ArticleCommunications biology2025
Hexokinase-I directly binds to a charged membrane-buried glutamate of mitochondrial VDAC1 and VDAC2.
Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Beyond Junk DNA: Emerging Roles of Non-Coding RNAs in Cancer and Therapeutic Innovation.Biomolecules · 2026Review
- Computational Insights into PB1-F2 Mediated Modulation of VDAC1: An Allosteric Mechanism in Mitochondrial Dysfunction.ACS omega · 2026Article
- Research progress on VDAC2 in mitochondrial dysfunction-related diseases.Molecular biology reports · 2026Review
- Mitochondrial Voltage-Dependent Anion Channel: From a Passive Pore to a Cellular Hub Through Protein Complexation.International journal of molecular sciences · 2026Review
- A pore is a pore is a pore (or a hub?): VDAC oligomerization in mitochondrial connectivity and modulation.Biochemical Society transactions · 2026Review
- Ceramide-rich extracellular vesicles as pathogenic biomarkers in traumatic brain injury.bioRxiv : the preprint server for biology · 2026Article
- Multiomics and Genomic Alteration Characterization Identifies VDAC1 as a Mitochondrial-Associated Biomarker in Pancreatic Cancer.Human mutation · 2026Article
- Mitochondrial membrane junction-mediated ATP channeling drives activity-dependent glucose metabolism.bioRxiv : the preprint server for biology · 2025Article
- Peri-mitochondrial actin filaments inhibit Parkin assembly by disrupting ER-mitochondria contacts.EMBO reports · 2025Article
- A Membrane-Disruptive Action of VBIT-4 Challenges Its Role as a Widely Used VDAC Oligomerization Inhibitor.bioRxiv : the preprint server for biology · 2025Article
- An integrative modelling approach to the mitochondrial cristae.Communications biology · 2025Article
- Hexokinase-I directly binds to a charged membrane-buried glutamate of mitochondrial VDAC1 and VDAC2.Communications biology · 2025Article
- Modulation of mitochondrial voltage dependent anion channel: studies on bilayer electrophysiology.Frontiers in physiology · 2025Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Binding of hexokinase HKI to mitochondrial voltage-dependent anion channels (VDACs) has far-reaching physiological implications. However, the structural basis of this interaction is unclear. Combining computer simulations with experiments in cells, we here show that complex assembly relies on intimate contacts between the N-terminal α-helix of HKI and a charged membrane-buried glutamate on the outer wall of VDAC1 and VDAC2. Protonation of this residue blocks complex formation in silico while acidification of the cytosol causes a reversable release of HKI from mitochondria. Membrane insertion of HKI occurs adjacent to the bilayer-facing glutamate where a pair of polar channel residues mediates a marked thinning of the cytosolic leaflet. Disrupting the membrane thinning capacity of VDAC1 dramatically impairs its ability to bind HKI in silico and in cells. Our data reveal key topological and mechanistic insights into HKI-VDAC complex assembly that may benefit the development of therapeutics to counter pathogenic imbalances in this process.
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