title: Cyclophilin D in mitochondrial pathophysiology.
abstract: Cyclophilins are a family of peptidyl-prolyl cis-trans isomerases whose enzymatic activity can be inhibited by cyclosporin A. Sixteen cyclophilins have been identified in humans, and cyclophilin D is a unique isoform that is imported into the mitochondrial matrix. Here we shall (i) review the best characterized functions of cyclophilin D in mitochondria, i.e. regulation of the permeability transition pore, an inner membrane channel that plays an important role in the execution of cell death; (ii) highlight new regulatory interactions that are emerging in the literature, including the modulation of the mitochondrial F1FO ATP synthase through an interaction with the lateral stalk of the enzyme complex; and (iii) discuss diseases where cyclophilin D plays a pathogenetic role that makes it a suitable target for pharmacologic intervention.
authors.affiliation: Department of Biomedical Sciences and CNR Institute of Neuroscience, University of Padova, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Giorgio
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Soriano
authors.forename: Emy
authors.initials: E
authors.lastname: Basso
authors.forename: Elena
authors.initials: E
authors.lastname: Bisetto
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lippe
authors.forename: Michael A
authors.initials: MA
authors.lastname: Forte
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernardi
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016572:Cyclosporine / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D008954:Models, Biological; D054730:Protein Interaction Domains and Motifs; D000097322:Peptidyl-Prolyl Isomerase D
chemical_list: D019703:Calcineurin; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D016572:Cyclosporine; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D025261:Mitochondrial Proton-Translocating ATPases; C000631446:PPIF protein, mouse; C114456:PPID protein, human; D000097322:Peptidyl-Prolyl Isomerase D