The molecular machinery of regulated cell death

Cell Research, Год журнала: 2019, Номер 29(5), С. 347 - 364

Опубликована: Апрель 4, 2019

Cells may die from accidental cell death (ACD) or regulated (RCD). ACD is a biologically uncontrolled process, whereas RCD involves tightly structured signaling cascades and molecularly defined effector mechanisms. A growing number of novel non-apoptotic forms have been identified are increasingly being implicated in various human pathologies. Here, we critically review the current state art regarding types RCD, including necroptosis, pyroptosis, ferroptosis, entotic death, netotic parthanatos, lysosome-dependent autophagy-dependent alkaliptosis oxeiptosis. The in-depth comprehension each these lethal subroutines their intercellular consequences uncover therapeutic targets for avoidance pathogenic loss.

Язык: Английский

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Targeting Ferroptosis to Iron Out Cancer

Cancer Cell, Год журнала: 2019, Номер 35(6), С. 830 - 849

Опубликована: Май 16, 2019

Язык: Английский

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Ferroptosis as a target for protection against cardiomyopathy

Proceedings of the National Academy of Sciences, Год журнала: 2019, Номер 116(7), С. 2672 - 2680

Опубликована: Янв. 28, 2019

Significance Nonapoptotic cell death-induced tissue damage has been implicated in a variety of diseases, including neurodegenerative disorder, inflammation, and stroke. In this study, we demonstrate that ferroptosis, newly defined iron-dependent death, mediates both chemotherapy- ischemia/reperfusion-induced cardiomyopathy. RNA-sequencing analysis revealed up-regulation heme oxygenase 1 by doxorubicin as major mechanism ferroptotic As result, degrades releases free iron cardiomyocytes, which turn leads to generation oxidized lipids the mitochondria membrane. Most importantly, chelation therapy pharmacologically blocking ferroptosis could significantly alleviate cardiomyopathy mice. These findings suggest targeting strategy for treating deadly heart disease.

Язык: Английский

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Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis

Oxidative Medicine and Cellular Longevity, Год журнала: 2019, Номер 2019, С. 1 - 13

Опубликована: Окт. 13, 2019

Reactive oxygen species- (ROS-) induced lipid peroxidation plays a critical role in cell death including apoptosis, autophagy, and ferroptosis. This fundamental conserved mechanism is based on an excess of ROS which attacks biomembranes, propagates chain reactions, subsequently induces different types death. A highly evolved sophisticated antioxidant system exists that acts to protect the cells from oxidative damage. In this review, we discussed how propagate reactions products initiate apoptosis autophagy current models. We also during ferroptosis, summarized pathological conditions illness. aim bring more global integrative sight know ROS-induced occurs among

Язык: Английский

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NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis

Redox Biology, Год журнала: 2019, Номер 23, С. 101107 - 101107

Опубликована: Янв. 12, 2019

The transcription factor nuclear erythroid 2-related 2 (NRF2) is a key regulator of the cellular antioxidant response, controlling expression genes that counteract oxidative and electrophilic stresses. Many pathological conditions are linked to imbalances in redox homeostasis, illustrating important role defense systems preventing pathogenic effects associated with accumulation reactive species. In particular, it becoming increasingly apparent lipid peroxides has an driving pathogenesis multiple disease states. A example this recent discovery novel form cell death termed ferroptosis. Ferroptosis iron-dependent, peroxidation-driven cascade become target development anti-cancer therapies, as well prevention neurodegenerative cardiovascular diseases. review, we will provide brief overview peroxidation, components involved ferroptotic cascade. We also highlight NRF2 signaling pathway mediating peroxidation ferroptosis, focusing on established mitigate these pathways, relevance NRF2-lipid peroxidation-ferroptosis axis disease.

Язык: Английский

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Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy

Protein & Cell, Год журнала: 2020, Номер 12(8), С. 599 - 620

Опубликована: Окт. 1, 2020

Abstract The cystine/glutamate antiporter SLC7A11 (also commonly known as xCT) functions to import cystine for glutathione biosynthesis and antioxidant defense is overexpressed in multiple human cancers. Recent studies revealed that overexpression promotes tumor growth partly through suppressing ferroptosis, a form of regulated cell death induced by excessive lipid peroxidation. However, cancer cells with high expression (SLC7A11 ) also have endure the significant cost associated SLC7A11-mediated metabolic reprogramming, leading glucose- glutamine-dependency cells, which presents potential vulnerabilities therapeutic targeting cancer. In this review, we summarize diverse regulatory mechanisms cancer, discuss ferroptosis-dependent -independent promoting development, explore mechanistic basis SLC7A11-induced nutrient dependency conceptualize strategies target treatment. This review will provide foundation further understanding dependency, biology developing novel effective therapies.

Язык: Английский

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Targeting ferroptosis as a vulnerability in cancer

Nature reviews. Cancer, Год журнала: 2022, Номер 22(7), С. 381 - 396

Опубликована: Март 25, 2022

Язык: Английский

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Recent Progress in Ferroptosis Inducers for Cancer Therapy

Advanced Materials, Год журнала: 2019, Номер 31(51)

Опубликована: Окт. 8, 2019

Abstract Ferroptosis is a newly discovered form of regulated cell death that the nexus between metabolism, redox biology, and human health. Emerging evidence shows potential triggering ferroptosis for cancer therapy, particularly eradicating aggressive malignancies are resistant to traditional therapies. Recently, there has been great deal effort design develop anticancer drugs based on induction. Recent advances ferroptosis‐inducing agents at intersection chemistry, materials science, biology presented. The basis summarized first highlight feasibility characteristics therapy. A literature review inducers (including small molecules nanomaterials) then presented delineate their design, action mechanisms, applications. Finally, some considerations research spotlighted, followed by discussion challenges future development directions this burgeoning field.

Язык: Английский

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The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression

Cell Research, Год журнала: 2020, Номер 30(2), С. 146 - 162

Опубликована: Янв. 16, 2020

Язык: Английский

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Ferroptosis: mechanisms and links with diseases

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Фев. 3, 2021

Abstract Ferroptosis is an iron-dependent cell death, which different from apoptosis, necrosis, autophagy, and other forms of death. The process ferroptotic death defined by the accumulation lethal lipid species derived peroxidation lipids, can be prevented iron chelators (e.g., deferiprone, deferoxamine) small lipophilic antioxidants ferrostatin, liproxstatin). This review summarizes current knowledge about regulatory mechanism ferroptosis its association with several pathways, including iron, lipid, cysteine metabolism. We have further discussed contribution to pathogenesis diseases such as cancer, ischemia/reperfusion, various neurodegenerative Alzheimer’s disease Parkinson’s disease), evaluated therapeutic applications inhibitors in clinics.

Язык: Английский

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