A Deep Insight into Ferroptosis in Renal Disease: Facts and Perspectives DOI Creative Commons
Zhongyu Han,

Yuanke Luo,

Haoran Chen

et al.

Kidney Diseases, Journal Year: 2024, Volume and Issue: 10(3), P. 224 - 236

Published: Jan. 1, 2024

Ferroptosis, a newly recognized form of programmed cell death, is distinguished by its reliance on reactive oxygen species and iron-mediated lipid peroxidation, setting it apart from established types like apoptosis, necrosis, autophagy. Recent studies suggest role in exacerbating or mitigating diseases influencing metabolic signaling pathways conditions such as tumors ischemic organ damage. Evidence also links ferroptosis to various kidney diseases, prompting review research status potential breakthroughs understanding treating these conditions.

Language: Английский

Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1 DOI Creative Commons
Piao Luo, Dandan Liu, Qian Zhang

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 12(5), P. 2300 - 2314

Published: Dec. 18, 2021

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic anti-inflammatory activities multiple hepatic diseases. However, the exact molecular mechanisms action direct protein targets celastrol treatment liver fibrosis remain largely elusive. Here, we discover that exerts effects via promoting production reactive oxygen species (ROS) inducing ferroptosis activated stellate cells (HSCs). By using activity-based profiling (ABPP) combination with bio-orthogonal click chemistry reaction cellular thermal shift assay (CETSA), show directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 PRDX6, through active cysteine sites, inhibits their anti-oxidant activities. Celastrol also heme oxygenase 1 (HO-1) upregulates its expression activated-HSCs. Knockdown PRDX4, PRDX6 or HO-1 HSCs, varying extent, elevated ROS levels induced ferroptosis. Taken together, our findings reveal which ameliorates fibrosis, thus supporting further development as promising therapeutic agent for fibrosis.

Language: Английский

Citations

203
Ferroptosis and ferritinophagy in diabetes complications DOI Creative Commons
Jiahui He, Zhangwang Li,

Panpan Xia

et al.

Molecular Metabolism, Journal Year: 2022, Volume and Issue: 60, P. 101470 - 101470

Published: March 15, 2022

With long-term metabolic malfunction, diabetes can cause serious damage to whole-body tissue and organs, resulting in a variety of complications. Therefore, it is particularly important further explore the pathogenesis complications develop drugs for prevention treatment. In recent years, different from apoptosis necrosis, ferroptosis has been recognized as new regulatory mode cell death involves regulation nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Evidence shows that ferritinophagy play significant role occurrence development

Language: Английский

Citations

109
Acyl-CoA synthase ACSL4: an essential target in ferroptosis and fatty acid metabolism DOI Creative Commons

Kaiyue Ding,

Chongbin Liu, Li Li

et al.

Chinese Medical Journal, Journal Year: 2023, Volume and Issue: unknown

Published: July 6, 2023

Long-chain acyl-coenzyme A (CoA) synthase 4 (ACSL4) is an enzyme that esterifies CoA into specific polyunsaturated fatty acids, such as arachidonic acid and adrenic acid. Based on accumulated evidence, the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to execution ferroptosis by triggering phospholipid peroxidation. Ferroptosis a type programmed cell death caused iron-dependent peroxidation lipids; ACSL4 glutathione peroxidase positively negatively regulate ferroptosis, respectively. In addition, essential regulator (FA) metabolism. remodels composition membranes, regulates steroidogenesis, balances eicosanoid biosynthesis. ACSL4-mediated metabolic reprogramming antitumor immunity have attracted much attention in cancer biology. Because it facilitates cross-talk between FA metabolism, also research hotspot diseases ischemia/reperfusion injuries. this review, we focus structure, biological function, unique role ASCL4 various human diseases. Finally, propose might be potential therapeutic target.

Language: Английский

Citations

77
Ferroptosis as a Novel Therapeutic Target for Diabetes and Its Complications DOI Creative Commons
Xi‐Ding Yang, Yong‐Yu Yang

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

Published: March 29, 2022

The global diabetes epidemic and its complications are increasing, thereby posing a major threat to public health. A comprehensive understanding of mellitus (DM) is necessary for the development effective treatments. Ferroptosis newly identified form programmed cell death caused by production reactive oxygen species an imbalance in iron homeostasis. Increasing evidence suggests that ferroptosis plays pivotal role pathogenesis diabetes-related complications. In this review, we summarize potential impact regulatory mechanisms on complications, as well inhibitors diabetic Therefore, developing drugs or agents target may provide new treatment strategies patients with diabetes.

Language: Английский

Citations

75
International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis DOI Creative Commons
Xin Chen,

Andrey S. Tsvetkov,

Han‐Ming Shen

et al.

Autophagy, Journal Year: 2024, Volume and Issue: 20(6), P. 1213 - 1246

Published: March 6, 2024

Macroautophagy/autophagy is a complex degradation process with dual role in cell death that influenced by the types are involved and stressors they exposed to. Ferroptosis an iron-dependent oxidative form of characterized unrestricted lipid peroxidation context heterogeneous plastic mechanisms. Recent studies have shed light on involvement specific autophagy (e.g. ferritinophagy, lipophagy, clockophagy) initiating or executing ferroptotic through selective anti-injury proteins organelles. Conversely, other forms reticulophagy lysophagy) enhance cellular defense against damage. Dysregulated autophagy-dependent ferroptosis has implications for diverse range pathological conditions. This review aims to present updated definition ferroptosis, discuss influential substrates receptors, outline experimental methods, propose guidelines interpreting results.

Language: Английский

Citations

63
Zooming in and out of ferroptosis in human disease DOI
Xue Wang, Ye Zhou, Junxia Min

et al.

