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

Investigating the Mitochondrial Permeability Transition Pore in Disease Phenotypes and Drug Screening. Curr Protoc Pharmacol. 2019 May 13;:e59 Authors: Bhosale G, Duchen MR 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. © 2019 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no mo...
Source: Current Protocols in Pharmacology - Category: Drugs & Pharmacology Tags: Curr Protoc Pharmacol Source Type: research