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Effect of peroxides on spermine transport in rat brain and liver mitochondria

Amino Acids volume 42, pages 741–749 (2012)Cite this article

Abstract

The polyamine spermine is transported into the matrix of various types of mitochondria by a specific uniporter system identified as a protein channel. This mechanism is regulated by the membrane potential; other regulatory effectors are unknown. This study analyzes the transport of spermine in the presence of peroxides in both isolated rat liver and brain mitochondria, in order to evaluate the involvement of the redox state in this mechanism, and to compare its effect in both types of mitochondria. In liver mitochondria peroxides are able to inhibit spermine transport. This effect is indicative of redox regulation by the transporter, probably due to the presence of critical thiol groups along the transport pathway, or in close association with it, with different accessibility for the peroxides and performing different functions. In brain mitochondria, peroxides have several effects, supporting the hypothesis of a different regulation of spermine transport. The fact that peroxovanadate can inhibit tyrosine phosphatases in brain mitochondria suggests that mitochondrial spermine transport is regulated by tyrosine phosphorylation in this organ. In this regard, the evaluation of spermine transport in the presence of Src inhibitors suggests the involvement of Src family kinases in this process. It is possible that phosphorylation sites for Src kinases are present in the channel pathway and have an inhibitory effect on spermine transport under regulation by Src kinases. The results of this study suggest that the activity of the spermine transporter probably depends on the redox and/or tyrosine phosphorylation state of mitochondria, and that its regulation may be different in distinct organs.

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Abbreviations

AIF:

Apoptosis-inducing factor

PP2:

Amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3,4d] pyrimidine

PTP-1B:

Protein tyrosine phosphatase 1B

RBM:

Rat brain mitochondria

RLM:

Rat liver mitochondria

ROS:

Reactive oxygen species

SFKs:

Src family kinases

SPM:

Spermine

SU6656:

2,3-Dihydro-N,N-dimethyl-2-oxo-3-[(4,5,6,7-tetrahydro-1H-indol-2-yl)methylene]-1H-indole-5-sulfonamide

tBOOH:

tert-Butyl-hydroperoxide

TPP+ :

Tetraphenylphosphonium

ΔΨ:

Electrical transmembrane potential

ΔμH + :

Transmembrane electrochemical gradient

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Acknowledgments

We would like to thank the Institute Pasteur-Cenci Bolognetti foundation for financial support.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Affiliations

  1. Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35121, Padua, Italy

    Valentina Battaglia, Elena Tibaldi, Silvia Grancara, Francesca Zonta, Anna Maria Brunati, Pamela Martinis & Antonio Toninello

  2. Department of Molecular Sciences and Nanosystems, Ca’ Foscari University of Venice, Dorsoduro 2137, 30123, Venice, Italy

    Marcantonio Bragadin

  3. Department of Medicine and Experimental Oncology, University of Turin, Via Michelangelo 27B, 10126, Turin, Italy

    Maria Angelica Grillo

  4. Department of Biochemical Sciences, CNR Institute Molecular Biology and Pathology and Istituto Pasteur-Fondazione Cenci Bolognetti, SAPIENZA, University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Giampiero Tempera & Enzo Agostinelli

Authors
  1. Valentina Battaglia
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  2. Elena Tibaldi
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  3. Silvia Grancara
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  4. Francesca Zonta
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  5. Anna Maria Brunati
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  6. Pamela Martinis
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  7. Marcantonio Bragadin
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  8. Maria Angelica Grillo
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  9. Giampiero Tempera
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  10. Enzo Agostinelli
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  11. Antonio Toninello
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Corresponding author

Correspondence to Antonio Toninello.

Additional information

V. Battaglia, E. Tibaldi contributed equally to this work.

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Battaglia, V., Tibaldi, E., Grancara, S. et al. Effect of peroxides on spermine transport in rat brain and liver mitochondria. Amino Acids 42, 741–749 (2012). https://doi.org/10.1007/s00726-011-0990-3

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  • DOI: https://doi.org/10.1007/s00726-011-0990-3

Keywords

  • Spermine transport
  • Mitochondria
  • Peroxides
  • Tyrosine phosphorylation
  • Src kinases family