Disease models of mitochondrial aminoacyl-tRNA synthetase defects

Mitochondrial aminoacyl-tRNA synthetases (mtARS) are enzymes critical for the first step of mitochondrial protein synthesis by charging mitochondrial tRNAs with their cognate amino acids. Pathogenic variants in all 19 nuclear mtARS genes are now recognized as causing recessive mitochondrial diseases. Most mtARS disorders affect the nervous system, but the phenotypes range from multisystem diseases to tissue-specific manifestations. However, the mechanisms behind the tissue specificities are poorly understood, and challenges remain in obtaining accurate disease models for developing and testing treatments. Here, some of the currently existing disease models that have increased our understanding of mtARS defects are discussed.

Automated summary

Mitochondrial aminoacyl-tRNA synthetases (mtARS) are enzymes essential for mitochondrial protein synthesis. Pathogenic variants in these genes can cause recessive mitochondrial diseases with a wide range of phenotypes. Understanding the tissue specificities and developing accurate disease models for treatment testing are ongoing challenges in this field. This article discusses current disease models that have improved our understanding of mtARS defects.