{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T15:12:22Z","timestamp":1777648342369,"version":"3.51.4"},"reference-count":69,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T00:00:00Z","timestamp":1640908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Istituto di Ricerca Pediatrica 'Citt\u00e0 della Speranza'","award":["19\/05"],"award-info":[{"award-number":["19\/05"]}]},{"DOI":"10.13039\/501100003500","name":"University of Padua","doi-asserted-by":"publisher","award":["SID-018"],"award-info":[{"award-number":["SID-018"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Deficit of the IDUA (\u03b1-L-iduronidase) enzyme causes the lysosomal storage disorder mucopolysaccharidosis type I (MPS I), a rare pediatric neurometabolic disease, due to pathological variants in the IDUA gene and is characterized by the accumulation of the undegraded mucopolysaccharides heparan sulfate and dermatan sulfate into lysosomes, with secondary cellular consequences that are still mostly unclarified. Here, we report a new fruit fly RNAi-mediated knockdown model of a IDUA homolog (D-idua) displaying a phenotype mimicking some typical molecular features of Lysosomal Storage Disorders (LSD). In this study, we showed that D-idua is a vital gene in Drosophila and that ubiquitous reduction of its expression leads to lethality during the pupal stage, when the precise degradation\/synthesis of macromolecules, together with a functional autophagic pathway, are indispensable for the correct development to the adult stage. Tissue-specific analysis of the D-idua model showed an increase in the number and size of lysosomes in the brain and muscle. Moreover, the incorrect acidification of lysosomes led to dysfunctional lysosome-autophagosome fusion and the consequent block of autophagy flux. A concomitant metabolic drift of glycolysis and lipogenesis pathways was observed. After starvation, D-idua larvae showed a quite complete rescue of both autophagy\/lysosome phenotypes and metabolic alterations. Metabolism and autophagy are strictly interconnected vital processes that contribute to maintain homeostatic control of energy balance, and little is known about this regulation in LSDs. Our results provide new starting points for future investigations on the disease\u2019s pathogenic mechanisms and possible pharmacological manipulations.<\/jats:p>","DOI":"10.3390\/cells11010129","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T20:49:38Z","timestamp":1641242978000},"page":"129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Drosophila D-idua Reduction Mimics Mucopolysaccharidosis Type I Disease-Related Phenotypes"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9001-1007","authenticated-orcid":false,"given":"Concetta","family":"De Filippis","sequence":"first","affiliation":[{"name":"Laboratory of Diagnosis and Therapy of Lysosomal Disorders, Department of Women\u2019s and Children\u2019s Health, University of Padova, Via Giustiniani 3, 35128 Padova, Italy"},{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, Corso Stati Uniti 4, 35127 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Napoli","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Scientific Institute, IRCCS Eugenio Medea, Via Don Luigi Monza 20, Bosisio Parini, 23842 Lecco, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0233-1677","authenticated-orcid":false,"given":"Laura","family":"Rigon","sequence":"additional","affiliation":[{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, Corso Stati Uniti 4, 35127 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2134-4649","authenticated-orcid":false,"given":"Giulia","family":"Guarato","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhard","family":"Bauer","sequence":"additional","affiliation":[{"name":"Molecular Developmental Biology Unit, Life & Medical Sciences Institute (LIMES), University of Bonn, Carl-Troll-Stra\u00dfe 31, 53115 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-9900","authenticated-orcid":false,"given":"Rosella","family":"Tomanin","sequence":"additional","affiliation":[{"name":"Laboratory of Diagnosis and Therapy of Lysosomal Disorders, Department of Women\u2019s and Children\u2019s Health, University of Padova, Via Giustiniani 3, 35128 Padova, Italy"},{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, Corso Stati Uniti 4, 35127 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genny","family":"Orso","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1590\/S1415-47572010005000093","article-title":"Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment","volume":"33","author":"Giugliani","year":"2010","journal-title":"Genet. 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