title: Regulating cell death at, on, and in membranes.
abstract: Bcl-2 family proteins are central regulators of apoptosis. Various family members are located in the cytoplasm, endoplasmic reticulum, and mitochondrial outer membrane in healthy cells. However during apoptosis most of the interactions between family members that determine the fate of the cell occur at the membranes of intracellular organelles. It has become evident that interactions with membranes play an active role in the regulation of Bcl-2 family protein interactions. Here we provide an overview of various models proposed to explain how the Bcl-2 family regulates apoptosis and discuss how membrane binding affects the structure and function of each of the three categories of Bcl-2 proteins (pro-apoptotic, pore-forming, and anti-apoptotic). We also examine how the Bcl-2 family regulates other aspects of mitochondrial and ER physiology relevant to cell death.
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Justin
authors.initials: J
authors.lastname: Kale
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Leber
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario L8N 3Z5, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada; Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario M4N 3M5, Canada; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada. Electronic address: david.andrews@sri.utoronto.ca.
authors.forename: David W
authors.initials: DW
authors.lastname: Andrews
mesh_terms: D000818:Animals; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D063154:Mitochondrial Dynamics; D008954:Models, Biological; D011487:Protein Conformation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2
keywords: Apoptosis; Bcl-2 family; Embedded Together; Endoplasmic reticulum; Membrane; Mitochondrion