Melatonin: an ancient molecule that makes oxygen metabolically tolerable.
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.
Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX, USA.
Lucien C
LC
Manchester
Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX, USA.
Ana
A
Coto-Montes
Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX, USA.
Jose Antonio
JA
Boga
Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX, USA.
Lars Peter H
LP
Andersen
Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX, USA.
Zhou
Z
Zhou
Departamento de Quimica, Universidad Autonoma Metropolitana-Iztapalapa, Mexico DF, Mexico.
Annia
A
Galano
Department of Human Anatomy and Cell Biology, University of Manitoba, Winnipeg, MA, Canada.
Jerry
J
Vriend
Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX, USA.
Dun-Xian
DX
Tan
Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX, USA.
Russel J
RJ
Reiter
D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology*; D002736:Chloroplasts / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D008550:Melatonin / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D008550:Melatonin; D010100:Oxygen
aging; antioxidant; free radicals; mitochondria; mitochondria-targeted antioxidant; oxidative stress; photosynthesis; plant