title: Cathepsin-mediated regulation of autophagy in saposin C deficiency.
abstract: Saposin C deficiency, a rare variant form of Gaucher disease, is due to mutations in the prosaposin gene (PSAP) affecting saposin C expression and/or function. We previously reported that saposin C mutations affecting one cysteine residue result in autophagy dysfunction. We further demonstrated that the accumulation of autophagosomes, observed in saposin C-deficient fibroblasts, is due to an impairment of autolysosome degradation, partially caused by the reduced amount and enzymatic activity of CTSB (cathepsin B) and CTSD (cathepsin D). The restoration of both proteases in pathological fibroblasts results in almost completely recovery of autophagic flux and lysosome homeostasis.
authors.affiliation: Department of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tatti
authors.forename: Marialetizia
authors.initials: M
authors.lastname: Motta
authors.forename: Sabrina
authors.initials: S
authors.lastname: Di Bartolomeo
authors.forename: Valentina
authors.initials: V
authors.lastname: Cianfanelli
authors.forename: Rosa
authors.initials: R
authors.lastname: Salvioli
mesh_terms: D001343:Autophagy; D002401:Cathepsin B / Q000378:metabolism*; D002402:Cathepsin D / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D049231:Saposins / Q000172:deficiency* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D049231:Saposins; D058570:TOR Serine-Threonine Kinases; D002401:Cathepsin B; D002402:Cathepsin D
keywords: Gaucher disease; autophagic lysosome reformation; autophagy; cathepsins; glucosylceramidase deficiency; glucosylceramide; lysosomal storage disorders; overexpression; saposin C deficiency