{"doi":"10.1101/2025.09.10.675383","title":"Early Proteomic and Metabolic Signatures of Liver and Eye in OAT-Deficient Mice","abstract":"mice, a whole-body OAT-deficient model. We found that the number of significantly altered proteins ranged from 5 to 254 across tissues and ages, with minimal changes in the adult retina and greatest changes in the adult RPE/Cho. OAT was the only protein consistently downregulated across all tissues. Neonatal liver proteome was more extensively altered than the adult liver proteome, primarily impacting metabolic pathways, including fatty acid oxidation, detoxification, cholesterol synthesis, and the urea cycle. In contrast, the adult liver showed changes mainly in detoxification and chromosome remodeling. Similarly, the neonatal retina was far more sensitive to OAT deficiency, with alterations not only in metabolism but also in visual transduction, ion and small molecule transport proteins. The RPE/Cho displayed the most pronounced changes in both age groups. In adults, several mitochondrial and signaling proteins were downregulated, while proteins in lipid metabolism, cytoskeleton, and extracellular matrix (ECM) were upregulated. In neonates, the alterations were enriched in chromatin organization, ECM, and vesicle transport. In summary, our findings reveal that OAT is crucial for maintaining age- and tissue-specific proteome homeostasis, with its deficiency leading to alterations in mitochondrial, metabolic processes, and signaling pathways that extend far beyond its canonical role in ornithine metabolism.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":575177,"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":0.8875,"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":109147,"name":"Rong Xu","orcid":"0000-0003-3127-4795","position":1,"is_corresponding":false},{"id":1483505,"name":"Isabella Mascari","orcid":null,"position":2,"is_corresponding":false},{"id":1483506,"name":"Tuan Ngo","orcid":null,"position":3,"is_corresponding":false},{"id":552601,"name":"Ying Zhang","orcid":"0000-0002-5885-0214","position":4,"is_corresponding":false},{"id":1483156,"name":"Qingyan Wang","orcid":"0000-0002-8565-8690","position":5,"is_corresponding":false},{"id":1060981,"name":"Meghashri Saravanan","orcid":null,"position":6,"is_corresponding":false},{"id":337164,"name":"Jianhai Du","orcid":"0000-0002-2019-8128","position":7,"is_corresponding":false},{"id":1423985,"name":"Artjola Puja","orcid":"0000-0001-5991-813X","position":0,"is_corresponding":true}],"reference_count":109,"raw_metadata":null,"created_at":"2026-07-19T02:57:48.486077Z","pmid":"41000928","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":[]}