首页 > 最新文献

Biochemical Society transactions最新文献

英文 中文
Calcium signaling in mitochondrial intermembrane space. 线粒体膜间隙中的钙信号传递。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-30 DOI: 10.1042/BST20240319
Shanikumar Goyani, Shatakshi Shukla, Pooja Jadiya, Dhanendra Tomar

The mitochondrial intermembrane space (IMS) is a highly protected compartment, second only to the matrix. It is a crucial bridge, coordinating mitochondrial activities with cellular processes such as metabolites, protein, lipid, and ion exchange. This regulation influences signaling pathways for metabolic activities and cellular homeostasis. The IMS harbors various proteins critical for initiating apoptotic cascades and regulating reactive oxygen species production by controlling the respiratory chain. Calcium (Ca2+), a key intracellular secondary messenger, enter the mitochondrial matrix via the IMS, regulating mitochondrial bioenergetics, ATP production, modulating cell death pathways. IMS acts as a regulatory site for Ca2+ entry due to the presence of different Ca2+ sensors such as MICUs, solute carriers (SLCs); ion exchangers (LETM1/SCaMCs); S100A1, mitochondrial glycerol-3-phosphate dehydrogenase, and EFHD1, each with unique Ca2+ binding motifs and spatial localizations. This review primarily emphasizes the role of these IMS-localized Ca2+ sensors concerning their spatial localization, mechanism, and molecular functions. Additionally, we discuss how these sensors contribute to the progression and pathogenesis of various human health conditions and diseases.

线粒体膜间隙(IMS)是一个高度受保护的腔室,仅次于基质。它是协调线粒体活动与代谢物、蛋白质、脂质和离子交换等细胞过程的重要桥梁。这种调节影响着代谢活动和细胞平衡的信号通路。IMS 含有多种蛋白质,对启动细胞凋亡级联和通过控制呼吸链调节活性氧的产生至关重要。钙(Ca2+)是细胞内重要的次级信使,通过 IMS 进入线粒体基质,调节线粒体生物能、ATP 的产生,并调节细胞死亡途径。由于存在不同的 Ca2+ 传感器,如 MICU、溶质运载体(SLC)、离子交换体(LETM1/SCaMC)、S100A1、线粒体甘油-3-磷酸脱氢酶和 EFHD1,每个传感器都有独特的 Ca2+ 结合基团和空间定位,因此 IMS 成为 Ca2+ 进入的调节场所。本综述主要强调这些 IMS 定位的 Ca2+ 传感器在空间定位、机制和分子功能方面的作用。此外,我们还讨论了这些传感器如何促进各种人类健康状况和疾病的发展和发病机制。
{"title":"Calcium signaling in mitochondrial intermembrane space.","authors":"Shanikumar Goyani, Shatakshi Shukla, Pooja Jadiya, Dhanendra Tomar","doi":"10.1042/BST20240319","DOIUrl":"10.1042/BST20240319","url":null,"abstract":"<p><p>The mitochondrial intermembrane space (IMS) is a highly protected compartment, second only to the matrix. It is a crucial bridge, coordinating mitochondrial activities with cellular processes such as metabolites, protein, lipid, and ion exchange. This regulation influences signaling pathways for metabolic activities and cellular homeostasis. The IMS harbors various proteins critical for initiating apoptotic cascades and regulating reactive oxygen species production by controlling the respiratory chain. Calcium (Ca2+), a key intracellular secondary messenger, enter the mitochondrial matrix via the IMS, regulating mitochondrial bioenergetics, ATP production, modulating cell death pathways. IMS acts as a regulatory site for Ca2+ entry due to the presence of different Ca2+ sensors such as MICUs, solute carriers (SLCs); ion exchangers (LETM1/SCaMCs); S100A1, mitochondrial glycerol-3-phosphate dehydrogenase, and EFHD1, each with unique Ca2+ binding motifs and spatial localizations. This review primarily emphasizes the role of these IMS-localized Ca2+ sensors concerning their spatial localization, mechanism, and molecular functions. Additionally, we discuss how these sensors contribute to the progression and pathogenesis of various human health conditions and diseases.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2215-2229"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
The role of prokaryotic argonautes in resistance to type II topoisomerases poison ciprofloxacin. 原核生物箭毒在抗 II 型拓扑异构酶毒环丙沙星中的作用。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-30 DOI: 10.1042/BST20240094
Alina Galivondzhyan, Dmitry Sutormin, Vladimir Panteleev, Andrey Kulbachinskiy, Konstantin Severinov

