Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene Regulation

Autores
Abarza, Silvia del Valle; Nasoni, Maria Gemma; Perrone, Serafina; Bargagni, Erik; Gentile, Carla; Manucha, Walter Ariel Fernando; Reiter, Russel; Luchetti, Francesca; Balduini, Walter
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mitochondria are central hubs of cellular bioenergetics, redox signaling, and cell fate determination, and their dysfunction represents a hallmark of several diseases, including neurodegenerative, cardiovascular, and metabolic disorders, as well as aging. Melatonin, classically considered a circadian hormone, has recently been recognized as an endogenous modulator of mitochondrial physiology. This review provides a comprehensive overview of the mechanisms by which melatonin preserves mitochondrial function through multifaceted mechanisms. At the bioenergetic level, melatonin enhances the activity of electron transport chain (ETC) complexes, stabilizes the mitochondrial membrane potential (Δψ), and prevents cardiolipin (CL) peroxidation, thereby limiting the opening of the permeability transition pore (mPTP) and the release of cytochrome c. Its potent radical scavenging activity, together with the upregulation of mitochondrial antioxidant enzymes, counteracts oxidative stress (OS) and preserves mitochondrial DNA integrity. Melatonin also finely regulates mitochondrial dynamics by promoting fusion and inhibiting pathological fission, while sustaining quality control pathways, including mitophagy, unfolded protein response (UPR), and proteostasis. At the transcriptional level, melatonin modulates canonical regulators of mitochondrial biogenesis and gene expression, thereby promoting mitochondrial resilience under stress conditions. Emerging data also highlight melatonin´s role in intercellular mitochondrial trafficking via tunneling nanotubes (TNTs) and in the modulation of mitokine signaling, linking mitochondrial homeostasis to systemic adaptation. In summary, melatonin emerges as a multifaceted regulator of mitochondrial function and dynamics, with significant translational implications for diseases associated with mitochondrial impairment.
Fil: Abarza, Silvia del Valle. Università Degli Studi Di Urbino Carlo Bo.; Italia
Fil: Nasoni, Maria Gemma. Università Degli Studi Di Urbino Carlo Bo.; Italia
Fil: Perrone, Serafina. Università di Parma; Italia
Fil: Bargagni, Erik. Università Degli Studi Di Urbino Carlo Bo.; Italia
Fil: Gentile, Carla. Università degli Studi di Palermo; Italia
Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad del Aconcagua. Facultad de Ciencias Médicas; Argentina
Fil: Reiter, Russel. University Of Texas At San Antonio; Estados Unidos
Fil: Luchetti, Francesca. Università Degli Studi Di Urbino Carlo Bo.; Italia
Fil: Balduini, Walter. Università Degli Studi Di Urbino Carlo Bo.; Italia
Materia
MELATONIN
MITOCHONDRIAL FUSION
BIOENERGETICS
GENE REGULATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/289473
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/289473
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene RegulationAbarza, Silvia del ValleNasoni, Maria GemmaPerrone, SerafinaBargagni, ErikGentile, CarlaManucha, Walter Ariel FernandoReiter, RusselLuchetti, FrancescaBalduini, WalterMELATONINMITOCHONDRIAL FUSIONBIOENERGETICSGENE REGULATIONhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Mitochondria are central hubs of cellular bioenergetics, redox signaling, and cell fate determination, and their dysfunction represents a hallmark of several diseases, including neurodegenerative, cardiovascular, and metabolic disorders, as well as aging. Melatonin, classically considered a circadian hormone, has recently been recognized as an endogenous modulator of mitochondrial physiology. This review provides a comprehensive overview of the mechanisms by which melatonin preserves mitochondrial function through multifaceted mechanisms. At the bioenergetic level, melatonin enhances the activity of electron transport chain (ETC) complexes, stabilizes the mitochondrial membrane potential (Δψ), and prevents cardiolipin (CL) peroxidation, thereby limiting the opening of the permeability transition pore (mPTP) and the release of cytochrome c. Its potent radical scavenging activity, together with the upregulation of mitochondrial antioxidant enzymes, counteracts oxidative stress (OS) and preserves mitochondrial DNA integrity. Melatonin also finely regulates mitochondrial dynamics by promoting fusion and inhibiting pathological fission, while sustaining quality control pathways, including mitophagy, unfolded protein response (UPR), and proteostasis. At the transcriptional level, melatonin modulates canonical regulators of mitochondrial biogenesis and gene expression, thereby promoting mitochondrial resilience under stress conditions. Emerging data also highlight melatonin´s role in intercellular mitochondrial trafficking via tunneling nanotubes (TNTs) and in the modulation of mitokine