Journal Article

Double-edge sword roles of iron in driving energy production versus instigating ferroptosis

Zhao, Jiajun, Gao, Ling, Liu, Sijin, Li, Ruibin, Xin, Wei, Zhang, Shuping, Anderson, Gregory J., Chen, Shuguang

2022

Overview

Iron is vital for many physiological functions, including energy production, and dysregulated iron homeostasis underlies a number of pathologies. Ferroptosis is a recently recognized form of regulated cell death that is characterized by iron dependency and lipid peroxidation, and this process has been reported to be involved in multiple diseases. The mechanisms underlying ferroptosis are complex, and involve both well-described pathways (including the iron-induced Fenton reaction, impaired antioxidant capacity, and mitochondrial dysfunction) and novel interactions linked to cellular energy production. In this review, we examine the contribution of iron to diverse metabolic activities and their relationship to ferroptosis. There is an emphasis on the role of iron in driving energy production and its link to ferroptosis under both physiological and pathological conditions. In conclusion, excess reactive oxygen species production driven by disordered iron metabolism, which induces Fenton reaction and/or impairs mitochondrial function and energy metabolism, is a key inducer of ferroptosis.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: 631/45 / 631/80 / Animals / Antibodies / Antioxidants / Biochemistry / Biomedical and Life Sciences / Cell Biology / Cell Culture / Cell death / Cell Death - physiology / Copper - metabolism / Energy metabolism / Energy Metabolism - physiology / Ferroptosis / Ferroptosis - physiology / Homeostasis / Humans / Immunology / Iron / Iron - metabolism / Iron Overload - metabolism / Iron Overload - pathology / Life Sciences / Lipid Peroxidation / Metabolism / Mitochondria / Mitochondria - metabolism / Mitochondria - pathology / Physiology / Reactive oxygen species / Review / Review Article