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.
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Abbreviations
- ΔΨ:
-
Electrical transmembrane potential
- FCCP:
-
Carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazone
- MPT:
-
Mitochondrial permeability transition
- PAO:
-
Polyamine oxidase
- Pi:
-
Phosphate
- RLM:
-
Rat liver mitochondria
- ROS:
-
Reactive oxygen species
- SMO:
-
Spermine oxidase
- SPM:
-
Spermine
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Acknowledgments
This work was partially supported by the Department of Molecular Sciences and Nanosystems, Ca’ Foscari Univesrity of Venice, Italy, “Centrale del Latte” Vicenza, Italy, Italian MIUR (Ministero dell’Istruzione, dell’Università e della Ricerca) (EA), by Istituto Superiore di Sanità “Project Italy-USA” (EA), funds MIUR-PRIN (Cofin) (EA), Fondazione Enrico and Enrica Sovena for the scholarship for Giampiero Tempera and by Istituto Pasteur Fondazione Cenci Bolognetti (EA).
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The authors declare that they have no conflict of interest.
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S. Grancara and P. Martinis contributed equally to this work.
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Grancara, S., Martinis, P., Manente, S. et al. Bidirectional fluxes of spermine across the mitochondrial membrane. Amino Acids 46, 671–679 (2014). https://doi.org/10.1007/s00726-013-1591-0
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DOI: https://doi.org/10.1007/s00726-013-1591-0