Related Experiment Video
Updated: Aug 19, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Proapoptotic BAX and BAK control multiple initiator caspases
Antonio Ruiz-Vela1, Joseph T Opferman, Emily H-Y Cheng
1Howard Hughes Medical Institute, Department of Pathology and Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. aruiz@cnb.uam.es
Abstract:
BAX and BAK operate at both the mitochondria and endoplasmic reticulum (ER) to regulate the intrinsic apoptotic pathway. An unresolved issue is whether any caspases can be activated in response to intrinsic apoptotic signals in the absence of BAX and BAK. Following organelle-specific intrinsic stress signals, including DNA damage and ER stress, we detected no activation of CARD-containing caspases (initiator CASP)-1, -2, -9, -11 and -12 in Bax(-/-)Bak(-/-) doubly deficient (DKO) cells. BCL-2 overexpression in these DKO cells provided no further protection to their already strong protection from DNA damage and ER stress. Moreover, there was no activation of effector CASP-3 and -7 in DKO cells, consistent with the lack of initiator caspase activity and disfavouring a BAX, BAK-independent intrinsic apoptotic pathway to activate initiator caspases. Thus, BAX and BAK confer an essential gateway for the activation of caspases in the intrinsic apoptotic pathway.
Related Concept Videos
The Intrinsic Apoptotic Pathway
Caspases
The Extrinsic Apoptotic Pathway
Apoptosis
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Cellular Injury V: Apoptosis and Autophagy

