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Mitochondrial Maintenance in Skeletal Muscle. 骨骼肌中的线粒体维护
IF 8.4 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-05-05 DOI: 10.1101/cshperspect.a041514
Laura M de Smalen, Christoph Handschin

Skeletal muscle is one of the tissues with the highest range of variability in metabolic rate, which, to a large extent, is critically dependent on tightly controlled and fine-tuned mitochondrial activity. Besides energy production, other mitochondrial processes, including calcium buffering, generation of heat, redox and reactive oxygen species homeostasis, intermediate metabolism, substrate biosynthesis, and anaplerosis, are essential for proper muscle contractility and performance. It is thus not surprising that adequate mitochondrial function is ensured by a plethora of mechanisms, aimed at balancing mitochondrial biogenesis, proteostasis, dynamics, and degradation. The fine-tuning of such maintenance mechanisms ranges from proper folding or degradation of individual proteins to the elimination of whole organelles, and in extremis, apoptosis of cells. In this review, the present knowledge on these processes in the context of skeletal muscle biology is summarized. Moreover, existing gaps in knowledge are highlighted, alluding to potential future studies and therapeutic implications.

骨骼肌是新陈代谢率变化范围最大的组织之一,而新陈代谢率在很大程度上取决于线粒体活动的严格控制和微调。除了产生能量外,线粒体的其他过程,包括钙缓冲、产生热量、氧化还原和活性氧平衡、中间代谢、底物生物合成和无氧代谢,对肌肉的正常收缩能力和表现都至关重要。因此,旨在平衡线粒体生物生成、蛋白稳态、动态和降解的大量机制确保了线粒体功能的充分发挥也就不足为奇了。这些维持机制的微调范围从单个蛋白质的适当折叠或降解到整个细胞器的消除,以及极端情况下的细胞凋亡。在这篇综述中,我们总结了目前在骨骼肌生物学背景下有关这些过程的知识。此外,还强调了现有的知识空白,暗示了未来潜在的研究和治疗意义。
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引用次数: 0
Neuronal Circuit Evolution: From Development to Structure and Adaptive Significance. 神经元回路进化:从发育到结构和适应意义。
IF 8.4 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-05-05 DOI: 10.1101/cshperspect.a041493
Nikolaos Konstantinides, Claude Desplan

Neuronal circuits represent the functional units of the brain. Understanding how the circuits are generated to perform computations will help us understand how the brain functions. Nevertheless, neuronal circuits are not engineered, but have formed through millions of years of animal evolution. We posit that it is necessary to study neuronal circuit evolution to comprehensively understand circuit function. Here, we review our current knowledge regarding the mechanisms that underlie circuit evolution. First, we describe the possible genetic and developmental mechanisms that have contributed to circuit evolution. Then, we discuss the structural changes of circuits during evolution and how these changes affected circuit function. Finally, we try to put circuit evolution in an ecological context and assess the adaptive significance of specific examples. We argue that, thanks to the advent of new tools and technologies, evolutionary neurobiology now allows us to address questions regarding the evolution of circuitry and behavior that were unimaginable until very recently.

神经元回路代表了大脑的功能单元。了解神经元回路是如何产生并执行计算的,将有助于我们理解大脑的功能。然而,神经元回路并不是设计出来的,而是经过数百万年的动物进化形成的。我们认为有必要研究神经元回路的进化,以全面了解回路的功能。在此,我们回顾了目前有关神经回路进化机制的知识。首先,我们描述了可能促进神经回路进化的遗传和发育机制。然后,我们讨论电路在进化过程中的结构变化以及这些变化如何影响电路功能。最后,我们试图将电路进化置于生态环境中,并评估具体实例的适应意义。我们认为,得益于新工具和新技术的出现,进化神经生物学现在可以让我们解决电路和行为进化方面的问题,而这些问题在不久前还是难以想象的。
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引用次数: 0
Forces Shaping the Blastocyst. 塑造囊胚的力量
IF 6.9 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-05-05 DOI: 10.1101/cshperspect.a041519
David Rozema, Jean-Léon Maître

The blastocyst forms during the first days of mammalian development. The structure of the blastocyst is conserved among placental mammals and is paramount to the establishment of the first mammalian lineages. The blastocyst is composed of an extraembryonic epithelium, the trophectoderm (TE), that envelopes a fluid-filled lumen and the inner cell mass (ICM). To shape the blastocyst, embryos transit through three stages driven by forces that have been characterized in the mouse embryo over the past decade. The morphogenetically quiescent cleavage stages mask dynamic cytoskeletal remodeling. Then, during the formation of the morula, cells pull themselves together and the strongest ones internalize. Finally, the blastocyst forms after the pressurized lumen breaks the radial symmetry of the embryo before expanding in cycles of collapses and regrowth. In this review, we delineate the force patterns sculpting the blastocyst, based on our knowledge on the mouse and, to some extent, human embryos.

囊胚形成于哺乳动物发育的最初几天。囊胚的结构在有胎盘的哺乳动物中是保留的,对哺乳动物第一代血统的建立至关重要。囊胚由胚外上皮--滋养外胚层(TE)--组成,滋养外胚层包裹着充满液体的管腔和内细胞团(ICM)。为了形成囊胚,胚胎要经历三个阶段,这三个阶段的驱动力在过去十年中已在小鼠胚胎中得到证实。形态发生静止的裂解阶段掩盖了动态细胞骨架重塑。然后,在形成蜕膜的过程中,细胞拉拢在一起,最强壮的细胞内部化。最后,在受压的管腔打破胚胎的径向对称后形成囊胚,然后在塌陷和再生长的循环中扩张。在这篇综述中,我们将根据对小鼠胚胎的了解,并在一定程度上根据对人类胚胎的了解,描述囊胚的受力模式。
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引用次数: 0
Life and Death without Telomerase: The Saccharomyces cerevisiae Model. 没有端粒酶的生与死:酿酒酵母模型。
IF 6.9 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-05-05 DOI: 10.1101/cshperspect.a041699
Veronica Martinez-Fernandez, Aurélia Barascu, Maria Teresa Teixeira

Saccharomyces cerevisiae, a model organism in telomere biology, has been instrumental in pioneering a comprehensive understanding of the molecular processes that occur in the absence of telomerase across eukaryotes. This exploration spans investigations into telomere dynamics, intracellular signaling cascades, and organelle-mediated responses, elucidating their impact on proliferative capacity, genome stability, and cellular variability. Through the lens of budding yeast, numerous sources of cellular heterogeneity have been identified, dissected, and modeled, shedding light on the risks associated with telomeric state transitions, including the evasion of senescence. Moreover, the unraveling of the intricate interplay between the nucleus and other organelles upon telomerase inactivation has provided insights into eukaryotic evolution and cellular communication networks. These contributions, akin to milestones achieved using budding yeast, such as the discovery of the cell cycle, DNA damage checkpoint mechanisms, and DNA replication and repair processes, have been of paramount significance for the telomere field. Particularly, these insights extend to understanding replicative senescence as an anticancer mechanism in humans and enhancing our understanding of eukaryotes' evolution.

酿酒酵母菌是端粒生物学中的一种模式生物,在全面了解真核生物端粒酶缺失时的分子过程方面发挥了重要作用。这一探索跨越了对端粒动力学、细胞内信号级联和细胞器介导反应的研究,阐明了它们对增殖能力、基因组稳定性和细胞变异性的影响。通过芽殖酵母的镜头,许多细胞异质性的来源已经被确定、解剖和建模,揭示了与端粒状态转变相关的风险,包括逃避衰老。此外,端粒酶失活过程中细胞核和其他细胞器之间错综复杂的相互作用的揭示,为真核生物进化和细胞通信网络提供了新的见解。这些贡献,类似于利用出芽酵母实现的里程碑,如发现细胞周期,DNA损伤检查点机制,DNA复制和修复过程,对端粒领域具有至关重要的意义。特别是,这些见解延伸到理解作为人类抗癌机制的复制性衰老和增强我们对真核生物进化的理解。
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引用次数: 0
Structural Biology of Telomerase and Associated Factors. 端粒酶及其相关因子的结构生物学研究。
IF 6.9 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-04-15 DOI: 10.1101/cshperspect.a041697
Zala Sekne, Patryk Ludzia, Sebastian Balch, Thi Hoang Duong Nguyen

Telomerase ribonucleoprotein (RNP) plays a crucial role in maintaining telomere length by processively adding telomeric repeats to the 3' ends of chromosomes. Telomerase activation is linked to cancer, while mutations that compromise telomerase function result in diseases such as dyskeratosis congenita. The synthesis of telomeric repeats necessitates two core telomerase components: telomerase reverse transcriptase (TERT) and telomerase RNA (TER). However, cellular telomerase holoenzymes encompass a diverse range of protein factors, both constitutively and transiently interacting. These factors are integral to telomerase assembly or regulation at telomeres. This review emphasizes recent advancements in structural studies of telomerase holoenzymes and their associated factors from Tetrahymena thermophila, Saccharomyces cerevisiae, Schizosaccharomyces pombe, and humans. These studies have significantly deepened our molecular understanding not only of the mechanism underlying telomeric repeat synthesis but also of the biological roles of telomerase-associated proteins.

端粒酶核糖核蛋白(RNP)通过在染色体的3'端不断添加端粒重复序列,在维持端粒长度方面起着至关重要的作用。端粒酶激活与癌症有关,而损害端粒酶功能的突变会导致先天性角化不良等疾病。端粒重复序列的合成需要两种核心端粒酶成分:端粒酶逆转录酶(TERT)和端粒酶RNA (TER)。然而,细胞端粒酶全酶包含多种蛋白质因子,既有组成性的,也有瞬时的相互作用。这些因子对于端粒酶的组装或调控是不可或缺的。本文综述了嗜热四膜菌、酿酒酵母、裂糖菌和人体内端粒酶全酶及其相关因子的结构研究进展。这些研究不仅大大加深了我们对端粒重复合成机制的分子认识,而且也加深了我们对端粒酶相关蛋白的生物学作用的认识。
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引用次数: 0
Biogenesis and Regulation of Telomerase during Development and Cancer. 端粒酶在发育和癌症中的生物发生和调控。
IF 8.4 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-04-10 DOI: 10.1101/cshperspect.a041692
Lu Chen, Luis Francisco Zirnberger Batista

Telomerase is a large ribonucleoprotein complex responsible for the addition of telomeric DNA repeats to chromosomal ends. Telomerase is composed of core and accessory components that work in coordination to ensure telomere length is maintained during development and in specific cell types. Telomerase activity is tightly regulated and is strongly increased in most tumor cells. On the other hand, loss-of-function mutations either in accessory factors or in core components of the complex impact telomere maintenance and cause a large spectrum of severe phenotypes, typically described as telomere biology disorders. A central element for efficient telomerase function is the proper biogenesis and assembly of the holoenzyme. Here, we discuss our current understanding of these processes and how they modulate telomerase efficiency. We consider how these processes are influenced by the specific subcellular localization of different telomerase components during different stages of the assembly of the holoenzyme. We describe the tremendous progress made in this area over the last decade and how recently discovered aspects of telomerase biogenesis can be exploited clinically, to actively benefit patients suffering from telomere biology disorders.

端粒酶是一种大型核糖核蛋白复合物,负责将端粒DNA重复序列添加到染色体末端。端粒酶由核心和辅助成分组成,它们协调工作以确保端粒在发育过程中和特定细胞类型中保持长度。端粒酶活性在大多数肿瘤细胞中受到严格调控,并显著增加。另一方面,无论是辅助因子还是复杂的核心成分的功能丧失突变都会影响端粒的维持,并导致大范围的严重表型,通常被描述为端粒生物学紊乱。高效端粒酶功能的核心要素是全酶的适当生物发生和组装。在这里,我们讨论了我们目前对这些过程的理解以及它们如何调节端粒酶的效率。我们考虑在全酶组装的不同阶段,不同端粒酶组分的特定亚细胞定位如何影响这些过程。我们描述了过去十年来在这一领域取得的巨大进展,以及最近发现的端粒酶生物发生方面如何在临床上被利用,以积极地造福端粒生物学疾病的患者。
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引用次数: 0
Telomere Dynamics in Zebrafish Aging and Disease. 斑马鱼衰老和疾病的端粒动力学。
IF 6.9 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041696
Miguel Godinho Ferreira

Fish telomere lengths vary significantly across the numerous species, implicating diverse life strategies and environmental adaptations. Zebrafish have telomere dynamics that are comparable to humans and are emerging as a key model in which to unravel the systemic effects of telomere shortening on aging and interorgan communication. Here, we discuss zebrafish telomere biology, focusing on the organismal impact of telomere attrition beyond cellular senescence, with particular emphasis on how telomeric shortening in specific tissues can unleash widespread organ dysfunction and disease. This highlights a novel aspect of tissue communication, whereby telomere shortening in one organ can propagate through biological networks, influencing the aging process systemically. These discoveries position zebrafish as a valuable model for studying the complex interactions between telomeres, aging, and tissue cross talk, providing important insights with direct relevance to human health and longevity.

