NADH dehydrogenase (ubiquinone), alpha 1

NDUFA1
Identifiers
Aliases	NDUFA1 , CI-MWFE, MWFE, ZNF183, NADH dehydrogenase (ubiquinone), alpha 1, NADH:ubiquinone oxidoreductase subunit A1, MC1DN12
External IDs	OMIM: 300078 MGI: 1929511 HomoloGene: 3337 GeneCards: NDUFA1
Gene location (Human)
Chr.	X chromosome (human)
End	119,876,662 bp
Gene location (Mouse)
Chr.	X chromosome (mouse)
End	36,454,816 bp
RNA expression pattern
	Top expressed in
	right ventricle; ; Brodmann area 10; ; renal medulla; ; Brodmann area 9; ; gastrocnemius muscle; ; kidney; ; frontal pole; ; nucleus accumbens; ; caudate nucleus; ; middle frontal gyrus;
	Top expressed in
	seminal vesicula; ; facial motor nucleus; ; molar; ; extraocular muscle; ; myocardium of ventricle; ; intercostal muscle; ; digastric muscle; ; sternocleidomastoid muscle; ; proximal tubule; ; motor neuron;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	NADH dehydrogenase (ubiquinone) activity ;
Cellular component	integral component of membrane ; mitochondrion ; mitochondrial respiratory chain complex I ; respirasome ; mitochondrial inner membrane ; membrane ; mitochondrial membrane ; cytosol ;
Biological process	mitochondrial electron transport, NADH to ubiquinone ; mitochondrial respiratory chain complex I assembly ;
	Sources:Amigo / QuickGO
Orthologs
	4694
	54405
	ENSG00000125356
	ENSMUSG00000016427
	O15239
	O35683
	NM_004541
	NM_019443
	NP_004532
	NP_062316
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated January 06, 2024

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 is a protein that in humans is encoded by the NDUFA1 gene.^[5]^[6] The NDUFA1 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.^[7] Mutations in the NDUFA1 gene are associated with mitochondrial Complex I deficiency.^[6]

Structure

The NDUFA1 gene is located on the long q arm of the X chromosome at position 24 and it spans 5,176 base pairs.^[6] The NDUFA1 gene produces an 8.1 kDa protein composed of 70 amino acids.^[8]^[9] NDUFA1 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.^[7] NDUFA1 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.^[6]

Function

The human NDUFA1 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.^[6] However, NDUFA1 is an accessory subunit of the complex that is believed not to be involved in catalysis.^[10] Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH₂. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH₂). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.^[7]

Clinical significance

Mitochondrial complex I deficiency (MT-C1D) is caused by mutations affecting the NDUFA1 gene. Complex I deficiency is a disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations, from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber's hereditary optic neuropathy, and some forms of Parkinson's disease.^[6]^[10] Mutations on the X chromosome that affect this gene have included the G94C mutation, which has been associated with lactic acidosis, hypotonia, increased beta-hydroxybutyrate/acetoacetate ratio, and complex I deficiency.^[11]

Interactions

NDUFA1 has been shown to have 7 binary protein-protein interactions including 3 co-complex interactions. NDUFA1 appears to interact with GOLGB1, TRIM63, and SMURF2.^[12]

Related Research Articles

NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial (NDUFS4) also known as NADH-ubiquinone oxidoreductase 18 kDa subunit is an enzyme that in humans is encoded by the NDUFS4 gene. This gene encodes a nuclear-encoded accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase. Complex I removes electrons from NADH and passes them to the electron acceptor ubiquinone. Mutations in this gene can cause mitochondrial complex I deficiencies such as Leigh syndrome.

NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial, also knowns as NADH-ubiquinone oxidoreductase 20 kDa subunit, Complex I-20kD (CI-20kD), or PSST subunit is an enzyme that in humans is encoded by the NDUFS7 gene. The NDUFS7 protein is a subunit of NADH dehydrogenase (ubiquinone) also known as Complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 is an enzyme that in humans is encoded by the NDUFA5 gene. The NDUFA5 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6, also known as complex I-B17, is a protein that in humans is encoded by the NDUFB6 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 6, is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial is an enzyme that in humans is encoded by the NDUFB8 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 is an enzyme that in humans is encoded by the NDUFA6 gene. The NDUFA6 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 is an enzyme that in humans is encoded by the NDUFB9 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 9 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 is a protein that in humans is encoded by the NDUFA2 gene. The NDUFA2 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in the NDUFA2 gene are associated with Leigh's syndrome.

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 is an enzyme that in humans is encoded by the NDUFA9 gene. The NDUFA9 protein is a subunit of NADH:ubiquinone oxidoreductase, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome. In the case of NDUFA9, a mutation to the MT-ND3 gene might interrupt their interaction and formation of subcomplexes, compromising Complex I function and leading to disease.

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 is an enzyme that in humans is encoded by the NDUFA8 gene. The NDUFA8 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.

Complex I intermediate-associated protein 30, mitochondrial (CIA30), or NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 1 (NDUFAF1), is a protein that in humans is encoded by the NDUFAF1 or CIA30 gene. The NDUFAF1 gene encodes a human homolog of a Neurospora crassa protein involved in the assembly of complex I. The NDUFAF1 protein is an assembly factor of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Variants of the NDUFAF1 gene are associated with hypertrophic cardiomyopathy, leukodystrophy, and cardioencephalomyopathy.

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 is an enzyme that in humans is encoded by the NDUFA12 gene. The NDUFA12 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome that result from mitochondrial complex I deficiency.

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10 is an enzyme that in humans is encoded by the NDUFA10 gene. The NDUFA10 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome. Furthermore, reduced NDUFA10 expression levels due to FOXM1-directed hypermethylation are associated with human squamous cell carcinoma and may be related to other forms of cancer.

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 is an enzyme that in humans is encoded by the NDUFB1 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 1, 7kDa is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial is an enzyme that in humans is encoded by the NDUFB2 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 2, 8kDa is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7, also known as complex I-B18, is an enzyme that in humans is encoded by the NDUFB7 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 7 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 is an enzyme that in humans is encoded by the NDUFB10 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 10 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial is an enzyme that in humans is encoded by the NDUFB11 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 11 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain. NDUFB11 mutations have been associated with linear skin defects with multiple congenital anomalies 3 and mitochondrial complex I deficiency.

NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3, 12kDa is a protein that in humans is encoded by the NDUFB3 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3, 12kDa is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain. Mutations in this gene contribute to mitochondrial complex I deficiency.

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 is an enzyme that in humans is encoded by the NDUFA11 gene. The NDUFA11 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome. Mutations in this gene are associated with severe mitochondrial complex I deficiency.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000125356 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000016427 - Ensembl, May 2017
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↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Zhuchenko O, Wehnert M, Bailey J, Sun ZS, Lee CC (November 1996). "Isolation, mapping, and genomic structure of an X-linked gene for a subunit of human mitochondrial complex I". Genomics. 37 (3): 281–8. doi:10.1006/geno.1996.0561. PMID 8938439.
1 2 3 4 5 6 "Entrez Gene: NDUFA1 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1, 7.5kDa".
1 2 3 Donald Voet; Judith G. Voet; Charlotte W. Pratt (2013). "18". Fundamentals of biochemistry : life at the molecular level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 9780470547847.
↑ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475 . PMID 23965338.
↑ "NDUFA1 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
1 2 "NDUFA1 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1". UniProt: a hub for protein information. The UniProt Consortium. Retrieved 24 March 2015.
↑ Mayr JA, Bodamer O, Haack TB, Zimmermann FA, Madignier F, Prokisch H, Rauscher C, Koch J, Sperl W (August 2011). "Heterozygous mutation in the X chromosomal NDUFA1 gene in a girl with complex I deficiency". Molecular Genetics and Metabolism. 103 (4): 358–61. doi:10.1016/j.ymgme.2011.04.010. PMID 21596602.
↑ "7 binary interactions found for search term NDUFA1". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-25.