Lipid biosynthesis perturbation impairs endoplasmic reticulum-associated degradation.

Autor:	Turk SM; Department of Biology, Ball State University, Muncie, Indiana, USA., Indovina CJ; Department of Biology, Ball State University, Muncie, Indiana, USA., Miller JM; Department of Biology, Ball State University, Muncie, Indiana, USA., Overton DL; Department of Biology, Ball State University, Muncie, Indiana, USA., Runnebohm AM; Department of Biology, Ball State University, Muncie, Indiana, USA., Orchard CJ; Department of Biology, Ball State University, Muncie, Indiana, USA., Tragesser-Tiña ME; Department of Biology, Ball State University, Muncie, Indiana, USA., Gosser SK; Department of Biology, Ball State University, Muncie, Indiana, USA., Doss EM; Department of Biology, Ball State University, Muncie, Indiana, USA., Richards KA; Department of Biology, Ball State University, Muncie, Indiana, USA., Irelan CB; Department of Biology, Ball State University, Muncie, Indiana, USA., Daraghmi MM; Department of Biology, Ball State University, Muncie, Indiana, USA., Bailey CG; Department of Biology, Ball State University, Muncie, Indiana, USA., Niekamp JM; Department of Biology, Ball State University, Muncie, Indiana, USA., Claypool KP; Department of Biology, Ball State University, Muncie, Indiana, USA., Engle SM; Department of Biology, Ball State University, Muncie, Indiana, USA., Buchanan BW; Department of Biology, Ball State University, Muncie, Indiana, USA., Woodruff KA; Department of Biology, Ball State University, Muncie, Indiana, USA., Olesen JB; Department of Biology, Ball State University, Muncie, Indiana, USA., Smaldino PJ; Department of Biology, Ball State University, Muncie, Indiana, USA., Rubenstein EM; Department of Biology, Ball State University, Muncie, Indiana, USA. Electronic address: emrubenstein@bsu.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2023 Aug; Vol. 299 (8), pp. 104939. Date of Electronic Publication: 2023 Jun 17.
DOI:	10.1016/j.jbc.2023.104939
Abstrakt:	The relationship between lipid homeostasis and protein homeostasis (proteostasis) is complex and remains incompletely understood. We conducted a screen for genes required for efficient degradation of Deg1-Sec62, a model aberrant translocon-associated substrate of the endoplasmic reticulum (ER) ubiquitin ligase Hrd1, in Saccharomyces cerevisiae. This screen revealed that INO4 is required for efficient Deg1-Sec62 degradation. INO4 encodes one subunit of the Ino2/Ino4 heterodimeric transcription factor, which regulates expression of genes required for lipid biosynthesis. Deg1-Sec62 degradation was also impaired by mutation of genes encoding several enzymes mediating phospholipid and sterol biosynthesis. The degradation defect in ino4Δ yeast was rescued by supplementation with metabolites whose synthesis and uptake are mediated by Ino2/Ino4 targets. Stabilization of a panel of substrates of the Hrd1 and Doa10 ER ubiquitin ligases by INO4 deletion indicates ER protein quality control is generally sensitive to perturbed lipid homeostasis. Loss of INO4 sensitized yeast to proteotoxic stress, suggesting a broad requirement for lipid homeostasis in maintaining proteostasis. A better understanding of the dynamic relationship between lipid homeostasis and proteostasis may lead to improved understanding and treatment of several human diseases associated with altered lipid biosynthesis. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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