Melatonin (N-acetyl-5-methoxytryptamine, aMT) is a highly conserved molecule present in unicellular to vertebrate organisms. Melatonin is synthesized from tryptophan in the pinealocytes by the pineal gland and also is produced in other organs, tissues and fluids (extrapineal melatonin). Melatonin has lipophilic and hydrophilic nature which allows it to cross biological membranes. Therefore, melatonin is present in all subcellular compartments predominantly in the nucleus and mitochondria. Melatonin has pleiotropic functions with powerful antioxidant, anti-inflammatory and oncostatic effects with a wide spectrum of action particularly at the level of mitochondria. » MiPNet article
Reference: Acuña-Castroviejo 2014 Cell Mol Life Sci
Melatonin and protection from mitochondrial damage
|Doerrier C (2015) Melatonin and attenuation of mitochondrial oxidative damage. Mitochondr Physiol Network 2015-03-03.|
Abstract: Melatonin (aMT) is a potent antioxidant and anti-inflammatory molecule able to attenuate mitochondrial oxidative damage, preserving mitochondrial function and organization.
Pineal and extrapineal melatonin
Melatonin (N-acetyl-5-methoxytryptamine, aMT) is a highly conserved molecule which is present in a broadrange of phylogenetic taxa, including bacteria, fungi, plants, algae, invertebrate and vertebrate organisms. Whereas pineal melatonin has been related with chronobiotic functions, extrapineal melatonin shows mainly antioxidant and antiinflammatory actions.
- Pineal melatonin: Pineal melatonin is synthesized from tryptophan in the pinealocytes by the pineal gland. Its production is controlled by a circadian signal from suprachiasmatic nucleus (SCN). At night photoreceptors of the retina generate a potential action which finally triggers an increment in the levels and activity of arylalkylamine N-acetyltransferase (AANAT) protein. AANAT is the penultimate enzyme in melatonin synthesis. However, during the day the light maintains these photoreceptors hyperpolarized, blocking melatonin synthesis. Therefore, melatonin presents maximum levels in plasma between 2-3 am, which are 10 times higher than diurnal levels. Once synthesized, melatonin is released into the bloodstream, accessing to cellular tissues and corporal fluids. Pineal melatonin is related to circadian functions.
- Extrapineal melatonin: Melatonin is produced in various tissues, fluids and organs other than the pineal gland. Extrapineal melatonin levels are in micromolar range and are thus much higher than the nanomolar pineal melatonin concentrations. The production of extrapineal melatonin is independent of the pineal synthesis and occurs in the tissues in a different functional context. Moreover, extrapineal melatonin differs from pineal melatonin in terms of its intracellular location and protection of the tissue.
Mechanisms of action
Two different mechanisms of action of melatonin have been described:
- Receptor-mediated mechanism: Melatonin binds to membrane receptors (such as MT1 and MT2), nuclear receptors (RZR/ROR) and cytosolic proteins (such calmodulin and calreticulin).
- Non receptor-mediated mechanism.
Due to its lipophilic and hydrophilic nature, melatonin can cross biological membranes. Therefore, melatonin is present in all subcellular compartments, predominantly in the nucleus and mitochondria. Melatonin exerts highly relevant functions at the level of mitochondria, which are the main target of melatonin. Mitochondria are an important source of reactive oxygen and nitrogen species (ROS/RNS) in the cell, and melatonin exerts important actions protecting against mitochondrial damage.
Main functions of extrapineal melatonin
Melatonin shows pleiotropic functions with a wide spectrum of properties.
Melatonin is a powerful antioxidant
- Melatonin presents direct free radical scavenging activity: Due to its structure and its high redox potential melatonin and its metabolites act as electron donors, scavenging ROS.
- Indirect antioxidant activity: Melatonin decreases ROS/RNS production, increases the expression and the activity of antioxidant systems (such as glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase).
