title: Modulation of mitochondrial ion transport by inorganic polyphosphate - essential role in mitochondrial permeability transition pore.
abstract: Inorganic polyphosphate (polyP) is a biopolymer of phosphoanhydride-linked orthophosphate residues. PolyP is involved in multiple cellular processes including mitochondrial metabolism and cell death. We used artificial membranes and isolated mitochondria to investigate the role of the polyP in mitochondrial ion transport and in activation of PTP. Here, we found that polyP can modify ion permeability of de-energised mitochondrial membranes but not artificial membranes. This permeability was selective for Ba2+and Ca2+but not for other monovalent and bivalent cations and can be blocked by inhibitors of the permeability transition pore - cyclosporine A or ADP. Lower concentrations of polyP modulate calcium dependent permeability transition pore opening. Increase in polyP concentrations and elongation chain length of the polymer causes calcium independent swelling in energized conditions. Physiologically relevant concentrations of inorganic polyP can regulate calcium dependent as well calcium independent mitochondrial permeability transition pore opening. This raises the possibility that cytoplasmic polyP can be an important contributor towards regulation of the cell death.
authors.affiliation: National University of Uzbekistan, Tashkent, Uzbekistan.|Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada.
authors.forename: Artyom Y
authors.initials: AY
authors.lastname: Baev
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Negoda
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK. a.abramov@ucl.ac.uk.
authors.forename: Andrey Y
authors.initials: AY
authors.lastname: Abramov
mesh_terms: D000818:Animals; D016923:Cell Death; D017136:Ion Transport / Q000187:drug effects*; D008567:Membranes, Artificial; D008930:Mitochondria, Liver; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D051336:Mitochondrial Membranes; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling; D010539:Permeability; D011122:Polyphosphates / Q000494:pharmacology*; D051381:Rats
chemical_list: D008567:Membranes, Artificial; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011122:Polyphosphates
keywords: Ca2+; Inorganic polyphosphate; Mitochondrial permeability transition pore