Omics approaches to better understand the molecular mechanism of necroptosis and their translational implications
Omics approaches to better understand the molecular mechanism of necroptosis and their translational implications
复制标题
组学方法可以更好地理解坏死性凋亡的分子机制及其转化意义
DOI：
10.1039/d2mo00318j
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发表时间：
2023
期刊：
影响因子：
2.9
通讯作者：
Atilla-Gokcumen, G. Ekin
中科院分区：
文献类型：
--
作者：
Pradhan, Apoorva J.;Atilla-Gokcumen, G. Ekin
坏死性凋亡是一种程序性细胞死亡，其特征是由于广泛的膜透化和破裂而导致的炎症表型。坏死性凋亡的起始涉及肿瘤坏死因子α（TNFα）激活肿瘤坏死因子受体，随后是受体相互作用蛋白激酶和混合谱系激酶样蛋白（MLKL）的协调活性。随后，MLKL经历磷酸化并易位至质膜，导致透化。这种透化导致各种细胞因子的释放，并在生物体水平上引起广泛的炎症活性。这种炎症活性是细胞凋亡和坏死性凋亡之间的主要差异之一，并且除了最终的细胞死亡表型之外，还将坏死性凋亡与表现出炎症的几种人类病理学联系起来。鉴于细胞死亡途径的激活和炎症活动之间的串扰，在全球水平上提供对转录物、蛋白质及其加工的调节的见解的方法大大提高了我们对坏死性凋亡及其参与不同疾病状态的理解。在这篇综述中，我们强调了最近的组学研究探索转录组，蛋白质组和脂质组，阐明潜在的新机制和信号通路在坏死性凋亡和坏死性凋亡相关的炎症活动中观察到的各种疾病。我们特别关注研究转录组和细胞内和释放的蛋白质组，有助于坏死性凋亡细胞的炎症性质。我们还强调了与坏死性凋亡有关的不同脂质，以及确定坏死性凋亡中脂质参与者的脂质组学研究。最后，我们回顾研究表明，某些坏死相关基因作为不同癌症的潜在预后标志物，并讨论其翻译的影响。
Necroptosis is a type of programed cell death characterized by an inflammatory phenotype due to extensive membrane permeabilization and rupture. Initiation of necroptosis involves activation of tumor necrosis factor receptors by tumor necrosis factor alpha (TNFα) followed by coordinated activities of receptor-interacting protein kinases and mixed lineage kinase-like protein (MLKL). Subsequently, MLKL undergoes phosphorylation and translocates to the plasma membrane, leading to permeabilization. Such permeabilization results in the release of various cytokines and causes extensive inflammatory activity at the organismal level. This inflammatory activity is one of the major differences between apoptosis and necroptosis and links necroptosis to several human pathologies that exhibit inflammation, in addition to the ultimate cell death phenotype. Given the crosstalk between the activation of cell death pathway and inflammatory activity, approaches that provide insights on the regulation of transcripts, proteins and their processing at the global level have substantially improved our understanding of necroptosis and its involvement in different disease states. In this review, we highlight recent omic studies probing the transcriptome, proteome and lipidome which elucidate potential new mechanisms and signaling pathways during necroptosis and the necroptosis-associated inflammatory activity observed in various diseases. We specifically focus on studies investigating the transcriptome and intracellular and released proteome that contribute to inflammatory nature of necroptotic cells. We also highlight different lipids that have been implicated in necroptosis and lipidomic studies identifying lipid players in necroptosis. Finally, we review studies which suggest certain necroptosis-related genes as potential prognosis markers for different cancers and discuss their translational implications.