Melatonin has anti-inflammatory properties
During inflammatory diseases (such as sepsis or fibromyalgia), an induction occurs in mitochondria of i-mtNOS (inducible mitochondrial isoform of nitric oxide synthase) which causes a significant rise in nitric oxide (NO●) production and consequently an increment in peroxinitrite anion (ONOO–) levels. Both NO● and ONOO– inhibit respiratory complexes, favoring electron leak and producing finally an oxidative-nitrosative stress able to damage cellular structures, resulting in mitochondrial failure and cell death. Melatonin inhibits iNOS (cytosolic isoform of nitric oxide synthase) and i-mtNOS expression, restoring NO● levels. Accordingly, melatonin decrease RNS and ROS production, maintaining an optimal mitochondrial function.
On the other hand, inflammatory processes result in the activation of the nuclear factor NF-kB which acts in the nucleus triggering the expression of several proinflammatory genes. Melatonin inhibits the activation of the NF-kB pathway.
Melatonin exhibits oncostatic effects
Melatonin inhibits cell proliferation or induces apoptosis activation of tumoral cells by different mechanisms of action.
The lipid composition of mitochondrial membranes is relevant to maintain an adequate fluidity and consequently the organization and function of mitochondria. Important phospholipids present in mitochondrial membranes are very susceptible to the ROS attack and to the damage by lipid peroxidation (LPO). Moreover, phospholipids such as cardiolipin (CL) are involved in CI and CIV activities, mitochondrial supramolecular organization in supercomplexes (SC), the integrity of mitochondrial network and apoptotic processes. Therefore, alterations in cardiolipin structure, content and/or acyl chains compositions have significant implications on mitochondrial function. Melatonin is able to protect these mitochondrial components against oxidative and nitrosative-related damage, providing and optimal membrane fluidity which is necessary for a proper mitochondrial function.
Mitochondrial dysfunction plays a key role in several pathologies such as neurodegenerative, cardiovascular and inflammatory diseases, metabolic disorders, ischemia-reperfusion, hypoxia, mucositis as well as in aging. Usually, mitochondrial dysfunction in these pathophysiological conditions is caused, at least in part, by an increment in oxidative and nitrosative stress. A large body of studies support that melatonin treatment protects against hyperoxidative damage mediated via various mechanisms. Melatonin allows an optimal mitochondrial function by their direct and indirect actions.
In summary, melatonin administration can counteract mitochondrial impairment mainly by decreasing ROS/RNS production, preventing LPO and hence reducing oxidative damage of relevant components of mitochondrial membranes such as cardiolipin and polyunsaturated fatty acid (PUFAs), allowing to maintain an adequate structure and function and consequently preserving bioenergetic processes.
- Ortiz F, Acuña-Castroviejo D, Doerrier C, Dayoub JC, López LC, Venegas C, García JA, López A, Volt H, Luna-Sánchez M, Escames G (2014) Melatonin blunts the mitochondrial/NLRP3 connection and protects against radiation-induced oral mucositis. J Pineal Res 58:34-49. »PMID: 25388914
- Doerrier C, García JA, Volt H, Díaz-Casado ME, Lima-Cabello E, Ortiz F, Luna-Sánchez M, Escames G, López LC, Acuña-Castroviejo D (2014) Identification of mitochondrial deficits and melatonin targets in liver of septic mice by high-resolution respirometry. Life Sci 121:158-65. »PMID: 25498899
- López A, García JA, Escames G, Venegas C, Ortiz F, López LC, Acuña-Castroviejo D (2009) Melatonin protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential, and superoxide anion production. J Pineal Res 46:188-98. »PMID: 19054298
- Acuña-Castroviejo D, Carretero C, Doerrier C, López LC, García-Corzo L, Tresguerres JA, Escames G (2012) Melatonin protects lung mitochondria from aging. Age (Dordr)34:681-692. »PMID: 21614449
- Acuña-Castroviejo D, Escames G, Venegas C, Díaz-Casado ME, Lima-Cabello E, López LC, Rosales-Corral S, Tan DX, Reiter RJ (2014) Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci 71:2997-25. »PMID: 24554058
- Acuña-Castroviejo D, López LC, Escames G, López A, García JA, Reiter RJ (2011) Melatonin-mitochondria interplay in health and disease. Curr Top Med Chem 11:221-240. »PMID: 21244359
- Tan DX, Manchester LC, Reiter RJ, Qi WB, Karbownik M, Calvo JR (2000) Significance of melatonin in antioxidative defense system: reactions and products. Biol Signals Recept 9:137-159. »PMID: 10899700
Melatonin and mitObesity
Work in progress by Gnaiger E 2020-02-10 linked to a preprint in preparation on BME and mitObesity.