鱼类端粒长度在许多物种之间差异很大,这意味着不同的生活策略和环境适应。斑马鱼具有与人类相当的端粒动力学,并且正在成为揭示端粒缩短对衰老和器官间通信的系统性影响的关键模型。在这里,我们讨论斑马鱼的端粒生物学,重点关注端粒损耗对细胞衰老以外的生物体影响,特别强调特定组织中的端粒缩短如何引发广泛的器官功能障碍和疾病。这突出了组织通信的一个新方面,即一个器官的端粒缩短可以通过生物网络传播,从而系统性地影响衰老过程。这些发现将斑马鱼定位为研究端粒、衰老和组织串扰之间复杂相互作用的有价值的模型,提供了与人类健康和长寿直接相关的重要见解。
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引用次数: 0
Rediscovering and Unrediscovering Gregor Mendel: His Life, Times, and Intellectual Context. 重新发现和重新发现格里高尔-孟德尔:他的生平、时代和思想背景》(Rediscovering and Unrediscovering Gregor Mendel: His Life, Times, and Intellectual Context.
IF 6.9 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041812
Sander Gliboff

Two things about Mendel were "rediscovered" in 1900: His famous paper of 1865 and the story of his life and long neglect. Unlike the paper, which anyone could read in its entirety, the story came out only gradually, and many of its elements were misconstrued by Western European scientists. They pictured him as a pure scientist like themselves and were puzzled by or disinterested in his career as a clergyman, his intellectual community in far-off Moravia, and the importance to him of practical plant breeding. This paper recapitulates the process of mythmaking that followed the rediscovery, then shows how more recent historical research has been able to undo it and, in a sense, "unrediscover" Mendel.

有关孟德尔的两件事在 1900 年被 "重新发现":他在 1865 年发表的著名论文,以及他的生平和长期被忽视的故事。论文的全文任何人都能读到,而孟德尔的故事则不同,它只是逐渐才被披露出来,其中的许多内容都被西欧科学家误解了。他们把他想象成和自己一样的纯粹科学家,对他的牧师生涯、他在遥远的摩拉维亚的知识分子群体以及实用植物育种对他的重要性感到困惑或不感兴趣。本文回顾了孟德尔被重新发现后的神话塑造过程,然后展示了最近的历史研究如何能够消除神话,并在某种意义上 "重新发现 "孟德尔。
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引用次数: 0
Enteric Glia. 肠胶质细胞
IF 8.4 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041368
Meenakshi Rao, Brian D Gulbransen

Enteric glia are a unique type of peripheral neuroglia that accompany neurons in the enteric nervous system (ENS) of the digestive tract. The ENS displays integrative neural circuits that are capable of governing moment-to-moment gut functions independent of input from the central nervous system. Enteric glia are interspersed with neurons throughout these intrinsic gut neural circuits and are thought to fulfill complex roles directed at maintaining homeostasis in the neuronal microenvironment and at neuroeffector junctions in the gut. Changes to glial functions contribute to a wide range of gastrointestinal diseases, but the precise roles of enteric glia in gut physiology and pathophysiology are still under examination. This review summarizes current concepts regarding enteric glial development, diversity, and functions in health and disease.

肠胶质细胞是一种独特的外周神经胶质细胞,伴随着消化道肠神经系统(ENS)中的神经元。肠神经系统具有整合神经回路,能够独立于来自中枢神经系统的输入,管理肠道的每时每刻的功能。肠胶质细胞与神经元交错分布在这些固有的肠道神经回路中,被认为能发挥复杂的作用,维持神经元微环境和肠道神经效应器连接处的平衡。神经胶质细胞功能的改变可导致多种胃肠道疾病,但肠神经胶质细胞在肠道生理和病理生理学中的确切作用仍在研究之中。本综述总结了当前有关肠胶质细胞发育、多样性以及在健康和疾病中的功能的概念。
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引用次数: 0
Physical Forces in Regeneration of Cells and Tissues. 细胞和组织再生中的物理力
IF 6.9 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041527
Sindy K Y Tang, Wallace F Marshall

The ability to regenerate after the loss of a part is a hallmark of living systems and occurs at both the tissue and organ scales, but also within individual cells. Regeneration entails many processes that are physical and mechanical in nature, including the closure of wounds, the repositioning of material from one place to another, and the restoration of symmetry following perturbations. However, we currently know far more about the genetics and molecular signaling pathways involved in regeneration, and there is a need to investigate the role of physical forces in the process. Here, we will provide an overview of how physical forces may play a role in wound healing and regeneration, in which we compare and contrast regenerative processes at the tissue and cell scales.

生命系统的一个特征是在失去一个部分后能够再生,这种再生不仅发生在组织和器官范围内,也发生在单个细胞内。再生包含许多物理和机械性质的过程,包括伤口闭合、将物质从一个地方重新放置到另一个地方,以及在受到干扰后恢复对称。然而,我们目前对再生过程中涉及的遗传学和分子信号通路的了解还远远不够,因此有必要研究物理力在这一过程中的作用。在此,我们将概述物理力如何在伤口愈合和再生中发挥作用,并在其中比较和对比组织和细胞尺度上的再生过程。
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引用次数: 0
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Cold Spring Harbor perspectives in biology
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