Phospholipid peroxidation inhibits autophagy via stimulating the delipidation of oxidized LC3-PE.
Phospholipid peroxidation inhibits autophagy via stimulating the delipidation of oxidized LC3-PE.
复制标题
磷脂过氧化通过刺激氧化 LC3-PE 的脱脂来抑制自噬。
DOI：
10.1016/j.redox.2022.102421
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发表时间：
2022-09
期刊：
影响因子：
11.4
通讯作者：
He, Rong-Rong
中科院分区：
文献类型：
--
作者：
Li, Wen;Luo, Lian-Xiang;Zhou, Qing-Qing;Gong, Hai-Biao;Fu, Yuan-Yuan;Yan, Chang-Yu;Li, E.;Sun, Jie;Luo, Zhuo;Ding, Zhao-Jun;Zhang, Qiong-Yi;Mu, Han-Lu;Cao, Yun-Feng;Ouyang, Shu-Hua;Kurihara, Hiroshi;Li, Yi-Fang;Sun, Wan-Yang;Li, Min;He, Rong-Rong
关键词：
Phospholipid peroxidation of polyunsaturated fatty acids at the bis-allylic position drives ferroptosis. Here we identify a novel role for phospholipid peroxidation in the inhibition of autophagy. Using in vitro and in vivo models, we report that phospholipid peroxidation induced by glutathione peroxidase-4 inhibition and arachidonate 15-lipoxygenase overexpression leads to overload of peroxidized phospholipids and culminate in inhibition of autophagy. Functional and lipidomics analysis further demonstrated that inhibition of autophagy was associated with an increase of peroxidized phosphatidylethanolamine (PE) conjugated LC3. We further demonstrate that autophagy inhibition occurred due to preferential cleavage of peroxidized LC3-PE by ATG4B to yield delipidated LC3. Mouse models of phospholipid peroxidation and autophagy additionally supported a role for peroxidized PE in autophagy inhibition. Our results agree with the recognized role of endoplasmic reticulum as the primary source for autophagosomal membranes. In summary, our studies demonstrated that phospholipid peroxidation inhibited autophagy via stimulating the ATG4B-mediated delipidation of peroxidized LC3-PE. A schematic model describing the roles of phospholipid peroxidation in regulating autophagosome formation. Lipidation of cytoplasmic LC3-I to LC3-II by covalent conjugation with PE at the C-terminal glycine of LC3 is an essential event for phagophore formation. PE peroxidation is induced by ALOX15, and the oxidized PE also acts as substrate for LC3 lipidation. ATG4B shows a higher protease activity for LC3-PE-OOH than LC3-PE.
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影响因子：
14.8
作者：
Kagan VE;Mao G;Qu F;Angeli JP;Doll S;Croix CS;Dar HH;Liu B;Tyurin VA;Ritov VB;Kapralov AA;Amoscato AA;Jiang J;Anthonymuthu T;Mohammadyani D;Yang Q;Proneth B;Klein-Seetharaman J;Watkins S;Bahar I;Greenberger J;Mallampalli RK;Stockwell BR;Tyurina YY;Conrad M;Bayır H
通讯作者：
Bayır H
铁死亡是一种溶酶体细胞死亡过程
DOI：
10.1016/j.bbrc.2018.07.078
发表时间：
2018-09-10
影响因子：
3.1
作者：
Gao, Huan;Bai, Yuansong;Dai, Enyong
通讯作者：
Dai, Enyong
影响因子：
3.7
作者：
Jang, Insook;Park, Sujin;Roth, Jurgen
通讯作者：
Roth, Jurgen
DOI：
10.1007/978-1-62703-401-2_24
发表时间：
2013-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Julkowska, Magdalena M;Rankenberg, Johanna M;Testerink, Christa
通讯作者：
Testerink, Christa
影响因子：
3.3
作者：
Fujita, Naonobu;Hayashi-Nishino, Mitsuko;Yoshimori, Tamotsu
通讯作者：
Yoshimori, Tamotsu