Lipid homeostasis is essential for a maximal ER stress response.
Elife
; 122023 07 25.
Article
in En
| MEDLINE
| ID: mdl-37489956
ABSTRACT
Changes in lipid metabolism are associated with aging and age-related diseases, including proteopathies. The endoplasmic reticulum (ER) is uniquely a major hub for protein and lipid synthesis, making its function essential for both protein and lipid homeostasis. However, it is less clear how lipid metabolism and protein quality may impact each other. Here, we identified let-767, a putative hydroxysteroid dehydrogenase in Caenorhabditis elegans, as an essential gene for both lipid and ER protein homeostasis. Knockdown of let-767 reduces lipid stores, alters ER morphology in a lipid-dependent manner, and blocks induction of the Unfolded Protein Response of the ER (UPRER). Interestingly, a global reduction in lipogenic pathways restores UPRER induction in animals with reduced let-767. Specifically, we find that supplementation of 3-oxoacyl, the predicted metabolite directly upstream of let-767, is sufficient to block induction of the UPRER. This study highlights a novel interaction through which changes in lipid metabolism can alter a cell's response to protein-induced stress.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Unfolded Protein Response
/
Endoplasmic Reticulum Stress
Limits:
Animals
Language:
En
Journal:
Elife
Year:
2023
Document type:
Article