Argonaute proteins are programmable nucleases found in all domains of life. Eukaryotic argonautes (eAgos) participate in genetic regulation, antiviral response, and transposon silencing during RNA interference. Prokaryotic argonautes (pAgos) are much more diverse than eAgos and have been implicated in defense against invading genetic elements. Recently, it was shown that pAgos protect bacterial cells from a topoisomerase poison ciprofloxacin, raising a possibility that they may play a role in DNA replication and/or repair. Here, we discuss possible models of pAgo-mediated ciprofloxacin resistance. We propose that pAgos could (i) participate in chromosome decatenation as a backup to topoisomerases; (ii) participate in the processing of DNA repair intermediates formed after topoisomerase poisoning, or (iii) induce SOS response that generally affects DNA repair and antibiotic resistance. These hypotheses should guide future investigations of the involvement of pAgos in the emergence of resistance to ciprofloxacin and, possibly, other antibiotics.

Argonaute蛋白是一种可编程核酸酶,存在于生命的各个领域。真核 argonautes(eAgos)参与遗传调控、抗病毒反应和 RNA 干扰过程中的转座子沉默。原核生物的拟鸟嘌呤核苷酸(pAgos)比真核生物的拟鸟嘌呤核苷酸(eAgos)种类更多,并参与抵御遗传因子的入侵。最近的研究表明,pAgos 能保护细菌细胞免受拓扑异构酶毒物环丙沙星的伤害,这就提出了一种可能性,即它们可能在 DNA 复制和/或修复中发挥作用。在此,我们讨论了 pAgo 介导的环丙沙星耐药性的可能模式。我们认为 pAgos 可能:(i) 作为拓扑异构酶的后备力量参与染色体解连接;(ii) 参与处理拓扑异构酶中毒后形成的 DNA 修复中间产物;或 (iii) 诱导 SOS 反应,从而普遍影响 DNA 修复和抗生素耐药性。这些假说将指导未来对 pAgos 参与环丙沙星耐药性以及可能的其他抗生素耐药性产生过程的研究。
{"title":"The role of prokaryotic argonautes in resistance to type II topoisomerases poison ciprofloxacin.","authors":"Alina Galivondzhyan, Dmitry Sutormin, Vladimir Panteleev, Andrey Kulbachinskiy, Konstantin Severinov","doi":"10.1042/BST20240094","DOIUrl":"10.1042/BST20240094","url":null,"abstract":"<p><p>Argonaute proteins are programmable nucleases found in all domains of life. Eukaryotic argonautes (eAgos) participate in genetic regulation, antiviral response, and transposon silencing during RNA interference. Prokaryotic argonautes (pAgos) are much more diverse than eAgos and have been implicated in defense against invading genetic elements. Recently, it was shown that pAgos protect bacterial cells from a topoisomerase poison ciprofloxacin, raising a possibility that they may play a role in DNA replication and/or repair. Here, we discuss possible models of pAgo-mediated ciprofloxacin resistance. We propose that pAgos could (i) participate in chromosome decatenation as a backup to topoisomerases; (ii) participate in the processing of DNA repair intermediates formed after topoisomerase poisoning, or (iii) induce SOS response that generally affects DNA repair and antibiotic resistance. These hypotheses should guide future investigations of the involvement of pAgos in the emergence of resistance to ciprofloxacin and, possibly, other antibiotics.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2157-2166"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Biogenesis of omegasomes and autophagosomes in mammalian autophagy. 哺乳动物自噬过程中的奥米加体和自噬体的生物生成。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-30 DOI: 10.1042/BST20240015
Puck N Norell, Daniele Campisi, Jagan Mohan, Thomas Wollert

