HIF1α-dependent uncoupling of glycolysis suppresses tumor cell proliferation

Urrutia Elorduy, Andrés Amalio; Mesa Ciller, Claudia Julia; Guajardo Grence, Andrea; Alkan, H. Furkan; Soro Arnáiz, Inés; Vandekeere, Anke; Ferreira Campos, Ana Margarida; Igelmann, Sebastian; Fernández Arroyo Camacho, Lucía; Rinaldi, Gianmarco; Lorendeau, Doriane; Bock, Katrien De; Fendt, Sarah Maria; Aragonés López, Julián

HIF1α-dependent uncoupling of glycolysis suppresses tumor cell proliferation

Hypoxia-inducible factor-1a (HIF1a) attenuates mitochondrial activity while promoting glycolysis. However, lower glycolysis is compromised in human clear cell renal cell carcinomas, in which HIF1a acts as a tumor suppressor by inhibiting cell-autonomous proliferation. Here, we find that, unexpectedl...

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Detalles Bibliográficos
Autores:	Urrutia Elorduy, Andrés Amalio, Mesa Ciller, Claudia Julia, Guajardo Grence, Andrea, Alkan, H. Furkan, Soro Arnáiz, Inés, Vandekeere, Anke, Ferreira Campos, Ana Margarida, Igelmann, Sebastian, Fernández Arroyo Camacho, Lucía, Rinaldi, Gianmarco, Lorendeau, Doriane, Bock, Katrien De, Fendt, Sarah Maria, Aragonés López, Julián
Tipo de recurso:	artículo
Fecha de publicación:	2024
País:	España
Institución:	Universidad Autónoma de Madrid
Repositorio:	Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:	inglés
OAI Identifier:	oai:repositorio.uam.es:10486/755080
Acceso en línea:	https://hdl.handle.net/10486/755080 https://dx.doi.org/10.1016/j.celrep.2024.114103
Access Level:	acceso abierto
Palabra clave:	HIF1α glycolysis oxygen renal cell carcinoma mitochondria NADH hypoxia tumor Medicina

