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Lipid bilayer stress‐activated IRE‐1 modulates autophagy during endoplasmic reticulum stress
Author(s) -
Thibault Guillaume,
Koh Jhee Hong,
Wang Lei,
BeaudoinChabot Caroline
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.476.28
Subject(s) - unfolded protein response , endoplasmic reticulum , microbiology and biotechnology , autophagy , proteostasis , atf6 , homeostasis , biology , biochemistry , apoptosis
Metabolic disorders, such as non‐alcoholic fatty liver disease (NAFLD), are emerging as 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 (also known as ERN1 in mammals) and PERK (also known as EIF2AK3 in mammals) 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. Here, we show that disrupted phosphatidylcholine (PC) synthesis in Caenorhabditis elegans causes lipid bilayer stress, lipid droplet accumulation and ER stress induction. Transcriptional profiling of PC‐deficient worms revealed 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 the lipid bilayer stress‐induced UPR. Support or Funding Information This work was supported by the Nanyang Assistant Professorship programme from the Nanyang Technological University, the Ministry of Education ‐ Singapore Academic Research Fund Tier 1 (2016‐T1‐001‐078), and the Nanyang Technological University Research Scholarship to J.H.K. (predoctoral fellowship). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .