Mitochondrial membrane permeabilisation by Bax/Bak.
Recent studies on cells derived from mice deficient in both multi-domain pro-apoptotic genes of the Bcl-2 family, Bax and Bak, suggest that one or other of these proteins are required for the release of apoptogens such as cytochrome c from mitochondria. In addition BH-3 only proteins of this family such as Bid are suggested to act as critical death inducing ligands via interactions with pro- and anti-apoptotic Bcl-2 family proteins with Bax or Bak at the mitochondrial surface. Despite this increase in knowledge it remains unclear precisely how Bak and Bax promote outer mitochondrial membrane (OMM) permeabilisation. We suggest that Bax and Bak may not operate in precisely the same manner and evaluate the current models for their function. We also consider the emerging information that lipid-protein interactions may be crucial to the actions of Bax and Bak.
Cancer Research UK Cellular and Molecular Pharmacology Group, School of Biological Sciences, University of Manchester, G38 Stopford Building, Oxford Road, Manchester M134 9PT, UK.
Mauro
M
Degli Esposti
Caroline
C
Dive
D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000378:metabolism; D002463:Cell Membrane Permeability; D019281:Dimerization; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D010455:Peptides / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D051023:BH3 Interacting Domain Death Agonist Protein; C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; C494815:Bid protein, mouse; D002352:Carrier Proteins; D008565:Membrane Proteins; D010455:Peptides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein