{"doi":"10.1038/emboj.2010.237","title":"Lysosomal fusion and SNARE function are impaired by cholesterol accumulation in lysosomal storage disorders","abstract":null,"journal":"The EMBO Journal","year":2010,"id":604992,"datarank":7.115391981027554,"base_score":5.393627546352361,"endowment":5.393627546352361,"self_citation_contribution":0.8090441319528543,"citation_network_contribution":6.3063478490747,"self_endowment_contribution":0.8090441319528543,"citer_contribution":6.3063478490747,"corpus_percentile":null,"corpus_rank":null,"citation_count":219,"citer_count":200,"citers_with_citation_signal":177,"citers_with_endowment":177,"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":1541244,"name":"Fabio Annunziata","orcid":null,"position":1,"is_corresponding":false},{"id":1552388,"name":"Alessia Lombardi","orcid":null,"position":2,"is_corresponding":false},{"id":1552389,"name":"Hermann‐Josef Kaiser","orcid":null,"position":3,"is_corresponding":false},{"id":1552390,"name":"Diego Luis Medina","orcid":null,"position":4,"is_corresponding":false},{"id":1541240,"name":"Carmine Spampanato","orcid":null,"position":5,"is_corresponding":false},{"id":1552391,"name":"Anthony Olind Fedele","orcid":null,"position":6,"is_corresponding":false},{"id":477146,"name":"Roman Polishchuk","orcid":"0000-0002-7698-1955","position":7,"is_corresponding":false},{"id":948347,"name":"Nicolina Cristina Sorrentino","orcid":"0000-0002-3426-5109","position":8,"is_corresponding":false},{"id":71013,"name":"Kai Simons","orcid":"0000-0002-9231-9996","position":9,"is_corresponding":false},{"id":121646,"name":"Andrea Ballabio","orcid":null,"position":10,"is_corresponding":false},{"id":1552386,"name":"Alessandro Fraldi","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Lysosomal fusion and SNARE function are impaired by cholesterol accumulation in lysosomal storage disorders","abstract":"The function of lysosomes relies on the ability of the lysosomal membrane to fuse with several target membranes in the cell. It is known that in lysosomal storage disorders (LSDs), lysosomal accumulation of several types of substrates is associated with lysosomal dysfunction and impairment of endocytic membrane traffic. By analysing cells from two severe neurodegenerative LSDs, we observed that cholesterol abnormally accumulates in the endolysosomal membrane of LSD cells, thereby reducing the ability of lysosomes to efficiently fuse with endocytic and autophagic vesicles. Furthermore, we discovered that soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNAREs), which are key components of the cellular membrane fusion machinery are aberrantly sequestered in cholesterol-enriched regions of LSD endolysosomal membranes. This abnormal spatial organization locks SNAREs in complexes and impairs their sorting and recycling. Importantly, reducing membrane cholesterol levels in LSD cells restores normal SNARE function and efficient lysosomal fusion. Our results support a model by which cholesterol abnormalities determine lysosomal dysfunction and endocytic traffic jam in LSDs by impairing the membrane fusion machinery, thus suggesting new therapeutic targets for the treatment of these disorders.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20871593","pmcid":"PMC2982760","openalex_id":null,"authors":[],"funders":[{"funder_name":"Telethon","grant_id":"GTF08001","title":null},{"funder_name":"Telethon","grant_id":"TGM06C01","title":null},{"funder_name":"European Research Council","grant_id":"250154","title":"Modulating cellular clearance to cure human disease"}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"Springer TDM","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1038%2Femboj.2010.237","host_type":"publisher"},{"url":"https://link.springer.com/content/pdf/10.1038/emboj.2010.237.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1038/emboj.2010.237","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full/10.1038/emboj.2010.237","host_type":"publisher"},{"url":"https://doi.org/10.15252/embj.2022112402","host_type":""},{"url":"https://doi.org/10.1038/emboj.2010.237","host_type":""},{"url":"https://europepmc.org/articles/pmc2982760?pdf=render","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/36321514","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/20871593","host_type":""},{"url":"http://hdl.handle.net/11588/373259","host_type":""},{"url":"https://dx.doi.org/10.1038/emboj.2010.237","host_type":""},{"url":"https://hdl.handle.net/21.11116/0000-0001-0BB1-B","host_type":""},{"url":"https://hdl.handle.net/11588/373259","host_type":""},{"url":"http://dx.doi.org/10.1038/emboj.2010.237","host_type":""}],"fields_of_study":["0301 basic medicine","03 medical and health sciences"],"mesh_terms":["Cells, Cultured","Lysosomes","Fibroblasts","Animals","Mice","Lysosomal Storage Diseases","Cholesterol","Phospholipids","RNA, Messenger","Fluorescent Antibody Technique","Blotting, Western","Immunoenzyme Techniques","Reverse Transcriptase Polymerase Chain Reaction","Immunoprecipitation","Endocytosis","Membrane Fusion","Autophagy","SNARE Proteins","Lysosomal-Associated Membrane Protein 1","Embryo, Mammalian","ErbB Receptors","Lysosomal Membrane Proteins"],"keywords":["Reverse Transcriptase Polymerase Chain Reaction","Blotting, Western","Fluorescent Antibody Technique","Fibroblasts","Embryo, Mammalian","Lysosomal Membrane Proteins","Membrane Fusion","Endocytosis","ErbB Receptors","Immunoenzyme Techniques","Lysosomal Storage Diseases","Mice","Cholesterol","Autophagy","Animals","Immunoprecipitation","RNA, Messenger","Lysosomes","Cells, Cultured","Phospholipids"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T01:20:22.465254Z","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":[]}