{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:05:24Z","timestamp":1789423524596,"version":"build-2803163510"},"reference-count":248,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T00:00:00Z","timestamp":1637280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Melatonin is synthesized in the pineal gland at night. Since melatonin is produced in the mitochondria of all other cells in a non-circadian manner, the amount synthesized by the pineal gland is less than 5% of the total. Melatonin produced in mitochondria influences glucose metabolism in all cells. Many pathological cells adopt aerobic glycolysis (Warburg effect) in which pyruvate is excluded from the mitochondria and remains in the cytosol where it is metabolized to lactate. The entrance of pyruvate into the mitochondria of healthy cells allows it to be irreversibly decarboxylated by pyruvate dehydrogenase (PDH) to acetyl coenzyme A (acetyl-CoA). The exclusion of pyruvate from the mitochondria in pathological cells prevents the generation of acetyl-CoA from pyruvate. This is relevant to mitochondrial melatonin production, as acetyl-CoA is a required co-substrate\/co-factor for melatonin synthesis. When PDH is inhibited during aerobic glycolysis or during intracellular hypoxia, the deficiency of acetyl-CoA likely prevents mitochondrial melatonin synthesis. When cells experiencing aerobic glycolysis or hypoxia with a diminished level of acetyl-CoA are supplemented with melatonin or receive it from another endogenous source (pineal-derived), pathological cells convert to a more normal phenotype and support the transport of pyruvate into the mitochondria, thereby re-establishing a healthier mitochondrial metabolic physiology.<\/jats:p>","DOI":"10.3390\/ijms222212494","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T08:29:17Z","timestamp":1637310557000},"page":"12494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Melatonin and Pathological Cell Interactions: Mitochondrial Glucose Processing in Cancer Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6763-4225","authenticated-orcid":false,"given":"Russel","family":"Reiter","sequence":"first","affiliation":[{"name":"Department of Cell Systems & Anatomy, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2346-5305","authenticated-orcid":false,"given":"Ramaswamy","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Cell Systems & Anatomy, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Rosales-Corral","sequence":"additional","affiliation":[{"name":"Centro de Investigacion Biomedica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 45150, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2279-7626","authenticated-orcid":false,"given":"Walter","family":"Manucha","sequence":"additional","affiliation":[{"name":"Instituto de Medicina y Biologia Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET), Mendoza 5500, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0199-3396","authenticated-orcid":false,"given":"Luiz Gustavo de Almeida","family":"Chuffa","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences of Botucatu, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0146-9041","authenticated-orcid":false,"given":"Debora Aparecida Pires de Campos","family":"Zuccari","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigacao Molecular do Cancer, Faculdade de Medicina de Sao Jose do Rio Preto, Sao Jose do Rio Preto 15080-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1600-079X.2009.00686.x","article-title":"Antineoplastic effects of melatonin on a rare malignancy of mesenchymal origin: Melatonin receptor-mediated inhibition of signal transduction, linoleic, acid metabolism and growth in tissue-isolated human leiomyosarcoma xenografts","volume":"47","author":"Dauchy","year":"2009","journal-title":"J. Pineal Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R183","DOI":"10.1530\/ERC-15-0030","article-title":"Melatonin: An inhibitor of breast cancer","volume":"22","author":"Hill","year":"2015","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Samec, M., Liskova, A., Koklesova, L., Zhai, K., Varghese, E., Samuel, S.M., Sudomova, M., Lucansky, V., Kassayova, M., and Pec, M. (2021). Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects. Cancers, 13.","DOI":"10.3390\/cancers13123018"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.4155\/fmc-2020-0086","article-title":"Understanding the oncostatic actions displayed by melatonin in colorectal cancer therapy","volume":"12","author":"Reiter","year":"2020","journal-title":"Future Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Laborda-Illanes, A., Sanchez-Alcoholado, L., Boutriq, S., Plaza-Andrades, I., Peralta-Linero, J., Alba, E., Gonzalez-Gonzalez, A., and Queipo-Ortuno, M.I. (2021). A New Paradigm in the Relationship between Melatonin and Breast Cancer: Gut Microbiota Identified as a Potential Regulatory Agent. Cancers, 13.","DOI":"10.3390\/cancers13133141"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1385\/ENDO:27:2:179","article-title":"Putting cancer to sleep at night: The neuroendocrine\/circadian mealtonin signal","volume":"27","author":"Blask","year":"2005","journal-title":"Endocrine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e449","DOI":"10.1002\/ctm2.449","article-title":"Melatonin inhibits lipid accumulation to repress prostate cancer progression by mediating the epigenetic modification of CES1","volume":"11","author":"Zhou","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111782","DOI":"10.1016\/j.biopha.2021.111782","article-title":"Molecular targets for the management of gastrointestinal cancer using melatonin, a natural endogenous body hormone","volume":"140","author":"Kohandel","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/fcp.12538","article-title":"The effects of melatonin on signaling pathways and molecules involved in glioma: Melatonin and glioblastoma pathophysiology and treatment","volume":"34","author":"Anderson","year":"2020","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4659","DOI":"10.1007\/s11033-021-06439-1","article-title":"Melatonin and neuroblastoma: A novel therapeutic approach","volume":"48","author":"Pourhanifeh","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1093\/carcin\/bgx054","article-title":"Melatonin as a promising agent to treat ovarian cancer: Molecular mechanisms","volume":"38","author":"Chuffa","year":"2017","journal-title":"Carcinogenesis"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yasin, H.K., Taylor, A.H., and Ayakannu, T. (2021). A Narrative Review of the Role of Diet and Lifestyle Factors in the Development and Prevention of Endometrial Cancer. Cancers, 13.","DOI":"10.3390\/cancers13092149"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1186\/s12935-020-01531-1","article-title":"Melatonin and urological cancers: A new therapeutic approach","volume":"20","author":"Mehrzadi","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/cbdd.13849","article-title":"Multiple interactions between melatonin and non-coding RNAs in cancer biology","volume":"98","author":"Maleki","year":"2021","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Reiter, R.J., Rosales-Corral, S.A., Tan, D.X., Acuna-Castroviejo, D., Qin, L., Yang, S.F., and Xu, K. (2017). Melatonin, a full service anti-cancer agent: Inhibition of initiation, progression and metastasis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040843"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2174\/2211536608666190219095426","article-title":"Therapeutic potential of melatonin in the regulation of MiR-148a-3p and angiogenic factors in breast cancer","volume":"8","author":"Lacerda","year":"2019","journal-title":"Microna"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.2174\/1871520618666180131112304","article-title":"Melatonin differentially modulates NF-B expression in breast and liver cancer cells","volume":"18","author":"Colombo","year":"2018","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12964-021-00723-0","article-title":"The inhibitory effect of melatonin on human prostate cancer","volume":"19","author":"Shen","year":"2021","journal-title":"Cell Commun. Signal"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s41598-018-37413-w","article-title":"RNA-Seq transcriptome analysis shows anti-tumor actions of melatonin in a breast cancer xenograft model","volume":"9","author":"Alexandre","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1007\/s11010-021-04151-z","article-title":"Melatonin and its mechanism of action in the female reproductive system and related malignancies","volume":"476","author":"Ezzati","year":"2021","journal-title":"Mol. Cell Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"108","DOI":"10.2174\/187221412800604581","article-title":"Breast cancer therapy based on melatonin","volume":"6","author":"Mediavilla","year":"2012","journal-title":"Recent Pat. Endocr. Metab. Immune Drug Discov."},{"key":"ref_22","first-page":"145894","article-title":"The role of circadin genes in eh pathogenesis of colorectal cancer","volume":"804","author":"Ahangari","year":"2021","journal-title":"Genes"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jin, Y., Choi, Y.J., Heo, K., and Park, S.J. (2021). Melatonin as an Oncostatic Molecule Based on Its Anti-Aromatase Role in Breast Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010438"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s00018-018-2963-0","article-title":"Mitochondrial functions and melatonin: A tour of the reproductive cancers","volume":"76","author":"Chuffa","year":"2019","journal-title":"Cell Mol. Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1021\/acs.jproteome.6b00713","article-title":"Quantitative proteomic profiling reveals that diverse metabolic pathways are influenced by melatonin in an in vivo model of ovarian carcinoma","volume":"15","author":"Chuffa","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.exger.2009.02.002","article-title":"Age-related changes in melatonin synthesis in rat extrapineal tissues","volume":"44","author":"Naranjo","year":"2009","journal-title":"Exp. Gerontol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Blask, D.E., Dauchy, R.T., Dauchy, E.M., Mao, L., Hill, S.M., Greene, M.W., Belancio, V.P., Sauer, L.A., and Davidson, L. (2014). Light exposure at night disrupts host\/cancer circadian regulatory dynamics: Impact on the Warburg effect, lipid signaling and tumor growth prevention. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102776"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"269","DOI":"10.30802\/AALAS-CM-17-000107","article-title":"Effect of daytime blue-enriched LED light on the nighttime circadian melatonin inhibition of hepatoma 7288CTC Warburg effect and progression","volume":"68","author":"Dauchy","year":"2018","journal-title":"Comp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/jpi.12298","article-title":"Melatonin suppression of aerobic glycolysis (Warburg effect), survival signalling and metastasis in human leiomyosarcoma","volume":"60","author":"Mao","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Reiter, R.J., Sharma, R., and Rosales-Corral, S. (2021). Anti-Warburg effect of melatonin: A proposed mechanism to explain its inhibition of multiple diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020764"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kopustinskiene, D.M., and Bernatoniene, J. (2021). Molecular mechanisms of melatonin-mediated cell protection and signaling in health and disease. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13020129"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/jcp.29886","article-title":"Regulation of cancer cell glucose metabolism is determinant for cancer cell fate after melatonin administration","volume":"236","author":"Rodriguez","year":"2021","journal-title":"J. Cell Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Duraj, T., Garcia-Romero, N., Carrion-Navarro, J., Madurga, R., de Mendivil, A.O., Prat-Acin, R., Garcia-Canamaque, L., and Ayuso-Sacido, A. (2021). Beyond the Warburg effect: Oxidative and glycolytic phenotypes coexist within the metabolic heterogeneity of glioblastoma. Cells, 10.","DOI":"10.3390\/cells10020202"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e12677","DOI":"10.1111\/jpi.12677","article-title":"Switching diseased cells from cytosolic aerobic glycolysis to mitochondrial oxidative phosphorylation: A metabolic rhythm regulated by melatonin?","volume":"70","author":"Reiter","year":"2021","journal-title":"J. Pineal Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1007\/s00018-019-03438-1","article-title":"Melatonin inhibits Warburg-dependent cancer by redirecting glucose oxidation to the mitochondria: A mechanistic hypothesis","volume":"77","author":"Reiter","year":"2020","journal-title":"Cell Mol. Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"119597","DOI":"10.1016\/j.lfs.2021.119597","article-title":"Part-time cancers and role of melatonin in determining their metabolic phenotype","volume":"8","author":"Reiter","year":"2021","journal-title":"Life Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/s41419-020-03162-w","article-title":"PDK4 promotes vascular calcification by interfering with autophagic activity and metabolic reprogramming","volume":"11","author":"Ma","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e1486","DOI":"10.1002\/wsbm.1486","article-title":"The immunologic Warburg effect: Evidence and therapeutic opportunities in autoimmunity","volume":"12","author":"Kornberg","year":"2020","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1021\/ja01543a060","article-title":"Isolation of melatonin, the pineal gland factor that lightens melanocytes","volume":"80","author":"Lerner","year":"1958","journal-title":"J. Am. Chem Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1210\/endo-89-1-301","article-title":"Retinal localization of the hydroxyindole-O-methyl transferase (HIOMT) in the rat","volume":"89","author":"Cardinali","year":"1971","journal-title":"Endocrinology"},{"key":"ref_41","first-page":"97","article-title":"Periodic changes in rat retinal and pineal melatonin synthesis","volume":"24","author":"Cardinali","year":"1974","journal-title":"Acta Physiol. Lat. Am."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1210\/endo-91-1-247","article-title":"Hydroxyindole-O-methyl transferases in rat pineal, retina and harderian gland","volume":"91","author":"Cardinali","year":"1972","journal-title":"Endocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1677\/joe.0.0910477","article-title":"Increase in the level of retinal melatonin and persistence of its diurnal rhythm in rats after pinealectomy","volume":"91","author":"Yu","year":"1981","journal-title":"J. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/0024-3205(83)90192-3","article-title":"Rhythms in immunoreactive melatonin in the retina and Harderian gland of rats; persistence after pinealectomy","volume":"32","author":"Reiter","year":"1983","journal-title":"Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0304-3940(84)90152-6","article-title":"Identification of melatonin in the compound eyes of an insect, the locust (Locusta migratoria), by radioimmunoassay and gas chromatography-mass spectrometry","volume":"49","author":"Pevet","year":"1984","journal-title":"Neurosci. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/S0016-6480(03)00008-X","article-title":"Melatonin and 5-methoxytryptophol (5-ML) in nervous and\/or neurosensory structures of a gastropod mollusca (Helix aspersa maxima): Synthesis and diurnal rhythms","volume":"131","author":"Blanc","year":"2003","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-079X.1994.tb00106.x","article-title":"Detection and quantification of melatonin in a dinoflagellate, Gonyaulax polyedra: Solutions to the problem of methoxyindole destruction in non-vertebrate material","volume":"17","author":"Poeggeler","year":"1994","journal-title":"J. Pineal Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1034\/j.1600-079X.2003.00040.x","article-title":"Non-vertebral melatonin","volume":"34","author":"Hardeland","year":"2003","journal-title":"J. Pineal Res."},{"key":"ref_49","first-page":"391","article-title":"Melatonin immunoreactivity in the photosynthetic prokaryote Rhodospirillum rubrum: Implications for an ancient antioxidant system","volume":"41","author":"Manchester","year":"1995","journal-title":"Cell Mol. Biol. Res."},{"key":"ref_50","first-page":"627","article-title":"Identification of melatonin in plants and its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates","volume":"35","author":"Hattori","year":"1995","journal-title":"Biochem. Mol. Biol. Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1600-079X.1995.tb00136.x","article-title":"Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography-mass spectrometry","volume":"18","author":"Dubbels","year":"1995","journal-title":"J. Pineal Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"E7997","DOI":"10.1073\/pnas.1705768114","article-title":"Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release","volume":"114","author":"Suofu","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"41236","DOI":"10.1038\/srep41236","article-title":"Chloroplastic biosynthesis of melatonin and its involvement in protection of plants from salt stress","volume":"7","author":"Zheng","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1111\/j.1749-6632.2002.tb02938.x","article-title":"Melatonin: An antioxidant in edible plants","volume":"957","author":"Reiter","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"89","DOI":"10.4161\/psb.1.3.2640","article-title":"The physiological function of melatonin in plants","volume":"1","author":"Arnao","year":"2006","journal-title":"Plant Signal. Behav."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/biof.23","article-title":"Melatonin: Signaling mechanisms of a pleiotropic agent","volume":"35","author":"Hardeland","year":"2009","journal-title":"Biofactors"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3389\/fpls.2016.00198","article-title":"Melatonin in plants\u2014Diversity of levels and multiplicity of functions","volume":"7","author":"Hardeland","year":"2016","journal-title":"Front. Plant Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1600-079X.2005.00276.x","article-title":"Melatonin in higher plants: Occurrence and possible functions","volume":"39","author":"Kolar","year":"2005","journal-title":"J. Pineal Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1111\/tpj.14915","article-title":"Melatonin metabolism, signaling and possible roles in plants","volume":"105","author":"Back","year":"2021","journal-title":"Plant J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/jpi.12364","article-title":"Melatonin biosynthesis in plants: Multiple pathways catalyze tryptophan to melatonin in the cytoplasm or chloroplasts","volume":"61","author":"Back","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e12737","DOI":"10.1111\/jpi.12737","article-title":"Melatonin synthesis genes N-acetylserotonin methyltransferases evolved into caffeic acid O-methyltransferases and both assisted in plant terrestrialization","volume":"71","author":"Zhao","year":"2021","journal-title":"J. Pineal Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3389\/fendo.2019.00249","article-title":"Melatonin synthesis and Function: Evolutionary history in animals and plants","volume":"10","author":"Zhao","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0079-6123(08)81008-4","article-title":"Melatonin: A multitasking molecule","volume":"181","author":"Reiter","year":"2010","journal-title":"Prog. Brain Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1210\/er.2018-00084","article-title":"Melatonin as a hormone: New physiological and clinical insights","volume":"39","author":"Amaral","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e12743","DOI":"10.1111\/jpi.12743","article-title":"Melatonin and the health of menopausal women: A systematic review","volume":"71","author":"Peleg","year":"2021","journal-title":"J. Pineal Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Arnao, M.B., and Hernandez-Ruiz, J. (2021). Melatonin against environmental plant stressors: A review. Curr. Protein Pept. Sci.","DOI":"10.2174\/13892037MTEynOTgc4"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7396","DOI":"10.3390\/molecules20047396","article-title":"Phytomelatonin: Assisting plants to survive and thrive","volume":"20","author":"Reiter","year":"2015","journal-title":"Molecules"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.tox.2010.04.008","article-title":"Melatonin: Action as antioxidant and potential applications in human disease and aging","volume":"278","author":"Collin","year":"2010","journal-title":"Toxicology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1111\/j.1742-4658.2006.05322.x","article-title":"Melatonin: Nature\u2019s most versatile biological signal?","volume":"273","author":"Srinivasan","year":"2006","journal-title":"FEBS J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/jpi.12267","article-title":"Melatonin: An ancient molecule that makes oxygen metabolically tolerable","volume":"59","author":"Manchester","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/jpi.12162","article-title":"Melatonin: A well-documented antioxidant with conditional pro-oxidant actions","volume":"57","author":"Zhang","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1089\/ars.2011.4085","article-title":"Mitochondria regulation of cell cycle and proliferation","volume":"16","author":"Elguero","year":"2012","journal-title":"Antioxid. Redox. Signal"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.semcancer.2017.04.005","article-title":"Mitochondrial ROS control of cancer","volume":"47","author":"Idelchik","year":"2017","journal-title":"Semin. Cancer Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2147\/CIA.S158513","article-title":"Oxidative stress, aging, and diseases","volume":"13","author":"Liguori","year":"2018","journal-title":"Clin. Interv. Aging"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"12370","DOI":"10.1111\/jpi.12370","article-title":"Cancer metastasis: Mechanisms of inhibition by melatonin","volume":"62","author":"Su","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ferreira, L.C., Orso, F., Dettori, D., Lacerda, J.Z., Borin, T.F., Taverna, D., and Zuccari, D.A.P.C. (2020). The role of melatonin on miRNAs modulation in triple-negative breast cancer cells. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0228062"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/jpi.12026","article-title":"Mitochondria and chloroplasts as the original sites of melatonin synthesis: A hypothesis related to melatonin\u2019s primary function and evolution in eukaryotes","volume":"54","author":"Tan","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_78","first-page":"373","article-title":"The universal nature, unequal distribution and antioxidant functions of melatonin and its derivatives","volume":"13","author":"Reiter","year":"2013","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0024-3205(01)01143-2","article-title":"Presence of melatonin in the human hepatobiliary-gastrointestinal tract","volume":"69","author":"Messner","year":"2001","journal-title":"Life Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1007\/s00018-014-1579-2","article-title":"Extrapineal melatonin: Sources, regulation, and potential functions","volume":"71","author":"Escames","year":"2014","journal-title":"Cell Mol. Life Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1600-079X.1999.tb00567.x","article-title":"Melatonin concentrations in the luminal fluid, mucosa, and muscularis of the bovine and porcine gastrointestinal tract","volume":"26","author":"Bubenik","year":"1999","journal-title":"J. Pineal Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s00429-013-0686-4","article-title":"Selective protection of the cerebellum against intracerebroventricular LPS is mediated by local melatonin synthesis","volume":"220","author":"Pinato","year":"2015","journal-title":"Brain Struct. Funct."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.molmet.2019.07.007","article-title":"Temporal expression patterns of the melatoninergic system in the human thymus of children","volume":"28","author":"Rubio","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0304-3940(97)00844-6","article-title":"Presence of the pineal hormone melatonin in rat cochlea: Its variations with lighting conditions","volume":"238","author":"Guerrero","year":"1997","journal-title":"Neurosci. Lett."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/112067219200200203","article-title":"The ciliary body\u2014The third organ found to synthesize indoleamines in humans","volume":"2","author":"Martin","year":"1992","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1034\/j.1600-079X.2000.280401.x","article-title":"Evidence for melatonin synthesis in mouse and human bone marrow cells","volume":"28","author":"Conti","year":"2000","journal-title":"J. Pineal Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"17705","DOI":"10.3390\/ijms151017705","article-title":"Local melatoninergic system as the protector of skin integrity","volume":"15","author":"Slominiski","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3913","DOI":"10.1007\/s00018-017-2617-7","article-title":"Melatonin, mitochondria, and the skin","volume":"74","author":"Slominiski","year":"2017","journal-title":"Cell Mol. Life Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0304-3940(90)90092-N","article-title":"Diurnal rhythms of immunoreactive melatonin in the aqueous humor and serum of male pigmented rabbits","volume":"116","author":"Yu","year":"1990","journal-title":"Neurosci. Lett."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1210\/jcem-64-4-865","article-title":"Melatonin in human preovulatory follicular fluid","volume":"64","author":"Brzezinski","year":"1987","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1007\/s00429-014-0719-7","article-title":"Delivery of pineal melatonin to the brain and SCN: Role of canaliculi, cerebrospinal fluid, tanycytes and Virchow-Robin perivascular spaces","volume":"219","author":"Reiter","year":"2014","journal-title":"Brain Struct. Funct."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.fertnstert.2008.05.016","article-title":"Melatonin and the ovary: Physiological and pathophysiological implications","volume":"92","author":"Tamura","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/S0304-4165(99)00125-7","article-title":"Identification of highly elevated levels of melatonin in bone marrow: Its origin and significance","volume":"1472","author":"Tan","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4788","DOI":"10.2174\/1381612819666131119105826","article-title":"Melatonin in the biliary tract and liver: Health implications","volume":"20","author":"Reiter","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Ostrycharz, E., Wasik, U., Kempinska-Podhorodecka, A., Banales, J.M., Milkiewicz, P., and Milkiewicz, M. (2020). Melatonin protects cholangiocytes from oxidative stress-induced proapoptotic and proinflammatory stimuli via miR-132 and miR-34. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249667"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1053\/jhep.2000.16332","article-title":"Melatonin prevents pigment gallstone formation induced by bile duct ligation in guinea pigs","volume":"32","author":"Shiesh","year":"2000","journal-title":"Hepatology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.3892\/or.2015.3738","article-title":"Melatonin induces apoptosis in cholangiocarcinoma cell lines by activating the reactive oxygen species-mediated mitochondrial pathway","volume":"33","author":"Laothrong","year":"2015","journal-title":"Oncol. Rept."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1007\/s10620-007-0195-5","article-title":"Reactive oxygen species and the hypomotility of the gall bladder as targets for the treatment of gallstones with melatonin: A review","volume":"53","author":"Koppisetti","year":"2008","journal-title":"Dig. Dis. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"125239","DOI":"10.1016\/j.jhazmat.2021.125239","article-title":"Melatonin alleviates Ochratoxin A-induced liver inflammation involved intestinal microbiota homeostasis and microbiota-independent manner","volume":"413","author":"Xia","year":"2021","journal-title":"J. Hazard Mater."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/0006-8993(87)91505-8","article-title":"Pineal indole metabolism in the mouse","volume":"416","author":"Ebihara","year":"1987","journal-title":"Brain Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1600-079X.1989.tb00667.x","article-title":"Melatonin content of the pineal gland in different mouse strains","volume":"7","author":"Goto","year":"1989","journal-title":"J. Pineal Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1600-079X.2009.00683.x","article-title":"Evidence of immune system melatonin production by two pineal melatonin deficient mice, C57BL\/6 and Swiss strains","volume":"47","author":"Cerrillo","year":"2009","journal-title":"J. Pineal Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/j.1600-079X.2009.00721.x","article-title":"Visualization of melatonin\u2019s multiple mitochondrial levels of protection against mitochondrial Ca2+-mediated permeability transition and beyond in rat brain astrocytes","volume":"48","author":"Jou","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e12538","DOI":"10.1111\/jpi.12538","article-title":"Protective stabilization of mitochondrial permeability transition and mitochondrial oxidation during mitochondrial Ca2+ stress by melatonin\u2019s cascade metabolites C3-OHM and AFMK in RBA1 astrocytes","volume":"66","author":"Jou","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1007\/s00018-017-2609-7","article-title":"Melatonin as a mitochondria-targeted antioxidant: One of evolution\u2019s best ideas","volume":"74","author":"Reiter","year":"2017","journal-title":"Cell Mol. Life Sci."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Reiter, R.J., Tan, D.X., Rosales-Corral, S., Galano, A., Zhou, X.J., and Xu, B. (2018). Mitochondria: Central organelles for melatonin\u2019s antioxidant and anti-aging actions. Molecules, 23.","DOI":"10.3390\/molecules23020509"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1007\/s00018-017-2610-1","article-title":"Melatonin, clock genes and mitochondria in sepsis","volume":"74","author":"Rahim","year":"2017","journal-title":"Cell Mol. Life Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1600-079X.2011.00931.x","article-title":"Extrapineal melatonin: Analysis of its subcellular distribution and daily fluctuations","volume":"52","author":"Venegas","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_109","first-page":"259","article-title":"Cytochemical investigation of acetyl-serotonin-transferase activity in the pineal gland","volume":"25","author":"Kerenyi","year":"1979","journal-title":"Cell. Mol. Biol. Incl. Cyto. Enzymol."},{"key":"ref_110","first-page":"101","article-title":"Symbiosis as a mechanism of evolution: Status of cell symbiosis theory","volume":"1","author":"Margulis","year":"1985","journal-title":"Symbiosis"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1146\/annurev.genet.33.1.351","article-title":"Mitochondrial genome evolution and the origin of eukaryotes","volume":"33","author":"Lang","year":"1999","journal-title":"Annu. Rev. Genet."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"He, C., Wang, J., Zhang, Z., Yang, M., Li, Y., Tian, X., Ma, T., Tao, J., Zhu, K., and Song, Y. (2016). Mitochondria synthesize melatonin to ameliorate its function and improve mice oocytes\u2019 quality under in vitro conditions. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060939"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/j.1600-079X.2007.00524.x","article-title":"Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate","volume":"44","author":"Tamura","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Yang, L., Zhao, Z., Cui, M., Zhang, L., and Li, Q. (2021). Melatonin restores the developmental competence of heat stressed porcine oocytes and alters the expression of genes related to oocyte maturation. Animals, 11.","DOI":"10.3390\/ani11041086"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1080\/15384101.2020.1767403","article-title":"Melatonin protects against chronic stress-induced oxidative meiotic defects in mice MII oocytes by regulating SIRT1","volume":"19","author":"Guo","year":"2020","journal-title":"Cell Cycle"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e12707","DOI":"10.1111\/jpi.12707","article-title":"Melatonin improves the effect of cryopreservation on human oocytes by suppressing oxidative stress and maintaining the permeability of the oolemma","volume":"70","author":"Zhang","year":"2021","journal-title":"J. Pineal Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/jpi.12297","article-title":"Melatonin inhibits paraquat-induced cell death in bovine preimplantation embryos","volume":"60","author":"Pang","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_118","first-page":"1","article-title":"Melatonin and IL-25 modulate apoptosis and angiogenesis mediators in metastatic (CF-41) and non-metastatic (CMT-U229) canine mammary tumour cells","volume":"1","author":"Gelaleti","year":"2017","journal-title":"Vet. Comp. Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"E1942","DOI":"10.1073\/pnas.1722131115","article-title":"Melatonin signaling in mitochondria extends beyond neurons and neuroprotection: Implications for angiogenesis and cardio\/gastroprotection","volume":"115","author":"Ahluwalia","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1124\/jpet.118.253260","article-title":"Is there sufficient evidence that the melatonin binding site MT3 is quinone reductase 2?","volume":"368","author":"Boutin","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1038\/bjp.2008.184","article-title":"Melatonin receptors, heterodimerization, signal transduction and binding sites: What\u2019s new?","volume":"154","author":"Jockers","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/jpi.12210","article-title":"Melatonin uptake through glucose transporters: A new target for melatonin inhibition of cancer","volume":"58","author":"Hevia","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3927","DOI":"10.1007\/s00018-017-2616-8","article-title":"Melatonin transport into mitochondria","volume":"74","author":"Mayo","year":"2017","journal-title":"Cell Mol. Life Sci."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Huo, X., Wang, C., Yu, Z., Peng, Y., Wang, S., Feng, S., Zhang, S., Tian, X., Sun, C., and Liu, K. (2017). Human transporters, PEPT1\/2, facilitate melatonin transportation into mitochondria of cancer cells: An implication of the therapeutic potential. J. Pineal Res., 62.","DOI":"10.1111\/jpi.12390"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"21","DOI":"10.32794\/mr11250002","article-title":"Melatonin actions in the heart; more than a hormone","volume":"1","author":"Reiter","year":"2018","journal-title":"Melatonin Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.pneurobio.2008.04.001","article-title":"Physiological effects of melatonin: Role of melatonin receptors and signal transduction pathways","volume":"85","author":"Trakht","year":"2008","journal-title":"Prog. Neurobiol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.mce.2012.01.004","article-title":"Melatonin membrane receptors in peripheral tissues: Distribution and functions","volume":"351","author":"Slominski","year":"2012","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"102","DOI":"10.2174\/1871524918666180531083944","article-title":"Recent findings in melatonin research and their relevance to the CNS","volume":"18","author":"Hardeland","year":"2018","journal-title":"Cent. Nerv. Syst. Agents Med. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"150","DOI":"10.2174\/1874467213666200421160835","article-title":"Melatonin receptor as a drug target for neuroprotection","volume":"14","author":"Wongprayoon","year":"2021","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.2147\/OTT.S298512","article-title":"Role and therapeutic potential of melatonin in various type of cancers","volume":"14","author":"Gurunathan","year":"2021","journal-title":"Onco. Targets Ther."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1385\/ENDO:27:2:101","article-title":"Functional MT1 and MT2 melatonin receptors in mammals","volume":"27","author":"Dubocovich","year":"2005","journal-title":"Endocrine"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1111\/bph.13950","article-title":"Melatonin receptors: Molecular pharmacology and signalling in the context of system bias","volume":"175","author":"Cecon","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1111\/bph.13536","article-title":"Update on melatonin receptors: IUPHAR Review 20","volume":"173","author":"Jockers","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev-pharmtox-010814-124742","article-title":"MT1 and MT2 melatonin receptors: A therapeutic perspective","volume":"56","author":"Liu","year":"2016","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"791","DOI":"10.3389\/fendo.2019.00791","article-title":"Melatonin target proteins: Too many or not enough?","volume":"10","author":"Liu","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1111\/febs.15128","article-title":"Structural insights into melatonin receptors","volume":"287","author":"Stauch","year":"2020","journal-title":"FEBS J."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"135","DOI":"10.5152\/eurasianjmed.2015.0267","article-title":"A review of melatonin, its receptors and drugs","volume":"48","author":"Emet","year":"2016","journal-title":"Eurasian J. Med."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1177\/1947601911407328","article-title":"The ERK cascade: Distinct functions within various subcellular organelles","volume":"2","author":"Wortzel","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1600-079X.2007.00468.x","article-title":"Involvement of protein kinase C in melatonin\u2019s oncostatic effect in C6 glioma cells","volume":"43","author":"Martin","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.pneurobio.2010.12.004","article-title":"Melatonin\u2014A pleiotropic, orchestrating regulator molecule","volume":"93","author":"Hardeland","year":"2011","journal-title":"Prog. Neurobiol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1167\/tvst.8.3.49","article-title":"Sleep-wake disturbance related to ocular disease: A systematic review of phase-shifting pharmaceutical therapies","volume":"8","author":"Andrews","year":"2019","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1080\/14728222.2016.1179284","article-title":"Melatonin receptors as therapeutic targets in the suprachiasmatic nucleus","volume":"20","author":"Pevet","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"101973","DOI":"10.1016\/j.redox.2021.101973","article-title":"Melatonin improves brain function in a model of chronic Gulf War illness with modulation of oxidative stress, NLRP3 inflammasomes, and BDNF-ERK-CREB pathway in the hippocampus","volume":"43","author":"Madhu","year":"2021","journal-title":"Redox Biol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/bs.ircmb.2018.02.002","article-title":"Melatonin receptor signaling: Impact of receptor oligomerization on receptor function","volume":"338","author":"Oishi","year":"2018","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Bonmati-Carrion, M.A., and Tomas-Loba, A. (2021). Melatonin and cancer: A polyhedral network where the source matters. Antioxidants, 10.","DOI":"10.3390\/antiox10020210"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1152\/physiol.00034.2019","article-title":"Melatonin in mitochondria: Mitigating clear and present dangers","volume":"35","author":"Reiter","year":"2020","journal-title":"Physiology"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1600-079X.1986.tb00760.x","article-title":"Human melatonin production decreases with age","volume":"3","author":"Sack","year":"1986","journal-title":"J. Pineal Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jpsychores.2016.05.005","article-title":"Physiological melatonin levels in healthy older people: A systematic review","volume":"86","author":"Scholtens","year":"2016","journal-title":"J. Psychosom. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3124","DOI":"10.1172\/JCI135026","article-title":"Melatonin inhibits cytosolic mitochondria DNA-induced neuroinflammatory signaling in accelerated aging and neurodegeneration","volume":"130","author":"Jauhari","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"11174","DOI":"10.1158\/0008-5472.CAN-05-1945","article-title":"Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats","volume":"65","author":"Blask","year":"2005","journal-title":"Cancer Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1177\/1534735409352320","article-title":"Circadian stage-dependent inhibition of human breast cancer metabolism and growth by the nocturnal melatonin signal: Consequences of its disruption by light at night in rats and women","volume":"8","author":"Blask","year":"2009","journal-title":"Integr. Cancer Ther."