Building blocks of the apoptotic pore: how Bax and Bak are activated and oligomerize during apoptosis
- 25 October 2013
- journal article
- review article
- Published by Springer Science and Business Media LLC in Cell Death & Differentiation
- Vol. 21 (2), 196-205
- https://doi.org/10.1038/cdd.2013.139
Abstract
The central role of the Bcl-2 family in regulating apoptotic cell death was first identified in the 1980s. Since then, significant in-roads have been made in identifying the multiple members of this family, characterizing their form and function and understanding how their interactions determine whether a cell lives or dies. In this review we focus on the recent progress made in characterizing the proapoptotic Bcl-2 family members, Bax and Bak. This progress has resolved longstanding controversies, but has also challenged established theories in the apoptosis field. We will discuss different models of how these two proteins become activated and different 'modes' by which they are inhibited by other Bcl-2 family members. We will also discuss novel conformation changes leading to Bak and Bax oligomerization and speculate how these oligomers might permeabilize the mitochondrial outer membrane.Keywords
This publication has 121 references indexed in Scilit:
- Bax Exists in a Dynamic Equilibrium between the Cytosol and Mitochondria to Control Apoptotic PrimingMolecular Cell, 2013
- Bak apoptotic function is not directly regulated by phosphorylationCell Death & Disease, 2013
- Inhibition of Bax protects neuronal cells from oligomeric Aβ neurotoxicityCell Death & Disease, 2012
- Sphingolipid Metabolism Cooperates with BAK and BAX to Promote the Mitochondrial Pathway of ApoptosisCell, 2012
- A Unified Model of Mammalian BCL-2 Protein Family Interactions at the MitochondriaMolecular Cell, 2011
- Mitochondria in Apoptosis: Bcl-2 Family Members and Mitochondrial DynamicsDevelopmental Cell, 2011
- Bcl-xL Retrotranslocates Bax from the Mitochondria into the CytosolCell, 2011
- BH3-Triggered Structural Reorganization Drives the Activation of Proapoptotic BAXMolecular Cell, 2010
- Stepwise Activation of BAX and BAK by tBID, BIM, and PUMA Initiates Mitochondrial ApoptosisMolecular Cell, 2009
- The Membrane Topography of the Diphtheria Toxin T Domain Linked to the A Chain Reveals a Transient Transmembrane Hairpin and Potential Translocation MechanismsBiochemistry, 2009