|Kleszczynski 2018 Int J Mol Sci||2018||Kleszczyński K, Bilska B, Stegemann A, Flis DJ, Ziolkowski W, Pyza E, Luger TA, Reiter RJ, Böhm M, Slominski AT (2018) Melatonin and its metabolites ameliorate UVR-induced mitochondrial oxidative stress in human MNT-1 melanoma cells. Int J Mol Sci 19:E3786.||Mouse||Liver|
|De Moura Alvorcem 2018 Mitochondrion||2018||De Moura Alvorcem L, Britto R, Parmeggiani B, Glanzel NM, Da Rosa-Junior NT, Cecatto C, Bobermin LD, Amaral AU, Wajner M, Leipnitz G (2018) Evidence that thiol group modification and reactive oxygen species are involved in hydrogen sulfide-induced mitochondrial permeability transition pore opening in rat cerebellum. Mitochondrion 47:141-50.||Rat||Nervous system|
|Jiki 2018 Front Physiol||2018||Jiki Z, Lecour S, Nduhirabandi F (2018) Cardiovascular benefits of dietary melatonin: a myth or a reality?. Front Physiol 9:528.||Human|
|Scarpelli 2018 J Pineal Res||2018||Scarpelli P, Almeida GT, Viçoso KL, Lima WR, Pereira LB, Meissner KA, Wrenger C, Rafaello A, Rizzuto R, Pozzan T, Garcia CRS (2018) Melatonin activate FIS1, DYN1 and DYN2 Plasmodium falciparum related-genes for mitochondria fission: mitoemerald-GFP as a tool to visualize mitochondria structure. J Pineal Res 66:e12484.|
|Da Silva 2017 Neurotox Res||2017||Da Silva JC, Amaral AU, Cecatto C, Wajner A, Dos Santos Godoy K, Ribeiro RT, de Mello Gonçalves A, Zanatta Â, da Rosa MS, Loureiro SO, Vargas CR, Leipnitz G, de Souza DOG, Wajner M (2017) α-Ketoadipic acid and α-aminoadipic acid cause disturbance of glutamatergic neurotransmission and induction of oxidative stress in vitro in brain of adolescent rats. Neurotox Res 32:276-90.||Rat||Nervous system|
|Lopez 2017 PLOS ONE||2017||López A, Ortiz F, Doerrier C, Venegas C, Fernández-Ortiz M, Aranda P, Díaz-Casado ME, Fernández-Gil B, Barriocanal-Casado E, Escames G, López L, Acuña-Castroviejo D (2017) Mitochondrial impairment and melatonin protection in parkinsonian mice do not depend of inducible or neuronal nitric oxide synthases. PLOS ONE 12:e0183090.||Mouse|
|De Moura 2017 Neurotox Res||2017||de Moura Alvorcem L, da Rosa MS, Glänzel NM, Parmeggiani B, Grings M, Schmitz F, Wyse ATS, Wajner M, Leipnitz G (2017) Disruption of energy transfer and redox status by sulfite in hippocampus, striatum, and cerebellum of developing rats. Neurotox Res 32:264-75.||Rat||Nervous system|
|Volt 2016 J Pineal Res||2016||Volt H, García JA, Doerrier C, Díaz-Casado ME, Guerra-Librero A, López LC, Escames G, Tresguerres JA, Acuña-Castroviejo D (2016) Same molecule but different expression: aging and sepsis trigger NLRP3 inflammasome activation, a target of melatonin. J Pineal Res 60:193-205.||Mouse||Heart|
|Maarman 2016 J Appl Physiol (1985)||2016||Maarman GJ, Andrew BM, Blackhurst DM, Ojuka EO (2016) Melatonin protects against uric acid-induced mitochondrial dysfunction, oxidative stress, and triglyceride accumulation in C2C12 myotubes. J Appl Physiol (1985) 122:1003-10.||Mouse||Skeletal muscle|
|Doerrier 2016 Mitochondrion||2016||Doerrier C, García JA, Volt H, Díaz-Casado ME, Luna-Sánchez M, Fernández-Gil B, Escames G, López LC, Acuña-Castroviejo D (2016) Permeabilized myocardial fibers as model to detect mitochondrial dysfunction during sepsis and melatonin effects without disruption of mitochondrial network. Mitochondrion 27:56-63.||Mouse||Heart|
