Mitochondria and chloroplasts as the original sites of melatonin synthesis: a hypothesis related to melatonin's primary function and evolution in eukaryotes

Abstract

Mitochondria and chloroplasts are major sources of free radical generation in living organisms. Because of this, these organelles require strong protection from free radicals and associated oxidative stress. Melatonin is a potent free radical scavenger and antioxidant. It meets the criteria as a mitochondrial and chloroplast antioxidant. Evidence has emerged to show that both mitochondria and chloroplasts may have the capacity to synthesize and metabolize melatonin. The activity of arylalkylamine N-acetyltransferase (AANAT), the reported rate-limiting enzyme in melatonin synthesis, has been identified in mitochondria, and high levels of melatonin have also been found in this organelle. From an evolutionary point of view, the precursor of mitochondria probably is the purple nonsulfur bacterium, particularly, Rhodospirillum rubrum, and chloroplasts are probably the descendents of cyanobacteria. These bacterial species were endosymbionts of host protoeukaryotes and gradually transformed into cellular organelles, that is, mitochondria and chloroplasts, respectively, thereby giving rise to eukaryotic cells. Of special importance, both purple nonsulfur bacteria (R. rubrum) and cyanobacteria synthesize melatonin. The enzyme activities required for melatonin synthesis have also been detected in these primitive species. It is our hypothesis that mitochondria and chloroplasts are the original sites of melatonin synthesis in the early stage of endosymbiotic organisms; this synthetic capacity was carried into host eukaryotes by the above-mentioned bacteria. Moreover, their melatonin biosynthetic capacities have been preserved during evolution. In most, if not in all cells, mitochondria and chloroplasts may continue to be the primary sites of melatonin generation. Melatonin production in other cellular compartments may have derived from mitochondria and chloroplasts. On the basis of this hypothesis, it is also possible to explain why plants typically have higher melatonin levels than do animals. In plants, both chloroplasts and mitochondria likely synthesize melatonin, while animal cells contain only mitochondria. The high levels of melatonin produced by mitochondria and chloroplasts are used to protect these important cellular organelles against oxidative stress and preserve their physiological functions. The superior beneficial effects of melatonin in both mitochondria and chloroplasts have been frequently reported.

Breastfeeding and the gut-brain axis: is there a role for melatonin?

“…Following a meal, gut melatonin synthesis can be 400-fold that of the pineal gland night-time peak release (30). Melatonin has been proposed to be produced in all mitochondria-containing cells (31), with recent work suggesting that melatonin may be produced within mitochondria (32). Melatonin synthesis is, therefore, widespread.…”

Melatonin production in Escherichia coli by dual expression of serotonin N-acetyltransferase and caffeic acid O-methyltransferase

“…Melatonin is found in all living organisms including bacteria, insects, fungi, animals, and plants that have been examined, and its ubiquitous presence matches the original sites of melatonin synthesis-mitochondria and chloroplasts (Tan et al 2013). Melatonin is predicted to have evolved from the precursor bacteria of mitochondria and chloroplasts, such as Rhodospirillum rubrum and Cyanobacteria, respectively, via an endosymbiotic event with their ancestral eukaryotic host (Sagan 1967).…”

The role of melatonin in development of gestational diabetes mellitus

“…Экстрапинеальный мелатонин обнаружен во всех органах: желудочно-кишечном тракте, печени, почках, надпочечниках, сердце, тимусе, половых железах, плаценте, матке, тромбоци-тах, эозинофилах, лейкоцитах и других клет-ках системы иммунитета [34,35]. При этом его синтез в митохондриях клеток эукариот сви-детельствует об уникальной защите мелатони-ном клеточных органелл от оксидативного по-вреждения и о сохранении их физиологической функции [36][37][38].…”

“…Влияние мела-тонина на панкреатические α-и β-клетки и на секрецию инсулина обеспечивается комплек-сом различных типов межклеточных и внутри-клеточных сигнальных путей [52]. кроме того, мелатонин защищает клетки поджелудочной железы от свободнорадикального поврежде-ния путем элиминации свободных радикалов и активации антиоксидантных ферментов [31,37,53]. Циркадная амплитуда уровня ме-латонина снижается с возрастом, особенно при работе и активном образе жизни в ночное вре-мя, при нарушениях сна, что ведет к гиперин-сулинемии, развитию инсулинорезистентности и гипергликемии, то есть симптомокомплекса, характерного для сахарного диабета 2-го типа [54][55][56][57].…”