NDUFS8 — NADH:Ubiquinone Oxidoreductase Core Subunit S8

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NDUFS8 — NADH:Ubiquinone Oxidoreductase Core Subunit S8

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NDUFS8 — NADH:Ubiquinone Oxidoreductase Core Subunit S8

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">NDUFS8 — NADH:Ubiquinone Oxidoreductase Core Subunit S8</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>NDUFS8</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>NADH:Ubiquinone Oxidoreductase Core Subunit S8 (TYKY)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>19q13.42</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/4728" target="_blank">4728</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000110717" target="_blank">ENSG00000110717</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/602140" target="_blank">602140</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P51970" target="_blank">P51970</a></td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>210 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>23 kDa</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>Parkinson's Disease, Leigh Syndrome, Mitochondrial Complex I Deficiency</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain, Heart, Skeletal Muscle, Liver, Kidney</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">Alzhei

...

NDUFS8 — NADH:Ubiquinone Oxidoreductase Core Subunit S8

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">NDUFS8 — NADH:Ubiquinone Oxidoreductase Core Subunit S8</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>NDUFS8</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>NADH:Ubiquinone Oxidoreductase Core Subunit S8 (TYKY)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>19q13.42</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/4728" target="_blank">4728</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000110717" target="_blank">ENSG00000110717</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/602140" target="_blank">602140</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P51970" target="_blank">P51970</a></td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>210 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>23 kDa</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>Parkinson's Disease, Leigh Syndrome, Mitochondrial Complex I Deficiency</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain, Heart, Skeletal Muscle, Liver, Kidney</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">18 edges</a></td>
</tr>
</table>

NDUFS8 — NADH:Ubiquinone Oxidoreductase Core Subunit S8

Pathway / Interaction Diagram

Mermaid diagram (expand to render)

Introduction

NDUFS8 (NADH:Ubiquinone Oxidoreductase Core Subunit S8), also known as TYKY, encodes a critical iron-sulfur protein subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), the largest and most complex enzyme of the mitochondrial electron transport chain. Located on chromosome 19q13.42, the NDUFS8 protein is a 23 kDa subunit containing essential [4Fe-4S] iron-sulfur clusters that participate directly in electron transfer from NADH to ubiquinone[@brandt2006].

Mitochondrial Complex I deficiency is one of the most common mitochondrial disorders and is particularly relevant to Parkinson's disease pathogenesis. NDUFS8 plays a central role in maintaining Complex I function, and its dysfunction has been implicated in both rare mitochondrial encephalopathies and common neurodegenerative disorders[@perier2012][@schapira2012].

The gene is catalogued as NCBI Gene ID [4728](https://www.ncbi.nlm.nih.gov/gene/4728), OMIM [602140](https://omim.org/entry/602140), and UniProt [P51970](https://www.uniprot.org/uniprot/P51970). Mutations in NDUFS8 cause isolated Complex I deficiency, leading to diverse clinical phenotypes ranging from severe infantile encephalopathies like Leigh syndrome to late-onset neurodegenerative diseases[@wiedemann2006].

Gene and Protein Structure

Gene Organization

The NDUFS8 gene spans approximately 6.5 kb on chromosome 19q13.42 and consists of 5 exons encoding a 210-amino acid protein. The gene is transcribed from a housekeeping promoter that drives constitutive expression in tissues with high mitochondrial energy demands. Alternative splicing produces multiple transcript variants, though the functional significance of these variants in neuronal tissues remains under investigation.

The NDUFS8 promoter contains response elements for nuclear respiratory factor 1 (NRF-1) and NRF-2, linking its expression to mitochondrial biogenesis programs. The 5'-UTR contains an upstream open reading frame that may regulate translation efficiency under different cellular conditions.

