Identification of essential sites of lipid peroxidation in ferroptosis.
Identification of essential sites of lipid peroxidation in ferroptosis.
复制标题
铁死亡中脂质过氧化关键位点的鉴定
DOI：
10.1038/s41589-022-01249-3
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发表时间：
2023-06
影响因子：
14.8
通讯作者：
Stockwell, Brent R.
中科院分区：
文献类型：
--
作者：
von Krusenstiern, A. Nikolai;Robson, Ryan N.;Qian, Naixin;Qiu, Baiyu;Hu, Fanghao;Reznik, Eduard;Smith, Nailah;Zandkarimi, Fereshteh;Estes, Verna M.;Dupont, Marcel;Hirschhorn, Tal;Shchepinov, Mikhail S.;Min, Wei;Woerpel, K. A.;Stockwell, Brent R.
铁凋亡是一种由脂质过氧化驱动的铁依赖性细胞死亡形式，为耐药癌症提供了潜在的治疗途径，并可能在一些退行性疾病的病理学中发挥作用。确定铁凋亡所必需的亚细胞膜及其过氧化反应的顺序将阐明药物发现策略和铁凋亡相关的疾病机制。我们采用荧光和受激拉曼散射成像来研究铁氰化钾调节化合物的结构-活性-分布关系。我们发现，虽然各种亚细胞膜的脂质过氧化作用可以诱导铁凋亡，内质网（ER）膜是脂质过氧化的关键部位。我们的研究结果表明，有序的进展模型，膜过氧化作用在ferroptosis，积累最初在ER膜，后来在质膜。因此，ER靶向的铁凋亡抑制剂和诱导剂的设计可用于最佳地控制经历铁凋亡的细胞中脂质过氧化的动力学。
Ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation, provides a potential treatment avenue for drug-resistant cancers and may play a role in the pathology of some degenerative diseases. Identifying the subcellular membranes essential for ferroptosis and the sequence of their peroxidation will illuminate drug discovery strategies and ferroptosis-relevant disease mechanisms. We employed fluorescence and stimulated Raman scattering imaging to examine the structure-activity-distribution relationship of ferroptosis-modulating compounds. We found that while lipid peroxidation in various subcellular membranes can induce ferroptosis, the endoplasmic reticulum (ER) membrane is a key site of lipid peroxidation. Our results suggest an ordered progression model of membrane peroxidation during ferroptosis that accumulates initially in the ER membrane, and later in the plasma membrane. Thus, the design of ER-targeted inhibitors and inducers of ferroptosis may be used to optimally control the dynamics of lipid peroxidation in cells undergoing ferroptosis.
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ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
通讯作者：
Conrad M
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
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
14.8
作者：
Gaschler MM;Andia AA;Liu H;Csuka JM;Hurlocker B;Vaiana CA;Heindel DW;Zuckerman DS;Bos PH;Reznik E;Ye LF;Tyurina YY;Lin AJ;Shchepinov MS;Chan AY;Peguero-Pereira E;Fomich MA;Daniels JD;Bekish AV;Shmanai VV;Kagan VE;Mahal LK;Woerpel KA;Stockwell BR
通讯作者：
Stockwell BR
DOI：
10.1126/science.aaw9872
发表时间：
2020-04-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badgley MA;Kremer DM;Maurer HC;DelGiorno KE;Lee HJ;Purohit V;Sagalovskiy IR;Ma A;Kapilian J;Firl CEM;Decker AR;Sastra SA;Palermo CF;Andrade LR;Sajjakulnukit P;Zhang L;Tolstyka ZP;Hirschhorn T;Lamb C;Liu T;Gu W;Seeley ES;Stone E;Georgiou G;Manor U;Iuga A;Wahl GM;Stockwell BR;Lyssiotis CA;Olive KP
通讯作者：
Olive KP