Melatonin

An ancient molecule that makes oxygen metabolically tolerable

Lucien C. Manchester, Ana Coto-Montes, Jose Antonio Boga, Lars Peter H Andersen, Zhou Zhou, Annia Galano, Jerry Vriend, Dun Xian Tan, Russel J Reiter

Research output: Contribution to journalArticle

367 Citations (Scopus)

Abstract

Melatonin is remarkably functionally diverse with actions as a free radical scavenger and antioxidant, circadian rhythm regulator, anti-inflammatory and immunoregulating molecule, and as an oncostatic agent. We hypothesize that the initial and primary function of melatonin in photosynthetic cyanobacteria, which appeared on Earth 3.5-3.2 billion years ago, was as an antioxidant. The evolution of melatonin as an antioxidant by this organism was necessary as photosynthesis is associated with the generation of toxic-free radicals. The other secondary functions of melatonin came about much later in evolution. We also surmise that mitochondria and chloroplasts may be primary sites of melatonin synthesis in all eukaryotic cells that possess these organelles. This prediction is made on the basis that mitochondria and chloroplasts of eukaryotes developed from purple nonsulfur bacteria (which also produce melatonin) and cyanobacteria when they were engulfed by early eukaryotes. Thus, we speculate that the melatonin-synthesizing actions of the engulfed bacteria were retained when these organelles became mitochondria and chloroplasts, respectively. That mitochondria are likely sites of melatonin formation is supported by the observation that this organelle contains high levels of melatonin that are not impacted by blood melatonin concentrations. Melatonin has a remarkable array of means by which it thwarts oxidative damage. It, as well as its metabolites, is differentially effective in scavenging a variety of reactive oxygen and reactive nitrogen species. Moreover, melatonin and its metabolites modulate a large number of antioxidative and pro-oxidative enzymes, leading to a reduction in oxidative damage. The actions of melatonin on radical metabolizing/producing enzymes may be mediated by the Keap1-Nrf2-ARE pathway. Beyond its direct free radical scavenging and indirect antioxidant effects, melatonin has a variety of physiological and metabolic advantages that may enhance its ability to limit oxidative stress.

Original languageEnglish (US)
Pages (from-to)403-419
Number of pages17
JournalJournal of Pineal Research
Volume59
Issue number4
DOIs
StatePublished - Nov 1 2015

Fingerprint

Melatonin
Oxygen
Mitochondria
Chloroplasts
Antioxidants
Organelles
Cyanobacteria
Eukaryota
Free Radicals
Rhodospirillaceae
Reactive Nitrogen Species
Free Radical Scavengers
Poisons
Photosynthesis
Eukaryotic Cells
Enzymes
Circadian Rhythm
Oxidative Stress
Anti-Inflammatory Agents

Keywords

  • aging
  • antioxidant
  • free radicals
  • mitochondria
  • mitochondria-targeted antioxidant
  • oxidative stress
  • photosynthesis
  • plant

ASJC Scopus subject areas

  • Endocrinology

Cite this

Manchester, L. C., Coto-Montes, A., Boga, J. A., Andersen, L. P. H., Zhou, Z., Galano, A., ... Reiter, R. J. (2015). Melatonin: An ancient molecule that makes oxygen metabolically tolerable. Journal of Pineal Research, 59(4), 403-419. https://doi.org/10.1111/jpi.12267

Melatonin : An ancient molecule that makes oxygen metabolically tolerable. / Manchester, Lucien C.; Coto-Montes, Ana; Boga, Jose Antonio; Andersen, Lars Peter H; Zhou, Zhou; Galano, Annia; Vriend, Jerry; Tan, Dun Xian; Reiter, Russel J.

In: Journal of Pineal Research, Vol. 59, No. 4, 01.11.2015, p. 403-419.

Research output: Contribution to journalArticle

Manchester, LC, Coto-Montes, A, Boga, JA, Andersen, LPH, Zhou, Z, Galano, A, Vriend, J, Tan, DX & Reiter, RJ 2015, 'Melatonin: An ancient molecule that makes oxygen metabolically tolerable', Journal of Pineal Research, vol. 59, no. 4, pp. 403-419. https://doi.org/10.1111/jpi.12267
Manchester LC, Coto-Montes A, Boga JA, Andersen LPH, Zhou Z, Galano A et al. Melatonin: An ancient molecule that makes oxygen metabolically tolerable. Journal of Pineal Research. 2015 Nov 1;59(4):403-419. https://doi.org/10.1111/jpi.12267
Manchester, Lucien C. ; Coto-Montes, Ana ; Boga, Jose Antonio ; Andersen, Lars Peter H ; Zhou, Zhou ; Galano, Annia ; Vriend, Jerry ; Tan, Dun Xian ; Reiter, Russel J. / Melatonin : An ancient molecule that makes oxygen metabolically tolerable. In: Journal of Pineal Research. 2015 ; Vol. 59, No. 4. pp. 403-419.
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