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The promiscuous ribosomal P-stalk: a new functional portrait. 混杂核糖体p -柄：一个新的功能肖像。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-10-07 DOI: 10.1016/j.tcb.2025.09.003
Marek Tchórzewski, Barbara Michalec-Wawiórka
{"title":"The promiscuous ribosomal P-stalk: a new functional portrait.","authors":"Marek Tchórzewski, Barbara Michalec-Wawiórka","doi":"10.1016/j.tcb.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.09.003","url":null,"abstract":"<p><p>The canonical role of the ribosome is to translate the genetic code into functional proteins. Recent discoveries, however, redefine the eukaryotic ribosome, as a regulatory hub, that senses cellular cues and transmits signals to downstream pathways. The P-stalk, an integral component of the ribosomal GTPase-associated center, once viewed as translational supporter, is now emerging as a key regulatory ribosomal module. It has recently been recognized as an activator of the integrated stress response, reshaping the Gcn1/Gcn20→Gcn2 axis into the new Gcn1/Gcn20/P-stalk→Gcn2 order. The P-stalk's structural plasticity allows also the ribosome to rewire gene expression in response to cellular demands, including cytokine response. In this review, an updated functional portrait of the P-stalk is presented, encompassing both ribosome-dependent and -independent activities.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253845","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
Is mitochondrial function at the heart of ribosome-related diseases? 线粒体功能是核糖体相关疾病的核心吗？
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-10-01 Epub Date: 2025-08-26 DOI: 10.1016/j.tcb.2025.07.007
Qiuxia Zhao, Elif Sarinay Cenik
{"title":"Is mitochondrial function at the heart of ribosome-related diseases?","authors":"Qiuxia Zhao, Elif Sarinay Cenik","doi":"10.1016/j.tcb.2025.07.007","DOIUrl":"10.1016/j.tcb.2025.07.007","url":null,"abstract":"<p><p>Defects in ribosomal machinery cause ribosomopathies such as Diamond Blackfan anemia, classically linked to impaired protein synthesis. However, emerging evidence places mitochondrial dysfunction as a critical downstream consequence of ribosomal insufficiency. Thus, is impaired energy metabolism, rather than translation alone, a key driver of ribosomopathies such as Diamond Blackfan anemia? This insight could reframe our understanding of disease mechanisms and could identify metabolic pathways as promising therapeutic targets.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"815-818"},"PeriodicalIF":18.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980073","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
Phosphoinositide dynamics in virus-associated malignancies. 病毒相关恶性肿瘤的磷酸肌苷动力学。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-10-01 DOI: 10.1016/j.tcb.2025.09.002
Mingchuan Li, Wenbin Zhong, Emilio Hirsch, Daoguang Yan
{"title":"Phosphoinositide dynamics in virus-associated malignancies.","authors":"Mingchuan Li, Wenbin Zhong, Emilio Hirsch, Daoguang Yan","doi":"10.1016/j.tcb.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.09.002","url":null,"abstract":"<p><p>Virus-associated cancers, which account for ~15-20% of the global cancer burden, arise from infections with human oncoviruses. These viruses drive malignant transformation through diverse mechanisms but share common oncogenic features, including reprogramming host membrane signaling and trafficking. Such processes are tightly regulated by phosphoinositides (PPIn), essential organizers of membrane dynamics and signal transduction implicated in cancer development and progression. Oncoviruses exploit host PPIn metabolism to facilitate their replication and persistence, often leading to its dysregulation. In turn, this disruption can activate oncogenic signaling pathways that promote malignant transformation. In this review, we summarize how oncoviruses manipulate PPIn metabolism to sustain their life cycle and drive long-term interactions with host cells, ultimately contributing to tumorigenesis.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214497","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
Phase separation of p62: roles and regulations in autophagy. p62相分离在自噬中的作用和调控。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-10-01 Epub Date: 2025-02-25 DOI: 10.1016/j.tcb.2025.01.010
Xue Huang, Jinpei Zhang, Jia Yao, Na Mi, Aimin Yang
{"title":"Phase separation of p62: roles and regulations in autophagy.","authors":"Xue Huang, Jinpei Zhang, Jia Yao, Na Mi, Aimin Yang","doi":"10.1016/j.tcb.2025.01.010","DOIUrl":"10.1016/j.tcb.2025.01.010","url":null,"abstract":"<p><p>The phase separation of the cargo receptor sequestome-1/p62 (SQSTM1/p62) is a critical mechanism for assembling signaling complexes in autophagy. During this process, p62 undergoes phase separation upon binding to polyubiquitin chains, concentrating ubiquitinated substrates within p62 droplets. These droplets further gather membrane sources and core autophagy machineries to facilitate autophagosome formation. The dynamics of p62 droplets are finely tuned in response to autophagy signals triggered by cellular stresses. Recent studies have revealed new regulatory mechanisms that highlight the significance of p62 phase separation in regulating autophagy. This review summarizes and discusses the molecular mechanisms of p62 phase separation and its roles in autophagy, with particular emphasis on the regulation of p62 droplets and their interaction modes with autophagic membranes.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"854-865"},"PeriodicalIF":18.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517403","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
Structural insights into actin filament turnover. 结构洞察肌动蛋白丝周转。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-10-01 Epub Date: 2025-01-23 DOI: 10.1016/j.tcb.2024.12.009
Wout Oosterheert, Micaela Boiero Sanders, Peter Bieling, Stefan Raunser
{"title":"Structural insights into actin filament turnover.","authors":"Wout Oosterheert, Micaela Boiero Sanders, Peter Bieling, Stefan Raunser","doi":"10.1016/j.tcb.2024.12.009","DOIUrl":"10.1016/j.tcb.2024.12.009","url":null,"abstract":"<p><p>The dynamic turnover of actin filaments drives the morphogenesis and migration of all eukaryotic cells. This review summarizes recent insights into the molecular mechanisms of actin polymerization and disassembly obtained through high-resolution structures of actin filament assemblies. We first describe how, upon polymerization, actin subunits age within the filament through changes in their associated adenine nucleotide. We then focus on the molecular basis of actin filament growth at the barbed end and how this process is modulated by core regulators such as profilin, formin, and capping protein (CP). Finally, the mechanisms underlying actin filament pointed-end depolymerization through disassembly factors cofilin/cyclase-associated protein (CAP) or DNase I are discussed. These findings contribute to a structural understanding of how actin filament dynamics are regulated in a complex cellular environment.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"893-906"},"PeriodicalIF":18.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030389","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
Mitochondrial DNA: how does it leave mitochondria? 线粒体DNA：它如何离开线粒体？
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-10-01 Epub Date: 2025-07-10 DOI: 10.1016/j.tcb.2025.06.005
Vladimir Gogvadze, Boris Zhivotovsky
{"title":"Mitochondrial DNA: how does it leave mitochondria?","authors":"Vladimir Gogvadze, Boris Zhivotovsky","doi":"10.1016/j.tcb.2025.06.005","DOIUrl":"10.1016/j.tcb.2025.06.005","url":null,"abstract":"<p><p>In recent years, studies have reported the presence of mitochondrial DNA (mtDNA) in the cytosol. However, a certain number of publications on the mechanisms of mtDNA release contain uncertainties. mtDNA is located in the mitochondrial matrix and cannot be released through the same pathways as intermembrane space proteins. This forum article aims to examine the assumptions and elucidate the processes underlying this phenomenon.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"819-822"},"PeriodicalIF":18.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621262","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
Metabolic control of replisome plasticity in genome surveillance. 基因组监测中复制体可塑性的代谢控制。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-10-01 Epub Date: 2025-02-12 DOI: 10.1016/j.tcb.2025.01.006
Mikkel Bo Petersen, Gita Chhetri, Kumar Somyajit
{"title":"Metabolic control of replisome plasticity in genome surveillance.","authors":"Mikkel Bo Petersen, Gita Chhetri, Kumar Somyajit","doi":"10.1016/j.tcb.2025.01.006","DOIUrl":"10.1016/j.tcb.2025.01.006","url":null,"abstract":"<p><p>Metabolic pathways and DNA replication are both adaptable and essential for early development and cancer progression. While each process is well understood individually, the mechanisms coordinating them are just beginning to emerge. Nucleotide biosynthesis serves as a crucial link, with fluctuating nucleotide pools leading to imbalanced deoxyribonucleotide (dNTP) and increased ribonucleotide (rNTP) levels, impairing DNA synthesis and triggering replication stress; ultimately driving developmental disorders and cancer. To counter these challenges, the replisome - the core machinery of DNA replication - continuously adjusts its architecture and speed in response to physiological changes, including nucleotide fluctuations. This review outlines recent insights into how the replisome aligns its function with metabolic changes in nucleotide levels and explores emerging links between metabolism and genome stability, and their roles in development and disease.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"880-892"},"PeriodicalIF":18.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415955","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
Metabolism and HSC fate: what NADPH is made for. 新陈代谢与造血干细胞的命运：NADPH 的作用。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-10-01 Epub Date: 2024-07-24 DOI: 10.1016/j.tcb.2024.07.003
Claudia Morganti, Massimo Bonora, Keisuke Ito
{"title":"Metabolism and HSC fate: what NADPH is made for.","authors":"Claudia Morganti, Massimo Bonora, Keisuke Ito","doi":"10.1016/j.tcb.2024.07.003","DOIUrl":"10.1016/j.tcb.2024.07.003","url":null,"abstract":"<p><p>Mitochondrial metabolism plays a central role in the regulation of hematopoietic stem cell (HSC) biology. Mitochondrial fatty acid oxidation (FAO) is pivotal in controlling HSC self-renewal and differentiation. Herein, we discuss recent evidence suggesting that NADPH generated in the mitochondria can influence the fate of HSCs. Although NADPH has multiple functions, HSCs show high levels of NADPH that are preferentially used for cholesterol biosynthesis. Endogenous cholesterol supports the biogenesis of extracellular vesicles (EVs), which are essential for maintaining HSC properties. We also highlight the significance of EVs in hematopoiesis through autocrine signaling. Elucidating the mitochondrial NADPH-cholesterol axis as part of the metabolic requirements of healthy HSCs will facilitate the development of new therapies for hematological disorders.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"866-879"},"PeriodicalIF":18.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762960","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
Design principles of gene circuits for longevity. 长寿基因回路的设计原则。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-10-01 Epub Date: 2025-03-12 DOI: 10.1016/j.tcb.2025.02.006
Paula Godoy, Nan Hao
{"title":"Design principles of gene circuits for longevity.","authors":"Paula Godoy, Nan Hao","doi":"10.1016/j.tcb.2025.02.006","DOIUrl":"10.1016/j.tcb.2025.02.006","url":null,"abstract":"<p><p>Aging is a dynamic process that is driven by cellular damage and disruption of homeostatic gene regulatory networks (GRNs). Traditional studies often focus on individual genes, but understanding their interplay is key to unraveling the mechanisms of aging. This review explores the gene circuits that influence longevity and highlights the role of feedback loops in maintaining cellular balance. The SIR2-HAP circuit in yeast serves as a model to explore how mutual inhibition between pathways influences aging trajectories and how engineering stable fixed points or oscillations within these circuits can extend lifespan. Feedback loops crucial for maintaining homeostasis are also reviewed, and we highlight how their destabilization accelerates aging. By leveraging systems and synthetic biology, strategies are proposed that may stabilize these loops within single cells, thereby enhancing their resilience to aging-related damage.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"840-853"},"PeriodicalIF":18.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626022","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
The gain and loss of plasticity during development and evolution. 发育和进化过程中可塑性的获得和丧失。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-10-01 Epub Date: 2025-03-03 DOI: 10.1016/j.tcb.2025.01.008
Amber Q Rock, Mansi Srivastava
{"title":"The gain and loss of plasticity during development and evolution.","authors":"Amber Q Rock, Mansi Srivastava","doi":"10.1016/j.tcb.2025.01.008","DOIUrl":"10.1016/j.tcb.2025.01.008","url":null,"abstract":"<p><p>Studies of embryonic plasticity, which were foundational for developmental biology, revealed variation across species and patterns of association with cleavage programs and adult regenerative capacity. Modern molecular and genetic tools now enable a reexamination of these classical experiments in diverse species and have the potential to reveal mechanisms that regulate plasticity over developmental time. This review synthesizes previous work on plasticity in embryos and adults and associated genetic mechanisms, providing a framework to organize data from a wide range of species. Mechanisms that explain how plasticity is lost in mammalian embryos are highlighted and crystallize a proposal for future studies in new research organisms that could identify shared principles for embryonic plasticity and, potentially, its maintenance into adulthood.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"823-839"},"PeriodicalIF":18.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558863","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
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