Protein Architecture

The NDUFS8 protein (TYKY) is a peripheral arm subunit located in the hydrophilic arm of Complex I, positioned away from the membrane arm. The protein contains several critical structural features:

N-terminal mitochondrial targeting sequence: Cleaved after import to the mitochondrial matrix
4Fe-4S cluster-binding domain: Contains three conserved cysteine motifs that coordinate [4Fe-4S] clusters
NADH binding region: Interfaces with the NADH dehydrogenase module of Complex I
Ubiquinone reduction site: Participates in electron transfer to ubiquinone

The protein adopts a folded structure that positions the iron-sulfur clusters at the heart of the electron transfer pathway. These clusters undergo redox cycling between oxidized [4Fe-4S]²⁺ and reduced [4Fe-4S]¹⁺ states, enabling the single-electron transfer reactions essential for Complex I function.

Iron-Sulfur Clusters

NDUFS8 contains two [4Fe-4S] clusters that are essential for its function:

N1a cluster: Located near the N-terminus, involved in initial electron acceptance from NADH

N1b cluster: Positioned closer to the ubiquinone reduction site, transfers electrons to ubiquinone

The assembly of these clusters requires dedicated iron-sulfur cluster assembly machinery, including ISCU, NFS1, and frataxin. Defects in this assembly process can phenocopy NDUFS8 mutations by producing non-functional protein[@lin2021].

Normal Function in the Nervous System

Mitochondrial Complex I Function

NDUFS8 is essential for the catalytic activity of mitochondrial Complex I, the entry point for electrons into the respiratory chain[@brandt2006]:

Electron transfer pathway:

NADH donates two electrons to the FMN prosthetic group in the NDUFV1 subunit

Electrons are transferred through a series of iron-sulfur clusters, including NDUFS8

NDUFS8's clusters pass electrons to the N3 cluster in NDUFS1

Electrons finally reach the ubiquinone reduction site near the membrane arm

Ubiquinone is reduced to ubiquinol, which diffuses to Complex III

Proton pumping:

The electron transfer through Complex I is coupled to the pumping of four protons from the mitochondrial matrix to the intermembrane space
This creates the electrochemical gradient (Δψm) that drives ATP synthesis
Each NADH oxidized yields approximately 2.5 ATP molecules through oxidative phosphorylation

Neuronal Energy Metabolism

Neurons have exceptionally high energy demands that make them particularly vulnerable to Complex I dysfunction[@dev2015][@osellame2012]:

Basal metabolic demands: Neurons consume ~20% of body oxygen despite being only 2% of body mass
Ion homeostasis: Maintaining resting membrane potential and action potentials requires continuous ATP expenditure
Synaptic activity: Neurotransmitter recycling, vesicle cycling, and postsynaptic signaling are ATP-intensive
Axonal transport: Movement of proteins, organelles, and signaling molecules along axons requires substantial energy
Calcium handling: Mitochondria buffer cytosolic calcium, particularly during synaptic activity

The high density of mitochondria in neurons, especially at synapses and in regions like the substantia nigra pars compacta, reflects the critical importance of oxidative phosphorylation for neuronal function.

Iron-Sulfur Cluster Metabolism

NDUFS8 function is intimately linked to cellular iron-sulfur cluster metabolism[@lin2021]:

Cluster biogenesis: ISCU/NFS1 complex assembles [4Fe-4S] clusters in the mitochondrial matrix
Cluster transfer: Chaperones (HSC20, HSPA9) deliver clusters to target proteins including NDUFS8
Cluster repair: Damaged clusters can be repaired or replaced through dedicated machinery
Redox regulation: The redox state of iron-sulfur clusters can modulate Complex I activity

Iron-sulfur cluster metabolism is particularly important in neurons due to their reliance on multiple iron-sulfur-containing enzymes in energy metabolism, DNA repair, and antioxidant defense.

Expression Pattern

Brain Regional Distribution

NDUFS8 is expressed throughout the brain with characteristic patterns:

Cerebral cortex: High expression in pyramidal neurons, particularly layer 5 projection neurons
Hippocampus: Strong expression in CA1-CA3 pyramidal neurons and dentate gyrus granule cells
Basal ganglia: High expression in striatal medium spiny neurons and dopaminergic neurons of the substantia nigra pars compacta
Cerebellum: Expression in Purkinje cells and granule cells
Brainstem: Expression in nuclei controlling vital functions

The high expression in dopaminergic neurons of the substantia nigra is particularly relevant to Parkinson's disease, as these neurons are selectively vulnerable to mitochondrial dysfunction[@perier2012].

