Autophagy exacerbates caspase-dependent apoptotic cell death after short times of starvation
Fecha de publicación2015-12
Yuste Mateos, Víctor J. (Víctor José)
MetadatosMostrar el registro completo del ítem
Autophagy 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.
Es parte deBiochemical Pharmacology, 2015, vol. 98, núm. 4, p. 573-586
Proyectos de investigación europeos
Showing items related by title, author, creator and subject.
Ribas i Fortuny, Judit; Yuste Mateos, Víctor J. (Víctor José); Garrofé Ochoa, Xènia; Meijer, Laurent; Esquerda Colell, Josep; Boix Torras, Jacint (Elsevier, 2008)The new 7-bromoindirubin-3′-oxime (7BIO) compound induces caspase-independent cell death in all cell lines tested to date. Irrespective of the cell line, a 25 μM treatment for 24 h is lethal for the entire cell population. ...
Ribas i Fortuny, Judit; Bettayeb, Karima; Ferandin, Yoan; Knockaert, Marie; Garrofé Ochoa, Xènia; Totzke, Frank; Schächtele, Christoph; Mester, Jan; Polychronopoulos, Panagiotis; Magiatis, Prokopios; Skaltsounis, Alexios-Leandros; Boix Torras, Jacint; Meijer, Laurent (Nature Publishing Group, 2006)Indirubin, an isomer of indigo, is a reported inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase-3 (GSK-3) as well as an agonist of the aryl hydrocarbon receptor (AhR). Indirubin is the active ...
Cell Death Triggered by the Autophagy Inhibitory Drug 3-Methyladenine in Growing Conditions Proceeds With DNA Damage Chicote, Javier; Yuste Mateos, Víctor J. (Víctor José); Boix Torras, Jacint; Ribas i Fortuny, Judit (Frontiers Media, 2020-10-15)Macroautophagy (hereafter autophagy) is a multistep intracellular catabolic process with pleiotropic implications in cell fate. Attending to its activation, autophagy can be classified into inducible or constitutive. ...