title: Influence of inositol pyrophosphates on cellular energy dynamics.
abstract: With its high-energy phosphate bonds, adenosine triphosphate (ATP) is the main intracellular energy carrier. It also functions in most signaling pathways, as a phosphate donor or a precursor for cyclic adenosine monophosphate. We show here that inositol pyrophosphates participate in the control of intracellular ATP concentration. Yeasts devoid of inositol pyrophosphates have dysfunctional mitochondria but, paradoxically, contain four times as much ATP because of increased glycolysis. We demonstrate that inositol pyrophosphates control the activity of the major glycolytic transcription factor GCR1. Thus, inositol pyrophosphates regulate ATP concentration by altering the glycolytic/mitochondrial metabolic ratio. Metabolic reprogramming through inositol pyrophosphates is an evolutionary conserved mechanism that is also preserved in mammalian systems.
authors.affiliation: Cell Biology Unit, Medical Research Council Laboratory for Molecular Cell Biology, and Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szijgyarto
authors.forename: Assegid
authors.initials: A
authors.lastname: Garedew
authors.forename: Cristina
authors.initials: C
authors.lastname: Azevedo
authors.forename: Adolfo
authors.initials: A
authors.lastname: Saiardi
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D007295:Inositol Phosphates / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C076227:GCR1 protein, S cerevisiae; D007295:Inositol Phosphates; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D009243:NAD; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005947:Glucose