title: Bidirectional fluxes of spermine across the mitochondrial membrane.
abstract: The polyamine spermine is transported into the mitochondrial matrix by an electrophoretic mechanism having as driving force the negative electrical membrane potential (ΔΨ). The presence of phosphate increases spermine uptake by reducing ΔpH and enhancing ΔΨ. The transport system is a specific uniporter constituted by a protein channel exhibiting two asymmetric energy barriers with the spermine binding site located in the energy well between the two barriers. Although spermine transport is electrophoretic in origin, its accumulation does not follow the Nernst equation for the presence of an efflux pathway. Spermine efflux may be induced by different agents, such as FCCP, antimycin A and mersalyl, able to completely or partially reduce the ΔΨ value and, consequently, suppress or weaken the force necessary to maintain spermine in the matrix. However this efflux may also take place in normal conditions when the electrophoretic accumulation of the polycationic polyamine induces a sufficient drop in ΔΨ able to trigger the efflux pathway. The release of the polyamine is most probably electroneutral in origin and can take place in exchange with protons or in symport with phosphate anion. The activity of both the uptake and efflux pathways induces a continuous cycling of spermine across the mitochondrial membrane, the rate of which may be prominent in imposing the concentrations of spermine in the inner and outer compartment. Thus, this event has a significant role on mitochondrial permeability transition modulation and consequently on the triggering of intrinsic apoptosis.
authors.affiliation: Department of Biomedical Sciences, University of Padua, Viale U. Bassi 58 B, 35131, Padua, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Grancara
authors.forename: Pamela
authors.initials: P
authors.lastname: Martinis
authors.forename: Sabrina
authors.initials: S
authors.lastname: Manente
authors.forename: Aida Nelly
authors.initials: AN
authors.lastname: García-Argáez
authors.forename: Giampiero
authors.initials: G
authors.lastname: Tempera
authors.forename: Marcantonio
authors.initials: M
authors.lastname: Bragadin
authors.forename: Lisa
authors.initials: L
authors.lastname: Dalla Via
authors.forename: Enzo
authors.initials: E
authors.lastname: Agostinelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Toninello
mesh_terms: D051336:Mitochondrial Membranes / Q000737:chemistry / Q000378:metabolism*; D013096:Spermine / Q000737:chemistry / Q000378:metabolism*
chemical_list: D013096:Spermine