Selenium: Tracing Another Essential Element of Ferroptotic Cell Death

Area of Science:

• Biochemistry
• Cell Biology
• Pathology

Background:

• Ferroptosis is a regulated form of necrotic cell death.
• Iron overload and lipid peroxidation are hallmarks of ferroptosis.
• The glutathione peroxidase 4 (GPX4) pathway, reliant on selenium, is a key inhibitor of ferroptosis.

Purpose of the Study:

• To elucidate the multifaceted roles of iron and selenium in ferroptosis.
• To explore the canonical GPX4-dependent and alternative GPX4-independent pathways regulating ferroptosis.
• To discuss the implications of ferroptosis dysregulation in diseases and potential therapeutic strategies.

Main Methods:

• Review of existing literature on ferroptosis mechanisms.
• Analysis of the biochemical roles of iron and selenium in cellular processes.
• Discussion of metabolic networks involved in ferroptosis regulation.

Main Results:

• Iron promotes ferroptosis through Fenton reactions and lipid autoxidation.
• Selenium, as GPX4, suppresses lipid peroxidation and ferroptosis.
• A second, selenium-independent ferroptosis suppression pathway involves ubiquinone and NAD(P)H.

Conclusions:

• Ferroptosis is a complex cell-death process influenced by multiple metabolic networks.
• Dysregulation of ferroptosis can lead to organ failure and diseases like neurodegeneration and ischemia/reperfusion injury.
• Targeting ferroptosis pathways, particularly those involving selenium, presents therapeutic opportunities.