Nature Reviews Molecular Cell Biology最新文献_第7页

Recommendations for robust and reproducible research on ferroptosis 建议对铁下垂进行可靠和可重复的研究

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2025-04-09 DOI: 10.1038/s41580-025-00843-2

Eikan Mishima, Toshitaka Nakamura, Sebastian Doll, Bettina Proneth, Maria Fedorova, Derek A. Pratt, José Pedro Friedmann Angeli, Scott J. Dixon, Adam Wahida, Marcus Conrad

{"title":"Recommendations for robust and reproducible research on ferroptosis","authors":"Eikan Mishima, Toshitaka Nakamura, Sebastian Doll, Bettina Proneth, Maria Fedorova, Derek A. Pratt, José Pedro Friedmann Angeli, Scott J. Dixon, Adam Wahida, Marcus Conrad","doi":"10.1038/s41580-025-00843-2","DOIUrl":"10.1038/s41580-025-00843-2","url":null,"abstract":"Ferroptosis is a necrotic, non-apoptotic cell death modality triggered by unrestrained iron-dependent lipid peroxidation. By unveiling the regulatory mechanisms of ferroptosis and its relevance to various diseases, research over the past decade has positioned ferroptosis as a promising therapeutic target. The rapid growth of this research field presents challenges, associated with potentially inadequate experimental approaches that may lead to misinterpretations in the assessment of ferroptosis. Typical examples include assessing whether an observed phenotype is indeed linked to ferroptosis, and selecting appropriate animal models and small-molecule modulators of ferroptotic cell death. This Expert Recommendation outlines state-of-the-art methods and tools to reliably study ferroptosis and increase the reproducibility and robustness of experimental results. We present highly validated compounds and animal models, and discuss their advantages and limitations. Furthermore, we provide an overview of the regulatory mechanisms and the best-studied players in ferroptosis regulation, such as GPX4, FSP1, SLC7A11 and ACSL4, discussing frequent pitfalls in experimental design and relevant guidance. These recommendations are intended for researchers at all levels, including those entering the expanding and exciting field of ferroptosis research. Ferroptosis is a non-apoptotic type of cell death that is induced by uncontrolled iron-dependent phospholipid peroxidation and has important roles in disease. This Expert Recommendation article summarizes ferroptosis regulation and mechanisms and provides recommendations to increase the reproducibility and robustness of ferroptosis research.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 8","pages":"615-630"},"PeriodicalIF":81.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

p53-regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases p53调控的非凋亡细胞死亡途径及其在癌症和其他疾病中的相关性

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2025-04-09 DOI: 10.1038/s41580-025-00842-3

Yanqing Liu, Brent R. Stockwell, Xuejun Jiang, Wei Gu

{"title":"p53-regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases","authors":"Yanqing Liu, Brent R. Stockwell, Xuejun Jiang, Wei Gu","doi":"10.1038/s41580-025-00842-3","DOIUrl":"10.1038/s41580-025-00842-3","url":null,"abstract":"Programmed cell death is a mechanism that is crucial for numerous physiological and pathological processes. Whereas p53-mediated apoptosis is a major cell death pathway in cancer, accumulating evidence indicates that p53 also has crucial roles in controlling different non-apoptotic cell death (NACD) pathways, including ferroptosis, necroptosis, pyroptosis, autophagy-dependent cell death, entotic cell death, parthanatos and paraptosis, and may regulate PANoptosis, cuproptosis and disulfidptosis. Notably, the function of p53 in these NACDs substantially contributes to its biological effects, particularly in cancer development and other pathological processes. In this Review, we discuss recent advances in understanding the roles and underlying mechanisms of p53-mediated NACDs, focusing on ferroptosis, necroptosis and pyroptosis. We discuss the complex and distinct physiological settings in which NACDs are regulated by p53, and potential targeting of p53-regulated NACDs for the treatment of cancer and other human diseases. Finally, we highlight several important questions concerning p53-regulated NACDs that warrant further investigation. The tumour suppressor p53 controls non-apoptotic cell death (NACD) pathways, including ferroptosis, necroptosis and pyroptosis. This Review discusses the roles, mechanisms and physiological settings in which NACDs are regulated by p53, and their potential targeting for the treatment of human diseases.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 8","pages":"600-614"},"PeriodicalIF":81.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blebbisomes are one bleb away from a functional cell 气泡体离功能细胞只有一个气泡之遥

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2025-04-09 DOI: 10.1038/s41580-025-00849-w

Lisa Heinke

引用次数: 0

Anticancer effects of zotatifin are mediated by RNA structure remodelling 佐他替芬的抗癌作用是通过RNA结构重塑介导的

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2025-04-07 DOI: 10.1038/s41580-025-00846-z

Caroline Barranco

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Understanding the machinery that reads the genome 了解解读基因组的机制

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2025-03-28 DOI: 10.1038/s41580-025-00844-1

Carrie Bernecky

引用次数: 0

Author Correction: Mechanism and regulation of kinesin motors 作者更正：运动马达的机制和调节

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2025-03-26 DOI: 10.1038/s41580-025-00845-0

Ahmet Yildiz

引用次数: 0

Mechanisms of COPII coat assembly and cargo recognition in the secretory pathway 分泌途径中COPII外壳组装和货物识别的机制

IF 112.7 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2025-03-25 DOI: 10.1038/s41580-025-00839-y

Katie W. Downes, Giulia Zanetti

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Mechanisms and regulation of DNA end resection in the maintenance of genome stability DNA末端切除在维持基因组稳定性中的机制和调控

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2025-03-25 DOI: 10.1038/s41580-025-00841-4

Raphael Ceccaldi, Petr Cejka

{"title":"Mechanisms and regulation of DNA end resection in the maintenance of genome stability","authors":"Raphael Ceccaldi, Petr Cejka","doi":"10.1038/s41580-025-00841-4","DOIUrl":"10.1038/s41580-025-00841-4","url":null,"abstract":"DNA end resection is a crucial early step in most DNA double-strand break (DSB) repair pathways. Resection involves the nucleolytic degradation of 5′ ends at DSB sites to generate 3′ single-stranded DNA overhangs. The first, short-range resection step is catalysed by the nuclease MRE11, acting as part of the MRE11–RAD50–NBS1 complex. Subsequent long-range resection is catalysed by the nucleases EXO1 and/or DNA2. Resected DNA is necessary for homology search and the priming of DNA synthesis in homologous recombination. DNA overhangs may also mediate DNA annealing in the microhomology-mediated end-joining and single-strand annealing pathways, and activate the DNA damage response. By contrast, DNA end resection inhibits DSB repair by non-homologous end-joining. In this Review, we discuss the importance of DNA end resection in various DSB repair pathways, the molecular mechanisms of end resection and its regulation, focusing on phosphorylation and other post-translational modifications that control resection throughout the cell cycle and in response to DNA damage. DNA end resection is crucial for most DNA double-strand break repair pathways. This Review discusses the molecular mechanisms of end resection and its regulation, focusing on the roles of post-translational modifications throughout the cell cycle and in response to DNA damage.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 8","pages":"586-599"},"PeriodicalIF":81.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanistic insights into gasdermin-mediated pyroptosis 气凝胶介导的焦亡机制

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2025-03-24 DOI: 10.1038/s41580-025-00837-0

Yang Bai, Youdong Pan, Xing Liu

{"title":"Mechanistic insights into gasdermin-mediated pyroptosis","authors":"Yang Bai, Youdong Pan, Xing Liu","doi":"10.1038/s41580-025-00837-0","DOIUrl":"10.1038/s41580-025-00837-0","url":null,"abstract":"Pyroptosis, a novel mode of inflammatory cell death, is executed by membrane pore-forming gasdermin (GSDM) family members in response to extracellular or intracellular injury cues and is characterized by a ballooning cell morphology, plasma membrane rupture and the release of inflammatory mediators such as interleukin-1β (IL-1β), IL-18 and high mobility group protein B1 (HMGB1). It is a key effector mechanism for host immune defence and surveillance against invading pathogens and aberrant cancerous cells, and contributes to the onset and pathogenesis of inflammatory and autoimmune diseases. Manipulating the pore-forming activity of GSDMs and pyroptosis could lead to novel therapeutic strategies. In this Review, we discuss the current knowledge regarding how GSDM-mediated pyroptosis is initiated, executed and regulated, its roles in physiological and pathological processes, and the crosstalk between different modes of programmed cell death. We also highlight the development of drugs that target pyroptotic pathways for disease treatment. Activation of gasdermins (GSDMs) in response to infection or cell damage triggers membrane pore formation, leading to pyroptotic cell death. This Review discusses recent molecular and structural insights into the regulation of GSDMs and explores their physiological roles and involvement in inflammatory diseases.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 7","pages":"501-521"},"PeriodicalIF":81.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nuclear and genome dynamics underlying DNA double-strand break repair DNA双链断裂修复背后的核和基因组动力学

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2025-03-17 DOI: 10.1038/s41580-025-00828-1

Irene Chiolo, Matthias Altmeyer, Gaëlle Legube, Karim Mekhail

{"title":"Nuclear and genome dynamics underlying DNA double-strand break repair","authors":"Irene Chiolo, Matthias Altmeyer, Gaëlle Legube, Karim Mekhail","doi":"10.1038/s41580-025-00828-1","DOIUrl":"10.1038/s41580-025-00828-1","url":null,"abstract":"Changes in nuclear shape and in the spatial organization of chromosomes in the nucleus commonly occur in cancer, ageing and other clinical contexts that are characterized by increased DNA damage. However, the relationship between nuclear architecture, genome organization, chromosome stability and health remains poorly defined. Studies exploring the connections between the positioning and mobility of damaged DNA relative to various nuclear structures and genomic loci have revealed nuclear and cytoplasmic processes that affect chromosome stability. In this Review, we discuss the dynamic mechanisms that regulate nuclear and genome organization to promote DNA double-strand break (DSB) repair, genome stability and cell survival. Genome dynamics that support DSB repair rely on chromatin states, repair-protein condensates, nuclear or cytoplasmic microtubules and actin filaments, kinesin or myosin motor proteins, the nuclear envelope, various nuclear compartments, chromosome topology, chromatin loop extrusion and diverse signalling cues. These processes are commonly altered in cancer and during natural or premature ageing. Indeed, the reshaping of the genome in nuclear space during DSB repair points to new avenues for therapeutic interventions that may take advantage of new cancer cell vulnerabilities or aim to reverse age-associated defects. Changes in nuclear and genome organization promote the repair of DNA double-strand breaks and genome stability. Processes that are involved include the modulation of chromatin state, condensates of repair proteins and cytoskeleton reorganization. The reshaping of the nucleus and genome is commonly altered in cancer and during ageing, which could be targeted to provide new therapeutic opportunities.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 7","pages":"538-557"},"PeriodicalIF":81.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0