English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/151307
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:

DC FieldValueLanguage
dc.contributor.authorSantacatterina, Fulvio-
dc.contributor.authorSánchez-Cenizo, Laura-
dc.contributor.authorFormentini, Laura-
dc.contributor.authorCasas, Estela-
dc.contributor.authorRueda, Carlos B.-
dc.contributor.authorMartínez-Reyes, Inmaculada-
dc.contributor.authorNúñez de Arenas, Cristina-
dc.contributor.authorGarcía-Bermúdez, Javier-
dc.contributor.authorSánchez-Aragó, María-
dc.contributor.authorSatrústegui, Jorgina-
dc.contributor.authorCuezva, José M.-
dc.identifierdoi: 10.18632/oncotarget.6357-
dc.identifierissn: 1949-2553-
dc.identifier.citationOncotarget 7: 490- 508 (2016)-
dc.description.abstractThe ATPase Inhibitory Factor 1 (IF1) is an inhibitor of the mitochondrial H+-ATP synthase that regulates the activity of both oxidative phosphorylation (OXPHOS) and cell death. Here, we have developed transgenic Tet-On and Tet-Off mice that express a mutant active form of hIF1 in the hepatocytes to restrain OXPHOS in the liver to investigate the relevance of mitochondrial activity in hepatocarcinogenesis. The expression of hIF1 promotes the inhibition of OXPHOS in both Tet-On and Tet- Off mouse models and induces a state of metabolic preconditioning guided by the activation of the stress kinases AMPK and p38 MAPK. Expression of the transgene significantly augmented proliferation and apoptotic resistance of carcinoma cells, which contributed to an enhanced diethylnitrosamine-induced liver carcinogenesis. Moreover, the expression of hIF1 also diminished acetaminophen-induced apoptosis, which is unrelated to differences in permeability transition pore opening. Mechanistically, cell survival in hIF1-preconditioned hepatocytes results from a nuclear factor-erythroid 2-related factor (Nrf2)-guided antioxidant response. The results emphasize in vivo that a metabolic phenotype with a restrained OXPHOS in the liver is prone to the development of cancer-
dc.description.sponsorshipMINECO (SAF2013-41945-R to JMC and SAF2012-33243 to AMV), CIBERER-ISCIII to JMC and CIBERDEM-ISCIII to AMV, Comunidad de Madrid (S2011/BMD-2402 to JMC and S2010/BMD-2423 to AMV), Fundación Ramón Areces (FRA) -
dc.relation.isversionofPublisher's version-
dc.subjectEnergy metabolism-
dc.subjectReactive oxygen species-
dc.subjectATPase inhibitory factor 1-
dc.titleDown-regulation of oxidative phosphorylation in the liver by expression of the ATPase inhibitory factor 1 induces a tumor-promoter metabolic state-
dc.description.versionPeer Reviewed-
dc.contributor.funderMinisterio de Economía y Competitividad (España)-
dc.contributor.funderComunidad de Madrid-
dc.contributor.funderFundación Ramón Areces-
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
SatrústeguiJ_DownRegulationOfOxidativePhosphorylation.pdf14,83 MBAdobe PDFThumbnail
Show simple item record

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.