|Ortiz 2015 J Pineal Res||2015||Ortiz F, Acuña-Castroviejo D, Doerrier C, Dayoub JC, López LC, Venegas C, García JA, López A, Volt H, Luna-Sánchez M, Escames G (2015) Melatonin blunts the mitochondrial/NLRP3 connection and protects against radiation-induced oral mucositis. J Pineal Res 58:34-49.|
|Garcia 2015 FASEB J||2015||García JA, Volt H, Venegas C, Doerrier C, Escames G, López LC, Acuña-Castroviejo D (2015) Disruption of the NF-κB/NLRP3 connection by melatonin requires retinoid-related orphan receptor-α and blocks the septic response in mice. FASEB J 29:3863-75.||Mouse||Heart|
|Agil 2015 J Pineal Res||2015||Agil A, El-Hammadi M, Jiménez-Aranda A, Tassi M, Abdo W, Fernández-Vázquez G, Reiter RJ (2015) Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats. J Pineal Res 59:70-9.||Rat||Liver|
|Ortiz 2014 J Pineal Res||2014||Ortiz F, García JA, Acuña-Castroviejo D, Doerrier C, López A, Venegas C, Volt H, Luna-Sánchez M, López LC, Escames G (2014) The beneficial effects of melatonin against heart mitochondrial impairment during sepsis: inhibition of iNOS and preservation of nNOS. J Pineal Res 56:71-81.|
|Acuña-Castroviejo 2014 Cell Mol Life Sci||2014||Acuña-Castroviejo D, Escames G, Venegas C, Díaz-Casado ME, Lima-Cabello E, López LC, Rosales-Corral S, Tan DX, Reiter RJ (2014) Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci 71:2997-25.|
|Doerrier 2014 Life Sci||2014||Doerrier C, García JA, Volt H, Díaz-Casado ME, Lima-Cabello E, Ortiz F, Luna-Sánchez M, Escames G, López LC, Acuña-Castroviejo D (2014) Identification of mitochondrial deficits and melatonin targets in liver of septic mice by high-resolution respirometry. Life Sci 121:158-65.||Mouse||Liver|
|Jimenez-Aranda 2014 J Pineal Res||2014||Jimenéz-Aranda A, Fernández-Vázquez G, Serrano MM, Reiter RJ, Agil A (2014) Melatonin improves mitochondrial function in inguinal white adipose tissue of Zücker diabetic fatty rats. J Pineal Res 57:103-9.||Rat||Fat|
|Escames 2013 Horm Mol Biol Clin Investig||2013||Escames G, Diaz-Casado ME, Doerrier C, Luna-Sanchez M, Lopez LC, Acuna-Castroviejo D (2013) Early gender differences in the redox status of the brain mitochondria with age: effects of melatonin therapy. Horm Mol Biol Clin Investig 16(2):91-100.|
|Rodriguez 2013 Int J Mol Sci||2013||Rodriguez C, Martín V, Herrera F, García-Santos G, Rodriguez-Blanco J, Casado-Zapico S, Sánchez-Sánchez AM, Suárez S, Puente-Moncada N, Anítua MJ, Antolín I (2013) Mechanisms Involved in the Pro-Apoptotic Effect of Melatonin in Cancer Cells. Int J Mol Sci 14:6597-613.|
|Sarti 2013 Int J Mol Sci||2013||Sarti P, Magnifico MC, Altieri F, Mastronicola D, Arese M (2013) New evidence for cross talk between melatonin and mitochondria mediated by a circadian-compatible interaction with nitric oxide. Int J Mol Sci 14:11259-76.||Human||Other cell lines|
|Acuña-Castroviejo 2012 Age (Dordr)||2012||Acuña-Castroviejo D, Carretero M, Doerrier C, López LC, García-Corzo L, Tresguerres JA, Escames G (2012) Melatonin protects lung mitochondria from aging. Age (Dordr) 34(3):681-92.||Mouse||Lung;gill|
|Acuña-Castroviejo 2011 Curr Top Med Chem||2011||Acuña-Castroviejo D; López LC; Escames G; López A; García JA; Reiter RJ (2011) Melatonin-mitochondria interplay in health and disease. Curr Top Med Chem 11:221-240.|
