| 1999 |
PSST (NDUFS7) subunit of complex I is the primary site of photoaffinity labeling by the potent inhibitor [3H]TDP (trifluoromethyldiazirinyl-pyridaben), establishing that PSST functionally couples electron transfer from iron-sulfur cluster N2 to ubiquinone; all structurally diverse potent complex I inhibitors (rotenone, piericidin A, bullatacin, pyridaben) compete for this same binding site on PSST, and the equivalent bacterial subunit NQO6 shares this conserved function. |
Photoaffinity labeling with [3H]TDP, protein sequencing, immunoprecipitation, competitive binding assays, enzyme inhibition assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
10097178
|
| 2001 |
PSST (NDUFS7) and ND1 subunits of complex I are functionally coupled at the quinone-binding region: NADH increases PSST labeling while decreasing ND1 labeling; MPP+ and stigmatellin show opposite effects (increased ND1, decreased PSST labeling), indicating dynamic interaction between these two subunits at a semiquinone binding site. |
Photoaffinity labeling with [3H]TDP, competitive binding, preincubation with NADH/inhibitors |
Biochimica et biophysica acta |
High |
11418099
|
| 2000 |
Conserved acidic residues D136 and E140 in the PSST homologue (Yarrowia lipolytica) play a central role in proton translocation and ubiquinone interaction; E89 (proposed fourth ligand of iron-sulfur center N2) is not a ligand of N2 as EPR spectra show unchanged N2 amount but shifted spectrum upon mutation to glutamine, alanine, or cysteine. |
Site-directed mutagenesis, EPR spectroscopy, enzymatic activity assays in Yarrowia lipolytica |
The Journal of biological chemistry |
High |
10811805
|
| 2003 |
Two aspartic acid residues D99 and D115 in the PSST homologue (NUKM, Yarrowia lipolytica) are essential for complex I catalytic activity; their mutation to Asn, Glu, or Gly reduces activity to 5–8% of wild-type and reduces the EPR N2 signal by ~50%, while complex I remains stably assembled. No conserved acidic residue in PSST serves as the fourth ligand of iron-sulfur cluster N2. |
Site-directed mutagenesis of all 8 conserved acidic residues, EPR spectroscopy, enzyme activity assays, Blue Native PAGE |
The Journal of biological chemistry |
High |
12930834
|
| 2012 |
Fenpyroximate binds at the interface between the PSST and 49 kDa subunits of complex I, not at the distal membrane domain (ND5); the pharmacophoric pyrazole ring orients toward PSST (labeled in region Ser43–Arg66) while the side chain orients toward the 49 kDa subunit, within the quinone-binding pocket formed at the PSST/49 kDa/ND1 interface. |
Photoaffinity labeling with two 125I-labeled fenpyroximate derivatives, limited proteolysis, doubled SDS-PAGE, mass spectrometry |
Biochemistry |
High |
22353032
|
| 2016 |
NDUFAF5, an S-adenosylmethionine-dependent assembly factor, hydroxylates Arg-73 of NDUFS7 early in the complex I assembly pathway, before formation of the junction between the peripheral and membrane arms. |
Mass spectrometry identification of hydroxylation, functional assembly analysis by Blue Native PAGE, biochemical characterization of NDUFAF5 activity |
The Journal of biological chemistry |
High |
27226634
|
| 2019 |
Conserved residues in the loop of PSST (NDUFS7) facing the ~30 Å quinone-binding tunnel are critical for ubiquinone reductase activity; mutation of conserved arginine residues drastically reduces Q reductase activity despite full complex I assembly, and molecular dynamics simulations show these residues dynamically control ubiquinone diffusion and retention near the terminal electron donor N2. |
Site-directed mutagenesis, enzymatic activity assays, Blue Native PAGE assembly analysis, molecular dynamics simulations (microsecond scale) |
Biochimica et biophysica acta. Bioenergetics |
High |
31226318
|
| 2007 |
NDUFS7 is essential for biogenesis of fully assembled complex I; an intronic mutation (c.17-1167 C>G) creates a cryptic exon producing a truncated 41-amino-acid protein, resulting in marked decrease in fully assembled complex I on Blue Native PAGE while other respiratory chain complexes are unaffected. |
Blue Native PAGE assembly analysis, patient-derived cell studies, RT-PCR demonstration of cryptic exon |
Molecular genetics and metabolism |
Medium |
17604671
|
| 2023 |
NDUFS7 contains a direct drug-binding site: exome sequencing of six independently selected DX2-201-resistant clones all revealed a p.V91M mutation in NDUFS7, demonstrating that this residue is within the compound's binding site and that NDUFS7 inhibition suppresses oxidative phosphorylation. |
Exome sequencing of resistant clones, cell viability assays, in vivo syngeneic tumor model |
ACS pharmacology & translational science |
Medium |
37588763
|
| 2024 |
NDUFS7 deficiency in HEK293T cells causes reduced cell proliferation, elevated cell death, and increased ROS; upregulation of SLC7A11 compensates by increasing cystine import and glutathione biosynthesis to mitigate apoptosis. |
NDUFS7 knockout in HEK293T cells, ROS measurement, SLC7A11 knockdown/overexpression, glutathione assays |
Biochemical and biophysical research communications |
Medium |
38823363
|
| 2024 |
The canine NDUFS7 p.Val179Met missense variant fails to rescue lethality upon knockdown of the Drosophila ortholog ND-20 (whereas wildtype NDUFS7 partially rescues), establishing this residue as functionally critical for NDUFS7 activity in vivo. |
Drosophila in vivo complementation assay with ubiquitous knockdown of ND-20 and overexpression of wildtype vs. mutant canine NDUFS7 |
Scientific reports |
Medium |
38316835
|
| 2026 |
NRF2 directly regulates NDUFS7 transcription (ChIP-seq confirmed binding), and NDUFS7 is required for mitochondrial complex I integrity in trabecular meshwork cells; restoration of NDUFS7 in NRF2-deficient cells or mice rescues mitochondrial impairment. |
ChIP-seq, NRF2 knockout mice, NRF2 knockdown/overexpression, NDUFS7 rescue experiments, mitochondrial function assays |
Research (Washington, D.C.) |
Medium |
41869290
|