The epigenetic regulatory mechanisms of ferroptosis and its implications for biological processes and diseases

Abstract

Ferroptosis is a form of regulated cell death triggered by the iron‐dependent peroxidation of phospholipids. Interactions of iron and lipid metabolism factors jointly promote ferroptosis. Ferroptosis has been demonstrated to be involved in the development of various diseases, such as tumors and degenerative diseases (e.g., aortic dissection), and targeting ferroptosis is expected to be an effective strategy for the treatment of these diseases. Recent studies have shown that the regulation of ferroptosis is affected by multiple mechanisms, including genetics, epigenetics, posttranscriptional modifications, and protein posttranslational modifications. Epigenetic changes have garnered considerable attention due to their importance in regulating biological processes and potential druggability. There have been many studies on the epigenetic regulation of ferroptosis, including histone modifications (e.g., histone acetylation and methylation), DNA methylation, and noncoding RNAs (e.g., miRNAs, circRNAs, and lncRNAs). In this review, we summarize recent advances in research on the epigenetic mechanisms involved in ferroptosis, with a description of RNA N6‐methyladenosine (m6A) methylation included, and the importance of epigenetic regulation in biological processes and ferroptosis‐related diseases, which provides reference for the clinical application of epigenetic regulators in the treatment of related diseases by targeting ferroptosis.

Oxidative stress drives vascular smooth muscle cell damage in acute Stanford type A aortic dissection through HIF-1α/HO-1 mediated ferroptosis

“…Consistently, previous studies observed upregulation of ferroptosis in ATAAD marked by overexpression of several FRGs including SLC7A11 and FSP1 and the downregulation of GPX4 [ 47 , 48 ]. In addition, targeting at ferroptosis might have the potential value in the alleviation of aortic dissection [ 47 , 49 ]. These studies supported that ferroptosis might participate in the pathogenesis of aortic dissection.…”

Insights into the Roles of Epigenetic Modifications in Ferroptosis

“…In mammals, the methylation modification of DNA is mediated by DNA methyltransferases (DNMTs), such as DNMT1, DNMT3A, and DNMT3B. This modification generally has a negative effect on gene expression [49,50].…”

The mechanism of ferroptosis and its related diseases

“…The role of ferroptosis in pathological cell death associated with degenerative diseases, carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia–reperfusion injury, and kidney degeneration is increasingly being recognized [ 10 , 858 – 861 ]. Moreover, the potential of ferroptosis as a tumor-suppressor function that could be harnessed for cancer therapy is an exciting development.…”