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2 The mechanism and regulation pathways of ferroptosis Ferroptosis is an iron-dependent form of programmed cell death, characterized by uncontrolled accumulation of lipid peroxidation, leading to disruption of cell membrane structure and cell death ( 2.1 Core driving role of iron metabolism As a core driver of ferroptosis, iron deeply participates in the cascade reaction of ferroptosis through its unique redox activity and metabolic network ( + is endocytosed, converted to Fe + by reductases such as STEAP3 in acidic endosomes, and then transported to the cytoplasm through DMT1 to form a labile iron pool (LIP)

Concomitantly, water influx causes matrix swelling, rupture of the rigid OMM and release of apoptogenic proteins sequestered in IMS although, apoptotic cell death under MPT is inhibited due to energetic failure and ATP exhaustion and oxidative stress-mediated caspase inactivation

Mol Neurobiol 44:16 Feldman EL, Nave KA, Jensen TS, Bennett DLH (2017) New horizons in diabetic neuropathy: mechanisms, bioenergetics, and pain