Skip to main content
SpringerLink
Log in

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

  • Original Article
  • Published:
Amino Acids Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

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

References

  • Arachiche A, Augereau O, Decossas M, Pertuiset C, Gontier E, Letellier T, Dachary-Prigent J (2008) Localization of PTP-1B, SHP-2, and Src exclusively in rat brain mitochondria and functional consequences. J Biol Chem 283:24406–24411

    Article  PubMed  CAS  Google Scholar 

  • Battaglia V, Grancara S, Mancon M, Cravanzola C, Colombatto S, Grillo MA, Tempera G, Agostinelli E, Toninello A (2010a) Agmatine transport in brain mitochondria: a different mechanism from that in liver mitochondria. Amino Acids 38:423–430

    Article  PubMed  CAS  Google Scholar 

  • Battaglia V, Grancara S, Satriano J, Saccoccio S, Agostinelli E, Toninello A (2010b) Agmatine prevents the Ca(2+)-dependent induction of permeability transition in rat brain mitochondria. Amino Acids 38:431–437

    Article  PubMed  CAS  Google Scholar 

  • Bernardi P (1996) The permeability transition pore. Control points of a cyclosporin A-sensitive mitochondrial channel involved in cell death. Biochim Biophys Acta 1275:5–9

    Article  PubMed  Google Scholar 

  • Dalla Via L, Di Noto V, Siliprandi D, Toninello A (1996) Spermine binding to liver mitochondria. Biochim Biophys Acta 1284:247–252

    Article  PubMed  Google Scholar 

  • Feng J, Lucchinetti E, Enkavi G, Wang Y, Gehrig P, Roschitzki B, Schaub MC, Tajkhorshid E, Zaugg K, Zaugg M (2010) Tyrosine phosphorylation by Src within the cavity of the adenine nucleotide translocase 1 regulates ADP/ATP exchange in mitochondria. Am J Physiol Cell Physiol 298:740–748

    Article  Google Scholar 

  • Frasson M, Vitadello M, Brunati AM, La Rocca N, Tibaldi E, Pinna La, gorza L, Donella-Deana A (2009) Grp94 is Tyr-phosphorylated by Fyn in the lumen of the endoplasmic reticulum and translocates to Golgi in differentating myoblasts. Biochim Biophys Acta 1793:239–252

    Article  PubMed  CAS  Google Scholar 

  • Gornall AG, Bardawill CJ, Davi MM (1949) Determination of serum protein by means of the biuret reaction. J Biol Chem 177:751–766

    PubMed  CAS  Google Scholar 

  • Grancara S, Battaglia V, Martinis P, Viceconte N, Agostinelli E, Toninello A, Deana R (2011) Mitochondrial oxidative stress induced by Ca2+ and monoamines. Different behavior of liver and brain mitochondria in undergoing to the permeability transition. Amino Acids, this issue

  • Gringeri E, Carraro A, Tibaldi E, D’amico FE, Mancon M, Toninello A, Pagano MA, Vio C, Cillo U, Brunati MA (2010) Lyn-mediated mitochondrial tyrosine phosphorylation is required to preserve mitochondrial integrity in early liver regeneration. Biochem J 425:401–412

    Article  CAS  Google Scholar 

  • Ha IG HC, Sirisoma NS, Kuppusamy P, Zweier JL, Woster PM, Casero RA Jr (1998) The natural polyamine spermine functions directly as a free radical scavenger. Proc Natl Acad Sci USA 95:11140–11145

    Article  Google Scholar 

  • Huyer G, Liu Skelly J, Moffat J, Payette P, Kennedy B, Tsaprailis G, Gresser MJ, Ramachandran C (1997) Mechanism of inhibition of protein-tyrosine phosphatases by vanadate and pervanadate. 272:843–851

    CAS  Google Scholar 

  • Kamo N, Muratsugu M, Hongoh R, Kobatake Y (1979) Membrane potential of mitochondria measured with an electrode sensitive to tetraphenyl phosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady state. J Membr Biol 49:105–121

    Article  PubMed  CAS  Google Scholar 

  • Lewandrowski U, Sickmann A, Cesaro L, Brunati AM, Toninello A, Salvi M (2008) Identification of new tyrosine phosphorylated proteins in rat brain mitochondria. FEBS Lett 582:1104–1110

    Article  PubMed  CAS  Google Scholar 

  • Pezzato E, Battaglia V, Brunati AM, Agostinelli E, Toninello A (2009) Ca2+-independent effects of spermine on pyruvate dehydrogenase complex activity in energized rat liver mitochondria incubated in the absence of exogenous Ca2+ and Mg2+. Amino Acids 36:449–456

