Ferroptosis is a form of regulated cell death, characterized by the iron-dependent accumulation of lipid peroxides that ultimately lead to cell membrane damage and cell death. It is different from other forms of cell death, such as apoptosis and necrosis, and has gained attention in the field of cell biology and medicine for its potential role in various diseases, including cancer, neurodegenerative disorders, and ischemia-reperfusion injury.
Key points:
Lipid Peroxidation: Ferroptosis involves the oxidative damage of lipids, specifically the peroxidation of polyunsaturated fatty acids in cell membranes. This process generates toxic lipid molecules known as lipid peroxides.
Iron Dependence: Iron plays a crucial role in ferroptosis. The presence of iron promotes the production of reactive oxygen species (ROS) that contribute to lipid peroxidation and ultimately cell damage.
Glutathione Depletion: Glutathione is an important antioxidant that helps protect cells from oxidative stress. In ferroptosis, there is a depletion of glutathione, which reduces the cell’s ability to neutralize ROS and protect against lipid peroxidation.
Glutathione Peroxidase 4 (GPX4): GPX4 is an enzyme that plays a key role in protecting cells from lipid peroxidation. In ferroptosis, GPX4 activity is inhibited or reduced, contributing to the accumulation of lipid peroxides.
Inhibition of System Xc-: System Xc- is a cellular transporter that imports cystine (a precursor to glutathione) into cells in exchange for glutamate. Inhibiting this system can reduce the availability of cystine and glutathione, further promoting ferroptosis.