Autophagy is a highly conserved catabolic pathway that maintains cellular homeostasis by promoting the degradation of damaged or superfluous cytoplasmic material. A hallmark of autophagy is the generation of membrane cisternae that sequester autophagic cargo. Expansion of these structures allows cargo to be engulfed in a highly selective and exclusive manner. Cytotoxic stress or starvation induces the formation of autophagosomes that sequester bulk cytoplasm instead of selected cargo. This rather nonselective pathway is essential for maintaining vital cellular functions during adverse conditions and is thus a major stress response pathway. Both selective and nonselective autophagy rely on the same molecular machinery. However, due to the different nature of cargo to be sequestered, the involved molecular mechanisms are fundamentally different. Although intense research over the past decades has advanced our understanding of autophagy, fundamental questions remain to be addressed. This review will focus on molecular principles and open questions regarding the formation of omegasomes and phagophores in nonselective mammalian autophagy.

自噬是一种高度保守的分解代谢途径,它通过促进受损或多余细胞质物质的降解来维持细胞的平衡。自噬的一个特征是产生能封存自噬货物的膜贮液器。这些结构的扩张使货物能够以高度选择性和排他性的方式被吞噬。细胞毒性应激或饥饿会诱导自噬体的形成,这些自噬体封存的是大量细胞质,而不是经过选择的货物。这种非选择性途径对于在不利条件下维持重要的细胞功能至关重要,因此是一种主要的应激反应途径。选择性和非选择性自噬都依赖于相同的分子机制。然而,由于需要螯合的货物性质不同,所涉及的分子机制也根本不同。尽管过去几十年的深入研究推进了我们对自噬的了解,但基本问题仍有待解决。本综述将重点探讨哺乳动物非选择性自噬过程中形成奥米加体和吞噬泡的分子原理和未决问题。
{"title":"Biogenesis of omegasomes and autophagosomes in mammalian autophagy.","authors":"Puck N Norell, Daniele Campisi, Jagan Mohan, Thomas Wollert","doi":"10.1042/BST20240015","DOIUrl":"10.1042/BST20240015","url":null,"abstract":"<p><p>Autophagy is a highly conserved catabolic pathway that maintains cellular homeostasis by promoting the degradation of damaged or superfluous cytoplasmic material. A hallmark of autophagy is the generation of membrane cisternae that sequester autophagic cargo. Expansion of these structures allows cargo to be engulfed in a highly selective and exclusive manner. Cytotoxic stress or starvation induces the formation of autophagosomes that sequester bulk cytoplasm instead of selected cargo. This rather nonselective pathway is essential for maintaining vital cellular functions during adverse conditions and is thus a major stress response pathway. Both selective and nonselective autophagy rely on the same molecular machinery. However, due to the different nature of cargo to be sequestered, the involved molecular mechanisms are fundamentally different. Although intense research over the past decades has advanced our understanding of autophagy, fundamental questions remain to be addressed. This review will focus on molecular principles and open questions regarding the formation of omegasomes and phagophores in nonselective mammalian autophagy.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2145-2155"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Safeguarding genomic integrity in beta-cells: implications for beta-cell differentiation, growth, and dysfunction. 保护β细胞基因组的完整性:对β细胞分化、生长和功能障碍的影响
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-30 DOI: 10.1042/BST20231519
Sneha S Varghese, Alessandro Giovanni Hernandez-De La Peña, Sangeeta Dhawan

