Bax monomers form dimer units in the membrane that further self-assemble into multiple oligomeric species.

Y Subburaj, K Cosentino, M Axmann, E Pedrueza-Villalmanzo, E Hermann, S Bleicken, J Spatz, AJ García-Sáez

Research output: Contribution to journalArticlepeer-review

86 Citations (Scopus)

Abstract

Bax is a key regulator of apoptosis that mediates the release of cytochrome c to the cytosol via oligomerization in the outer mitochondrial membrane before pore formation. However, the molecular mechanism of Bax assembly and regulation by other Bcl-2 members remains obscure. Here, by analysing the stoichiometry of Bax oligomers at the single-molecule level, we find that Bax binds to the membrane in a monomeric state and then self-assembles in <1min. Strikingly, active Bax does not exist in a unique oligomeric state, but as several different species based on dimer units. Moreover, we show that cBid activates Bax without affecting its assembly, while Bcl-xL induces the dissociation of Bax oligomers. On the basis of our experimental data and theoretical modelling, we propose a new mechanism for the molecular pathway of Bax assembly to form the apoptotic pore.

Original languageEnglish
Article number8042
Pages (from-to)8042
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 14 Aug 2015

Keywords

  • Lipid Bilayers
  • Microscopy/methods
  • Protein Binding
  • Spectrometry, Fluorescence/methods
  • bcl-2-Associated X Protein/chemistry

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