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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/13698

Mitochondrial apoptosis induced by BH3-only molecules in the exclusive presence of endoplasmic reticular Bak

AutorKlee, Martina; Pallauf, Kathrin; Alcalá, Sonia; Fleischer, Aarne ; Pimentel-Muiños, Felipe X.
Palabras claveBak
Endoplasmic reticulum
ER-to-mitochondria apoptotic communication
Mitochondrial apoptosis
Signal transduction
Differentiation & death
Fecha de publicación2-abr-2009
EditorEuropean Molecular Biology Organization
Nature Publishing Group
CitaciónEMBO Journal 28(12): 1757-1768 (2009)
ResumenBak and Bax are critical apoptotic mediators that naturally localize to both mitochondria and the endoplasmic reticulum (ER). Although it is generally accepted that mitochondrial expression of Bak or Bax suffices for apoptosis initiated by BH3-only homologues, it is currently unclear whether their reticular counterparts may have a similar potential. In this study, we show that cells exclusively expressing Bak in endoplasmic membranes undergo cytochrome c mobilization and mitochondrial apoptosis in response to BimEL and Puma, even when these BH3-only molecules are also targeted to the ER. Surprisingly, calcium was necessary but not sufficient to drive the pathway, despite normal ER calcium levels. We provide evidence that calcium functions coordinately with the ER-stress surveillance machinery IRE1alpha/TRAF2 to transmit apoptotic signals from the reticulum to mitochondria. These results indicate that BH3-only mediators can rely on reticular Bak to activate an ER-to-mitochondria signalling route able to induce cytochrome c release and apoptosis independently of the canonical Bak,Bax-dependent mitochondrial gateway, thus revealing a new layer of complexity in apoptotic regulation.
Descripción12 pages, 7 figures.-- PMID: 19339988 [PubMed].-- Printed version published Jun 17, 2009.
Supporting information (Suppl. figs S1-S13) available at: http://www.nature.com/emboj/journal/vaop/ncurrent/suppinfo/emboj200990as1.html
Versión del editorhttp://dx.doi.org/10.1038/emboj.2009.90
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