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Mitochondria and cell death signalling 线粒体和细胞死亡信号
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-04-11 DOI: 10.1016/j.ceb.2025.102510
Ella Hall-Younger , Stephen WG. Tait
Mitochondria are essential organelles in the life and death of a cell. During apoptosis, mitochondrial outer membrane permeabilisation (MOMP) engages caspase activation and cell death. Under nonlethal apoptotic stress, some mitochondria undergo permeabilisation, termed minority MOMP. Nonlethal apoptotic signalling impacts processes including genome stability, senescence and innate immunity. Recent studies have shown that upon MOMP, mitochondria and consequent signalling can trigger inflammation. We discuss how this occurs, and how mitochondrial inflammation might be targeted to increase tumour immunogenicity. Finally, we highlight how mitochondria contribute to other types of cell death including pyroptosis and ferroptosis. Collectively, these studies reveal critical new insights into how mitochondria regulate cell death, highlighting that mitochondrial signals engaged under nonlethal apoptotic stress have wide-ranging biological functions.
线粒体是细胞生死过程中必不可少的细胞器。在细胞凋亡过程中，线粒体外膜通透性（MOMP）参与了半胱天冬酶的激活和细胞死亡。在非致死性凋亡应激下，一些线粒体发生通透性，称为少数MOMP。非致死性凋亡信号影响包括基因组稳定性、衰老和先天免疫在内的过程。最近的研究表明，在MOMP上，线粒体和随后的信号传导可以引发炎症。我们讨论了这是如何发生的，以及线粒体炎症如何靶向增加肿瘤的免疫原性。最后，我们强调线粒体如何促进其他类型的细胞死亡，包括焦亡和铁亡。总的来说，这些研究揭示了线粒体如何调节细胞死亡的重要新见解，强调了在非致死性凋亡应激下参与的线粒体信号具有广泛的生物学功能。
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引用次数: 0
Beyond mechanosensing: How cells sense and shape their physical environment during development 超越机械感知：细胞在发育过程中如何感知和塑造其物理环境
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-04-10 DOI: 10.1016/j.ceb.2025.102514
Matyas Bubna-Litic, Roberto Mayor
The role of mechanics as a regulator of cell behaviour and embryo development has been widely recognised. However, much of the focus in mechanobiology during embryo development has been on how the mechanical properties of a cell affect its behaviour and fate determination. We discuss the role of mechanosignalling in development and propose that an equally important aspect of embryo mechanobiology is understanding how dynamic changes in tissue mechanics are regulated. Comparably to how chemical signals influence the fate of responding tissues during embryonic induction, we suggest that embryonic cell populations can alter the mechanical properties of adjacent tissues in a process we name ‘actuation’. Several examples of embryonic actuation and mechanical feedback are discussed.
力学作为细胞行为和胚胎发育的调节者的作用已被广泛认识。然而，在胚胎发育过程中，机械生物学的大部分焦点都集中在细胞的机械特性如何影响其行为和命运决定上。我们讨论了机械信号在发育中的作用，并提出胚胎力学生物学的一个同样重要的方面是理解如何调节组织力学的动态变化。与化学信号如何影响胚胎诱导过程中响应组织的命运相比，我们认为胚胎细胞群可以在我们称之为“驱动”的过程中改变邻近组织的机械特性。讨论了胚胎驱动和机械反馈的几个例子。
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引用次数: 0
Nanoscale mechano-adaption of integrin-based cell adhesions: New tools and techniques lead the way 基于整合素的细胞粘附的纳米级机械适应：新工具和新技术引领未来
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-04-06 DOI: 10.1016/j.ceb.2025.102509
Ryosuke Nishimura , Pakorn Kanchanawong
Force generation and transmission in biological systems are driven by protein-based machinery organized at the nanoscale. Thus, technological advances that allow for the measurement or manipulation of molecular-scale features are key to new mechanobiological insights. Integrins, a superfamily of adhesion receptors, function by forming supramolecular complexes that mediate mechanobiological processes such as migration and matrix remodeling. This review highlights recent findings that harness advanced techniques in microscopy, nanotechnology, and biosensors to uncover nanoscale transformations that accompany integrin responses to mechanobiological stimuli. Recent discoveries are sharpening our understanding of the diverse functions and structural organization of different integrin heterodimers and their molecular partners, highlighting their critical roles in cellular processes.
生物系统中的力的产生和传递是由纳米级组织的基于蛋白质的机器驱动的。因此，允许测量或操纵分子尺度特征的技术进步是新的机械生物学见解的关键。整合素是粘附受体的一个超家族，其功能是形成超分子复合物，介导诸如迁移和基质重塑等机械生物学过程。这篇综述强调了利用显微镜、纳米技术和生物传感器的先进技术来揭示整合素对机械生物学刺激反应的纳米级转化的最新发现。最近的发现加深了我们对不同整合素异源二聚体及其分子伙伴的不同功能和结构组织的理解，突出了它们在细胞过程中的关键作用。
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引用次数: 0
Inter-organ communication in Drosophila: Lipoproteins, adipokines, and immune-metabolic coordination 果蝇的器官间通讯：脂蛋白、脂肪因子和免疫代谢协调
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-04-04 DOI: 10.1016/j.ceb.2025.102508
Akhila Rajan , Jason Karpac
Inter-organ communication networks are essential for maintaining systemic homeostasis in multicellular organisms. In Drosophila melanogaster, studies of adipokines and lipoproteins reveal evolutionarily conserved mechanisms coordinating metabolism, immunity, and behavior. This mini-review focuses on two key pathways: the adipokine Unpaired 2 (Upd2) and lipoprotein-mediated signaling. Upd2, a leptin analog, mediates fat-brain communication to regulate insulin secretion, sleep, and feeding behavior. Recent work has uncovered an LC3/Atg8-dependent secretion mechanism for Upd2, linking nutrient sensing to systemic adaptation. Lipoproteins, particularly ApoLpp and LTP, function beyond lipid transport, orchestrating neural maintenance and immune responses. During infection, macrophage-derived signals trigger lipoprotein-mediated lipid redistribution to support host defense. Additionally, muscle tissue emerges as an unexpected mediator of immune-metabolic coordination through inter-organ signaling. These findings highlight the intricate cross-talk between organs required for organismal survival and suggest therapeutic strategies for metabolic disorders.
在多细胞生物中，器官间通讯网络对于维持系统稳态至关重要。在黑腹果蝇中，对脂肪因子和脂蛋白的研究揭示了协调代谢、免疫和行为的进化保守机制。这篇综述主要关注两个关键途径：脂肪因子Unpaired 2 （Upd2）和脂蛋白介导的信号传导。Upd2是一种瘦素类似物，介导脂肪与大脑的交流，调节胰岛素分泌、睡眠和摄食行为。最近的研究揭示了Upd2的LC3/ atg8依赖性分泌机制，将营养感知与系统适应联系起来。脂蛋白，尤其是ApoLpp和LTP，除了脂质转运之外，还具有协调神经维持和免疫反应的功能。在感染过程中，巨噬细胞来源的信号触发脂蛋白介导的脂质再分配来支持宿主防御。此外，肌肉组织通过器官间信号传导成为免疫代谢协调的意想不到的中介。这些发现强调了生物体生存所需的器官之间复杂的串扰，并提出了代谢紊乱的治疗策略。
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引用次数: 0
Learning physics and biology from cytoskeletal and condensate interactions 从细胞骨架和凝聚相互作用中学习物理和生物学
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-04-04 DOI: 10.1016/j.ceb.2025.102506
Julia Bourdeau, Prashali Chauhan, Jennifer L. Ross
Two important mechanisms for self-organization in cells include condensation of biomolecules, such as proteins and nucleic acids into phase-separated droplets to form membraneless organelles and organization of the cytoskeletal filaments into larger-scale systems such as the actin cortex and the microtubule-based mitotic spindle. Recent publications highlight that these two intracellular organization schemes are coordinated, with condensates controlling cytoskeletal organizations and cytoskeleton organizing the condensates. Here, we focus on recent progress from the past 2 years at the interface between condensates and cytoskeleton. We split the discussion into the physical and biological principles we can learn from these recent studies.
细胞中自组织的两个重要机制包括生物分子（如蛋白质和核酸）凝聚成相分离的液滴形成无膜细胞器，以及细胞骨架细丝组织成更大的系统，如肌动蛋白皮层和基于微管的有丝分裂纺锤体。最近的出版物强调，这两种细胞内组织方案是协调的，凝聚体控制细胞骨架组织和细胞骨架组织凝聚体。在这里，我们重点介绍了近2年来在凝析物和细胞骨架界面方面的最新进展。我们将讨论分为我们可以从这些最近的研究中学到的物理和生物学原理。
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引用次数: 0
Structuring of the endolysosomal system by HOPS and CORVET tethering complexes HOPS和CORVET系带复合物构建内溶酶体系统
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-04-04 DOI: 10.1016/j.ceb.2025.102504
Christian Ungermann , Arne Moeller
Eukaryotic cells depend on their endolysosomal system for membrane protein and organelle turnover, plasma membrane quality control, or regulation of their nutrient uptake. All material eventually ends up in the lytic environment of the lysosome for cellular recycling. At endosomes and lysosomes, the multisubunit complexes CORVET and HOPS tether membranes by binding both their cognate Rab GTPase and specific membrane lipids. Additionally, they carry one Sec1/Munc18-like subunit at their center and thus promote SNARE assembly and, subsequently, bilayer mixing. Recent structural and functional analysis provided insights into their organization and suggested how these complexes combine tethering with fusion catalysis. This review discusses the function and structural organization of HOPS and CORVET in the context of recent studies in yeast and metazoan cells.
真核细胞依靠其内溶酶体系统进行膜蛋白和细胞器的更新、质膜质量控制或营养摄取的调节。所有的物质最终在溶酶体的分解环境中结束，进行细胞循环。在核内体和溶酶体中，多亚基复合物CORVET和HOPS通过结合其同源的Rab GTPase和特定的膜脂来系住膜。此外，它们在其中心携带一个Sec1/ munc18样亚基，从而促进SNARE组装和随后的双层混合。最近的结构和功能分析提供了对它们的组织的见解，并提出了这些络合物是如何结合捆绑和融合催化的。本文就近年来酵母和后生动物细胞中啤酒花和CORVET的功能和结构组织进行了综述。
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引用次数: 0
Dynamic structure of the cytoplasm 细胞质的动态结构
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-04-04 DOI: 10.1016/j.ceb.2025.102507
Hyojun Kim, Morgan Delarue
The cytoplasm is a dense and complex milieu in which a plethora of biochemical reactions occur. Its structure is not understood so far, albeit being central to cellular functioning. In this review, we highlight a novel perspective in which the physical properties of the cytoplasm are regulated in space and time and actively contribute to cellular function. Furthermore, we underscore recent findings that the dynamic formation of local assemblies within the cytoplasm, such as condensates and polysomes, serves as a key regulator of mesoscale cytoplasmic dynamics.
细胞质是一个密集而复杂的环境，在其中发生了大量的生化反应。尽管它是细胞功能的核心，但其结构至今仍不为人所知。在这篇综述中，我们强调了一个新的观点，即细胞质的物理特性在空间和时间上受到调节，并积极地参与细胞功能。此外，我们强调了最近的发现，即细胞质内局部组装的动态形成，如凝聚体和多聚体，是中尺度细胞质动力学的关键调节因子。
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引用次数: 0
Structural insights into traffic through the Golgi complex 高尔基大厦交通结构分析
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-03-28 DOI: 10.1016/j.ceb.2025.102505
Bryce A. Brownfield , J. Christopher Fromme
The Golgi complex is the central sorting station of eukaryotic cells. Several unique trafficking pathways direct the transport of proteins between the Golgi and the endoplasmic reticulum, plasma membrane, and endolysosomal system. In this review we highlight several recent studies that use structural biology approaches to discover and characterize novel mechanisms cells use to control the flow of traffic through the Golgi. These studies provide important new insights into how activation of Arf and Rab GTPases is regulated, how cargo proteins are sorted during vesicle biogenesis, and how vesicle tethers identify their target compartments.
高尔基复合体是真核细胞的中心分选站。几种独特的运输途径指导蛋白质在高尔基体与内质网、质膜和内溶酶体系统之间的运输。在这篇综述中，我们重点介绍了最近的几项研究，这些研究使用结构生物学方法来发现和表征细胞用于控制高尔基体流量的新机制。这些研究为研究Arf和Rab gtpase的激活是如何被调节的，在囊泡生物发生过程中货物蛋白是如何被分类的，以及囊泡系链如何识别它们的靶室提供了重要的新见解。
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引用次数: 0
Advances in mitophagy initiation mechanisms 线粒体自噬起始机制的研究进展。
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-03-20 DOI: 10.1016/j.ceb.2025.102493
Catharina Küng , Michael Lazarou , Thanh Ngoc Nguyen
Mitophagy is an important lysosomal degradative pathway that removes damaged or unwanted mitochondria to maintain cellular and organismal homeostasis. The mechanisms behind how mitophagy is initiated to form autophagosomes around mitochondria have gained a lot of interest since they can be potentially targeted by mitophagy-inducing therapeutics. Mitophagy initiation can be driven by various autophagy receptors or adaptors that respond to different cellular and mitochondrial stimuli, ranging from mitochondrial damage to metabolic rewiring. This review will cover recent advances in our understanding of how mitophagy is initiated, and by doing so reveal the mechanistic plasticity of how autophagosome formation can begin.
线粒体自噬是一种重要的溶酶体降解途径，它可以去除受损或不需要的线粒体，以维持细胞和生物体的稳态。自噬如何在线粒体周围形成自噬体的机制已经引起了人们的极大兴趣，因为它们可能是自噬诱导疗法的潜在靶点。线粒体自噬起始可以由各种自噬受体或接头驱动，这些自噬受体或接头响应不同的细胞和线粒体刺激，从线粒体损伤到代谢重布线。这篇综述将涵盖我们对有丝自噬如何启动的理解的最新进展，并通过这样做揭示自噬体形成如何开始的机制可塑性。
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引用次数: 0
License to drive: Receptor-mediated ER exit of proteins and lipids 驾驶执照：受体介导的蛋白质和脂质内质网出口。
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-03-20 DOI: 10.1016/j.ceb.2025.102501
Xiao Wang , Tiantian Li , Yusong Guo , Xiao-Wei Chen
The secretory pathway, which begins at the endoplasmic reticulum (ER) through the COPII complex, is responsible for transporting proteins and lipid carriers to various destined cellular compartments or extracellular space. The fundamental mechanism by which the COPII operates is evolutionarily conserved. Nevertheless, the vast diversity of mammalian cargos poses significant challenges to the secretory pathway, especially considering the intricate physiology in vivo. Particularly, certain physiologically essential cargos, including procollagen and lipoproteins, appear to be oversized for these canonical carriers, implying the need for additional sophisticated regulation at the onset step so-called ER exit. Emerging evidence highlights the critical role of cargo receptors in selective sorting for ER export, illuminating the complex biology of the trafficking dynamics, which holds broad implications for human health and diseases.
分泌途径始于内质网（ER），通过COPII复合物，负责将蛋白质和脂质载体运送到各种指定的细胞室或细胞外空间。COPII运作的基本机制是进化保守的。然而，哺乳动物物质的巨大多样性对分泌途径提出了重大挑战，特别是考虑到复杂的体内生理。特别是，某些生理上必需的货物，包括前胶原蛋白和脂蛋白，对于这些典型的载体来说似乎过大，这意味着需要在所谓的内质网退出的起始阶段进行额外的复杂调节。新出现的证据突出了货物受体在ER出口的选择性分类中的关键作用，阐明了贩运动态的复杂生物学，这对人类健康和疾病具有广泛的影响。
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引用次数: 0
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