Peroxisome-driven ether-linked phospholipids biosynthesis is essential for ferroptosis
In: Cell Death and Differentiation, Jg. 28 (2021-03-01), Heft 8, S. 2536-2551
Online
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Zugriff:
It is well established that ferroptosis is primarily induced by peroxidation of long-chain poly-unsaturated fatty acid (PUFA) through nonenzymatic oxidation by free radicals or enzymatic stimulation of lipoxygenase. Although there is emerging evidence that long-chain saturated fatty acid (SFA) might be implicated in ferroptosis, it remains unclear whether and how SFA participates in the process of ferroptosis. Using endogenous metabolites and genome-wide CRISPR screening, we have identified FAR1 as a critical factor for SFA-mediated ferroptosis. FAR1 catalyzes the reduction of C16 or C18 saturated fatty acid to fatty alcohol, which is required for the synthesis of alkyl-ether lipids and plasmalogens. Inactivation of FAR1 diminishes SFA-dependent ferroptosis. Furthermore, FAR1-mediated ferroptosis is dependent on peroxisome-driven ether phospholipid biosynthesis. Strikingly, TMEM189, a newly identified gene which introduces vinyl-ether double bond into alkyl-ether lipids to generate plasmalogens abrogates FAR1-alkyl-ether lipids axis induced ferroptosis. Our study reveals a new FAR1-ether lipids-TMEM189 axis dependent ferroptosis pathway and suggests TMEM189 as a promising druggable target for anticancer therapy.
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Peroxisome-driven ether-linked phospholipids biosynthesis is essential for ferroptosis
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Autor/in / Beteiligte Person: | Cui, Weiwei ; Gu, Wei ; Liu, Dong ; Chu, Bo |
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Zeitschrift: | Cell Death and Differentiation, Jg. 28 (2021-03-01), Heft 8, S. 2536-2551 |
Veröffentlichung: | Nature Publishing Group UK, 2021 |
Medientyp: | unknown |
ISSN: | 1476-5403 (print) ; 1350-9047 (print) |
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