NADH dehydrogenase [ubiquinone] iron-sulfur protein 5

NDUFS5 (NADH dehydrogenase [ubiquinone] iron-sulfur protein 5) is an accessory subunit of mitochondrial Complex I (UniProt: O43920). It functions as part of the respiratory chain NADH dehydrogenase complex, facilitating electron transfer from NADH to ubiquinone, though it is not directly involved in catalysis.

As a structural component of Complex I, NDUFS5 is embedded in the mitochondrial membrane and participates in oxidative phosphorylation across multiple tissues. The UniProt record lists no specific inherited disease associations for NDUFS5.

NDUFS5 is upregulated in Alzheimer's disease brain tissue. Chaparral AD proteomics analysis of post-mortem AD brain versus age-matched controls using TMT-labeled quantitative mass spectrometry detected NDUFS5 elevation across one subcellular fraction, with a mean log2 fold-change of +1.22 (Chaparral AD proteomics). This upregulation may reflect compensatory mitochondrial activity or altered bioenergetics in AD pathology.