title: The membrane activity of BOK involves formation of large, stable toroidal pores and is promoted by cBID.
abstract: The BCL-2 family members are key regulators of the intrinsic apoptotic pathway, which is defined by permeabilization of the mitochondrial outer membrane by members of the BAX-like subfamily. BOK is classified as a BAX-like protein; however, its (patho-)physiological role remains largely unclear. We therefore assessed the membrane permeabilization potential of C-terminally truncated recombinant BOK, BOK∆C. We show that BOK∆Ccan permeabilize liposomes mimicking the composition of mitochondrial outer membrane, but not of endoplasmic reticulum, forming large and stable pores over time. Importantly, pore formation was enhanced by the presence of cBID and refractory to the addition of antiapoptotic BCL-XL. However, isolated mitochondria from Bax-/-Bak-/-cells were resistant to BOK-induced cytochrome c release, even in the presence of cBID. Taken together, we show that BOK∆Ccan permeabilize liposomes, and cooperate with cBID, but its role in directly mediating mitochondrial permeabilization is unclear and may underlie a yet to be determined negative regulation.
authors.affiliation: Institute of Pharmacology, University of Bern, Switzerland.
authors.forename: Yuniel
authors.initials: Y
authors.lastname: Fernández-Marrero
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bleicken
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Germany.
authors.forename: Kushal Kumar
authors.initials: KK
authors.lastname: Das
authors.affiliation: Institute of Pharmacology, University of Bern, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bachmann
authors.affiliation: Institute of Pharmacology, University of Bern, Switzerland.
authors.forename: Thomas
authors.identifier: 0000-0001-9906-874X
authors.initials: T
authors.lastname: Kaufmann
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Germany.
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Garcia-Saez
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002463:Cell Membrane Permeability / Q000235:genetics*; D045304:Cytochromes c / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics; D055786:Gene Knockout Techniques; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D051336:Mitochondrial Membranes / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051020:bcl-X Protein / Q000235:genetics
chemical_list: C494812:Bcl2l1 protein, mouse; C111858:Bok protein, mouse; D008081:Liposomes; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051020:bcl-X Protein; D045304:Cytochromes c
keywords: 
  BOK
  ; apoptosis; liposome; mitochondria; pore