{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nGlutathione peroxidase 4 (GPx4), also known as phospholipid hydroperoxide glutathione peroxidase (PHGPx), is a unique selenoenzyme that directly reduces phospholipid hydroperoxides in cellular membranes and lipoproteins. By detoxifying lipid peroxides, GPx4 prevents the induction of ferroptosis—a regulated, non‐apoptotic cell death pathway—and thereby maintains mitochondrial integrity, protects neuronal and cardiac tissues, and supports overall cell viability. Genetic ablation or down‐regulation of GPx4 leads to catastrophic tissue damage including acute renal failure, embryonic lethality, neurodegeneration, and cardiomyopathy, underscoring its essential role in cellular redox homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical antioxidant role, GPx4 is critical for modulating immune responses. It stabilizes innate immunity by preserving proper STING activation and protects regulatory T cells from lipid peroxidation–induced ferroptosis, while also dampening excessive pro‐inflammatory cell death responses in macrophages."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its enzymatic activity, GPx4 also fulfills non‐canonical, structural roles in the male reproductive system. In spermatids, GPx4 is expressed as a soluble peroxidase, whereas in mature spermatozoa it becomes enzymatically inactive yet functionally indispensable as a structural protein that stabilizes the mitochondrial capsule and ensures proper sperm head morphology and motility. This dual function is essential for male fertility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGPx4 further influences developmental and therapeutic processes across multiple organ systems. It governs embryonic development and differentiation by regulating redox‐sensitive signaling pathways, impacts photoreceptor survival in the retina, and modulates liver homeostasis through its interplay with lipid peroxidation and vitamin E status. Moreover, dysregulation of GPx4 has been linked to impaired erythrocyte maturation, aberrant skin and retinal cell homeostasis, and even tumor cell resistance to ferroptotic stimuli. Such diverse roles highlight GPx4 as a promising therapeutic target for conditions ranging from cancer and acute myocardial injury to neurodegenerative and metabolic diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Levi J Yant, Qitao Ran, Lin Rao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Free Radic Biol Med (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0891-5849(02)01360-6"}], "href": "https://doi.org/10.1016/s0891-5849(02"}, {"type": "t", "text": "01360-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12566075"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12566075"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hirotaka Imai, Fumi Hirao, Taro Sakamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(03)00734-4"}], "href": "https://doi.org/10.1016/s0006-291x(03"}, {"type": "t", "text": "00734-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12745070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12745070"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Qitao Ran, Hanyu Liang, Minjun Gu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transgenic mice overexpressing glutathione peroxidase 4 are protected against oxidative stress-induced apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M410387200"}], "href": "https://doi.org/10.1074/jbc.M410387200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15496407"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15496407"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Christoph Ufer, Chi Chiu Wang, Michael Fähling, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Translational regulation of glutathione peroxidase 4 expression through guanine-rich sequence-binding factor 1 is essential for embryonic brain development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.466308"}], "href": "https://doi.org/10.1101/gad.466308"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18593884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18593884"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Alexander Seiler, Manuela Schneider, Heidi Förster, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2008.07.005"}], "href": "https://doi.org/10.1016/j.cmet.2008.07.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18762024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18762024"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Eva K Wirth, Marcus Conrad, Jochen Winterer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuronal selenoprotein expression is required for interneuron development and prevents seizures and neurodegeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.09-143974"}], "href": "https://doi.org/10.1096/fj.09-143974"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19890015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19890015"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Takashi Ueta, Tatsuya Inoue, Takahisa Furukawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glutathione peroxidase 4 is required for maturation of photoreceptor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.335174"}], "href": "https://doi.org/10.1074/jbc.M111.335174"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22207760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22207760"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jose Pedro Friedmann Angeli, Manuela Schneider, Bettina Proneth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3064"}], "href": "https://doi.org/10.1038/ncb3064"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25402683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25402683"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Liuji Chen, William Sealy Hambright, Ren Na, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ablation of the Ferroptosis Inhibitor Glutathione Peroxidase 4 in Neurons Results in Rapid Motor Neuron Degeneration and Paralysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.680090"}], "href": "https://doi.org/10.1074/jbc.M115.680090"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26400084"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26400084"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "William Sealy Hambright, Rene Solano Fonseca, Liuji Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Redox Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.redox.2017.01.021"}], "href": "https://doi.org/10.1016/j.redox.2017.01.