The Mechanism of Long-Chain acyl-CoA Synthetase 4-mediated Ferroptosis
Ferroptosis is an iron and lipid peroxidation-dependent mode of programmed death,and it is triggered when the accumulation of reactive oxygen species reaches a lethal level within the cell.Lipid reactive oxygen species produced by lipid peroxidation act on lipid molecules on cell membranes,resulting in lipid peroxidation and membrane damage,so lipid peroxidation is a prominent feature of ferroptosis.Long-chain acyl-CoA synthetase 4(ACSL4)plays a crucial role in regulating lipid metabolism,primarily by esterifying polyunsaturated fatty acids and incorporating them into membrane phospholipids,thereby accelerating lipid peroxidation and driving ferroptosis.ACSL4-mediated ferroptosis is mainly regulated at transcriptional,post-transcriptional,and post-translational levels and plays an important role in lipid peroxidation-dependent diseases.The purpose of this study is to elucidate the mechanisms underlying ferroptosis,focusing on the upstream regulation of ACSL4 and consequently mechanism of ferroptosis,providing a theoretical basis for investigation into the mechanisms of ACSL4-mediated ferroptosis.
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