Ferroptosis: machinery and regulation

Oxidative Damage and Antioxidant Defense in Ferroptosis

“…This is because the core signals of ferroptosis (iron accumulation and lipid peroxidation) are often observed abnormally in various diseases and pathological conditions. Like other types of regulated cell death, ferroptosis may be caused by an imbalance between oxidation and antioxidant systems (Chen et al, 2020). In particular, NOX-dependent and mitochondrial respiratory chain-dependent ROS formation facilitates lipid peroxidation, whereas the GSH, CoQ10, and BH 4 systems play a major role in limiting oxidative damage during ferroptosis.…”

The Regulation of Ferroptosis by Tumor Suppressor p53 and its Pathway

“…Recent studies have revealed a novel function of p53 in regulation of ferroptosis, a unique irondependent form of cell death driven by the accumulation of lipid-based reactive oxygen species (ROS) in cells [14][15][16][17][18]. Ferroptosis is a specific form of cell death that was originally found to be induced by small molecules erastin and RSL3 (RAS-selective lethal 3), which were identified in the synthetic lethal screening for small molecules targeting cancer cells with overexpression of oncogenic RAS [14,19,20].…”

“…Ferroptosis is a specific form of cell death that was originally found to be induced by small molecules erastin and RSL3 (RAS-selective lethal 3), which were identified in the synthetic lethal screening for small molecules targeting cancer cells with overexpression of oncogenic RAS [14,19,20]. Ferroptosis has been reported to be involved in different physiological and pathological processes, including cancer, neurodegenerative diseases, tissue ischemia/reperfusion injuries and immune response [15][16][17][18]21]. Recent studies reported that the regulation of ferroptosis by p53 contributes to the tumor suppressive function of p53 and furthermore, mutp53 protein accumulation in cancer cells sensitizes cancer cells to ferroptosis [22][23][24].…”

“…In addition to tumor suppression, p53 has also been demonstrated to be involved in the regulation of many other biological and pathological processes, including antiinfection, immune response, maternal reproduction, development, tissue ischemia/reperfusion injuries, neurodegenerative diseases and aging [2][3][4][26][27][28][29][30][31][32]. Interestingly, recent studies have revealed that ferroptosis is also involved in tumor suppression, tissue ischemia/reperfusion injuries, neurodegeneration and immune response [15][16][17]21]. While p53 is regulated by many different mechanisms, the post-translational modifications, especially the ubiquitination modification, are the most critical and efficient mechanism to regulate the level and activity of p53 [4,[33][34][35][36].…”

“…Furthermore, the iron chelator deferiprone, which blocks ferroptosis, was reported to be beneficial in a randomized controlled clinical trial for Parkinson's disease [53]. Interestingly, ferroptosis has also been reported to be involved in different types of human cancers, including breast, colorectal, lung, pancreatic, kidney and liver cancers [15][16][17][18]. Many recent studies have suggested that ferroptosis can act as a tumor suppressive mechanism, including studies on p53 and ferroptosis [15][16][17][18].…”