title: cBid, Bax and Bcl-xL exhibit opposite membrane remodeling activities.
abstract: The proteins of the Bcl-2 family have a crucial role in mitochondrial outer membrane permeabilization during apoptosis and in the regulation of mitochondrial dynamics. Current models consider that Bax forms toroidal pores at mitochondria that are responsible for the release of cytochrome c, whereas Bcl-xL inhibits pore formation. However, how Bcl-2 proteins regulate mitochondrial fission and fusion remains poorly understood. By using a systematic analysis at the single vesicle level, we found that cBid, Bax and Bcl-xL are able to remodel membranes in different ways. cBid and Bax induced a reduction in vesicle size likely related to membrane tethering, budding and fission, besides membrane permeabilization. Moreover, they are preferentially located at highly curved membranes. In contrast, Bcl-xL not only counterbalanced pore formation but also membrane budding and fission. Our findings support a mechanism of action by which cBid and Bax induce or stabilize highly curved membranes including non-lamellar structures. This molecular activity reduces the energy for membrane remodeling, which is a necessary step in toroidal pore formation, as well as membrane fission and fusion, and provides a common mechanism that links the two main functions of Bcl-2 proteins.
authors.affiliation: Membrane Biophysics, Max Planck Institute for Intelligent Systems, Heisenbergstrasse 3, Stuttgart 70569, Germany.|German Cancer Research Center, Im Neuenheimer Feld 267, Heidelberg 69120, Germany.|Membrane Biophysics, Interfaculty Institute of Biochemistry, Eberhard Karls University Tübingen, Hoppe-Seyler-Strasse 4, Tübingen 72076, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Bleicken
authors.affiliation: CellNetworks, Bioquant, Heidelberg University, Im Neuenheimer Feld 267, Heidelberg, 69120, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Hofhaus
authors.affiliation: Membrane Biophysics, Max Planck Institute for Intelligent Systems, Heisenbergstrasse 3, Stuttgart 70569, Germany.|German Cancer Research Center, Im Neuenheimer Feld 267, Heidelberg 69120, Germany.|Membrane Biophysics, Interfaculty Institute of Biochemistry, Eberhard Karls University Tübingen, Hoppe-Seyler-Strasse 4, Tübingen 72076, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Ugarte-Uribe
authors.affiliation: CellNetworks, Bioquant, Heidelberg University, Im Neuenheimer Feld 267, Heidelberg, 69120, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schröder
authors.affiliation: Membrane Biophysics, Max Planck Institute for Intelligent Systems, Heisenbergstrasse 3, Stuttgart 70569, Germany.|German Cancer Research Center, Im Neuenheimer Feld 267, Heidelberg 69120, Germany.|Membrane Biophysics, Interfaculty Institute of Biochemistry, Eberhard Karls University Tübingen, Hoppe-Seyler-Strasse 4, Tübingen 72076, Germany.
authors.forename: A J
authors.initials: AJ
authors.lastname: García-Sáez
mesh_terms: D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D008954:Models, Biological; D010539:Permeability; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D053835:Unilamellar Liposomes / Q000737:chemistry / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D011994:Recombinant Proteins; D053835:Unilamellar Liposomes; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein