title: Developmental accumulation of inorganic polyphosphate affects germination and energetic metabolism in Dictyostelium discoideum.
abstract: Inorganic polyphosphate (polyP) is composed of linear chains of phosphate groups linked by high-energy phosphoanhydride bonds. However, this simple, ubiquitous molecule remains poorly understood. The use of nonstandardized analytical methods has contributed to this lack of clarity. By using improved polyacrylamide gel electrophoresis we were able to visualize polyP extracted from Dictyostelium discoideum. We established that polyP is undetectable in cells lacking the polyphosphate kinase (DdPpk1). Generation of this ppk1 null strain revealed that polyP is important for the general fitness of the amoebae with the mutant strain displaying a substantial growth defect. We discovered an unprecedented accumulation of polyP during the developmental program, with polyP increasing more than 100-fold. The failure of ppk1 spores to accumulate polyP results in a germination defect. These phenotypes are underpinned by the ability of polyP to regulate basic energetic metabolism, demonstrated by a 2.5-fold decrease in the level of ATP in vegetative ppk1. Finally, the lack of polyP during the development of ppk1 mutant cells is partially offset by an increase of both ATP and inositol pyrophosphates, evidence for a model in which there is a functional interplay between inositol pyrophosphates, ATP, and polyP.
authors.affiliation: Medical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, United Kingdom;
authors.forename: Thomas Miles
authors.initials: TM
authors.lastname: Livermore
authors.affiliation: Medical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, United Kingdom; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Jonathan Robert
authors.initials: JR
authors.lastname: Chubb
authors.affiliation: Medical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, United Kingdom; dmcbado@ucl.ac.uk.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Saiardi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D004023:Dictyostelium / Q000378:metabolism*; D004734:Energy Metabolism; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000502:physiology; D011122:Polyphosphates / Q000378:metabolism*
chemical_list: D011122:Polyphosphates; D000255:Adenosine Triphosphate; D017856:Phosphotransferases (Phosphate Group Acceptor); C022424:polyphosphate kinase
keywords: inorganic polyphosphate; inositol pyrophosphate; metabolism; mitochondria; phosphate