English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/151307
Share/Impact:
Statistics
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
Exportar a otros formatos:

Title

Down-regulation of oxidative phosphorylation in the liver by expression of the ATPase inhibitory factor 1 induces a tumor-promoter metabolic state

AuthorsSantacatterina, Fulvio ; Sánchez-Cenizo, Laura ; Formentini, Laura ; Casas, Estela; Rueda, Carlos B. ; Martínez-Reyes, Inmaculada ; Núñez de Arenas, Cristina ; García-Bermúdez, Javier ; Sánchez-Aragó, María ; Satrústegui, Jorgina ; Cuezva, José M.
KeywordsEnergy metabolism
Cancer
Mitochondria
Reactive oxygen species
ATPase inhibitory factor 1
Issue Date22-Nov-2015
CitationOncotarget 7: 490- 508 (2016)
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
URIhttp://hdl.handle.net/10261/151307
DOI10.18632/oncotarget.6357
Identifiersdoi: 10.18632/oncotarget.6357
issn: 1949-2553
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
SatrústeguiJ_DownRegulationOfOxidativePhosphorylation.pdf14,83 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


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