Open AccessLipid bilayer stress-activated IRE-1 modulates autophagy during endoplasmic reticulum stress
Author(s) -
Jhee Hong Koh,
Lei Wang,
Caroline BeaudoinChabot,
Guillaume Thibault
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.217992
Subject(s) - unfolded protein response , endoplasmic reticulum , biology , microbiology and biotechnology , autophagy , proteostasis , atf6 , homeostasis , biochemistry , apoptosis
Metabolic disorders such as nonalcoholic fatty liver disease (NAFLD) are emerging epidemics that affect the global population. One facet of these disorders is attributed to the disturbance of membrane lipid composition. Perturbation of endoplasmic reticulum (ER) homeostasis through alteration in membrane phospholipids activates the unfolded protein response (UPR) and causes dramatic transcriptional and translational changes in the cell. To restore cellular homeostasis, the three highly conserved UPR transducers ATF6, IRE1, and PERK mediate adaptive responses upon ER stress. The homeostatic UPR cascade is well characterised under conditions of proteotoxic stress, but much less so under lipid bilayer stress induced-UPR. Disrupted phosphatidylcholine (PC) synthesis in C. elegans causes lipid bilayer stress, lipid droplet accumulation and ER stress induction. Transcriptional profiling of PC-deficient worms shows a unique subset of genes regulated in a UPR-dependent manner that is independent from proteotoxic stress. Among these, we show that autophagy is modulated through the conserved IRE-1/XBP-1 axis, strongly suggesting of the importance of autophagy in maintaining cellular homeostasis during lipid bilayer induced-UPR.