VDAC3 Protein

VDAC3 Protein

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<div class="infobox-header">VDAC3 Protein</div>
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VDAC3 Structure
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<table class="infobox-data">
<tr><th>Protein Name</th><td>Voltage-Dependent Anion Channel 3</td></tr>
<tr><th>Gene</th><td>[VDAC3](/genes/vdac3)</td></tr>
<tr><th>UniProt ID</th><td><a href="https://www.uniprot.org/uniprot/Q9Y277" target="_blank">Q9Y277</a></td></tr>
<tr><th>PDB ID</th><td>4CMU, 4CNO</td></tr>
<tr><th>Molecular Weight</th><td>~34 kDa</td></tr>
<tr><th>Subcellular Localization</th><td>Outer mitochondrial membrane, Plasma membrane</td></tr>
<tr><th>Protein Family</th><td>VDAC/Porin family</td></tr>
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<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
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Introduction

VDAC3 (Voltage-Dependent Anion Channel 3) is a mitochondrial outer membrane protein that functions as a voltage-gated anion channel. VDAC3 is one of three VDAC isoforms in mammals (VDAC1, VDAC2, VDAC3) and plays critical roles in mitochondrial metabolism, [apoptosis](/entities/apoptosis) regulation, and cellular homeostasis. Recent research has implicated VDAC3 dysfunction in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease [1].

VDAC3 Protein

<div class="infobox infobox-protein">
<div class="infobox-header">VDAC3 Protein</div>
<div class="infobox-image">
<div style="background: linear-gradient(135deg, #2d1b4e 0%, #1a1a2e 100%); height: 150px; display: flex; align-items: center; justify-content: center; color: #fff; font-size: 12px; border-radius: 4px;">
VDAC3 Structure
</div>
</div>
<table class="infobox-data">
<tr><th>Protein Name</th><td>Voltage-Dependent Anion Channel 3</td></tr>
<tr><th>Gene</th><td>[VDAC3](/genes/vdac3)</td></tr>
<tr><th>UniProt ID</th><td><a href="https://www.uniprot.org/uniprot/Q9Y277" target="_blank">Q9Y277</a></td></tr>
<tr><th>PDB ID</th><td>4CMU, 4CNO</td></tr>
<tr><th>Molecular Weight</th><td>~34 kDa</td></tr>
<tr><th>Subcellular Localization</th><td>Outer mitochondrial membrane, Plasma membrane</td></tr>
<tr><th>Protein Family</th><td>VDAC/Porin family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Introduction

VDAC3 (Voltage-Dependent Anion Channel 3) is a mitochondrial outer membrane protein that functions as a voltage-gated anion channel. VDAC3 is one of three VDAC isoforms in mammals (VDAC1, VDAC2, VDAC3) and plays critical roles in mitochondrial metabolism, [apoptosis](/entities/apoptosis) regulation, and cellular homeostasis. Recent research has implicated VDAC3 dysfunction in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease [1].

Structure

Domain Architecture

VDAC3 possesses the characteristic porin fold:

• β-barrel structure: 19 β-strands forming a cylindrical barrel
• N-terminal α-helix: Located inside the pore, involved in channel gating
• Loop regions: External loops contain binding sites for various ligands and proteins

Key Structural Features

Post-Translational Modifications

• Phosphorylation: Tyrosine phosphorylation at multiple sites modulates channel activity
• Oxidation: [Reactive oxygen species](/entities/reactive-oxygen-species) (ROS) can modify cysteine residues
• S-nitrosylation: Regulates VDAC3 function in response to nitric oxide signaling

Normal Function

Channel Physiology

VDAC3 functions as a voltage-dependent anion channel:

Mitochondrial Function

VDAC3 is essential for:

• ATP/ADP exchange: Facilitates cytosolic energy exchange
• Calcium signaling: Participates in mitochondrial calcium uptake
• Apoptosis regulation: Modulates release of cytochrome c and other pro-apoptotic factors
• Mitochondrial dynamics: Influences mitochondrial morphology and distribution

Expression in the Nervous System

In [neurons](/entities/neurons), VDAC3 is enriched in:

• Synaptic terminals
• Dendritic mitochondria
• Axonal compartments

Role in Neurodegeneration

Alzheimer's Disease

VDAC3 contributes to AD pathogenesis through multiple mechanisms:

• Mitochondrial dysfunction: Altered VDAC3 activity leads to impaired energy metabolism
• [Amyloid-beta](/proteins/amyloid-beta) interaction: Aβ can bind to VDAC3, disrupting channel function
• Calcium dysregulation: Impaired calcium handling contributes to excitotoxicity
• Apoptosis: VDAC3 dysregulation promotes neuronal apoptosis [2]

Parkinson's Disease

In PD, VDAC3 dysfunction is implicated in:

• Mitophagy impairment: Altered VDAC3 affects PINK1/Parkin-mediated mitophagy
• Mitochondrial DNA damage: VDAC3 dysfunction increases susceptibility to mtDNA damage
• Dopaminergic neuron vulnerability: Energy deficits accelerate degeneration [3]

Huntington's Disease

VDAC3 plays a role in HD through:

• Metabolic deficits: Mutant [huntingtin](/proteins/huntingtin) impairs VDAC3 function
• Mitochondrial dysfunction: Contributes to energy failure in striatal neurons
• Calcium dysregulation: Exacerbates excitotoxic cell death [4]

Therapeutic Targeting

Therapeutic Strategies

• VDAC-targeting peptides that restore channel function
• Small molecules that normalize VDAC3 activity

• Coenzyme Q10
• L-carnitine
• Alpha-lipoic acid

• VDAC3 overexpression vectors
• CRISPR editing to enhance VDAC3 expression

Challenges

• isoform-specific targeting (VDAC1, VDAC2, VDAC3 have overlapping functions)
• [Blood-brain barrier](/entities/blood-brain-barrier) penetration
• Balancing channel activity (too open or too closed is problematic)

Key Publications

Related Pages

• [VDAC3 Gene](/genes/vdac3)
• [Mitochondrial Dynamics](/mechanisms/mitochondrial-dynamics)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Huntington's Disease](/diseases/huntington-disease)

References

See Also

• (Add relevant links here)

External Links

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