Activation of the integrated stress response contributes to developmental delay and seizures caused by mitochondrial prolyl-tRNA synthetase (PARS2) deficiency.

ABSTRACT: Mutations in mitochondrial aminoacyl-tRNA synthetases (mtARSs) causes mitochondrial defects and serious, progressive and usually lethal diseases with exceptional heterogeneous and tissue-specific clinical manifestations. However, the pathogenic mechanisms for specific mtARS related diseases are largely unknown and currently there is no highly effective treatment or cure for these diseases. In the present study, we generate Drosophila models with human mitochondrial prolyl-tRNA synthetase (PARS2) deficiency by knocking out or knocking down dPARS2, the Drosophila ortholog of human PARS2, and further characterize the disease-associated defects and explore the molecular basis of these phenotypes. Inactivation of dPARS2 in Drosophila causes developmental delay and seizure, two main clinical fea

SUBMITTER: Xu M 

PROVIDER: S-EPMC12754399 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature