Ferroptosis in cancer and cancer immunotherapy DOI Creative Commons
Lei Zhao, Xiaoxue Zhou, Feng Xie

et al.

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(2), P. 88 - 116

Published: Feb. 1, 2022

Abstract The hallmark of tumorigenesis is the successful circumvention cell death regulation for achieving unlimited replication and immortality. Ferroptosis a newly identified type dependent on lipid peroxidation which differs from classical programmed in terms morphology, physiology biochemistry. broad spectrum injury tumor tolerance are main reasons radiotherapy chemotherapy failure. effective rate immunotherapy as new treatment method less than 30%. can be seen radiotherapy, chemotherapy, immunotherapy; therefore, ferroptosis activation may potential strategy to overcome drug resistance mechanism traditional cancer treatments. In this review, characteristics causes by briefly described. addition, three metabolic regulations its crosstalk with signaling pathways summarized. Collectively, these findings suggest vital role based interaction immunotherapy, thus, indicating remarkable treatment.

Language: Английский

Copper induces cell death by targeting lipoylated TCA cycle proteins DOI
Peter Tsvetkov, Shannon Coy, Boryana Petrova

et al.

Science, Journal Year: 2022, Volume and Issue: 375(6586), P. 1254 - 1261

Published: March 17, 2022

Copper is an essential cofactor for all organisms, and yet it becomes toxic if concentrations exceed a threshold maintained by evolutionarily conserved homeostatic mechanisms. How excess copper induces cell death, however, unknown. Here, we show in human cells that copper-dependent, regulated death distinct from known mechanisms dependent on mitochondrial respiration. We copper-dependent occurs means of direct binding to lipoylated components the tricarboxylic acid (TCA) cycle. This results protein aggregation subsequent iron-sulfur cluster loss, which leads proteotoxic stress ultimately death. These findings may explain need ancient

Language: Английский

Citations

2960
Ferroptosis: molecular mechanisms and health implications DOI Creative Commons
Daolin Tang, Xin Chen, Rui Kang

et al.

Cell Research, Journal Year: 2020, Volume and Issue: 31(2), P. 107 - 125

Published: Dec. 2, 2020

Abstract Cell death can be executed through different subroutines. Since the description of ferroptosis as an iron-dependent form non-apoptotic cell in 2012, there has been mounting interest process and function ferroptosis. Ferroptosis occur two major pathways, extrinsic or transporter-dependent pathway intrinsic enzyme-regulated pathway. is caused by a redox imbalance between production oxidants antioxidants, which driven abnormal expression activity multiple redox-active enzymes that produce detoxify free radicals lipid oxidation products. Accordingly, precisely regulated at levels, including epigenetic, transcriptional, posttranscriptional posttranslational layers. The transcription factor NFE2L2 plays central role upregulating anti-ferroptotic defense, whereas selective autophagy may promote ferroptotic death. Here, we review current knowledge on integrated molecular machinery describe how dysregulated involved cancer, neurodegeneration, tissue injury, inflammation, infection.

Language: Английский

Citations

2678
Broadening horizons: the role of ferroptosis in cancer DOI
Xin Chen, Rui Kang, Guido Kroemer

et al.

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 18(5), P. 280 - 296

Published: Jan. 29, 2021

Language: Английский

Citations

2104
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1 DOI Creative Commons

Daniel J. Klionsky,

Amal Kamal Abdel‐Aziz, Sara Abdelfatah

et al.

Autophagy, Journal Year: 2021, Volume and Issue: 17(1), P. 1 - 382

Published: Jan. 2, 2021

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered field. Our knowledge base relevant new technologies also been expanding. Thus, it is important to formulate on a regular basis updated monitoring autophagy different organisms. Despite numerous reviews, there continues be confusion regarding acceptable methods evaluate autophagy, especially multicellular eukaryotes. Here, present investigators select interpret examine related processes, reviewers provide realistic reasonable critiques reports that are focused these processes. These not meant dogmatic rules, because appropriateness any assay largely depends question being asked system used. Moreover, no individual perfect every situation, calling use multiple techniques properly monitor each experimental setting. Finally, several core components machinery implicated distinct autophagic processes (canonical noncanonical autophagy), implying genetic approaches block should rely targeting two or more autophagy-related genes ideally participate steps pathway. Along similar lines, proteins involved regulate other cellular pathways including apoptosis, all them can used as specific marker bona fide responses. critically discuss current assessing information they can, cannot, provide. ultimate goal encourage intellectual technical innovation

Language: Английский

Citations

2014
Necroptosis, pyroptosis and apoptosis: an intricate game of cell death DOI Creative Commons
Damien Bertheloot, Eicke Latz, Bernardo S. Franklin

et al.

