Ferroptosis: A unique form of iron-dependent regulated cell death and its role in different diseases

Abstract

Ferroptosis, a unique, non-apoptotic, iron-dependent, controlled cell death associated with excessive iron accumulation and phospholipid peroxidation. It causes a reduction in cell volume and an increased density of the mitochondrial membrane. This form of controlled cell death is genetically, biochemically, and morphologically unique from other cell deaths, such as apoptosis, uncontrolled necrosis, and necroptosis. Directly or indirectly, alteration of glutathione peroxidase by ferroptosis inducers, through various mechanisms, causes a loss of antioxidant potential and a build-up of lipid reactive oxygen species (ROS) in cells. Inhibition of glutathione peroxidase 4 (GPX-4), system Xc-cystine/glutathione antiporter, and arachidonoyl (AA) peroxidation induces ferroptosis in cells, which can be mediated by the mitochondrial VDAC3, p53 genes, and a variety of additional regulator genes such as HSPB1, CARS, and NFR2. Aside from these, a number of drugs like sorafenib, lanperisone, artemisinin, and sulfasalazine can induce ferroptosis. Recent research has linked ferroptosis to the pathophysiology of many diseases, including tumors, cancers, strokes, neurodegenerative, hepatic, kidney, and pulmonary diseases. In this article, we focused on the process of ferroptosis, its inducers and regulators, and its role in various diseases based on current evidence.