|Lopez 2009 J Pineal Res||2009||López A, García JA, Escames G, Venegas C, Ortiz F, López LC, Acuña-Castroviejo D (2009) Melatonin protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential, and superoxide anion production. J Pineal Res 46:188-98.||Mouse||Liver|
|Hardeland 2009 Biofactors||2009||Hardeland R (2009) Melatonin: signaling mechanisms of a pleiotropic agent. Biofactors 35:183-92.|
|Morota 2009 Exp Neurol||2009||Morota S, Månsson R, Hansson Magnus J, Kasuya K, Shimazu M, Hasegawa E, Yanagi S, Omi A, Uchino H, Elmér E (2009) Evaluation of putative inhibitors of mitochondrial permeability transition for brain disorders-specificity vs. toxicity. Exp Neurol 218:353-62.||Human||Liver|
|Bromme 2008 J Pineal Res||2008||Brömme HJ, Peschke E, Israel G (2008) Photo-degradation of melatonin: influence of argon, hydrogenperoxide, and ethanol. J Pineal Res 44:366-72.|
|Reiter 2003 Acta Biochim Pol||2003||Reiter RJ, Tan DX, Mayo JC, Sainz RM, Leon J, Czarnocki Z (2003) Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta Biochim Pol 50:1129-46.|
|Bromme 2000 J Pineal Res||2000||Brömme HJ, Mörke W, Peschke E, Ebelt H, Peschke D (2000) Scavenging effect of melatonin on hydroxyl radicals generated by alloxan. J Pineal Res 44:366-72.|
|Tan 2000 Biol Signals Recept||2000||Tan DX, Manchester LC, Reiter RJ, Qi WB, Karbownik M, Calvo JR (2000) Significance of melatonin in antioxidative defense system: reactions and products. Biol Signals Recept 9:137-59.|
|Ortiz 2013 Abstract SEOR||2013||Molecular Basis of the radiotherapy-induced mucositis, beneficial effects of melatonin.||Rat|
- Tümentemur G, Altunkaynak BZ, Kaplan S (2020) Is melatonin, leptin or their combination more effective on oxidative stress and folliculogenesis in the obese rats? J Obstet Gynaecol 40:116-27. - https://www.ncbi.nlm.nih.gov/pubmed/31625776
- Maes M, Anderson G, Betancort Medina SR, Seo M, Ojala JO () Integrating autism spectrum disorder pathophysiology: mitochondria, vitamin A, CD38, oxytocin, serotonin and melatonergic alterations in the placenta and gut. Curr Pharm Des. 2019 Nov 2. - https://www.ncbi.nlm.nih.gov/pubmed/31682209
- Farias TDSM, Paixao RID, Cruz MM, de Sa RDCDC, Simão JJ, Antraco VJ, Alonso-Vale MIC (2019) Melatonin supplementation attenuates the pro-inflammatory adipokines expression in visceral fat from obese mice induced by a high-fat diet. Cells 8. pii: E1041. - https://www.ncbi.nlm.nih.gov/pubmed/31489938
- Xu Z, You W, Liu J, Wang Y, Shan T (2019) Elucidating the regulatory role of melatonin in brown, white, and beige adipocytes. Adv Nutr 2019 Jul 29. pii: nmz070. - https://www.ncbi.nlm.nih.gov/pubmed/31355852
- Shafabakhsh R, Reiter RJ, Davoodabadi A, Asemi Z (2019) Melatonin as a potential inhibitor of colorectal cancer: molecular mechanisms. J Cell Biochem 120:12216-23. - https://www.ncbi.nlm.nih.gov/pubmed/31087705
- Dantas-Ferreira RF, Raingard H, Dumont S, Schuster-Klein C, Guardiola-Lemaitre B, Pevet P, Challet E (2018) Melatonin potentiates the effects of metformin on glucose metabolism and food intake in high-fat-fed rats. Endocrinol Diabetes Metab 1:e00039. - https://www.ncbi.nlm.nih.gov/pubmed/30815567
- Liu K, Yu W, Wei W, Zhang X, Tian Y, Sherif M, Liu X, Dong C, Wu W, Zhang L, Chen J (2019) Melatonin reduces intramuscular fat deposition by promoting lipolysis and increasing mitochondrial function. J Lipid Res 60:767-82. - https://www.ncbi.nlm.nih.gov/pubmed/30552289
