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Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
Published on: June 1, 2022
Mitochondrial Voltage-Dependent Anion Channel: From a Passive Pore to a Cellular Hub Through Protein Complexation
Megha Rajendran1, Sergey M Bezrukov1, Tatiana K Rostovtseva1
1Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
International Journal of Molecular Sciences
|July 15, 2026
Summary
Voltage-dependent anion channel (VDAC) interactions with proteins, not just pore structure, dictate isoform function. This protein complexation governs VDAC
Area of Science:
- Mitochondrial biology
- Molecular cell biology
- Biophysics
Background:
- The voltage-dependent anion channel (VDAC) is crucial for mitochondrial transport.
- VDAC isoforms (VDAC1-3) share structural similarity but differ in protein interactions.
- VDAC acts as a hub for protein complexation, influencing its function.
Purpose of the Study:
- To review the molecular mechanisms and physiological roles of VDAC complexation with various protein partners.
- To evaluate the evidence for VDAC isoform specificity in these interactions.
- To identify knowledge gaps in VDAC complexation and its implications.
Main Methods:
- Literature review of structural, biophysical, and genetic studies on VDAC complexes.
- Analysis of VDAC interactions with hexokinase, tubulin, α-synuclein, BCL-2 family proteins, and TOM complex.
- Evaluation of isoform-specific binding affinities and functional consequences.
Main Results:
- VDAC isoform function is primarily determined by differential protein binding affinities, not solely pore architecture.
- Specific VDAC complexes exhibit isoform selectivity, impacting cellular processes.
- Mechanistic understanding varies across different VDAC-partner interactions.
Conclusions:
- Differential VDAC complexation is a key determinant of functionally nonredundant isoform contributions.
- This principle impacts understanding of mitochondrial diseases like cancer and neurodegeneration.
- Targeting VDAC complexation offers therapeutic potential for mitochondria-associated pathologies.
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