School of Life and Environmental Sciences, Shaoxing University, Shaoxing City, Zhejiang, China.
Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan, ROC.
Apoptosis. 2024 Feb;29(1-2):45-65. doi: 10.1007/s10495-023-01890-w. Epub 2023 Sep 27.
Ferroptosis has been conceptualized as a novel cell death modality distinct from apoptosis, necroptosis, pyroptosis and autophagic cell death. The sensitivity of cellular ferroptosis is regulated at multiple layers, including polyunsaturated fatty acid metabolism, glutathione-GPX4 axis, iron homeostasis, mitochondria and other parallel pathways. In addition, microRNAs (miRNAs) have been implicated in modulating ferroptosis susceptibility through targeting different players involved in the execution or avoidance of ferroptosis. A growing body of evidence pinpoints the deregulation of miRNA-regulated ferroptosis as a critical factor in the development and progression of various pathophysiological conditions related to iron overload. The revelation of mechanisms of miRNA-dependent ferroptosis provides novel insights into the etiology of diseases and offers opportunities for therapeutic intervention. In this review, we discuss the interplay of emerging miRNA regulators and ferroptosis players under different pathological conditions, such as cancers, ischemia/reperfusion, neurodegenerative diseases, acute kidney injury and cardiomyopathy. We emphasize on the relevance of miRNA-regulated ferroptosis to disease progression and the targetability for therapeutic interventions.
铁死亡被概念化为一种不同于细胞凋亡、细胞坏死、细胞焦亡和自噬性细胞死亡的新型细胞死亡方式。细胞铁死亡的敏感性受到多个层面的调控，包括多不饱和脂肪酸代谢、谷胱甘肽-GPX4 轴、铁稳态、线粒体和其他平行途径。此外，microRNAs（miRNAs）通过靶向参与铁死亡执行或避免的不同因子，被认为可以调节铁死亡的敏感性。越来越多的证据表明，miRNA 调控的铁死亡失调是与铁过载相关的各种生理病理条件发展和进展的关键因素。miRNA 依赖性铁死亡机制的揭示为疾病的病因提供了新的见解，并为治疗干预提供了机会。在这篇综述中，我们讨论了在不同病理条件下新兴的 miRNA 调节剂和铁死亡调控因子之间的相互作用，如癌症、缺血/再灌注、神经退行性疾病、急性肾损伤和心肌病。我们强调了 miRNA 调控的铁死亡与疾病进展的相关性，以及治疗干预的靶向性。
