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Updated: Sep 16, 2025

Modified Annexin V/Propidium Iodide Apoptosis Assay For Accurate Assessment of Cell Death
Published on: April 24, 2011
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.
Abstract:
VDAC1, a large conductance channel in the outer mitochondrial membrane, plays a crucial role in mitochondrial physiology. VDAC1 supports cellular metabolism and survival by serving as a mitochondrial Ca2+-uptake and ATP-exit system. Conversely, VDAC1 also contributes to apoptosis by forming oligomeric pores mediating cytochrome c release. Recently, Oflaz et al., EMBO J, 2025, identified the Ca2+-binding protein Annexin A5 as a dynamic, Ca2+-dependent switch that enhances VDAC1's Ca2+-transport function while at the same time preventing pro-apoptotic VDAC1 oligomer formation.
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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