Open AccessRegulation of lipid metabolism by the unfolded protein response
Author(s) -
Moncan Matthieu,
Mnich Katarzyna,
Blomme Arnaud,
Almanza Aitor,
Samali Afshin,
Gorman Adrienne M.
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16255
Subject(s) - unfolded protein response , endoplasmic reticulum , lipid metabolism , atf6 , microbiology and biotechnology , protein kinase a , kinase , endoplasmic reticulum associated protein degradation , biology , protein folding , biochemistry , chemistry
Abstract The endoplasmic reticulum (ER) is the site of protein folding and secretion, Ca 2+ storage and lipid synthesis in eukaryotic cells. Disruption to protein folding or Ca 2+ homeostasis in the ER leads to the accumulation of unfolded proteins, a condition known as ER stress. This leads to activation of the unfolded protein response (UPR) pathway in order to restore protein homeostasis. Three ER membrane proteins, namely inositol‐requiring enzyme 1 (IRE1), protein kinase RNA‐like ER kinase (PERK) and activating transcription factor 6 (ATF6), sense the accumulation of unfolded/misfolded proteins and are activated, initiating an integrated transcriptional programme. Recent literature demonstrates that activation of these sensors can alter lipid enzymes, thus implicating the UPR in the regulation of lipid metabolism. Given the presence of ER stress and UPR activation in several diseases including cancer and neurodegenerative diseases, as well as the growing recognition of altered lipid metabolism in disease, it is timely to consider the role of the UPR in the regulation of lipid metabolism. This review provides an overview of the current knowledge on the impact of the three arms of the UPR on the synthesis, function and regulation of fatty acids, triglycerides, phospholipids and cholesterol.