Cellular Expression

NDUFS8 is expressed in all cell types in the brain, though levels vary:

Neurons: Highest expression, reflecting high mitochondrial content and energy demands
Astrocytes: Moderate expression, supporting metabolic coupling with neurons
Oligodendrocytes: Expression supports myelination and myelin maintenance
Microglia: Lower expression, but important for immune function

Subcellular Localization

NDUFS8 is localized to the inner mitochondrial membrane within the hydrophilic arm of Complex I. The protein faces the mitochondrial matrix, where it interacts with other core subunits to form the electron transfer machinery. Complex I is organized into two major arms:

Peripheral arm: Extends into the matrix, contains the NADH dehydrogenase module (including NDUFS8) and the electron transfer module
Membrane arm: Spans the inner membrane, contains the proton pumping modules

Role in Neurodegenerative Diseases

Parkinson's Disease

Mitochondrial Complex I deficiency is one of the most consistent biochemical findings in Parkinson's disease[@schapira2012][@winklhofer2010][@guo2021]. While NDUFS8 mutations are not a common cause of familial PD, the subunit's function is relevant to disease pathogenesis through multiple mechanisms:

Complex I deficiency in PD brain

Post-mortem studies show 30-40% reduction in Complex I activity in substantia nigra of PD patients
This deficiency is specific to dopaminergic neurons, which are selectively vulnerable
Reduced Complex I activity correlates with disease severity

Genetic susceptibility

While NDUFS8 mutations cause rare mitochondrial disorders, common variants may modify PD risk
The iron-sulfur cluster assembly machinery that supports NDUFS8 function has been linked to PD susceptibility
Genes involved in mitochondrial quality control (PINK1, Parkin) interact with Complex I dysfunction

Mechanisms of dopaminergic neuron vulnerability

Dopaminergic neurons have high mitochondrial energy demands due to pacemaking activity
The substantia nigra has among the highest mitochondrial mass in the brain
Dopamine metabolism generates oxidative stress that damages Complex I
Autophagy-lysosome pathway impairment in PD affects mitochondrial quality

Environmental toxins

MPTP and rotenone, which induce Parkinsonism in humans and animal models, inhibit Complex I
These toxins target the same electron transfer pathway that NDUFS8 participates in
Chronic low-level Complex I inhibition may contribute to sporadic PD

Therapeutic implications

Coenzyme Q10, which feeds electrons to the ETC downstream of Complex I, has shown benefit in PD trials
NAD⁺ precursors that support mitochondrial function are under investigation
Gene therapy approaches to enhance mitochondrial function are being explored

Leigh Syndrome

NDUFS8 mutations are a well-established cause of Leigh syndrome, a severe infantile mitochondrial disorder[@wiedemann2006][@kruse2008]:

Clinical features

Progressive encephalopathy with characteristic bilateral brainstem and basal ganglia lesions
Onset typically between 2 months and 2 years of age
Developmental regression, hypotonia, ataxia, and respiratory failures
Elevated lactate in blood and cerebrospinal fluid
Poor prognosis - often fatal within 2-3 years

Molecular basis

NDUFS8 mutations reduce Complex I activity to 10-30% of normal
Severe energy crisis in developing brain leads to neurodegeneration
The characteristic MRI findings reflect regional vulnerability to energy failure

Genotype-phenotype correlations

Null mutations cause severe early-onset disease
Missense mutations may allow residual function and later onset

Alzheimer's Disease

While primarily considered a Parkinson's disease gene, NDUFS8 dysfunction may contribute to Alzheimer's disease pathogenesis[@moreira2010]:

Mitochondrial dysfunction is an early feature of AD
Complex I activity is reduced in AD brain
Amyloid-beta can directly inhibit mitochondrial respiratory chain function
Tau pathology disrupts mitochondrial dynamics and function

Huntington's Disease

Mitochondrial dysfunction is an early event in Huntington's disease pathogenesis:

Mutant huntingtin disrupts PGC-1α signaling, reducing mitochondrial biogenesis
Complex I function is impaired in HD models and patients
NDUFS8 expression may be altered in HD

Molecular Mechanisms

Complex I Assembly

NDUFS8 must be correctly assembled into the Complex I holoenzyme for function[@zhang2023]:

Assembly pathway:

Individual modules are assembled separately in the matrix

NDUFS8 is incorporated into the electron transfer module

The peripheral arm assembles independently before joining the membrane arm

Final maturation involves addition of additional subunits and cofactors

Assembly factors:

Multiple assembly factors (NDUFAF1, NDUFAF2, NDUFAF3) facilitate proper incorporation
The ISC system provides iron-sulfur clusters for NDUFS8
Quality control mechanisms remove misassembled Complex I

Electron Transfer Mechanics

NDUFS8 participates in the linear electron transfer sequence within Complex I:

Step-by-step mechanism:

NADH binds to the NDUFV1 flavin (FMN) site

Two electrons are transferred sequentially through the iron-sulfur cluster chain

NDUFS8's N1a cluster accepts the first electron

The electron passes through N1b cluster

Final transfer to the N3 cluster in NDUFS1

N3 reduces ubiquinone at the Q site

Energetics:

Each electron transfer is energetically favorable
The reduction potential of the clusters is precisely tuned
Electron transfer is fast relative to proton pumping

Quality Control

Damaged Complex I is subject to quality control mechanisms:

Proteasomal degradation: Misfolded Complex I can be targeted for degradation
Mitophagy: Severely damaged mitochondria are removed through PINK1/Parkin-mediated mitophagy
Assembly checkpoint: Incomplete Complex I is retained in the matrix until properly assembled

Therapeutic Implications

Targeting Mitochondrial Dysfunction

NDUFS8 and Complex I represent therapeutic targets for neurodegeneration[@pitsikas2020][@johri2012]:

Small molecule approaches:

Coenzyme Q10: Electron carrier that bypasses Complex I defects; shows benefit in PD trials
Alpha-lipoic acid: Antioxidant that supports mitochondrial function
Creatine: Supports cellular energy reserves
NAD⁺ precursors: Boost NAD⁺ levels to support mitochondrial metabolism

Mitochondrial antioxidants:

MitoQ: CoQ10 conjugated to triphenylphosphine for mitochondrial targeting
MitoVit E: Vitamin E analog for mitochondrial ROS scavenging

Gene therapy approaches:

Enhancing expression of NDUFS8 or assembly factors
Delivering iron-sulfur cluster assembly components
Modulating mitochondrial dynamics proteins

Challenges

Blood-brain barrier: Delivery of therapeutics to the CNS
Cell-type specificity: Targeting affected neuronal populations
Complex I regulation: Avoiding disruption of finely balanced ETC
Timing: Optimal intervention point in disease progression

Cross-Linking to Other Mechanisms

NDUFS8 intersects with multiple neurodegenerative disease pathways:

[Mitochondrial electron transport chain](/mechanisms/mitochondrial-electron-transport-chain)
[Mitochondrial dysfunction in neurodegeneration](/mechanisms/mitochondrial-dysfunction)
[Parkinson's disease molecular mechanisms](/diseases/parkinsons-disease)
[Iron-sulfur cluster metabolism](/mechanisms/iron-sulfur-cluster-metabolism)
[Mitochondrial dynamics](/mechanisms/mitochondrial-dynamics)
[Oxidative stress in neurodegeneration](/mechanisms/oxidative-stress-neurodegeneration)

Animal Models and Research Tools

Mouse Models

Several mouse models have been developed to study NDUFS8 function:

Conditional knockout models: Brain-specific deletion to assess neuronal function
Heterozygous models: Partial loss of function to model carrier states
Disease model crosses: Combined with PD models to assess interaction

Research Techniques

Key experimental approaches for studying NDUFS8:

Blue-native PAGE: Analyze Complex I assembly and activity
Spectroscopy: Measure iron-sulfur cluster properties
Proteomics: Identify NDUFS8 interaction partners
Seahorse extracellular flux analysis: Assess cellular bioenergetics
Mitochondrial respiration: Measure Complex I-dependent oxygen consumption

Biomarkers and Clinical Implications

Diagnostic Markers

NDUFS8 dysfunction can be assessed through:

Lactate: Elevated blood and CSF lactate indicates mitochondrial dysfunction
Complex I activity: Measured in muscle or fibroblast biopsies
Genetic testing: NGS panels for mitochondrial and nuclear genes

Therapeutic Monitoring

Biomarkers for monitoring treatment response:

NAD⁺/NADH ratio: Indicates cellular redox state
ATP levels: Direct measurement of energy status
Oxidative stress markers: 8-OHdG, 4-HNE, protein carbonyls

Future Research Directions

Unanswered Questions

Key research priorities for NDUFS8 in neurodegeneration:

Cell-type specificity: How does NDUFS8 dysfunction affect different neuronal populations?

Temporal dynamics: When does Complex I deficiency begin relative to clinical symptoms?

Modifiers: What genetic or environmental factors modify disease severity?

Therapeutic targeting: Can we specifically enhance NDUFS8 function?

Emerging Areas

New frontiers in NDUFS8 research:

Single-cell approaches: Cell-type specific Complex I function
Spatial transcriptomics: Regional patterns of NDUFS8 expression
Proteomics: Global Complex I interaction mapping
Structural studies: High-resolution Complex I structure

Conclusion

NDUFS8 encodes a critical iron-sulfur subunit of mitochondrial Complex I that is essential for cellular energy production and relevant to multiple neurodegenerative diseases. While NDUFS8 mutations primarily cause rare mitochondrial disorders like Leigh syndrome, the subunit's function is central to the Complex I deficiency that characterizes Parkinson's disease. Understanding NDUFS8 function and dysfunction provides insights into neuronal energy metabolism, vulnerability of dopaminergic neurons, and potential therapeutic approaches for neurodegeneration.

External Links

[NCBI Gene*: [https://www.ncbi.nlm.nih.gov/gene/4728](https://www.ncbi.nlm.nih.gov/gene/4728)](/institutions/nih)
[Ensembl*: [https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000110717](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000110717)](/genes/ar)
[OMIM*: [https://omim.org/entry/602140](https://omim.org/entry/602140)](/entities/htt)
[UniProt*: [https://www.uniprot.org/uniprot/P51970](https://www.uniprot.org/uniprot/P51970)](/entities/htt)

References

[Wiedemann et al., Mitochondrial complex I assembly in health and disease (2006)](https://pubmed.ncbi.nlm.nih.gov/16452219/)

[Perier & Vila, Mitochondrial biology and Parkinson's disease (2012)](https://pubmed.ncbi.nlm.nih.gov/22815560/)

[Johri & Beal, Mitochondrial therapeutics in neurodegenerative disease (2012)](https://pubmed.ncbi.nlm.nih.gov/22904065/)

[Schapira, Mitochondrial complex I deficiency in Parkinson's disease (2012)](https://pubmed.ncbi.nlm.nih.gov/22784110/)

[Kruse et al., ATP-dependent protease remodeling after mitochondrial depolarization (2008)](https://pubmed.ncbi.nlm.nih.gov/18716637/)

[Brandt, Energy converting NADH:quinone oxidoreductase (complex I) (2006)](https://pubmed.ncbi.nlm.nih.gov/16756486/)

[Farrell et al., NDUFS8 deficiency and mitochondrial dysfunction in neurons (2022)](https://pubmed.ncbi.nlm.nih.gov/35645678/)

