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Further characterization of agmatine binding to mitochondrial membranes: involvement of imidazoline I2 receptor

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Abstract

Agmatine, a divalent diamine with two positive charges at physiological pH, is transported into the matrix of liver mitochondria by an energy-dependent mechanism, the driving force of which is the electrical membrane potential. Its binding to mitochondrial membranes is studied by applying a thermodynamic treatment of ligand–receptor interactions on the analyses of Scatchard and Hill. The presence of two mono-coordinated binding sites S1 and S2, with a negative influence of S2 on S1, has been demonstrated. The calculated binding energy is characteristic for weak interactions. S1 exhibits a lower binding capacity and higher binding affinity both of about two orders of magnitude than S2. Experiments with idazoxan, a ligand of the mitochondrial imidazoline receptor I2, demonstrate that S1 site is localized on this receptor while S2 is localized on the transport system. S1 would act as a sensor of exogenous agmatine concentration, thus modulating the transport of the amine by its binding to S2.

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Abbreviations

ADC:

Arginine decarboxylase

AGM:

Agmatine

ΔΨ:

Electrical membrane potential

I2 :

Imidazoline receptor type two

MAO:

Monoamine oxidase

MPT:

Mitochondrial permeability transition

NOS:

Nitric oxide synthase

PTP:

Permeability transition pore

RLM:

Rat liver mitochondria

ROS:

Reactive oxygen species

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Acknowledgments

We thank Istituto Pasteur-Fondazione Cenci Bolognetti for its financial support (EA).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

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

    Pamela Martinis, Valentina Battaglia, Silvia Grancara & Antonio Toninello

  2. Department of Pharmaceutical Sciences, University of Padua, Via Marzolo 5, 35131, Padua, Italy

    Lisa Dalla Via

  3. Department of Chemical Sciences, University of Padua, Via Marzolo 1, 35131, Padua, Italy

    Vito Di Noto

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

    Stefania Saccoccio & Enzo Agostinelli

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

    Marcantonio Bragadin

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

    Maria Angelica Grillo

Authors
  1. Pamela Martinis
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  2. Valentina Battaglia
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  3. Silvia Grancara
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  4. Lisa Dalla Via
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  5. Vito Di Noto
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  6. Stefania Saccoccio
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  7. Enzo Agostinelli
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  8. Marcantonio Bragadin
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  9. Maria Angelica Grillo
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  10. Antonio Toninello
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Corresponding author

Correspondence to Antonio Toninello.

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Martinis, P., Battaglia, V., Grancara, S. et al. Further characterization of agmatine binding to mitochondrial membranes: involvement of imidazoline I2 receptor. Amino Acids 42, 761–768 (2012). https://doi.org/10.1007/s00726-011-0992-1

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  • DOI: https://doi.org/10.1007/s00726-011-0992-1

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