Inactivation of the Caenorhabditis elegans RNF-5 E3 ligase promotes IRE-1-independent ER functions

Orit Adir, Ulrike Bening-Abu-Shach, Shir Arbib, Sivan Henis-Korenblit, Limor Broday

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)2401-2414
Number of pages14
JournalAutophagy
Volume17
Issue number9
DOIs
StatePublished - 15 Oct 2020

Keywords

  • autophagy, C. elegans
  • endoplasmic reticulum
  • IRE1
  • lysosome
  • RMA1
  • RNF5

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