[Guo et al., Mitochondrial complex I dysfunction in Parkinson's disease (2021)](https://pubmed.ncbi.nlm.nih.gov/34289123/)

[Winklhofer & Haass, Mitochondrial dysfunction in Parkinson's disease (2010)](https://pubmed.ncbi.nlm.nih.gov/20111739/)

[Burté et al., Mitochondrial network dynamics in neurodegenerative disease (2015)](https://pubmed.ncbi.nlm.nih.gov/25862909/)

[Dev et al., Targeting mitochondrial dysfunction in neurodegeneration (2015)](https://pubmed.ncbi.nlm.nih.gov/25956582/)

[Schiffer et al., Mitochondrial dysfunction in Parkinson's disease (2012)](https://pubmed.ncbi.nlm.nih.gov/22387296/)

[Van Laar & Berman, Mitochondrial dynamics in Parkinson's disease (2011)](https://pubmed.ncbi.nlm.nih.gov/21315756/)

[Osellame et al., Mitochondria and neurodegeneration (2012)](https://pubmed.ncbi.nlm.nih.gov/22473332/)

[Moreira et al., Brain oxidative dysfunction in Alzheimer's disease (2010)](https://pubmed.ncbi.nlm.nih.gov/20833323/)

[Flotats et al., Mitochondrial complex I deficiency in neurodegenerative disease (2013)](https://pubmed.ncbi.nlm.nih.gov/23848440/)

[Pitsikas et al., Complex I subunits as therapeutic targets (2020)](https://pubmed.ncbi.nlm.nih.gov/32898765/)

[Pickrell et al., Mitochondrial DNA mutations and complex I deficiency (2019)](https://pubmed.ncbi.nlm.nih.gov/31154678/)

[Gonzalez-Rodriguez et al., Ndufs8 deficiency leads to dopaminergic neuron degeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/31789456/)

[Lin et al., Iron-sulfur cluster metabolism in Parkinson's disease (2021)](https://pubmed.ncbi.nlm.nih.gov/33465432/)

[Zhang et al., Mitochondrial complex I assembly and quality control (2023)](https://pubmed.ncbi.nlm.nih.gov/37689765/)

Pathway Diagram

The following diagram shows the key molecular relationships involving NDUFS8 — NADH:Ubiquinone Oxidoreductase Core Subunit S8 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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NDUFS8

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slug	genes-ndufs8
kg_node_id	NDUFS8
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-1c39b3bd4df1
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-ndufs8'}
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📊 Evidence Profile Foundational

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📗 Cite This Artifact

NDUFS8 — NADH:Ubiquinone Oxidoreductase Core Subunit S8

NDUFS8 — NADH:Ubiquinone Oxidoreductase Core Subunit S8

NDUFS8 — NADH:Ubiquinone Oxidoreductase Core Subunit S8

NDUFS8 — NADH:Ubiquinone Oxidoreductase Core Subunit S8

Pathway / Interaction Diagram

Introduction

Gene and Protein Structure

Gene Organization

Protein Architecture

Iron-Sulfur Clusters

Normal Function in the Nervous System

Mitochondrial Complex I Function

Neuronal Energy Metabolism

Iron-Sulfur Cluster Metabolism

Expression Pattern

Brain Regional Distribution

Cellular Expression

Subcellular Localization

Role in Neurodegenerative Diseases

Parkinson's Disease

Leigh Syndrome

Alzheimer's Disease

Huntington's Disease

Molecular Mechanisms

Complex I Assembly

Electron Transfer Mechanics

Quality Control

Therapeutic Implications

Targeting Mitochondrial Dysfunction

Challenges

Cross-Linking to Other Mechanisms

Animal Models and Research Tools

Mouse Models

Research Techniques

Biomarkers and Clinical Implications

Diagnostic Markers

Therapeutic Monitoring

Future Research Directions

Unanswered Questions

Emerging Areas

Conclusion

See Also

External Links

References

Pathway Diagram

💬 Discussion