Department of Cellular and Structural Biology UT Health San Antonio, San Antonio, SD 78229, USA.
Centro de Investigacion Biomedica de Occidente, Instituo Mexicana del Seguro Social, Guadalajara 44346, Mexico.
Molecules. 2018 Feb 24;23(2):509. doi: 10.3390/molecules23020509.
Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or cells exposed to toxins. Oxidative damage is a result of free radicals produced in cells, especially in mitochondria. When measured, melatonin, a potent antioxidant, was found to be in higher concentrations in mitochondria than in other organelles or subcellular locations. Recent evidence indicates that mitochondrial membranes possess transporters that aid in the rapid uptake of melatonin by these organelles against a gradient. Moreover, we predicted several years ago that, because of their origin from melatonin-producing bacteria, mitochondria likely also synthesize melatonin. Data accumulated within the last year supports this prediction. A high content of melatonin in mitochondria would be fortuitous, since these organelles produce an abundance of free radicals. Thus, melatonin is optimally positioned to scavenge the radicals and reduce the degree of oxidative damage. In light of the "free radical theory of aging", including all of its iterations, high melatonin levels in mitochondria would be expected to protect against age-related organismal decline. Also, there are many age-associated diseases that have, as a contributing factor, free radical damage. These multiple diseases may likely be deferred in their onset or progression if mitochondrial levels of melatonin can be maintained into advanced age.
褪黑素及其代谢产物长期以来一直被认为可以显著减轻衰老细胞或暴露于毒素的细胞的氧化应激负担。氧化损伤是细胞中自由基产生的结果，尤其是在线粒体中。研究发现，褪黑素作为一种有效的抗氧化剂，其浓度在细胞器中比在其他细胞器或亚细胞位置更高。最近的证据表明，线粒体膜具有转运蛋白，可以帮助这些细胞器逆浓度梯度快速摄取褪黑素。此外，我们几年前预测，由于它们起源于产生褪黑素的细菌，线粒体可能也会合成褪黑素。去年积累的数据支持了这一预测。线粒体中含有大量的褪黑素是很幸运的，因为这些细胞器会产生大量的自由基。因此，褪黑素可以很好地清除自由基并降低氧化损伤的程度。根据“衰老自由基理论”及其所有迭代，线粒体中高浓度的褪黑素应该可以预防与年龄相关的机体衰退。此外，还有许多与年龄相关的疾病，其发病因素之一就是自由基损伤。如果能够维持线粒体中褪黑素的水平，那么这些多种疾病的发病或进展可能会推迟。
