NDUFS1

Official Full Name

NADH:ubiquinone oxidoreductase core subunit S1

Organism

Homo sapiens

Gene ID

4719

Background

The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized. Mutations in this gene are associated with complex I deficiency. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

Synonyms

CI-75k; MC1DN5; CI-75Kd; PRO1304

Cat.No.	Product Name	Price
CSC-DC010263	Panoply™ Human NDUFS1 Knockdown Stable Cell Line	Inquiry
CSC-SC010263	Panoply™ Human NDUFS1 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD10653Z	Human NDUFS1 adenoviral particles	Inquiry
LV19322L	human NDUFS1 (NM_005006) lentivirus particles	Inquiry
LV19323L	human NDUFS1 (NM_001199983) lentivirus particles	Inquiry
LV19324L	human NDUFS1 (NM_001199982) lentivirus particles	Inquiry
LV19325L	human NDUFS1 (NM_001199981) lentivirus particles	Inquiry
LV19326L	human NDUFS1 (NM_001199984) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH350840	shRNA set against Human NDUFS1 (NM_005006.6)	Inquiry
SHH350844	shRNA set against Mouse NDUFS1 (NM_145518.2)	Inquiry
SHH350848	shRNA set against Rat NDUFS1 (NM_001005550.1)	Inquiry
SHW000598	shRNA set against Chicken NDUFS1 (NM_001006518)	Inquiry
SHW007727	shRNA set against Danio rerio NDUFS1 (NM_001007765)	Inquiry

Cat.No.	Product Name	Price
MiUTR3H-01428	NDUFS1 miRNA 3'UTR clone	Inquiry
CDFR001472	Rat Ndufs1 cDNA Clone(NM_001005550.1)	Inquiry
CDCS409525	Human NDUFS1 ORF Clone (BC022368)	Inquiry
CDCR368533	Rat Ndufs1 ORF Clone(NM_001005550.1)	Inquiry
MiUTR1R-04150	NDUFS1 miRNA 3'UTR clone	Inquiry
CDCS409524	Human NDUFS1 ORF Clone (BC012068)	Inquiry
CDCR267365	Mouse Ndufs1 ORF Clone(NM_145518.2)	Inquiry
CDCR238863	Mouse Ndufs1 ORF Clone(NM_001160040.1)	Inquiry
CDCR238861	Mouse Ndufs1 ORF Clone(NM_001160039.1)	Inquiry
CDCL137321	Human NDUFS1 ORF clone (NM_001199981.1)	Inquiry
CDCL137317	Mouse NDUFS1 ORF clone (NM_001199982.1)	Inquiry
CDCL137315	Mouse NDUFS1 ORF clone (NM_001199984.1)	Inquiry
CDCL137313	Human NDUFS1 ORF clone (NM_001199983.1)	Inquiry
CDCB192516	Rabbit NDUFS1 ORF clone (XM_002712574.2)	Inquiry
CDCB169202	Danio rerio NDUFS1 ORF Clone (NM_001007765)	Inquiry
CDCL137327	Human Ndufs1 ORF clone (NM_001160038.1)	Inquiry
CDCB162073	Chicken NDUFS1 ORF Clone (NM_001006518)	Inquiry

Detailed Information

NDUFS1 (NADH dehydrogenase (ubiquinone) Fe-S protein 1) plays a key role in the maintenance of mitochondrial function as the largest subunit of mitochondrial complex I. In recent years, studies have found that the expression of NDUFS1 is decreased in tumor cells, which may be closely related to tumor development.

Complex I, i.e. NADH dehydrogenase, is the entry point for oxidative phosphorylation. By changing the mitochondrial membrane potential, NADH is converted to NAD+, producing ATP and by-product ROS. It is the largest complex in the electron transport chain of mitochondria and consists of a total of 45 subunits, 14 of which are core subunits. Seven of the 14 core subunits are encoded by mitochondrial DNA (mtDNA) and seven by nuclear DNA (nDNA). The core subunits encoded by nuclear DNA (nDNA) are: NDUFS1, which belongs to the NADH dehydrogenase module. NDUFV1 and NDUFV2; and NDUFS2, NDUFS3, NDUFS7, and NDUFS8 belonging to the oxidase module. NDUFS1 is the largest subunit of complex I (and thus considered to be a marker for complex I) and has NADH dehydrogenase and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain.

Figure 1. MDM2 integrates cellular respiration and apoptotic signaling through NDUFS1 and the mitochondrial network. (Elkholi, R., et al. 2019)

NDUFS1 Mutation

In human fibroblasts with NDUFS1 subunit mutations, a decrease in mitochondrial membrane potential and an increase in mitochondrial DNA-encoded respiratory complex subunit expression (compensatory response) occurred. The level of NDUFS1 and serum tumor necrosis factor (TNF)-α in renal cell carcinoma patients increased with the increase of cancer stage. It was analyzed that TNF-α may be involved in NDUFS 1 gene silencing, resulting in decreased NDUFS1 expression. NDUFS1 gene expression is regulated by NUBPL (nucleotide binding protein), and knockdown of NDUBPL results in decreased expression of NDUFS 1 accompanied by a decrease in complex I activity. The above experimental phenomena indicate that NDUFS1, as a core subunit encoded by the nuclear gene in mitochondrial complex I, may cause loss and abnormal expression of related mitochondria-associated subunits if its gene is mutated or abnormal during transcription and translation. This causes mitochondrial dysfunction, leading to diseases such as cancer.

When external physical, chemical, biological and other factors oxidatively stimulate mitochondria in the body, glutathionization is inactivated in the core subunit NDUFS1 of mitochondrial complex I. This causes the electronic respiratory transfer chain to be blocked, and the body produces a large amount of ROS, which in turn causes a series of corresponding changes.

The Regulation Mechanism of NDUFS1 on Tumor Progression

When mitochondrial function is normal, ROS in the body are maintained in a balanced state and participate in activities such as redox regulation and biological information transmission in the body. When the body is in oxidative stress, the NDUFS1 subunit is inactivated, resulting in an obstacle to the electronic respiratory transmission chain and a large amount of reactive oxygen species. However, the regulation of tumors by reactive oxygen species shows a dual effect, so it can be considered that the inactivation of NDUFS1 has a double effect on tumor development.

After conducting experiments on the expression of NDUFS1 in lung cancer and renal cancer patients, the results of the analysis of patient-related data revealed that NDUFS1 can be used as a diagnostic marker for renal cancer, as well as pathological staging and grading of lung cancer and renal cancer. There is a significant correlation between lymph node and distant metastasis and patient survival. The expression of NDUFS1 is the lower, and the stage of cancer patients is the higher. It has been found that NDUFS1 shows a strong independent prognostic effect.

References:

Jacquemin, G. , Margiotta, D. , Kasahara, A. , Bassoy, E. Y. , Walch, M. , & Thiery, J. , et al. (2015). Granzyme b-induced mitochondrial ros are required for apoptosis. Cell Death and Differentiation, 22(5), 862-874.
Su, C. Y. , Chang, Y. C. , Yang, C. J. , Huang, M. S. , & Hsiao, M. . (2016). The opposite prognostic effect of ndufs1 and ndufs8 in lung cancer reflects the oncojanus role of mitochondrial complex i. Scientific Reports, 6, 31357.
Elkholi, R., Abraham-Enachescu, I., Trotta, A. P., Rubio-Patiño, C., Mohammed, J. N., & Luna-Vargas, M. P. A., et al. Mdm2 integrates cellular respiration and apoptotic signaling through ndufs1 and the mitochondrial network. Molecular Cell.

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