Tyrosine--tRNA ligase, mitochondrial (YARS2)

Tyrosine--tRNA ligase, mitochondrial—commonly abbreviated as YARS2—is an essential enzyme that catalyzes the attachment of L‑tyrosine to its corresponding tRNA(Tyr) within mitochondria, enabling accurate translation of the genetic code into proteins required for oxidative phosphorylation and other critical cellular functions[1][3][9]. In addition to its canonical aminoacylation activity, the enzyme exhibits bifunctionality in certain fungi such as Neurospora crassa, where it also acts as a cofactor promoting RNA splicing of group I introns—a property linked to specific structural adaptations not found in non-fungal homologs[1][7]. Mutations or deficiencies in human YARS2 disrupt proper assembly and function of respiratory chain complexes, leading to defects such as optic neuropathy and broader manifestations typical of mitochondrial disease syndromes including impaired vision and neuromuscular symptoms[5]. While no approved drugs directly target this enzyme therapeutically, its unique features have been proposed as potential antifungal targets given their absence from human homologs. The fundamental importance of YARS2 for cell viability means that any therapeutic intervention must be approached cautiously due to high risk for off-target toxicity affecting energy metabolism throughout the body.

Other names

Mitochondrial tyrosyl-tRNA synthetaseYARS2CYT-18 (in Neurospora crassa and some fungi)mt-TyrRS

No drugs with defined mechanisms targeting this enzyme; however, inhibition would be expected to impair mitochondrial translation and energy production.