The maintenance of optimal glucose levels in the body requires a healthy reserve of the insulin producing pancreatic beta-cells. Depletion of this reserve due to beta-cell dysfunction and death results in development of diabetes. Recent findings highlight unresolved DNA damage as a key contributor to beta-cell defects in diabetes. Beta-cells face various stressors and metabolic challenges throughout life, rendering them susceptible to DNA breaks. The post-mitotic, long-lived phenotype of mature beta-cells further warrants robust maintenance of genomic integrity. Failure to resolve DNA damage during beta-cell development, therefore, can result in an unhealthy reserve of beta-cells and predispose to diabetes. Yet, the molecular mechanisms safeguarding beta-cell genomic integrity remain poorly understood. Here, we focus on the significance of DNA damage in beta-cell homeostasis and postulate how cellular expansion, epigenetic programming, and metabolic shifts during development may impact beta-cell genomic integrity and health. We discuss recent findings demonstrating a physiological role for DNA breaks in modulating transcriptional control in neurons, which share many developmental programs with beta-cells. Finally, we highlight key gaps in our understanding of beta-cell genomic integrity and discuss emerging areas of interest.

要维持体内最佳的血糖水平,就需要有一个健康的胰岛素分泌胰岛β细胞储备。由于β细胞功能障碍和死亡导致这种储备消耗殆尽,从而引发糖尿病。最近的研究结果表明,未解决的 DNA 损伤是导致糖尿病β细胞缺陷的关键因素。β细胞在整个生命过程中面临着各种压力和新陈代谢的挑战,使它们很容易发生DNA断裂。成熟β细胞的有丝分裂后长寿命表型进一步要求对基因组完整性进行强有力的维护。因此,如果不能在β细胞发育过程中解决DNA损伤问题,就会导致β细胞储备不健康,并容易诱发糖尿病。然而,人们对保护β细胞基因组完整性的分子机制仍然知之甚少。在这里,我们将重点关注 DNA 损伤在β细胞稳态中的意义,并推测细胞扩增、表观遗传编程和发育过程中的代谢转变可能会如何影响β细胞基因组的完整性和健康。我们讨论了最近的研究结果,这些结果表明DNA断裂在调节神经元转录控制中的生理作用,而神经元与β细胞共享许多发育程序。最后,我们强调了我们在了解β细胞基因组完整性方面存在的主要差距,并讨论了新出现的关注领域。
{"title":"Safeguarding genomic integrity in beta-cells: implications for beta-cell differentiation, growth, and dysfunction.","authors":"Sneha S Varghese, Alessandro Giovanni Hernandez-De La Peña, Sangeeta Dhawan","doi":"10.1042/BST20231519","DOIUrl":"10.1042/BST20231519","url":null,"abstract":"<p><p>The maintenance of optimal glucose levels in the body requires a healthy reserve of the insulin producing pancreatic beta-cells. Depletion of this reserve due to beta-cell dysfunction and death results in development of diabetes. Recent findings highlight unresolved DNA damage as a key contributor to beta-cell defects in diabetes. Beta-cells face various stressors and metabolic challenges throughout life, rendering them susceptible to DNA breaks. The post-mitotic, long-lived phenotype of mature beta-cells further warrants robust maintenance of genomic integrity. Failure to resolve DNA damage during beta-cell development, therefore, can result in an unhealthy reserve of beta-cells and predispose to diabetes. Yet, the molecular mechanisms safeguarding beta-cell genomic integrity remain poorly understood. Here, we focus on the significance of DNA damage in beta-cell homeostasis and postulate how cellular expansion, epigenetic programming, and metabolic shifts during development may impact beta-cell genomic integrity and health. We discuss recent findings demonstrating a physiological role for DNA breaks in modulating transcriptional control in neurons, which share many developmental programs with beta-cells. Finally, we highlight key gaps in our understanding of beta-cell genomic integrity and discuss emerging areas of interest.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2133-2144"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Mechanisms conferring bacterial cell wall variability and adaptivity. 赋予细菌细胞壁可变性和适应性的机制
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-30 DOI: 10.1042/BST20230027
Gabriel Torrens, Felipe Cava

The bacterial cell wall, a sophisticated and dynamic structure predominantly composed of peptidoglycan (PG), plays a pivotal role in bacterial survival and adaptation. Bacteria actively modify their cell walls by editing PG components in response to environmental challenges. Diverse variations in peptide composition, cross-linking patterns, and glycan strand structures empower bacteria to resist antibiotics, evade host immune detection, and adapt to dynamic environments. This review comprehensively summarizes the most common modifications reported to date and their associated adaptive role and further highlights how regulation of PG synthesis and turnover provides resilience to cell lysis.

