Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Combined Automated Annotation using Multiple IEA Methods
Determination of the cDNA sequence for the human mitochondrial 75-kDa Fe-S protein of NADH-coenzyme Q reductase.
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Original characterization of NDUFS1 cDNA, establishing it as the 75 kDa Fe-S protein of the NADH-coenzyme Q reductase complex with homology to bacterial enzymes.
"It proved to be highly similar to the cDNA sequence for the bovine 75-kDa Fe--S protein."
cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed.
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Completion of the characterization of all nuclear-encoded Complex I subunit cDNAs, establishing the full subunit composition of human Complex I (41 subunits at the time).
"Now all currently known 41 proteins of human NADH:ubiquinone oxidoreductase have been characterized and reported in literature, which enables more complete mutational analysis studies of isolated complex I-deficient patients."
The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification.
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Direct identification of NDUFS1 as a subunit of immunopurified human Complex I by mass spectrometry, confirming 42 subunits in the complex.
"Using small amounts of immunoisolated protein, one-dimensional and two-dimensional gel electrophoresis, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) peptide mass finger printing (PMF), and nanoflow liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS), we can resolve and identify the human homologues of 42 polypeptides detected so far in the more extensively studied beef heart complex I."
Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain.
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NDUFS1 (p75) is a critical caspase substrate in mitochondria. Caspase cleavage of NDUFS1 during apoptosis disrupts electron transport, causes loss of membrane potential, and promotes ROS production. Cells expressing noncleavable NDUFS1 sustain respiration during apoptosis.
"Here, we identify NDUFS1, the 75 kDa subunit of respiratory complex I, as a critical caspase substrate in the mitochondria."
Leigh syndrome associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFS1 gene.
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A novel homozygous L231V mutation in NDUFS1 causes Leigh syndrome with isolated Complex I deficiency in muscle.
"RESULTS: Muscle biochemistry results showed a complex I defect of the mitochondrial respiratory chain."
Dysfunctions of cellular oxidative metabolism in patients with mutations in the NDUFS1 and NDUFS4 genes of complex I.
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NDUFS1 Q522K mutation causes reduced Complex I assembly, marked activity inhibition, mitochondrial ROS accumulation, decreased glutathione, and enhanced susceptibility to oxidative damage. cAMP treatment partially restored activity and eliminated ROS.
"The mutation (Q522K replacement) in NDUFS1 gene, coding for the 75-kDa Fe-S subunit of the complex, was associated with (a) reduced level of the mature complex, (b) marked, albeit not complete, inhibition of the activity, (c) accumulation of H(2)O(2) and O(2)(.-) in mitochondria, (d) decreased cellular content of glutathione, (e) enhanced expression and activity of glutathione peroxidase, and (f) decrease of the mitochondrial potential and enhanced mitochondrial susceptibility to reactive oxygen species (ROS) damage"
cAMP controls oxygen metabolism in mammalian cells.
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A genetic defect in the NDUFS1 75 kDa Fe-S protein subunit inhibits Complex I activity and enhances ROS production, both reversible by cAMP.
"In fibroblasts from a patient a genetic defect in the 75 kDa FeS-protein subunit of complex I resulted in inhibition of the activity of the complex and enhanced ROS production, which were reversed by cAMP."
TIMMDC1/C3orf1 functions as a membrane-embedded mitochondrial complex I assembly factor through association with the MCIA complex.
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Interaction proteomics study mapping Complex I subunit and assembly factor associations. NDUFS1 interacts with NDUFA9 and other Complex I subunits.
"We employed interaction proteomics to interrogate the molecular associations of 15 core subunits and assembly factors previously linked to human CI deficiency, resulting in a network of 101 proteins and 335 interactions (edges)."
Architecture of Human Mitochondrial Respiratory Megacomplex I(2)III(2)IV(2).
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Cryo-EM structure of the human respiratory megacomplex I2III2IV2 at 3.4A resolution, revealing the precise assignment of all CI subunits including NDUFS1 in the peripheral arm.
"The structure not only reveals the precise assignment of individual subunits of human CI and CIII, but also enables future in-depth analysis of the electron transport chain as a whole."
A Map of Human Mitochondrial Protein Interactions Linked to Neurodegeneration Reveals New Mechanisms of Redox Homeostasis and NF-κB Signaling.
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Large-scale mitochondrial protein interaction map. Detected NDUFS1-SOAT1 interaction.
"we report a high-confidence MP network including 1,964 interactions among 772 proteins"
Assembly of mammalian oxidative phosphorylation complexes I-V and supercomplexes.
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Comprehensive review of OXPHOS complex assembly. Complex I assembly is a stepwise process involving multiple assembly factors. The N-module containing NDUFS1 is added late in the assembly pathway.
"The assembly of the five oxidative phosphorylation system (OXPHOS) complexes in the inner mitochondrial membrane is an intricate process."
MDM2 Integrates Cellular Respiration and Apoptotic Signaling through NDUFS1 and the Mitochondrial Network.
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MDM2 directly binds and sequesters NDUFS1, preventing its mitochondrial localization, causing Complex I and supercomplex destabilization, decreased respiration, oxidative stress, and apoptosis. This is independent of p53.
"MDM2 negatively regulates NADH:ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1), leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis."
Mutations in NDUFS1 Cause Metabolic Reprogramming and Disruption of the Electron Transfer.
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NDUFS1 biallelic mutations (V228A and D252G) lead to decreased N-module stability, disrupted electron transfer between Fe-S clusters N4 and N5, impaired Complex I assembly, loss of enzymatic activity, and metabolic reprogramming with altered glutathione levels indicative of ROS stress. Val228 is critical for electron tunneling between N4 and N5 clusters (35-fold reduction in tunneling rate upon V228A mutation).
"the biallelic mutations in NDUFS1 led to a decreased stability of the entire N-module of CI and disrupted the electron transfer between two iron-sulfur clusters."
OSMR controls glioma stem cell respiration and confers resistance of glioblastoma to ionizing radiation.
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OSMR interacts with NDUFS1/NDUFS2 in the mitochondrial matrix and promotes Complex I respiration. Loss of OSMR impairs spare respiratory capacity and increases ROS.
"OSMR interacts with NADH ubiquinone oxidoreductase 1/2 (NDUFS1/2) of complex I and promotes mitochondrial respiration."
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
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Large-scale proteomics study detecting NDUFS1-NDUFA9 interaction as part of Complex I subunit interactions.
"Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks."
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
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NDUFS1 identified as a high-confidence mitochondrial protein in quantitative proteomics study.
"We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)."
Multimodal cell maps as a foundation for structural and functional genomics.
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Large-scale multimodal cell mapping study detecting NDUFS1-NDUFA9 interaction.
"Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells."
Complex I oxidises NADH to NAD+, reduces CoQ to CoQH2
NUBPL transfers 4Fe-4S to Complex I subunits
Peripheral arm subunits bind the 815kDa complex to form a 980kDa complex
The MCIA complex, NDUFAF2-7 all dissociate from the 980kDa complex, resulting in Complex I
NDUF subunits bind to form the FP subcomplex
CLPXP binds mitochondrial matrix proteins
LONP1 degrades mitochondrial matrix proteins
LONP1 binds mitochondrial matrix proteins
CLPXP degrades mitochondrial matrix proteins
Deep research review of NDUFS1 gene function (Falcon provider)
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NDUFS1 is a core subunit of the N-module of Complex I containing Fe-S clusters essential for electron transfer. Structural studies place NDUFS1 at the N/Q-module interface. Mutations cause Complex I deficiency and Leigh syndrome spectrum disorders.
"NDUFS1 encodes the NADH:ubiquinone oxidoreductase 75 kDa core subunit of mitochondrial complex I in Homo sapiens. It is a core subunit of the hydrophilic N-module of complex I, positioned where NADH oxidation and iron-sulfur Fe-S chain electron transfer occur."