The Deubiquitinating Enzyme UBPY Is Required for Lysosomal Biogenesis and Productive Autophagy in Drosophila.

Anne-Claire Jacomin (1) , Amandine Bescond (1) , Emmanuelle Soleilhac (1) , Benoit Gallet (2) , Guy Schoehn (2) , Marie-Odile Fauvarque (1) , Emmanuel Taillebourg (1)

1 CEA Grenoble/DSV
2 IBS - UMR 5075 - Institut de biologie structurale

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.

Domaines: Biologie structurale [q-bio.BM]

Anne-Claire Jacomin, Amandine Bescond, Emmanuelle Soleilhac, Benoit Gallet, Guy Schoehn, et al.. The Deubiquitinating Enzyme UBPY Is Required for Lysosomal Biogenesis and Productive Autophagy in Drosophila.. PLoS ONE, 2015, 10 (11), pp.e0143078. ⟨hal-01251974⟩