Glutamyl-tRNA synthetase 2, mitochondrial (EARS2)

Glutamyl-tRNA synthetase 2, mitochondrial (EARS2) is a nuclear-encoded mitochondrial enzyme responsible for attaching the amino acid glutamate to corresponding tRNAs (tRNA^Glu^, tRNA^Gln^) within the mitochondrion[1][2][5]. This process is essential for synthesizing the 13 mitochondrial DNA-encoded subunits of the electron transport chain, thus critically supporting mitochondrial energy production, protein synthesis, and metabolic homeostasis[4]. EARS2 acts via a two-step reaction: activating glutamate with ATP to form Glu-AMP, then transferring the glutamate to the tRNA. For tRNA^Gln^, EARS2 first aminoacylates it with glutamate, which is then converted to glutaminyl-tRNA in a separate transamidation step by the GatCAB complex[3][4]. Pathogenic mutations in EARS2 disrupt mitochondrial translation, impair oxidative phosphorylation, and cause diseases such as COXPD12 and LTBL, characterized by lactic acidosis, central nervous system dysfunction, and metabolic abnormalities[1][2][4]. Biomarker studies show characteristic changes in TCA cycle metabolites, nucleotide metabolism, and elevated lactate, which help stratify phenotypes and may inform prognosis[1][4]. At present, EARS2 is considered an essential enzyme for mitochondrial function rather than a direct drug target; disease-modifying interventions would need to address the downstream metabolic consequences of its deficiency[4][5].

Other names

Nondiscriminating glutamyl-tRNA synthetase EARS2, mitochondrialEARS2KIAA1970GluRSmtGluRSMSE1mtGlnRSGlutamate--tRNA(Gln) ligase EARS2, mitochondrialGlutamyl-tRNA synthetaseMitochondrial glutamyl-tRNA synthetaseglutamate tRNA ligase 2, mitochondrialCOXPD12glutamate--tRNA ligaseprobable glutamyl-tRNA synthetase, mitochondrial

Not directly targeted by drugs; but impaired function could theoretically be ameliorated by therapies aiming to enhance mitochondrial function, redox balance, or metabolic compensation