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Schafer B, Quispe J, Choudhary V, Chipuk JE, Ajero TG, Du H, Schneiter R, Kuwana T.
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Mitochondrial outer membrane permeabilization (MOMP) is a critical step in apoptosis and is regulated by Bcl-2 family proteins. In vitro systems using cardiolipin-containing liposomes have demonstrated the key features of MOMP induced by Bax and cleaved Bid; however, the nature of the "pores" and how they are formed remain obscure. We found that mitochondrial outer membranes contained very little cardiolipin, far less than that required for liposome permeabilization, despite their responsiveness to Bcl-2 family proteins. Strikingly, the incorporation of isolated mitochondrial outer membrane (MOM) proteins into liposomes lacking cardiolipin conferred responsiveness to cleaved Bid and Bax. Cardiolipin dependence was observed only when permeabilization was induced with cleaved Bid but not with Bid or Bim BH3 peptide or oligomerized Bax. Therefore, we conclude that MOM proteins specifically assist cleaved Bid in Bax-mediated permeabilization. Cryoelectron microscopy of cardiolipin-liposomes revealed that cleaved Bid and Bax produced large round holes with diameters of 25-100 nm, suggestive of lipidic pores. In sum, we propose that activated Bax induces lipidic pore formation and that MOM proteins assist cleaved Bid in this process in the absence of cardiolipin.
Almgren,
Mixed micelles and other structures in the solubilization of bilayer lipid membranes by surfactants.
2000, Pubmed
Almgren,
Mixed micelles and other structures in the solubilization of bilayer lipid membranes by surfactants.
2000,
Pubmed Antonsson,
Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells.
2001,
Pubmed Ardail,
Mitochondrial contact sites. Lipid composition and dynamics.
1990,
Pubmed Arnold,
Gene duplication of the eight-stranded beta-barrel OmpX produces a functional pore: a scenario for the evolution of transmembrane beta-barrels.
2007,
Pubmed Baines,
Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death.
2007,
Pubmed Basañez,
Bax-type apoptotic proteins porate pure lipid bilayers through a mechanism sensitive to intrinsic monolayer curvature.
2002,
Pubmed Basañez,
Bax, but not Bcl-xL, decreases the lifetime of planar phospholipid bilayer membranes at subnanomolar concentrations.
1999,
Pubmed Billen,
Bcl-XL inhibits membrane permeabilization by competing with Bax.
2008,
Pubmed Brown,
Caspase inhibition blocks cell death and results in cell cycle arrest in cytokine-deprived hematopoietic cells.
2007,
Pubmed Brown,
The role of apoptosis in cancer development and treatment response.
2005,
Pubmed Chipuk,
Do inducers of apoptosis trigger caspase-independent cell death?
2005,
Pubmed Colell,
GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation.
2007,
Pubmed Cory,
The Bcl2 family: regulators of the cellular life-or-death switch.
2002,
Pubmed Dejean,
Oligomeric Bax is a component of the putative cytochrome c release channel MAC, mitochondrial apoptosis-induced channel.
2005,
Pubmed Du,
Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition.
2000,
Pubmed Fesik,
Promoting apoptosis as a strategy for cancer drug discovery.
2005,
Pubmed Frederik,
Cryoelectron microscopy of liposomes.
2005,
Pubmed García-Sáez,
Pore formation by a Bax-derived peptide: effect on the line tension of the membrane probed by AFM.
2007,
Pubmed Goldstein,
The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant.
2000,
Pubmed Green,
Pharmacological manipulation of cell death: clinical applications in sight?
2005,
Pubmed Grinberg,
Mitochondrial carrier homolog 2 is a target of tBID in cells signaled to die by tumor necrosis factor alpha.
2005,
Pubmed Gross,
Mitochondrial carrier homolog 2: a clue to cracking the BCL-2 family riddle?
2005,
Pubmed Guihard,
The mitochondrial apoptosis-induced channel (MAC) corresponds to a late apoptotic event.
2004,
Pubmed Hardwick,
Bax, along with lipid conspirators, allows cytochrome c to escape mitochondria.
2002,
Pubmed Iverson,
Cardiolipin is not required for Bax-mediated cytochrome c release from yeast mitochondria.
2004,
Pubmed Johnsson,
Liposomes, disks, and spherical micelles: aggregate structure in mixtures of gel phase phosphatidylcholines and poly(ethylene glycol)-phospholipids.
