{"doi":"10.1016/j.celrep.2024.114148","title":"4-Hydroxybenzoic acid rescues multisystemic disease and perinatal lethality in a mouse model of mitochondrial disease","abstract":"<h2>Summary</h2> Coenzyme Q (CoQ) deficiency syndrome is conventionally treated with limited efficacy using exogenous CoQ<sub>10</sub>. Poor outcomes result from low absorption and bioavailability of CoQ<sub>10</sub> and the clinical heterogenicity of the disease. Here, we demonstrate that supplementation with 4-hydroxybenzoic acid (4HB), the precursor of the benzoquinone ring in the CoQ biosynthetic pathway, completely rescues multisystemic disease and perinatal lethality in a mouse model of CoQ deficiency. 4HB stimulates endogenous CoQ biosynthesis in tissues of <i>Coq2</i> mutant mice, normalizing mitochondrial function and rescuing cardiac insufficiency, edema, and neurodevelopmental delay. In contrast, exogenous CoQ<sub>10</sub> supplementation falls short in fully restoring the phenotype. The treatment is translatable to human use, as proven by <i>in vitro</i> studies in skin fibroblasts from patients with pathogenic variants in <i>COQ2</i>. The therapeutic approach extends to other disorders characterized by deficiencies in the production of 4HB and early steps of CoQ biosynthesis and instances of secondary CoQ deficiency.","journal":"Cell Reports","year":2024,"id":425044,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"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":646119,"name":"Juan Manuel Martinez Galvez","orcid":"0000-0003-1526-5282","position":1,"is_corresponding":false},{"id":1222625,"name":"Pilar González‐García","orcid":"0000-0002-9560-2957","position":2,"is_corresponding":false},{"id":857194,"name":"Olivia Wendling","orcid":null,"position":3,"is_corresponding":false},{"id":1222626,"name":"Laura Jiménez-Sánchez","orcid":"0000-0003-4693-8427","position":4,"is_corresponding":false},{"id":1222627,"name":"Sergio López-Herrador","orcid":"0000-0003-1720-3018","position":5,"is_corresponding":false},{"id":248229,"name":"Catarina M. Quinzii","orcid":null,"position":6,"is_corresponding":false},{"id":1223190,"name":"María Elena Díaz-Casado","orcid":null,"position":7,"is_corresponding":false},{"id":397892,"name":"Luís C. López","orcid":"0000-0003-3355-0298","position":8,"is_corresponding":false},{"id":1222624,"name":"Julia Corral-Sarasa","orcid":"0000-0002-2311-2393","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T01:58:26.927596Z","pmid":"38697100","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":[]}