Building blocks of the apoptotic pore: how Bax and Bak are activated and oligomerize during apoptosis

Cell Death Differ. 2014 Feb;21(2):196-205. doi: 10.1038/cdd.2013.139. Epub 2013 Oct 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis*
  • Humans
  • Mitochondrial Membranes / metabolism*
  • Protein Binding
  • Protein Multimerization*
  • bcl-2 Homologous Antagonist-Killer Protein / chemistry*
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism*
  • bcl-2-Associated X Protein / chemistry*
  • bcl-2-Associated X Protein / metabolism*


  • BAK1 protein, human
  • BAX protein, human
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein