A functional endosomal pathway is necessary for lysosome biogenesis in $Drosophila$

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Jacomin, Anne-Claire | Fauvarque, Marie-Odile | Taillebourg, Emmanuel

Edité par CCSD ; BioMed Central -

International audience. Background: Lysosomes are the major catabolic compartment within eukaryotic cells, and their biogenesis requires the integration of the biosynthetic and endosomal pathways. Endocytosis and autophagy are the primary inputs of the lysosomal degradation pathway. Endocytosis is specifically needed for the degradation of membrane proteins whereas autophagy is responsible for the degradation of cytoplasmic components. We previously identified the deubiquitinating enzyme UBPY/USP8 as being necessary for lysosomal biogenesis and productive autophagy in Drosophila. Because UBPY/USP8 has been widely described for its function in the endosomal system, we hypothesized that disrupting the endosomal pathway itself may affect the biogenesis of the lysosomes. Results: In the present study, we blocked the progression of the endosomal pathway at different levels ofmaturation of the endosomes by expressing in fat body cells either dsRNAs or dominant negative mutantstargeting components of the endosomal machinery: Shibire, Rab4, Rab5, Chmp1 and Rab7. We observed thatinhibition of endosomal trafficking at different steps in vivo is systematically associated with defects in lysosomebiogenesis, resulting in autophagy flux blockade.Conclusion: Our results show that the integrity of the endosomal system is required for lysosome biogenesis andproductive autophagy in vivo.

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