InterPro2GO mapping of the complex I 49 kDa / NuoD domain signature, the source of the electronic NADH dehydrogenase, complex I membership and electron-transport annotations for NDUFS2. Domain-based mapping is well suited to this deeply conserved core subunit.

Curator-judged ISS transfer from characterised orthologues of the 49 kDa core subunit; NDUFS2 is one of the 14 subunits conserved from bacterial complex I, so sequence-similarity transfer here rests on unusually strong homology.

Source of the PANTHER phylogenetically-inferred (IBA) annotations for NDUFS2, propagating NADH dehydrogenase (ubiquinone) activity, complex I membership, mitochondrial inner-membrane location and NADH-to-ubiquinone electron transport across the conserved NuoD/49 kDa clade.

UniProtKB keyword-to-GO mapping, contributing generic transport and oxidoreductase terms; correct but less informative than the quinone-site and core-subunit evidence from structural and patient studies.

Ensembl Compara orthology projection from experimentally characterised mammalian orthologues; reasonable for a core complex I subunit but carrying no independent experimental weight for the human protein.

Inter-ontology logical inference; for NDUFS2 these terms are downstream consequences of the complex I activity and electron-transport assertions rather than new evidence.

Combined multi-method IEA pipeline, converging on complex I membership, inner-membrane location and NADH-to-ubiquinone electron transport in agreement with the manual and phylogenetic evidence.

Monoclonal antibodies against complex I subunits were used to profile assembly patterns in patients, including two carrying NDUFS2 mutations.

Subunit-level antibody profiling combined with sucrose gradients distinguishes catalytic from assembly defects, the distinction that later proved central to interpreting NDUFS2 mutations.

Immunopurification resolved and identified the human homologues of 42 complex I polypeptides by mass spectrometry. The cached abstract does not name individual subunits; NDUFS2's presence among them is what the GOA IDA annotation from this paper records.

Blue native electrophoresis of fibroblasts from complex I-deficient patients showed that mutations in nuclear-encoded subunits including NDUFS2 reduce assembled complex I, indicating compromised assembly or stability.

NDUFS2 mutations also destabilise complex III, evidence that the core subunit contributes to supercomplex integrity beyond complex I itself.

An immunopurified subcomplex containing the 23, 30 and 49 kDa (NDUFS2) subunits also contained prohibitin, the first report of a prohibitin-complex I subunit association.

Complex I assembles stepwise through six discrete NDUFS3-GFP-containing subcomplexes. The cached abstract tracks the NDUFS3 tag rather than NDUFS2; the NDUFS2/NDUFS3 intermediate being the nucleus of this pathway rests on the full text and on the Reactome assembly steps cited elsewhere in this review.

NDUFAF3 was established as a genuine complex I assembly factor that interacts with complex I subunits, the assembly context in which the NDUFS2-containing early intermediate forms.

Protein correlation profiling across blue native gel slices used the NDUFS2 abundance profile to identify candidate complex I biogenesis factors, an approach that reports NDUFS2 co-migration with assembly intermediates.

NDUFS2 was recovered among tandem-affinity-purified interactants of the E3 ubiquitin ligase Parkin, a large-scale interaction data point rather than evidence for a distinct NDUFS2 function.

Yeast two-hybrid and pull-down experiments showed that Dictyostelium and human MidA interact with NDUFS2, and MidA loss reduces assembled complex I.

Depletion of the NDUFS2-interacting MidA protein causes a specific complex I defect, implicating it in complex I assembly or stability.

The homozygous NDUFS2 Asp446Asn mutation leaves complex I amounts normal while strongly reducing activity, direct evidence that NDUFS2 contributes catalytically rather than only structurally.

The mutated residue sits near the coenzyme Q binding pocket, placing NDUFS2 at the quinone reduction site of complex I.

The authors propose that the defect lies in coenzyme Q reduction or in coupling that reduction to the conformational changes driving proton pumping.

NDUFAF7 symmetrically dimethylates Arg-85 of NDUFS2, a specific post-translational modification of this subunit occurring early in complex I assembly.

Arg-85 methylation of NDUFS2 stabilises the ~400 kDa subcomplex that nucleates the peripheral arm and its junction with the membrane arm.

The extrinsic arm of complex I holds the NADH and FMN sites and the Fe-S wire terminating at the ubiquinone site located at the junction between the arms, where NDUFS2 acts.

Interaction proteomics around 15 core complex I subunits and assembly factors, including NDUFS2, defined the network in which TIMMDC1 was identified as a membrane-embedded assembly factor.

A mitochondrial pool of cyclin B1/Cdk1 phosphorylates complex I subunits and enhances complex I activity; this describes regulation of NDUFS2 by another kinase rather than a cell-cycle function of NDUFS2 itself.

Affinity-enrichment mass spectrometry map of mitochondrial protein interactions; an NDUFS2 association here is a high-throughput interaction data point in a survey aimed at uncharacterised mitochondrial proteins.

