The emerging role of nuclear receptor coactivator 4 in health and disease: a novel bridge between iron metabolism and immunity DOI Creative Commons
Yue Le, Qinjie Liu, Yi Yang

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: July 3, 2024

Nuclear receptor coactivator 4 (NCOA4) has recently been recognized as a selective cargo of ferritinophagy participating in ferroptosis. However, NCOA4 is also that modulates the transcriptional activity many vital nuclear receptors. Recent novel studies have documented role healthy and pathogenic conditions via its modulation iron- non-iron-dependent metabolic pathways. exhibits non-ferritinophagic iron-independent features such promoting tumorigenesis erythropoiesis, immunomodulation, regulating autophagy, DNA replication mitosis. Full-length human-NCOA4 composed 614 amino acids, which N-terminal (1-237) contains nuclear-receptor-binding domains, while C-terminal (238-614) principally ferritin-binding domain. The exploration protein structure suggests possesses additional significant complex functions based on structural domains. Intriguingly, another three isoforms are produced by alternative splicing identified, may display disparate activities physiological pathological processes. Thus, become an important bridge encompasses interactions between immunity metabolism. In this review, we outline latest advances mechanisms underlying actions health disease conditions, providing insights into potential therapeutic interventions.

Language: Английский

YAP1 alleviates sepsis-induced acute lung injury via inhibiting ferritinophagy-mediated ferroptosis DOI Creative Commons
Jing Zhang, Yong‐Ping Zheng, Yun Wang

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 1, 2022

Ferroptosis is a phospholipid peroxidation-mediated and iron-dependent cell death form, involved in sepsis-induced organ injury other lung diseases. Yes-associated protein 1 (YAP1), key regulator of the Hippo signaling pathway, could target multiple ferroptosis regulators. Herein, this study aimed to explore involvement etiopathogenesis acute (ALI) demonstrate that YAP1 disrupt ferritinophagy moderate ALI. Cecal ligation puncture (CLP) models were constructed wild-type (WT) pulmonary epithelium-conditional knockout (YAP1 f/f ) mice induce ALI, while MLE-12 cells with or without overexpression stimulated by lipopolysaccharide (LPS) vitro . In-vivo modes showed aggravated CLP-induced ALI also accelerated ferroptosis, as presented downregulated expression GPX4, FTH1, SLC7A11, along upregulated SFXN1 NCOA4. Transcriptome research identified these genes pathways In-vitro consistently verified deficiency boosted ferrous iron accumulation mitochondrial dysfunction response LPS. Furthermore, co-IP assay revealed prevent degradation ferritin mass Fe 2+ (ferritinophagy) via disrupting NCOA4–FTH1 interaction, which blocked transport cytoplasmic into mitochondria membrane (SFXN1), further reducing generation ROS. Therefore, findings inhibit ferritinophagy-mediated manner, thus alleviating may provide new approach therapeutic orientation for

Language: Английский

Citations

133
The mechanism of ferroptosis and its related diseases DOI Creative Commons
Shijian Feng, Dan Tang, Yichang Wang

et al.

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 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.

Language: Английский

Citations

69
Cell senescence in liver diseases: pathological mechanism and theranostic opportunity DOI
David Sanfeliu-Redondo, Albert Gibert‐Ramos, Jordi Gracia‐Sancho

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 21(7), P. 477 - 492

Published: March 14, 2024

Language: Английский

Citations

24
Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance DOI Creative Commons
Peng Zhao,

Shuangshuang Yin,

Yuling Qiu

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 17, 2025

Drug resistance is a common challenge in clinical tumor treatment. A reduction drug sensitivity of cells often accompanied by an increase autophagy levels, leading to autophagy-related resistance. The effectiveness combining chemotherapy drugs with inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear. Ferroptosis and pyroptosis can be affected various types autophagy. Therefore, ferroptosis have crosstalk via autophagy, potentially switch cell death under certain conditions. As two forms inflammatory programmed death, different effects on inflammation, cGAS-STING signaling pathway also involved. it plays important role progression some chronic diseases. This review discusses relationship between pyroptosis, attempts uncover reasons behind evasion nature

Language: Английский

Citations

3
Nuclear receptor coactive 4-mediated ferritinophagy: a key role of heavy metals toxicity DOI

Wan-Xue Xu,

Wen Xue, Yupeng Fu

et al.

