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Investigating the Mitochondrial Permeability Transition Pore in Disease Phenotypes and Drug Screening

Bhosale, G; Duchen, MR; (2019) Investigating the Mitochondrial Permeability Transition Pore in Disease Phenotypes and Drug Screening. Current Protocols in Pharmacology , 85 (1) , Article e59. 10.1002/cpph.59. (In press). Green open access

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Abstract

Mitochondria act as 'sinks' for Ca2+ signaling, with mitochondrial Ca2+ uptake linking physiological stimuli to increased ATP production. However, mitochondrial Ca2+ overload can induce a cellular catastrophe by opening of the mitochondrial permeability transition pore (mPTP). This pore is a large conductance pathway in the inner mitochondrial membrane that causes bioenergetic collapse and appears to represent a final common path to cell death in many diseases. The role of the mPTP as a determinant of disease outcome is best established in ischemia/reperfusion injury in the heart, brain, and kidney, and it is also implicated in neurodegenerative disorders and muscular dystrophies. As the probability of pore opening can be modulated by drugs, it represents a useful pharmacological target for translational research in drug discovery. Described in this unit is a protocol utilizing isolated mitochondria to quantify this phenomenon and to develop a high-throughput platform for phenotypic screens for Ca2+ dyshomeostasis.

Type: Article
Title: Investigating the Mitochondrial Permeability Transition Pore in Disease Phenotypes and Drug Screening
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/cpph.59
Publisher version: https://doi.org/10.1002/cpph.59
Language: English
Additional information: © 2019 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: calcium, mitochondria, permeability transition pore
UCL classification: UCL > Provost and Vice Provost Offices
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 Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10076196
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