Effects of DNA, RNA, and Protein Methylation on the Regulation of Ferroptosis

作者：X R Wang, Xianghai Kong, Xin Feng, Ding‐Sheng Jiang · 发表于：International Journal of Biological Sciences · 年份：2023 · DOI：10.7150/ijbs.85454 · 被引用次数：59 · 研究领域：Epigenetics and DNA Methylation、Ferroptosis and cancer prognosis、RNA modifications and cancer

Ferroptosis is a form of programmed cell death characterized by elevated intracellular ferrous ion levels and increased lipid peroxidation.Since its discovery and characterization in 2012, considerable progress has been made in understanding the regulatory mechanisms and pathophysiological functions of ferroptosis.Recent findings suggest that numerous organ injuries (e.g., ischemia/reperfusion injury) and degenerative pathologies (e.g., aortic dissection and neurodegenerative disease) are driven by ferroptosis.Conversely, insufficient ferroptosis has been linked to tumorigenesis.Furthermore, a recent study revealed the effect of ferroptosis on hematopoietic stem cells under physiological conditions.The regulatory mechanisms of ferroptosis identified to date include mainly iron metabolism, such as iron transport and ferritinophagy, and redox systems, such as glutathione peroxidase 4 (GPX4)-glutathione (GSH), ferroptosis-suppressor-protein 1 (FSP1)-CoQ10, FSP1-vitamin K (VK), dihydroorotate dehydrogenase (DHODH)-CoQ, and GTP cyclohydrolase 1 (GCH1)-tetrahydrobiopterin (BH4).Recently, an increasing number of studies have demonstrated the important regulatory role played by epigenetic mechanisms, especially DNA, RNA, and protein methylation, in ferroptosis.In this review, we provide a critical analysis of the molecular mechanisms and regulatory networks of ferroptosis identified to date, with a focus on the regulatory role of DNA, RNA, and protein methylation.Furthermore, we disc...