Iron Metabolism in Ferroptosis.

Xin Chen,Daolin Tang,Chunhua Yu,Rui Kang

doi:10.3389/fcell.2020.590226

Abstract

Ferroptosis is a form of regulated cell death that is characterized by iron-dependent oxidative damage and subsequent plasma membrane ruptures and the release of damage-associated molecular patterns. Due to the role of iron in mediating the production of reactive oxygen species and enzyme activity in lipid peroxidation, ferroptosis is strictly controlled by regulators involved in many aspects of iron metabolism, such as iron uptake, storage, utilization, and efflux. Translational and transcriptional regulation of iron homeostasis provide an integrated network to determine the sensitivity of ferroptosis. Impaired ferroptosis is implicated in various iron-related pathological conditions or diseases, such as cancer, neurodegenerative diseases, and ischemia-reperfusion injury. Understanding the molecular mechanisms underlying the regulation of iron metabolism during ferroptosis may provide effective strategies for the treatment of ferroptosis-associated diseases. Indeed, iron chelators effectively prevent the occurrence of ferroptosis, which may provide new approaches for the treatment of iron-related disorders. In this review, we summarize recent advances in the theoretical modeling of iron-dependent ferroptosis, and highlight the therapeutic implications of iron chelators in diseases.

Highlights

Despite its essential role in life, excessive iron is toxic due to its ability to generate reactive oxygen species (ROS) and to even trigger cell death
Ferroptosis is a type of oxidative cell death that is induced by the accumulation of iron-mediated lipid peroxidation (Xie et al, 2016a; Stockwell et al, 2017)
Erastin induces the downregulation of SLC40A1 expression in SHSY5H neuroblastoma cells, which can be reversed by ferroptosis inhibitors, such as ferrostatin-1, an iron chelator, or N-acetyl cysteine (NAC) (Geng et al, 2018)

Summary

Introduction

Despite its essential role in life, excessive iron is toxic due to its ability to generate reactive oxygen species (ROS) and to even trigger cell death. Ferroptosis is a type of oxidative cell death that is induced by the accumulation of iron-mediated lipid peroxidation (Xie et al, 2016a; Stockwell et al, 2017). The inhibition of SLC7A11 and GPX4 leads to the accumulation of iron-dependent lipid peroxidation, causing ferroptotic cell death.

Results

Conclusion