Ferroptosis: mechanisms and therapeutic targets DOI Creative Commons
Qian Zhou, Yu Meng,

Jiayuan Le

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(12)

Published: Nov. 20, 2024

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation in membrane phospholipids. Since its identification 2012, extensive research has unveiled involvement the pathophysiology numerous diseases, including cancers, neurodegenerative disorders, organ injuries, infectious autoimmune conditions, metabolic and skin diseases. Oxidizable lipids, overload iron, compromised antioxidant systems are known as critical prerequisites for driving overwhelming peroxidation, ultimately leading to plasma rupture ferroptotic death. However, precise regulatory networks governing ferroptosis ferroptosis-targeted therapy these diseases remain largely undefined, hindering development pharmacological agonists antagonists. In this review, we first elucidate core mechanisms summarize epigenetic modifications (e.g., histone modifications, DNA methylation, noncoding RNAs, N6-methyladenosine modification) nonepigenetic genetic mutations, transcriptional regulation, posttranslational modifications). We then discuss association between disease pathogenesis explore therapeutic approaches targeting ferroptosis. also introduce potential clinical monitoring strategies Finally, put forward several unresolved issues which progress needed better understand hope review will offer promise application therapies context human health disease.

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 cancer: From molecular mechanisms to therapeutic strategies DOI Creative Commons
Qian Zhou,

Yu Meng,

Daishi Li

et al.

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

Published: March 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Language: Английский

Citations

166
FSP1: a key regulator of ferroptosis DOI Creative Commons
Wentao Li,

Longteng Liang,

Siyi Liu

et al.

Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(9), P. 753 - 764

Published: June 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

Language: Английский

Citations

110
Autophagy mediates an amplification loop during ferroptosis DOI Creative Commons
Seung-Hee Lee, Narae Hwang, Byeong Geun Seok

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 25, 2023

Ferroptosis, a programmed cell death, has been identified and associated with cancer various other diseases. Ferroptosis is defined as reactive oxygen species (ROS)-dependent death related to iron accumulation lipid peroxidation, which different from apoptosis, necrosis, autophagy, forms of death. However, accumulating evidence revealed link between autophagy ferroptosis at the molecular level suggested that involved in regulating iron-dependent peroxidation ROS during ferroptosis. Understanding roles pathophysiological processes may provide effective strategies for treatment ferroptosis-related In this review, we summarize current knowledge regarding regulatory mechanisms underlying ferroptosis, including metabolism, its association pathway. addition, discuss contribution elucidate role enhancer ROS-dependent

Language: Английский

Citations

105
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
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

64
Tubastatin A potently inhibits GPX4 activity to potentiate cancer radiotherapy through boosting ferroptosis DOI Creative Commons
Shan Liu,

Hai‐Liang Zhang,

Jing Li

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 62, P. 102677 - 102677

Published: March 17, 2023

Ferroptosis, an iron-dependent lipid peroxidation-driven programmed cell death, is closely related to cancer therapy. The development of druggable ferroptosis inducers and their rational application in therapy are critical. Here, we identified Tubastatin A, HDAC6 inhibitor as a novel inducer through large-scale drug screening. A directly bonded GPX4 inhibited enzymatic activity biotin-linked putdown LC/MS analysis, which independent its inhibition HDAC6. In addition, our results showed that radiotherapy not only activated Nrf2-mediated transcription but also lysosome-mediated degradation, subsequently inducing tolerance radioresistance cells. overcame resistance cells by inhibiting activity. More importantly, has excellent bioavailability, demonstrated ability significantly promote radiotherapy-induced peroxidation tumour suppression mouse xenograft model. Our findings identify inducer, enhances radiotherapy-mediated antitumor effects. This work provides compelling rationale for the clinical evaluation especially combination with radiotherapy.

Language: Английский

Citations

55
Ferroptosis in colorectal cancer: a future target? DOI
Hong Yan, Ronan Talty, Oladimeji Aladelokun

et al.

British Journal of Cancer, Journal Year: 2023, Volume and Issue: 128(8), P. 1439 - 1451

Published: Jan. 26, 2023

Language: Английский

Citations

49
Ferroptotic therapy in cancer: benefits, side effects, and risks DOI Creative Commons
Jiandong Diao, Yuanyuan Jia, Enyong Dai

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 3, 2024

Abstract Ferroptosis is a type of regulated cell death characterized by iron accumulation and uncontrolled lipid peroxidation, leading to plasma membrane rupture intracellular content release. Originally investigated as targeted therapy for cancer cells carrying oncogenic RAS mutations, ferroptosis induction now exhibits potential complement chemotherapy, immunotherapy, radiotherapy in various types. However, it can lead side effects, including immune death, bone marrow impairment, liver kidney damage, cachexia (severe weight loss muscle wasting), secondary tumorigenesis. In this review, we discuss the advantages offer an overview diverse range documented effects. Furthermore, examine underlying mechanisms explore strategies effect mitigation.

Language: Английский

Citations

31
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