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T cell lipid peroxidation induces ferroptosis and prevents immunity to infection
Open accessAbstract
The selenoenzyme glutathione peroxidase 4 (Gpx4) is a major scavenger of phospholipid hydroperoxides. Although Gpx4 represents a key component of the reactive oxygen species-scavenging network, its relevance in the immune system is yet to be defined. Here, we investigated the importance of Gpx4 for physiological T cell responses by using T cell–specific Gpx4-deficient mice. Our results revealed that, despite normal thymic T cell development, CD8+ T cells from TΔGpx4/ΔGpx4 mice had an intrinsic defect in maintaining homeostatic balance in the periphery. Moreover, both antigen-specific CD8+ and CD4+ T cells lacking Gpx4 failed to expand and to protect from acute lymphocytic choriomeningitis virus and Leishmania major parasite infections, which were rescued with diet supplementation of high dosage of vitamin E. Notably, depletion of the Gpx4 gene in the memory phase of viral infection did not affect T cell recall responses upon secondary infection. Ex vivo, Gpx4-deficient T cells rapidly accumulated membrane lipid peroxides and concomitantly underwent cell death driven by ferroptosis but not necroptosis. These studies unveil an essential role of Gpx4 for T cell immunity.
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“the inducible or tissue-specific ablation of Gpx4 in mice provokes a variety of pathological conditions, including acute renal or hepatic injury [547, 563, 589], neurodegeneration [550, 590, 591], and defective immunity to infection [567], all of which can be prevented or mitigated by ferroptosis-inhibiting strategies.”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [567]
In the citing paper
“GPX4 is essential for the survival and expansion of recently activated T cells, indicating the importance of preventing lipid peroxidation and of iron dysregulation resulting in ferroptosis, in T cell proliferation (Matsushita et al., 2015).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Matsushita et al., 2015
In the citing paper
“GPX4 is essential for the survival and expansion of recently activated T cells, indicating the importance of preventing lipid peroxidation and of iron dysregulation resulting in ferroptosis, in T cell proliferation (Matsushita et al., 2015).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Matsushita et al., 2015
In the citing paper
“Gpx4 exerts important effects on the immune system as it is crucial for the survival of CD8+ T cells and for the expansion of both CD4+ and CD8+ T cells upon T cell receptor triggering in response to infection by preventing membrane lipid peroxidation and ferroptosis”
From Iron in immune cell function and host defense (2021) · cites this paper as [112]
In the citing paper
“and high levels of reactive oxygen species in T cells impair cytotoxicity, perhaps mediated by T cell lipid peroxidation, resulting in failure to control viruses (Henson et al. 2014; Matsushita et al. 2015).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Matsushita et al. 2015
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Cites
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Ferroptosis: mechanisms, biology and role in disease
Jiang, X., Stockwell, B. R., & Conrad, M. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00324-8 · Cited by 7,973
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BackgroundInfluentialFerroptosis: Death by Lipid Peroxidation
Yang, W. S., & Stockwell, B. R. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.014 · Cited by 3,088
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BackgroundOxidized arachidonic and adrenic PEs navigate cells to ferroptosis
Kagan, V. E., Mao, G., Qu, F., Angeli, J. P. F., Doll, S., Croix, C. S., Dar, H. H., Liu, B., Tyurin, V. A., Ritov, V. B., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2238 · Cited by 3,029
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Ferroptosis: machinery and regulation
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Role of GPX4 in ferroptosis and its pharmacological implication
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Ferroptosis: Mechanisms and links with diseases
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“However, both antigenspecific CD8 and CD4 T cells failed to expand and to protect from acute infections, and CD8 T cells had an intrinsic defect in maintaining homeostatic balance in the periphery,(190) which can be rescued with a high dosage of vitamin E.(190) Ferroptosis also plays a significant role in CD8 T cell-i…”
BackgroundThe Metabolic Underpinnings of Ferroptosis
Zheng, J., & Conrad, M. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.10.011 · Cited by 1,368
Self-citationFerroptosis at the crossroads of cancer-acquired drug resistance and immune evasion
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“5 days post conception (dpc), conditional-Gpx4-mutant mice revealed that GPX4 loss not only induces ferroptosis, but also results in neurodegeneration [19], loss of antiviral immunity [61], infertility, and ischemia/reperfusion injury in kidney and liver [27,28,62,63].”
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Ferroptosis is a type of autophagy-dependent cell death
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The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity
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“…prevents nuclear accumulation of DPP4 and then triggers membrane-associated DPP4-mediated lipid peroxidation, which finally results in ferroptosis. are sensitive to erastin (Friedmann Angeli et al., 2014; Jiang et al., 2015; Linkermann et al., 2014; Matsushita et al., 2015; Skouta et al., 2014).”
The development of the concept of ferroptosis
Hirschhorn, T., & Stockwell, B. R. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.043 · Cited by 1,052
Ferroptosis in cancer: from molecular mechanisms to therapeutic strategies
Zhou, Q., Meng, Y., Li, D., Yao, L., Le, J., Liu, Y., Sun, Y., Zeng, F., Chen, X., & Deng, G. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01769-5 · Cited by 1,056
“35,42 However, genetic deletion of Alox15 in Gpx4 knockout mice failed to avert ferroptosis in vivo, 8 and Alox12/15 failed to restore the viability of Gpx4 de fi cient T cells, 79 suggesting the existence of alternative mechanisms in certain contexts of ferroptosis.”
BackgroundRegulators of Iron Homeostasis: New Players in Metabolism, Cell Death, and Disease
Bogdan, A. R., Miyazawa, M., Hashimoto, K., & Tsuji, Y. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.11.012 · Cited by 907
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BackgroundInfluentialALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway
Chu, B., Kon, N., Chen, D., Li, T., Liu, T., Jiang, L., Song, S., Tavana, O., & Gu, W. J. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0305-6 · Cited by 892
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“Subsequently, it was shown that ablation of Gpx4 induces ferroptosis in cell types such as renal tubular cells and T lymphocytes [13,18].”
BackgroundPlasticity of ether lipids promotes ferroptosis susceptibility and evasion
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“Third, the genetic depletion of Gpx4 or treatment with GPX4 inhibitors (e.g., RSL3, ML162, and ML210) induces lipid peroxidation and concomitantly ferroptotic cell death in T cells in vitro (Drijvers et al., 2021; Matsushita et al., 2015).”
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Mechanisms controlling cellular and systemic iron homeostasis
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“Acute lymphocytic choriomeningitis virus and Leishmania major parasite infections benefit from ferroptosis (8).”
BackgroundResolving the Role of Lipoxygenases in the Initiation and Execution of Ferroptosis
Shah, R., Shchepinov, M. S., & Pratt, D. A. (2018) · ACS Central Science · doi:10.1021/acscentsci.7b00589 · Cited by 782
AMPK-Mediated BECN1 Phosphorylation Promotes Ferroptosis by Directly Blocking System Xc– Activity
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A non-canonical vitamin K cycle is a potent ferroptosis suppressor
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Self-citationGPx4, Lipid Peroxidation, and Cell Death: Discoveries, Rediscoveries, and Open Issues
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“For instance, suf-ficient a -tocopherol content in the mouse chow or supra-nutritional a -tocopherol supplementation was demonstrated to compensate for the loss of GPx4 in endothelial cells (115), CD8 + T cells (72), and hepatocytes of newborn pups (18).”
Self-citationThe interaction between ferroptosis and lipid metabolism in cancer
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BackgroundCold and hot tumors: from molecular mechanisms to targeted therapy
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“In addition to cancer therapy,((28)) impaired ferroptosis involves tissue injury,((26,35)) immunity tolerance,((36)) and stem cell division.”
BackgroundThe tumor suppressor protein p53 and the ferroptosis network
Kang, R., Kroemer, G., & Tang, D. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.05.074 · Cited by 714
“Genetic depletion of GPX4 can trigger ferroptosis in an iron-, MEK-, and ROS-dependent manner in vitro or in vivo [23,24,31].”
Redox lipid reprogramming commands susceptibility of macrophages and microglia to ferroptotic death
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Amino Assets: How Amino Acids Support Immunity
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GPX4 in cell death, autophagy, and disease
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“A mouse model with conditional knockout of Gpx4 in T cells displays a phenotype of accumulated membrane lipid peroxides, leading to an intrinsic defect in protecting against acute lymphocytic choriomeningitis virus and Leishmania major parasite infections [28].”
BackgroundInfluentialRegulated necrosis: disease relevance and therapeutic opportunities
Conrad, M., Angeli, J. P. F., Vandenabeele, P., & Stockwell, B. R. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.6 · Cited by 630
Self-citationFerroptosis is induced following siramesine and lapatinib treatment of breast cancer cells
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“The cystine uptake inhibitor erastin has been shown to block GSH activation leading to accumulation of ROS and ferroptosis.(23,33)We found that both erastin and the combination of siramesine and lapatinib-induced cell death was promoted by inhibition of cystine transport.”
BackgroundLipid Peroxidation-Dependent Cell Death Regulated by GPx4 and Ferroptosis
Imai, H., Matsuoka, M., Kumagai, T., Sakamoto, T., & Koumura, T. (2016) · Current topics in microbiology and immunology · doi:10.1007/82_2016_508 · Cited by 635
Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis
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“, 2015), viral and parasitic infections (Matsushita et al., 2015), male subfertility (Brutsch et al.”
BackgroundTargeting ferroptosis opens new avenues for the development of novel therapeutics
Sun, S., Shen, J., Jiang, J., Wang, F., & Min, J. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01606-1 · Cited by 674
“85 With respect to B cells, various B cell populations have been shown to respond differently to ferroptosis induction.”
BackgroundSepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options
Liu, D., Huang, S., Sun, J., Zhang, H., Cai, Q., Gao, C., Li, L., Cao, J., Xu, F., Zhou, Y., et al. (2022) · Military Medical Research · doi:10.1186/s40779-022-00422-y · Cited by 646
“T-cell-specific Gpx4-deficient mice are more sensitive to viral and parasitic infections due to T-cell death caused by ferroptosis [65].”
BackgroundMitochondrial regulation of ferroptosis
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HSPA5 Regulates Ferroptotic Cell Death in Cancer Cells
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“Conditional knockout of GPX4 in mice enhances ferroptosis in vivo (5-7).”
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GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment
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Glutathione primes t cell metabolism for inflammation
Mak, T. W., Grusdat, M., Duncan, G. S., Dostert, C., Nonnenmacher, Y., Cox, M., Binsfeld, C., Hao, Z., Brüstle, A., Itsumi, M., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.019 · Cited by 511
“Prevention of lipid oxidationbyglutathioneperoxidase 4 (Gpx4) is crucial for T cell survival and activation (Matsushita et al., 2015).”
BackgroundManganese Oxide Nanomaterials: Synthesis, Properties, and Theranostic Applications
Ding, B., Zheng, P., Ma, P., & Lin, J. (2020) · Advanced Materials · doi:10.1002/adma.201905823 · Cited by 527
Li, Y., Cao, Y., Xiao, J., Shang, J., Tan, Q., Feng, P., Huang, W.-F., Wu, F., Zhang, H., & Zhang, X. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0528-x · Cited by 515
“This finding is in line with results from previous studies suggesting that ferroptosis is involved in the pathogenesis of human diseases such as Huntington’s disease, periventricular leukomalacia, and kidney dysfunction [25], as well as I/R injury [13, 25] and infectious diseases [26].”
ResultCISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation
Yuan, H., Li, X., Zhang, X., Kang, R., & Tang, D. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.08.034 · Cited by 511
Redox regulation of immunometabolism
Muri, J., & Köpf, M. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-00478-8 · Cited by 519
Striking while the iron is hot: Iron metabolism and ferroptosis in neurodegeneration
Masaldan, S., Bush, A. I., Devos, D., Rolland, A., & Moreau, C. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.033 · Cited by 494
“Aberrant ferroptosis activation in T cells of the immune system has been shown to affect their ability to mount a response to Leishmania parasite infection [140].”
