{"doi":"10.26508/lsa.202402924","title":"<i>idh-1</i>neomorphic mutation confers sensitivity to vitamin B12 in<i>Caenorhabditis elegans</i>","abstract":"In humans, a neomorphic isocitrate dehydrogenase mutation ( idh-1neo ) causes increased levels of cellular D-2-hydroxyglutarate (D-2HG), a proposed oncometabolite. However, the physiological effects of increased D-2HG and whether additional metabolic changes occur in the presence of an idh-1neo mutation are not well understood. We created a Caenorhabditis elegans model to study the effects of the idh-1neo mutation in a whole animal. Comparing the phenotypes exhibited by the idh-1neo to ∆dhgd-1 (D-2HG dehydrogenase) mutant animals, which also accumulate D-2HG, we identified a specific vitamin B12 diet-dependent vulnerability in idh-1neo mutant animals that leads to increased embryonic lethality. Through a genetic screen, we found that impairment of the glycine cleavage system, which generates one-carbon donor units, exacerbates this phenotype. In addition, supplementation with alternate sources of one-carbon donors suppresses the lethal phenotype. Our results indicate that the idh-1neo mutation imposes a heightened dependency on the one-carbon pool and provides a further understanding of how this oncogenic mutation rewires cellular metabolism.","journal":"Life Science Alliance","year":2024,"id":447112,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9466,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1071181,"name":"Alyxandra N. Starbard","orcid":null,"position":1,"is_corresponding":false},{"id":310866,"name":"Alexandra Belfi","orcid":"0000-0001-9237-5085","position":2,"is_corresponding":false},{"id":1265233,"name":"Amanda V Anderson","orcid":null,"position":3,"is_corresponding":false},{"id":310871,"name":"Meera V. Sundaram","orcid":"0000-0002-2940-8750","position":4,"is_corresponding":false},{"id":305730,"name":"Albertha J.M. Walhout","orcid":"0000-0001-5587-3608","position":5,"is_corresponding":false},{"id":305726,"name":"Olga Ponomarova","orcid":"0000-0001-6331-9949","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:01:59.101070Z","pmid":"39009411","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":[]}