The crystal structure of human ferroptosis suppressive protein 1 in complex with flavin adenine dinucleotide and nicotinamide adenine nucleotide DOI Creative Commons
Shijian Feng,

Xiaofang Huang,

Dan Tang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(3)

Published: Feb. 26, 2024

Ferroptosis is a recently discovered form of regulated cell death characterized by its distinct dependence on iron and the peroxidation lipids within cellular membranes. plays crucial role in physiological pathological situations has attracted attention numerous scientists. suppressive protein 1 (FSP1) one main regulators that negatively regulates ferroptosis through GPX4-independent FSP1-CoQ10-NAD(P)H axis potential therapeutic target for ferroptosis-related diseases. However, crystal structure FSP1 not been resolved, which hinders development strategies targeting FSP1. To unravel this puzzle, we purified human (hFSP1) using baculovirus eukaryotic expression system solved at resolution 1.75 Å. Furthermore, evaluated oxidoreductase activity hFSP1 with NADH as substrate identified E156 key amino acid maintaining activity. Interestingly, our results indicated exists functions monomeric state. Mutagenesis analysis revealed critical C-terminal domain binding substrate. These findings significantly enhance understanding functional mechanism provide precise model further drug development.

Language: Английский

Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects DOI Creative Commons

Qin Ru,

Yusheng Li,

Lin Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Language: Английский

Citations

56
Cellular metabolism: A key player in cancer ferroptosis DOI Creative Commons

Xianjie Jiang,

Qiu Peng,

Mingjing Peng

et al.

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(2), P. 185 - 204

Published: Jan. 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.

Language: Английский

Citations

23
Ferroptosis inhibitors: past, present and future DOI Creative Commons
Lei Zhang, Yi Luo, Yang Xiang

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 23, 2024

Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed mechanisms its formation continue to explore effective inhibitors in disease. Recent studies shown correlation between pathological neurodegenerative diseases, as well diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for treatment ferroptosis-mediated diseases. This article specifically describes metabolic pathways summarizes reported action natural synthetic small molecule their efficacy The paper also treatments such gene therapy, nanotechnology, summarises challenges encountered clinical translation inhibitors. Finally, relationship other modes discussed, hopefully paving way future drug design discovery.

Language: Английский

Citations

20
Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors DOI Creative Commons

Carolina Punziano,

Silvia Trombetti, Elena Cesaro

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 298 - 298

Published: Feb. 28, 2024

Ferroptosis is a type of programmed cell death that differs from apoptosis, autophagy, and necrosis related to several physio-pathological processes, including tumorigenesis, neurodegeneration, senescence, blood diseases, kidney disorders, ischemia–reperfusion injuries. linked iron accumulation, eliciting dysfunction antioxidant systems, which favor the production lipid peroxides, membrane damage, ultimately, death. Thus, signaling pathways evoking ferroptosis are strongly associated with those protecting cells against excess and/or lipid-derived ROS. Here, we discuss interaction between metabolic particular focus on transcription factors implicated in regulation ferroptosis, either as triggers peroxidation or defense pathways.

Language: Английский

Citations

17
Cuproptosis: molecular mechanisms, cancer prognosis, and therapeutic applications DOI Creative Commons
Y. Cong, Na Li, Zixin Zhang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 22, 2025

Cuproptosis differs from other forms of cell death, such as apoptosis, necroptosis, and ferroptosis, in its unique molecular mechanisms signaling pathways. In this review, we delve into the cellular metabolic pathways copper, highlighting role copper biomolecule synthesis, mitochondrial respiration, antioxidant defense. Furthermore, elucidate relationship between cuproptosis-related genes (CRGs) cancer prognosis, analyzing their expression patterns across various tumor types impact on patient outcomes. Our review also uncovers potential therapeutic applications chelators, ionophores, copper-based nanomaterials oncology. addition, discuss emerging cuproptosis remodeling microenvironment, enhancing immune infiltration, converting "cold tumors" "hot that respond better to immunotherapy. short, underscores pivotal importance biology highlights translational a novel target.

Language: Английский

Citations

6
YTHDC1 as a tumor progression suppressor through modulating FSP1-dependent ferroptosis suppression in lung cancer DOI
Shuai Yuan,

Shu Xi,

Hong Weng

et al.

