Einzeltreffer — DigiBib

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 (UPR ER ). Interestingly, a global reduction in lipogenic pathways restores UPR ER 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 UPR ER . This study highlights a novel interaction through which changes in lipid metabolism can alter a cell's response to protein-induced stress.

Competing Interests: GG, HZ, SM, CT, BW, RH, AD No competing interests declared

Titel:	Lipid homeostasis is essential for a maximal ER stress response.
Autor/in / Beteiligte Person:	Garcia, G ; Zhang, H ; Moreno, S ; Tsui, CK ; Webster, BM ; Higuchi-Sanabria, R ; Dillin, A
Zeitschrift:	ELife, Jg. 12 (2023-07-25)
Veröffentlichung:	Cambridge, UK : eLife Sciences Publications, Ltd., 2012-, 2023
Medientyp:	academicJournal
ISSN:	2050-084X (electronic)
DOI:	10.7554/eLife.83884
Schlagwort:	Animals Aging Caenorhabditis elegans Homeostasis Lipids Endoplasmic Reticulum Stress Unfolded Protein Response
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Elife] 2023 Jul 25; Vol. 12. <i>Date of Electronic Publication: </i>2023 Jul 25. MeSH Terms: Endoplasmic Reticulum Stress* ; Unfolded Protein Response* ; Animals ; Aging ; Caenorhabditis elegans ; Homeostasis ; Lipids References: Biochim Biophys Acta. 2015 Oct;1853(10 Pt A):2481-91. (PMID: 26025681) ; EMBO Rep. 2017 Nov;18(11):1905-1921. (PMID: 29074503) ; Endocrinology. 2010 Apr;151(4):1893-901. (PMID: 20130115) ; Cells. 2019 Jan 07;8(1):. (PMID: 30621069) ; Exp Mol Med. 2019 Sep 20;51(9):1-11. (PMID: 31541078) ; Mol Cell. 2009 Apr 24;34(2):191-200. (PMID: 19394296) ; Mol Biol Cell. 2018 Oct 15;29(21):2522-2527. (PMID: 30133343) ; Genes Dev. 2012 Mar 15;26(6):554-66. (PMID: 22426533) ; J Lipid Res. 2017 Dec;58(12):2239-2254. (PMID: 28298292) ; J Environ Sci Health B. 2016 Aug 2;51(8):546-52. 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(PMID: 12482854) Grant Information: R01 AG059566 United States AG NIA NIH HHS; P40 OD010440 United States OD NIH HHS; T32AG052374 United States AG NIA NIH HHS; F32AG069388 United States AG NIA NIH HHS; United States HHMI Howard Hughes Medical Institute; T32 AG052374 United States AG NIA NIH HHS; F32 AG069388 United States AG NIA NIH HHS; R00AG065200 United States AG NIA NIH HHS; R00 AG065200 United States AG NIA NIH HHS; R01AG059566 United States AG NIA NIH HHS Contributed Indexing: Keywords: C. elegans; ER UPR; cell biology; genetics; genomics; lipid homeostasis; proteostasis; stress response Substance Nomenclature: 0 (Lipids) Entry Date(s): Date Created: 20230725 Date Completed: 20230726 Latest Revision: 20231102 Update Code: 20240514 PubMed Central ID: PMC10368420

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Lipid homeostasis is essential for a maximal ER stress response.