The mitochondrial permeability transition pore: Molecular nature and role as a target in cardioprotection. (January 2015)

• Record Type: Journal Article
• Authors: Bernardi, Paolo; Di Lisa, Fabio
• Is Part Of: Journal of molecular and cellular cardiology. Volume 78(2015:Jan.)
• Page Start: 100
• Page End: 106
• Publication Date: 2015-01
• Subjects: ANT adenine nucleotide translocase -- CsA cyclosporin A -- CyP cyclophilin -- Drp1 dynamin-related protein 1 -- Δψm mitochondrial membrane potential -- ERK extracellular signal regulated kinase -- GSK glycogen synthase kinase -- IMM inner mitochondrial membrane -- I/R ischemia–reperfusion -- MMC mitochondrial megachannel -- OMM outer mitochondrial membrane -- PKA cyclic AMP-dependent protein kinase -- PKG cyclic GMP-dependent protein kinase -- PPIase peptidylprolyl cis-trans isomerase -- PT permeability transition -- PTP permeability transition pore -- ROS reactive oxygen species -- TSPO transport protein of 18 kDa -- VDAC voltage-dependent anion channel; Mitochondria -- Permeability transition pore -- Ischemia–reperfusion injury; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2014.09.023
• Languages: English
• ISSNs: 0022-2828

Abstract

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: The mitochondrial permeability transition pore plays a key role in heart disease. Existing models for the permeability transition pore are critically reviewed. F-ATP synthase is the best molecular candidate for pore formation. Cyclophilin D is an important pore regulator but not a structural component. Cyclophilin inhibitors are promising but promiscuous drugs.