Frontiers of Medicine, Journal Year: 2023, Volume and Issue: 17(2), P. 173 - 206

Published: April 1, 2023

Language: Английский

Citations

54
LPCAT3 Is Transcriptionally Regulated by YAP/ZEB/EP300 and Collaborates with ACSL4 and YAP to Determine Ferroptosis Sensitivity DOI
Jiangtao Cui, Yikun Wang, Xiaoting Tian

et al.

Antioxidants and Redox Signaling, Journal Year: 2023, Volume and Issue: 39(7-9), P. 491 - 511

Published: May 11, 2023

Aims: Lipid peroxidation occurring in lung adenocarcinoma (LUAD) cells leads to ferroptosis. Lysophosphatidylcholine acyl-transferase 3 (LPCAT3) plays a key role providing raw materials for lipid by promoting esterification of polyunsaturated fatty acids phospholipids. Whether LPCAT3 determines ferroptosis sensitivity and the mechanism which its expression is regulated LUAD has not been reported. Results: acyl-coenzyme A (CoA) synthetase long-chain family member (ACSL)4 levels were positively associated with cell lines. Overexpression ACSL4 sensitized ferroptosis, while knockout showed opposite effect. Zinc-finger E-box-binding (ZEB) was shown directly bind promoter stimulate transcription Yes-associated protein (YAP)-dependent manner. An interaction between YAP ZEB also observed. E1A-binding p300 (EP300) simultaneously bound ZEB, induced H3K27Ac transcription. This verified primary xenograft models. The ACSL4, LPCAT3, combination can jointly determine sensitivity. Innovation: binding site exists -1600 -1401 nt region promoter, promotes after binding. bind, zinc-finger cluster domain WW are crucial their EP300 may via Bromo CBP/p300-HAT domain. In addition, better than prostaglandin-endoperoxide synthase 2 (PTGS2), transferrin receptor (TFRC), or NADPH oxidase 1 (NOX1). Conclusion: YAP, EP300. be determined YAP. Antioxid. Redox Signal. 39, 491-511.

Language: Английский

Citations

49
Emerging Role of Ferroptosis in Diabetic Kidney Disease: Molecular Mechanisms and Therapeutic Opportunities DOI Creative Commons
Hui Wang, Dongwei Liu, Bin Zheng

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(9), P. 2678 - 2694

Published: Jan. 1, 2023

Diabetic kidney disease (DKD) is one of the most common and severe microvascular complications diabetes mellitus (DM), has become leading cause end-stage renal (ESRD) worldwide.Although exact pathogenic mechanism DKD still unclear, programmed cell death been demonstrated to participate in occurrence development diabetic injury, including ferroptosis.Ferroptosis, an iron-dependent form driven by lipid peroxidation, identified play a vital role therapeutic responses variety diseases, such as acute injury (AKI), carcinoma DKD.In past two years, ferroptosis well investigated patients animal models, but specific mechanisms effects have not fully revealed.Herein, we reviewed regulatory ferroptosis, summarized recent findings associated with involvement DKD, discussed potential promising target for treatment, thereby providing valuable reference basic study clinical therapy DKD.

Language: Английский

Citations

45
The crosstalk of CD8+ T cells and ferroptosis in cancer DOI Creative Commons
Zhengjun Lin,

Songzhu Zou,

Kunming Wen

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 15, 2024

Ferroptosis is an iron-dependent, novel form of programmed cell death characterized by lipid peroxidation and glutathione depletion widespread in a variety diseases. CD8+ T cells are the most important effector cytotoxic cells, capable specifically recognizing killing cancer cells. Traditionally, thought to induce mainly through perforin granzyme, Fas-L/Fas binding. In recent years, cell-derived IFN-γ was found promote ferroptosis multiple mechanisms, including upregulation IRF1 IRF8, downregulation system XC-, while shown enhance anti-tumor effects heating tumor immune microenvironment exposure release tumor-associated specific antigens, which results positive feedback pathway. Unfortunately, intra-tumoral more sensitive than limits application inducers cancer. addition, susceptible being regulated other TME, such as macrophages, dendritic Treg, bone marrow-derived immunosuppressive Together, these factors build complex network Therefore, we aim integrate relevant studies reveal potential mechanisms crosstalk between ferroptosis, summarize preclinical models therapy find new therapeutic strategies this review.

Language: Английский

Citations

25
Ferritinophagy: A novel insight into the double‐edged sword in ferritinophagy–ferroptosis axis and human diseases DOI Creative Commons

Jing‐Yan Li,

Yan‐Hua Feng,

Yuxuan Li

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(7)

Published: Feb. 23, 2024

Abstract Nuclear receptor coactive 4 (NCOA4), which functions as a selective cargo receptor, is critical regulator of the particularly autophagic degradation ferritin, process known ferritinophagy. Mechanistically, NCOA4‐mediated ferritinophagy performs an increasingly vital role in maintenance intracellular iron homeostasis by promoting ferritin transport and release needed. Ferritinophagy not only involved iron‐dependent responses but also pathogenesis progression various human diseases, including metabolism‐related, neurodegenerative, cardiovascular infectious diseases. Therefore, great importance maintaining cell viability function represents potential therapeutic target. Recent studies indicated that regulates signalling pathway associated with ferroptosis, newly discovered type death characterised lipid peroxidation. Although accumulating evidence clearly demonstrates interplay between dysfunction metabolism deeper understanding double‐edged sword effect ferroptosis has remained elusive. Details mechanisms underlying ferritinophagy–ferroptosis axis regulating relevant diseases remain to be elucidated. In this review, we discuss latest research findings regarding regulate biological its contribution pathophysiology ferroptosis. The important will discussed detail, highlighting targeting treatment

Language: Английский

Citations

20