Yan, Y., Xie, Y., Cao, L., Yang, L., Yang, M., Lotze, M. T., Zeh, H. J., Kang, R., & Tang, D. (2015) · Molecular & Cellular Oncology · doi:10.1080/23723556.2015.1054549 · Cited by 476
Iron and ferroptosis: A still ill‐defined liaison
Doll, S. G., & Conrad, M. (2017) · IUBMB Life · doi:10.1002/iub.1616 · Cited by 478
“(29) demonstrated that Gpx4 is essential for neuroprotection in hippocampus, cortex, cerebellum and motor neurons (29,64–66), as well as for photoreceptor cells (67), kidney tubular cells (6), and CD8-positive T cells (68).”
BackgroundSelf-citationGlutathione peroxidase 4–regulated neutrophil ferroptosis induces systemic autoimmunity
Li, P., Jiang, M., Li, K., Li, H., Zhou, Y., Xiao, X., Xu, Y., Krishfield, S., Lipsky, P. E., Tsokos, G. C., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-00993-3 · Cited by 449
Li, F., Long, H., Zhou, Z.-W., Luo, H., Xu, S., & Gao, L. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.910292 · Cited by 476
“2014), CD8 T cells (Matsushita et al., 2015), vascular endothelial cells (Wortmann et al.”
BackgroundSwitching Apoptosis to Ferroptosis: Metal–Organic Network for High-Efficiency Anticancer Therapy
Zheng, D., Lei, Q., Zhu, J., Fan, J., Li, C., Li, C., Xu, Z., Cheng, S., & Zhang, X. (2016) · Nano Letters · doi:10.1021/acs.nanolett.6b04060 · Cited by 437
Paradoxical Roles of Antioxidant Enzymes: Basic Mechanisms and Health Implications
Lei, X. G., Zhu, J., Cheng, W.-H., Bao, Y., Ho, Y.-S., Reddi, A. R., Holmgren, A., & Arnér, E. S. J. (2015) · Physiological Reviews · doi:10.1152/physrev.00010.2014 · Cited by 455
The application of Ferroptosis in diseases
Qiu, Y., Cao, Y., Cao, W., Jia, Y., & Lu, N. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104919 · Cited by 415
Metabolic regulation of the immune system in health and diseases: mechanisms and interventions
Hu, T., Liu, C., Lei, M., Zeng, Q., Li, L., Tang, H., & Zhang, N. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01954-6 · Cited by 438
Selenium–GPX4 axis protects follicular helper T cells from ferroptosis
Yao, Y., Chen, Z., Zhang, H., Chen, C., Zeng, M., Yunis, J., Wei, Y., Wan, Y., Wang, N., Zhou, M., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-00996-0 · Cited by 387
Oxidative Stress: Signaling Pathways, Biological Functions, and Disease
Liu, S., Liu, J., Wang, Y., Deng, F., & Deng, Z. (2025) · MedComm · doi:10.1002/mco2.70268 · Cited by 485
Ferroptosis and necroinflammation, a yet poorly explored link
Proneth, B., & Conrad, M. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0173-9 · Cited by 380
“lethality caused by the systemic loss of GPX4 [85], and the defects in the viability of GPX4 deficient T cells [41].”
BackgroundSelf-citationFerroptosis in Cancer Cell Biology
Bebber, C. M., Müller, F., Clemente, L. P., Weber, J., & von Karstedt, S. (2020) · Cancers · doi:10.3390/cancers12010164 · Cited by 372
Myeloid Cell-Derived Reactive Oxygen Species Induce Epithelial Mutagenesis
Canli, Ö., Nicolas, A. M., Gupta, J. R. P., Finkelmeier, F., Goncharova, O., Pesic, M. H., Neumann, T., Horst, D. A., Löwer, M., Şahin, U., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.11.004 · Cited by 375
“Recently, we and other groups have demonstrated that genetic ablation ofGpx4 causes spontaneous ferroptosis or necroptosis depending on the cell type (Canli et al., 2016; Matsushita et al., 2015; Seiler et al., 2008; Ueta et al., 2012; Yang et al., 2014).”
