ArticleBritish journal of pharmacology2020
The antiarrhythmic compound efsevin directly modulates voltage-dependent anion channel 2 by binding to its inner wall and enhancing mitochondrial Ca
Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- Research progress on VDAC2 in mitochondrial dysfunction-related diseases.Molecular biology reports · 2026Review
- A pore is a pore is a pore (or a hub?): VDAC oligomerization in mitochondrial connectivity and modulation.Biochemical Society transactions · 2026Review
- Alogliptin Reduces Oxidative Stress in Cardiomyocytes and Ameliorates Diabetic Cardiomyopathy via the AURKB/NLGN2 Signaling.The Kaohsiung journal of medical sciences · 2026Article
- Anti-cancer drugs targeting the NADH-binding site of VDAC rewire channel electrophysiology and partially suppress cation selectivity.The FEBS journal · 2026Article
- A small molecule VDAC ligand inhibits ERAD and induces selective cancer cell death via disruption of calcium homeostasis.Nature communications · 2026Article
- Zebrafish in Cardiovascular Disease Research: from Model to Application.International journal of biological sciences · 2026Review
- VDAC2 primes myeloma cells for BAK-dependent apoptosis and represents a novel therapeutic target.Leukemia · 2025Article
- Metabolic remodelling in atrial fibrillation: manifestations, mechanisms and clinical implications.Nature reviews. Cardiology · 2024Review
- STING Suppresses Mitochondrial VDAC2 to Govern RCC Growth Independent of Innate Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- E as in Enigma: The Mysterious Role of the Voltage-Dependent Anion Channel Glutamate E73.International journal of molecular sciences · 2022Review
- VDAC2 as a novel target for heart failure: CaCell calcium · 2022Review
- Therapeutic Strategies Targeting Mitochondrial Calcium Signaling: A New Hope for Neurological Diseases?Antioxidants (Basel, Switzerland) · 2022Review
- Article
- VDAC regulation of mitochondrial calcium flux: From channel biophysics to disease.Cell calcium · 2021Review
- A Calcium Guard in the Outer Membrane: Is VDAC a Regulated Gatekeeper of Mitochondrial Calcium Uptake?International journal of molecular sciences · 2021Review
- Glutamate 73 Promotes Anti-arrhythmic Effects of Voltage-Dependent Anion Channel Through Regulation of Mitochondrial CaFrontiers in physiology · 2021Article
- Cellular and mitochondrial mechanisms of atrial fibrillation.Basic research in cardiology · 2020Review
- The antiarrhythmic compound efsevin directly modulates voltage-dependent anion channel 2 by binding to its inner wall and enhancing mitochondrial CaBritish journal of pharmacology · 2020Article
- Targeting the Multiple Physiologic Roles of VDAC With Steroids and Hydrophobic Drugs.Frontiers in physiology · 2020Review
- Mitochondrial and Sarcoplasmic Reticulum Interconnection in Cardiac Arrhythmia.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
background and purposeThe synthetic compound efsevin was recently identified to suppress arrhythmogenesis in models of cardiac arrhythmia, making it a promising candidate for antiarrhythmic therapy. Its activity was shown to be dependent on the voltage-dependent anion channel 2 (VDAC2) in the outer mitochondrial membrane. Here, we investigated the molecular mechanism of the efsevin-VDAC2 interaction. EXPERIMENTAL APPROACH: To evaluate the functional interaction of efsevin and VDAC2, we measured currents through recombinant VDAC2 in planar lipid bilayers. Using molecular ligand-protein docking and mutational analysis, we identified the efsevin binding site on VDAC2. Finally, physiological consequences of the efsevin-induced modulation of VDAC2 were analysed in HL-1 cardiomyocytes. KEY
resultsIn lipid bilayers, efsevin reduced VDAC2 conductance and shifted the channel's open probability towards less anion-selective closed states. Efsevin binds to a binding pocket formed by the inner channel wall and the pore-lining N-terminal α-helix. Exchange of amino acids N207, K236 and N238 within this pocket for alanines abolished the channel's efsevin-responsiveness. Upon heterologous expression in HL-1 cardiomyocytes, both channels, wild-type VDAC2 and the efsevin-insensitive VDAC2 CONCLUSION AND IMPLICATIONS: In summary, our data indicate a direct interaction of efsevin with VDAC2 inside the channel pore that leads to modified gating and results in enhanced SR-mitochondria Ca
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