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"170","DOI":"10.2174\/1874609811205030002","article-title":"Light-at-night-induced circadian disruption, cancer and aging","volume":"5","author":"Anisimov","year":"2012","journal-title":"Curr. Aging Sci."},{"key":"ref_153","first-page":"311","article-title":"Cervical spinal cord lesions disrupt the rhythm in human melatonin excretion","volume":"13","author":"Kneisley","year":"1978","journal-title":"J. Neural Transm. Suppl."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1210\/endo-79-6-1168","article-title":"Interrelationships of the pineal gland, the superior cervical ganglia and the photoperiod in the regulation of the endocrine systems of hamsters","volume":"79","author":"Reiter","year":"1966","journal-title":"Endocrinology"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3389\/fendo.2017.00370","article-title":"Alterations n metabolism and diurnal rhythms following bilateral surgical removal of the superior cervical ganglia in rats","volume":"8","author":"Galiana","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/jpi.12293","article-title":"Melatonergic system-based two-gene index is prognostic in human gliomas","volume":"60","author":"Kinker","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physiolgenomics.00095.2018","article-title":"Aging, melatonin biosynthesis, and circadian clockworks in the gastrointestinal system of the laboratory mouse","volume":"51","author":"Paulose","year":"2019","journal-title":"Physiol. Genom."},{"key":"ref_158","first-page":"R1855","article-title":"Responsiveness to melatonin and its receptor expression in aging circadian clock of mice","volume":"273","author":"Benloucif","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Sharma, P., and Sampath, H. (2019). Mitochondrial DNA integrity: Role in health and disease. Cells, 8.","DOI":"10.3390\/cells8020100"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1111\/joim.13064","article-title":"Mitochondrial diseases in adults","volume":"287","author":"Maresca","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41580-020-0210-7","article-title":"The cell biology of mitochondrial membrane dynamics","volume":"21","author":"Giacomello","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.3109\/10715762.2012.717273","article-title":"Susceptibility of mitochondrial electron-transport complexes to oxidative damage. Focus on Cytochrome c oxidase","volume":"46","author":"Musatov","year":"2012","journal-title":"Free Radic. Res."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00109-020-02004-8","article-title":"Mitochondrial respiratory supercomplexes in mammalian cells: Structural versus functional role","volume":"99","author":"Javadov","year":"2021","journal-title":"J. Mol. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"7857251","DOI":"10.1155\/2018\/7857251","article-title":"Mitochondrial antioxidants and the maintenance of cellular hydrogen peroxide levels","volume":"2018","author":"Mailloux","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Hernansanz-Agustin, P., and Enriquez, J.A. (2021). Generation of reactive oxygen species by mitochondria. Antioxidants, 10.","DOI":"10.3390\/antiox10030415"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1600-079X.2006.00407.x","article-title":"One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species?","volume":"42","author":"Tan","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2119\/molmed.2008.00117","article-title":"Melatonin: An established antioxidant worthy of use in clinical trials","volume":"15","author":"Korkmaz","year":"2009","journal-title":"Mol. Med."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Reiter, R.J., Tan, D.X., Rosales-Corral, S., Galano, A., Zhou, M.J., and Acuna-Castroviejo, D. (2018). Melatonin mitigates mitochondrial meltdown: Interactions with SIRT3. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082439"},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Baburina, Y., Lomovsky, A., and Krestinina, O. (2021). Melatonin as a potential multitherapeutic agent. J. Pers. Med., 11.","DOI":"10.3390\/jpm11040274"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Liu, L., Cao, Q., Gao, W., Li, B., Xia, Z., and Zhao, B. (2021). Melatonin protects against cerebral ischemia-perfusion injury in diabetic mice by ameliorating mitochondrial impairments: Involvement of the Akt-SIRT3-SOD2 signaling pathway. Aging, in press.","DOI":"10.18632\/aging.203137"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"8315","DOI":"10.7150\/thno.45922","article-title":"Mitochondrial sirtuin 3: New emerging biological function and therapeutic target","volume":"10","author":"Zhang","year":"2020","journal-title":"Theranostics"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.pbi.2016.04.007","article-title":"Pyruvate transport systems in organelles: Future directions in C4 biology research","volume":"31","author":"Furumoto","year":"2016","journal-title":"Curr. Opin. Plant Biol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1021\/acsptsci.0c00208","article-title":"Pyruvate dehydrogenase as a therapeutic target for nonalcoholic fatty liver disease","volume":"4","author":"Saed","year":"2021","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"188568","DOI":"10.1016\/j.bbcan.2021.188568","article-title":"Targeting pyruvate dehydrogenase kinase signaling in the development of effective cancer therapy","volume":"1876","author":"Anwar","year":"2021","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1007\/s00018-015-1840-3","article-title":"Dysregulated glycolysis as an oncogenic event","volume":"72","author":"Mikawa","year":"2015","journal-title":"Cell Mol. Life Sci."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s10555-019-09792-7","article-title":"Causes, consequences, and therapy of tumors acidosis","volume":"38","author":"Pillai","year":"2019","journal-title":"Cancer Metastasis Rev."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/978-3-030-68748-9_11","article-title":"Redox role of ROS and inflammation in pulmonary Diseases","volume":"1304","author":"Zuo","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"906","DOI":"10.3390\/md9050906","article-title":"Molecular evolution of multiple arylalkylamine N-acetyltransferase (AANAT) in fish","volume":"9","author":"Klein","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"105","DOI":"10.32794\/mr11250033","article-title":"Inhibition of mitochondrial pyruvate dehydrogenase kinase: A proposed mechanism by which melatonin causes cancer cells to overcome cytosolic glycolysis, reduce tumor biomass and reverse insensitivity to chemotherapy","volume":"2","author":"Reiter","year":"2019","journal-title":"Melatonin Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"362","DOI":"10.32794\/mr11250068","article-title":"Plasticity of glucose metabolism in activated immune cells: Advantages for melatonin inhibition of COVID-19 disease","volume":"3","author":"Reiter","year":"2020","journal-title":"Melatonin Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s10522-020-09888-6","article-title":"Cancer and Alzheimer\u2019s disease: Intracellular pH scales the metabolic disorders","volume":"21","author":"Schwartz","year":"2020","journal-title":"Biogerontology"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"BSR20204402","DOI":"10.1042\/BSR20204402","article-title":"Pyruvate dehydrogenase kinases (PDKs): An overview toward clinical applications","volume":"41","author":"Wang","year":"2021","journal-title":"Biosci. Rep."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Prochownik, E.V., and Wang, H. (2021). The metabolic fates of pyruvate in normal and neoplastic cells. Cells, 10.","DOI":"10.3390\/cells10040762"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"6643382","DOI":"10.1155\/2021\/6643382","article-title":"Crosstalk between oxidative stress and ferroptosis\/oxytosis in ischemic stroke: Possible targets and molecular mechanisms","volume":"2021","author":"Ren","year":"2021","journal-title":"Oxid Med. Cell Longev."},{"key":"ref_185","first-page":"B5054","article-title":"Oxidative and inflammatory biomarkers of ischemia and reperfusion injuries","volume":"62","author":"Halladin","year":"2015","journal-title":"Dan. Med. J."