Ferroptosis in health and disease

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103211 - 103211

Published: May 30, 2024

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark ferroptosis uncontrolled overwhelming peroxidation polyunsaturated fatty acids contained membrane phospholipids, which eventually leads to rupture the plasma membrane. unique that it essentially spontaneous, uncatalyzed chemical process based on perturbed iron redox homeostasis contributing process, but nonetheless modulated by many metabolic nodes impinge cells' susceptibility ferroptosis. Among affecting sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets treatment numerous currently incurable diseases. Herein, current members Germany-wide research consortium focusing research, well key external experts who made seminal contributions this rapidly growing exciting field gathered provide comprehensive, state-of-the-art review Specific topics include: basic mechanisms, vivo relevance, specialized methodologies, tools, potential contribution disease etiopathology progression. We hope article will not only established scientists newcomers with an overview multiple facets ferroptosis, also encourage additional efforts characterize further molecular pathways modulating ultimate goal develop novel pharmacotherapies tackle associated - or caused

Language: Английский

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Ferroptosis: principles and significance in health and disease

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 6, 2024

Abstract Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic pathway in 2012, ferroptosis has emerged crucial mechanism numerous physiological pathological contexts, leading to significant therapeutic advancements across wide range diseases. This review summarizes the fundamental mechanisms regulatory pathways underlying ferroptosis, including both GPX4-dependent -independent antioxidant mechanisms. Additionally, we examine involvement various conditions, cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, metabolic disorders. Specifically, explore role response chemotherapy, radiotherapy, immunotherapy, nanotherapy, targeted therapy. Furthermore, discuss pharmacological strategies for modulating potential biomarkers monitoring this process. Lastly, elucidate interplay between other forms regulated death. Such insights hold promise advancing our understanding context human health disease.

Language: Английский

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Exploiting ferroptosis vulnerabilities in cancer

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(9), P. 1407 - 1419

Published: June 10, 2024

Language: Английский

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Emerging targets in lipid metabolism for cancer therapy

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(6), P. 537 - 551

Published: May 17, 2024

Cancer cells perturb lipid metabolic pathways for a variety of pro-tumorigenic functions, and deregulated cellular metabolism is hallmark cancer cells. Although alterations in have been appreciated over 20 years, there are no FDA-approved treatments that target lipid-related pathways. Recent advances pertaining to cell fatty acid synthesis (FAS), desaturation, uptake, microenvironmental dietary lipids, tumor-infiltrating immune illuminated promising clinical applications targeting metabolism. This review highlights emerging targets tumor may soon impact treatment.

Language: Английский

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Fatal COVID-19 pulmonary disease involves ferroptosis

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 20, 2024

Abstract SARS-CoV-2 infection causes severe pulmonary manifestations, with poorly understood mechanisms and limited treatment options. Hyperferritinemia disrupted lung iron homeostasis in COVID-19 patients imply that ferroptosis, an iron-dependent cell death, may occur. Immunostaining lipidomic analysis autopsies reveal increases ferroptosis markers, including transferrin receptor 1 malondialdehyde accumulation fatal cases. lungs display dysregulation of lipids involved metabolism ferroptosis. We find increased ferritin light chain associated pathology. Iron overload promotes both primary cells cancerous epithelial cells. In addition, markers strongly correlate injury severity a disease model using male Syrian hamsters. These results role for disease; pharmacological inhibition serve as adjuvant therapy to prevent damage during infection.

