NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial

NDUFS4 is an accessory subunit of mitochondrial Complex I (NADH dehydrogenase), a multi-protein enzyme complex embedded in the inner mitochondrial membrane. Although NDUFS4 is not directly involved in catalysis, it supports Complex I's function in transferring electrons from NADH to ubiquinone along the respiratory chain (UniProt: O43181).

NDUFS4 is implicated in mitochondrial oxidative phosphorylation and neurological function. Mutations in NDUFS4 cause mitochondrial complex I deficiency, nuclear type 1 (MC1DN1), a heterogeneous disorder affecting 1 in 5–10,000 live births with variable presentations including progressive leukodystrophy, encephalopathy, cardiomyopathy, and neurodegenerative phenotypes such as Parkinson disease (UniProt: O43181).

NDUFS4 is upregulated in Alzheimer's Disease brain tissue. Post-mortem analysis of AD brain compared to age-matched controls revealed increased NDUFS4 protein levels (mean log2 fold-change: 0.89) in human samples analyzed by quantitative proteomics (Chaparral AD proteomics), suggesting altered mitochondrial Complex I composition or abundance in the AD brain.