signaling, linking mitochondrial homeostasis to systemic adaptation. In summary, melatonin emerges as a multifaceted regulator of mitochondrial function and dynamics, with significant translational implications for diseases associated with mitochondrial impairment.Fil: Abarza, Silvia del Valle. Università Degli Studi Di Urbino Carlo Bo.; ItaliaFil: Nasoni, Maria Gemma. Università Degli Studi Di Urbino Carlo Bo.; ItaliaFil: Perrone, Serafina. Università di Parma; ItaliaFil: Bargagni, Erik. Università Degli Studi Di Urbino Carlo Bo.; ItaliaFil: Gentile, Carla. Università degli Studi di Palermo; ItaliaFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad del Aconcagua. Facultad de Ciencias Médicas; ArgentinaFil: Reiter, Russel. University Of Texas At San Antonio; Estados UnidosFil: Luchetti, Francesca. Università Degli Studi Di Urbino Carlo Bo.; ItaliaFil: Balduini, Walter. Università Degli Studi Di Urbino Carlo Bo.; ItaliaTech Science Press2026-02-14info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/289473Abarza, Silvia del Valle; Nasoni, Maria Gemma; Perrone, Serafina; Bargagni, Erik; Gentile, Carla; et al.; Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene Regulation; Tech Science Press; Biocell; 50; 2; 14-2-2026; 1-220327-95451667-5746CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.techscience.com/biocell/v50n2/66251info:eu-repo/semantics/altIdentifier/doi/10.32604/biocell.2025.073776info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:40:13Zoai:ri.conicet.gov.ar:11336/289473instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-08-25 14:40:14.417CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene Regulation
title Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene Regulation
spellingShingle Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene Regulation
Abarza, Silvia del Valle
MELATONIN
MITOCHONDRIAL FUSION
BIOENERGETICS
GENE REGULATION
title_short Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene Regulation
title_full Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene Regulation
title_fullStr Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene Regulation
title_full_unstemmed Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene Regulation
title_sort Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene Regulation
dc.creator.none.fl_str_mv Abarza, Silvia del Valle
Nasoni, Maria Gemma
Perrone, Serafina
Bargagni, Erik
Gentile, Carla
Manucha, Walter Ariel Fernando
Reiter, Russel
Luchetti, Francesca
Balduini, Walter
author Abarza, Silvia del Valle
author_facet Abarza, Silvia del Valle
Nasoni, Maria Gemma
Perrone, Serafina
Bargagni, Erik
Gentile, Carla
Manucha, Walter Ariel Fernando
Reiter, Russel
Luchetti, Francesca
Balduini, Walter
author_role author
author2 Nasoni, Maria Gemma
Perrone, Serafina
Bargagni, Erik
Gentile, Carla
Manucha, Walter Ariel Fernando
Reiter, Russel
Luchetti, Francesca
Balduini, Walter
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MELATONIN
MITOCHONDRIAL FUSION
BIOENERGETICS
GENE REGULATION
topic MELATONIN
MITOCHONDRIAL FUSION
BIOENERGETICS
GENE REGULATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Mitochondria are central hubs of cellular bioenergetics, redox signaling, and cell fate determination, and their dysfunction represents a hallmark of several diseases, including neurodegenerative, cardiovascular, and metabolic disorders, as well as aging. Melatonin, classically considered a circadian hormone, has recently been recognized as an endogenous modulator of mitochondrial physiology. This review provides a comprehensive overview of the mechanisms by which melatonin preserves mitochondrial function through multifaceted mechanisms. At the bioenergetic level, melatonin enhances the activity of electron transport chain (ETC) complexes, stabilizes the mitochondrial membrane potential (Δψ), and prevents cardiolipin (CL) peroxidation, thereby limiting the opening of the permeability transition pore (mPTP) and the release of cytochrome c. Its potent radical scavenging activity, together with the upregulation of mitochondrial antioxidant enzymes, counteracts oxidative stress (OS) and preserves mitochondrial DNA integrity. Melatonin also finely regulates mitochondrial dynamics by promoting fusion and inhibiting pathological fission, while sustaining quality control pathways, including mitophagy, unfolded protein response (UPR), and proteostasis. At the transcriptional level, melatonin modulates canonical regulators of mitochondrial biogenesis and gene expression, thereby promoting mitochondrial resilience under stress conditions. Emerging data also highlight melatonin´s role in intercellular mitochondrial trafficking via tunneling nanotubes (TNTs) and in the modulation of mitokine signaling, linking mitochondrial homeostasis to systemic adaptation. In summary, melatonin emerges as a multifaceted regulator of mitochondrial function and dynamics, with significant translational implications for diseases associated with mitochondrial impairment.
