{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zheng WQ"],"funding":["the National Sicence Foundation of China","the national key research and development program of China"],"pagination":["e2309714120"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10500172"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["120(37)"],"pubmed_abstract":["Proofreading (editing) of mischarged tRNAs by cytoplasmic aminoacyl-tRNA synthetases (aaRSs), whose impairment causes neurodegeneration and cardiac diseases, is of high significance for protein homeostasis. However, whether mitochondrial translation needs fidelity and the significance of editing by mitochondrial aaRSs have been unclear. Here, we show that mammalian cells critically depended on the editing of mitochondrial threonyl-tRNA synthetase (mtThrRS, encoded by <i>Tars2</i>), disruption of which accumulated Ser-tRNA<sup>Thr</sup> and generated a large abundance of Thr-to-Ser misincorporated peptides in vivo. Such infidelity impaired mitochondrial translation and oxidative phosphorylation, causing oxidative stress and cell cycle arrest in the G0/G1 phase. Notably, reactive oxygen spec"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Mammalian mitochondrial translation infidelity leads to oxidative stress-induced cell cycle arrest and cardiomyopathy."],"pmcid":["PMC10500172"],"funding_grant_id":["32271300","2021YFA1300800"],"pubmed_authors":["Liu X","Zheng WQ","Huang S","Li J","Zhang Y","Zhang JH","Zhou B","Eriani G","Zhou XL","Wang ED","Li ZH"],"additional_accession":[]},"is_claimable":false,"name":"Mammalian mitochondrial translation infidelity leads to oxidative stress-induced cell cycle arrest and cardiomyopathy.","description":"Proofreading (editing) of mischarged tRNAs by cytoplasmic aminoacyl-tRNA synthetases (aaRSs), whose impairment causes neurodegeneration and cardiac diseases, is of high significance for protein homeostasis. However, whether mitochondrial translation needs fidelity and the significance of editing by mitochondrial aaRSs have been unclear. Here, we show that mammalian cells critically depended on the editing of mitochondrial threonyl-tRNA synthetase (mtThrRS, encoded by <i>Tars2</i>), disruption of which accumulated Ser-tRNA<sup>Thr</sup> and generated a large abundance of Thr-to-Ser misincorporated peptides in vivo. Such infidelity impaired mitochondrial translation and oxidative phosphorylation, causing oxidative stress and cell cycle arrest in the G0/G1 phase. Notably, reactive oxygen spec","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Sep","modification":"2025-04-05T11:39:08.708Z","creation":"2025-04-05T11:39:08.708Z"},"accession":"S-EPMC10500172","cross_references":{"pubmed":["37669377"],"doi":["10.1073/pnas.2309714120"]}}