Prominin2 Drives Ferroptosis Resistance by Stimulating Iron Export.
Prominin2 Drives Ferroptosis Resistance by Stimulating Iron Export.
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DOI：
10.1016/j.devcel.2019.10.007
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发表时间：
2019-12-02
影响因子：
11.8
通讯作者：
Mercurio AM
中科院分区：
文献类型：
--
作者：
Brown CW;Amante JJ;Chhoy P;Elaimy AL;Liu H;Zhu LJ;Baer CE;Dixon SJ;Mercurio AM
铁凋亡是一种以铁依赖性致死脂质活性氧积累为特征的受调节的细胞死亡，有助于组织稳态和许多病理学，并且可用于治疗。然而，细胞对铁凋亡的敏感性不同，一个关键的挑战是了解有助于抵抗的机制。使用RNA-Seq鉴定有助于铁凋亡抗性的基因，我们发现促铁凋亡刺激包括抑制脂质过氧化氢酶GPX 4和从细胞外基质脱离诱导pentaspanin 2的表达，pentaspanin蛋白参与脂质动力学的调节。Prominin 2促进乳腺上皮细胞和乳腺癌细胞的铁凋亡抵抗。从机制上讲，E2促进含铁蛋白的多囊泡体（MVB）和外泌体的形成，这些外泌体将铁转运出细胞，抑制铁凋亡。这些发现揭示了铁凋亡抗性可以由一个铁蛋白2-MVB/外泌体-铁蛋白途径驱动，并且对铁稳态、细胞内运输和癌症具有广泛的意义。
Ferroptosis, regulated cell death characterized by the iron-dependent accumulation of lethal lipid reactive oxygen species, contributes to tissue homeostasis and numerous pathologies, and it may be exploited for therapy. Cells differ in their sensitivity to ferroptosis, however, and a key challenge is to understand mechanisms that contribute to resistance. Using RNA-Seq to identify genes that contribute to ferroptosis resistance, we discovered that pro-ferroptotic stimuli including inhibition of the lipid hydroperoxidase GPX4 and detachment from the extracellular matrix induce expression of prominin2, a pentaspanin protein implicated in regulation of lipid dynamics. Prominin2 facilitates ferroptosis resistance in mammary epithelial and breast carcinoma cells. Mechanistically, prominin2 promotes the formation of ferritin-containing multi-vesicular bodies (MVBs) and exosomes that transport iron out of the cell, inhibiting ferroptosis. These findings reveal that ferroptosis resistance can be driven by a prominin2-MVB/exosome-ferritin pathway and have broad implications for iron homeostasis, intracellular trafficking and cancer.
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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：
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
DOI：
10.1083/jcb.101.3.942
发表时间：
1985-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Pan BT;Teng K;Wu C;Adam M;Johnstone RM
通讯作者：
Johnstone RM
影响因子：
21.3
作者：
Friedmann Angeli JP;Schneider M;Proneth B;Tyurina YY;Tyurin VA;Hammond VJ;Herbach N;Aichler M;Walch A;Eggenhofer E;Basavarajappa D;Rådmark O;Kobayashi S;Seibt T;Beck H;Neff F;Esposito I;Wanke R;Förster H;Yefremova O;Heinrichmeyer M;Bornkamm GW;Geissler EK;Thomas SB;Stockwell BR;O'Donnell VB;Kagan VE;Schick JA;Conrad M
通讯作者：
Conrad M
影响因子：
64.8
作者：
Jiang, Le;Kon, Ning;Li, Tongyuan;Wang, Shang-Jui;Su, Tao;Hibshoosh, Hanina;Baer, Richard;Gu, Wei
通讯作者：
Gu, Wei