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Cellular and Molecular Life Sciences

, Volume 74, Issue 21, pp 3927–3940 | Cite as

Melatonin transport into mitochondria

  • Juan C. MayoEmail author
  • Rosa M. Sainz
  • Pedro González-Menéndez
  • David Hevia
  • Rafael Cernuda-Cernuda
Multi-author review

Abstract

Melatonin is a well-known, nighttime-produced indole found in bacteria, eukaryotic unicellulars, animals or vascular plants. In vertebrates, melatonin is the major product of the pineal gland, which accounts for its increase in serum during the dark phase, but it is also produced by many other organs and cell types. Such a wide distribution is consistent with its multiple and well-described functions which include from the circadian regulation and adaptation to seasonal variations to immunomodulatory and oncostatic actions in different types of tumors. The discovery of its antioxidant properties in the early 1990s opened a new field of potential protective functions in multiple tissues. A special mention should be made regarding the nervous system, where the indole is considered a major neuroprotector. Furthermore, mitochondria appear as one of the most important targets for the indole’s protective actions. Melatonin’s mechanisms of action vary from the direct molecular interaction with free radicals (free radical scavenger) to the binding to membrane (MLT1A and MLT1B) or nuclear receptors (RZR/RORα). Receptor binding has been associated with some, but not all of the indole functions reported to date. Recently, two new mechanisms of cellular uptake involving the facilitative glucose transporters GLUT/SLC2A and the proton-driven oligopeptide transporter PEPT1/2 have been reported. Here we discuss the potential importance that these newly discovered transport systems could have in determining the actions of melatonin, particularly in the mitochondria. We also argue the relative importance of passive diffusion vs active transport in different parts of the cell.

Keywords

Melatonin Mitochondria GLUT transporters MTNR Uptake Diffusion 

Notes

Acknowledgments

This work was supported by funding from ‘Ministerio de Economía y Competitividad’ (Grant# MINECO-17-BFU2016-79139-R). PGM acknowledges sponsorship from Ministerio de Educación, Cultura y Deporte (AP2012-4924).

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Juan C. Mayo
    • 1
    • 2
    Email author
  • Rosa M. Sainz
    • 1
    • 2
  • Pedro González-Menéndez
    • 1
    • 2
  • David Hevia
    • 1
    • 2
  • Rafael Cernuda-Cernuda
    • 1
  1. 1.Departamento de Morfología y Biología Celular, Facultad de MedicinaUniversidad de OviedoOviedoSpain
  2. 2.Instituto Universitario Oncológico del Principado de AsturiasUniversidad de OviedoOviedoSpain

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