title: The BCL-2 family of proteins and mitochondrial outer membrane permeabilisation.
abstract: Apoptosis is a form of programmed cell death critical for the development and homeostasis of multicellular organisms. A key event within the mitochondrial pathway to apoptosis is the permeabilisation of the mitochondrial outer membrane (MOM), a point of no return in apoptotic progression. This event is governed by a complex interplay of interactions between BCL-2 family members. Here we discuss the roles of opposing factions within the family. We focus on the structural details of these interactions, how they promote or prevent apoptosis and recent developments towards understanding the conformational changes of BAK and BAX that lead to MOM permeabilisation. These interactions and structural insights are of particular interest for drug discovery, as highlighted by the development of therapeutics that target pro-survival family members and restore apoptosis in cancer cells.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Birkinshaw
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: czabotar@wehi.edu.au.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Czabotar
mesh_terms: D000818:Animals; D017209:Apoptosis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D010539:Permeability; D011487:Protein Conformation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2
keywords: Apoptosis; BAK; BAX; BCL-2 family proteins; Mitochondrial outer membrane permeabilisation; Oligomers