ArticleThe Journal of biological chemistry2014
Acidification asymmetrically affects voltage-dependent anion channel implicating the involvement of salt bridges.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- A membrane-disruptive action of VBIT-4 challenges its role as a widely used VDAC1 oligomerization inhibitor.eLife · 2026Article
- Linking cellular metabolism to mitochondrial outer membrane potential.Mitochondrion · 2026Article
- Elliptical β-barrel deformation underlies gating in VDAC1.Protein science : a publication of the Protein Society · 2026Article
- A small molecule VDAC ligand inhibits ERAD and induces selective cancer cell death via disruption of calcium homeostasis.Nature communications · 2026Article
- Conformational plasticity of mitochondrial VDAC2 controls the kinetics of its interaction with cytosolic proteins.Science advances · 2025Article
- Gating of β-Barrel Protein Pores, Porins, and Channels: An Old Problem with New Facets.International journal of molecular sciences · 2023Review
- The Single Residue K12 Governs the Exceptional Voltage Sensitivity of Mitochondrial Voltage-Dependent Anion Channel Gating.Journal of the American Chemical Society · 2022Article
- Restricting α-synuclein transport into mitochondria by inhibition of α-synuclein-VDAC complexation as a potential therapeutic target for Parkinson's disease treatment.Cellular and molecular life sciences : CMLS · 2022Article
- A Deep Dive into VDAC1 Conformational Diversity Using All-Atom Simulations Provides New Insights into the Structural Origin of the Closed States.International journal of molecular sciences · 2022Article
- Exploring lipid-dependent conformations of membrane-bound α-synuclein with the VDAC nanopore.Biochimica et biophysica acta. Biomembranes · 2021Article
- Article
- VDAC Gating Thermodynamics, but Not Gating Kinetics, Are Virtually Temperature Independent.Biophysical journal · 2020Article
- Molecular mechanism of olesoxime-mediated neuroprotection through targeting α-synuclein interaction with mitochondrial VDAC.Cellular and molecular life sciences : CMLS · 2020Article
- Cell organelles as targets of mammalian cadmium toxicity.Archives of toxicology · 2020Review
- A lower affinity to cytosolic proteins reveals VDAC3 isoform-specific role in mitochondrial biology.The Journal of general physiology · 2020Article
- Targeting the Multiple Physiologic Roles of VDAC With Steroids and Hydrophobic Drugs.Frontiers in physiology · 2020Review
- Multiple neurosteroid and cholesterol binding sites in voltage-dependent anion channel-1 determined by photo-affinity labeling.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Article
- Assessing the role of residue E73 and lipid headgroup charge in VDAC1 voltage gating.Biochimica et biophysica acta. Bioenergetics · 2019Article
- Structure of voltage-dependent anion channel-tethered bilayer lipid membranes determined using neutron reflectivity.Acta crystallographica. Section D, Structural biology · 2018Article
- Determining the molecular basis of voltage sensitivity in membrane proteins.The Journal of general physiology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
The voltage-dependent anion channel (VDAC) is the major pathway for ATP, ADP, and other respiratory substrates through the mitochondrial outer membrane, constituting a crucial point of mitochondrial metabolism regulation. VDAC is characterized by its ability to "gate" between an open and several "closed" states under applied voltage. In the early stages of tumorigenesis or during ischemia, partial or total absence of oxygen supply to cells results in cytosolic acidification. Motivated by these facts, we investigated the effects of pH variations on VDAC gating properties. We reconstituted VDAC into planar lipid membranes and found that acidification reversibly increases its voltage-dependent gating. Furthermore, both VDAC anion selectivity and single channel conductance increased with acidification, in agreement with the titration of the negatively charged VDAC residues at low pH values. Analysis of the pH dependences of the gating and open channel parameters yielded similar pKa values close to 4.0. We also found that the response of VDAC gating to acidification was highly asymmetric. The presumably cytosolic (cis) side of the channel was the most sensitive to acidification, whereas the mitochondrial intermembrane space (trans) side barely responded to pH changes. Molecular dynamic simulations suggested that stable salt bridges at the cis side, which are susceptible to disruption upon acidification, contribute to this asymmetry. The pronounced sensitivity of the cis side to pH variations found here in vitro might provide helpful insights into the regulatory role of VDAC in the protective effect of cytosolic acidification during ischemia in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.