BackgroundFerroptosis in health and disease
Berndt, C., Alborzinia, H., Skafar, V., Ayton, S., Barayeu, U., Bartelt, A., Bayır, H., Bebber, C. M., Birsoy, K., Böttcher, J. P., et al. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103211 · Cited by 372
Self-citationQi, J., Kim, J.-W., Zhou, Z., Lim, C.-W., & Kim, B. (2020) · The American Journal of Pathology · doi:10.1016/j.ajpath.2019.09.011 · Cited by 338
Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications
Zheng, Y., Sun, J., Luo, Z., Li, Y., & Huang, Y. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-07244-x · Cited by 378
“A T cell-speci fi c GPX4-de fi cient mice displays a phenotype of accumulated lipid peroxides, leading to an intrinsic defect in defending acute lymphocytic choriomeningitis virus (LCMV) and Leishmania major parasite infections [256].”
Reactive Oxygen Species Regulate T Cell Immune Response in the Tumor Microenvironment
Chen, X., Song, M., Zhang, B., & Zhang, Y. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/1580967 · Cited by 326
Dixon, S. J. (2017) · Immunological Reviews · doi:10.1111/imr.12533 · Cited by 314
Programmed Cell Death Tunes Tumor Immunity
Liu, J., Hong, M., Li, Y., Chen, D., Wu, Y., & Hu, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.847345 · Cited by 330
Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration
Carlson, B. A., Tobe, R., Yefremova, E., Tsuji, P. A., Hoffmann, V. J., Schweizer, U., Gladyshev, V. N., Hatfield, D. L., & Conrad, M. (2016) · Redox Biology · doi:10.1016/j.redox.2016.05.003 · Cited by 316
“As reported in earlier studies [6,13], vitamin E can compensate for Gpx4 loss in some tissues in vivo (i.”
BackgroundSelf-citationFerroptosis Detection: From Approaches to Applications
Zeng, F., Nijiati, S., Tang, L., Ye, J., Zhou, Z., & Chen, X. S. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202300379 · Cited by 324
The Role of Iron Regulation in Immunometabolism and Immune-Related Disease
Cronin, S. J. F., Woolf, C. J., Weiss, G., & Penninger, J. M. (2019) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2019.00116 · Cited by 299
“GPX4 is essential for the survival and expansion of recently activated T cells, indicating the importance of preventing lipid peroxidation and of iron dysregulation resulting in ferroptosis, in T cell proliferation (Matsushita et al., 2015).”
BackgroundZhang, X., Sui, S., Wang, L., Li, H., Zhang, L., Xu, S., & Zheng, X. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29232 · Cited by 293
“Furthermore, ferroptosis was discovered to associate with other biological processes such as autophagy (Kang, Zhu, Zeh, Klionsky, & Tang, 2018), metabolism (Murphy, 2018), and immune (Matsushita et al., 2015) in cancer cells, indicating that maybe ferroptosis could be used to enhance other anticancer therapies.”
BackgroundFerroptosis in the tumor microenvironment: perspectives for immunotherapy
Xu, H., Ye, D., Ren, M., Zhang, H., & Bi, F. (2021) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2021.06.014 · Cited by 306
A guideline on the molecular ecosystem regulating ferroptosis
Dai, E., Chen, X., Linkermann, A., Jiang, X., Kang, R., Kagan, V. E., Bayır, H., Yang, W. S., García‐Sáez, A. J., Ioannou, M. S., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01360-8 · Cited by 327
“Conditional knockout of Gpx4 in various tissues (for example, kidney 8 ) or cells (for example, T cells 10 or B cells 9 ) can cause ferroptotic damage, highlighting its role in developmental biology.”
BackgroundJiang, Y., Mao, C., Yang, R., Yan, B., Shi, Y., Liu, X., Lai, W., Liu, Y., Wang, X., Xiao, D., et al. (2017) · Theranostics · doi:10.7150/thno.19988 · Cited by 298
“Vitamin E is regarded as a high efficient ferroptosis inhibitor[53, 54].”
