ER quality control: how cells detoxify their own membrane from lipid stress
Abstract
The endoplasmic reticulum (ER) is the principal site of glycerolipid synthesis in eukaryotic cells. The continuous production of lipid intermediates, including phosphatidic acid (PA), diacylglycerol (DAG), and triacylglycerol (TAG), destabilizes the ER membrane when they accumulate. To maintain bilayer integrity, cells deploy two sequential strategies: enzymatic conversion of these intermediates into membrane-compatible phospholipids, and their physical sequestration into lipid droplets (LDs), ERderived organelles whose biogenesis is actively regulated by the seipin complex. LD growth is further sustained by the relocalization of TAG-synthesizing enzymes to the LD surface and by bridge-like lipid transfer proteins at ER-LD contact sites. When these mechanisms are overwhelmed, the accumulation of non-bilayer lipids drives ER stress and lipotoxicity, thereby contributing to the development of metabolic diseases. Here, we review the molecular logic of ER lipid quality control, from intermediatedriven membrane stress to the regulated responses that neutralize it.
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BibTeX
@article{elhan2026quality,
title = {{ER quality control: how cells detoxify their own membrane from lipid stress}},
author = {Helin Elhan and Abdou Rachid Thiam},
journal = {Biochimie},
year = {2026},
month = jul,
doi = {10.1016/j.biochi.2026.07.007},
url = {https://hal.science/hal-05768674v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - ER quality control: how cells detoxify their own membrane from lipid stress
AU - Helin Elhan
AU - Abdou Rachid Thiam
PY - 2026
DA - 2026/07/17
JO - Biochimie
DO - 10.1016/j.biochi.2026.07.007
UR - https://hal.science/hal-05768674v1
AB - The endoplasmic reticulum (ER) is the principal site of glycerolipid synthesis in eukaryotic cells. The continuous production of lipid intermediates, including phosphatidic acid (PA), diacylglycerol (DAG), and triacylglycerol (TAG), destabilizes the ER membrane when they accumulate. To maintain bilayer integrity, cells deploy two sequential strategies: enzymatic conversion of these intermediates into membrane-compatible phospholipids, and their physical sequestration into lipid droplets (LDs), ERderived organelles whose biogenesis is actively regulated by the seipin complex. LD growth is further sustained by the relocalization of TAG-synthesizing enzymes to the LD surface and by bridge-like lipid transfer proteins at ER-LD contact sites. When these mechanisms are overwhelmed, the accumulation of non-bilayer lipids drives ER stress and lipotoxicity, thereby contributing to the development of metabolic diseases. Here, we review the molecular logic of ER lipid quality control, from intermediatedriven membrane stress to the regulated responses that neutralize it.
SN - 0300-9084
SN - 1638-6183
ER -