Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting complex i activity

The fine regulation of mitochondrial function has proved to be an essential metabolic adaptation to fluctuations in oxygen availability. During hypoxia, cells activate an anaerobic switch that favors glycolysis and attenuates the mitochondrial activity. This switch involves the hypoxia-inducible tra...

Descripción completa

Detalles Bibliográficos
Autores: Tello, Daniel, Balsa Martínez, Eduardo, Acosta-Iborra, Bárbara, Fuertes-Yebra, Esther, Elorza, Ainara, Ordóñez, Ángel, Corral-Escariz, María, Soro, Inés, López-Bernardo, Elia, Perales-Clemente, Ester, Martínez-Ruiz, Antonio, Enríquez, José Antonio, Aragonés López, Julián, Cadenas, Susana, Landázuri, Manuel O.
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/710316
Acceso en línea:http://hdl.handle.net/10486/710316
https://dx.doi.org/10.1016/j.cmet.2011.10.008
Access Level:acceso abierto
Palabra clave:Renal Cell Carcinoma
Kidney Neoplasms
Acetyl Coenzyme A Acetyltransferase
Biología y Biomedicina / Biología
id ES_bcb3c06b70850dae4549949ecb2d0752
oai_identifier_str oai:repositorio.uam.es:10486/710316
network_acronym_str ES
network_name_str España
repository_id_str
spelling Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting complex i activityTello, DanielBalsa Martínez, EduardoAcosta-Iborra, BárbaraFuertes-Yebra, EstherElorza, AinaraOrdóñez, ÁngelCorral-Escariz, MaríaSoro, InésLópez-Bernardo, EliaPerales-Clemente, EsterMartínez-Ruiz, AntonioEnríquez, José AntonioAragonés López, JuliánCadenas, SusanaLandázuri, Manuel O.Renal Cell CarcinomaKidney NeoplasmsAcetyl Coenzyme A AcetyltransferaseBiología y Biomedicina / BiologíaThe fine regulation of mitochondrial function has proved to be an essential metabolic adaptation to fluctuations in oxygen availability. During hypoxia, cells activate an anaerobic switch that favors glycolysis and attenuates the mitochondrial activity. This switch involves the hypoxia-inducible transcription factor-1 (HIF-1). We have identified a HIF-1 target gene, the mitochondrial NDUFA4L2 (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 4-like 2). Our results, obtained employing NDUFA4L2-silenced cells and NDUFA4L2 knockout murine embryonic fibroblasts, indicate that hypoxia-induced NDUFA4L2 attenuates mitochondrial oxygen consumption involving inhibition of Complex I activity, which limits the intracellular ROS production under low-oxygen conditions. Thus, reducing mitochondrial Complex I activity via NDUFA4L2 appears to be an essential element in the mitochondrial reprogramming induced by HIF-1This work was supported by Ministerio de Ciencia e Innovación (SAF 2007-06592, SAF2010-14851), Comunidad Autónoma de Madrid (SAL 2006/ 0311), Metoxia Project-Health (F2 2009-222741), and Recava Network (RD 06/0014/0031) to M.O.L.; PS09/00101 and CP07/00143 to A.M.-R.; PI060701, PS09/00116, and CP08/00204 to S.C.; BFU2008-03407/BMC to J.A.; SAF2009-08007 to J.A.E.; and CSD2007-00020 to A.M.-R. and J.A.E. The CNIC is supported by the Instituto de Salud Carlos III-MICINN and the Pro-CNIC Foundation. We are grateful to Mike Murphy (Mitochondrial Biology Unit, MRC, Cambridge, UK) for the gift of MitoQ. We also thank Stephen Y. Chan and Joseph Loscalzo (Harvard Medical School, Boston, MA) for providing us ISCU expression vectorsElsevierDepartamento de Biología MolecularFacultad de Ciencias20112011-11-17research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/710316https://dx.doi.org/10.1016/j.cmet.2011.10.008reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7103162026-06-23T12:46:27Z
dc.title.none.fl_str_mv Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting complex i activity
title Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting complex i activity
spellingShingle Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting complex i activity
Tello, Daniel
Renal Cell Carcinoma
Kidney Neoplasms
Acetyl Coenzyme A Acetyltransferase
Biología y Biomedicina / Biología
title_short Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting complex i activity
title_full Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting complex i activity
title_fullStr Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting complex i activity
title_full_unstemmed Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting complex i activity
title_sort Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting complex i activity
dc.creator.none.fl_str_mv Tello, Daniel
Balsa Martínez, Eduardo
Acosta-Iborra, Bárbara
Fuertes-Yebra, Esther
Elorza, Ainara
Ordóñez, Ángel
Corral-Escariz, María
Soro, Inés
López-Bernardo, Elia
Perales-Clemente, Ester
Martínez-Ruiz, Antonio
Enríquez, José Antonio
Aragonés López, Julián
Cadenas, Susana
Landázuri, Manuel O.
author Tello, Daniel
author_facet Tello, Daniel
Balsa Martínez, Eduardo
Acosta-Iborra, Bárbara
Fuertes-Yebra, Esther
Elorza, Ainara
Ordóñez, Ángel
Corral-Escariz, María
Soro, Inés
López-Bernardo, Elia
Perales-Clemente, Ester
Martínez-Ruiz, Antonio
Enríquez, José Antonio
Aragonés López, Julián
Cadenas, Susana
Landázuri, Manuel O.
author_role author
author2 Balsa Martínez, Eduardo
Acosta-Iborra, Bárbara
Fuertes-Yebra, Esther
Elorza, Ainara
Ordóñez, Ángel
Corral-Escariz, María
Soro, Inés
López-Bernardo, Elia
Perales-Clemente, Ester
Martínez-Ruiz, Antonio
Enríquez, José Antonio
Aragonés López, Julián
Cadenas, Susana
Landázuri, Manuel O.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv Renal Cell Carcinoma
Kidney Neoplasms
Acetyl Coenzyme A Acetyltransferase
Biología y Biomedicina / Biología
topic Renal Cell Carcinoma
Kidney Neoplasms
Acetyl Coenzyme A Acetyltransferase
Biología y Biomedicina / Biología
description The fine regulation of mitochondrial function has proved to be an essential metabolic adaptation to fluctuations in oxygen availability. During hypoxia, cells activate an anaerobic switch that favors glycolysis and attenuates the mitochondrial activity. This switch involves the hypoxia-inducible transcription factor-1 (HIF-1). We have identified a HIF-1 target gene, the mitochondrial NDUFA4L2 (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 4-like 2). Our results, obtained employing NDUFA4L2-silenced cells and NDUFA4L2 knockout murine embryonic fibroblasts, indicate that hypoxia-induced NDUFA4L2 attenuates mitochondrial oxygen consumption involving inhibition of Complex I activity, which limits the intracellular ROS production under low-oxygen conditions. Thus, reducing mitochondrial Complex I activity via NDUFA4L2 appears to be an essential element in the mitochondrial reprogramming induced by HIF-1
publishDate 2011
dc.date.none.fl_str_mv 2011
2011-11-17
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/710316
https://dx.doi.org/10.1016/j.cmet.2011.10.008
url http://hdl.handle.net/10486/710316
https://dx.doi.org/10.1016/j.cmet.2011.10.008
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
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
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
_version_ 1869418136606867456
score 15.301603

Similares en LA Referencia