Deciphering the role of the MALT1–RC3H1 axis in regulating GPX4 protein stability DOI Creative Commons
Jun Wang, Long Liao, Beiping Miao

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 122(1)

Published: Dec. 31, 2024

Ferroptosis, a unique form of iron-dependent cell death triggered by lipid peroxidation accumulation, holds great promise for cancer therapy. Despite the crucial role GPX4 in regulating ferroptosis, our understanding protein regulation remains limited. Through FACS-based genome-wide CRISPR screening, we identified MALT1 as regulator protein. Inhibition expression enhances ubiquitination-mediated degradation up-regulating E3 ubiquitin ligase RC3H1. Using both rescue assays and functional genetic demonstrate that pharmacologically targeting triggers ferroptosis liver cells. Moreover, show synergizes with sorafenib or regorafenib to induce across multiple types. These findings elucidate modulatory effects MALT1-RC3H1 axis on stability, revealing molecular mechanism could be exploited

Language: Английский

The cell biology of ferroptosis DOI
Scott J. Dixon, James A. Olzmann

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(6), P. 424 - 442

Published: Feb. 16, 2024

Language: Английский

Citations

305
Ferroptosis in health and disease DOI Creative Commons
Carsten Berndt, Hamed Alborzinia,

Vera Skafar Amen

et al.

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

Citations

75
Ferroptosis: principles and significance in health and disease DOI Creative Commons
Fangquan Chen, Rui Kang, Daolin Tang

et al.

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

Citations

58
Exploiting ferroptosis vulnerabilities in cancer DOI
Toshitaka Nakamura, Marcus Conrad

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

Published: June 10, 2024

Language: Английский

Citations

28
The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders DOI Creative Commons

Yejia Xu,

Bowen Jia,

Jing Li

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 395 - 395

Published: March 26, 2024

Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain traumatic injury, epilepsy, depression, more. The involved pathogenesis is notably intricate diverse. Ferroptosis neuroinflammation play pivotal roles elucidating the causes of cognitive impairment stemming from these diseases. Given concurrent occurrence ferroptosis due metabolic shifts such as iron ROS, well their critical central nervous disorders, investigation into co-regulatory mechanism has emerged a prominent area research. This paper delves mechanisms along with interrelationship. It specifically emphasizes core molecules within shared pathways governing neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, how different immune cells structures contribute dysfunction through mechanisms. Researchers’ findings suggest that mutually promote each other may represent key factors progression disorders. A deeper comprehension common pathway between cellular holds promise for improving symptoms prognosis related

Language: Английский

Citations

18
FSP1-mediated lipid droplet quality control prevents neutral lipid peroxidation and ferroptosis DOI Creative Commons

Mike Lange,

Michele Wölk,

Cody E. Doubravsky

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

ABSTRACT Lipid droplets (LDs) are organelles that store and supply lipids based on cellular needs. While mechanisms preventing oxidative damage to membrane phospholipids established, the vulnerability of LD neutral peroxidation protective unknown. Here, we identify LD-localized Ferroptosis Suppressor Protein 1 (FSP1) as a critical regulator prevents lipid by recycling coenzyme Q10 (CoQ10) its lipophilic antioxidant form. Lipidomics reveal FSP1 loss leads accumulation oxidized triacylglycerols cholesteryl esters, biochemical reconstitution with CoQ10 NADH suppresses triacylglycerol in vitro . Notably, polyunsaturated fatty acid (PUFA)-rich enhance cancer cell sensitivity inducing PUFA-rich LDs triggers LD-initiated ferroptosis when activity is impaired. These findings uncover first quality control pathway, wherein maintains integrity prevent buildup induction ferroptosis.

Language: Английский

Citations

5
In defence of ferroptosis DOI Creative Commons
Francesca M. Alves, Darius J.R. Lane,

Triet Phu Minh Nguyen

et al.

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

Citations

3
Cross-talks of GSH, mitochondria, RNA m6A modification, NRF2, and p53 between ferroptosis and cuproptosis in HCC: A review DOI

Leihan Wang,

Zhenni ChenLiu,

Daorong Wang

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 302, P. 140523 - 140523

Published: Feb. 1, 2025

Language: Английский

Citations

2
Cancer drug-tolerant persister cells: from biological questions to clinical opportunities DOI
Mariangela Russo,

Mengnuo Chen,

Elisa Mariella

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(10), P. 694 - 717

Published: Sept. 2, 2024

Language: Английский

Citations

15
Oxidative Metabolism as a Cause of Lipid Peroxidation in the Execution of Ferroptosis DOI Open Access
Junichi Fujii, Hirotaka Imai

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

Citations

14