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1055\/s-0035-1548765","article-title":"Oxidative stress in hypertension: Mechanisms and therapeutic opportunities","volume":"123","author":"Brito","year":"2015","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Zampieri, L.X., Silva-Almeida, C., Rondeau, J.D., and Sonveaux, P. (2021). Mitochondrial transfer in cancer: A comprehensive review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063245"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"143","DOI":"10.2174\/1570159X13666150703154541","article-title":"Mitochondrial biology and neurological diseases","volume":"14","author":"Arun","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1034\/j.1600-079X.2001.310409.x","article-title":"Increased levels of malondialdehyde and nitrate\/nitrate in the blood of asphyxiated newborns: Reduction by melatonin","volume":"31","author":"Fulia","year":"2001","journal-title":"J. Pineal Res."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1080\/13510002.2021.1891808","article-title":"Contribution of oxidative stress in mechanisms of postoperative complications and multiple organ dysfunction syndrome","volume":"26","author":"Rodrigo","year":"2021","journal-title":"Redox Rep."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"110664","DOI":"10.1016\/j.biopha.2020.110664","article-title":"Medical prevention and treatment of radiation-induced carotid injury","volume":"131","author":"Zheng","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"3941","DOI":"10.1007\/s00018-017-2611-0","article-title":"Melatonin, mitochondria, and the metabolic syndrome","volume":"74","author":"Cardinali","year":"2017","journal-title":"Cell Mol. Life Sci."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Martinelli, I., Tomassoni, D., Moruzzi, M., Roy, P., Cifani, C., Amenta, F., and Tayebati, S.K. (2020). Cardiovascular changes related to metabolic syndrome: Evidence in obese Zucker rats. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062035"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"3999","DOI":"10.1007\/s00018-017-2614-x","article-title":"Melatonin as a mitochondrial protector in neurodegenerative diseases","volume":"74","author":"Wongprayoon","year":"2017","journal-title":"Cell Mol. Life Sci."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"4015","DOI":"10.1007\/s00018-017-2612-z","article-title":"Melatonin, mitochondria, and the cancer cell","volume":"74","author":"Proietti","year":"2017","journal-title":"Cell Mol. Life Sci."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"635083","DOI":"10.3389\/fcvm.2021.635083","article-title":"Melatonin and cardioprotection in humans: A systematic and meta-analysis of randomized controlled trials","volume":"8","author":"Reiter","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Rusanova, I., Martinez-Ruiz, L., Florido, J., Rodriguez-Santana, C., Guerra-Librero, A., Acuna-Castroviejo, D., and Escames, G. (2019). Protective effects of melatonin on the skin: Future perspectives. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194948"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1113\/JP278930","article-title":"Mitochondrial lactate metabolism: History and implications for exercise and disease","volume":"599","author":"Glancy","year":"2021","journal-title":"J. Physiol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1126\/science.124.3215.269","article-title":"On respiratory impairment in cancer cells","volume":"124","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"23111","DOI":"10.1074\/jbc.M202487200","article-title":"Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis","volume":"277","author":"Lu","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1593\/neo.04430","article-title":"Hypoxia-inducible factor-1alpha and the glycolytic phenotype in tumors","volume":"7","author":"Robey","year":"2005","journal-title":"Neoplasia"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/j.1600-079X.2007.00498.x","article-title":"Melatonin modulates the expression of VEGF and HIF-1 alpha induced by CoCl2 in cultured cancer cells","volume":"44","author":"Dai","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1600-079X.2009.00678.x","article-title":"Melatonin down-regulates HIF-1 alpha expression through inhibition of protein translation in prostate cancer cells","volume":"46","author":"Park","year":"2009","journal-title":"J. Pineal Res."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/jpi.12052","article-title":"Melatonin antagonizes hypoxia-mediated glioblastoma cell migration and invasion via inhibition of HIF-1\u03b1","volume":"55","author":"Zhang","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"83","DOI":"10.32794\/mr11250042","article-title":"Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1\u03b1 and energy metabolic pathway in the in vitro and in vivo models of breast cancer","volume":"2","author":"Mota","year":"2019","journal-title":"Melatonin Res."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"104511","DOI":"10.1016\/j.phrs.2019.104511","article-title":"Targeting glucose metabolism to suppress cancer progression: Prospective of anti-glycolytic cancer therapy","volume":"150","author":"Mahmoud","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Mart\u00edn Gim\u00e9nez, V.M., de Las Heras, N., Ferder, L., Lahera, V., Reiter, R.J., and Manucha, W. (2021). Potential effects of mealtonin and mirconutrients on mitochondrial dysfunction during a cytokine storm typical of oxidative\/inflammatory diseases. Diseases, 9.","DOI":"10.3390\/diseases9020030"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"174193","DOI":"10.1016\/j.ejphar.2021.174193","article-title":"Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment","volume":"904","author":"Hosseini","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s00210-020-01972-5","article-title":"Melatonin alleviates sepsis-induced heart injury through activating the Nrf2 pathway ad inhibition the NLRP3 inflammasome","volume":"394","author":"Rahim","year":"2021","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jpi.12189","article-title":"Melatonin feedback on clock genes: A theory involving the proteasome","volume":"58","author":"Vriend","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_211","first-page":"176","article-title":"Melatonin and the von Hippel-Lindau\/HIF-1 oxygen sensing mechanism: A review","volume":"1865","author":"Vriend","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"248","DOI":"10.2174\/0929867033457746","article-title":"The role of nitric oxide (NO) in stability regulation of hypoxia inducible factor-1\u03b1 (HIF-1\u03b1)","volume":"10","author":"Brune","year":"2003","journal-title":"Curr. Med. Chem."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"8201079","DOI":"10.1155\/2019\/8201079","article-title":"Dichloroacetate (DCA) and cancer: An overview towards clinical applications","volume":"2019","author":"Tataranni","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/bs.irn.2019.05.003","article-title":"Dichloroacetate-induced peripheral neuropathy","volume":"145","author":"Stacpoole","year":"2019","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"83","DOI":"10.4140\/TCP.n.2021.83","article-title":"A systematic review of the efficacy and safety of over-the-counter medications used in older people for the treatment of primary insomnia","volume":"36","author":"Almond","year":"2021","journal-title":"Sr. Care Pharm."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1600-079X.2009.00697.x","article-title":"Potential roles of melatonin and chronotherapy among the new trends in hypertension treatment","volume":"47","author":"Simko","year":"2009","journal-title":"J. Pineal Res."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1248\/bpb.b21-00277","article-title":"Chrono-drug discovery a development of circadian rhythm of molecular, cellular and organ level","volume":"44","author":"Ohdo","year":"2021","journal-title":"Biol. Pharm. Bull."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"105595","DOI":"10.1016\/j.jsbmb.2020.105595","article-title":"Daily and seasonal mitochondrial protection: Unraveling common possible mechanisms involving vitamin D and melatonin","volume":"199","author":"Ferder","year":"2020","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/fcp.12659","article-title":"Can chronopharmacology improve the therapeutic management of neurological diseases?","volume":"35","author":"Sion","year":"2021","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/jpi.12176","article-title":"Mitochondrial catastrophe during doxorubicin-induced cardiotoxicity: A review of the protective role of melatonin","volume":"57","author":"Govender","year":"2014","journal-title":"J. Pineal. Res. J."