title: The mPTP and its regulatory proteins: final common targets of signalling pathways for protection against necrosis.
abstract: The mitochondrial permeability transition pore (mPTP) is a non-selective, large-conductance channel that is closed under physiological conditions. Opening of the mPTP, leading to abolition of mitochondrial functions, is a major mechanism of myocyte necrosis by ischaemia/reperfusion, and direct inhibition of mPTP opening by use of pharmacological or genetic manipulations limits infarct size in vivo. Multiple pro-survival signal pathways commonly target the mPTP and inhibit its opening. Although the molecular structure of the mPTP has not been established, recent studies have characterized roles of each mPTP subunit and functions of several proteins directly interacting with the mPTP. This article briefly describes the understanding of mPTP regulation and interaction of the mPTP with four proteins (hexokinase II, glycogen synthase kinase-3β, signal transducer and activator of transcription 3, and sirtuin 3) that are downstream of signal pathways relevant to protection from ischaemia/reperfusion injury.
authors.affiliation: Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. miura@sapmed.ac.jp
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Miura
authors.forename: Masaya
authors.initials: M
authors.lastname: Tanno
mesh_terms: D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006593:Hexokinase / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D015427:Reperfusion Injury / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D056566:Sirtuin 3 / Q000378:metabolism
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D050796:STAT3 Transcription Factor; D006593:Hexokinase; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D056566:Sirtuin 3