Melatonin synthesis in and uptake by mitochondria: implications for diseased cells with dysfunctional mitochondria

Autores
Reiter, Russel; Sharma, Ramaswamy; Pires De Campos Zuccari, Debora Aparecida; Almeida Chuffa, Luiz Gustavo de; Manucha, Walter Ariel Fernando; Rodriguez, Carmen
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Although there is one exception (red blood cells), the lack of energy (ATP) provided by mitochondrial oxidative phosphorylation (OXPHOS) would not be compatible with the long-term survival of normal cells. During conventional metabolism, pyruvate, the cytosolic glycolysis product, enters mitochondria where it is metabolized to acetyl-coenzyme A (acetyl-CoA) under the influence of the enzyme pyruvate dehydrogenase complex (PDC). Acetyl-CoA makes an important contribution to the tricarboxylic acid (TCA) cycle which feeds NADH and FADH2 to the respiratory chain which benefits ATP´s generation by OXPHOS. In some diseased cells, however, pyruvate metabolism becomes aberrant since its transport into the mitochondria is blunted due to the downregulation of PDC due to its inhibition by pyruvate dehydrogenase kinase (PDK), which is upregulated by hypoxia-inducible factor 1 (HIF-1). Therefore, pyruvate undergoes fermentation to lactate in the cytosol. This alternate pathway of pyruvate metabolism is known as the Warburg effect, named after the individual who discovered it, Otto Warburg [1]. Since pyruvate does not enter the mitochondria, mitochondrial ATP synthesis is depressed. Warburg-type metabolism, however, compensates for this by rapidly, albeit inefficiently, synthesizing ATP in the cytosol. Warburg metabolism (also known as aerobic glycolysis) is almost always associated with pathological cells.
Fil: Reiter, Russel. University Of Texas At San Antonio. University Of Texas Health Science Center At San Antonio (ut Health San Antonio); Estados Unidos
Fil: Sharma, Ramaswamy. University Of Texas At San Antonio. University Of Texas Health Science Center At San Antonio (ut Health San Antonio); Estados Unidos
Fil: Pires De Campos Zuccari, Debora Aparecida. Faculdade de Medicina de São José Do Rio Preto; Brasil
Fil: Almeida Chuffa, Luiz Gustavo de. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil
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
Fil: Rodriguez, Carmen. Universidad de Oviedo; España
Materia
AEROBIC GLYCOLYSIS
GLYCOLYTICS
HYPOXIA-INDUCIBLE FACTOR 1Α
OXIDATIVE PHOSPHORYLATION
PYRUVATE DEHYDROGENASE
REACTIVE OXYGEN SPECIES
SUPEROXIDE DISMUTASE 2
WARBURG EFFECT
ZYGOTE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/173273
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/173273
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Melatonin synthesis in and uptake by mitochondria: implications for diseased cells with dysfunctional mitochondriaReiter, RusselSharma, RamaswamyPires De Campos Zuccari, Debora AparecidaAlmeida Chuffa, Luiz Gustavo deManucha, Walter Ariel FernandoRodriguez, CarmenAEROBIC GLYCOLYSISGLYCOLYTICSHYPOXIA-INDUCIBLE FACTOR 1ΑOXIDATIVE PHOSPHORYLATIONPYRUVATE DEHYDROGENASEREACTIVE OXYGEN SPECIESSUPEROXIDE DISMUTASE 2WARBURG EFFECTZYGOTEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Although there is one exception (red blood cells), the lack of energy (ATP) provided by mitochondrial oxidative phosphorylation (OXPHOS) would not be compatible with the long-term survival of normal cells. During conventional metabolism, pyruvate, the cytosolic glycolysis product, enters mitochondria where it is metabolized to acetyl-coenzyme A (acetyl-CoA) under the influence of the enzyme pyruvate dehydrogenase complex (PDC). Acetyl-CoA makes an important contribution to the tricarboxylic acid (TCA) cycle which feeds NADH and FADH2 to the respiratory chain which benefits ATP´s generation by OXPHOS. In some diseased cells, however, pyruvate metabolism becomes aberrant since its transport into the mitochondria is blunted due to the downregulation of PDC due to its inhibition by pyruvate dehydrogenase kinase (PDK), which is upregulated by hypoxia-inducible factor 1 (HIF-1). Therefore, pyruvate undergoes fermentation to lactate in the cytosol. This alternate pathway of pyruvate metabolism is known as the Warburg effect, named after the individual who discovered it, Otto Warburg [1]. Since pyruvate does not enter the mitochondria, mitochondrial ATP synthesis is depressed. Warburg-type metabolism, however, compensates for this by rapidly, albeit inefficiently, synthesizing ATP in the cytosol. Warburg metabolism (also known as aerobic glycolysis) is almost always associated with pathological cells.Fil: Reiter, Russel. University Of Texas At San Antonio. University Of Texas Health Science Center At San Antonio (ut Health San Antonio); Estados UnidosFil: Sharma, Ramaswamy. University Of Texas At San Antonio. University Of Texas Health Science Center At San Antonio (ut Health San Antonio); Estados UnidosFil: Pires De Campos Zuccari, Debora Aparecida. Faculdade de Medicina de São José Do Rio Preto; BrasilFil: Almeida Chuffa, Luiz Gustavo de. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Rodriguez, Carmen. Universidad de Oviedo; EspañaFuture Medicine2021-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/173273Reiter, Russel; Sharma, Ramaswamy; Pires De Campos Zuccari, Debora Aparecida; Almeida Chuffa, Luiz Gustavo de; Manucha, Walter Ariel Fernando; et al.; Melatonin synthesis in and uptake by mitochondria: implications for diseased cells with dysfunctional mitochondria; Future Medicine; Future Medicinal Chemistry; 13; 4; 2-2021; 335-3391756-89191756-8927CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.future-science.com/doi/10.4155/fmc-2020-0326info:eu-repo/semantics/altIdentifier/doi/10.4155/fmc-2020-0326info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:32:13Zoai:ri.conicet.gov.ar:11336/173273instacron: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:34982025-09-29 10:32:13.747CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Melatonin synthesis in and uptake by mitochondria: implications for diseased cells with dysfunctional mitochondria
title Melatonin synthesis in and uptake by mitochondria: implications for diseased cells with dysfunctional mitochondria
spellingShingle Melatonin synthesis in and uptake by mitochondria: implications for diseased cells with dysfunctional mitochondria
Reiter, Russel
AEROBIC GLYCOLYSIS
GLYCOLYTICS
HYPOXIA-INDUCIBLE FACTOR 1Α
OXIDATIVE PHOSPHORYLATION
PYRUVATE DEHYDROGENASE
REACTIVE OXYGEN SPECIES
SUPEROXIDE DISMUTASE 2
WARBURG EFFECT
ZYGOTE
title_short Melatonin synthesis in and uptake by mitochondria: implications for diseased cells with dysfunctional mitochondria
title_full Melatonin synthesis in and uptake by mitochondria: implications for diseased cells with dysfunctional mitochondria
title_fullStr Melatonin synthesis in and uptake by mitochondria: implications for diseased cells with dysfunctional mitochondria
title_full_unstemmed Melatonin synthesis in and uptake by mitochondria: implications for diseased cells with dysfunctional mitochondria
title_sort Melatonin synthesis in and uptake by mitochondria: implications for diseased cells with dysfunctional mitochondria
dc.creator.none.fl_str_mv Reiter, Russel
Sharma, Ramaswamy
Pires De Campos Zuccari, Debora Aparecida
Almeida Chuffa, Luiz Gustavo de
Manucha, Walter Ariel Fernando
Rodriguez, Carmen
author Reiter, Russel
author_facet Reiter, Russel
Sharma, Ramaswamy
Pires De Campos Zuccari, Debora Aparecida
Almeida Chuffa, Luiz Gustavo de
Manucha, Walter Ariel Fernando
Rodriguez, Carmen
author_role author
author2 Sharma, Ramaswamy
Pires De Campos Zuccari, Debora Aparecida
Almeida Chuffa, Luiz Gustavo de
Manucha, Walter Ariel Fernando
Rodriguez, Carmen
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv AEROBIC GLYCOLYSIS
GLYCOLYTICS
HYPOXIA-INDUCIBLE FACTOR 1Α
OXIDATIVE PHOSPHORYLATION
PYRUVATE DEHYDROGENASE
REACTIVE OXYGEN SPECIES
SUPEROXIDE DISMUTASE 2
WARBURG EFFECT
ZYGOTE
topic AEROBIC GLYCOLYSIS
GLYCOLYTICS
HYPOXIA-INDUCIBLE FACTOR 1Α
OXIDATIVE PHOSPHORYLATION
PYRUVATE DEHYDROGENASE
REACTIVE OXYGEN SPECIES
SUPEROXIDE DISMUTASE 2
WARBURG EFFECT
ZYGOTE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Although there is one exception (red blood cells), the lack of energy (ATP) provided by mitochondrial oxidative phosphorylation (OXPHOS) would not be compatible with the long-term survival of normal cells. During conventional metabolism, pyruvate, the cytosolic glycolysis product, enters mitochondria where it is metabolized to acetyl-coenzyme A (acetyl-CoA) under the influence of the enzyme pyruvate dehydrogenase complex (PDC). Acetyl-CoA makes an important contribution to the tricarboxylic acid (TCA) cycle which feeds NADH and FADH2 to the respiratory chain which benefits ATP´s generation by OXPHOS. In some diseased cells, however, pyruvate metabolism becomes aberrant since its transport into the mitochondria is blunted due to the downregulation of PDC due to its inhibition by pyruvate dehydrogenase kinase (PDK), which is upregulated by hypoxia-inducible factor 1 (HIF-1). Therefore, pyruvate undergoes fermentation to lactate in the cytosol. This alternate pathway of pyruvate metabolism is known as the Warburg effect, named after the individual who discovered it, Otto Warburg [1]. Since pyruvate does not enter the mitochondria, mitochondrial ATP synthesis is depressed. Warburg-type metabolism, however, compensates for this by rapidly, albeit inefficiently, synthesizing ATP in the cytosol. Warburg metabolism (also known as aerobic glycolysis) is almost always associated with pathological cells.
