Dynamic Regulation of Ferroptosis by Lipid Metabolism DOI
Nathchar Naowarojna, Tianshu William Wu, Zijian Pan

и другие.

Antioxidants and Redox Signaling, Год журнала: 2023, Номер 39(1-3), С. 59 - 78

Опубликована: Март 28, 2023

Significance: Ferroptosis is featured by the accumulation of polyunsaturated-lipid peroxidation on cellular membranes in an iron-dependent manner. has been implicated various pathophysiological processes, including cancer, neurodegeneration, and ischemia-reperfusion tissue injury. However, our understanding about dynamic context-specific regulation ferroptosis remains incomplete. Recent Advances: As major substrate for peroxidation, lipidome regulates sensitivity execution controlling abundance availability polyunsaturated-lipids peroxidative modifications. In turn, regulated a complex network enzymes transporters, as well upstream layers receptors, kinases, transcription factors. A number research shed light link between lipid metabolism ferroptosis. Here, we summarize current knowledge role associated protein regulators stages ferroptosis, ranging from initiation, to cell death evasion cells experiencing ferroptotic stress. Critical Issues: This review provides overview mechanisms underlying discussing species that directly contribute how regulate abundances these pro-ferroptosis lipids, causes death, prevent repair membrane damage under conditions. Future Directions: Cell fate vivo could be different vitro culture settings. We envision comprehensive detailed important questions will accelerate development ferroptosis-targeted therapies improve human health.

Язык: Английский

Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies DOI Creative Commons
Qian Zhou,

Yu Meng,

Daishi Li

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Язык: Английский

Процитировано

182
Tryptophan Metabolism Acts as a New Anti‐Ferroptotic Pathway to Mediate Tumor Growth DOI Creative Commons
Dong Liu, Chunhui Liang, Bin Huang

и другие.

Advanced Science, Год журнала: 2023, Номер 10(6)

Опубликована: Янв. 10, 2023

Abstract Emerging evidence reveals that amino acid metabolism plays an important role in ferroptotic cell death. The conversion of methionine to cysteine is well known protect tumour cells from ferroptosis upon starvation through transamination. However, whether acids‐produced metabolites participate independent the pathway largely unknown. Here, authors show tryptophan serotonin (5‐HT) and 3‐hydroxyanthranilic (3‐HA) remarkably facilitate escape distinct cysteine‐mediated inhibition. Mechanistically, both 5‐HT 3‐HA act as potent radical trapping antioxidants (RTA) eliminate lipid peroxidation, thereby inhibiting Monoamine oxidase A (MAOA) markedly abrogates protective effect via degrading 5‐HT. Deficiency MAOA renders cancer resistant treatment. Kynureninase (KYNU), which essential for production, confers death, whereas 3‐hydroxyanthranilate 3,4‐dioxygenase (HAAO) significantly blocks mediated inhibition by consuming 3‐HA. In addition, expression level HAAO positively correlated with peroxidation clinical outcome. Together, findings demonstrate works a new anti‐ferroptotic promote growth, targeting this will be promising therapeutic approach

Язык: Английский

Процитировано

89
Gut microbial metabolite facilitates colorectal cancer development via ferroptosis inhibition DOI
Weiwei Cui, Meng Guo, Dong Liu

и другие.

Nature Cell Biology, Год журнала: 2024, Номер 26(1), С. 124 - 137

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

75
The mechanism of ferroptosis and its related diseases DOI Creative Commons
Shijian Feng, Dan Tang, Yichang Wang

и другие.

Molecular Biomedicine, Год журнала: 2023, Номер 4(1)

Опубликована: Окт. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Язык: Английский

Процитировано

70
Ferroptosis: principles and significance in health and disease DOI Creative Commons
Fangquan Chen, Rui Kang, Daolin Tang

и другие.

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Июнь 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.

Язык: Английский

Процитировано

59
Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer DOI Creative Commons
Guoshu Bi, Jiaqi Liang, Yunyi Bian

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 19, 2024

Abstract Targeting ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal overload lipid peroxides, in cancer therapy is impeded our limited understanding intersection tumour’s metabolic feature and ferroptosis vulnerability. In present study, arginine identified as a ferroptotic promoter using metabolites library. This effect mainly achieved through arginine’s conversion to polyamines, which exerts their potent ferroptosis-promoting property H 2 O -dependent manner. Notably, expression ornithine decarboxylase 1 (ODC1), critical enzyme catalysing polyamine synthesis, significantly activated signal——iron overload——through WNT/MYC signalling, well subsequent elevated thus forming ferroptosis-iron overload-WNT/MYC-ODC1-polyamine-H positive feedback loop that amplifies ferroptosis. Meanwhile, we notice cells release enhanced polyamine-containing extracellular vesicles into microenvironment, thereby further sensitizing neighbouring accelerating “spread” tumour region. Besides, supplementation also sensitizes or xenograft tumours radiotherapy chemotherapy inducing Considering are often characterized intracellular pools, results indicate metabolism exposes targetable vulnerability represents exciting opportunity for therapeutic strategies cancer.

Язык: Английский

Процитировано

45
Identification of a targeted ACSL4 inhibitor to treat ferroptosis-related diseases DOI Creative Commons
Qian Huang, Yi Ru, Ying‐Li Luo

и другие.

Science Advances, Год журнала: 2024, Номер 10(13)

Опубликована: Март 29, 2024

Ferroptosis is a form of iron-dependent, lipid peroxidation–driven regulatory cell death that has been implicated in the pathogenesis multiple diseases, including organ injury, ischemia/reperfusion, and neurodegenerative diseases. However, inhibitors directly specifically target ferroptosis are not yet available. Here, we identify compound AS-252424 (AS) as potent inhibitor through kinase library screening. Our results show AS effectively inhibits peroxidation both human mouse cells. Mechanistically, binds to glutamine 464 ACSL4 inhibit its enzymatic activity, resulting suppression ferroptosis. By using nanoparticle-based delivery systems, treatment with AS-loaded nanoparticles alleviate ferroptosis-mediated injury models, kidney ischemia/reperfusion acute liver (ALI). Thus, our specific targeted remarkable antiferroptosis function, providing potential therapeutic for ferroptosis-related

Язык: Английский

Процитировано

43
Cellular metabolism: A key player in cancer ferroptosis DOI Creative Commons

Xianjie Jiang,

Qiu Peng,

Mingjing Peng

и другие.

Cancer Communications, Год журнала: 2024, Номер 44(2), С. 185 - 204

Опубликована: Янв. 13, 2024

Abstract Cellular metabolism is the fundamental process by which cells maintain growth and self‐renewal. It produces energy, furnishes raw materials, intermediates for biomolecule synthesis, modulates enzyme activity to sustain normal cellular functions. foundation of life processes plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis recently discovered form iron‐dependent The inhibition ferroptosis crucial tumorigenesis tumor progression. However, metabolism, particularly glucose amino acid cancer not well understood. Here, we reviewed glucose, lipid, acid, iron selenium involvement elucidate impact different metabolic pathways on this process. Additionally, provided detailed overview agents used induce ferroptosis. We explained that maintaining intracellular redox homeostasis disrupting these renders them more susceptible iron‐induced death, resulting enhanced killing. combination inducers inhibitors may be novel approach future therapy an important strategy advance development treatments.

Язык: Английский

Процитировано

24
The effects of metabolism on the immune microenvironment in colorectal cancer DOI Creative Commons

Xingzhao Chen,

Zhiyuan Ma, Zhiqiang Yi

и другие.

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Март 7, 2024

Abstract Colorectal cancer (CRC) is a malignancy that widely prevalent worldwide. Due to its unsatisfactory treatment outcome and extremely poor prognosis, many studies on the molecular mechanisms pathological of CRC have been published in recent years. The tumor microenvironment (TME) an important feature tumorigenesis one hallmarks development. Metabolic reprogramming currently hot topic research, this provided insights into In particular, metabolic causes changes composition energy nutrients TME. Furthermore, it can alter complex crosstalk between immune cells associated factors, such as macrophages T cells, which play roles TME, turn affecting escape tumors by altering surveillance. review, we summarize several metabolism-related processes tumors. Our results showed regulated influences development CRC.

Язык: Английский

Процитировано

22
Targeting pancreatic cancer glutamine dependency confers vulnerability to GPX4-dependent ferroptosis DOI Creative Commons
Xuqing Shen,

Yueyue Chen,

Yingying Tang

и другие.

Cell Reports Medicine, Год журнала: 2025, Номер unknown, С. 101928 - 101928

Опубликована: Янв. 1, 2025

Pancreatic ductal adenocarcinoma (PDAC) relies heavily on glutamine (Gln) utilization to meet its metabolic and biosynthetic needs. How epigenetic regulators contribute the flexibility PDAC's response adaptation Gln scarcity in tumor milieu remains largely unknown. Here, we elucidate that prolonged restriction or treatment with antagonist, 6-diazo-5-oxo-L-norleucine (DON), leads growth inhibition ferroptosis program activation PDAC. A CRISPR-Cas9 screen identifies an regulator, Paxip1, which promotes H3K4me3 upregulation Hmox1 transcription upon DON treatment. Additionally, ferroptosis-related repressors (e.g., Slc7a11 Gpx4) are increased as adaptive response, thereby predisposing PDAC cells deprivation. Moreover, sensitizes GPX4 inhibitor-induced ferroptosis, both vitro patient-derived xenografts (PDXs). Taken together, our findings reveal targeting dependency confers susceptibility GPX4-dependent via remodeling provides a combination strategy for therapy.

Язык: Английский

Процитировано

3