title: The Deubiquitinating Enzyme UBPY Is Required for Lysosomal Biogenesis and Productive Autophagy in Drosophila.
abstract: Autophagy is a catabolic process that delivers cytoplasmic components to the lysosomes. Protein modification by ubiquitination is involved in this pathway: it regulates the stability of autophagy regulators such as BECLIN-1 and it also functions as a tag targeting specific substrates to autophagosomes. In order to identify deubiquitinating enzymes (DUBs) involved in autophagy, we have performed a genetic screen in the Drosophila larval fat body. This screen identified Uch-L3, Usp45, Usp12 and Ubpy. In this paper, we show that Ubpy loss of function results in the accumulation of autophagosomes due to a blockade of the autophagy flux. Furthermore, analysis by electron and confocal microscopy of Ubpy-depleted fat body cells revealed altered lysosomal morphology, indicating that Ubpy inactivation affects lysosomal maintenance and/or biogenesis. Lastly, we have shown that shRNA mediated inactivation of UBPY in HeLa cells affects autophagy in a different way: in UBPY-depleted HeLa cells autophagy is deregulated.
authors.affiliation: Université Grenoble-Alpes, F-38041, Grenoble, France; CEA-DSV-iRTSV-BGE-Gen&Chem, F-38054, Grenoble, France; INSERM, U1038, F-38054, Grenoble, France.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Jacomin
authors.affiliation: Université Grenoble-Alpes, F-38041, Grenoble, France; CEA-DSV-iRTSV-BGE-Gen&Chem, F-38054, Grenoble, France; INSERM, U1038, F-38054, Grenoble, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Bescond
authors.affiliation: Université Grenoble-Alpes, F-38041, Grenoble, France; CEA-DSV-iRTSV-BGE-Gen&Chem, F-38054, Grenoble, France; INSERM, U1038, F-38054, Grenoble, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Soleilhac
authors.affiliation: Université Grenoble Alpes, IBS, F-38044, Grenoble, France; CNRS, IBS, F-38044, Grenoble, France; CEA, IBS, F-38044, Grenoble, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Gallet
authors.affiliation: Université Grenoble Alpes, IBS, F-38044, Grenoble, France; CNRS, IBS, F-38044, Grenoble, France; CEA, IBS, F-38044, Grenoble, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Schoehn
authors.affiliation: Université Grenoble-Alpes, F-38041, Grenoble, France; CEA-DSV-iRTSV-BGE-Gen&Chem, F-38054, Grenoble, France; INSERM, U1038, F-38054, Grenoble, France.
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Fauvarque
authors.affiliation: Université Grenoble-Alpes, F-38041, Grenoble, France; CEA-DSV-iRTSV-BGE-Gen&Chem, F-38054, Grenoble, France; INSERM, U1038, F-38054, Grenoble, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Taillebourg
mesh_terms: D000818:Animals; D001343:Autophagy; D055162:Biocatalysis; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology* / Q000648:ultrastructure; D010450:Endopeptidases / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D020868:Gene Silencing; D005820:Genetic Testing; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D001678:Organelle Biogenesis; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D050505:Mutant Proteins; D010450:Endopeptidases; C000608556:USP8 protein, Drosophila; C541534:USP8 protein, human; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases