NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5

NDUFA5 is an accessory subunit of mitochondrial Complex I (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex), a key enzyme in the electron transport chain. Although not directly involved in catalysis, NDUFA5 supports Complex I's function in transferring electrons from NADH to ubiquinone during oxidative phosphorylation (UniProt: Q16718).

As a structural component of Complex I, NDUFA5 participates in mitochondrial oxidative metabolism, a fundamental process affecting neuronal energy production and cellular redox balance. The protein is expressed in tissues with high metabolic demand, particularly the brain (UniProt: Q16718).

NDUFA5 is significantly downregulated in Alzheimer's disease brain tissue compared to age-matched controls (mean log2 fold-change −0.331, Chaparral AD proteomics). This reduction in a Complex I accessory subunit may contribute to impaired mitochondrial function observed in AD, potentially affecting neuronal bioenergetics and increasing oxidative stress vulnerability in affected neurons.