- Karamitri A, Jockers R (2019) Melatonin in type 2 diabetes mellitus and obesity. Nat Rev Endocrinol 15:105-25. - https://www.ncbi.nlm.nih.gov/pubmed/30531911
- Valenzuela-Melgarejo FJ, Caro-Díaz C, Cabello-Guzmán G (2018) Potential crosstalk between fructose and melatonin: a new role of melatonin-inhibiting the metabolic effects of fructose. Int J Endocrinol 2018:7515767. - https://www.ncbi.nlm.nih.gov/pubmed/30154843
- Liu Y, Li LN, Guo S, Zhao XY, Liu YZ, Liang C, Tu S, Wang D, Li L, Dong JZ, Gao L, Yang HB (2018) Melatonin improves cardiac function in a mouse model of heart failure with preserved ejection fraction. Redox Biol 18:211-21. - https://www.ncbi.nlm.nih.gov/pubmed/30031269
- Nabavi SM, Nabavi SF, Sureda A, Xiao J, Dehpour AR, Shirooie S, Silva AS, Baldi A, Khan H, Daglia M (2019) Anti-inflammatory effects of melatonin: a mechanistic review. Crit Rev Food Sci Nutr 59(sup1):S4-16. - https://www.ncbi.nlm.nih.gov/pubmed/29902071
- Prado NJ, Ferder L, Manucha W, Diez ER (2018) Anti-inflammatory effects of melatonin in obesity and hypertension. Curr Hypertens Rep 20:45. - https://www.ncbi.nlm.nih.gov/pubmed/29744660
- Fernández Vázquez G, Reiter RJ, Agil A (2018) Melatonin increases brown adipose tissue mass and function in Zücker diabetic fatty rats: implications for obesity control. J Pineal Res 64:e12472. - https://www.ncbi.nlm.nih.gov/pubmed/29405372
- Stacchiotti A, Favero G, Giugno L, Golic I, Korac A, Rezzani R (2017) Melatonin efficacy in obese leptin-deficient mice heart. Nutrients 9 pii: E1323. - https://www.ncbi.nlm.nih.gov/pubmed/29206172
- Szewczyk-Golec K, Rajewski P, Gackowski M, Mila-Kierzenkowska C, Wesołowski R, Sutkowy P, Pawłowska M, Woźniak A (2017) Melatonin supplementation lowers oxidative stress and regulates adipokines in obese patients on a calorie-restricted diet. Oxid Med Cell Longev 2017:8494107. - https://www.ncbi.nlm.nih.gov/pubmed/29142618
- Rubio-González A, Bermejo-Millo JC, de Luxán-Delgado B, Potes Y, Pérez-Martínez Z, Boga JA, Vega-Naredo I, Caballero B, Solano JJ, Coto-Montes A; Members of Research Team cROS (cellular Response to Oxidative Stress) (2018) Melatonin prevents the harmful effects of obesity on the brain, including at the behavioral level. Mol Neurobiol 55:5830-46. - https://www.ncbi.nlm.nih.gov/pubmed/29086246
- Zhou H, Du W, Li Y, Shi C, Hu N, Ma S, Wang W, Ren J (2018) Effects of melatonin on fatty liver disease: The role of NR4A1/DNA-PKcs/p53 pathway, mitochondrial fission, and mitophagy. J Pineal Res 64(1). - https://www.ncbi.nlm.nih.gov/pubmed/28981157
- Cardinali DP, Vigo DE (2017) Melatonin, mitochondria, and the metabolic syndrome. Cell Mol Life Sci 74:3941-54. - https://www.ncbi.nlm.nih.gov/pubmed/28819865
- Han L, Wang H, Li L, Li X, Ge J, Reiter RJ, Wang Q (2017) Melatonin protects against maternal obesity-associated oxidative stress and meiotic defects in oocytes via the SIRT3-SOD2-dependent pathway. J Pineal Res 63(3). - https://www.ncbi.nlm.nih.gov/pubmed/28658527
- Ireland KE, Maloyan A, Myatt L (2018) Melatonin improves mitochondrial respiration in syncytiotrophoblasts from placentas of obese women. Reprod Sci 25:120-30. - https://www.ncbi.nlm.nih.gov/pubmed/28443479
- Xu P, Wang J, Hong F, Wang S, Jin X, Xue T, Jia L, Zhai Y (2017) Melatonin prevents obesity through modulation of gut microbiota in mice. J Pineal Res 62(4). - https://www.ncbi.nlm.nih.gov/pubmed/28199741
