VDAC1 — Voltage Dependent Anion Channel 1

VDAC1 — Voltage Dependent Anion Channel 1

VDAC1 — Voltage Dependent Anion Channel 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">VDAC1 — Voltage Dependent Anion Channel 1</th> [@madesh2001]
</tr> [@yu2020]
<tr> [@vdac2019]
<td class="label">Symbol</td> [@thinnes2014]
<td><strong>VDAC1</strong></td> [@giorgio2018]
</tr>
<tr>
<td class="label">Full Name</td>
<td>Voltage Dependent Anion Channel 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>5q31</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/7416" target="_blank">7416</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000110833" target="_blank">ENSG00000110833</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P21796" target="_blank">P21796</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Parkinson's Disease](/diseases/parkinsons-disease), [Alzheimer's Disease](/diseases/alzheimers), [ALS](/diseases/als), [Huntington's Disease](/diseases/huntingtons)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain, Heart, Liver, Kidney</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Information</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">Mitochondrial porin, ATP/ADP transporter, mPTP component</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a hre

VDAC1 — Voltage Dependent Anion Channel 1

VDAC1 — Voltage Dependent Anion Channel 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">VDAC1 — Voltage Dependent Anion Channel 1</th> [@madesh2001]
</tr> [@yu2020]
<tr> [@vdac2019]
<td class="label">Symbol</td> [@thinnes2014]
<td><strong>VDAC1</strong></td> [@giorgio2018]
</tr>
<tr>
<td class="label">Full Name</td>
<td>Voltage Dependent Anion Channel 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>5q31</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/7416" target="_blank">7416</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000110833" target="_blank">ENSG00000110833</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P21796" target="_blank">P21796</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Parkinson's Disease](/diseases/parkinsons-disease), [Alzheimer's Disease](/diseases/alzheimers), [ALS](/diseases/als), [Huntington's Disease](/diseases/huntingtons)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain, Heart, Liver, Kidney</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Information</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">Mitochondrial porin, ATP/ADP transporter, mPTP component</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">Alzheimer's disease</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">280 edges</a></td>
</tr>
</table>

Pathway Diagram

VDAC1 — Voltage Dependent Anion Channel 1

Introduction

Vdac1 — Voltage Dependent Anion Channel 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

VDAC1 (Voltage Dependent Anion Channel 1) is a gene located on chromosome 5q31 that encodes a voltage-dependent anion channel protein found in the outer mitochondrial membrane. VDAC1 is a crucial component of the mitochondrial permeability transition pore (mPTP) and regulates metabolite exchange between the cytosol and mitochondria.

Structure

VDAC1 is a 31 kDa β-barrel protein that forms voltage-gated channels in the mitochondrial outer membrane:

• β-barrel structure: Composed of 19 β-strands forming a hollow pore
• N-terminal α-helix: Located inside the channel, involved in gating
• Voltage sensor: Positive charges on the N-terminal domain respond to membrane potential
• NADH binding site: Located in the N-terminal region
• ATP binding site: C-terminal region interacts with nucleotides

Function

VDAC1 encodes the voltage-dependent anion channel 1, also known as porin. This protein forms large, voltage-gated channels in the outer mitochondrial membrane that allow the passage of small molecules (<5 kDa) including ATP, ADP, ions, and metabolites.

Mitochondrial Metabolism

• ATP/ADP exchange: VDAC1 allows ATP produced in mitochondria to exit to the cytosol while permitting ADP to enter
• Calcium handling: Regulates mitochondrial Ca²⁺ uptake and release
• Metabolite flux: Permits passage of Krebs cycle intermediates, nucleotides, and ions
• [ROS](/entities/reactive-oxygen-species) signaling: Modulates release of reactive oxygen species

Apoptosis Regulation

VDAC1 plays a central role in apoptosis:

• mPTP component: VDAC1 is a key component of the mitochondrial permeability transition pore
• Cytochrome c release: VDAC1 oligomerization facilitates cytochrome c release
• Pro-apoptotic interactions: Interacts with pro-apoptotic proteins (Bax, Bak, tBid)
• Anti-apoptotic effects: VDAC1-hexamer interactions with Bcl-2 family proteins

Cellular Energy Metabolism

• Metabolic coupling: Couples cytosolic and mitochondrial metabolism
• Creatine kinase shuttle: Works with mitochondrial creatine kinase
• Hexokinase binding: Interaction with hexokinase enhances glycolysis

Brain Expression

VDAC1 is ubiquitously expressed, with high levels in brain, heart, liver, and kidney. In the brain, it is expressed in [neurons](/entities/neurons) and glia throughout the [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), basal ganglia, and cerebellum. [Astrocytes](/entities/astrocytes) and [microglia](/entities/microglia) also express VDAC1, with elevated levels in reactive states.