Fil: Abarza, Silvia del Valle. Università Degli Studi Di Urbino Carlo Bo.; Italia
Fil: Nasoni, Maria Gemma. Università Degli Studi Di Urbino Carlo Bo.; Italia
Fil: Perrone, Serafina. Università di Parma; Italia
Fil: Bargagni, Erik. Università Degli Studi Di Urbino Carlo Bo.; Italia
Fil: Gentile, Carla. Università degli Studi di Palermo; Italia
Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad del Aconcagua. Facultad de Ciencias Médicas; Argentina
Fil: Reiter, Russel. University Of Texas At San Antonio; Estados Unidos
Fil: Luchetti, Francesca. Università Degli Studi Di Urbino Carlo Bo.; Italia
Fil: Balduini, Walter. Università Degli Studi Di Urbino Carlo Bo.; Italia
description Mitochondria are central hubs of cellular bioenergetics, redox signaling, and cell fate determination, and their dysfunction represents a hallmark of several diseases, including neurodegenerative, cardiovascular, and metabolic disorders, as well as aging. Melatonin, classically considered a circadian hormone, has recently been recognized as an endogenous modulator of mitochondrial physiology. This review provides a comprehensive overview of the mechanisms by which melatonin preserves mitochondrial function through multifaceted mechanisms. At the bioenergetic level, melatonin enhances the activity of electron transport chain (ETC) complexes, stabilizes the mitochondrial membrane potential (Δψ), and prevents cardiolipin (CL) peroxidation, thereby limiting the opening of the permeability transition pore (mPTP) and the release of cytochrome c. Its potent radical scavenging activity, together with the upregulation of mitochondrial antioxidant enzymes, counteracts oxidative stress (OS) and preserves mitochondrial DNA integrity. Melatonin also finely regulates mitochondrial dynamics by promoting fusion and inhibiting pathological fission, while sustaining quality control pathways, including mitophagy, unfolded protein response (UPR), and proteostasis. At the transcriptional level, melatonin modulates canonical regulators of mitochondrial biogenesis and gene expression, thereby promoting mitochondrial resilience under stress conditions. Emerging data also highlight melatonin´s role in intercellular mitochondrial trafficking via tunneling nanotubes (TNTs) and in the modulation of mitokine signaling, linking mitochondrial homeostasis to systemic adaptation. In summary, melatonin emerges as a multifaceted regulator of mitochondrial function and dynamics, with significant translational implications for diseases associated with mitochondrial impairment.
publishDate 2026
dc.date.none.fl_str_mv 2026-02-14
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/289473
Abarza, Silvia del Valle; Nasoni, Maria Gemma; Perrone, Serafina; Bargagni, Erik; Gentile, Carla; et al.; Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene Regulation; Tech Science Press; Biocell; 50; 2; 14-2-2026; 1-22
0327-9545
1667-5746
CONICET Digital
CONICET
url http://hdl.handle.net/11336/289473
identifier_str_mv Abarza, Silvia del Valle; Nasoni, Maria Gemma; Perrone, Serafina; Bargagni, Erik; Gentile, Carla; et al.; Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene Regulation; Tech Science Press; Biocell; 50; 2; 14-2-2026; 1-22
0327-9545
1667-5746
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.techscience.com/biocell/v50n2/66251
info:eu-repo/semantics/altIdentifier/doi/10.32604/biocell.2025.073776
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Tech Science Press
publisher.none.fl_str_mv Tech Science Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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