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Property "Has-20abstract" (as page type) with input value "-5B-5BFile:Dario.JPG-7Cright-7C200px-7CDario-20Acuna-2DCastroviejo-5D-5D-0AThe-20first-20relationship-20between-20melatonin-20and-20mitochondria-20came-20from-20histological-20studies-20showing-20changes-20in-20mitochondrial-20density-20and-20morphology-20after-20pinealectomy-20or-20melatonin-20administration-20to-20experimental-20animals.-20After-20the-20discovery-20of-20the-20antioxidant-20activity-20of-20melatonin-20in-201993,-20the-20possibility-20that-20melatonin-20exerts-20its-20effects-20on-20the-20mitochondria,-20the-20main-20ROS-2Dproducing-20organelle,-20was-20hypothesized.-20The-20first-20experiments-20demonstrated-20a-20highly-20efficient-20ability-20of-20melatonin-20to-20counteract-20the-20mitochondrial-20oxidative-20stress-20-27-27in-20vitro-27-27-20and-20-27-27in-20vivo-27-27.-20In-20parallel,-20melatonin-20increases-20the-20respiratory-20chain-20activity,-20reduces-20the-20oxygen-20consumption,-20and-20increases-20the-20ATP-20production.-20In-20some-20of-20these-20experiments-20we-20could-20demonstrated-20that-20the-20mitochondria-20take-20up-20melatonin-20in-20a-20time-2D-20and-20concentration-2Ddependent-20manner.-20To-20further-20analyze-20the-20ability-20of-20melatonin-20to-20prevent-20and-2For-20counteract-20mitochondrial-20dysfunction,-20different-20experimental-20models-20of-20aging-20and-20disease,-20including-20sepsis,-20Parkinson’s-20disease,-20and-20Alzheimer’s-20disease,-20was-20evaluated.-20In-20all-20of-20them,-20melatonin-20administration-20restored-20the-20full-20bioenergetic-20capacity-20of-20the-20mitochondria,-20restoring-20or-20even-20increasing-20their-20ATP-20production.-20Along-20this-20time,-20it-20was-20shown-20that-20most-20of-20the-20tissues-20and-20organs-20produce-20melatonin-20independently-20of-20the-20pineal-20gland.-20An-20important-20feature-20of-20this-20extrapineal-20source-20of-20melatonin-20is-20that-20its-20synthetizing-20enzymes,-20AANAT-20and-20ASMT,-20are-20inducible,-20i.e.,-20the-20cells-20produce-20melatonin-20when-20they-20require-20it-20for-20protective-20purposes.-20This-20melatonin-20does-20not-20exit-20to-20the-20extracellular-20fluid.-20To-20further-20analyze-20the-20dynamics-20of-20the-20extrapineal-20melatonin,-20we-20recently-20studied-20the-20subcellular-20distribution-20of-20the-20indoleamine-20in-20liver-20and-20brain.-20These-20studies-20showed-20that-20melatonin-20is-20produced-20in-20considerably-20higher-20amounts-20in-20these-20tissues-20than-20in-20the-20pineal-20gland,-20it-20is-20not-20uniformly-20distributed-20in-20the-20cell,-20and-20is-20mainly-20located-20in-20the-20membrane,-20mitochondria-20and-20nucleus.-20Interestingly,-20membrane-20content-20of-20melatonin-20increased-20in-20a-20dose-2Ddependent-20manner-20after-20administration-20of-20melatonin-20to-20rats,-20but-20the-20content-20of-20the-20indoleamine-20in-20the-20nucleus-20and-20mitochondria-20is-20saturated.-20There-20are-20now-20evidences-20of-20the-20ability-20of-20mitochondria-20(and-20chloroplasts)-20to-20synthesize-20melatonin,-20which-20explains-20the-20high-20levels-20of-20the-20indoleamine-20in-20this-20organelle.-20The-20phylogenetic-20origins-20of-20the-20mitochondria,-20and-20the-20presence-20of-20melatonin-20in-20ancient-20one-20cell-20organisms,-20speak-20in-20favor-20of-20a-20melatonin-2Dmitochondrion-20connection-20along-20the-20evolution,-20and-20the-20role-20of-20melatonin-20in-20mitochondrial-20homeostasis.-0A-23-20-5Bhttp:-2F-2Fwww.ncbi.nlm.nih.gov-2Fpubmed-2F21244359-20Acuna-20Castroviejo-20D,-20Lopez-20LC,-20Escames-20G,-20Lopez-20A,-20Garcia-20JA,-20Reiter-20RJ-20(2011)-20Melatonin-2Dmitochondria-20interplay-20in-20health-20and-20disease.-20Curr-20Top-20Med-20Chem-2011:-20221-2D240.-5D-0A-23-20-5Bhttp:-2F-2Fwww.ncbi.nlm.nih.gov-2Fpubmed-3Fterm=Mitochondria-2520and-2520chloroplasts-2520as-2520the-2520original-2520sites-2520of-2520melatonin-2520synthesis-253A-2520a-2520hypothesis-2520related-2520to-2520melatonin's-2520primary-2520function-2520and-2520evolution-2520in-2520eukaryotes-20Tan-20DX,-20Manchester-20LC,-20Liu-20X,-20Rosales-2DCorral-20SA,-20Acuna-2DCastroviejo-20D,-20Reiter-20RJ-20(2012)-20Mitochondria-20and-20chloroplasts-20as-20the-20original-20sites-20of-20melatonin-20synthesis:-20a-20hypothesis-20related-20to-20melatonin's-20primary-20function-20and-20evolution-20in-20eukaryotes.-20J-20Pineal-20Res.-20doi:-2010.1111-2Fjpi.12026-5D" contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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