{"doi":"10.1101/2025.02.03.636310","title":"Loss of an uncharacterized mitochondrial methionine tRNA-synthetase induces mitochondrial unfolded protein response in <i>Caenorhabditis elegans</i>","abstract":"Abstract Aminoacyl-tRNA synthetases (aaRSs) are essential for translation, as they charge tRNA molecules with their corresponding amino acids. Alterations in aaRSs can significantly disrupt both cytosolic and mitochondrial translation. Through a forward genetic screen for mitochondrial unfolded protein response (UPR mt ) activators in C. elegans , we identified a missense mutation (P447V) in the previously uncharacterized gene Y105E8A.20, which encodes a dually localized methionine tRNA synthetase (MetRS). Here, we characterize the UPR mt induction by Y105E8A.20, which we call mars-2 , and demonstrate that the P447V allele is a loss-of-function mutation. Furthermore, we show impaired mars-2 activity in the mitochondria triggers UPR mt . This strain provides a valuable tool for studying mitochondrial translation and understanding how aaRSs are involved in mitochondrial homeostasis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":561572,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1463579,"name":"Mohit Das","orcid":"0000-0001-8224-5500","position":1,"is_corresponding":false},{"id":944279,"name":"James P Held","orcid":"0000-0003-4322-2108","position":2,"is_corresponding":false},{"id":337125,"name":"Maulik Patel","orcid":"0000-0003-3749-0122","position":3,"is_corresponding":false},{"id":1463578,"name":"Bharat Vivan Thapa","orcid":"0000-0002-5269-2139","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:55:58.259104Z","pmid":"39975410","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}