Lipid Metabolism and Ferroptosis.
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TLDR
In this paper, the authors summarize the current knowledge of how various lipid metabolic pathways are associated with lipid peroxidation and ferroptosis and provide insight into treatment strategies for ferro-ptosis-related diseases.Abstract:
Ferroptosis is a type of iron-dependent regulated necrosis induced by lipid peroxidation that occurs in cellular membranes. Among the various lipids, polyunsaturated fatty acids (PUFAs) associated with several phospholipids, such as phosphatidylethanolamine (PE) and phosphatidylcholine (PC), are responsible for ferroptosis-inducing lipid peroxidation. Since the de novo synthesis of PUFAs is strongly restricted in mammals, cells take up essential fatty acids from the blood and lymph to produce a variety of PUFAs via PUFA biosynthesis pathways. Free PUFAs can be incorporated into the cellular membrane by several enzymes, such as ACLS4 and LPCAT3, and undergo lipid peroxidation through enzymatic and non-enzymatic mechanisms. These pathways are tightly regulated by various metabolic and signaling pathways. In this review, we summarize our current knowledge of how various lipid metabolic pathways are associated with lipid peroxidation and ferroptosis. Our review will provide insight into treatment strategies for ferroptosis-related diseases.read more
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References
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Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Scott J. Dixon,Kathryn M. Lemberg,Michael R. Lamprecht,Rachid Skouta,Eleina M. Zaitsev,Caroline E Gleason,Darpan N Patel,Andras J. Bauer,Alexandra M. Cantley,Wan Seok Yang,Barclay Morrison,Brent R. Stockwell,Brent R. Stockwell +12 more
TL;DR: This paper identified the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes.
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Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases
Michael T. Lin,M. Flint Beal +1 more
TL;DR: Treatments targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria hold great promise in ageing-related neurodegenerative diseases.
Journal ArticleDOI
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TL;DR: This review focuses on biochemical concepts of lipidPeroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting geneexpression and promoting cell death.
Journal ArticleDOI
AMPK: a nutrient and energy sensor that maintains energy homeostasis
TL;DR: AMP-activated protein kinase conserves ATP levels through the regulation of processes other than metabolism, such as the cell cycle and neuronal membrane excitability.
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Regulation of Ferroptotic Cancer Cell Death by GPX4
Wan Seok Yang,Rohitha SriRamaratnam,Matthew Welsch,Kenichi Shimada,Rachid Skouta,Vasanthi S. Viswanathan,Vasanthi S. Viswanathan,Jaime H. Cheah,Paul A. Clemons,Alykhan F. Shamji,Clary B. Clish,Lewis M. Brown,Albert W. Girotti,Virginia W. Cornish,Stuart L. Schreiber,Brent R. Stockwell +15 more
TL;DR: Targeted metabolomic profiling and chemoproteomics revealed that GPX4 is an essential regulator of ferroptotic cancer cell death and sensitivity profiling in 177 cancer cell lines revealed that diffuse large B cell lymphomas and renal cell carcinomas are particularly susceptible to GPx4-regulated ferroPTosis.
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