title: Molecular identity of the mitochondrial permeability transition pore and its role in ischemia-reperfusion injury.
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".
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Morciano
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Giorgi
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bonora
authors.affiliation: Cardiovascular Institute, Azienda Ospedaliero-Universitaria S. Anna and LTTA Center, Ferrara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Punzetti
authors.affiliation: Cardiovascular Institute, Azienda Ospedaliero-Universitaria S. Anna and LTTA Center, Ferrara, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Pavasini
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Mariusz R
authors.initials: MR
authors.lastname: Wieckowski
authors.affiliation: Cardiovascular Institute, Azienda Ospedaliero-Universitaria S. Anna and LTTA Center, Ferrara, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Campo
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy. Electronic address: pnp@unife.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism; D058990:Molecular Targeted Therapy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D009336:Necrosis / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002316:Cardiotonic Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D021122:Protein Subunits; D017382:Reactive Oxygen Species; D025261:Mitochondrial Proton-Translocating ATPases; D002118:Calcium
keywords: Apoptosis; Cell death; Ischemia reperfusion injury; Mitochondrial permeability transition pore, MPTP; Necrosis; Permeability transition pore, PTP