Abstract
RNF5 is implicated in ERAD and in negative regulation of macroautophagy/autophagy. To better understand the function of RNF-5 under ER-stress conditions, we studied the ability of Caenorhabditis elegans rnf-5(tm794) mutant animals to cope with stress in the background of impaired UPR machinery. We demonstrate that downregulation of RNF-5 decreased sensitivity to tunicamycin both in wild type and in an ire-1 mutant. Double-mutant rnf-5;ire-1 animals showed increased starvation resistance and extended lifespan when compared to the ire-1 mutant. This partial rescue of ire-1 required functional autophagy. Downregulation of RNF-5 rescued ER maturation defects and protein secretion of a DAF-28::GFP intestinal reporter in the ire-1 background. Proteomics and functional studies revealed an increase in lysosomal protease levels, in the frequency of intestinal lysosomes, and in lysosomal protease activity in rnf-5(tm794) animals. Together, these data suggest that RNF-5 is a negative regulator of ER stress, and that inactivation of RNF-5 promotes IRE-1-independent elevation of ER capacity.
Original language | English |
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Pages (from-to) | 2401-2414 |
Number of pages | 14 |
Journal | Autophagy |
Volume | 17 |
Issue number | 9 |
Early online date | 15 Oct 2020 |
DOIs | |
State | Published - Sep 2021 |
Keywords
- IRE1
- RMA1
- RNF5
- autophagy, C. elegans
- endoplasmic reticulum
- lysosome
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology