Mitochondria: Central Organelles for Melatonin's Antioxidant and Anti-Aging Actions. Author: Reiter RJ1, Tan DX2, Rosales-Corral S3, Galano A4, Zhou XJ5, Xu B6 Affiliation: <sup>1</sup>Department of Cellular and Structural Biology UT Health San Antonio, San Antonio, SD 78229, USA. reiter@uthscsa.edu. <sup>2</sup>Department of Cellular and Structural Biology UT Health San Antonio, San Antonio, SD 78229, USA. tan@uthscsa.edu. <sup>3</sup>Centro de Investigacion Biomedica de Occidente, Instituo Mexicana del Seguro Social, Guadalajara 44346, Mexico. espiral17@gmail.com. <sup>4</sup>Departamento de Quimica, Universidad Autonoma Metropolitana-Iztapatapa, Mexico D.F. 09340, Mexico. agalano@prodigy.net.mx. <sup>5</sup>Department of Cellular and Structural Biology UT Health San Antonio, San Antonio, SD 78229, USA. ZhouX4@uthscsa.edu. <sup>6</sup>Department of Cellular and Structural Biology UT Health San Antonio, San Antonio, SD 78229, USA. doctxu@126.com. Conference/Journal: Molecules. Date published: 2018 Feb 24 Other: Volume ID: 23 , Issue ID: 2 , Special Notes: doi: 10.3390/molecules23020509. , Word Count: 233 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. KEYWORDS: electron transport chain; free radical theory of aging; free radicals; melatonin synthesis; melatonin uptake; oxidative phosphorylation; oxidative stress PMID: 29495303 DOI: 10.3390/molecules23020509