NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4

NDUFB4 (NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4) is an accessory subunit of mitochondrial Complex I that supports the transfer of electrons from NADH to ubiquinone in the respiratory chain (UniProt: O95168). Although not directly involved in catalysis, NDUFB4 is essential for Complex I assembly and function, forming part of the membrane-anchored beta subcomplex. The protein localizes to the inner mitochondrial membrane where it participates in oxidative phosphorylation.

Complex I dysfunction is implicated in neurodegenerative disease pathways, and mitochondrial electron transport chain components are known to be affected in Alzheimer's Disease. NDUFB4 shows downregulation in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.59 (Chaparral AD proteomics). This reduction was detected across subcellular fractions in TMT-labeled proteomic analysis of human brain samples. The downregulation of Complex I subunits may reflect compromised mitochondrial bioenergetics and oxidative stress responses characteristic of AD pathology.