In vivo inhibition of the mitochondrial H+-ATP synthase in neurons promotes metabolic preconditioning

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Show simple item record Formentini, Laura Pereira, Marta P. Sánchez-Cenizo, Laura Santacatterina, Fulvio Lucas, José J. Navarro, Carmen Martínez-Serrano, Alberto Cuezva, José M.
dc.contributor.other UAM. Departamento de Biología Molecular es_ES 2015-06-16T13:28:21Z 2015-06-16T13:28:21Z 2014-04-01
dc.identifier.citation EMBO Journal 33.7 (2014): 762-778 en_US
dc.identifier.issn 0261-4189 (print) en_US
dc.identifier.issn 1460-2075 (online) en_US
dc.description.abstract A key transducer in energy conservation and signaling cell death is the mitochondrial H+-ATP synthase. The expression of the ATPase inhibitory factor 1 (IF1) is a strategy used by cancer cells to inhibit the activity of the H+-ATP synthase to generate a ROS signal that switches on cellular programs of survival. We have generated a mouse model expressing a mutant of human IF1 in brain neurons to assess the role of the H+-ATP synthase in cell death in vivo. The expression of hIF1 inhibits the activity of oxidative phosphorylation and mediates the shift of neurons to an enhanced aerobic glycolysis. Metabolic reprogramming induces brain preconditioning affording protection against quinolinic acid-induced excitotoxicity. Mechanistically, preconditioning involves the activation of the Akt/p70S6K and PARP repair pathways and Bcl-xL protection from cell death. Overall, our findings provide the first in vivo evidence highlighting the H +-ATP synthase as a target to prevent neuronal cell death en_US
dc.description.sponsorship This work was supported by grants from the MEC (BFU2010-18903), CIBERER and by Comunidad de Madrid (S2011/BMD-2402) to JMC; MINECO (PLE2009-0101 and SAF2010-17167), TerCel (RD12/0019/0013), and Neurostem-CM (S2010-BMD-2336) to AMS and ISCIII Grant PI 10/02628 to CN, Spain en_US
dc.format.extent 52 pag. en
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher EMBO Press
dc.relation.ispartof EMBO Journal en_US
dc.rights © 2014 The Authors en_US
dc.subject.other brain preconditioning en_US
dc.subject.other energy metabolism en_US
dc.subject.other inhibitory factor 1 (IF1) en_US
dc.subject.other mitochondria en_US
dc.title In vivo inhibition of the mitochondrial H+-ATP synthase in neurons promotes metabolic preconditioning en_US
dc.type article en
dc.subject.eciencia Biología y Biomedicina / Biología es_ES
dc.identifier.doi 10.1002/embj.201386392 es_ES
dc.identifier.publicationfirstpage 762 es_ES
dc.identifier.publicationissue 7 es_ES
dc.identifier.publicationlastpage 778 es_ES
dc.identifier.publicationvolume 33 es_ES
dc.relation.projectID Comunidad de Madrid. S2010/BMD-2402/MITOLAB es_ES
dc.relation.projectID Comunidad de Madrid. S2010/BMD-2336/NEUROSTEM es_ES
dc.type.version info:eu-repo/semantics/acceptedVersion en
dc.rights.accessRights openAccess en
dc.authorUAM Cuezva Marcos, José Manuel (260156)
dc.authorUAM Formentini , Laura (264360)
dc.authorUAM Santacatterina , Fulvio (264700)

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