title: The mitochondrial permeability transition pore in AD 2016: An update.
abstract: Over the past 30years the mitochondrial permeability transition - the permeabilization of the inner mitochondrial membrane due to the opening of a wide pore - has progressed from being considered a curious artifact induced in isolated mitochondria by Ca(2+) and phosphate to a key cell-death-inducing process in several major pathologies. Its relevance is by now universally acknowledged and a pharmacology targeting the phenomenon is being developed. The molecular nature of the pore remains to this day uncertain, but progress has recently been made with the identification of the FOF1 ATP synthase as the probable proteic substrate. Researchers sharing this conviction are however divided into two camps: these believing that only the ATP synthase dimers or oligomers can form the pore, presumably in the contact region between monomers, and those who consider that the ring-forming c subunits in the FO sector actually constitute the walls of the pore. The latest development is the emergence of a new candidate: Spastic Paraplegia 7 (SPG7), a mitochondrial AAA-type membrane protease which forms a 6-stave barrel. This review summarizes recent developments of research on the pathophysiological relevance and on the molecular nature of the mitochondrial permeability transition pore. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
authors.affiliation: CNR Neuroscience Institute, Viale G. Colombo 3, 35121 Padova, Italy; University of Padova, Department of Biomedical Sciences, Viale G. Colombo 3, 35121 Padova, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Biasutto
authors.affiliation: CNR Neuroscience Institute, Viale G. Colombo 3, 35121 Padova, Italy; University of Padova, Department of Biomedical Sciences, Viale G. Colombo 3, 35121 Padova, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Azzolini
authors.affiliation: CNR Neuroscience Institute, Viale G. Colombo 3, 35121 Padova, Italy; University of Padova, Department of Biology, Viale G. Colombo 3, 35121 Padova, Italy.
authors.forename: Ildikò
authors.initials: I
authors.lastname: Szabò
authors.affiliation: CNR Neuroscience Institute, Viale G. Colombo 3, 35121 Padova, Italy; University of Padova, Department of Biomedical Sciences, Viale G. Colombo 3, 35121 Padova, Italy. Electronic address: zoratti@mail.bio.unipd.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Zoratti
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000378:metabolism
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D000255:Adenosine Triphosphate; D008666:Metalloendopeptidases; C112889:SPG7 protein, human; D006180:Proton-Translocating ATPases; D000074183:ATPases Associated with Diverse Cellular Activities; D021983:Cyclophilins
keywords: Cyclophilin D; F(O)F(1) ATP synthase; Mitochondrial permeability transition pore (mPTP); Spastic paraplegia 7 (SPG7)