Acid sphingomyelinase-dependent autophagic degradation of GPX4 is critical for the execution of ferroptosis

GPX4 酸性鞘磷脂酶 自噬 活性氧 细胞生物学 神经酰胺 NADPH氧化酶 烟酰胺腺嘌呤二核苷酸磷酸 程序性细胞死亡 脂质过氧化 化学 氧化酶试验 细胞内 生物化学 生物 细胞凋亡 氧化应激 谷胱甘肽 谷胱甘肽过氧化物酶
作者
Faisal Thayyullathil,Anees Rahman Cheratta,Ameer Alakkal,S. Karthikeyan,Siraj Pallichankandy,Yusuf A. Hannun,Sehamuddin Galadari
出处
期刊:Cell Death and Disease [Springer Nature]
卷期号:12 (1) 被引量:49
标识
DOI:10.1038/s41419-020-03297-w
摘要

Ferroptosis is a type of regulated cell death characterized by ROS accumulation and devastating lipid peroxidation (LPO). The role of acid sphingomyelinase (ASM), a key enzyme in sphingolipid metabolism, in the induction of apoptosis has been studied; however, to date its role in ferroptosis is unclear. In this study, we report that ASM plays a hitherto unanticipated role in promoting ferroptosis. Mechanistically, Erastin (Era) treatment results in the activation of ASM and generation of ceramide, which are required for the Era-induced reactive oxygen species (ROS) generation and LPO. Inhibition of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) or removal of intracellular ROS, significantly reduced Era-induced ASM activation, suggesting that NADPH oxidase-derived ROS regulated ASM-initiated redox signaling in a positive feedback manner. Moreover, ASM-mediated activation of autophagy plays a critical role in ferroptosis inducers (FINs)-induced glutathione peroxidase 4 (GPX4) degradation and ferroptosis activation. Genetic or pharmacological inhibition of ASM diminishes Era-induced features of autophagy, GPX4 degradation, LPO, and subsequent ferroptosis. Importantly, genetic activation of ASM increases ferroptosis in cancer cells induced by various FINs. Collectively, these findings reveal that ASM plays a novel role in ferroptosis that could be exploited to improve pathological conditions that link to ferroptosis.
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
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
wwwwc发布了新的文献求助10
2秒前
香蕉觅云应助南风不竞采纳,获得10
3秒前
5秒前
咕噜发布了新的文献求助10
8秒前
细腻的尔蓝完成签到,获得积分10
9秒前
木子九应助GGG采纳,获得10
11秒前
muzi完成签到,获得积分20
12秒前
ljj521314完成签到 ,获得积分10
13秒前
海鸥发布了新的文献求助10
17秒前
19秒前
20秒前
南风不竞发布了新的文献求助10
22秒前
文康发布了新的文献求助10
22秒前
任乐乐发布了新的文献求助10
23秒前
24秒前
24秒前
遇见完成签到,获得积分10
24秒前
25秒前
犹豫觅翠完成签到,获得积分10
26秒前
perry4rosa应助小可采纳,获得10
28秒前
派大星发布了新的文献求助10
29秒前
lcf完成签到,获得积分10
29秒前
科研通AI2S应助喜悦咖啡豆采纳,获得10
30秒前
圭义完成签到 ,获得积分10
30秒前
30秒前
枣3完成签到,获得积分20
30秒前
30秒前
萤火虫发布了新的文献求助10
31秒前
赫向雪完成签到,获得积分10
31秒前
32秒前
zz发布了新的文献求助10
34秒前
34秒前
马婷发布了新的文献求助10
34秒前
aiyozz关注了科研通微信公众号
37秒前
彭于晏应助yyf采纳,获得10
39秒前
Ducr发布了新的文献求助10
40秒前
41秒前
科研通AI2S应助asd123456采纳,获得10
41秒前
弧狸完成签到,获得积分10
41秒前
41秒前
高分求助中
Sraffa and applied economics: are there classical supply curves? 1000
Heun’s Differential Equations 600
《Fundamentals of Power Supply Design》Robert A. Mammano 510
谁能看见前面有梦可想 500
Wind Effects on Structures: An Introduction to Wind Engineering and Wind Forces in Engineering (2nd Edition) 300
Against the Grain: The Vayda Tradition in Human Ecology and Ecological Anthropology 300
High Wire: How China Regulates Big Tech and Governs Its Economy 260
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2248382
求助须知:如何正确求助?哪些是违规求助? 1897782
关于积分的说明 4731135
捐赠科研通 1686845
什么是DOI,文献DOI怎么找? 855912
版权声明 544983
科研通“疑难数据库(出版商)”最低求助积分说明 453015