36
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references197

          • Record: found
          • Abstract: found
          • Article: not found

          ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis.

          Reactive oxygen species (ROS) have been shown to be toxic but also function as signalling molecules. This biological paradox underlies mechanisms that are important for the integrity and fitness of living organisms and their ageing. The pathways that regulate ROS homeostasis are crucial for mitigating the toxicity of ROS and provide strong evidence about specificity in ROS signalling. By taking advantage of the chemistry of ROS, highly specific mechanisms have evolved that form the basis of oxidant scavenging and ROS signalling systems.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The role of mitochondria in aging.

            Over the last decade, accumulating evidence has suggested a causative link between mitochondrial dysfunction and major phenotypes associated with aging. Somatic mitochondrial DNA (mtDNA) mutations and respiratory chain dysfunction accompany normal aging, but the first direct experimental evidence that increased mtDNA mutation levels contribute to progeroid phenotypes came from the mtDNA mutator mouse. Recent evidence suggests that increases in aging-associated mtDNA mutations are not caused by damage accumulation, but rather are due to clonal expansion of mtDNA replication errors that occur during development. Here we discuss the caveats of the traditional mitochondrial free radical theory of aging and highlight other possible mechanisms, including insulin/IGF-1 signaling (IIS) and the target of rapamycin pathways, that underlie the central role of mitochondria in the aging process.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The sites and topology of mitochondrial superoxide production.

              Mitochondrial superoxide production is an important source of reactive oxygen species in cells, and may cause or contribute to ageing and the diseases of ageing. Seven major sites of superoxide production in mammalian mitochondria are known and widely accepted. In descending order of maximum capacity they are the ubiquinone-binding sites in complex I (site IQ) and complex III (site IIIQo), glycerol 3-phosphate dehydrogenase, the flavin in complex I (site IF), the electron transferring flavoprotein:Q oxidoreductase (ETFQOR) of fatty acid beta-oxidation, and pyruvate and 2-oxoglutarate dehydrogenases. None of these sites is fully characterized and for some we only have sketchy information. The topology of the sites is important because it determines whether or not a site will produce superoxide in the mitochondrial matrix and be able to damage mitochondrial DNA. All sites produce superoxide in the matrix; site IIIQo and glycerol 3-phosphate dehydrogenase also produce superoxide to the intermembrane space. The relative contribution of each site to mitochondrial reactive oxygen species generation in the absence of electron transport inhibitors is unknown in isolated mitochondria, in cells or in vivo, and may vary considerably with species, tissue, substrate, energy demand and oxygen tension. Copyright (c) 2010 Elsevier Inc. All rights reserved.
                Bookmark

                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                MDPI
                1420-3049
                24 February 2018
                February 2018
                : 23
                : 2
                : 509
                Affiliations
                [1 ]Department of Cellular and Structural Biology UT Health San Antonio, San Antonio, SD 78229, USA; tan@ 123456uthscsa.edu (D.X.T.); ZhouX4@ 123456uthscsa.edu (X.J.Z.); doctxu@ 123456126.com (B.X.)
                [2 ]Centro de Investigacion Biomedica de Occidente, Instituo Mexicana del Seguro Social, Guadalajara 44346, Mexico; espiral17@ 123456gmail.com
                [3 ]Departamento de Quimica, Universidad Autonoma Metropolitana-Iztapatapa, Mexico D.F. 09340, Mexico; agalano@ 123456prodigy.net.mx
                Author notes
                [* ]Correspondence: reiter@ 123456uthscsa.edu ; Tel.: +1-210-567-3859
                Article
                molecules-23-00509
                10.3390/molecules23020509
                6017324
                29495303
                a776406b-004b-4476-9dbd-30ee702962ef
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 January 2018
                : 16 February 2018
                Categories
                Review

                oxidative stress,free radicals,electron transport chain,oxidative phosphorylation,free radical theory of aging,melatonin uptake,melatonin synthesis

                Comments

                Comment on this article