Fil: Reiter, Russel. University Of Texas At San Antonio. University Of Texas Health Science Center At San Antonio (ut Health San Antonio); Estados Unidos
Fil: Sharma, Ramaswamy. University Of Texas At San Antonio. University Of Texas Health Science Center At San Antonio (ut Health San Antonio); Estados Unidos
Fil: Pires De Campos Zuccari, Debora Aparecida. Faculdade de Medicina de São José Do Rio Preto; Brasil
Fil: Almeida Chuffa, Luiz Gustavo de. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil
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
Fil: Rodriguez, Carmen. Universidad de Oviedo; España
description Although there is one exception (red blood cells), the lack of energy (ATP) provided by mitochondrial oxidative phosphorylation (OXPHOS) would not be compatible with the long-term survival of normal cells. During conventional metabolism, pyruvate, the cytosolic glycolysis product, enters mitochondria where it is metabolized to acetyl-coenzyme A (acetyl-CoA) under the influence of the enzyme pyruvate dehydrogenase complex (PDC). Acetyl-CoA makes an important contribution to the tricarboxylic acid (TCA) cycle which feeds NADH and FADH2 to the respiratory chain which benefits ATP´s generation by OXPHOS. In some diseased cells, however, pyruvate metabolism becomes aberrant since its transport into the mitochondria is blunted due to the downregulation of PDC due to its inhibition by pyruvate dehydrogenase kinase (PDK), which is upregulated by hypoxia-inducible factor 1 (HIF-1). Therefore, pyruvate undergoes fermentation to lactate in the cytosol. This alternate pathway of pyruvate metabolism is known as the Warburg effect, named after the individual who discovered it, Otto Warburg [1]. Since pyruvate does not enter the mitochondria, mitochondrial ATP synthesis is depressed. Warburg-type metabolism, however, compensates for this by rapidly, albeit inefficiently, synthesizing ATP in the cytosol. Warburg metabolism (also known as aerobic glycolysis) is almost always associated with pathological cells.
publishDate 2021
dc.date.none.fl_str_mv 2021-02
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/11336/173273
Reiter, Russel; Sharma, Ramaswamy; Pires De Campos Zuccari, Debora Aparecida; Almeida Chuffa, Luiz Gustavo de; Manucha, Walter Ariel Fernando; et al.; Melatonin synthesis in and uptake by mitochondria: implications for diseased cells with dysfunctional mitochondria; Future Medicine; Future Medicinal Chemistry; 13; 4; 2-2021; 335-339
1756-8919
1756-8927
CONICET Digital
CONICET
url http://hdl.handle.net/11336/173273
identifier_str_mv Reiter, Russel; Sharma, Ramaswamy; Pires De Campos Zuccari, Debora Aparecida; Almeida Chuffa, Luiz Gustavo de; Manucha, Walter Ariel Fernando; et al.; Melatonin synthesis in and uptake by mitochondria: implications for diseased cells with dysfunctional mitochondria; Future Medicine; Future Medicinal Chemistry; 13; 4; 2-2021; 335-339
1756-8919
1756-8927
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.future-science.com/doi/10.4155/fmc-2020-0326
info:eu-repo/semantics/altIdentifier/doi/10.4155/fmc-2020-0326
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Future Medicine
publisher.none.fl_str_mv Future Medicine
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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score 13.070432

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