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Review
. 2017 Nov;74(21):3927-3940.
doi: 10.1007/s00018-017-2616-8. Epub 2017 Aug 21.

Melatonin transport into mitochondria

Juan C Mayo  1   2 , Rosa M Sainz  3   4 , Pedro González-Menéndez  3   4 , David Hevia  3   4 , Rafael Cernuda-Cernuda  3
Affiliations
Review

Melatonin transport into mitochondria

Juan C Mayo et al. Cell Mol Life Sci. 2017 Nov.

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: Diffusion; GLUT transporters; MTNR; Melatonin; Mitochondria; Uptake.

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Figures

Fig. 1
Fig. 1
Cell membrane models proposed for melatonin:lipid bilayer interaction, depending on the indole concentration. A portion of a standard lipid bilayer a is shown. The interactions of phospholipids with low (b) or high concentrations (c) of melatonin are also shown. Models were modified from Dies et al. [178]
Fig. 2
Fig. 2
Interaction of melatonin with GLUT1/SLC2A1 transporter. Model deduced from docking studies of melatonin binding to the XylE transporter, a highly GLUT1 homologous protein, showing the position of melatonin relative to the active site residues (a). Bottom list shows that most of the XylE amino acids involved in the interaction of melatonin are common to GLUT1. Another docking study using Suk1, a virtual chimera employed to study GLUT1 binding compounds, also shows the same position of melatonin within the glucose-binding active site of the transporter. Taken from Hevia et al. [183] with permission
Fig. 3
Fig. 3
3D Models deduced after docking studies for the binding of melatonin to PEPT1 (a) and PEPT2 (b). The key residues and the relative position of melatonin is shown for PEPT1 (c) and PEPt2 (d). Taken from Huo et al. [187] with permission
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References

    1. Pelham RW. A serum melatonin rhythm in chickens and its abolition by pinealectomy. Endocrinology. 1975;96:543–546. doi: 10.1210/endo-96-2-543. - DOI - PubMed
    1. Reiter RJ, Rollag MD, Panke ES, Banks AF. Melatonin: reproductive effects. J Neural Transm Suppl. 1978;13:209–223. - PubMed
    1. Lerner AB, Case JD, Takahashi Y, Lee TH, Mori W. Isolation of melatonin, the pineal gland factor that lightens melanocytes. J Am Chem Soc. 1958;80:2587. doi: 10.1021/ja01543a060. - DOI
    1. Lerner AB, Case JD, Heinzelman RV. Structure of melatonin. J Am Chem Soc. 1959;81:6084–6085. doi: 10.1021/ja01531a060. - DOI
    1. Fao C. Hypertrophie des testicules et de la crete après l’extirpation de la glande pineale chez le coq. Arch Ital Biol. 1912;57:233–252.

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