Compound heterozygous NDUFS2 mutations (p.Tyr53Cys; p.Tyr308Cys) cause non-syndromic LHON-like optic neuropathy, extending the NDUFS2 disease spectrum beyond Leigh syndrome.

Modelling the mutations in the Yarrowia lipolytica orthologue NUCM abolished complex I or reduced NADH-ubiquinone oxidoreductase activity, confirming pathogenicity in a tractable system.

Mutation severity correlates with disease severity, supporting a dose-dependent relationship between residual NDUFS2 function and phenotype.

BioPlex 2.0 affinity-purification interactome; NDUFS2 entries derived from it are systematic co-complex data points that corroborate complex I membership but do not define a molecular function.

Cryo-EM of the human respiratory megacomplex assigned individual complex I subunits, placing NDUFS2 within complex I in a higher-order supercomplex.

Review distinguishing the catalytic core proteins of the OXPHOS complexes, which include NDUFS2, from the supernumerary subunits that act in assembly and stability.

Ndufs2, which forms the rotenone binding site of complex I, was tested directly as the molecular oxygen sensor underlying hypoxic pulmonary vasoconstriction.

Ndufs2 knockdown in pulmonary artery smooth muscle cells prevented the hypoxic calcium rise and phenocopied chronic hypoxia, whereas knockdown of other candidate sensors did not.

The authors conclude that Ndufs2 is essential for oxygen sensing and hypoxic pulmonary vasoconstriction, a tissue-specific role layered on the core catalytic function; note that this evidence is from rat, not human, cells.

A mitochondrial pool of the cytokine receptor OSMR interacts with NDUFS1/NDUFS2 of complex I and promotes mitochondrial respiration in brain tumour stem cells.

The radioresistance phenotype described here is a property of OSMR, not of NDUFS2; NDUFS2 features as the complex I interaction partner through which OSMR acts.

BioPlex 3.0 proteome-scale interaction networks across two cell lines; NDUFS2 entries are systematic affinity-purification data points supporting complex membership rather than a specific molecular function.

NDUFS2 is a member of the stringently defined human mitochondrial high-confidence proteome (MitoCoP), corroborating mitochondrial localization.

Maps the human NDUFS2 gene encoding the 49 kDa complex I subunit to chromosome 1q23 and reports immunodetection of the mature protein in mitochondria. Only the citation record is cached (no abstract text), so no verbatim quote is available.

The NDUFS2 cDNA encoding the 49 kDa iron-sulfur protein (IP) fraction subunit was cloned, completing the human complex I IP fraction.

NDUFS2 belongs to the iron-sulfur protein subfraction of complex I, which carries the conserved prosthetic groups, and its sequence is 96% identical to the bovine protein.

Defines the reaction catalysed by the complex to which NDUFS2 contributes - electron transfer from NADH to ubiquinone coupled to proton translocation.

Reactome reaction for the catalytic output of complex I - NADH oxidation with ubiquinone reduction coupled to proton pumping. NDUFS2 is a core catalytic subunit contributing the quinone-binding site of this reaction.

NUBPL-mediated transfer of 4Fe-4S clusters into complex I subunits; Reactome names NDUFS2 among the matrix-located subunits receiving an iron-sulfur cluster. Reported as stated by Reactome only - the eight clusters of mammalian complex I are accounted for by NDUFV1, NDUFV2, NDUFS1, NDUFS7 and NDUFS8, so this subunit list should not be read as evidence that NDUFS2 carries a cluster in the electron-transfer wire.

Assembly step in which the hydrophobic protein (HP) fraction joins Intermediate 1, downstream of the NDUFS2-nucleated core.

Late assembly step adding flavoprotein (FP) peripheral-arm subunits; NDUFS2 has already been incorporated at the earliest stage and is not added here.

Formation of the 315 kDa subcomplex centred on the NDUFS2/NDUFS3 core and anchored to the inner membrane by MT-ND1, the intermediate in which NDUFS2 first meets the membrane arm.

Final step of complex I biogenesis in which assembly factors dissociate to leave the mature holoenzyme containing NDUFS2.

Distal membrane-arm assembly step integrating MT-ND4 and MT-ND5; downstream of the NDUFS2-containing intermediates and not a step in which NDUFS2 acts directly.

Assembly step joining the NDUFS2-containing 315 kDa subcomplex to the 370 kDa membrane-arm subcomplex.

Reactome states that complex I assembly begins with a 315 kDa subcomplex centred on NDUFS2 and NDUFS3, that NDUFS2 is bound by the assembly factor NDUFAF7, and that NDUFS2 defects cause mitochondrial complex I deficiency - direct pathway support for the core, nucleating role of this subunit.

Formation of the IP subcomplex in which NDUFS7, NDUFS8 and NDUFA9 associate with NDUFS2 and NDUFS3 to build the evolutionarily conserved hydrogenase module of complex I.