title: Bax-type apoptotic proteins porate pure lipid bilayers through a mechanism sensitive to intrinsic monolayer curvature.
abstract: During apoptosis, Bax-type proteins permeabilize the outer mitochondrial membrane to release intermembrane apoptogenic factors into the cytosol via a poorly understood mechanism. We have proposed that Bax and DeltaN76Bcl-x(L) (the Bax-like cleavage fragment of Bcl-x(L)) function by forming pores that are at least partially composed of lipids (lipidic pore formation). Since the membrane monolayer must bend during lipidic pore formation, we here explore the effect of intrinsic membrane monolayer curvature on pore formation. Nonlamellar lipids with positive intrinsic curvature such as lysophospholipids promoted membrane permeabilization, whereas nonlamellar lipids with negative intrinsic curvature such as diacylglycerol and phosphatidylethanolamine inhibited membrane permeabilization. The differential effects of nonlamellar lipids on membrane permeabilization were not correlated with lipid-induced changes in membrane binding or insertion of Bax or DeltaN76Bcl-x(L). Altogether, these results are consistent with a model whereby Bax-type proteins change the bending propensity of the membrane to form pores comprised at least in part of lipids in a structure of net positive monolayer curvature.
authors.affiliation: Laboratory of Cellular and Molecular Biophysics, NICHD/National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Gorka
authors.initials: G
authors.lastname: Basañez
authors.forename: Juanita C
authors.initials: JC
authors.lastname: Sharpe
authors.forename: Jennifer
authors.initials: J
authors.lastname: Galanis
authors.forename: Teresa B
authors.initials: TB
authors.lastname: Brandt
authors.forename: J Marie
authors.initials: JM
authors.lastname: Hardwick
authors.forename: Joshua
authors.initials: J
authors.lastname: Zimmerberg
mesh_terms: D017209:Apoptosis; D001669:Biochemical Phenomena; D001671:Biochemistry; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013053:Spectrophotometry; D051028:bcl-2-Associated X Protein
chemical_list: D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein