Alanine--tRNA ligase, mitochondrial (AARS2) (AARS2)

Alanine--tRNA ligase, mitochondrial (AARS2) is a nuclear-encoded enzyme essential for the translation of the 13 proteins encoded by the mitochondrial genome, which are critical subunits of the oxidative phosphorylation (OXPHOS) system (UniProt: Q5JTZ9). It catalyzes the attachment of alanine to its cognate tRNA(Ala) in the mitochondrial matrix, a process vital for maintaining cellular energy production (NCBI Gene: 57505). Mutations in the AARS2 gene are primarily associated with two distinct clinical phenotypes: a fatal infantile-onset hypertrophic cardiomyopathy and a later-onset neurodegenerative disorder characterized by leukoencephalopathy and premature ovarian failure (OMIM: 612035). While there are currently no FDA-approved drugs specifically targeting AARS2, it is a significant focus for genetic diagnostics and potential gene therapy interventions aimed at restoring mitochondrial function (PubMed: 21258343). Furthermore, because some cancer cells exhibit a high dependency on mitochondrial biogenesis, AARS2 and other mitochondrial aminoacyl-tRNA synthetases are being investigated as potential targets for metabolic interference in oncology (PubMed: 22962524). This enzyme's dual role in severe genetic disease and potential cancer metabolism makes it a target of interest for both diagnostic and therapeutic development.

Other names

Alanyl-tRNA synthetase 2, mitochondrialAlaRSMT-ALARSAlanine--tRNA ligase 2, mitochondrial

None currently approved; research focuses on gene replacement therapy or potential inhibition of mitochondrial translation in oncology.