NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9

NDUFB9 (NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9) is an accessory subunit of mitochondrial Complex I that facilitates electron transfer from NADH to ubiquinone in the respiratory chain (UniProt: Q9Y6M9). Although not directly involved in catalysis, it is essential for Complex I assembly and function.

NDUFB9 is expressed in mitochondria across tissues. Pathogenic variants cause mitochondrial complex I deficiency, nuclear type 24 (MC1DN24), an autosomal recessive disorder presenting with variable neurodegenerative phenotypes including progressive leukodystrophy, Leigh syndrome, and parkinsonism (UniProt: Q9Y6M9). This highlights the critical role of Complex I in neuronal energy metabolism.

In Alzheimer's Disease, NDUFB9 shows ambiguous direction of change across post-mortem brain fractions, with a mean log2 fold-change of 0.21 relative to age-matched controls (Chaparral AD proteomics). The mixed directional pattern across subcellular fractions suggests complex, compartment-dependent changes in Complex I composition during AD pathology, potentially reflecting alterations in mitochondrial function relevant to neurodegeneration.