Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis.
Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis.
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脂质过氧化与铁代谢：铁死亡稳态调控的两大基石
DOI：
10.3390/ijms24010449
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发表时间：
2022-12-27
影响因子：
5.6
通讯作者：
Vergely, Catherine
中科院分区：
文献类型：
--
作者：
Rochette, Luc;Dogon, Geoffrey;Rigal, Eve;Zeller, Marianne;Cottin, Yves;Vergely, Catherine
调节细胞死亡（RCD）对发育、组织稳态和各种疾病的发生具有重要影响。在不同形式的RCD中，铁下垂被认为是一种依赖活性氧（ROS）的调节坏死。ROS可与脂质(L)膜上的多不饱和脂肪酸（PUFAs）通过形成脂质自由基L•发生反应，诱导脂质过氧化形成L-ROS。铁下垂是由脂质过氧化氢（LOOH）解毒和铁依赖性L-ROS积累之间的不平衡引发的。细胞内铁积累和脂质过氧化是导致铁下垂的两个主要生化事件。包括线粒体和溶酶体在内的细胞器参与铁代谢和氧化还原失衡的调节。在这篇综述中，我们将提供脂质过氧化的概述，以及参与铁亲级联的关键成分。减少ROS的主要机制是谷胱甘肽（GSH）的氧化还原能力。谷胱甘肽是一种包括谷氨酸、半胱氨酸和甘氨酸的三肽，具有抗氧化剂的作用，是谷胱甘肽过氧化物酶4 （GPX4）的底物，GPX4随后转化为氧化谷胱甘肽（GSSG）。增加GSH表达可抑制铁下垂。我们强调了xc- GSH-GPX4通路作为调节铁下垂的主要途径的作用。系统xc-由亚基溶质载体家族成员（SLC7A11和SLC3A2）组成，介导胱氨酸和谷氨酸在质膜上的交换合成谷胱甘肽。越来越多的证据表明，铁下垂需要自噬机制来执行。铁蛋白自噬是用来描述自噬机制去除主要的铁储存蛋白铁蛋白。核受体共激活因子4 （NCOA4）是一种细胞质自噬受体，用于结合铁蛋白，随后通过铁蛋白自噬降解。在铁蛋白吞噬过程中，储存的铁被释放出来用于生物合成途径。功能失调的紧铁反应与多种病理条件有关。针对氧化还原或铁代谢相关蛋白和信号转导的铁下垂诱导剂或抑制剂已经开发出来。同时检测细胞内和细胞外标记物可能有助于诊断和治疗与铁致损伤相关的疾病。
Regulated cell death (RCD) has a significant impact on development, tissue homeostasis, and the occurrence of various diseases. Among different forms of RCD, ferroptosis is considered as a type of reactive oxygen species (ROS)-dependent regulated necrosis. ROS can react with polyunsaturated fatty acids (PUFAs) of the lipid (L) membrane via the formation of a lipid radical L• and induce lipid peroxidation to form L-ROS. Ferroptosis is triggered by an imbalance between lipid hydroperoxide (LOOH) detoxification and iron-dependent L-ROS accumulation. Intracellular iron accumulation and lipid peroxidation are two central biochemical events leading to ferroptosis. Organelles, including mitochondria and lysosomes are involved in the regulation of iron metabolism and redox imbalance in ferroptosis. In this review, we will provide an overview of lipid peroxidation, as well as key components involved in the ferroptotic cascade. The main mechanism that reduces ROS is the redox ability of glutathione (GSH). GSH, a tripeptide that includes glutamic acid, cysteine, and glycine, acts as an antioxidant and is the substrate of glutathione peroxidase 4 (GPX4), which is then converted into oxidized glutathione (GSSG). Increasing the expression of GSH can inhibit ferroptosis. We highlight the role of the xc- GSH-GPX4 pathway as the main pathway to regulate ferroptosis. The system xc-, composed of subunit solute carrier family members (SLC7A11 and SLC3A2), mediates the exchange of cystine and glutamate across the plasma membrane to synthesize GSH. Accumulating evidence indicates that ferroptosis requires the autophagy machinery for its execution. Ferritinophagy is used to describe the removal of the major iron storage protein ferritin by the autophagy machinery. Nuclear receptor coactivator 4 (NCOA4) is a cytosolic autophagy receptor used to bind ferritin for subsequent degradation by ferritinophagy. During ferritinophagy, stored iron released becomes available for biosynthetic pathways. The dysfunctional ferroptotic response is implicated in a variety of pathological conditions. Ferroptosis inducers or inhibitors targeting redox- or iron metabolism-related proteins and signal transduction have been developed. The simultaneous detection of intracellular and extracellular markers may help diagnose and treat diseases related to ferroptotic damage.
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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：
5.5
作者：
Chen X;Yu C;Kang R;Tang D
通讯作者：
Tang D
影响因子：
--
作者：
Ayala A;Muñoz MF;Argüelles S
通讯作者：
Argüelles S
影响因子：
10.1
作者：
Aydin, Ebru;Johansson, Junko;Martner, Anna
通讯作者：
Martner, Anna
DOI：
10.1016/j.bbrc.2020.03.079
发表时间：
2020-05-28
影响因子：
3.1
作者：
Chen, Liang;Qiao, Linlin;Sun, Xiuju
通讯作者：
Sun, Xiuju