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spelling	HIF1α-dependent uncoupling of glycolysis suppresses tumor cell proliferationUrrutia Elorduy, Andrés AmalioMesa Ciller, Claudia JuliaGuajardo Grence, AndreaAlkan, H. FurkanSoro Arnáiz, InésVandekeere, AnkeFerreira Campos, Ana MargaridaIgelmann, SebastianFernández Arroyo Camacho, LucíaRinaldi, GianmarcoLorendeau, DorianeBock, Katrien DeFendt, Sarah MariaAragonés López, JuliánHIF1αglycolysisoxygenrenal cell carcinomamitochondriaNADHhypoxiatumorMedicinaHypoxia-inducible factor-1a (HIF1a) attenuates mitochondrial activity while promoting glycolysis. However, lower glycolysis is compromised in human clear cell renal cell carcinomas, in which HIF1a acts as a tumor suppressor by inhibiting cell-autonomous proliferation. Here, we find that, unexpectedly, HIF1a suppresses lower glycolysis after the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) step, leading to reduced lactate secretion in different tumor cell types when cells encounter a limited pyruvate supply such as that typically found in the tumor microenvironment in vivo. This is because HIF1a-dependent attenuation of mitochondrial oxygen consumption increases the NADH/NAD+ ratio that suppresses the activity of the NADHsensitive GAPDH glycolytic enzyme. This is manifested when pyruvate supply is limited, since pyruvate acts as an electron acceptor that prevents the increment of the NADH/NAD+ ratio. Furthermore, this antiglycolytic function provides a molecular basis to explain how HIF1a can suppress tumor cell proliferation by increasing the NADH/NAD+ ratioElsevierFacultad de MedicinaDepartamento de Medicina20242024-04-23research articlehttp://purl.org/coar/resource_type/c_2df8fbb1EVoRhttp://purl.org/coar/version/c_dc82b40f9837b551info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10486/755080https://dx.doi.org/10.1016/j.celrep.2024.11410338607920reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7550802026-06-23T12:46:27Z
dc.title.none.fl_str_mv	HIF1α-dependent uncoupling of glycolysis suppresses tumor cell proliferation
title	HIF1α-dependent uncoupling of glycolysis suppresses tumor cell proliferation
spellingShingle	HIF1α-dependent uncoupling of glycolysis suppresses tumor cell proliferation Urrutia Elorduy, Andrés Amalio HIF1α glycolysis oxygen renal cell carcinoma mitochondria NADH hypoxia tumor Medicina
title_short	HIF1α-dependent uncoupling of glycolysis suppresses tumor cell proliferation
title_full	HIF1α-dependent uncoupling of glycolysis suppresses tumor cell proliferation
title_fullStr	HIF1α-dependent uncoupling of glycolysis suppresses tumor cell proliferation
title_full_unstemmed	HIF1α-dependent uncoupling of glycolysis suppresses tumor cell proliferation
title_sort	HIF1α-dependent uncoupling of glycolysis suppresses tumor cell proliferation
dc.creator.none.fl_str_mv	Urrutia Elorduy, Andrés Amalio Mesa Ciller, Claudia Julia Guajardo Grence, Andrea Alkan, H. Furkan Soro Arnáiz, Inés Vandekeere, Anke Ferreira Campos, Ana Margarida Igelmann, Sebastian Fernández Arroyo Camacho, Lucía Rinaldi, Gianmarco Lorendeau, Doriane Bock, Katrien De Fendt, Sarah Maria Aragonés López, Julián
author	Urrutia Elorduy, Andrés Amalio
author_facet	Urrutia Elorduy, Andrés Amalio Mesa Ciller, Claudia Julia Guajardo Grence, Andrea Alkan, H. Furkan Soro Arnáiz, Inés Vandekeere, Anke Ferreira Campos, Ana Margarida Igelmann, Sebastian Fernández Arroyo Camacho, Lucía Rinaldi, Gianmarco Lorendeau, Doriane Bock, Katrien De Fendt, Sarah Maria Aragonés López, Julián
author_role	author
author2	Mesa Ciller, Claudia Julia Guajardo Grence, Andrea Alkan, H. Furkan Soro Arnáiz, Inés Vandekeere, Anke Ferreira Campos, Ana Margarida Igelmann, Sebastian Fernández Arroyo Camacho, Lucía Rinaldi, Gianmarco Lorendeau, Doriane Bock, Katrien De Fendt, Sarah Maria Aragonés López, Julián
author2_role	author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Facultad de Medicina Departamento de Medicina
dc.subject.none.fl_str_mv	HIF1α glycolysis oxygen renal cell carcinoma mitochondria NADH hypoxia tumor Medicina
topic	HIF1α glycolysis oxygen renal cell carcinoma mitochondria NADH hypoxia tumor Medicina
description	Hypoxia-inducible factor-1a (HIF1a) attenuates mitochondrial activity while promoting glycolysis. However, lower glycolysis is compromised in human clear cell renal cell carcinomas, in which HIF1a acts as a tumor suppressor by inhibiting cell-autonomous proliferation. Here, we find that, unexpectedly, HIF1a suppresses lower glycolysis after the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) step, leading to reduced lactate secretion in different tumor cell types when cells encounter a limited pyruvate supply such as that typically found in the tumor microenvironment in vivo. This is because HIF1a-dependent attenuation of mitochondrial oxygen consumption increases the NADH/NAD+ ratio that suppresses the activity of the NADHsensitive GAPDH glycolytic enzyme. This is manifested when pyruvate supply is limited, since pyruvate acts as an electron acceptor that prevents the increment of the NADH/NAD+ ratio. Furthermore, this antiglycolytic function provides a molecular basis to explain how HIF1a can suppress tumor cell proliferation by increasing the NADH/NAD+ ratio
publishDate	2024
dc.date.none.fl_str_mv	2024 2024-04-23
dc.type.none.fl_str_mv	research article http://purl.org/coar/resource_type/c_2df8fbb1 EVoR http://purl.org/coar/version/c_dc82b40f9837b551
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/10486/755080 https://dx.doi.org/10.1016/j.celrep.2024.114103 38607920
url	https://hdl.handle.net/10486/755080 https://dx.doi.org/10.1016/j.celrep.2024.114103
identifier_str_mv	38607920
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Elsevier
publisher.none.fl_str_mv	Elsevier
dc.source.none.fl_str_mv	reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid
instname_str	Universidad Autónoma de Madrid
reponame_str	Biblos-e Archivo. Repositorio Institucional de la UAM
collection	Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,812429

HIF1α-dependent uncoupling of glycolysis suppresses tumor cell proliferation

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