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Modulation of mitochondrial ion transport by inorganic polyphosphate - essential role in mitochondrial permeability transition pore

Baev, AY; Negoda, A; Abramov, AY; (2017) Modulation of mitochondrial ion transport by inorganic polyphosphate - essential role in mitochondrial permeability transition pore. Journal of Bioenergetics and Biomembranes , 49 (1) pp. 49-55. 10.1007/s10863-016-9650-3. Green open access

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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 Ba(2+) and Ca(2+) 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.

Type: Article
Title: Modulation of mitochondrial ion transport by inorganic polyphosphate - essential role in mitochondrial permeability transition pore
Identifier: 10.1007/s10863-016-9650-3
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s10863-016-9650-3
Publisher version: http://dx.doi.org/10.1007/s10863-016-9650-3
Language: English
Additional information: © The Author(s) 2016. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Keywords: Ca2+, Inorganic polyphosphate, Mitochondrial permeability transition pore
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/1476866
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