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Neuronal AMPK regulates lipid transport to microglia. 神经元 AMPK 调节向小胶质细胞的脂质运输
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-09-01 DOI: 10.1016/j.tcb.2024.08.001
Ju-Young Bae, Julie Jacquemyn, Maria S Ioannou

In neurodegeneration, neurons release lipids that accumulate in glial lipid droplets (LDs). But what controls lipid transport and how does this affect glia? A recent study by Li et al. discovered that the loss of neuronal AMP-activated protein kinase (AMPK) activity promotes lipid efflux, which drives a proinflammatory state in microglia.

在神经变性过程中,神经元会释放脂质,这些脂质会积聚在胶质细胞脂滴(LD)中。但是,是什么控制了脂质的运输,这又是如何影响胶质细胞的呢?李等人最近的一项研究发现,神经元 AMP 激活蛋白激酶(AMPK)活性的丧失会促进脂质外流,从而推动小胶质细胞的促炎状态。
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引用次数: 0
RNA G-quadruplexes and stress: emerging mechanisms and functions. RNA G-四链体与压力:新出现的机制和功能。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-02-09 DOI: 10.1016/j.tcb.2024.01.005
Prakash Kharel, Pavel Ivanov

RNA G-quadruplexes (rG4s) are noncanonical secondary structures formed by guanine-rich sequences that are found in different regions of RNA molecules. These structures have been implicated in diverse biological processes, including translation, splicing, and RNA stability. Recent studies have suggested that rG4s play a role in the cellular response to stress. This review summarizes the current knowledge on rG4s under stress, focusing on their formation, regulation, and potential functions in stress response pathways. We discuss the molecular mechanisms that regulate the formation of rG4 under different stress conditions and the impact of these structures on RNA metabolism, gene expression, and cell survival. Finally, we highlight the potential therapeutic implications of targeting rG4s for the treatment of stress-related diseases through modulating cell survival.

RNA G-quadruplexes (rG4s) 是富含鸟嘌呤的序列形成的非正则二级结构,存在于 RNA 分子的不同区域。这些结构与多种生物过程有关,包括翻译、剪接和 RNA 稳定性。最近的研究表明,rG4s 在细胞应激反应中发挥作用。本综述总结了目前有关应激状态下 rG4s 的知识,重点关注它们的形成、调控以及在应激反应途径中的潜在功能。我们讨论了在不同应激条件下调控 rG4 形成的分子机制,以及这些结构对 RNA 代谢、基因表达和细胞存活的影响。最后,我们强调了靶向 rG4s 通过调节细胞存活来治疗应激相关疾病的潜在治疗意义。
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引用次数: 0
Modulation of extrinsic apoptotic pathway by intracellular glycosylation. 细胞内糖基化对细胞外凋亡途径的调节。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-02-08 DOI: 10.1016/j.tcb.2024.01.003
Kamil Seyrek, Nikita V Ivanisenko, Corinna König, Inna N Lavrik

The importance of post-translational modifications (PTMs), particularly O-GlcNAcylation, of cytoplasmic proteins in apoptosis has been neglected for quite a while. Modification of cytoplasmic proteins by a single N-acetylglucosamine sugar is a dynamic and reversible PTM exhibiting properties more like phosphorylation than classical O- and N-linked glycosylation. Due to the sparse information existing, we have only limited understanding of how GlcNAcylation affects cell death. Deciphering the role of GlcNAcylation in cell fate may provide further understanding of cell fate decisions. This review focus on the modulation of extrinsic apoptotic pathway via GlcNAcylation carried out by O-GlcNAc transferase (OGT) or by other bacterial effector proteins.

细胞质蛋白质的翻译后修饰(PTMs),特别是O-GlcNAcylation,在细胞凋亡中的重要性一直被忽视。单个 N-乙酰葡糖胺糖对细胞质蛋白质的修饰是一种动态、可逆的 PTM,与经典的 O- 和 N-连接糖基化相比,其性质更类似于磷酸化。由于现有信息稀少,我们对 GlcNAcylation 如何影响细胞死亡的了解十分有限。破译 GlcNAcylation 在细胞命运中的作用可能有助于进一步了解细胞命运的决定。这篇综述主要探讨了 O-GlcNAc转移酶(OGT)或其他细菌效应蛋白通过 GlcNAcylation 对细胞凋亡外途径的调节作用。
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引用次数: 0
Translational control of papillomavirus mRNAs in the spotlight. 聚光灯下的乳头瘤病毒 mRNA 翻译控制。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-27 DOI: 10.1016/j.tcb.2024.07.001
Alejandra García, Giovanna Maldonado, Greco Hernández

High-risk human papillomaviruses (HPVs) cause most cases of cervical cancer, a disease with an increasing impact worldwide. Recent studies have shown that the synthesis of viral oncoproteins is strongly subject to translational control. Thus, targeting the protein synthesis machinery might open novel avenues to develop innovative therapies aiming to improve patients' survival.

高危人乳头瘤病毒(HPV)是导致大多数宫颈癌病例的原因,这种疾病对全世界的影响越来越大。最近的研究表明,病毒癌蛋白的合成在很大程度上受制于翻译控制。因此,以蛋白质合成机制为靶点可能会为开发创新疗法开辟新的途径,从而提高患者的生存率。
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引用次数: 0
Membrane remodeling and trafficking piloted by SARS-CoV-2. 由 SARS-CoV-2 主导的膜重塑和贩运。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-01-22 DOI: 10.1016/j.tcb.2023.12.006
Maria Concetta Sergio, Simona Ricciardi, Andrea M Guarino, Laura Giaquinto, Maria Antonietta De Matteis

The molecular mechanisms underlying SARS-CoV-2 host cell invasion and life cycle have been studied extensively in recent years, with a primary focus on viral entry and internalization with the aim of identifying antiviral therapies. By contrast, our understanding of the molecular mechanisms involved in the later steps of the coronavirus life cycle is relatively limited. In this review, we describe what is known about the host factors and viral proteins involved in the replication, assembly, and egress phases of SARS-CoV-2, which induce significant host membrane rearrangements. We also discuss the limits of the current approaches and the knowledge gaps still to be addressed.

近年来,人们对 SARS-CoV-2 宿主细胞入侵和生命周期的分子机制进行了广泛的研究,主要侧重于病毒的进入和内化,目的是确定抗病毒疗法。相比之下,我们对冠状病毒生命周期后期所涉及的分子机制的了解相对有限。在这篇综述中,我们描述了参与 SARS-CoV-2 复制、组装和排出阶段的宿主因子和病毒蛋白的已知情况,这些阶段会引起宿主膜的显著重排。我们还讨论了目前研究方法的局限性以及有待解决的知识空白。
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引用次数: 0
Metabolic regulation of mRNA splicing. mRNA 剪接的代谢调节。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-03-01 DOI: 10.1016/j.tcb.2024.02.002
Haissi Cui, Qingyu Shi, Colette Maya Macarios, Paul Schimmel

Alternative mRNA splicing enables the diversification of the proteome from a static genome and confers plasticity and adaptiveness on cells. Although this is often explored in development, where hard-wired programs drive the differentiation and specialization, alternative mRNA splicing also offers a way for cells to react to sudden changes in outside stimuli such as small-molecule metabolites. Fluctuations in metabolite levels and availability in particular convey crucial information to which cells react and adapt. We summarize and highlight findings surrounding the metabolic regulation of mRNA splicing. We discuss the principles underlying the biochemistry and biophysical properties of mRNA splicing, and propose how these could intersect with metabolite levels. Further, we present examples in which metabolites directly influence RNA-binding proteins and splicing factors. We also discuss the interplay between alternative mRNA splicing and metabolite-responsive signaling pathways. We hope to inspire future research to obtain a holistic picture of alternative mRNA splicing in response to metabolic cues.

另类 mRNA 剪接使蛋白质组从静态基因组中多样化,并赋予细胞可塑性和适应性。在发育过程中,硬连线程序会驱动细胞的分化和特化,尽管人们经常在发育过程中探讨这一点,但替代 mRNA 剪接也为细胞提供了一种方法,使其能够对外界刺激(如小分子代谢物)的突然变化做出反应。代谢物水平和可用性的波动尤其能传递关键信息,使细胞做出反应和适应。我们总结并重点介绍了围绕 mRNA 剪接的代谢调控的研究成果。我们讨论了 mRNA 剪接的生物化学和生物物理特性的基本原理,并提出了这些原理与代谢物水平之间的相互关系。此外,我们还介绍了代谢物直接影响 RNA 结合蛋白和剪接因子的实例。我们还讨论了替代 mRNA 剪接与代谢物反应信号通路之间的相互作用。我们希望能对未来的研究有所启发,以便全面了解替代 mRNA 剪接对代谢线索的响应。
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引用次数: 0
The idiosyncrasies of oocytes. 卵细胞的特异性。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-08-13 DOI: 10.1016/j.tcb.2024.07.006
Jun Wei Pek

Animal oocytes face extreme challenges. They remain dormant in the body for long periods of time. To support offspring development and health, they need to store genetic material and maternal factors stably and at the same time manage cellular damage in a reliable manner. Recent studies have provided new insights on how oocytes cope with such challenges. This review discusses the many unusual or idiosyncratic nature of oocytes and how understanding oocyte biology can help us address issues of reproduction and intergenerational inheritance.

动物卵母细胞面临着极大的挑战。它们在体内长期处于休眠状态。为了支持后代的发育和健康,它们需要稳定地储存遗传物质和母体因子,同时以可靠的方式处理细胞损伤。最近的研究为卵母细胞如何应对这些挑战提供了新的见解。本综述将讨论卵母细胞的许多不寻常或特异性质,以及了解卵母细胞生物学如何帮助我们解决繁殖和代际遗传问题。
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引用次数: 0
Subscription and Copyright Information 订阅和版权信息
IF 19 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-08-08 DOI: 10.1016/s0962-8924(24)00151-x
No Abstract
无摘要
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引用次数: 0
Advisory Board and Contents 咨询委员会和内容
IF 19 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-08-08 DOI: 10.1016/s0962-8924(24)00148-x
No Abstract
无摘要
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引用次数: 0
Mitochondrial regulation in stem cells. 干细胞中的线粒体调节。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-08-01 Epub Date: 2023-10-31 DOI: 10.1016/j.tcb.2023.10.003
Yifei Wang, Marine Barthez, Danica Chen

Stem cells persist throughout the lifespan to repair and regenerate tissues due to their unique ability to self-renew and differentiate. Here we reflect on the recent discoveries in stem cells that highlight a mitochondrial metabolic checkpoint at the restriction point of the stem cell cycle. Mitochondrial activation supports stem cell proliferation and differentiation by providing energy supply and metabolites as signaling molecules. Concomitant mitochondrial stress can lead to loss of stem cell self-renewal and requires the surveillance of various mitochondrial quality control mechanisms. During aging, a mitochondrial protective program mediated by several sirtuins becomes dysregulated and can be targeted to reverse stem cell aging and tissue degeneration, giving hope for targeting the mitochondrial metabolic checkpoint for treating tissue degenerative diseases.

干细胞因其独特的自我更新和分化能力而在整个生命周期中持续存在,以修复和再生组织。在这里,我们回顾了最近在干细胞中的发现,这些发现突出了干细胞周期限制点的线粒体代谢检查点。线粒体激活通过提供能量供应和代谢产物作为信号分子来支持干细胞增殖和分化。伴随的线粒体应激会导致干细胞自我更新的丧失,需要监测各种线粒体质量控制机制。在衰老过程中,由几种sirtuins介导的线粒体保护程序变得失调,可以靶向逆转干细胞衰老和组织变性,为靶向线粒体代谢检查点治疗组织变性疾病带来了希望。
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引用次数: 0
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Trends in Cell Biology
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