亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Plasticity of ether lipids promotes ferroptosis susceptibility and evasion

细胞生物学 程序性细胞死亡 过氧化物酶体 脂类学 细胞凋亡 细胞 GPX4 生物化学 化学 生物 氧化应激 基因 超氧化物歧化酶 谷胱甘肽过氧化物酶
作者
Yilong Zou,Whitney S. Henry,Emily L. Ricq,Emily Graham,Vaishnavi V. Phadnis,Pema Maretich,Sateja Paradkar,Natalie Boehnke,Amy Deik,Ferenc Reinhardt,John K. Eaton,Bryan Ferguson,Wenyu Wang,Joshua Fairman,Heather R. Keys,Vlado Dančík,Clary B. Clish,Paul A. Clemons,Paula T. Hammond,Laurie A. Boyer,Robert A. Weinberg,Stuart L. Schreiber
出处
期刊:Nature [Springer Nature]
卷期号:585 (7826): 603-608 被引量:495
标识
DOI:10.1038/s41586-020-2732-8
摘要

Ferroptosis—an iron-dependent, non-apoptotic cell death process—is involved in various degenerative diseases and represents a targetable susceptibility in certain cancers1. The ferroptosis-susceptible cell state can either pre-exist in cells that arise from certain lineages or be acquired during cell-state transitions2–5. However, precisely how susceptibility to ferroptosis is dynamically regulated remains poorly understood. Here we use genome-wide CRISPR–Cas9 suppressor screens to identify the oxidative organelles peroxisomes as critical contributors to ferroptosis sensitivity in human renal and ovarian carcinoma cells. Using lipidomic profiling we show that peroxisomes contribute to ferroptosis by synthesizing polyunsaturated ether phospholipids (PUFA-ePLs), which act as substrates for lipid peroxidation that, in turn, results in the induction of ferroptosis. Carcinoma cells that are initially sensitive to ferroptosis can switch to a ferroptosis-resistant state in vivo in mice, which is associated with extensive downregulation of PUFA-ePLs. We further find that the pro-ferroptotic role of PUFA-ePLs can be extended beyond neoplastic cells to other cell types, including neurons and cardiomyocytes. Together, our work reveals roles for the peroxisome–ether-phospholipid axis in driving susceptibility to and evasion from ferroptosis, highlights PUFA-ePL as a distinct functional lipid class that is dynamically regulated during cell-state transitions, and suggests multiple regulatory nodes for therapeutic interventions in diseases that involve ferroptosis. The cellular organelles peroxisomes contribute to the sensitivity of cells to ferroptosis by synthesizing polyunsaturated ether phospholipids, and changes in the abundances of these lipids are associated with altered sensitivity to ferroptosis during cell-state transitions.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
anan_0528完成签到 ,获得积分10
2秒前
所所应助科研通管家采纳,获得10
3秒前
苦行僧发布了新的文献求助30
3秒前
养乐多敬你完成签到 ,获得积分10
8秒前
感动白开水完成签到,获得积分10
13秒前
15秒前
lalal完成签到 ,获得积分10
17秒前
糊涂涂发布了新的文献求助10
21秒前
科研通AI2S应助动听葵阴采纳,获得10
22秒前
CodeCraft应助strawberrylucky采纳,获得10
30秒前
48秒前
超级裁缝发布了新的文献求助10
54秒前
manye完成签到,获得积分10
57秒前
zmx完成签到 ,获得积分10
59秒前
苦行僧完成签到,获得积分20
1分钟前
大胆含蕾完成签到,获得积分20
1分钟前
1分钟前
1分钟前
共享精神应助谷粱夏山采纳,获得10
1分钟前
1分钟前
spark810完成签到 ,获得积分10
1分钟前
1分钟前
可久斯基完成签到 ,获得积分10
1分钟前
chenbring发布了新的文献求助30
1分钟前
LUJyyyy完成签到,获得积分10
1分钟前
又村完成签到 ,获得积分10
1分钟前
1分钟前
Delight完成签到 ,获得积分10
1分钟前
大胆含蕾发布了新的文献求助30
1分钟前
2分钟前
完美世界应助科研通管家采纳,获得10
2分钟前
科研通AI2S应助科研通管家采纳,获得10
2分钟前
科研通AI2S应助科研通管家采纳,获得10
2分钟前
香蕉觅云应助科研通管家采纳,获得10
2分钟前
共享精神应助DL采纳,获得10
2分钟前
POWER完成签到,获得积分10
2分钟前
2分钟前
2分钟前
2分钟前
DL发布了新的文献求助10
2分钟前
高分求助中
Contemporary Issues in Evaluating Treatment Outcomes in Neurodevelopmental Disorders 1000
rhetoric, logic and argumentation: a guide to student writers 1000
QMS18Ed2 | process management. 2nd ed 1000
One Man Talking: Selected Essays of Shao Xunmei, 1929–1939 1000
A Chronicle of Small Beer: The Memoirs of Nan Green 1000
From Rural China to the Ivy League: Reminiscences of Transformations in Modern Chinese History 900
Eric Dunning and the Sociology of Sport 850
热门求助领域 (近24小时)
化学 医学 材料科学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 免疫学 细胞生物学 电极
热门帖子
关注 科研通微信公众号,转发送积分 2915809
求助须知:如何正确求助?哪些是违规求助? 2555186
关于积分的说明 6912229
捐赠科研通 2216264
什么是DOI,文献DOI怎么找? 1178011
版权声明 588370
科研通“疑难数据库(出版商)”最低求助积分说明 576593