FSP1: a key regulator of ferroptosis

Trends in Molecular Medicine, Год журнала: 2023, Номер 29(9), С. 753 - 764

Опубликована: Июнь 24, 2023

Ferroptosis suppressor protein 1 (FSP1) is one of the main regulatory molecules ferroptosis. FSP1 functions through FSP1-coenzyme Q10 (CoQ10)-NAD(P)H axis and vitamin K redox cycle. regulated by upstream factors, including transcription factors noncoding RNA (ncRNA), subject to epigenetic modifications, which affect progress FSP1-related diseases. closely associated with poor prognosis malignant tumors plays an important role in disease treatment. This review aims provide a comprehensive understanding ferroptosis regulation summarizing pathways, possible mechanisms involving FSP1, relationship between

Язык: Английский

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Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Дек. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Язык: Английский

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Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance

Advanced Science, Год журнала: 2023, Номер 10(26)

Опубликована: Июль 12, 2023

In recent years, the incidence of gastrointestinal cancers is increasing, particularly in younger population. Effective treatment crucial for improving patients' survival outcomes. Programmed cell death, regulated by various genes, plays a fundamental role growth and development organisms. It also critical maintaining tissue organ homeostasis takes part multiple pathological processes. addition to apoptosis, there are other types programmed such as ferroptosis, necroptosis, pyroptosis, which can induce severe inflammatory responses. Notably, besides pyroptosis contribute occurrence cancers. This review aims provide comprehensive summary on biological roles molecular mechanisms well their regulators hope open up new paths tumor targeted therapy near future.

Язык: Английский

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Idebenone alleviates doxorubicin-induced cardiotoxicity by stabilizing FSP1 to inhibit ferroptosis

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(6), С. 2581 - 2597

Опубликована: Март 11, 2024

Doxorubicin (DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients, but related pharmacotherapeutic measures are relatively limited. Ferroptosis was recently identified as a major mechanism of DOX-induced cardiotoxicity. Idebenone, novel ferroptosis inhibitor, is well-described clinical drug widely used. However, its role and pathological still unclear. In this study, we demonstrated the effects idebenone on elucidated underlying mechanism. A single intraperitoneal injection DOX (15 mg/kg) administrated to establish The results showed that significantly attenuated cardiac dysfunction due ability regulate acute Fe2+ ROS overload, which resulted ferroptosis. CESTA BLI further revealed idebenone's anti-ferroptosis effect mediated by FSP1. Interestingly, increased FSP1 protein levels did not affect Fsp1 mRNA presence DOX. Idebenone could form stable hydrogen bonds with at K355, may influence association ubiquitin. confirmed stabilized inhibiting ubiquitination degradation. conclusion, study demonstrates via regulation FSP1, making it potential for patients receiving treatment.

Язык: Английский

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Ferroptosis in ulcerative colitis: Potential mechanisms and promising therapeutic targets

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 175, С. 116722 - 116722

Опубликована: Май 9, 2024

Ulcerative colitis (UC) is a complex immune-mediated chronic inflammatory bowel disease. It mainly characterized by diffuse inflammation of the colonic and rectal mucosa with barrier function impairment. Identifying new biomarkers for development more effective UC therapies remains pressing task current research. Ferroptosis newly identified form regulated cell death iron-dependent lipid peroxidation. As research deepens, ferroptosis has been demonstrated to be involved in pathological processes numerous diseases. A growing body evidence suggests that pathogenesis associated ferroptosis, regulation provides opportunities treatment. However, specific mechanisms which participates remain fully thoroughly investigated. Therefore, this review, we focus on advances mechanism recent years describe potential role UC. In addition, explore underlying crosslinked pathway between other such as macrophages, neutrophils, autophagy, endoplasmic reticulum stress, gut microbiota Finally, also summarize compounds may act inhibitors future.

Язык: Английский

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FTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC

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

Опубликована: Июнь 4, 2024

Abstract Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older exhibit increased ferroptosis during HIRI. Inhibiting significantly attenuates HIRI phenotypes. Mass spectrometry reveals that fat mass and obesity-associated gene (FTO) expression is downregulated livers, especially Overexpressing FTO improves phenotypes by inhibiting ferroptosis. Mechanistically, acyl-CoA synthetase long chain family 4 (ACSL4) transferrin receptor protein 1 (TFRC), two key positive contributors ferroptosis, targets. For ameliorative effect, requires the inhibition of Acsl4 Tfrc mRNA stability a m6A-dependent manner. Furthermore, nicotinamide mononucleotide can upregulate demethylase activity, suppressing decreasing Collectively, these findings reveal an FTO-ACSL4/TFRC regulatory pathway contributes pathogenesis HIRI, providing insight into clinical translation strategies related activity improve graft function after donor

Язык: Английский

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The ubiquitin codes in cellular stress responses

Protein & Cell, Год журнала: 2023, Номер 15(3), С. 157 - 190

Опубликована: Июль 19, 2023

Ubiquitination/ubiquitylation, one of the most fundamental post-translational modifications, regulates almost every critical cellular process in eukaryotes. Emerging evidence has shown that essential components numerous biological processes undergo ubiquitination mammalian cells upon exposure to diverse stresses, from exogenous factors reactions, causing a dazzling variety functional consequences. Various forms ubiquitin signals generated by ubiquitylation events specific milieus, known as codes, constitute an intrinsic part myriad stress responses. These events, leading proteolytic turnover substrates or just switch functionality, initiate, regulate, supervise multiple stress-associated responses, supporting adaptation, homeostasis recovery, and survival stressed cells. In this review, we attempted summarize crucial roles response different environmental intracellular while discussing how stresses modulate system. This review also updates recent advances understanding machinery well responses discusses some important questions may warrant future investigation.

Язык: Английский

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Ferroptosis in hepatocellular carcinoma: from bench to bedside

Hepatology, Год журнала: 2023, Номер 80(3), С. 721 - 739

Опубликована: Апрель 4, 2023

The most widespread type of liver cancer, HCC, is associated with disabled cellular death pathways. Despite therapeutic advancements, resistance to current systemic treatments (including sorafenib) compromises the prognosis patients driving search for agents that might target novel cell Ferroptosis, a form iron-mediated nonapoptotic death, has gained considerable attention as potential cancer therapy, especially in HCC. role ferroptosis HCC complex and diverse. On one hand, can contribute progression through its involvement both acute chronic conditions. In contrast, having affect cells be desirable. This review examines from cellular, animal, human perspectives while examining mechanisms, regulation, biomarkers, clinical implications.

Язык: Английский

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Ferroptosis in gastrointestinal cancer: from mechanisms to implications

Cancer Letters, Год журнала: 2023, Номер 561, С. 216147 - 216147

Опубликована: Март 24, 2023

Язык: Английский

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The ubiquitin–proteasome system links NADPH metabolism to ferroptosis

Trends in Cell Biology, Год журнала: 2023, Номер 33(12), С. 1088 - 1103

Опубликована: Авг. 7, 2023

Язык: Английский

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