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Cellular and Molecular Life Sciences

, Volume 74, Issue 21, pp 3863–3881 | Cite as

Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas

  • Russel J. Reiter
  • Sergio Rosales-Corral
  • Dun Xian Tan
  • Mei Jie Jou
  • Annia Galano
  • Bing Xu
Multi-author review

Abstract

Melatonin is an ancient antioxidant. After its initial development in bacteria, it has been retained throughout evolution such that it may be or may have been present in every species that have existed. Even though it has been maintained throughout evolution during the diversification of species, melatonin’s chemical structure has never changed; thus, the melatonin present in currently living humans is identical to that present in cyanobacteria that have existed on Earth for billions of years. Melatonin in the systemic circulation of mammals quickly disappears from the blood presumably due to its uptake by cells, particularly when they are under high oxidative stress conditions. The measurement of the subcellular distribution of melatonin has shown that the concentration of this indole in the mitochondria greatly exceeds that in the blood. Melatonin presumably enters mitochondria through oligopeptide transporters, PEPT1, and PEPT2. Thus, melatonin is specifically targeted to the mitochondria where it seems to function as an apex antioxidant. In addition to being taken up from the circulation, melatonin may be produced in the mitochondria as well. During evolution, mitochondria likely originated when melatonin-forming bacteria were engulfed as food by ancestral prokaryotes. Over time, engulfed bacteria evolved into mitochondria; this is known as the endosymbiotic theory of the origin of mitochondria. When they did so, the mitochondria retained the ability to synthesize melatonin. Thus, melatonin is not only taken up by mitochondria but these organelles, in addition to many other functions, also probably produce melatonin as well. Melatonin’s high concentrations and multiple actions as an antioxidant provide potent antioxidant protection to these organelles which are exposed to abundant free radicals.

Keywords

Free radical-related diseases SIRT3 Melatonin transporters Reactive oxygen species Mitochondrial transition pore Cytochrome c Apoptosis Inner mitochondrial membrane 

Notes

Acknowledgements

This work was supported in part by Grants CMRPD1C0511-3 (from the Chang Gung Memorial Hospital, Taiwan), MOST 105-2320-B-182-011 and MOST 104-2320-B-182-008 (to MJJ).

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Russel J. Reiter
    • 1
  • Sergio Rosales-Corral
    • 2
  • Dun Xian Tan
    • 1
  • Mei Jie Jou
    • 3
    • 4
  • Annia Galano
    • 5
  • Bing Xu
    • 1
  1. 1.Department of Cell Systems and AnatomyUT Health San AntonioSan AntonioUSA
  2. 2.Centro de Investigacion Biomedica de OccidenteDel Instituto Mexicana del Seguro SocialGuadalajaraMexico
  3. 3.Department of Physiology and Pharmacology, College of MedicineChang Gung UniversityTaoyüanTaiwan
  4. 4.Department of Neurology, Kee-Lung Medical CenterChang Gung Memorial HospitalKeelungTaiwan
  5. 5.Departemento de QuimicaUninversidad Autonoma Metropolitana-IztapalapaMexico CityMexico

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