BackgroundFerroptosis and Its Potential Role in Human Diseases
Han, C., Liu, Y., Dai, R., Ismail, N., Su, W., & Li, B. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00239 · Cited by 283
GPX4-independent ferroptosis—a new strategy in disease’s therapy
Ma, T., Du, J., Zhang, Y., Wang, Y., Wang, B., & Zhang, T. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01212-0 · Cited by 291
“INOS/NO PATHWAY It has been found that ferroptosis plays a role in different mammalian cells, but some specific types of cells, especially cells of the innate immune system (such as macrophages), show significant resistance to ferroptosis [44].”
BackgroundWeaver, K., & Skouta, R. (2022) · Biomedicines · doi:10.3390/biomedicines10040891 · Cited by 288
Mechanism of Ferroptosis and Its Role in Type 2 Diabetes Mellitus
Sha, W., Hu, F., Yang, X., Chu, Y., & Bu, S. (2021) · Journal of Diabetes Research · doi:10.1155/2021/9999612 · Cited by 276
Persister cancer cells: Iron addiction and vulnerability to ferroptosis
Rodriguez, R., Schreiber, S. L., & Conrad, M. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.12.001 · Cited by 280
Self-citationRethinking peripheral T cell tolerance: checkpoints across a T cell’s journey
ElTanbouly, M. A., & Noelle, R. J. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-00454-2 · Cited by 282
Role of Selenoproteins in Redox Regulation of Signaling and the Antioxidant System: A Review
Zhang, Y., Roh, Y. J., Han, S.-J., Park, I., Lee, H. M., Ok, Y. S., Lee, B. C., & Lee, S.-R. (2020) · Antioxidants · doi:10.3390/antiox9050383 · Cited by 267
“It has also been reported that GPx dysfunction is associated with the incidence of various types of cancer [40,41], muscle disorders [42], CVDs [43,44], hepatopathies [45], renal failure [46,47], neurological disorders (such as Alzheimer’s disease (AD) and Parkinson’s disease (PD)) [48–50], immune defense dysfunction…”
BackgroundThe complexity of p53-mediated metabolic regulation in tumor suppression
Liu, Y., & Gu, W. J. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.03.010 · Cited by 267
Metadata
- Authors
- Matsushita, M., Freigang, S., Schneider, C., Conrad, M., Bornkamm, G. W., & Kopf, M.
- Affiliations
- ETH Zurich (CH)
- Helmholtz Munich (DE)
- Molecular Biomedicine, Institute of Molecular Health Science, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland 1
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2015-03-30
- Volume
- 212
- Issue
- 4
- Pages
- 555-568
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC4387287
- OpenAlex
- W2065934830
- Cited by
- 672
- References
- 57
- Citations by year
- 2026: 65 · 2025: 77 · 2024: 90 · 2023: 90 · 2022: 95 · 2021: 92 · 2020: 56 · 2019: 28 · 2018: 25 · 2017: 22 · 2016: 24 · 2015: 8
- FWCI
- 12.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Repository for Publications and Research Data (ETH Zurich) (publishedVersion, cc-by-nc-sa)
- Bern Open Repository and Information System (University of Bern) (submittedVersion, cc-by-nc-sa)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- ETH Zürich Research Collection
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (141175, 310030B_141175/1)
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Keywords
- GPX4, ferroptosis, lipid peroxidation, T cell immunity, CD8+ T cells, CD4+ T cells, phospholipid hydroperoxides, vitamin E, lymphocytic choriomeningitis virus, Leishmania major, antiviral immunity, antiparasitic immunity, T cell homeostasis, T cell-specific knockout mice
- MeSH terms
- Phospholipid Hydroperoxide Glutathione Peroxidase, Animals, Cell Membrane, Glutathione Peroxidase, Immunologic Memory, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Thymus Gland, Vitamin E, Vitamins, Lipid Peroxidation, CD4-Positive T-Lymphocytes, Leishmaniasis, Cutaneous, Cell Death, Leishmania major, Mice, Knockout, CD8-Positive T-Lymphocytes, Mice
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