Unsolved mysteries: How does lipid peroxidation cause ferroptosis?
By Huizhong Feng, Brent R. Stockwell. PLoS Biology, 2018
715 citations recorded by the source corpus.
Ferroptosis is a cell death process driven by damage to cell membranes and linked to numerous human diseases. Ferroptosis is caused by loss of activity of the key enzyme that is tasked with repairing oxidative damage to cell membranes—glutathione peroxidase 4 (GPX4). GPX4 normally removes the dangerous products of iron-dependent lipid peroxidation, protecting cell membranes from this type of damage; when GPX4 fails, ferroptosis ensues. Ferroptosis is distinct from apoptosis, necroptosis, necrosis, and other modes of cell death. Several key mysteries regarding how cells die during ferroptosis remain unsolved. First, the drivers of lipid peroxidation are not yet clear. Second, the subcellular location of lethal lipid peroxides remains an outstanding question. Finally, how exactly lipid peroxidation leads to cell death is an unsolved mystery. Answers to these questions will provide insights into the mechanisms of ferroptotic cell death and associated human diseases, as well as new therapeutic strategies for such diseases.
Subfields: Cancer Research, Pulmonary and Respiratory Medicine, Surgery
View Paper: https://www.semanticscholar.org/paper/6b7200fb27ac13421859d7aefb4dbecdb01b8da8
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Citations in the corpus
- FerrDb: a manually curated resource for regulators and markers of ferroptosis and ferroptosis-disease associations (2020, background): “It is morphologically, biochemically and genetically distinct from apoptosis, necroptosis, necrosis, autophagy and other modes of cell death (4, 5).”
- RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer (2018, background): “Ferroptosis is tightly controlled by GPX4 and some iron transport regulatory proteins (Feng and Stockwell, 2018).”
- Ferroptosis: mechanisms and links with diseases (2021, background): “These by-products are produced by the decomposition of AA and other PUFAs through enzymatic and nonenzymatic pathways.(50) 4-HNE and MDA were reported as the major toxic products which could react with DNA bases, proteins, and other nucleophilic molecules leading to serious cytotoxicity.”
- Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis (2019, background): “Although the products of lipid peroxidation have been extensively studied and excessive accumulation of lipid peroxidation has been shown to promote apoptosis and autophagy, their role in ferroptosis is unclear [66, 71, 108].”
- Ferroptosis as a target for protection against cardiomyopathy (2019, background): “However, there are still several key questions in the lipid peroxidation process that drives ferroptosis, one of which is the location in which lipid peroxidation takes place during ferroptosis (29).”
- Transferrin Receptor Is a Specific Ferroptosis Marker (2020, background): “It has been suggested that ferroptosis plays a role in the progression of degenerative diseases of the kidney, heart, liver, and brain (Feng and Stockwell, 2018); stroke, Alzheimer disease, Huntington disease (HD), and Parkinson disease are among the candidates for neurodegenerative diseases that ma”