{"doi":"10.1101/2020.11.10.376046","title":"Dihydroceramide desaturase promotes the formation of intraluminal vesicles and inhibits autophagy to increase exosome production","abstract":"Summary Exosomes are important for cell-cell communication. Deficiencies in the human dihydroceramide desaturase gene, DEGS1 , increase the dihydroceramide-to-ceramide ratio and causes hypomyelinating leukodystrophy. However, the disease mechanism remains unknown. Here, we developed an in vivo assay with spatially controlled expression of exosome markers in Drosophila eye imaginal discs and showed that the level and activity of the DEGS1 ortholog, ifc , correlated with exosome production. Knocking out ifc decreased the density of the exosome precursor intraluminal vesicles (ILVs) in the multivesicular endosomes and reduced the number of exosomes released. While ifc overexpression and autophagy inhibition both enhanced exosome production, combining the two had no additive effect. Moreover, DEGS1 activity was sufficient to drive ILV formation in vitro . Together, DEGS1/Ifc controls the dihydroceramide-to-ceramide ration and enhances exosome secretion by promoting ILV formation and preventing the autophagic degradation of MVEs. These findings provide a potential cause for the neuropathy associated with DEGS1-deficient mutations. Graphical Abstract Highlights An in vivo system was developed for observing exosome production in Drosophila . Dihydroceramide desaturase (DEGS1/Ifc) promotes exosome production by two means. Ifc drives membrane invagination to promote the formation of intraluminal vesicles. Ifc inhibits autophagic degradation of MVEs and increases exosome release. eTOC Blurb The level and activity of dihydroceramide desaturase (human DEGS1 and Drosophila Ifc) correlate with exosome production. Wu et al. show that DEGS1 drives the formation of intraluminal vesicles in vivo and in vitro . Overexpressing Ifc inhibits autophagy and reduces the degradation of multivesicular endosomes, thus increases exosome release.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":132298,"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":0.9637,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":588406,"name":"Jhih-Gang Jhang","orcid":null,"position":1,"is_corresponding":false},{"id":588407,"name":"Wan-Syuan Lin","orcid":null,"position":2,"is_corresponding":false},{"id":587928,"name":"Chih-Wei Lin","orcid":"0000-0003-4247-6747","position":3,"is_corresponding":false},{"id":587929,"name":"Li‐An Chu","orcid":"0000-0002-4092-3024","position":4,"is_corresponding":false},{"id":588408,"name":"Ann‐Shyn Chiang","orcid":null,"position":5,"is_corresponding":false},{"id":587930,"name":"Han‐Chen Ho","orcid":"0000-0002-8638-9760","position":6,"is_corresponding":false},{"id":66118,"name":"Chih-Chiang Chan","orcid":"0000-0003-2626-3805","position":7,"is_corresponding":false},{"id":66111,"name":"Shu-Yi Huang","orcid":"0000-0002-3522-0500","position":8,"is_corresponding":false},{"id":588405,"name":"Chen-Yi Wu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-18T23:16:10.654971Z","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":[]}