Serine--tRNA ligase, mitochondrial

Serine–tRNA ligase, mitochondrial (SARS2) is an aminoacyl-tRNA synthetase that catalyzes the attachment of serine to tRNA(Ser) and participates in selenocysteinyl-tRNA(Sec) formation (UniProt: Q9NP81). The enzyme localizes to the mitochondria, where it functions in protein synthesis. Beyond its canonical role, SARS2 mutations have been associated with HUPRAS (hyperuricemia, pulmonary hypertension, renal failure, and alkalosis syndrome; MIM 613845), a severe multisystem disorder presenting in infancy with progressive renal dysfunction, metabolic alkalosis, and neurodevelopmental delay.

In Alzheimer's Disease, SARS2 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC –1.30; Chaparral AD proteomics). This reduction was detected via TMT-labeled tandem mass spectrometry across subcellular fractions of human brain homogenate. The consistent downregulation suggests impaired mitochondrial protein synthesis capacity may contribute to AD pathology, though the functional consequence of reduced SARS2 levels in AD neurodegeneration remains to be elucidated.