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Language: Английский

Citations

2
YAP1 protects against septic liver injury via ferroptosis resistance DOI Creative Commons
Jin Wang, Qian Zhu, Rui Li

et al.

Cell & Bioscience, Journal Year: 2022, Volume and Issue: 12(1)

Published: Oct. 1, 2022

Abstract Background The liver plays crucial roles in sepsis and is one of the major targets for sepsis-related injuries. Ferroptosis, a newly emerged form lytic cell death, has been implicated related organ failure. Yes-associated protein1 (YAP1), key regulator Hippo signaling pathway, may be involved ferroptosis development. This study aimed to elucidate role YAP1 septic injury through regulating ferroptosis, especially ferritinophagy-mediated ferroptosis. Results Cecal ligation puncture (CLP) models were constructed control ( Yap1 flfl ) liver-conditional knockout mice fl/fl Alb-Cre) induce injury, while LO2 cells with or without overexpression/deletion stimulated by lipopolysaccharide (LPS) vitro. Our showed knockdown aggravated CLP-induced inflammation, as well accelerated hepatocyte revealed down-regulated expression GPX4, FTH1 SLC7A11, along up-regulated SFXN1 NCOA4. Consistently, deficiency but overexpression alleviated LPS-induced ferritinophagy, evidenced reduced mitochondrial ROS Fe 2+ , Further co-IP assay verified that disrupted interaction between NCOA4 FTH1, thus prevent degradation ferritin further production suppressed Conclusion inhibits hepatocytes, aggravates sepsis-induced injury.

Language: Английский

Citations

53
Ferroptosis and its interaction with tumor immune microenvironment in liver cancer DOI
Yilan Huang, Siwei Wang, Ai‐Wu Ke

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2022, Volume and Issue: 1878(1), P. 188848 - 188848

Published: Dec. 9, 2022

Language: Английский

Citations

50
Mineral metabolism and ferroptosis in non-alcoholic fatty liver diseases DOI
Chenhui Ma,

Han Li,

Zheying Zhu

et al.

Biochemical Pharmacology, Journal Year: 2022, Volume and Issue: 205, P. 115242 - 115242

Published: Sept. 7, 2022

Language: Английский

Citations

45
Ferritinophagy, a form of autophagic ferroptosis: New insights into cancer treatment DOI Creative Commons
Kai Sun, Chenyuan Li,

Shichong Liao

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 21, 2022

Ferritinophagy, a form of autophagy, is also an important part ferroptosis, type regulated cell death resulting from abnormal iron metabolism involving the production reactive oxygen species. As autophagy and cancer have been revealed, ferritinophagy has attracted increasing attention in development. In this review, we discuss latest research progress on autophagy-associated ferroptosis led by ferritinophagy, regulators promising treatments that target ferritinophagy. Ferritinophagy at intersection plays significant role The discussed studies provide new insights into mechanisms related for cancer.

Language: Английский

Citations

42
Ferritinophagy and Ferroptosis in Cerebral Ischemia Reperfusion Injury DOI Creative Commons
Xiaoyue Liu,

Can-Ming Xie,

Yao Wang

et al.

Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(8), P. 1965 - 1979

Published: June 4, 2024

Abstract Cerebral ischemia–reperfusion injury (CIRI) is the second leading cause of death worldwide, posing a huge risk to human life and health. Therefore, investigating pathogenesis underlying CIRI developing effective treatments are essential. Ferroptosis an iron-dependent mode cell death, which caused by disorders in iron metabolism lipid peroxidation. Previous studies demonstrated that ferroptosis also form autophagic nuclear receptor coactivator 4(NCOA4) mediated ferritinophagy was found regulate interfering with metabolism. Ferritinophagy important pathogenic mechanisms CIRI. This review mainly summarizes link regulation between further discusses their In addition, potential treatment methods targeting for presented, providing new ideas prevention clinical future.

Language: Английский

Citations

10