Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed by molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic cell death pathway in 2012, ferroptosis has emerged as a crucial mechanism in numerous physiological and pathological contexts, leading to significant therapeutic advancements across a wide range of diseases. This review summarizes the fundamental molecular mechanisms and regulatory pathways underlying ferroptosis, including both GPX4-dependent and -independent antioxidant mechanisms. Additionally, we examine the involvement of ferroptosis in various pathological conditions, including cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, and metabolic disorders. Specifically, we explore the role of ferroptosis in response to chemotherapy, radiotherapy, immunotherapy, nanotherapy, and targeted therapy. Furthermore, we discuss pharmacological strategies for modulating ferroptosis and potential biomarkers for monitoring this process. Lastly, we elucidate the interplay between ferroptosis and other forms of regulated cell death. Such insights hold promise for advancing our understanding of ferroptosis in the context of human health and disease.

中文翻译：

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铁死亡：健康和疾病的原则和意义


铁死亡是一种铁依赖性的细胞死亡形式，其特征是脂质过氧化不受控制，由涉及不同分子和细胞器的分子网络控制。自 2012 年被确认为非凋亡细胞死亡途径以来，铁死亡已成为许多生理和病理背景下的重要机制，导致多种疾病的治疗取得重大进展。本文总结了铁死亡的基本分子机制和调控途径，包括 GPX4 依赖性和非依赖性抗氧化机制。此外，我们检查了铁死亡与各种病理状况的关系，包括癌症、神经退行性疾病、败血症、缺血再灌注损伤、自身免疫性疾病和代谢紊乱。具体来说，我们探讨了铁死亡在响应化疗、放疗、免疫疗法、纳米疗法和靶向治疗中的作用。此外，我们讨论了调节铁死亡的药理学策略和监测这一过程的潜在生物标志物。最后，我们阐明了铁死亡与其他形式的调节细胞死亡之间的相互作用。这些见解有望在人类健康和疾病的背景下推进我们对铁死亡的理解。