO, Centre of Systems Biology, Milan, Italy; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy. Electronic address: paola.coccetti@unimib.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Coccetti
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000172:deficiency* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D055162:Biocatalysis / Q000187:drug effects; D002244:Carbon / Q000378:metabolism; D049109:Cell Proliferation; D065150:Cellular Reprogramming / Q000187:drug effects; D002952:Citric Acid Cycle / Q000187:drug effects; D005227:Fatty Acids / Q000096:biosynthesis; D005285:Fermentation / Q000187:drug effects; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal; D005947:Glucose / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics; D008954:Models, Biological; D010085:Oxidative Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000596:Amino Acids; D005227:Fatty Acids; D018698:Glutamic Acid; D002244:Carbon; D000255:Adenosine Triphosphate; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: Budding yeast; Gene chip; Glucose; Metabolism; Respiration; Saccharomyces cerevisiae