Function of intramitochondrial melatonin and its association with Warburg metabolism

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorLong School of Medicine-
Autor(es): dc.contributorSchool of Osteopathic Medicine-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorTongji University School of Medicine-
Autor(es): dc.contributorPontificia Universidad Católica Argentina-
Autor(es): dc.creatorReiter, Russel J.-
Autor(es): dc.creatorSharma, Ramaswamy-
Autor(es): dc.creatorBai, Yidong-
Autor(es): dc.creatorChuffa, Luiz Gustavo de Almeida-
Autor(es): dc.creatorLoh, Doris-
Autor(es): dc.creatorFan, Lihong-
Autor(es): dc.creatorCardinali, Daniel P.-
Data de aceite: dc.date.accessioned2025-08-21T15:23:06Z-
Data de disponibilização: dc.date.available2025-08-21T15:23:06Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2025-07-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.cellsig.2025.111754-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/305195-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/305195-
Descrição: dc.descriptionWarburg metabolism (aerobic glycolysis) is accompanied by high mitochondrial reactive oxygen species (ROS) generation from the electron transport chain; this is a “Hallmark of Cancer”. The elevated ROS sustain the growth and proliferation of the cancer cells. Melatonin is a potent and functionally diverse free radical scavenger and antioxidant that is synthesized in the mitochondria of non-pathological cells and normally aids in keeping mitochondrial ROS levels low and in maintaining redox homeostasis. Because the glucose metabolite, pyruvate, does not enter mitochondria of Warburg metabolizing cells due to the inhibition of pyruvate dehydrogenase complex (PDH), acetyl coenzyme A production is diminished. Acetyl coenzyme A is a necessary co-substrate with serotonin for melatonin synthesis; thus, intramitochondrial melatonin levels become reduced in cancer cells. The hypothesis is that the depressed melatonin levels initiate aerobic glycolysis and allow the exaggerated ROS concentrations to go uncontested; the authors speculate that the elevated mtROS upregulates hypoxia inducible factor 1α (HIF-1α)/pyruvate dehydrogenase kinase (PDK) axis which inhibits PDH, thereby supporting cancer cell proliferation and stimulating cancer biomass. Exposing Warburg metabolizing cancer cells to melatonin elevates intramitochondrial melatonin, thereby reducing mtROS and concurrently interrupting aerobic glycolysis and inhibiting tumor cell proliferation. Mechanistically, higher mitochondrial melatonin levels by supplementation directly upregulates the sirtuin 3 (SIRT3)/FOXO/PDH axis, allowing pyruvate entry into mitochondria and enhancing intrinsic mitochondrial melatonin production as in non-pathological cells. Additionally, melatonin inhibits HIF1α, thereby decreasing PDK activity and disinhibiting PDH, so pyruvate enters mitochondria and is metabolized to acetyl coenzyme A, resulting in reversal of Warburg metabolism.-
Descrição: dc.descriptionDepartment of Cell Systems and Anatomy UT Health San Antonio Long School of Medicine-
Descrição: dc.descriptionApplied Biomedical Sciences University of the Incarnate Word School of Osteopathic Medicine-
Descrição: dc.descriptionDepartment of Structural and Functional Biology UNESP – Saõ Paulo State University Institute of Biosciences, Sao Paulo-
Descrição: dc.descriptionDepartment of Respiratory Medicine Shanghai Tenth People's Hospital Tongji University School of Medicine-
Descrição: dc.descriptionInstitute of Energy Metabolism and Health Shanghai Tenth People's Hospital Tongji University School of Medicine-
Descrição: dc.descriptionCENECON Faculty of Medical Sciences Universidad de Buenos Aires and Pontificia Universidad Católica Argentina-
Descrição: dc.descriptionDepartment of Structural and Functional Biology UNESP – Saõ Paulo State University Institute of Biosciences, Sao Paulo-
Idioma: dc.languageen-
Relação: dc.relationCellular Signalling-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectAcetyl coenzyme A-
Palavras-chave: dc.subjectAntioxidant-
Palavras-chave: dc.subjectHypoxia inducible factor-
Palavras-chave: dc.subjectPyruvate dehydrogenase-
Palavras-chave: dc.subjectPyruvate metabolism-
Palavras-chave: dc.subjectReactive oxygen species-
Título: dc.titleFunction of intramitochondrial melatonin and its association with Warburg metabolism-
Tipo de arquivo: dc.typevídeo-
Aparece nas coleções:Repositório Institucional - Unesp

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