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      Conventional and emerging roles of the energy sensor Snf1/AMPK in Saccharomyces cerevisiae

      review-article
      1 , 2 , * , 1 , 3 , 1 , 2
      Microbial Cell
      Shared Science Publishers OG
      budding yeast, metabolism, stress response, aging, transcription, signaling, cell cycle, endocytosis, DNA damage, glucose repression

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          Abstract

          All proliferating cells need to match metabolism, growth and cell cycle progression with nutrient availability to guarantee cell viability in spite of a changing environment. In yeast, a signaling pathway centered on the effector kinase Snf1 is required to adapt to nutrient limitation and to utilize alternative carbon sources, such as sucrose and ethanol. Snf1 shares evolutionary conserved functions with the AMP-activated Kinase (AMPK) in higher eukaryotes which, activated by energy depletion, stimulates catabolic processes and, at the same time, inhibits anabolism. Although the yeast Snf1 is best known for its role in responding to a number of stress factors, in addition to glucose limitation, new unconventional roles of Snf1 have recently emerged, even in glucose repressing and unstressed conditions. Here, we review and integrate available data on conventional and non-conventional functions of Snf1 to better understand the complexity of cellular physiology which controls energy homeostasis.

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          Integration of biological networks and gene expression data using Cytoscape.

          Cytoscape is a free software package for visualizing, modeling and analyzing molecular and genetic interaction networks. This protocol explains how to use Cytoscape to analyze the results of mRNA expression profiling, and other functional genomics and proteomics experiments, in the context of an interaction network obtained for genes of interest. Five major steps are described: (i) obtaining a gene or protein network, (ii) displaying the network using layout algorithms, (iii) integrating with gene expression and other functional attributes, (iv) identifying putative complexes and functional modules and (v) identifying enriched Gene Ontology annotations in the network. These steps provide a broad sample of the types of analyses performed by Cytoscape.
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            Dynamics and diversity in autophagy mechanisms: lessons from yeast.

            Autophagy is a fundamental function of eukaryotic cells and is well conserved from yeast to humans. The most remarkable feature of autophagy is the synthesis of double membrane-bound compartments that sequester materials to be degraded in lytic compartments, a process that seems to be mechanistically distinct from conventional membrane traffic. The discovery of autophagy in yeast and the genetic tractability of this organism have allowed us to identify genes that are responsible for this process, which has led to the explosive growth of this research field seen today. Analyses of autophagy-related (Atg) proteins have unveiled dynamic and diverse aspects of mechanisms that underlie membrane formation during autophagy.
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              AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo.

              AMPK is a metabolic sensor that helps maintain cellular energy homeostasis. Despite evidence linking AMPK with tumor suppressor functions, the role of AMPK in tumorigenesis and tumor metabolism is unknown. Here we show that AMPK negatively regulates aerobic glycolysis (the Warburg effect) in cancer cells and suppresses tumor growth in vivo. Genetic ablation of the α1 catalytic subunit of AMPK accelerates Myc-induced lymphomagenesis. Inactivation of AMPKα in both transformed and nontransformed cells promotes a metabolic shift to aerobic glycolysis, increased allocation of glucose carbon into lipids, and biomass accumulation. These metabolic effects require normoxic stabilization of the hypoxia-inducible factor-1α (HIF-1α), as silencing HIF-1α reverses the shift to aerobic glycolysis and the biosynthetic and proliferative advantages conferred by reduced AMPKα signaling. Together our findings suggest that AMPK activity opposes tumor development and that its loss fosters tumor progression in part by regulating cellular metabolic pathways that support cell growth and proliferation. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Microb Cell
                Microb Cell
                Microb Cell
                Microb Cell
                Microbial Cell
                Shared Science Publishers OG
                2311-2638
                29 September 2018
                05 November 2018
                : 5
                : 11
                : 482-494
                Affiliations
                [1 ]Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
                [2 ]SYSBIO, Centre of Systems Biology, Milan, Italy.
                [3 ]Present address: Department of Biology, University of Fribourg, Fribourg, Switzerland.
                Author notes

                Conflict of interest: The authors have no conflicts of interest to declare.

                Please cite this article as: Paola Coccetti, Raffaele Nicastro and Farida Tripodi ( 2018). Conventional and emerging roles of the energy sensor Snf1/AMPK in Saccharomyces cerevisiae. Microbial Cell 5(11): 482-494. doi: 10.15698/mic2018.11.655

                Article
                MIC0178E139
                10.15698/mic2018.11.655
                6244292
                30483520
                05da57ec-5aa7-4cd3-9d4c-db8d3d0e5ecb
                Copyright @ 2018

                This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

                History
                : 29 June 2018
                : 23 August 2018
                Funding
                Work in the authors' laboratory was supported by SysBioNet project, a MIUR initiative from the Italian Roadmap of European Strategy Forum on Research Infrastructures (ESFRI). F.T. has been supported by fellowships from MIUR, R.N. was funded by a fellowship from SysBioNet.
                Categories
                Microbiology
                Applied Microbiology
                Molecular Biology
                Genetics

                budding yeast,metabolism,stress response,aging,transcription,signaling,cell cycle,endocytosis,dna damage,glucose repression

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