Junxia Min, Fudi Wang, et al., at Zhejiang University School of Medicine, China, provided an in-depth review on the programmed cell death known as ferroptosis, which is driven by iron-dependent lipid peroxidation. The review highlights the unique characteristics and mechanisms of ferroptosis, distinguishing it from other forms of regulated cell death such as apoptosis, necroptosis, and pyroptosis.
It underscores the role of ferroptosis in the pathogenesis of various diseases, including cancers, neurodegenerative disorders, cardiovascular diseases, and more. Ferroptosis is characterized by the accumulation of reactive oxygen species (ROS) and the peroxidation of polyunsaturated fatty acids (PUFAs) in the presence of iron. This process is distinct because it does not require caspase activation or ATP and can be inhibited by iron chelators like deferoxamine (DFO).
The review discusses the intricate molecular pathways involved in ferroptosis, such as the regulation of lipid peroxidation, the antioxidant system, and iron metabolism. It emphasizes the importance of the GPX4-GSH system in inhibiting lipid peroxidation and the role of ACSL4 and LPCAT3 enzymes in the metabolism and incorporation of PUFAs into membrane lipids. The article further explores the implications of ferroptosis in human diseases, suggesting that it could be a potential target for clinical therapy.
It details the involvement of ferroptosis in several diseases, such as Alzheimer's disease (AD), Parkinson's disea.