Molecular identity of the mitochondrial permeability transition pore and its role in ischemia-reperfusion injury. (January 2015)

• Record Type: Journal Article
• Authors: Morciano, Giampaolo; Giorgi, Carlotta; Bonora, Massimo; Punzetti, Silvia; Pavasini, Rita; Wieckowski, Mariusz R.; Campo, Gianluca; Pinton, Paolo
• Is Part Of: Journal of molecular and cellular cardiology. Volume 78(2015:Jan.)
• Page Start: 142
• Page End: 153
• Publication Date: 2015-01
• Subjects: ADP adenosine diphosphate -- ANT adenine nucleotide transporter -- ATP adenine triphosphate -- C1QBP complement component 1Q subcomponent-binding protein -- Ca2 + calcium -- CK creatine kinase -- CsA cyclosporine A -- CYCLE CYCLosporinE A in reperfused acute myocardial infarction -- ER endoplasmic reticulum -- ETC electron transport chain -- FADD Fas-activated with death domain -- FLIP FLICE-inhibitory protein -- GIK glucose-insulin-potassium -- GLP-1 glucagon-like peptide 1 -- GSK3-β glycogen synthase kinase 3 beta -- HF heart failure -- HK hexokinase -- Hot-DOG 3H 2-deoxyglucose -- IHD ischemic heart disease -- IF-1 inhibitor protein F1 -- IMM inner mitochondrial membrane -- IMS intermembrane space -- IRI ischemia-reperfusion injury -- K+ potassium -- LV left ventricular -- Mg2 + magnesium -- MI myocardial infarction -- MITOCARE prospective, multicenter, randomized, double-blind, placebo-controlled, phase IIa study -- MPT mitochondrial permeability transition -- mPTP mitochondrial permeability transition pore -- mtCypD mitochondrial cyclophilin D -- MRI magnetic resonance imaging -- mTOR mammalian target of rapamycin -- MVO microvascular obstruction -- Na+ sodium -- NO nitric oxide -- OMM outer mitochondrial membrane -- OSCP oligomycin sensitivity conferring protein -- OXPHOS oxidative phosphorylation -- PCI percutaneous coronary intervention -- PEG polyethylene glycol -- Pi inorganic phosphate -- PiC inorganic phosphate carrier -- PM plasma membrane -- PPIF peptidylprolyl isomerase f -- PK11195 N-butan-2-yl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide -- PK protein kinase -- RISK reperfusion injury survival kinase -- RO5-4864 4′-chlorodiazepam -- ROS reactive oxygen species -- SAFE survivor activating factor enhancement -- SR sarcoplasmic reticulum -- STEMI ST elevation myocardial infarction -- TIMI thrombolysis in MI -- TNFα tumor necrosis factor alpha -- TNFR1 TNF receptor 1 -- TRAIL TNF-related apoptosis-inducing ligand -- TRO40303 3, 5-seco-4-nor-cholestan-5-one oxime-3-ol -- TSPO translocator protein -- VDAC voltage-dependent anion channel; Mitochondrial permeability transition pore, MPTP -- Permeability transition pore, PTP -- Cell death -- Apoptosis -- Necrosis -- Ischemia reperfusion injury; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2014.08.015
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: The mitochondrial permeability transition is a key event in cell death. Intense research efforts have been focused on elucidating the molecular components of the mitochondrial permeability transition pore (mPTP) to improve the understanding and treatment of various pathologies, including neurodegenerative disorders, cancer and cardiac diseases. Several molecular factors have been proposed as core components of the mPTP; however, further investigation has indicated that these factors are among a wide range of regulators. Thus, the scientific community lacks a clear model of the mPTP. Here, we review the molecular factors involved in the regulation and formation of the mPTP. Furthermore, we propose that the mitochondrial ATP synthase, specifically its c subunit, is the central core component of the mPTP complex. Moreover, we discuss the involvement of the mPTP in ischemia and reperfusion as well as the results of clinical studies targeting the mPTP to ameliorate ischemia-reperfusion injury. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease". Highlights: The c ring of mitochondrial ATP synthase is a critical component of the mPTP. Mitochondria play a key role in necrosis and apoptosis in myocardial infarction. mPTP is an important player in ischemia-reperfusion injury. Ischemia-reperfusion injury induces dramatic increases in mitochondrial permeability. mPTP represents an important therapeutic target to treat myocardial ischemia-reperfusion injury.