Lipidic pore formation by the concerted action of proapoptotic BAX and tBID

Oihana Terrones, Bruno Antonsson, Hirohito Yamaguchi, Hong Gang Wang, Jihua Liu, Ray M. Lee, Andreas Herrmann, Gorka Basañez

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188 Scopus citations

Abstract

BCL-2 homology 3 (BH3)-only proteins of the BCL-2 family such as tBID and BIMEL assist BAX-type proteins to breach the permeability barrier of the outer mitochondrial membrane, thereby allowing cytoplasmic release of cytochrome c and other active inducers of cell death normally confined to the mitochondrial inter-membrane space. However, the exact mechanism by which tBID and BIMEL aid BAX and its close homologues in this mitochondrial protein release remains enigmatic. Here, using pure lipid vesicles, we provide evidence that tBID acts in concert with BAX to 1) form large membrane openings through both BH3-dependent and BH3-independent mechanisms, 2) cause lipid transbilayer movement concomitant with membrane permeabilization, and 3) disrupt the lipid bilayer structure of the membrane by promoting positive monolayer curvature stress. None of these effects were observed with BAX when BIM EL was substituted for tBID. Based on these data, we propose a novel model in which tBID assists BAX not only via protein-protein but also via protein-lipid interactions to form lipidic pore-type non-bilayer structures in the outer mitochondrial membrane through which intermembrane prodeath molecules exit mitochondria during apoptosis.

Original languageEnglish (US)
Pages (from-to)30081-30091
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number29
DOIs
StatePublished - Jul 16 2004

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Terrones, O., Antonsson, B., Yamaguchi, H., Wang, H. G., Liu, J., Lee, R. M., Herrmann, A., & Basañez, G. (2004). Lipidic pore formation by the concerted action of proapoptotic BAX and tBID. Journal of Biological Chemistry, 279(29), 30081-30091. https://doi.org/10.1074/jbc.M313420200