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28212525"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28212525"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Irina Ingold, Carsten Berndt, Sabine Schmitt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2017.11.048"}], "href": "https://doi.org/10.1016/j.cell.2017.11.048"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29290465"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29290465"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Rui Kang, Ling Zeng, Shan Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Host Microbe (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chom.2018.05.009"}], "href": "https://doi.org/10.1016/j.chom.2018.05.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29937272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29937272"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Tomonori Tadokoro, Masataka Ikeda, Tomomi Ide, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondria-dependent ferroptosis plays a pivotal role in doxorubicin cardiotoxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JCI Insight (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/jci.insight.132747"}], "href": "https://doi.org/10.1172/jci.insight.132747"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32376803"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32376803"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Mutian Jia, Danhui Qin, Chunyuan Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Redox homeostasis maintained by GPX4 facilitates STING activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41590-020-0699-0"}], "href": "https://doi.org/10.1038/s41590-020-0699-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32541831"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32541831"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Chengxian Xu, Shaogang Sun, Travis Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2021.109235"}], "href": "https://doi.org/10.1016/j.celrep.2021.109235"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34133924"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34133924"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "F Ursini, S Heim, M Kiess, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dual function of the selenoprotein PHGPx during sperm maturation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (1999)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.285.5432.1393"}], "href": "https://doi.org/10.1126/science.285.5432.1393"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10464096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10464096"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Astrid Borchert, Nicolai E Savaskan, Hartmut Kuhn "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of expression of the phospholipid hydroperoxide/sperm nucleus glutathione peroxidase gene. Tissue-specific expression pattern and identification of functional cis- and trans-regulatory elements."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M209064200"}], "href": "https://doi.org/10.1074/jbc.M209064200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12427732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12427732"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "M Conrad, S G Moreno, F Sinowatz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The nuclear form of phospholipid hydroperoxide glutathione peroxidase is a protein thiol peroxidase contributing to sperm chromatin stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.17.7637-7644.2005"}], "href": "https://doi.org/10.1128/MCB.25.17.7637-7644.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16107710"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16107710"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Qitao Ran, Hanyu Liang, Yuji Ikeno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gerontol A Biol Sci Med Sci (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/gerona/62.9.932"}], "href": "https://doi.org/10.1093/gerona/62.9.932"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17895430"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17895430"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Manuela Schneider, Heidi Förster, Auke Boersma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial glutathione peroxidase 4 disruption causes male infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.09-132795"}], "href": "https://doi.org/10.1096/fj.09-132795"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19417079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19417079"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Hirotaka Imai, Nao Hakkaku, Ryo Iwamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Depletion of selenoprotein GPx4 in spermatocytes causes male infertility in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.016139"}], "href": "https://doi.org/10.1074/jbc.M109.016139"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19783653"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19783653"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Gaigai Wang, Yibo Wu, Tao Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mapping of the N-linked glycoproteome of human spermatozoa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Proteome Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/pr400753f"}], "href": "https://doi.org/10.1021/pr400753f"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24191733"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24191733"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Astrid Borchert, Chi Chiu Wang, Christoph Ufer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of phospholipid hydroperoxide glutathione peroxidase isoforms in murine embryogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M601195200"}], "href": "https://doi.org/10.1074/jbc.M601195200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16684775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16684775"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Hanyu Liang, Holly Van Remmen, Victoria Frohlich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gpx4 protects mitochondrial ATP generation against oxidative damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2007.03.045"}], "href": "https://doi.org/10.1016/j.bbrc.2007.03.045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17395155"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17395155"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Lili Lu, Brain C Oveson, Young-Joon Jo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of glutathione peroxidase 4 strongly protects retina from oxidative damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Antioxid Redox Signal (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ars.2008.2171"}], "href": "https://doi.org/10.1089/ars.2008.2171"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18823256"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18823256"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Aniruddha Sengupta, Ulrike F Lichti, Bradley A Carlson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted disruption of glutathione peroxidase 4 in mouse skin epithelial cells impairs postnatal hair follicle morphogenesis that is partially rescued through inhibition of COX-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2013.52"}], "href": "https://doi.org/10.1038/jid.2013.52"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23364477"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23364477"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Khajag Koulajian, Alexander Ivovic, Kaitai Ye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of glutathione peroxidase 4 prevents β-cell dysfunction induced by prolonged elevation of lipids in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00481.2012"}], "href": "https://doi.org/10.1152/ajpendo.00481.2012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23695217"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23695217"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Simone Hanna Brütsch, Chi Chiu Wang, Lu Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of inactive glutathione peroxidase 4 leads to embryonic lethality, and inactivation of the Alox15 gene does not rescue such knock-in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Antioxid Redox Signal (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ars.2014.5967"}], "href": "https://doi.org/10.1089/ars.2014.5967"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25313597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25313597"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Bradley A Carlson, Ryuta Tobe, Elena Yefremova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Redox Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.redox.2016.05.003"}], "href": "https://doi.org/10.1016/j.redox.2016.05.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27262435"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27262435"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Sandro Altamura, Naidu M Vegi, Philipp S Hoppe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glutathione peroxidase 4 and vitamin E control reticulocyte maturation, stress erythropoiesis and iron homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Haematologica (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3324/haematol.2018.212977"}], "href": "https://doi.org/10.3324/haematol.2018.212977"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31248967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31248967"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Yang Liu, Yuan Wang, Jiao Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interplay between MTOR and GPX4 signaling modulates autophagy-dependent ferroptotic cancer cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Gene Ther (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41417-020-0182-y"}], "href": "https://doi.org/10.1038/s41417-020-0182-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32457486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32457486"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Faisal Thayyullathil, Anees Rahman Cheratta, Ameer Alakkal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acid sphingomyelinase-dependent autophagic degradation of GPX4 is critical for the execution of ferroptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-020-03297-w"}], "href": "https://doi.org/10.1038/s41419-020-03297-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33414455"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33414455"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Liuji Chen, Ren Na, Kirsten Danae McLane, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of ferroptosis defense enzyme Gpx4 retards motor neuron disease of SOD1G93A mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-92369-8"}], "href": "https://doi.org/10.1038/s41598-021-92369-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34145375"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34145375"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Yuan Yuan, Yanyu Zhai, Jingjiong Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kaempferol Ameliorates Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Ferroptosis by Activating Nrf2/SLC7A11/GPX4 Axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomolecules (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/biom11070923"}], "href": "https://doi.org/10.3390/biom11070923"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34206421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34206421"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Kai Fan, Wei Huang, Hanping Qi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Egr-1/miR-15a-5p/GPX4 axis regulates ferroptosis in acute myocardial infarction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pharmacol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejphar.2021.174403"}], "href": "https://doi.org/10.1016/j.ejphar.2021.174403"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34339707"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34339707"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Zhuan Feng, Yifei Qin, Fei Huo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NMN recruits GSH to enhance GPX4-mediated ferroptosis defense in UV irradiation induced skin injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Basis Dis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2021.166287"}], "href": "https://doi.org/10.1016/j.bbadis.2021.166287"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34626772"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34626772"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Jingbo Li, Jiao Liu, Zhuan Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor-specific GPX4 degradation enhances ferroptosis-initiated antitumor immune response in mouse models of pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Transl Med (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scitranslmed.adg3049"}], "href": "https://doi.org/10.1126/scitranslmed.adg3049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37910602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37910602"}]}]}]}