title: Mitochondrial Permeability Transition: New Findings and Persisting Uncertainties.
abstract: Several insults cause the inner mitochondrial membrane to abruptly lose osmotic homeostasis, hence initiating a regulated variant of cell death known as 'mitochondrial permeability transition' (MPT)-driven necrosis. MPT provides an etiological contribution to several human disorders characterized by the acute loss of post-mitotic cells, including cardiac and cerebral ischemia. Nevertheless, the precise molecular determinants of MPT remain elusive, which considerably hampers the development of clinically implementable cardio- or neuroprotective strategies targeting this process. We summarize recent findings shedding new light on the supramolecular entity that mediates MPT, the so-called 'permeability transition pore complex' (PTPC). Moreover, we discuss hitherto unresolved controversies on MPT and analyze the major obstacles that still preclude the complete understanding and therapeutic targeting of this process.
authors.affiliation: Equipe 11 labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1138, 75006 Paris, France; Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France; Université Pierre et Marie Curie/Paris VI, 75006 Paris, France.
authors.forename: Valentina
authors.initials: V
authors.lastname: Izzo
authors.affiliation: Equipe 11 labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1138, 75006 Paris, France; Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France; Université Pierre et Marie Curie/Paris VI, 75006 Paris, France.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Bravo-San Pedro
authors.affiliation: Equipe 11 labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1138, 75006 Paris, France; Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France; Université Pierre et Marie Curie/Paris VI, 75006 Paris, France; Faculté de Medicine, Université Paris Sud/Paris XI, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sica
authors.affiliation: Equipe 11 labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1138, 75006 Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France; Université Pierre et Marie Curie/Paris VI, 75006 Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France; Department of Women's and Children's Health, Karolinska University Hospital, 17176 Stockholm, Sweden. Electronic address: kroemer@orange.fr.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: Equipe 11 labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1138, 75006 Paris, France; Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France; Université Pierre et Marie Curie/Paris VI, 75006 Paris, France. Electronic address: deadoc@vodafone.it.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
mesh_terms: D000818:Animals; D006801:Humans; D028361:Mitochondrial Diseases / Q000378:metabolism / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D008954:Models, Biological
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore
keywords: Bcl-2 protein family; adenine nucleotide translocator; cyclosporin A; mitochondrial F(1)F(O)-ATPase; necroptosis; p53; voltage-dependent anion channel