Show simple item record

dc.contributor.authorMattiolo, Paolo
dc.contributor.authorYuste Mateos, Víctor J. (Víctor José)
dc.contributor.authorBoix Torras, Jacint
dc.contributor.authorRibas i Fortuny, Judit
dc.date.accessioned2015-11-19T17:57:44Z
dc.date.available2015-11-19T17:57:44Z
dc.date.issued2015-12
dc.identifier.issn0006-2952
dc.identifier.urihttp://hdl.handle.net/10459.1/49017
dc.description.abstractAutophagy is generally regarded as a mechanism to promote cell survival. However, autophagy can occasionally be the mechanism responsible of cell demise. We have found that a concomitant depletion of glucose, nutrients and growth factors provoked cell death in a variety of cell lines. This death process was contingent upon caspase activation and was mediated by BAX/BAK proteins, thus indicating its apoptotic nature and the engagement of an intrinsic pathway. In order to abrogate autophagy, 3-methyladenine (3-MA), BECLIN-1 siRNA and Atg5 knock-out (Tet-Off type) approaches were alternatively employed. Irrespective of the procedure, at short times of starvation, we found that the ongoing autophagy was sensitizing cells to the permeabilization of the mitochondrial outer membrane (MOMP), caspase activation and, therefore, apoptosis. On the contrary, at longer times of starvation, autophagy displayed its characteristic pro-survival effect on cells. As far as we know, we provide the first experimental paradigm where time is the only variable determining the final outcome of autophagy. In other words, we have circumscribed in time the shift transforming autophagy from a cell death to a protection mechanism. Moreover, at short times, starvation-driven autophagy exacerbated the apoptotic cell death caused by several antitumor agents. In agreement with this fact, their apoptotic effects were greatly diminished by autophagy inhibition. The implications of these facts in tumor biology will be discussed.
dc.description.sponsorshipThe author’s thanks Dr. P. Codogno for the Atg5 Tet-Off MEFs m5-7 (originated at Prof. Mizushima’s laboratory) and Dr. S.E. Lupold for the PC3 and DU145 cell lines. This work was supported by Ministerio de Economía y Competitividad SAF2011-29730. VJY is under a “Retention of Research Talent” contract of “Programa Banco de Santander”. PM was supported by a fellowship (AH9815758) from AGAUR (Generalitat de Catalunya). University of Lleida Funds (Ajuts Pont 2015) contributed to the completion of this work.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherElsevier
dc.relationMICINN/PN2008-2011/SAF2011-29730
dc.relation.isformatofVersió preprint del document publicat a: https://doi.org/10.1016/j.bcp.2015.09.021.
dc.relation.ispartofBiochemical Pharmacology, 2015, vol. 98, núm. 4, p. 573-586
dc.rights(c) Elsevier, 2015
dc.subjectApoptosis
dc.subjectAutophagy
dc.subjectCell starvation
dc.subjectmitochondrial outer membrane permeabilization
dc.subjectCaspases
dc.subject.classificationApoptosi
dc.subject.classificationAutofàgia
dc.subject.otherApoptosis
dc.subject.otherAutophagy
dc.titleAutophagy exacerbates caspase-dependent apoptotic cell death after short times of starvation
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2015-11-19T17:57:44Z
dc.identifier.idgrec023320
dc.type.versioninfo:eu-repo/semantics/submittedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.1016/j.bcp.2015.09.021


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record