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|Title:||A BAX/BAK and Cyclophilin D-Independent Intrinsic Apoptosis Pathway|
|Authors:||Zamorano, Sebastián;Rojas-Rivera, Diego;Lisbona, Fernanda;Parra, Valentina;Court, Felipe A.;Villegas, Rosario;Cheng, Emily H.;Korsmeyer, Stanley J.;Lavandero, Sergio;Hetz, Claudio|
|Keywords:||Biology;Biochemistry;Bioenergetics;Energy-Producing Organelles;Proteins;Regulatory Proteins;Molecular Cell Biology;Cellular Structures;Subcellular Organelles;Signal Transduction;Signaling Cascades;Apoptotic Signaling Cascade;Signaling in Cellular Processes;Apoptotic Signaling;Cell Death;Cellular Stress Responses|
|Publisher:||Public Library of Science|
|Description:||Most intrinsic death signals converge into the activation of pro-apoptotic BCL-2 family members BAX and BAK at the mitochondria, resulting in the release of cytochrome c and apoptosome activation. Chronic endoplasmic reticulum (ER) stress leads to apoptosis through the upregulation of a subset of pro-apoptotic BH3-only proteins, activating BAX and BAK at the mitochondria. Here we provide evidence indicating that the full resistance of BAX and BAK double deficient (DKO) cells to ER stress is reverted by stimulation in combination with mild serum withdrawal. Cell death under these conditions was characterized by the appearance of classical apoptosis markers, caspase-9 activation, release of cytochrome c, and was inhibited by knocking down caspase-9, but insensitive to BCL-X\(_L\) overexpression. Similarly, the resistance of BIM and PUMA double deficient cells to ER stress was reverted by mild serum withdrawal. Surprisingly, BAX/BAK-independent cell death did not require Cyclophilin D (CypD) expression, an important regulator of the mitochondrial permeability transition pore. Our results suggest the existence of an alternative intrinsic apoptosis pathway emerging from a cross talk between the ER and the mitochondria.|
|URI:||Zamorano, Sebastián, Diego Rojas-Rivera, Fernanda Lisbona, Valentina Parra, Felipe A. Court, Rosario Villegas, Emily H. Cheng, Stanley J. Korsmeyer, Sergio Lavandero, and Claudio Hetz. 2012. A BAX/BAK and cyclophilin D-independent intrinsic apoptosis pathway. PLoS ONE 7(6): e37782.|
|Appears in Collections:||HSPH Scholarly Articles|
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