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 18(5), P. 1106 - 1121

Published: March 30, 2021

Abstract Cell death is a fundamental physiological process in all living organisms. Its roles extend from embryonic development, organ maintenance, and aging to the coordination of immune responses autoimmunity. In recent years, our understanding mechanisms orchestrating cellular its consequences on immunity homeostasis has increased substantially. Different modalities what become known as ‘programmed cell death’ have been described, some key players these processes identified. We learned more about intricacies that fine tune activity common ultimately shape different types death. These studies highlighted complex tipping balance between fates. Here, we summarize latest discoveries three most well understood death, namely, apoptosis, necroptosis, pyroptosis, highlighting unique pathways their effect surrounding cells organism whole.

Language: Английский

Citations

1442
Ferroptosis: machinery and regulation DOI Open Access
Xin Chen, Jingbo Li, Rui Kang

et al.

Autophagy, Journal Year: 2020, Volume and Issue: 17(9), P. 2054 - 2081

Published: Aug. 19, 2020

Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death caused by lipid peroxidation, which controlled integrated oxidation and antioxidant systems. The iron-containing enzyme lipoxygenase the main promoter ferroptosis producing hydroperoxides, its function relies on activation ACSL4-dependent biosynthesis. In contrast, selenium-containing GPX4 currently recognized as a central repressor ferroptosis, activity depends glutathione produced from cystine-glutamate antiporter SLC7A11. Many metabolic (especially involving iron, lipids, amino acids) degradation pathways (macroautophagy/autophagy ubiquitin-proteasome system) orchestrate complex ferroptotic response through direct or indirect regulation iron accumulation peroxidation. Although detailed mechanism membrane injury during remains mystery, ESCRT III-mediated plasma repair can make cells resistant to ferroptosis. Here, we review recent rapid progress in understanding molecular mechanisms focus epigenetic, transcriptional, posttranslational this process.Abbreviations: 2ME: beta-mercaptoethanol; α-KG: α-ketoglutarate; ccRCC: clear renal carcinoma; EMT: epithelial-mesenchymal transition; FAO: fatty acid beta-oxidation; GSH: glutathione; MEFs: mouse embryonic fibroblasts; MUFAs: monounsaturated acids; NO: nitric oxide; NOX: NADPH oxidase; PPP: pentose phosphate pathway; PUFA: polyunsaturated acid; RCD: death; RNS: reactive nitrogen species; ROS: oxygen RTAs: radical-trapping antioxidants; UPS: system; UTR: untranslated region.

Language: Английский

Citations

1400
Emerging concepts in the science of vaccine adjuvants DOI Open Access
Bali Pulendran, Prabhu S. Arunachalam,

Derek T. O’Hagan

et al.

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(6), P. 454 - 475

Published: April 6, 2021

Language: Английский

Citations

1021
Hallmarks of neurodegenerative diseases DOI Creative Commons

David M. Wilson,

Mark Cookson,

Ludo Van Den Bosch

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(4), P. 693 - 714

Published: Feb. 1, 2023

Summary

Decades of research have identified genetic factors and biochemical pathways involved in neurodegenerative diseases (NDDs). We present evidence for the following eight hallmarks NDD: pathological protein aggregation, synaptic neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA RNA defects, inflammation, cell death. describe hallmarks, their biomarkers, interactions as a framework to study NDDs using holistic approach. The can serve basis defining pathogenic mechanisms, categorizing different based on primary stratifying patients within specific NDD, designing multi-targeted, personalized therapies effectively halt NDDs.

Language: Английский

Citations

879
Consensus guidelines for the definition, detection and interpretation of immunogenic cell death DOI Creative Commons
Lorenzo Galluzzi, Ilio Vitale, Sarah H. Warren

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2020, Volume and Issue: 8(1), P. e000337 - e000337

Published: March 1, 2020

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular microenvironmental features determine the propensity of RCD drive immunity. Here, we provide updated operational definition immunogenic (ICD), discuss key factors that dictate ability dying cells response, summarize experimental assays are currently available for assessment ICD in vitro vivo, formulate guidelines their interpretation.

Language: Английский

Citations

871
Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis DOI
Xiaoguang Liu, Litong Nie, Yilei Zhang

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 404 - 414

Published: Feb. 6, 2023

Language: Английский

Citations

705