| Full Name | NADH:Ubiquinone Oxidoreductase Core Subunit S5 |
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| Chromosomal Location | 1p33 |
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| NCBI Gene ID | 4723 |
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| OMIM | 603835 |
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| Ensembl ID | ENSG00000168653 |
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| UniProt | O43920 |
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| Associated Diseases | Parkinson's Disease, Leigh Syndrome, Mitochondrial Complex I Deficiency |
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NDUFS5 (NADH:Ubiquinone Oxidoreductase Core Subunit S5) encodes a core accessory subunit of mitochondrial complex I (NADH:ubiquinone oxidoreductase). Located on chromosome 1p33, NDUFS5 plays a structural role in complex I assembly and function, and its dysfunction contributes to neurodegenerative processes.
The NDUFS5 gene encodes a 15 kDa protein that is part of the hydrophilic peripheral arm of mitochondrial complex I:
- Complex I assembly: Essential for the proper assembly of the Q-binding module
- Electron transfer: Facilitates electron transfer within the complex
- Structural stability: Contributes to the overall architecture of complex I
- Mitochondrial respiration: Critical for NADH oxidation and proton pumping
- Cellular energy metabolism: Maintains ATP production in high-energy tissues
| Feature |
Details |
| Molecular weight |
~15 kDa |
| Protein class |
Accessory subunit of complex I |
| Location in Complex I |
Q module, 15 kDa subunit |
| Structure |
Predominantly alpha-helical |
- Evidence: NDUFS5 polymorphisms and reduced expression have been associated with PD risk
- Mechanism:
- Complex I deficiency in substantia nigra is a hallmark of PD
- Impaired electron transport leads to increased ROS and dopaminergic neuron death
- Mitochondrial complex I dysfunction is present in sporadic and genetic PD
- Therapeutic targeting: CoQ10, nicotinamide riboside, and complex I protectants
- Inheritance: Autosomal recessive
- Clinical features: Progressive neurodegeneration, developmental regression, characteristic brain lesions
- Mechanism: Severe complex I deficiency causes energy failure in the brain
- Phenotype: Encephalomyopathy, cardiomyopathy, lactic acidosis
- NDUFS5 mutations: Cause isolated complex I deficiency
NDUFS5 is ubiquitously expressed with highest levels in:
- Brain: Cerebral cortex, cerebellum, substantia nigra
- Heart: Cardiac muscle
- Skeletal muscle
- Kidney and liver
Expression is regulated by nuclear respiratory factors (NRF-1, NRF-2) and PGC-1α.
- Loeffen et al., NDUFS5 mutations and complex I deficiency (2001)
- Schapira, Complex I in Parkinson's disease (2010)
- Gandhi et al., Mitochondrial complex I and neurodegeneration (2009)