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A new view of the lethal apoptotic pore

Gorka Basañez1, Lucian Soane, J Marie Hardwick

  • 1Biophysics Unit, Spanish Science Research Council-CSIC and University of the Basque Country-UPV/EHU, Bilbao, Spain. gorka_basanez@ehu.es

Plos Biology
|October 11, 2012
PubMed

Insights

Researchers discovered a new factor essential for forming BAX-dependent apoptotic pores in mitochondria. This finding challenges the view of pores as solely protein structures and suggests membrane remodeling is involved in cell death.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Apoptosis is vital for multicellular life, and its dysregulation is linked to diseases like cancer.
  • Mitochondrial outer membrane pore formation, releasing cytochrome c, is a key event in apoptosis.
  • BCL-2 family proteins, particularly BAX, are known effectors of these apoptotic pores.

Purpose of the Study:

  • To investigate the molecular pathway and precise nature of apoptotic pores at the mitochondrial outer membrane.
  • To analyze the dynamics of BAX-dependent apoptotic pore formation in native mitochondrial outer membranes.

Main Methods:

  • Novel kinetic analysis of BAX-dependent apoptotic pore formation.
  • Recapitulation of pore formation dynamics in native mitochondrial outer membranes.

Main Results:

  • Identified a previously unknown outer mitochondrial membrane factor critical for BAX-mediated pore formation.
  • Challenged the model of apoptotic pores as purely proteinaceous BAX assemblies.
  • Provided evidence supporting the involvement of membrane remodeling in forming lipid-containing apoptotic pores.

Conclusions:

  • Apoptotic pore formation involves a novel mitochondrial factor and membrane remodeling.
  • The apoptotic pore is likely not exclusively a BAX protein assembly.
  • This research offers new insights into the mechanisms of programmed cell death.

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