细菌细胞壁是一种复杂而动态的结构,主要由肽聚糖(PG)组成,在细菌的生存和适应中发挥着关键作用。细菌通过编辑肽聚糖成分积极改造细胞壁,以应对环境挑战。肽组成、交联模式和糖链结构的多种变化使细菌有能力抵抗抗生素、躲避宿主免疫检测并适应动态环境。这篇综述全面总结了迄今为止报道的最常见修饰及其相关的适应作用,并进一步强调了对 PG 合成和周转的调控是如何提供抗细胞溶解的能力的。
{"title":"Mechanisms conferring bacterial cell wall variability and adaptivity.","authors":"Gabriel Torrens, Felipe Cava","doi":"10.1042/BST20230027","DOIUrl":"10.1042/BST20230027","url":null,"abstract":"<p><p>The bacterial cell wall, a sophisticated and dynamic structure predominantly composed of peptidoglycan (PG), plays a pivotal role in bacterial survival and adaptation. Bacteria actively modify their cell walls by editing PG components in response to environmental challenges. Diverse variations in peptide composition, cross-linking patterns, and glycan strand structures empower bacteria to resist antibiotics, evade host immune detection, and adapt to dynamic environments. This review comprehensively summarizes the most common modifications reported to date and their associated adaptive role and further highlights how regulation of PG synthesis and turnover provides resilience to cell lysis.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1981-1993"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 Dsc complex and its role in Golgi quality control. Dsc 复合物及其在高尔基体质量控制中的作用。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-30 DOI: 10.1042/BST20230375
Yannick Weyer, David Teis

Membrane proteins play crucial roles in cellular functions. However, processes such as the insertion of membrane proteins into the endoplasmic reticulum (ER), their folding into native structures, the assembly of multi-subunit membrane protein complexes, and their targeting from the ER to specific organelles are prone to errors and have a relatively high failure rate. To prevent the accumulation of defective or orphaned membrane proteins, quality control mechanisms assess folding, quantity, and localization of these proteins. This quality control is vital for preserving organelle integrity and maintaining cellular health. In this mini-review, we will focus on how selective membrane protein quality control at the Golgi apparatus, particularly through the defective for SREBP cleavage (Dsc) ubiquitin ligase complex, detects orphaned proteins and prevents their mis-localization to other organelles.

膜蛋白在细胞功能中发挥着至关重要的作用。然而,膜蛋白插入内质网(ER)、折叠成原生结构、组装多亚基膜蛋白复合物以及从ER定向到特定细胞器等过程容易出错,失败率相对较高。为了防止有缺陷或无主膜蛋白的积累,质量控制机制要对这些蛋白的折叠、数量和定位进行评估。这种质量控制对于保持细胞器完整性和维持细胞健康至关重要。在这篇微型综述中,我们将重点讨论高尔基体上的选择性膜蛋白质量控制,特别是如何通过 SREBP 裂解缺陷(Dsc)泛素连接酶复合物检测孤岛蛋白并防止它们错误定位到其他细胞器。
{"title":"The Dsc complex and its role in Golgi quality control.","authors":"Yannick Weyer, David Teis","doi":"10.1042/BST20230375","DOIUrl":"10.1042/BST20230375","url":null,"abstract":"<p><p>Membrane proteins play crucial roles in cellular functions. However, processes such as the insertion of membrane proteins into the endoplasmic reticulum (ER), their folding into native structures, the assembly of multi-subunit membrane protein complexes, and their targeting from the ER to specific organelles are prone to errors and have a relatively high failure rate. To prevent the accumulation of defective or orphaned membrane proteins, quality control mechanisms assess folding, quantity, and localization of these proteins. This quality control is vital for preserving organelle integrity and maintaining cellular health. In this mini-review, we will focus on how selective membrane protein quality control at the Golgi apparatus, particularly through the defective for SREBP cleavage (Dsc) ubiquitin ligase complex, detects orphaned proteins and prevents their mis-localization to other organelles.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2023-2034"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 dynamic regulatory network of phosphatidic acid metabolism: a spotlight on substrate cycling between phosphatidic acid and diacylglycerol. 磷脂酸代谢的动态调控网络:磷脂酸和二酰甘油之间的底物循环聚焦。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-30 DOI: 10.1042/BST20231511
Reika Tei

