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How has the evolution of our understanding of the compartmentalization of sphingolipid biosynthesis over the past 30 years altered our view of the evolution of the pathway? 在过去 30 年中,我们对鞘脂生物合成的分区的理解发生了怎样的变化,从而改变了我们对该途径进化的看法?
4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-06-24 DOI: 10.1016/bs.ctm.2024.06.001
Assaf Biran, Tamir Dingjan, Anthony H Futerman

Sphingolipids are unique among cellular lipids inasmuch as their biosynthesis is compartmentalized between the endoplasmic reticulum (ER) and the Golgi apparatus. This compartmentalization was first recognized about thirty years ago, and the current review not only updates studies on the compartmentalization of sphingolipid biosynthesis, but also discusses the ramifications of this feature for our understanding of how the pathway could have evolved. Thus, we augment some of our recent studies by inclusion of two further molecular pathways that need to be considered when analyzing the evolutionary requirements for generation of sphingolipids, namely contact sites between the ER and the Golgi apparatus, and the mechanism(s) of vesicular transport between these two organelles. Along with evolution of the individual enzymes of the pathway, their subcellular localization, and the supply of essential metabolites via the anteome, it becomes apparent that current models to describe evolution of the sphingolipid biosynthetic pathway may need substantial refinement.

鞘磷脂在细胞脂质中是独一无二的,因为它们的生物合成是在内质网(ER)和高尔基体之间分区进行的。这种分隔在大约三十年前首次被认识到,目前的综述不仅更新了有关鞘脂生物合成分隔的研究,还讨论了这一特征对我们理解该途径如何演变的影响。因此,我们对最近的一些研究进行了补充,纳入了在分析鞘脂生成的进化要求时需要考虑的另外两个分子途径,即 ER 和高尔基体之间的接触点以及这两个细胞器之间的囊泡运输机制。随着鞘磷脂生物合成途径中各个酶的进化、它们的亚细胞定位以及通过前体提供必需代谢物,目前描述鞘磷脂生物合成途径进化的模型显然需要大量改进。
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引用次数: 0
Lysosomal membrane contact sites: Integrative hubs for cellular communication and homeostasis. 溶酶体膜接触点:细胞通讯和平衡的整合枢纽。
4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 Epub Date: 2024-07-17 DOI: 10.1016/bs.ctm.2024.07.001
Sumit Bandyopadhyay, Daniel Adebayo, Eseiwi Obaseki, Hanaa Hariri

Lysosomes are more than just cellular recycling bins; they play a crucial role in regulating key cellular functions. Proper lysosomal function is essential for growth pathway regulation, cell proliferation, and metabolic homeostasis. Impaired lysosomal function is associated with lipid storage disorders and neurodegenerative diseases. Lysosomes form extensive and dynamic close contacts with the membranes of other organelles, including the endoplasmic reticulum, mitochondria, peroxisomes, and lipid droplets. These membrane contacts sites (MCSs) are vital for many lysosomal functions. In this chapter, we will explore lysosomal MCSs focusing on the machinery that mediates these contacts, how they are regulated, and their functional implications on physiology and pathology.

溶酶体不仅仅是细胞的回收箱,它们在调节关键的细胞功能方面发挥着至关重要的作用。溶酶体的正常功能对生长途径调节、细胞增殖和代谢平衡至关重要。溶酶体功能受损与脂质储存障碍和神经退行性疾病有关。溶酶体与其他细胞器(包括内质网、线粒体、过氧物酶体和脂滴)的膜形成广泛而动态的密切接触。这些膜接触点(MCS)对溶酶体的许多功能至关重要。在本章中,我们将探讨溶酶体膜接触点,重点是介导这些接触点的机制、如何调节这些接触点以及它们对生理和病理的功能影响。
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引用次数: 0
Extracellular vesicles in parasitic protozoa: Impact of Leishmania exosomes containing Leishmania RNA virus 1 (LRV1) on Leishmania infectivity and disease progression. 寄生原生动物的胞外囊泡:含有利什曼病RNA病毒1(LRV1)的利什曼病外泌体对利什曼病感染性和疾病进展的影响。
4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 Epub Date: 2024-07-16 DOI: 10.1016/bs.ctm.2024.07.002
Marine Leroux, Andrea Lafleur, Carlos Villalba-Guerrero, Myriam Beaulieu, Andressa Brito Lira, Martin Olivier

This chapter focuses on the interplay between Leishmania parasites and their host, particularly on Leishmania RNA virus (LRVs) and extracellular vesicles (EVs) in modulating host-pathogen interactions. Leishmania EVs have been shown to facilitate gene transfer, including drug-resistance genes, enhancing the parasites' survival and resistance to antileishmanial therapeutics. These EVs also play a significant role in host immune modulation by altering cytokine production in macrophages and promoting an anti-inflammatory environment that favours parasitic persistence. The presence of virulence factors such as GP63 within these EVs further underscores their role in the parasite's immunopathogenesis. Over the last few decades, LRVs have been established as drivers of the severity and persistence of leishmaniasis by exacerbating inflammatory responses and potentially influencing treatment outcomes. This chapter discusses the evolutionary origins and classification of these viruses, and explores their role in parasitic pathogenicity, highlighting their ubiquity across protozoan parasites and their impact on disease progression.

