{"doi":"10.1093/braincomms/fcac002","title":"SLC13A5/sodium-citrate co-transporter overexpression causes disrupted white matter integrity and an autistic-like phenotype","abstract":"-lysine acetylation serves as an important protein quality control system for the secretory pathway. Dysfunctional endoplasmic reticulum-based acetylation, as caused by overexpression of the acetyl coenzyme A transporter AT-1 in the mouse, results in altered glycoprotein flux through the secretory pathway and an autistic-like phenotype. AT-1 works in concert with SLC25A1, the citrate/malate antiporter in the mitochondria, SLC13A5, the plasma membrane sodium/citrate symporter and ATP citrate lyase, the cytosolic enzyme that converts citrate into acetyl coenzyme A. Here, we report that mice with neuron-specific overexpression of SLC13A5 exhibit autistic-like behaviours with a jumping stereotypy. The mice displayed disrupted white matter integrity and altered synaptic structure and function. Analysis of both the proteome and acetyl-proteome revealed unique adaptations in the hippocampus and cortex, highlighting a metabolic response that likely plays an important role in the SLC13A5 neuron transgenic phenotype. Overall, our results support a mechanistic link between aberrant intracellular citrate/acetyl coenzyme A flux and the development of an autistic-like phenotype.","journal":"Brain Communications","year":2022,"id":253114,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":177860,"name":"Nicola Salvatore Orefice","orcid":"0000-0001-8135-3737","position":1,"is_corresponding":false},{"id":445993,"name":"Alexis J. Lawton","orcid":"0000-0002-1065-0846","position":2,"is_corresponding":false},{"id":588185,"name":"M Ma","orcid":"0000-0002-3529-0330","position":3,"is_corresponding":false},{"id":710810,"name":"Samantha L. Shapiro","orcid":null,"position":4,"is_corresponding":false},{"id":405387,"name":"Sue Y. Yi","orcid":"0000-0002-1121-9097","position":5,"is_corresponding":false},{"id":704213,"name":"Inca A. Dieterich","orcid":null,"position":6,"is_corresponding":false},{"id":710811,"name":"Alyssa Frelka","orcid":null,"position":7,"is_corresponding":false},{"id":574465,"name":"Hannah N. Miles","orcid":"0000-0002-0952-552X","position":8,"is_corresponding":false},{"id":255057,"name":"Robert A. Pearce","orcid":"0000-0002-1516-6260","position":9,"is_corresponding":false},{"id":405389,"name":"John‐Paul J. Yu","orcid":"0000-0003-1878-052X","position":10,"is_corresponding":false},{"id":289711,"name":"Lingjun Li","orcid":"0000-0003-0056-3869","position":11,"is_corresponding":false},{"id":281307,"name":"John M. Denu","orcid":"0000-0001-9415-0365","position":12,"is_corresponding":false},{"id":299645,"name":"Luigi Puglielli","orcid":"0000-0003-0259-8424","position":13,"is_corresponding":false},{"id":299643,"name":"Michael J. Rigby","orcid":"0000-0001-8809-2648","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T00:24:55.325369Z","pmid":"35146426","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":[]}