Alpha-aminoadipic semialdehyde synthase, mitochondrial

Alpha-aminoadipic semialdehyde synthase (AASS) is a mitochondrial bifunctional enzyme that catalyzes the first two steps in lysine degradation (UniProt: Q9UDR5). The protein functions in amino acid metabolism within mitochondria, a critical compartment for cellular energy production and metabolic homeostasis. Loss-of-function mutations in AASS cause hyperlysinemia and related inborn errors of metabolism affecting lysine and fatty acid processing, which can result in encephalopathy and neurologic abnormalities in severe cases (UniProt: Q9UDR5).

In Alzheimer's Disease, AASS is upregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is +0.7026 across three subcellular fractions in a TMT-labeled quantitative proteomics study of four subcellular compartments. This elevation may reflect compensatory changes in mitochondrial lysine catabolism or energy metabolism in response to AD-related neurodegeneration. The functional significance of increased AASS expression in AD pathogenesis remains to be determined.