VDAC1 as Janus in cell death and survival: Annexin A5 to the rescue

Ophélie Champion1, Jacek J Litewka2, Pawel E Ferdek3

  • 1KU Leuven, Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, Campus Gasthuisberg O/N-1 bus 802, Herestraat 49 BE-3000 Leuven, Belgium.

Cell Calcium
|July 8, 2025
PubMed

Insights

Outer mitochondrial membrane protein VDAC1 regulates cell metabolism and apoptosis. Annexin A5 acts as a calcium-dependent switch, enhancing VDAC1

Area of Science:

  • Mitochondrial physiology
  • Cellular metabolism
  • Apoptosis regulation

Background:

  • Voltage-dependent anion channel 1 (VDAC1) is a key outer mitochondrial membrane protein.
  • VDAC1 regulates cellular metabolism and survival via calcium uptake and ATP export.
  • VDAC1 also mediates apoptosis through cytochrome c release via pore formation.

Purpose of the Study:

  • To investigate the role of calcium-binding proteins in VDAC1 function.
  • To identify regulators of VDAC1's dual role in cell metabolism and apoptosis.

Main Methods:

  • Biochemical assays to study protein-protein interactions.
  • Electrophysiological recordings of VDAC1 channel activity.
  • Cell-based assays to assess VDAC1's role in calcium transport and apoptosis.

Main Results:

  • Annexin A5 was identified as a Ca2+-binding protein interacting with VDAC1.
  • Annexin A5 dynamically regulates VDAC1 channel activity in a Ca2+-dependent manner.
  • Annexin A5 enhances VDAC1's Ca2+-transport function while inhibiting pro-apoptotic VDAC1 oligomerization.

Conclusions:

  • Annexin A5 acts as a critical Ca2+-dependent switch for VDAC1.
  • This regulation balances VDAC1's roles in cellular metabolism and apoptosis.
  • Targeting the Annexin A5-VDAC1 interaction may offer therapeutic strategies for diseases involving mitochondrial dysfunction.

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