本章重点探讨利什曼病寄生虫与其宿主之间的相互作用,特别是利什曼病RNA病毒(LRVs)和胞外囊泡(EVs)在调节宿主与病原体相互作用方面的作用。研究表明,利什曼原虫的细胞外囊泡能促进基因转移,包括耐药基因的转移,从而提高寄生虫的存活率和对抗利什曼病治疗药物的耐药性。这些 EVs 还通过改变巨噬细胞中细胞因子的产生和促进有利于寄生虫存活的抗炎环境,在宿主免疫调节中发挥重要作用。这些 EVs 中存在 GP63 等毒力因子,进一步突出了它们在寄生虫免疫发病机制中的作用。过去几十年来,LRVs 通过加剧炎症反应并可能影响治疗效果,已被证实是利什曼病严重性和持续性的驱动因素。本章讨论了这些病毒的进化起源和分类,并探讨了它们在寄生虫致病性中的作用,强调了它们在原生动物寄生虫中的普遍性及其对疾病进展的影响。
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引用次数: 0
Involvement of extracellular vesicles in the interaction of hosts and Toxoplasma gondii. 细胞外囊泡参与宿主与弓形虫的相互作用。
4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 Epub Date: 2024-08-29 DOI: 10.1016/bs.ctm.2024.06.003
Letícia Pereira Pedrini Vicentini, Vera Lucia Pereira-Chioccola, Blima Fux

Toxoplasma gondii, the causative agent of toxoplasmosis, is widely distributed. This protozoan parasite is one of the best adapted, being able to infect innumerous species of animals and different types of cells. This chapter reviews current literature on extracellular vesicles secreted by T. gondii and by its hosts. The topics describe the life cycle and transmission (1); toxoplasmosis epidemiology (2); laboratorial diagnosis approach (3); The T. gondii interaction with extracellular vesicles and miRNAs (4); and the perspectives on T. gondii infection. Each topic emphases the host immune responses to the parasite antigens and the interaction with the extracellular vesicles and miRNAs.

弓形虫是弓形虫病的病原体,分布广泛。这种原生动物寄生虫是适应性最强的寄生虫之一,能够感染无数种动物和不同类型的细胞。本章回顾了目前有关淋球菌及其宿主分泌的细胞外囊泡的文献。这些主题描述了弓形虫的生命周期和传播(1)、弓形虫流行病学(2)、实验室诊断方法(3)、弓形虫与细胞外囊泡和 miRNA 的相互作用(4)以及对弓形虫感染的展望。每个主题都强调宿主对寄生虫抗原的免疫反应以及与细胞外囊泡和 miRNA 的相互作用。
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引用次数: 0
Impact of coat protein on evolution of ilarviruses. 衣壳蛋白对伊拉病毒进化的影响。
4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 Epub Date: 2024-06-04 DOI: 10.1016/bs.ctm.2024.05.002
Ali Çelik, Adyatma Irawan Santosa

The genomic sequences attributed to the coat protein play a pivotal role in the evolutionary trajectory of plant viruses. The coat protein region, particularly scrutinized in the genus of Ilarvirus phylogroups, actively shapes the regional and host-specific dispersion. Within this chapter, assorted insights pertaining to the roles undertaken by coat proteins of frequently encountered Ilarviruses in their evolutionary processes are consolidated. Nonetheless, it is discerned that the availability of genomic data for RNA1 and RNA2 remains markedly limited, impeding the provision of lucid elucidations in this domain. Hence, to comprehensively delineate the evolution of Ilarviruses, a requisite exists for supplementary nucleotide sequence data, with a particular emphasis on taxa that have received lesser attention in research endeavors.

衣壳蛋白的基因组序列在植物病毒的进化轨迹中起着举足轻重的作用。衣壳蛋白区域,尤其是在伊拉病毒属系统中被仔细研究的区域,积极地影响着区域和宿主特异性的传播。在本章中,我们将对经常遇到的伊拉病毒的衣壳蛋白在其进化过程中所起的作用进行深入分析。然而,我们发现 RNA1 和 RNA2 的基因组数据仍然非常有限,阻碍了对这一领域的清晰阐释。因此,要全面描述伊拉病毒的进化过程,就需要补充核苷酸序列数据,尤其要重视在研究工作中关注较少的类群。
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引用次数: 0
Extracellular vesicles in neurodegenerative, mental, and other neurological disorders: Perspectives into mechanisms, biomarker potential, and therapeutic implications. 神经退行性疾病、精神疾病和其他神经系统疾病中的细胞外囊泡:对机制、生物标志物潜力和治疗意义的展望。
4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 Epub Date: 2024-08-31 DOI: 10.1016/bs.ctm.2024.06.002
Gustavo Satoru Kajitani, Gabriela Xavier, Beatriz Enguidanos Villena-Rueda, Bruno Takao Real Karia, Marcos Leite Santoro

Extracellular vesicles (EVs) are produced, secreted, and targeted by most human cells, including cells that compose nervous system tissues. EVs carry several types of biomolecules, such as lipids, proteins and microRNA, and can function as signaling agents in physiological and pathological processes. In this chapter, we will focus on EVs and their cargo secreted by brain cells, especially neurons and glia, and how these aspects are affected in pathological conditions. The chapter covers neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, as well as several psychiatric disorders, namely schizophrenia, autism spectrum disorder and major depressive disorder. This chapter also addresses other types of neurological dysfunctions, epilepsy and traumatic brain injury. EVs can cross the blood brain barrier, and thus brain EVs may be detected in more accessible peripheral tissue, such as circulating blood. Alterations in EV composition and contents can therefore impart valuable clues into the molecular etiology of these disorders, and serve biomarkers regarding disease prevalence, progression and treatment. EVs can also be used to carry drugs and biomolecules into brain tissue, considered as a promising drug delivery agent for neurological diseases. Therefore, although this area of research is still in its early development, it offers great potential in further elucidating and in treating neurological disorders.

大多数人类细胞,包括组成神经系统组织的细胞,都会产生、分泌细胞外囊泡 (EV),并以其为靶标。EVs携带多种类型的生物大分子,如脂类、蛋白质和微RNA,可在生理和病理过程中发挥信号传递作用。在本章中,我们将重点讨论脑细胞(尤其是神经元和神经胶质细胞)分泌的EV及其货物,以及在病理情况下这些方面如何受到影响。本章涵盖神经退行性疾病,包括阿尔茨海默病、帕金森病和肌萎缩侧索硬化症,以及几种精神疾病,即精神分裂症、自闭症谱系障碍和重度抑郁症。本章还讨论了其他类型的神经功能障碍、癫痫和脑外伤。EVs 可以穿过血脑屏障,因此可以在循环血液等更容易进入的外周组织中检测到脑 EVs。因此,EV 成分和含量的改变可为这些疾病的分子病因学提供有价值的线索,并可作为有关疾病流行、进展和治疗的生物标志物。EVs 还可用于携带药物和生物分子进入脑组织,被认为是治疗神经系统疾病的一种很有前景的药物输送剂。因此,尽管这一研究领域仍处于早期发展阶段,但它在进一步阐明和治疗神经系统疾病方面具有巨大潜力。
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引用次数: 0
Extracellular vesicles and sleep deprivation. 细胞外囊泡和睡眠不足
4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 Epub Date: 2024-09-14 DOI: 10.1016/bs.ctm.2024.06.011
Ronni Rômulo Novaes E Brito

Sleep is vital in preserving mental and physical well-being by aiding bodily recovery, strengthening the immune system, and regulating hormones. It enhances memory, concentration, and mood regulation, reducing stress and anxiety. Sleep deprivation, a common phenomenon affecting approximately 20% of adults, decreases performance, alertness, and health integrity. Furthermore, it triggers physiological changes, including increased stress hormone levels, leading to various disorders such as hyperglycemia and hypertension. Recent research explores the role of extracellular vesicles (EVs) in sleep-related conditions. EVs, released by cells, play vital roles in intercellular communication and biomarker potential. Studies indicate that sleep deprivation influences EV release, impacting cancer progression, endothelial inflammation, and thrombosis risk. Understanding these mechanisms offers insights into therapeutic interventions. Thus, multidisciplinary approaches are crucial to unraveling the complex interactions between sleep, EVs, and health, providing direction for effective prevention and treatment approaches for sleep disorders and related conditions.

