Disease models of mitochondrial aminoacyl‐tRNA synthetase defects

Abstract

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.

SSIEM 2022 Annual Symposium in Freiburg, Germany

“…Metabolism meets genetics focused on mitochondria. Henna Tyynisma reviewed how genetics changed the face of mitochondrial disease and demonstrated disease models of mitochondrial aminoacyl‐tRNA synthetase defects 5 . Holger Prokisch presented multiomics pipelines as a tool to improve understanding of variant pathogenicity in mitochondrial disorders as outlined in his article “Integrative omics approaches to advance rare disease diagnostics” 6…”