Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells

B Antonsson1, S Montessuit, B Sanchez

  • 1Serono Pharmaceutical Research Institute, Serono International S.A., 14 chemin des Aulx, CH-1228 Plan-les Ouates, Geneva, Switzerland. bruno.antonsson@serono.com

Insights

Bax protein oligomerization is essential for apoptosis. This process involves Bax forming large complexes integrated into the mitochondrial membrane, leading to cytochrome c release.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Bax is a proapoptotic protein in the Bcl-2 family.
  • Bax induces cytochrome c release from mitochondria.
  • In HeLa cells, Bax exists as a monomer in the cytosol and weakly associated with mitochondria.

Purpose of the Study:

  • To investigate the molecular mechanism of Bax-mediated apoptosis.
  • To characterize Bax oligomerization and its role in cytochrome c release.

Main Methods:

  • Apoptosis induction in HeLa cells using staurosporine or UV irradiation.
  • Analysis of Bax molecular weight and mitochondrial association using gel filtration.
  • Investigating the interaction of Bax with mitochondrial membrane proteins.

Main Results:

  • Staurosporine or UV irradiation treatment induced Bax oligomerization into 96,000 and 260,000 Da complexes.
  • These Bax oligomers integrated into the mitochondrial membrane.
  • Bcl-2 inhibited Bax oligomerization and mitochondrial insertion.
  • Specific mitochondrial proteins did not coelute with Bax oligomers.

Conclusions:

  • Bax oligomerization is a critical step for its proapoptotic activity.
  • Bax oligomers/complexes may form the cytochrome c-conducting channel in the outer mitochondrial membrane.

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