Ferroptosis
Specificities
Iron dependence: Iron catalyzes ROS production.
Oxidative stress: Produced ROS lead to lipid peroxidation, resulting in membrane damage, which is one of the core events of ferroptosis.
Non-apoptotic: The whole process does not depend on caspase regulation.
Iron dependence: Iron catalyzes ROS production.
Oxidative stress: Produced ROS lead to lipid peroxidation, resulting in membrane damage, which is one of the core events of ferroptosis.
Non-apoptotic: The whole process does not depend on caspase regulation.
Indicators
Iron metabolism: Iron entry involves DMT1, iron storage involves FTH1, and iron release involves ferroportin.
Lipid peroxidation: The Fenton reaction catalyzed by iron produces ROS, leading to lipid peroxidation.
GPX4 inhibition: GPX4 uses GSH to reduce lipid peroxides, and its inhibition is a critical step in ferroptosis.
Iron metabolism: Iron entry involves DMT1, iron storage involves FTH1, and iron release involves ferroportin.
Lipid peroxidation: The Fenton reaction catalyzed by iron produces ROS, leading to lipid peroxidation.
GPX4 inhibition: GPX4 uses GSH to reduce lipid peroxides, and its inhibition is a critical step in ferroptosis.
Inhibitors and Inducers
Inducers: RSL3, Erastin, IFN-γ, Statins
Lipid peroxidation inhibitors: Ferrostatins, vitamin E
Iron chelators: DFO, DFP
Inducers: RSL3, Erastin, IFN-γ, Statins
Lipid peroxidation inhibitors: Ferrostatins, vitamin E
Iron chelators: DFO, DFP
Related Genes and Proteins
Iron metabolism: DMT1, FTH, Ferroportin
Lipid metabolism: LOX, PLA2
Antioxidant system: GPX4, FSP-1, SOD, PRDX6
Iron metabolism: DMT1, FTH, Ferroportin
Lipid metabolism: LOX, PLA2
Antioxidant system: GPX4, FSP-1, SOD, PRDX6
Mechanisms of Resistance to Ferroptosis
Antioxidant defense: 7-DHC effectively protects (phospho)lipids from autoxidation due to its superior reactivity with peroxyl radicals.
Regulation of iron metabolism: Upregulation of Par-4 promotes ferritinophagy increasing free iron release.
Regulation of sensitivity: Lysosomal cystine governs ferroptosis sensitivity in cancer via the cysteine stress response.
Antioxidant defense: 7-DHC effectively protects (phospho)lipids from autoxidation due to its superior reactivity with peroxyl radicals.
Regulation of iron metabolism: Upregulation of Par-4 promotes ferritinophagy increasing free iron release.
Regulation of sensitivity: Lysosomal cystine governs ferroptosis sensitivity in cancer via the cysteine stress response.
Organella Relations to Ferroptosis
Mitochondria: Overexpression of cytosolic STARD7 increases cellular resistance to ferroptosis and reduces the availability of coenzyme Q in mitochondria.
Lysosome: Lysosomal protein prosaposin (PSAP), the knockdown of which caused the formation of lipofuscin which traps iron, generating reactive oxygen species and triggering ferroptosis.
Mitochondria: Overexpression of cytosolic STARD7 increases cellular resistance to ferroptosis and reduces the availability of coenzyme Q in mitochondria.
Lysosome: Lysosomal protein prosaposin (PSAP), the knockdown of which caused the formation of lipofuscin which traps iron, generating reactive oxygen species and triggering ferroptosis.
Therapeutic Approaches
Cancer treatment: Recent studies have shown that in cancer treatment, especially in eradicating resistance to conventional therapies. When there is resistance to malignant tumors, ferroptosis may be triggered.
Neuroprotection: Parkinson's disease and Alzheimer's disease, where iron accumulation and lipid peroxidation occur. Ferroptosis inhibitors may improve the symptoms and prognosis of the disease.
Aging: Senescence is known to drive iron accumulation and promote ferroptosis. However, recent research on iron dynamics reveals that senescence can also lead to functional iron deficiency, conferring resistance to ferroptosis.
Cancer treatment: Recent studies have shown that in cancer treatment, especially in eradicating resistance to conventional therapies. When there is resistance to malignant tumors, ferroptosis may be triggered.
Neuroprotection: Parkinson's disease and Alzheimer's disease, where iron accumulation and lipid peroxidation occur. Ferroptosis inhibitors may improve the symptoms and prognosis of the disease.
Aging: Senescence is known to drive iron accumulation and promote ferroptosis. However, recent research on iron dynamics reveals that senescence can also lead to functional iron deficiency, conferring resistance to ferroptosis.
