NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial

NDUFS1 (NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial) is a core subunit of mitochondrial Complex I that catalyzes electron transfer from NADH through the respiratory chain using ubiquinone as an electron acceptor (UniProt: P28331). It is essential for efficient electron transfer within Complex I and plays a key role in assembly, stability, and formation of respiratory supercomplexes with Complex III (UniProt: P28331).

NDUFS1 is part of the oxidative phosphorylation pathway and mutations cause mitochondrial complex I deficiency, nuclear type 5 (MC1DN5), a rare autosomal recessive disorder characterized by defective mitochondrial respiration with phenotypes ranging from neonatal lethality to adult-onset neurodegeneration, including Leigh syndrome and Parkinson disease (UniProt: P28331).

In Alzheimer's disease, NDUFS1 is upregulated in post-mortem AD brain tissue relative to age-matched controls, with a mean log2 fold-change of 0.726 (Chaparral AD proteomics). This modest elevation was detected by TMT-labeled quantitative proteomics in human brain samples, suggesting altered Complex I expression in AD pathology.