NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial

NDUFA9 encodes NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, a 377-amino acid accessory subunit of mitochondrial Complex I (UniProt: Q16795). Although not directly involved in catalysis, NDUFA9 is required for proper Complex I assembly and participates in electron transfer from NADH to ubiquinone within the respiratory chain.

The protein is located in the mitochondrial membrane and functions as part of oxidative phosphorylation machinery. UniProt documents associations with mitochondrial complex I deficiency (MC1DN26, MIM: 618247), an autosomal recessive disorder characterized by defective energy metabolism and variable neurological presentations including leukodystrophy, encephalopathy, and neurodegenerative features.

NDUFA9 shows elevated expression in Alzheimer's disease brain tissue. In post-mortem AD brain compared to age-matched controls (assessed via TMT-labeled proteomics across four subcellular fractions), NDUFA9 is upregulated with a mean log2 fold-change of +1.177 (Chaparral AD proteomics). This upregulation may reflect compensatory responses to mitochondrial dysfunction or altered energy metabolism characteristic of AD pathology.