Novel Insights into Ferroptosis

Ferroptosis is a recently defined form of programmed cell death characterized by the involvement of labile iron the accumulation of lipid peroxidation. Ferroptosis can be triggered by oxidative stresses or various chemical agents that interfere with cellular protective mechanism against ferroptosis. The lipid peroxidation results from oxidative stresses generated by NADPH oxidase(s) (NOXs) that is often repaired by glutathione peroxidase 4 (GPX4) using the glutathione as a co-factor. Therefore, ferroptosis can be induced by removal of cystine (limiting component for glutathione synthesis), inhibition of GPX4, or activation of NOXs. For example, the canonical ferroptosis inducer, erastin, is an inhibitor of cystine-glutamate transporter (xCT) that reduces cystine import and depletes glutathione1. The relevance of ferroptosis for various human diseases, including cancer, ischemia-reperfusion, neurodegeneration is now receiving attention. Inducing ferroptosis may also have therapeutic potential toward cancer. However, the biological progresses, the underlying mechanisms and regulators of ferroptosis remain unknown.

In light of that, this Research Topic aims to answer the following questions:
1. What are the novel genetic and non-genetic determinants of ferroptosis?
2. What are the processes and mechanisms underlying ferroptosis ?
3. What is the role of ferroptosis in human diseases, including cancer and neurodegeneration?
4. What are the potential uses of ferroptosis as a therapeutic approach?

In particular, these topics are welcome:
• Basic processes of ferroptosis
• Different stimuli that may trigger ferroptosis
• Genetic determinants of ferroptosis
• Non-genetic determinants of ferroptosis
• Role of autophagy in ferroptosis
• Neuro-degenerative diseases that involve ferroptosis
• Physiological role of ferroptosis
• The role of ferroptosis in various human diseases