2003,
Pubmed Knudson,
Mitochondria potential, bax "activation," and programmed cell death.
2008,
Pubmed Kuwana,
BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly.
2005,
Pubmed Kuwana,
Bcl-2-family proteins and the role of mitochondria in apoptosis.
2003,
Pubmed Kuwana,
Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane.
2002,
Pubmed
,
Xenbase Leber,
Embedded together: the life and death consequences of interaction of the Bcl-2 family with membranes.
2007,
Pubmed Lindsten,
The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues.
2000,
Pubmed Liu,
Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c.
1996,
Pubmed Lowe,
Intrinsic tumour suppression.
2004,
Pubmed Lucken-Ardjomande,
Contributions to Bax insertion and oligomerization of lipids of the mitochondrial outer membrane.
2008,
Pubmed Lucken-Ardjomande,
Bax activation and stress-induced apoptosis delayed by the accumulation of cholesterol in mitochondrial membranes.
2008,
Pubmed Lutter,
The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact sites.
2001,
Pubmed Lutter,
Cardiolipin provides specificity for targeting of tBid to mitochondria.
2000,
Pubmed McCarthy,
Inhibition of Ced-3/ICE-related proteases does not prevent cell death induced by oncogenes, DNA damage, or the Bcl-2 homologue Bak.
1997,
Pubmed Nechushtan,
Bax and Bak coalesce into novel mitochondria-associated clusters during apoptosis.
2001,
Pubmed Nechushtan,
Conformation of the Bax C-terminus regulates subcellular location and cell death.
1999,
Pubmed Ott,
Role of cardiolipin in cytochrome c release from mitochondria.
2007,
Pubmed Pautsch,
Strategy for membrane protein crystallization exemplified with OmpA and OmpX.
1999,
Pubmed Pautsch,
Structure of the outer membrane protein A transmembrane domain.
1998,
Pubmed Pavlov,
A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast.
2001,
Pubmed Polcic,
Cardiolipin and phosphatidylglycerol are not required for the in vivo action of Bcl-2 family proteins.
2005,
Pubmed Qian,
Structure of transmembrane pore induced by Bax-derived peptide: evidence for lipidic pores.
2008,
Pubmed Roucou,
Bax oligomerization in mitochondrial membranes requires tBid (caspase-8-cleaved Bid) and a mitochondrial protein.
2002,
Pubmed Roucou,
Bid induces cytochrome c-impermeable Bax channels in liposomes.
2002,
Pubmed Saito,
BAX-dependent transport of cytochrome c reconstituted in pure liposomes.
2000,
Pubmed Shai,
Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides.
1999,
Pubmed
,
Xenbase Shanmugavadivu,
Correct folding of the beta-barrel of the human membrane protein VDAC requires a lipid bilayer.
2007,
Pubmed Shimizu,
Electrophysiological study of a novel large pore formed by Bax and the voltage-dependent anion channel that is permeable to cytochrome c.
2000,
Pubmed Shimizu,
Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC.
1999,
Pubmed Sobko,
Effect of lipids with different spontaneous curvature on the channel activity of colicin E1: evidence in favor of a toroidal pore.
2004,
Pubmed Sorice,
Cardiolipin and its metabolites move from mitochondria to other cellular membranes during death receptor-mediated apoptosis.
2004,
Pubmed Suloway,
Automated molecular microscopy: the new Leginon system.
2005,
Pubmed Surrey,
Refolding and oriented insertion of a membrane protein into a lipid bilayer.
1992,
Pubmed Suzuki,
A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death.
2001,
Pubmed Tamm,
Folding and assembly of beta-barrel membrane proteins.
2004,
Pubmed Terrones,
Lipidic pore formation by the concerted action of proapoptotic BAX and tBID.
2004,
Pubmed Tilley,
Structural basis of pore formation by the bacterial toxin pneumolysin.
2005,
Pubmed Tilley,
The mechanism of pore formation by bacterial toxins.
2006,
Pubmed Verhagen,
Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins.
2000,
Pubmed Wei,
Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death.
2001,
Pubmed Xiang,
BAX-induced cell death may not require interleukin 1 beta-converting enzyme-like proteases.
1996,
Pubmed Yethon,
Interaction with a membrane surface triggers a reversible conformational change in Bax normally associated with induction of apoptosis.
2003,
Pubmed Youle,
The BCL-2 protein family: opposing activities that mediate cell death.
2008,
Pubmed
