NDUFV2 Gene

NDUFV2 Gene

Introduction

NDUFV2 (NADH:Ubiquinone Oxidoreductase Core Subunit V2) encodes a core subunit of mitochondrial complex I (NADH:ubiquinone oxidoreductase). It is a key component of the NADH dehydrogenase module and is essential for electron transfer from NADH to ubiquinone. Mutations in NDUFV2 are associated with mitochondrial complex I deficiency and neurodegenerative diseases.

Overview

NDUFV2 is a key subunit of complex I, part of the N-module responsible for NADH oxidation. It interacts closely with NDUFV1 and contains binding sites for the electron carriers involved in the initial steps of electron transfer. [@ndufv2021]

NDUFV2 Gene

Introduction

NDUFV2 (NADH:Ubiquinone Oxidoreductase Core Subunit V2) encodes a core subunit of mitochondrial complex I (NADH:ubiquinone oxidoreductase). It is a key component of the NADH dehydrogenase module and is essential for electron transfer from NADH to ubiquinone. Mutations in NDUFV2 are associated with mitochondrial complex I deficiency and neurodegenerative diseases.

Overview

NDUFV2 is a key subunit of complex I, part of the N-module responsible for NADH oxidation. It interacts closely with NDUFV1 and contains binding sites for the electron carriers involved in the initial steps of electron transfer. [@ndufv2021]

<div class="infobox infobox-gene"> [@mitochondrial2021]
<table> [@ndufv2020]
<tr><th colspan="2" style="background:#f0f0f0;">NADH:Ubiquinone Oxidoreductase Core Subunit V2</th></tr> [@coq2022]
<tr><td><strong>Gene Symbol</strong></td><td>NDUFV2</td></tr> [@ndufv2021a]
<tr><td><strong>Full Name</strong></td><td>NADH:Ubiquinone Oxidoreductase Core Subunit V2</td></tr> [@mitochondrial2020]
<tr><td><strong>Chromosome</strong></td><td>25p13</td></tr> [@complex2019]
<tr><td><strong>NCBI Gene ID</strong></td><td>[4729](https://www.ncbi.nlm.nih.gov/gene/4729)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[161017](https://www.omim.org/entry/161017)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>[ENSG00000170921](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000170921)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P23378](https://www.uniprot.org/uniprot/P23378)</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/lung-cancer" style="color:#ef9a9a">Lung Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">14 edges</a></td>
</tr>
</table>
</div>

Molecular Mechanism

NDUFV2 is essential for complex I function:

Electron Transfer

Complex I Structure

NDUFV2 is part of the N-module:

• NDUFV1: FMN binding
• NDUFV2: NADH binding site
• NDUFV3: Additional subunit
• Multiple Fe-S clusters for electron transfer

Function in Neurodegeneration

Parkinson's Disease

NDUFV2 dysfunction is linked to PD:

• Complex I deficiency: Documented in PD substantia nigra
• Oxidative stress: Increased [ROS](/entities/reactive-oxygen-species) from electron leak
• Dopaminergic neuron vulnerability: Energy deficit contributes to death
• [α-Synuclein](/proteins/alpha-synuclein) interaction: Mitochondrial dysfunction promotes aggregation

Alzheimer's Disease

NDUFV2 contributes to AD:

• Mitochondrial dysfunction: Early and prominent feature
• Energy deficit: Reduced ATP in affected brain regions
• Oxidative stress: Accumulation of oxidative damage
• Calcium dysregulation: Impaired mitochondrial homeostasis

Leigh Syndrome

NDUFV2 mutations cause:

• Progressive encephalopathy: Developmental regression
• Basal ganglia involvement: Characteristic lesions
• Lactic acidosis: Metabolic dysfunction

Huntington's Disease

NDUFV2 is implicated in HD:

• Complex I impairment: Documented in HD models
• Energy deficit: Contributes to neuronal dysfunction
• Oxidative damage: Increased ROS production

Therapeutic Targeting

NDUFV2-based therapies are under investigation:

| Agent | Mechanism | Status | Disease |
|-------|-----------|--------|---------|
| CoQ10 | Electron shuttle | Clinical trial | PD |
| Nicotinamide riboside | NAD+ precursor | Research | Mitochondrial disease |
| Mitochondrial peptides | Improve function | Preclinical | Neuroprotection |

Disease Associations

| Disease | Role | Evidence |
|---------|------|----------|
| Parkinson's Disease | Complex I deficiency | Reduced NDUFV2 in SN |
| Alzheimer's Disease | Mitochondrial dysfunction | Impaired complex I |
| Leigh syndrome | Primary deficiency | NDUFV2 mutations |
| Huntington's disease | Secondary deficiency | Complex I defects |

Expression

NDUFV2 is expressed in brain tissue:

• High expression in cerebral [cortex](/brain-regions/cortex)
• High expression in basal ganglia
• Expressed in [neurons](/entities/neurons)

See Also

• [NDUFV1 Gene](/genes/ndufv1) - Related complex I subunit
• [Complex I](/entities/electron-transport-chain) - Mitochondrial complex I
• [Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Alzheimer's Disease](/diseases/alzheimers-disease)

External Links

• [NCBI Gene: ndufv2](https://www.ncbi.nlm.nih.gov/gene/)
• [PubMed: ndufv2](https://pubmed.ncbi.nlm.nih.gov/?term=ndufv2+neurodegeneration)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving NDUFV2 Gene discovered through SciDEX knowledge graph analysis: