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HELLS: the transcriptional sentinel. 地狱：转录哨兵。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-04-01 Epub Date: 2025-01-30 DOI: 10.1016/j.tcb.2025.01.004
Selene Mallia, Giulia Gambarelli, Alessia Ciarrocchi, Valentina Fragliasso
{"title":"HELLS: the transcriptional sentinel.","authors":"Selene Mallia, Giulia Gambarelli, Alessia Ciarrocchi, Valentina Fragliasso","doi":"10.1016/j.tcb.2025.01.004","DOIUrl":"10.1016/j.tcb.2025.01.004","url":null,"abstract":"<p><p>The role of the chromatin remodeler HELicase Lymphoid Specific (HELLS) has been historically associated with DNA methylation and DNA damage repair. However, recent studies have shed light on an unexpected, multimodal, and direct participation of HELLS in transcriptional regulation. This forum article aims to discuss how, through different and context-specific mechanisms, HELLS modulates the expression of functionally related genes favoring transcriptional plasticity and phenotypic adaptation, ultimately safeguarding the genome organization and stability.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"269-273"},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076341","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
The endoplasmic reticulum as a cradle for virus and extracellular vesicle secretion. 内质网是病毒和细胞外囊泡分泌的摇篮。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-04-01 Epub Date: 2024-12-26 DOI: 10.1016/j.tcb.2024.11.008
Yonis Bare, Kyra Defourny, Marine Bretou, Guillaume Van Niel, Esther Nolte-'t Hoen, Raphael Gaudin
{"title":"The endoplasmic reticulum as a cradle for virus and extracellular vesicle secretion.","authors":"Yonis Bare, Kyra Defourny, Marine Bretou, Guillaume Van Niel, Esther Nolte-'t Hoen, Raphael Gaudin","doi":"10.1016/j.tcb.2024.11.008","DOIUrl":"10.1016/j.tcb.2024.11.008","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are small membranous carriers of protein, lipid, and nucleic acid cargoes and play a key role in intercellular communication. Recent work has revealed the previously under-recognized participation of endoplasmic reticulum (ER)-associated proteins (ERAPs) during EV secretion, using pathways reminiscent of viral replication and secretion. Here, we present highlights of the literature involving ER/ERAPs in EV biogenesis and propose mechanistic parallels with ERAPs exploited during viral infections. We propose that ERAPs play an active role in the release of EVs and viral particles, and we present views on whether viruses hijack or enhance pre-existing ERAP-dependent secretory machineries or whether they repurpose ERAPs to create new secretory pathways.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"282-293"},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900578","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
Smooth operator(s): dialing up and down neurotransmitter responses by G-protein regulators. 平稳的操作者：通过 G 蛋白调节器调节神经递质的反应。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-04-01 Epub Date: 2024-07-24 DOI: 10.1016/j.tcb.2024.07.002
Clementine E Philibert, Mikel Garcia-Marcos
{"title":"Smooth operator(s): dialing up and down neurotransmitter responses by G-protein regulators.","authors":"Clementine E Philibert, Mikel Garcia-Marcos","doi":"10.1016/j.tcb.2024.07.002","DOIUrl":"10.1016/j.tcb.2024.07.002","url":null,"abstract":"<p><p>G-protein-coupled receptors (GPCRs) are essential mediators of neuromodulation and prominent pharmacological targets. While activation of heterotrimeric G-proteins (Gαβɣ) by GPCRs is essential in this process, much less is known about the postreceptor mechanisms that influence G-protein activity. Neurons express G-protein regulators that shape the amplitude and kinetics of GPCR-mediated synaptic responses. Although many of these operate by directly altering how G-proteins handle guanine-nucleotides enzymatically, recent discoveries have revealed alternative mechanisms by which GPCR-stimulated G-protein responses are modulated at the synapse. In this review, we cover the molecular basis for, and consequences of, the action of two G-protein regulators that do not affect the enzymatic activity of G-proteins directly: Gα inhibitory interacting protein (GINIP), which binds active Gα subunits, and potassium channel tetramerization domain-containing 12 (KCTD12), which binds active Gβγ subunits.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"330-340"},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transcription-coupled repair of DNA-protein crosslinks. dna -蛋白交联的转录偶联修复。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-04-01 Epub Date: 2024-11-30 DOI: 10.1016/j.tcb.2024.11.003
Christopher J Carnie, Stephen P Jackson, Julian Stingele
{"title":"Transcription-coupled repair of DNA-protein crosslinks.","authors":"Christopher J Carnie, Stephen P Jackson, Julian Stingele","doi":"10.1016/j.tcb.2024.11.003","DOIUrl":"10.1016/j.tcb.2024.11.003","url":null,"abstract":"<p><p>DNA-protein crosslinks (DPCs) are highly toxic DNA lesions that are relevant to multiple human diseases. They are caused by various endogenous and environmental agents, and from the actions of enzymes such as topoisomerases. DPCs impede DNA polymerases, triggering replication-coupled DPC repair. Until recently the consequences of DPC blockade of RNA polymerases remained unclear. New methodologies for studying DPC repair have enabled the discovery of a transcription-coupled (TC) DPC repair pathway. Briefly, RNA polymerase II (RNAPII) stalling initiates TC-DPC repair, leading to sequential engagement of Cockayne syndrome (CS) proteins CSB and CSA, and to proteasomal degradation of the DPC. Deficient TC-DPC repair caused by loss of CSA or CSB function may help to explain the complex clinical presentation of CS patients.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"316-329"},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774760","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
The epitranscriptome: reshaping the DNA damage response. 表转录组：重塑 DNA 损伤反应。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-04-01 Epub Date: 2024-07-23 DOI: 10.1016/j.tcb.2024.06.008
Vivian Kalamara, George A Garinis
{"title":"The epitranscriptome: reshaping the DNA damage response.","authors":"Vivian Kalamara, George A Garinis","doi":"10.1016/j.tcb.2024.06.008","DOIUrl":"10.1016/j.tcb.2024.06.008","url":null,"abstract":"<p><p>Genomic instability poses a formidable threat to cellular vitality and wellbeing, prompting cells to deploy an intricate DNA damage response (DDR) mechanism. Recent evidence has suggested that RNA is intricately linked to the DDR by serving as template, scaffold, or regulator during the repair of DNA damage. Additionally, RNA molecules undergo modifications, contributing to the epitranscriptome, a dynamic regulatory layer influencing cellular responses to genotoxic stress. The intricate interplay between RNA and the DDR sheds new light on how the RNA epigenome contributes to the maintenance of genomic integrity and ultimately shapes the fate of damaged cells.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"294-304"},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762962","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
The fate of mitochondrial respiratory complexes in aging. 线粒体呼吸复合体在衰老过程中的命运。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-03-26 DOI: 10.1016/j.tcb.2025.02.008
Hanna Salmonowicz, Karolina Szczepanowska
{"title":"The fate of mitochondrial respiratory complexes in aging.","authors":"Hanna Salmonowicz, Karolina Szczepanowska","doi":"10.1016/j.tcb.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.02.008","url":null,"abstract":"<p><p>While mitochondrial dysfunction is one of the canonical hallmarks of aging, it remains only vaguely defined. Its core feature embraces defects in energy-producing molecular machinery, the mitochondrial respiratory complexes (MRCs). The causes and consequences of these defects hold research attention. In this review, we assess the lifecycle of respiratory complexes, from biogenesis to degradation, and look closely at the mechanisms that could underpin their dysfunction in aged cells. We discuss how these processes could be altered by aging and expand on the fate of MRCs in age-associated pathologies. Given the complexity behind MRC maintenance and functionality, several traits could contribute to the phenomenon known as age-associated mitochondrial dysfunction. New advances will help us better understand the fate of this machinery in aging and age-related diseases.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733352","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
BBB breakdown caused by plasma membrane pore formation. 质膜孔形成引起血脑屏障破裂。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-03-25 DOI: 10.1016/j.tcb.2025.02.012
Chao Wei, Wei Jiang, Minmin Luo, Feng Shao
{"title":"BBB breakdown caused by plasma membrane pore formation.","authors":"Chao Wei, Wei Jiang, Minmin Luo, Feng Shao","doi":"10.1016/j.tcb.2025.02.012","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.02.012","url":null,"abstract":"<p><p>The blood-brain barrier, recently reintroduced as the blood-brain border (BBB), is a dynamic interface between the central nervous system (CNS) and the bloodstream. Disruption of the BBB exposes the CNS to peripheral pathogens and harmful substances, causing or worsening various CNS diseases. While traditional views attribute BBB failure to tight junction disruption or increased transcytosis, recent studies highlight the critical role of gasdermin D (GSDMD) pore formation in brain endothelial cells (bECs) during BBB disruption by lipopolysaccharide (LPS) or bacterial infections. This mechanism may also be involved in neurological complications like the 'brain fog' seen in long COVID. Pore formation in bECs may represent a prevalent mechanism causing BBB leakage. Investigating membrane-permeabilizing pores or channels and their effects on BBB integrity is a growing area of research. Further exploration of molecular processes that maintain, disrupt, and restore bEC membrane integrity will advance our understanding of brain vasculature and aid in developing new therapies for BBB-related diseases.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722678","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
Versatility of gasdermin D beyond pyroptosis. 除焦亡外，气皮素D的多功能性。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-03-21 DOI: 10.1016/j.tcb.2025.02.011
Tianming Zhao, Zhexu Chi, Di Wang
{"title":"Versatility of gasdermin D beyond pyroptosis.","authors":"Tianming Zhao, Zhexu Chi, Di Wang","doi":"10.1016/j.tcb.2025.02.011","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.02.011","url":null,"abstract":"<p><p>Gasdermin D (GSDMD) has garnered significant attention primarily for the pore-forming role of its p30 N-terminal fragment (NT-p30) generated during pyroptosis, a proinflammatory form of cell death. However, emerging evidence suggests that the formation of GSDMD-NT pores is reversible, and the activation of GSDMD does not necessarily lead to pyroptosis. Instead, this process may take part either in other forms of cell death, or in various state changes of living cells, including (i) inflammation regulation, (ii) endolysosomal pathway rewiring, (iii) granule exocytosis, (iv) type II immunity, (v) food tolerance maintenance, and (vi) temporary permeability alteration. This review explores the latest insights into the involvement of GSDMD in cell death and homeostasis maintenance, aiming to underscore the pleiotropic nature of GSDMD.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694577","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
Epigenetic drivers of metalloproteinases and metastasis. 金属蛋白酶及其转移的表观遗传驱动。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-03-14 DOI: 10.1016/j.tcb.2025.02.010
Marco Seehawer, Kornelia Polyak
{"title":"Epigenetic drivers of metalloproteinases and metastasis.","authors":"Marco Seehawer, Kornelia Polyak","doi":"10.1016/j.tcb.2025.02.010","DOIUrl":"10.1016/j.tcb.2025.02.010","url":null,"abstract":"<p><p>Metalloproteinases (MPs) are crucial for development and homeostasis due to their diverse physiological functions, from the cellular to the organismal level. Their activity is tightly regulated at multiple levels, including epigenetic regulation through DNA methylation and histone modifications. Aberrant MP expression can result in pathological events, involving extracellular matrix remodeling, which can facilitate cancer cell invasion and dissemination. As clinical testing of MP inhibitors has been limited by toxicity, alternative approaches are needed. Epigenetically-driven MP expression is often specific to cancer cells, giving an enticing possibility for cancer cell-specific targeting. Moreover, aberrant epigenetic activity can also drive other metastatic events. Therefore, targeting the epigenetic regulators of MP expression may be a promising alternative approach for the prevention and treatment of metastatic disease.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Quality control of mitochondrial nucleoids. 线粒体类核的质量控制。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-03-07 DOI: 10.1016/j.tcb.2025.02.005
Hao Liu, Haixia Zhuang, Du Feng
{"title":"Quality control of mitochondrial nucleoids.","authors":"Hao Liu, Haixia Zhuang, Du Feng","doi":"10.1016/j.tcb.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.02.005","url":null,"abstract":"<p><p>Mitochondrial nucleoids, organized complexes that house and protect mitochondrial DNA (mtDNA), are normally confined within the mitochondrial double-membrane system. Under cellular stress conditions, particularly oxidative and inflammatory stress, these nucleoids can undergo structural alterations that lead to their aberrant release into the cytoplasm. This mislocalization of nucleoid components, especially mtDNA, can trigger inflammatory responses and cell death pathways, highlighting the critical importance of nucleoid quality control mechanisms. The release of mitochondrial nucleoids occurs through specific membrane channels and transport pathways, fundamentally disrupting cellular homeostasis. Cells have evolved multiple clearance mechanisms to manage cytoplasmic nucleoids, including nuclease-mediated degradation, lysosomal elimination, and cellular excretion. This review examines the molecular mechanisms governing nucleoid quality control and explores the delicate balance between mitochondrial biology and cellular immunity. Our analysis provides insights that could inform therapeutic strategies for mtDNA-associated diseases and inflammatory disorders.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588394","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
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