Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular metabolism.In this study,we established a protein interaction landscape for ferroptosis pa...Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular metabolism.In this study,we established a protein interaction landscape for ferroptosis pathways through proteomic analyses,and identified choline/ethanolamine phosphotransferase 1(CEPT1)as a lysophosphatidylcholine acyltransferase 3(LPCAT3)-interacting protein that regulates LPCAT3 protein stability.In contrast to its known role in promoting phospholipid synthesis,we showed that CEPT1 suppresses ferroptosis potentially by interacting with phospholipases and breaking down certain pro-ferroptotic polyunsaturated fatty acid(PUFA)-containing phospholipids.Together,our study reveals a previously unrecognized role of CEPT1 in suppressing ferroptosis.展开更多
Ferroptosis is an iron-dependent form of regulated cell death that results from oxidative damages of membrane phospholipids,and is mechanistically and morphologically unique compared to other cell death modalities,suc...Ferroptosis is an iron-dependent form of regulated cell death that results from oxidative damages of membrane phospholipids,and is mechanistically and morphologically unique compared to other cell death modalities,such as apoptosis and necroptosis[1].Excessive ferroptosis is indicative of many pathological conditions,including cardiovascular diseases,neurodegenerative diseases,and acute organ injury,whereas ferroptosis impairment has been shown to fuel tumor progression and metastasis;therefore,targeting ferroptosis represents a promising strategy for treating these diseases[2-10].Ferroptosis is triggered by a lethal accumulation of lipid peroxides on the cell membrane.展开更多
基金supported by the Bridge Fund from MD Anderson Cancer Center,Cancer Prevention and Research Institute of Texas grants RP230072grants R01CA181196,R01CA244144,R01CA247992,R01CA269646,and U54CA274220 from the National Institutes of Health(to B.G.)supported by the National Institutes of Health Cancer Center Support Grant P30CA016672 to The University of Texas MD Anderson Cancer Center.
文摘Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular metabolism.In this study,we established a protein interaction landscape for ferroptosis pathways through proteomic analyses,and identified choline/ethanolamine phosphotransferase 1(CEPT1)as a lysophosphatidylcholine acyltransferase 3(LPCAT3)-interacting protein that regulates LPCAT3 protein stability.In contrast to its known role in promoting phospholipid synthesis,we showed that CEPT1 suppresses ferroptosis potentially by interacting with phospholipases and breaking down certain pro-ferroptotic polyunsaturated fatty acid(PUFA)-containing phospholipids.Together,our study reveals a previously unrecognized role of CEPT1 in suppressing ferroptosis.
基金supported by The University of TexasMDAnderson Cancer Center,National Institutes of Health grants R01CA181196,R01CA244144,and R01CA247992Cancer Prevention&Research Institute of Texas grant RP220258(to Boyi Gan)by Cancer Center Support(Core)Grant P30 CA016672 from the National Cancer Institute(to The University of Texas MD Anderson Cancer Center).
文摘Ferroptosis is an iron-dependent form of regulated cell death that results from oxidative damages of membrane phospholipids,and is mechanistically and morphologically unique compared to other cell death modalities,such as apoptosis and necroptosis[1].Excessive ferroptosis is indicative of many pathological conditions,including cardiovascular diseases,neurodegenerative diseases,and acute organ injury,whereas ferroptosis impairment has been shown to fuel tumor progression and metastasis;therefore,targeting ferroptosis represents a promising strategy for treating these diseases[2-10].Ferroptosis is triggered by a lethal accumulation of lipid peroxides on the cell membrane.
