Inhibition of autophagy, lysosome and VCP function impairs stress granule assembly

• DOI: 10.1038/cdd.2014.103
• Publication Date: 2014-07-18T12:20:20Z
• Authors: S J Seguin; F F Morelli; J Vinet; D Amore; S De Biasi; A Poletti; D C Rubinsztein; S Carra
• Keywords: Stress granule; Polysome

Stress granules (SGs) are mRNA-protein aggregates induced during stress, which accumulate in many neurodegenerative diseases. Previously, the autophagy-lysosome pathway and valosin-containing protein (VCP), key players of quality control (PQC), were shown to regulate SG degradation. This is consistent with idea that PQC may survey and/or assist dynamics. However, despite these observations, it currently unknown whether actively participates assembly. Here, we describe inhibition autophagy, lysosomes VCP causes defective formation after induction. Silencing co-factors UFD1L PLAA, degrade ribosomal products (DRIPs) 60S ribosomes, also impaired Intriguingly, DRIPs 60S, released from disassembling polysomes normally excluded SGs, significantly retained within SGs cells lysosome or function. Our results suggest deregulated lysosomal activities, occur several (VCP-associated) diseases, alter morphology composition.