{"doi":"10.1074/jbc.ra120.015175","title":"Cholesterol stimulates the cellular uptake of L-carnitine by the carnitine/organic cation transporter novel 2 (OCTN2)","abstract":null,"journal":"Journal of Biological Chemistry","year":2021,"id":602317,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1544652,"name":"Ting Gui","orcid":null,"position":1,"is_corresponding":false},{"id":1544653,"name":"Lara Console","orcid":"0000-0002-0238-0946","position":2,"is_corresponding":false},{"id":1544654,"name":"Mariafrancesca Scalise","orcid":"0000-0003-3860-6844","position":3,"is_corresponding":false},{"id":763414,"name":"Cesare Indiveri","orcid":"0000-0001-9818-6621","position":4,"is_corresponding":false},{"id":1544655,"name":"Stephanie Hausler","orcid":null,"position":5,"is_corresponding":false},{"id":1016896,"name":"Gerd A. Kullak‐Ublick","orcid":"0000-0002-0757-4408","position":6,"is_corresponding":false},{"id":1544656,"name":"Zhibo Gai","orcid":"0000-0003-1673-6541","position":7,"is_corresponding":false},{"id":1544657,"name":"Michele Visentin","orcid":"0000-0002-0209-5600","position":8,"is_corresponding":false},{"id":1128466,"name":"Lu Zhang","orcid":"0000-0001-8358-6112","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Cholesterol stimulates the cellular uptake of L-carnitine by the carnitine/organic cation transporter novel 2 (OCTN2)","abstract":"The carnitine/organic cation transporter novel 2 (OCTN2) is responsible for the cellular uptake of carnitine in most tissues. Being a transmembrane protein OCTN2 must interact with the surrounding lipid microenvironment to function. Among the main lipid species that constitute eukaryotic cells, cholesterol has highly dynamic levels under a number of physiopathological conditions. This work describes how plasma membrane cholesterol modulates OCTN2 transport of L-carnitine in human embryonic kidney 293 cells overexpressing OCTN2 (OCTN2-HEK293) and in proteoliposomes harboring human OCTN2. We manipulated the cholesterol content of intact cells, assessed by thin layer chromatography, through short exposures to empty and/or cholesterol-saturated methyl-β-cyclodextrin (mβcd), whereas free cholesterol was used to enrich reconstituted proteoliposomes. We measured OCTN2 transport using [ 3 H]L-carnitine, and expression levels and localization by surface biotinylation and Western blotting. A 20-min preincubation with mβcd reduced the cellular cholesterol content and inhibited L-carnitine influx by 50% in comparison with controls. Analogously, the insertion of cholesterol in OCTN2-proteoliposomes stimulated L-carnitine uptake in a dose-dependent manner. Carnitine uptake in cells incubated with empty mβcd and cholesterol-saturated mβcd to preserve the cholesterol content was comparable with controls, suggesting that the mβcd effect on OCTN2 was cholesterol dependent. Cholesterol stimulated L-carnitine influx in cells by markedly increasing the affinity for L-carnitine and in proteoliposomes by significantly enhancing the affinity for Na + and, in turn, the L-carnitine maximal transport capacity. Because of the antilipogenic and antioxidant features of L-carnitine, the stimulatory effect of cholesterol on L-carnitine uptake might represent a novel protective effect against lipid-induced toxicity and oxidative stress.","is_dataset_classified":null,"base_score":2.833213344056216,"endowment":2.833213344056216,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33334877","pmcid":"PMC7948396","openalex_id":"https://openalex.org/W3111458291","authors":[],"funders":[{"funder_name":"Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung","grant_id":"310030_175639","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"175639","title":"Role of drug transporters and nuclear receptors in drug-induced liver and kidney injury"},{"funder_name":"Università della Calabria","grant_id":"","title":null},{"funder_name":"Chengdu University of Traditional Chinese Medicine","grant_id":"","title":null}],"total_grants":4,"fwci":0.7449,"citation_percentile":0.68522484,"influential_citations":0,"citation_trend":[{"year":2021,"count":2},{"year":2022,"count":3},{"year":2023,"count":1},{"year":2024,"count":5},{"year":2025,"count":1},{"year":2026,"count":4}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S0021925820002008/pdf","host_type":"journal"},{"url":"http://www.jbc.org/article/S0021925820002008/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820002008?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820002008?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.RA120.015175","host_type":"publisher"},{"url":"https://doi.org/10.1074/jbc.ra120.015175","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33334877","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7948396","host_type":"repository"},{"url":"https://doi.org/10.5167/uzh-199987","host_type":""},{"url":"https://europepmc.org/articles/PMC7948396","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7948396?pdf=render","host_type":"Europe_PMC"},{"url":"https://dx.doi.org/10.5167/uzh-199987","host_type":""},{"url":"http://dx.doi.org/10.1074/jbc.RA120.015175","host_type":""},{"url":"https://dx.doi.org/10.1074/jbc.ra120.015175","host_type":""},{"url":"https://hdl.handle.net/20.500.14243/520674","host_type":""},{"url":"https://doi.org/10.1074/jbc.RA120.015175","host_type":""},{"url":"https://hdl.handle.net/20.500.11770/324546","host_type":""},{"url":"https://www.zora.uzh.ch/id/eprint/199987/","host_type":""}],"fields_of_study":["Metabolism and Genetic Disorders","Amino Acid Enzymes and Metabolism","Mitochondrial Function and Pathology","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Solute Carrier Family 22 Member 5","Biological Transport","Carnitine","Cholesterol","Humans","Proteolipids","HEK293 Cells"],"keywords":["Carnitine","Organic cation transport proteins","Transporter","Chemistry","Biochemistry","Cholesterol","Gene","Membrane lipid","L-Carnitine","Membrane Transport","Methyl-β-cyclodextrin","Proteoliposomes","Proteolipids","610 Medicine & health","Biological Transport","Cell Biology","HEK293 Cells","10199 Clinic for Clinical Pharmacology and Toxicology","Humans","Solute Carrier Family 22 Member 5","Molecular Biology","Research Article"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T19:01:58.108984Z","pmid":null,"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":[]}