Role in Neurodegenerative Diseases

Parkinson's Disease

VDAC1 is critically involved in PD pathophysiology:

• Mitochondrial dysfunction: VDAC1 dysfunction contributes to mitochondrial defects in dopaminergic neurons
• Complex I deficiency: VDAC1 interacts with damaged complex I subunits
• [α-Synuclein](/proteins/alpha-synuclein) interactions: α-Synuclein oligomers can bind to VDAC1, forming abnormal channels
• Apoptosis: Enhanced VDAC1-mediated cytochrome c release in PD neurons
• Therapeutic target: VDAC1 modulators are being explored for PD treatment

Alzheimer's Disease

VDAC1 involvement in AD:

• Amyloid-β effects: [Aβ](/proteins/amyloid-beta) interacts with VDAC1, altering channel function
• Mitochondrial dysfunction: VDAC1 contributes to mitochondrial bioenergetic deficits
• Calcium dysregulation: Altered mitochondrial Ca²⁺ handling through VDAC1
• Energy failure: Reduced ATP export via VDAC1 in neurons
• Apoptosis: Enhanced VDAC1 oligomerization and cytochrome c release

Amyotrophic Lateral Sclerosis

VDAC1 in ALS:

• Mitochondrial dysfunction: Central to motor neuron mitochondrial defects
• Mutant SOD1: Mutant SOD1 can interact with VDAC1, disrupting function
• Energy crisis: Impaired ATP production and export
• Apoptotic pathways: VDAC1-mediated apoptosis contributes to motor neuron loss

Huntington's Disease

VDAC1 involvement in HD:

• Mutant [huntingtin](/proteins/huntingtin): Interacts with VDAC1, impairing channel function
• Energy deficit: Reduced mitochondrial ATP export
• Calcium dysregulation: Altered mitochondrial calcium handling
• Apoptosis: Enhanced VDAC1-dependent cell death

Post-Translational Modifications

VDAC1 is modified by:

• Phosphorylation: Multiple serine/threonine phosphorylation sites (PKA, PKC)
• Oxidation: ROS can oxidize VDAC1 cysteine residues
• Nitrosylation: S-nitrosylation affects channel function
• Acetylation: Lysine acetylation modulates interactions

Interactions

VDAC1 interacts with multiple proteins:

• Metabolic enzymes: Hexokinase, creatine kinase, glyceraldehyde-3-phosphate dehydrogenase
• Bcl-2 family: Bcl-2, Bcl-xL (anti-apoptotic), Bax, Bak (pro-apoptotic)
• Cytoskeletal proteins: Tubulin, actin
• Ion channels: mitochondrial calcium uniporter (MCU)
• Proteins: Hsp90, PARK2 (Parkin)

Therapeutic Implications

Targeting VDAC1:

• VDAC1 modulators: Small molecules that regulate VDAC1 activity
• Apoptosis inhibitors: Blocking VDAC1 oligomerization
• Metabolic enhancers: Improving mitochondrial function
• Neuroprotective agents: Targeting VDAC1-mediated pathways

Biomarker Potential

VDAC1 as a biomarker:

• [Blood-brain barrier](/entities/blood-brain-barrier) dysfunction: VDAC1 in CSF indicates mitochondrial damage
• Disease progression: VDAC1 levels correlate with disease severity
• Therapeutic monitoring: Changes with treatment response

See Also

• [VDAC1 Protein](/proteins/vdac1-protein)
• [Mitochondria](/entities/mitochondria)
• [Mitochondrial Permeability Transition Pore](/entities/mptp)
• [Apoptosis](/entities/apoptosis)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [ALS](/diseases/als)
• [Huntington's Disease](/diseases/huntingtons)

External Links

• [UniProt: P21796](https://www.uniprot.org/uniprot/P21796)
• [NCBI Gene: VDAC1](https://www.ncbi.nlm.nih.gov/gene/7416)
• [Ensembl: ENSG00000110833](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000110833)
• [VDAC Database](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997642/)

Background

The study of Vdac1 — Voltage Dependent Anion Channel 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

Pathway Diagram

The following diagram shows the key molecular relationships involving VDAC1 — Voltage Dependent Anion Channel 1 discovered through SciDEX knowledge graph analysis: