Apoptosis regulation at the mitochondria membrane level

Biochim Biophys Acta Biomembr. 2021 Dec 1;1863(12):183716. doi: 10.1016/j.bbamem.2021.183716. Epub 2021 Jul 31.


Mitochondrial outer membrane permeabilization (MOMP) is a key checkpoint in apoptosis that activates the caspase cascade and irreversibly causes the majority of cells to die. The proteins of the Bcl-2 family are master regulators of apoptosis that form a complex interaction network within the mitochondrial membrane that determines the induction of MOMP. This culminates in the activation of the effector members Bax and Bak, which permeabilize the mitochondrial outer membrane to mediate MOMP. Although the key role of Bax and Bak has been established, many questions remain unresolved regarding molecular mechanisms that control the apoptotic pore. In this review, we discuss the recent progress in our understanding of the regulation of Bax/Bak activity within the mitochondrial membrane.

Keywords: Apoptosis; BCL-2 proteins; Lipids; MOMP; Membrane dynamics; Protein-protein interaction.

Publication types

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

MeSH terms

  • Apoptosis / genetics*
  • Caspases / genetics
  • Humans
  • Mitochondria / genetics*
  • Mitochondrial Membranes*
  • Permeability*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • bcl-2 Homologous Antagonist-Killer Protein / genetics
  • bcl-2-Associated X Protein / genetics


  • BAK1 protein, human
  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • Caspases