title: Role of inorganic polyphosphate in mammalian cells: from signal transduction and mitochondrial metabolism to cell death.
abstract: Inorganic polyphosphate (polyP) is a polymer compromised of linearly arranged orthophosphate units that are linked through high-energy phosphoanhydride bonds. The chain length of this polymer varies from five to several thousand orthophosphates. PolyP is distributed in the most of the living organisms and plays multiple functions in mammalian cells, it is important for blood coagulation, cancer, calcium precipitation, immune response and many others. Essential role of polyP is shown for mitochondria, from implication into energy metabolism and mitochondrial calcium handling to activation of permeability transition pore (PTP) and cell death. PolyP is a gliotransmitter which transmits the signal in astrocytes via activation of P2Y1 receptors and stimulation of phospholipase C. PolyP-induced calcium signal in astrocytes can be stimulated by different lengths of this polymer but only long chain polyP induces mitochondrial depolarization by inhibition of respiration and opening of the PTP. It leads to induction of astrocytic cell death which can be prevented by inhibition of PTP with cyclosporine A. Thus, medium- and short-length polyP plays role in signal transduction and mitochondrial metabolism of astrocytes and long chain of this polymer can be toxic for the cells.
authors: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, WC1N 3BG London, U.K.
authors: Plamena R
authors: PR
authors: Angelova
authors: Faculty of Biology and Soil Science, National University of Uzbekistan, Tashkent 100174, Uzbekistan.
authors: Artyom Y
authors: AY
authors: Baev
authors: Institute of the Cell Biophysics, Russian Academy of Science, Pushchino, Moscow Region 142290, Russia.
authors: Alexey V
authors: AV
authors: Berezhnov
authors: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, WC1N 3BG London, U.K. a.abramov@ucl.ac.uk.
authors: Andrey Y
authors: AY
authors: Abramov
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D011122:Polyphosphates / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D018377:Neurotransmitter Agents; D011122:Polyphosphates
keywords: astrocytes; cell death; gliotransmitter; inorganic polyphosphate; mitochondria