The mitochondrial permeability transition pore: Molecular nature and role as a target in cardioprotection

Abstract

The mitochondrial permeability transition (PT) – an abrupt increase permeability of the inner membrane to solutes – is a causative event in ischemia–reperfusion injury of the heart, and the focus of intense research in cardioprotection. The PT is due to opening of the PT pore (PTP), a high conductance channel that is critically regulated by a variety of pathophysiological effectors. Very recent work indicates that the PTP forms from the F-ATP synthase, which would switch from an energy-conserving to an energy-dissipating device. This review provides an update on the current debate on how this transition is achieved, and on the PTP as a target for therapeutic intervention. This article is part of a Special Issue entitled "Mitochondria: from basic mitochondrial biology to cardiovascular disease".

Highlights

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  The mitochondrial permeability transition pore plays a key role in heart disease.

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  Existing models for the permeability transition pore are critically reviewed.

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  F-ATP synthase is the best molecular candidate for pore formation.

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  Cyclophilin D is an important pore regulator but not a structural component.

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  Cyclophilin inhibitors are promising but promiscuous drugs.