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Spermine cycling in mitochondria is mediated by adenine nucleotide translocase activity: mechanism and pathophysiological implications

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Abstract

Spermine, besides to be transported in mitochondria by an energy dependent electrophoretic mechanism, can be also released by two different mechanisms. The first one is induced in deenergizing conditions by FCCP or antimycin A and it is mediated by an electroneutral exchange spermine protons. The second one takes place in energizing conditions during the activity of the adenine nucleotide translocase and is mediated by an electroneutral symport mechanism involving the efflux in co-transport of spermine and phosphate and the exchange of exogenous ADP with endogenous ATP. The triggering of this mechanism permits an alternating cycling of spermine across the mitochondrial membrane, that is spermine is transported or released by energized mitochondria in the absence or presence of ATP synthesis, respectively. The physiological implications of this cycling of spermine are related to the induction or prevention of mitochondrial permeability transition and, consequently, on apoptosis or its prevention.

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Abbreviations

AdNT:

Adenine nucleotide translocase

FCCP:

Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone

MPT:

Mitochondrial permeability transition

PAO:

Polyamine oxidase

RLM:

Rat liver mitochondria

ROS:

Reactive oxygen species

mtSMO:

Mitochondrial spermine oxidizing activity

TPP+ :

Tetraphenylphosphonium

ΔΨ:

Electrical transmembrane potential

Δμ +H :

Transmembrane electrochemical gradient

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Acknowledgments

The Authors thank Sapienza University of Rome and Italian MIUR (Ministero dell’Istruzione, dell’Universita` e della Ricerca) for Grant Support (Silvia Grancara Assegno di Ricerca) (EA), the Grant from REGIONE LAZIO Prot. FILAS-RU-2014—1020 is gratefully acknowledged (EA).

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Authors and Affiliations

  1. Department of Biochemical Sciences, SAPIENZA University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Silvia Grancara, Shinji Ohkubo & Enzo Agostinelli

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

    Lisa Dalla Via & Aida Nelly García-Argáez

  3. Department of Sense Organs, Faculty Medicine and Dentistry, SAPIENZA University of Rome, Viale del Policlinico 155, 00161, Rome, Italy

    Elena Pacella

  4. Department of Molecular Sciences and Nanosystems, Ca’ Foscari University of Venice, Venice, Italy

    Sabrina Manente & Marcantonio Bragadin

  5. Department of Biomedical Sciences, University of Padua, Viale U. Bassi 58 B, 35131, Padua, Italy

    Antonio Toninello

  6. Department of Biomedical Sciences, University of Padua, Viale G. Colombo 3, 35131, Padua, Italy

    Antonio Toninello

Authors
  1. Silvia Grancara
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  2. Lisa Dalla Via
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  3. Aida Nelly García-Argáez
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  4. Shinji Ohkubo
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  5. Elena Pacella
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  6. Sabrina Manente
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  7. Marcantonio Bragadin
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  8. Antonio Toninello
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  9. Enzo Agostinelli
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Correspondence to Antonio Toninello.

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The authors declare that they have no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Handling Editor: E. Agostinell.

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Grancara, S., Dalla Via, L., García-Argáez, A.N. et al. Spermine cycling in mitochondria is mediated by adenine nucleotide translocase activity: mechanism and pathophysiological implications. Amino Acids 48, 2327–2337 (2016). https://doi.org/10.1007/s00726-016-2264-6

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  • DOI: https://doi.org/10.1007/s00726-016-2264-6

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