MitoPedia: mitObesity drugs
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|Curcumin||Curcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant and anti-infective effects. The protective effects of curcumin on rat heart mitochondrial injuries induced by in vitro anoxia–reoxygenation were evaluated by Xu et al 2013. It was found that curcumin added before anoxia or immediately prior to reoxygenation exhibited remarkable protective effects against anoxia–reoxygenation induced oxidative damage to mitochondria.|
|Elamipretide||Bendavia||Bendavia (Elamipretide) was developed as a mitochondria-targeted drug against degenerative diseases, including cardiac ischemia-reperfusion injury. Clinical trials showed variable results. It is a cationic tetrapeptide which readily passes cell membranes, associates with cardiolipin in the mitochondrial inner membrane. Supercomplex-associated CIV activity significantly improved in response to elamipretide treatment in the failing human heart.|
|Flavonoids||Flavonoids are a group of bioactive polyphenols with potential antioxidant and anti-inflammatory effects, abundant in fruits and vegetables, and in some medicinal herbs. Flavonoids are synthesized in plants from phenylalanine. Dietary intake of flavonoids as nutraceuticals is discussed for targeting T2D and other degenerative diseases.|
|Melatonin||aMT||Melatonin (N-acetyl-5-methoxytryptamine, aMT) is a highly conserved molecule present in unicellular to vertebrate organisms. Melatonin is synthesized from tryptophan in the pinealocytes by the pineal gland and also is produced in other organs, tissues and fluids (extrapineal melatonin). Melatonin has lipophilic and hydrophilic nature which allows it to cross biological membranes. Therefore, melatonin is present in all subcellular compartments predominantly in the nucleus and mitochondria. Melatonin has pleiotropic functions with powerful antioxidant, anti-inflammatory and oncostatic effects with a wide spectrum of action particularly at the level of mitochondria. » MiPNet article|
|Metformin||Metformin is mainly known as an important antidiabetic drug which is effective, however, in a wide spectrum of degenerative diseases. It is an inhibitor of Complex I.|
|Rapamycin||Rapamycin is an inhibitor of the mammalian/mechanistic target of rapamycin, complex 1 (mTORC1). Rapamycin induces autophagy and dyscouples mitochondrial respiration. Rapamycin delays senescence in human cells, and extends lifespan in mice without detrimental effects on mitochondrial fitness in skeletal muscle.|
|Resveratrol||Resveratrol is a natural bioactive phenol prouced by several plants with antioxidant and anti-inflammatory effects. Dietary intake as nutraceutical is discussed for targeting mitochondria with a wide spectrum of action in degenerative diseases.|
|Spermidine||Spermidine is a polycationic bioactive polyamine mainly found in wheat germ, soybean and various vegetables, involved in the regulation of mitophagy, cell growth and cell death. Like other caloric restriction mimetics, spermidine is effective in cardioprotection, neuroprotection and anticancer immunosuppression by preserving mitochondrial function and control of autophagy.|
|Healthy reference population||Body mass excess||BFE||BME cutoffs||BMI||H||M||VO2max||mitObesity drugs|
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