    Article  PubMed  CAS  Google Scholar 

  • Salvi M, Toninello A, Schweizer M, Friess SD, Richter C (2002) Peroxovanadate inhibits Ca2+release from mitochondria. Cell Mol Life Sci 59:1190–1197

    Article  PubMed  CAS  Google Scholar 

  • Salvi M, Stringaro A, Brunati AM, Agostinelli E, Arancia G, Clari G, Toninello A (2004) Tyrosine phosphatase activity in mitochondria: presence of Shp-2 phosphatase in mitochondria. Cell Mol Life Sci 61:2393–2404

    Article  PubMed  CAS  Google Scholar 

  • Salvi M, Brunati AM, Toninello A (2005) Tyrosine phosphorylation in mitochondria: a new frontier in mitochondrial signalling. Free Radic Biol Med 38:1267–1277

    Article  PubMed  CAS  Google Scholar 

  • Salvi M, Battaglia V, Mancon M, Colombatto S, Cravanzola C, Calheiros R, Marques MP, Grillo MA, Toninello A (2006) Agmatine is transported into liver mitochondria by a specific electrophoretic mechanism. Biochem J 396:337–345

    Article  PubMed  CAS  Google Scholar 

  • Sava IG, Battaglia V, Rossi CA, Salvi M, Toninello A (2006) Free radical scavenging action of the natural polyamine spermine in rat liver mitochondria. Free Radic Biol Med 41:1272–1281

    Article  PubMed  CAS  Google Scholar 

  • Schneider WC, Hogeboom GH (1950) Intracellular distribution of enzymes. V. Further studies on the distribution of cytochrome c in rat homogenate. J Biol Chem 183:123–128

    CAS  Google Scholar 

  • Shaver A, Ng JB, Hall DA, Posner BI (1995) The chemistry of peroxovanadium compounds relevant to insulin mimesis. Mol Cell Biochem 153:5–15

    Article  PubMed  CAS  Google Scholar 

  • Siliprandi D, Toninello A, Dalla Via L (1992) Bidirectional transport of spermine in rat liver mitochondria. Biochim Biophys Acta 1102:62–66

    Article  PubMed  CAS  Google Scholar 

  • Tahin QS, Blum M, Carafoli E (1981) The fatty acid composition of subcellular membranes of rat liver, heart and brain: diet-induced modification. Eur J Biochem 121:5–13

    Article  PubMed  CAS  Google Scholar 

  • Tassani V, Ciman M, Sartorelli L, Toninello A, Siliprandi D (1995) Polyamine content and spermine transport in rat brain mitochondria. Neurosci Res Commun 16:11–18

    CAS  Google Scholar 

  • Toninello A, Di Lisa F, Siliprandi D, Siliprandi N (1985) Uptake of spermine by rat liver mitochondria and its influence on the transport of phosphate. Biochim Biophys Acta 815:399–404

    Article  PubMed  CAS  Google Scholar 

  • Toninello A, Miotto G, Siliprandi D, Siliprandi N, Garlid KD (1988) On the mechanism of spermine transport in liver mitochondria. J Biol Chem 263:19407–19411

    PubMed  CAS  Google Scholar 

  • Toninello A, Dalla Via L, Siliprandi D, Garlid KD (1992) Evidence that spermine, spermidine, and putrescine are transported electrophoretically in mitochondria by a specific polyamine uniporter. J Biol Chem 267:18393–18397

    PubMed  CAS  Google Scholar 

  • Toninello A, Dalla Via L, Stevanato R, Yagisawa S (2000) Kinetics and free energy profiles of spermine transport in liver mitochondria. Biochemistry 39:324–331

    Article  PubMed  CAS  Google Scholar 

  • Toninello A, Salvi M, Mondovì B (2004) Interaction of biologically active amines with mitochondria and their role in the mitochondrial-mediated pathway of apoptosis. Curr Med Chem 11:2349–2374

    PubMed  CAS  Google Scholar 

  • Zoratti M, Szabò I (1995) The mitochondrial permeability transition. Biochem Biophys Acta 1241:139–176

    PubMed  Google Scholar 

Download references

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.

Author information

Authors and 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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elena Tibaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Silvia Grancara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francesca Zonta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anna Maria Brunati
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pamela Martinis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marcantonio Bragadin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maria Angelica Grillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Giampiero Tempera
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Enzo Agostinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Antonio Toninello
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antonio Toninello.

Additional information

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

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

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

Keywords

Search

Navigation