睡眠有助于身体恢复、增强免疫系统和调节荷尔蒙,对保持身心健康至关重要。它能增强记忆力、集中力和情绪调节能力,减轻压力和焦虑。睡眠不足是一种常见现象,影响着约 20% 的成年人,会降低工作表现、警觉性和健康完整性。此外,睡眠不足还会引发生理变化,包括应激激素水平升高,导致高血糖和高血压等各种疾病。最新研究探讨了细胞外囊泡 (EVs) 在与睡眠有关的疾病中的作用。细胞外囊泡由细胞释放,在细胞间通信和生物标记潜能方面发挥着重要作用。研究表明,睡眠不足会影响EV的释放,从而影响癌症的发展、内皮炎症和血栓风险。了解这些机制有助于深入了解治疗干预措施。因此,多学科方法对于揭示睡眠、EVs 和健康之间复杂的相互作用至关重要,为睡眠障碍和相关疾病的有效预防和治疗方法提供了方向。
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引用次数: 0
Biogenesis of EVs in Trypanosomatids. 锥虫体内 EVs 的生物生成。
4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 Epub Date: 2024-09-07 DOI: 10.1016/bs.ctm.2024.06.004
Nadjania Saraiva De Lira Silva, Sergio Schenkman

Trypanosomes are protozoan parasites responsible for human diseases such as Chagas disease, African trypanosomiasis, and leishmaniasis. These organisms' growth in various environments and exhibit multiple morphological stages, while adapting their surface components. They acquire and release materials extensively to get nutrients and manage interactions with the extracellular environment. They acquire and utilize proteins, lipids, and carbohydrates for growth via using membrane transport and endocytosis. Endocytosis takes place through distinct membrane areas known as the flagellar pocket and cytostome, depending on the parasite species and its developmental stage. Some forms establish a complex endocytic system to either store or break down the absorbed materials. In contrast, membrane transport facilitates the uptake of small molecules like amino acids, carbohydrates, and iron via particular receptors on the plasma membrane. Concurrently, these parasites secrete various molecules such as proteins, enzymes, nucleic acids, and glycoconjugates either in soluble form or enclosed in extracellular vesicles, which significantly contribute to their parasitic behavior. These activities require exocytosis through a secretory pathway in certain membrane domains such as the flagellum, flagellar pocket, and plasma membrane, which are controlled at various developmental stages. The main features of the endocytic and exocytic mechanisms, as well as the organelles involved, are discussed in this chapter along with their connection to the formation of exosomes and extracellular vesicles in the Tritryp species.

锥虫是原生动物寄生虫,是恰加斯病、非洲锥虫病和利什曼病等人类疾病的元凶。这些生物在各种环境中生长,表现出多个形态阶段,同时调整其表面成分。它们广泛获取和释放物质,以获取营养并处理与细胞外环境的相互作用。它们通过膜转运和内吞作用获取和利用蛋白质、脂类和碳水化合物以促进生长。内吞作用通过不同的膜区域进行,这些区域被称为鞭毛袋和细胞寄生体,具体取决于寄生虫的种类及其发育阶段。有些寄生虫会建立复杂的内吞系统来储存或分解吸收的物质。与此相反,膜运输可通过质膜上的特定受体吸收氨基酸、碳水化合物和铁等小分子物质。与此同时,这些寄生虫还以可溶的形式或包裹在细胞外囊泡中分泌各种分子,如蛋白质、酶、核酸和糖结合物,这对它们的寄生行为有很大的帮助。这些活动需要通过某些膜域(如鞭毛、鞭毛袋和质膜)的分泌途径进行外排,而这些膜域在不同的发育阶段受到控制。本章将讨论内吞和外吞机制的主要特征以及所涉及的细胞器,并讨论它们与Tritryp物种中外泌体和胞外囊泡的形成之间的联系。
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引用次数: 0
Preface. 序言
4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1016/S1063-5823(24)00031-0
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引用次数: 0
Extracellular vesicles: Methods for purification and characterization. 细胞外囊泡:纯化和表征方法。
4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 Epub Date: 2024-08-23 DOI: 10.1016/bs.ctm.2024.06.005
Paula Meneghetti, Mariana Ottaiano Gonçalves, Gabriela Villa Marin, Juliana Fortes Di Iorio, Náthani Gabrielly Silva Negreiros, Ana Claudia Torrecilhas

Extracellular vesicles (EVs) are membrane-bound particles released by cells that play a significant role in intercellular communication. They can be obtained from a variety of sources, including conditioned culture medium, blood and urine. In this chapter we detail the methods for EV isolation and characterization. Isolating and characterizing EVs is essential for understanding their functions in physiological and pathological processes. Advances in isolation and characterization techniques provide opportunities for deeper research into EV biology and its potential applications in diagnostics and therapeutics.

细胞外囊泡(EVs)是细胞释放的膜结合颗粒,在细胞间通信中发挥着重要作用。它们可从多种来源获得,包括条件培养基、血液和尿液。本章将详细介绍 EVs 的分离和表征方法。分离和表征 EV 对于了解它们在生理和病理过程中的功能至关重要。分离和表征技术的进步为深入研究 EV 生物学及其在诊断和治疗中的潜在应用提供了机会。
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引用次数: 0
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Current topics in membranes
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