Language: Английский

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In defence of ferroptosis

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 2, 2025

Abstract Rampant phospholipid peroxidation initiated by iron causes ferroptosis unless this is restrained cellular defences. Ferroptosis increasingly implicated in a host of diseases, and unlike other cell death programs the physiological initiation conceived to occur not an endogenous executioner, but withdrawal guardians that otherwise constantly oppose induction. Here, we profile key ferroptotic defence strategies including regulation, modulation enzymes metabolite systems: glutathione reductase (GR), suppressor protein 1 (FSP1), NAD(P)H Quinone Dehydrogenase (NQO1), Dihydrofolate (DHFR), retinal reductases dehydrogenases (RDH) thioredoxin (TR). A common thread uniting all metabolites combat lipid during dependence on reductant, nicotinamide adenine dinucleotide phosphate (NADPH). We will outline how cells control central carbon metabolism produce NADPH necessary precursors defend against ferroptosis. Subsequently discuss evidence for dysregulation different disease contexts glucose-6-phosphate dehydrogenase deficiency, cancer neurodegeneration. Finally, several anti-ferroptosis therapeutic spanning use radical trapping agents, dependent redox support highlight current landscape clinical trials focusing

Language: Английский

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VSTM2L protects prostate cancer cells against ferroptosis via inhibiting VDAC1 oligomerization and maintaining mitochondria homeostasis

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 29, 2025

Ferroptosis is a form of iron-dependent programmed cell death, which distinct from apoptosis, necrosis, and autophagy. Mitochondria play critical role in initiating amplifying ferroptosis cancer cells. Voltage-Dependent Anion Channel 1 (VDAC1) embedded the mitochondrial outer membrane, exerts roles regulation ferroptosis. However, mechanisms VDAC1 oligomerization regulating are not well elucidated. Here, we identify that binding protein V-Set Transmembrane Domain Containing 2 Like (VSTM2L), mainly localized to mitochondria, positively associated with prostate (PCa) progression, key regulator Moreover, VSTM2L knockdown PCa cells enhances sensitivity RSL3-induced Mechanistically, forms complex hexokinase (HK2), enhancing their affinity preventing oligomerization, thereby inhibiting maintaining mitochondria homeostasis vitro vivo. Collectively, our findings reveal pivotal for mitochondria-localized driving resistance highlight its potential as ferroptosis-inducing therapeutic target treatment PCa.

Language: Английский

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FSP1-mediated ferroptosis in cancer: from mechanisms to therapeutic applications

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(7-8), P. 1019 - 1037

Published: April 14, 2024

Language: Английский

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Oxidative Metabolism as a Cause of Lipid Peroxidation in the Execution of Ferroptosis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7544 - 7544

Published: July 9, 2024

Ferroptosis is a type of nonapoptotic cell death that characteristically caused by phospholipid peroxidation promoted radical reactions involving iron. Researchers have identified many the protein factors are encoded genes promote ferroptosis. Glutathione peroxidase 4 (GPX4) key enzyme protects phospholipids from and suppresses ferroptosis in glutathione-dependent manner. Thus, dysregulation involved cysteine and/or glutathione metabolism closely associated with From perspective dynamics, actively proliferating cells more prone to than quiescent cells, which suggests species generated during oxygen-involved responsible for lipid peroxidation. Herein, we discuss initial events dominantly occur process energy metabolism, association deficiency. Accordingly, tricarboxylic acid cycle coupled respiratory chain mitochondria main subjects here, this likely source both electrons free Since not only carbohydrates, but also amino acids, especially glutamate, major substrates central dealing nitrogen derived groups contributes subject discussion.

Language: Английский

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Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 2485 - 2529

Published: June 1, 2024

Abstract: Ferroptosis, a unique form of programmed cell death, is initiated by an excess iron accumulation and lipid peroxidation-induced damage. There growing body evidence indicating that ferroptosis plays critical role in the advancement tumors. The increased metabolic activity higher levels tumor cells make them particularly vulnerable to ferroptosis. As result, targeted induction becoming increasingly promising approach for cancer treatment. This review offers overview regulatory mechanisms ferroptosis, delves into mechanism action traditional small molecule inducers their effects on various In addition, latest progress inducing using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic (SDT) nanomaterials summarized. Finally, this discusses challenges opportunities development ferroptosis-inducing agents, focusing discovering targets, improving selectivity, reducing toxic side effects. Keywords: inducers, molecules, PROTACs, PDT, SDT,

Language: Английский

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