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/jpi.12288","article-title":"Melatonin sensitizes human cervical cancer HeLa cells to cisplatin-induced cytotoxicity and apoptosis: Effects on oxidative stress and DNA fragmentation","volume":"60","author":"Pariente","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.rbmo.2020.10.001","article-title":"Melatonin provides protection against cisplatin-induced ovarian damage and loss of fertility in mice","volume":"42","author":"Huang","year":"2021","journal-title":"Reprod. Biomed. Online"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1158\/0008-5472.CAN-13-3156","article-title":"Circadian and melatonin disruption by exposure to light at night drives intrinsic resistance to tamoxifen therapy in breast cancer","volume":"74","author":"Dauchy","year":"2014","journal-title":"Cancer Res."},{"key":"ref_224","doi-asserted-by":"crossref","unstructured":"Chuffa, L.G., Ferreira Selva, F.R., Alonso Novais, A.A., Simko, V.A., Martin Gimenez, V.M., Manucha, W., Zuccari, D.A.P.C., and Reiter, R.J. (2021). Melatonin-loaded nanocarriers: New horizons for therapeutic applications. Molecules, 26.","DOI":"10.3390\/molecules26123562"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"9373","DOI":"10.18632\/aging.202894","article-title":"Differential role of melatonin in healthy brain aging: A systematic review and meta-analysis of the SAMP8 model","volume":"13","author":"Sumsuzzman","year":"2021","journal-title":"Aging"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"18886","DOI":"10.3390\/molecules201018886","article-title":"Melatonin as a potent and inducible endogenous antioxidant: Synthesis and metabolism","volume":"20","author":"Tan","year":"2015","journal-title":"Molecules"},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Talib, W.H., Alsayed, A.R., Abuawad, A., Daoud, S., and Mahmod, A.I. (2021). Melatonin in cancer treatment: Current knowledge and future opportunities. Molecules, 26.","DOI":"10.3390\/molecules26092506"},{"key":"ref_228","first-page":"2110","article-title":"Immunohistochemical expression of melatonin receptor MT1 and glucose transporter GLUT1 in human breast cancer","volume":"18","author":"Mota","year":"2018","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"24","DOI":"10.21614\/chirurgia.116.2Suppl.S24","article-title":"The intricate relationship between melatonin and breast cancer: A short review","volume":"116","author":"Pistioli","year":"2021","journal-title":"Chirurgia"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1002\/iub.2384","article-title":"Melatonin as a potential inhibitor of kidney cancer: A survey of the molecular processes","volume":"72","author":"Maleki","year":"2020","journal-title":"IUBMB Life"},{"key":"ref_231","doi-asserted-by":"crossref","unstructured":"Hardeland, R. (2021). Divergent importance of chronobiological considerations in high- and low-dose melatonin therapies. Diseases, 9.","DOI":"10.3390\/diseases9010018"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"e12513","DOI":"10.1111\/jpi.12513","article-title":"Antiarrhythmic effect linked to melatonin cardiorenal protection involves AT(1) reduction and Hsp70-VDR increase","volume":"65","author":"Prado","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"101491","DOI":"10.1016\/j.smrv.2021.101491","article-title":"The efficacy of combined bright light and melatonin therapies on sleep and circadian outcomes: A systematic review","volume":"58","author":"Cheng","year":"2021","journal-title":"Sleep Med. Rev."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.biochi.2020.11.010","article-title":"The key role of Warburg effect in SARS-CoV-2 replication and associated inflammatory response","volume":"180","author":"Icard","year":"2021","journal-title":"Biochimie"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"e4560","DOI":"10.1002\/nbm.4560","article-title":"Visualizing the effects of lactate dehydrogenase (LDH) inhibition and LDH-A genetic ablation in breast and lung cancer with hyperpolarized pyruvate NMR","volume":"34","author":"Varma","year":"2021","journal-title":"NMR Biomed."},{"key":"ref_236","doi-asserted-by":"crossref","unstructured":"Da Veiga Moreira, J., De Staercke, L., Cesar Martinez-Basilio, P., Gauthier-Thibodeau, S., Montegut, L., Schwartz, L., and Jolicoeur, M. (2021). Hyperosmolarity triggers the Warburg effect in Chinese hamster ovary cells and reveals a reduced mitochondria horsepower. Metabolites, 11.","DOI":"10.3390\/metabo11060344"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s11926-020-00920-9","article-title":"Mitochondria, aging, and cellular senescence: Implications for scleroderma","volume":"22","author":"Bueno","year":"2020","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_238","doi-asserted-by":"crossref","unstructured":"Bottani, E., Lamperti, C., Prigione, A., Tiranti, V., Persico, N., and Brunetti, D. (2020). Therapeutic approaches to treat mitochondrial diseases: \u201cOne-size-fits-all\u201d and \u201cPrecision Medicine\u201d Strategies. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12111083"},{"key":"ref_239","doi-asserted-by":"crossref","unstructured":"Orsucci, D., Caldarazzo, I.E., Rossi, A., Siciliano, G., and Mancuso, M. (2021). Mitochondrial syndromes revisited. J. Clin. Med., 10.","DOI":"10.3390\/jcm10061249"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"612888","DOI":"10.3389\/fendo.2021.612888","article-title":"Dimming the powerhouse: Mitochondrial dysfunction in the liver and skeletal muscle of intrauterine growth restricted fetuses","volume":"12","author":"Pendleton","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"e12429","DOI":"10.1111\/jpi.12429","article-title":"Plant mitochondria synthesize melatonin and enhance the tolerance of plants to drought stress","volume":"63","author":"Wang","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"4677","DOI":"10.1093\/jxb\/eraa235","article-title":"An evolutionary view of melatonin synthesis and metabolism related to its biological functions in plants","volume":"71","author":"Tan","year":"2020","journal-title":"J. Exp. Bot."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2165\/11318620-000000000-00000","article-title":"Neurobiology of circadian systems","volume":"23","author":"Schulz","year":"2009","journal-title":"CNS Drugs"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1080\/07420520600651073","article-title":"A network of (autonomic) clock outputs","volume":"23","author":"Kalsbeek","year":"2006","journal-title":"Chronobiol. Int."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1177\/074873001129002033","article-title":"Of rodents and ungulates and melatonin: Creating a uniform code for darkness by different signaling mechanisms","volume":"16","author":"Stehle","year":"2001","journal-title":"J. Biol. Rhythm."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s10552-005-9001-x","article-title":"Artificial lighting in the industrialized world: Circadian disruption and breast cancer","volume":"17","author":"Stevens","year":"2006","journal-title":"Cancer Causes Control"},{"key":"ref_247","first-page":"139","article-title":"Gut clock: Implication of circadian rhythms in the gastrointestinal tract","volume":"62","author":"Konturek","year":"2011","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"743","DOI":"10.2741\/S404","article-title":"Melatonin and clock genes expression in the cardiovascular system","volume":"5","author":"Zeman","year":"2013","journal-title":"Front. Biosci. Schol. Ed."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12494\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:32:51Z","timestamp":1760167971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,19]]},"references-count":248,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222212494"],"URL":"https:\/\/doi.org\/10.3390\/ijms222212494","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,19]]}}}