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(12), P. 2477 - 2490

Published: Oct. 30, 2023

Language: Английский

Citations

23
Sensing of mitochondrial DNA by ZBP1 promotes RIPK3-mediated necroptosis and ferroptosis in response to diquat poisoning DOI

Kunmei Lai,

Junjie Wang,

Siyi Lin

et al.

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: 31(5), P. 635 - 650

Published: March 16, 2024

Language: Английский

Citations

15
Underlying Mechanisms behind the Brain–Gut–Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update DOI Open Access

Júlia Pauli De Cól,

Enzo Pereira de Lima,

Fernanda Moris Pompeu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3694 - 3694

Published: March 26, 2024

Metabolic-associated fatty liver disease (MAFLD) includes several metabolic dysfunctions caused by dysregulation in the brain–gut–liver axis and, consequently, increases cardiovascular risks and dysfunction. In MAFLD, type 2 diabetes mellitus, obesity, syndrome are frequently present; these conditions related to lipogenesis systemic inflammation. This study aimed review connection between MAFLD. The inflammatory process, cellular alterations hepatocytes stellate cells, hypercaloric diet, sedentarism aggravate prognosis of patients with Thus, understand modulation physiopathology it is necessary include organokines involved this process (adipokines, myokines, osteokines, hepatokines) their clinical relevance project future perspectives condition bring light new possibilities therapeutic approaches. Adipokines responsible for activation distinct signaling different tissues, such as insulin pro-inflammatory cytokines, which important balancing substances avoid MAFLD its progression. Myokines improve quantity quality adipose contributing avoiding development Finally, hepatokines decisive improving or not progression through regulation anti-inflammatory organokines.

Language: Английский

Citations

13
Ferroptosis-Based Therapeutic Strategies toward Precision Medicine for Cancer DOI

Tianqi Shi,

Xiaofei Chen, Huihui Ti

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(4), P. 2238 - 2263

Published: Feb. 2, 2024

Ferroptosis is a type of iron-dependent programmed cell death characterized by the dysregulation iron metabolism and accumulation lipid peroxides. This nonapoptotic mode implicated in various physiological pathological processes. Recent findings have underscored its potential as an innovative strategy for cancer treatment, particularly against recalcitrant malignancies that are resistant to conventional therapies. article focuses on ferroptosis-based therapeutic strategies precision covering molecular mechanisms ferroptosis, four major types ferroptosis inducers their inhibitory effects diverse carcinomas, detection fluorescent probes, implementation image-guided therapy. These state-of-the-art tactics manifested enhanced selectivity efficacy malignant carcinomas. Given administration therapy still at burgeoning stage, some challenges future perspectives discussed clinical translation into treatment.

Language: Английский

Citations

12
Insight into Iron, Oxidative Stress and Ferroptosis: Therapy Targets for Approaching Anticancer Strategies DOI Open Access
Marialuisa Piccolo, Maria Grazia Ferraro,

Federica Iazzetti

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(6), P. 1220 - 1220

Published: March 20, 2024

Based on the multifaceted molecular machinery that tightly controls iron cellular homeostasis, this review delves into its paradoxical, potentially dangerous role in biological systems, with a special focus double-edged sword correlations cancer. Indeed, though is vital micronutrient and required cofactor participating several essential cell functions, tendency to cause oxidative stress can be related both cancer risk activation of death pathways. In scenario, ferroptosis refers an iron-dependent form regulated (RCD) powered by overload lethal peroxides sharing distinctive oxidized phospholipid profiles. As unique pathway, morphologically mechanistically different from other types programmed involving executioner family proteins. The accumulation cytotoxic lipid encompasses antagonism between execution defense occurring when ferroptosis-promoting activities significantly exceed antioxidant defenses. most recent breakthroughs have aroused great consideration tumor biology, as targeting provide new tools for exploring therapeutic strategies suppression. Mutations death/survival pathway alterations, well metabolic regulations cells, including propensity generate ROS, are seen features render cells unprotected ferroptosis, thereby exposing vulnerabilities which deserve further attention regarded targetable cancers limited options.

Language: Английский

Citations

12