Reiter Russel J, Rosales-Corral Sergio, Tan Dun Xian, Jou Mei Jie, Galano Annia, Xu Bing
Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, TX, 78229, USA.
Centro de Investigacion Biomedica de Occidente, Del Instituto Mexicana del Seguro Social, 44340, Guadalajara, Mexico.
Cell Mol Life Sci. 2017 Nov;74(21):3863-3881. doi: 10.1007/s00018-017-2609-7. Epub 2017 Sep 1.
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.
褪黑素是一种古老的抗氧化剂。在细菌中最初形成后，它在整个进化过程中得以保留，以至于它可能或可能已经存在于所有已存在的物种中。尽管在物种多样化的整个进化过程中它一直被保留下来，但褪黑素的化学结构从未改变；因此，目前活着的人类体内的褪黑素与数十亿年前地球上存在的蓝细菌中的褪黑素是相同的。哺乳动物体循环中的褪黑素会迅速从血液中消失，大概是因为它被细胞摄取了，尤其是当细胞处于高氧化应激条件下时。褪黑素亚细胞分布的测量表明，这种吲哚在线粒体中的浓度大大超过血液中的浓度。褪黑素大概是通过寡肽转运体PEPT1和PEPT2进入线粒体的。因此，褪黑素被特异性地靶向运送到线粒体，在那里它似乎起着顶级抗氧化剂的作用。除了从循环中摄取外，褪黑素也可能在线粒体中产生。在进化过程中，线粒体可能起源于形成褪黑素的细菌被原始原核生物作为食物吞噬的时候。随着时间的推移，被吞噬的细菌进化成了线粒体；这就是线粒体起源的内共生理论。当它们这样做时，线粒体保留了合成褪黑素的能力。因此，褪黑素不仅被线粒体摄取，而且这些细胞器除了许多其他功能外，可能也会产生褪黑素。褪黑素作为抗氧化剂的高浓度和多种作用为这些暴露于大量自由基的细胞器提供了强大的抗氧化保护。
