title: Spermine cycling in mitochondria is mediated by adenine nucleotide translocase activity: mechanism and pathophysiological implications.
abstract: Spermine, besides to be transported in mitochondria by an energy dependent electrophoretic mechanism, can be also released by two different mechanisms. The first one is induced in deenergizing conditions by FCCP or antimycin A and it is mediated by an electroneutral exchange spermine protons. The second one takes place in energizing conditions during the activity of the adenine nucleotide translocase and is mediated by an electroneutral symport mechanism involving the efflux in co-transport of spermine and phosphate and the exchange of exogenous ADP with endogenous ATP. The triggering of this mechanism permits an alternating cycling of spermine across the mitochondrial membrane, that is spermine is transported or released by energized mitochondria in the absence or presence of ATP synthesis, respectively. The physiological implications of this cycling of spermine are related to the induction or prevention of mitochondrial permeability transition and, consequently, on apoptosis or its prevention.
authors.affiliation: Department of Biochemical Sciences, SAPIENZA University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Grancara
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via F. Marzolo 5, 35131, Padua, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Dalla Via
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via F. Marzolo 5, 35131, Padua, Italy.
authors.forename: Aida Nelly
authors.initials: AN
authors.lastname: García-Argáez
authors.affiliation: Department of Biochemical Sciences, SAPIENZA University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohkubo
authors.affiliation: Department of Sense Organs, Faculty Medicine and Dentistry, SAPIENZA University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Pacella
authors.affiliation: Department of Molecular Sciences and Nanosystems, Ca' Foscari University of Venice, Venice, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Manente
authors.affiliation: Department of Molecular Sciences and Nanosystems, Ca' Foscari University of Venice, Venice, Italy.
authors.forename: Marcantonio
authors.initials: M
authors.lastname: Bragadin
authors.affiliation: Department of Biomedical Sciences, University of Padua, Viale U. Bassi 58 B, 35131, Padua, Italy. antonio.toninello@unipd.it.|Department of Biomedical Sciences, University of Padua, Viale G. Colombo 3, 35131, Padua, Italy. antonio.toninello@unipd.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Toninello
authors.affiliation: Department of Biochemical Sciences, SAPIENZA University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Agostinelli
mesh_terms: D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D017209:Apoptosis; D001693:Biological Transport, Active / Q000187:drug effects; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D013096:Spermine; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000968:Antimycin A; D000226:Mitochondrial ADP, ATP Translocases
keywords: Adenine nucleotide translocase; Mitochondria; Mitochondrial permeability transition; Polyamines; Reactive oxygen species