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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
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Published on: June 29, 2011

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Structural basis of apoptosis induction by the mitochondrial voltage-dependent anion channel

Melina Daniilidis1, Umut Günsel1,2, Georgios Broutzakis3

  • 1Structural Membrane Biochemistry and Bavarian NMR Center (BNMRZ), Department of Bioscience, School of Natural Sciences, Technical University of Munich, Garching, Germany.

Nature Communications
|October 28, 2025
PubMed

Insights

Voltage-dependent anion channel (VDAC) oligomers expose a key helix, initiating apoptosis. This VDAC pathway involves interaction with Bcl-xL and Bak, mimicking BH3-only proteins during mitochondrial stress.

Area of Science:

  • Mitochondrial biology
  • Cell death pathways
  • Structural biology

Background:

  • Voltage-dependent anion channel (VDAC) regulates mitochondrial metabolite transport.
  • VDAC oligomerization is linked to apoptosis, but mechanisms are unclear.

Purpose of the Study:

  • Elucidate the structural and mechanistic basis of VDAC-induced apoptosis.
  • Investigate VDAC1's role in apoptosis regulation.

Main Methods:

  • Cryo-electron microscopy (cryo-EM)
  • Nuclear magnetic resonance (NMR) spectroscopy
  • X-ray crystallography
  • Biochemical assays

Main Results:

  • VDAC1 oligomerization exposes its N-terminal α-helix (VDAC1-N).
  • VDAC1-N binds to the anti-apoptotic Bcl-xL protein.
  • VDAC1-N promotes Bak pore formation by neutralizing Bcl-xL, inducing apoptosis.

Conclusions:

  • VDAC1 acts as a pro-apoptotic factor by interacting with Bcl-xL and Bak.
  • This VDAC pathway resembles BH3-only protein function in apoptosis.
  • The VDAC pathway likely responds to mitochondrial stress or damage.

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