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Mol Biol Cell 2009 Apr 01;208:2276-85. doi: 10.1091/mbc.e08-10-1056.
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Mitochondrial outer membrane proteins assist Bid in Bax-mediated lipidic pore formation.

Schafer B , Quispe J , Choudhary V , Chipuk JE , Ajero TG , Du H , Schneiter R , Kuwana T .

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.

PubMed ID: 19244344
PMC ID: PMC2669034
Article link: Mol Biol Cell
Grant support: [+]

Species referenced: Xenopus
Genes referenced: bax bcl2l11 bid

References [+] :
Almgren, Mixed micelles and other structures in the solubilization of bilayer lipid membranes by surfactants. 2000, Pubmed