Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China.
College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China.
Cell Commun Signal. 2023 Aug 14;21(1):200. doi: 10.1186/s12964-023-01170-9.
Ferroptosis, a newform of programmed cell death, driven by peroxidative damages of polyunsaturated-fatty-acid-containing phospholipids in cellular membranes and is extremely dependent on iron ions, which is differs characteristics from traditional cell death has attracted greater attention. Based on the curiosity of this new form of regulated cell death, there has a tremendous progress in the field of mechanistic understanding of ferroptosis recent years. Ferroptosis is closely associated with the development of many diseases and involved in many diseases related signaling pathways. Not only a variety of oncoproteins and tumor suppressors can regulate ferroptosis, but multiple oncogenic signaling pathways can also have a regulatory effect on ferroptosis. Ferroptosis results in the accumulation of large amounts of lipid peroxides thus involving the onset of oxidative stress and energy stress responses. The MAPK pathway plays a critical role in oxidative stress and AMPK acts as a sensor of cellular energy and is involved in the regulation of the energy stress response. Moreover, activation of AMPK can induce the occurrence of autophagy-dependent ferroptosis and p53-activated ferroptosis. In recent years, there have been new advances in the study of molecular mechanisms related to the regulation of ferroptosis by both pathways. In this review, we will summarize the molecular mechanisms by which the MAPK-AMPK signaling pathway regulates ferroptosis. Meanwhile, we sorted out the mysterious relationship between MAPK and AMPK, described the crosstalk among ferroptosis and MAPK-AMPK signaling pathways, and summarized the relevant ferroptosis inducers targeting this regulatory network. This will provide a new field for future research on ferroptosis mechanisms and provide a new vision for cancer treatment strategies. Video Abstract.
铁死亡是一种新的细胞程序性死亡形式，由细胞膜中多不饱和脂肪酸含量的磷脂的过氧化损伤驱动，并且极其依赖于铁离子，这与传统的细胞死亡有很大的不同，因此引起了人们的极大关注。基于对这种新形式的调控性细胞死亡的好奇心，近年来在铁死亡的机制理解领域取得了巨大进展。铁死亡与许多疾病的发展密切相关，并涉及许多与疾病相关的信号通路。不仅各种癌蛋白和肿瘤抑制因子可以调节铁死亡，而且多种致癌信号通路也可以对铁死亡进行调节。铁死亡会导致大量脂质过氧化物的积累，从而涉及氧化应激和能量应激反应的发生。MAPK 通路在氧化应激中起着关键作用，AMPK 作为细胞能量的传感器，参与能量应激反应的调节。此外，AMPK 的激活可以诱导自噬依赖性铁死亡和 p53 激活的铁死亡的发生。近年来，在研究两条通路调控铁死亡的分子机制方面取得了新的进展。在这篇综述中，我们将总结 MAPK-AMPK 信号通路调控铁死亡的分子机制。同时，我们梳理了 MAPK 和 AMPK 之间的神秘关系，描述了铁死亡与 MAPK-AMPK 信号通路之间的串扰，并总结了针对该调控网络的相关铁死亡诱导剂。这将为铁死亡机制的未来研究提供一个新的领域，并为癌症治疗策略提供一个新的视角。视频摘要。