Mammalian cells utilize over 1000 different lipid species to maintain cell and organelle membrane properties, control cell signaling and processes, and store energy. Lipid synthesis and metabolism are mediated by highly interconnected and spatiotemporally regulated networks of lipid-metabolizing enzymes and supported by vesicle trafficking and lipid-transfer at membrane contact sites. However, the regulatory mechanisms that achieve lipid homeostasis are largely unknown. Phosphatidic acid (PA) serves as the central hub for phospholipid biosynthesis, acting as a key intermediate in both the Kennedy pathway and the CDP-DAG pathway. Additionally, PA is a potent signaling molecule involved in various cellular processes. This dual role of PA, both as a critical intermediate in lipid biosynthesis and as a significant signaling molecule, suggests that it is tightly regulated within cells. This minireview will summarize the functional diversity of PA molecules based on their acyl tail structures and subcellular localization, highlighting recent tools and findings that shed light on how the physical, chemical, and spatial properties of PA species contribute to their differential metabolic fates and functions. Dysfunctional effects of altered PA metabolism as well as the strategies cells employ to maintain PA regulation and homeostasis will also be discussed. Furthermore, this review will explore the differential regulation of PA metabolism across distinct subcellular membranes. Our recent proximity labeling studies highlight the possibility that substrate cycling between PA and DAG may be location-dependent and have functional significance in cell signaling and lipid homeostasis.

哺乳动物细胞利用 1000 多种不同的脂质来维持细胞和细胞器膜的特性、控制细胞信号传导和过程以及储存能量。脂质的合成和代谢由高度相互关联和时空调控的脂质代谢酶网络介导,并由膜接触点的囊泡贩运和脂质转移提供支持。然而,实现脂质平衡的调节机制在很大程度上还不为人知。磷脂酸(PA)是磷脂生物合成的中心枢纽,是肯尼迪途径和 CDP-DAG 途径的关键中间体。此外,PA 还是一种参与各种细胞过程的强效信号分子。PA 既是脂质生物合成的关键中间体,又是重要的信号分子,这种双重作用表明 PA 在细胞内受到严格调控。本小视图将根据 PA 分子的酰基尾部结构和亚细胞定位,总结 PA 分子的功能多样性,重点介绍最新的工具和发现,这些工具和发现揭示了 PA 物种的物理、化学和空间特性如何导致其不同的代谢命运和功能。本综述还将讨论 PA 代谢改变的功能障碍以及细胞为维持 PA 调节和平衡而采用的策略。此外,本综述还将探讨不同亚细胞膜对 PA 代谢的不同调控。我们最近的近距离标记研究强调了 PA 和 DAG 之间的底物循环可能是位置依赖性的,在细胞信号传导和脂质稳态中具有重要的功能意义。
{"title":"The dynamic regulatory network of phosphatidic acid metabolism: a spotlight on substrate cycling between phosphatidic acid and diacylglycerol.","authors":"Reika Tei","doi":"10.1042/BST20231511","DOIUrl":"10.1042/BST20231511","url":null,"abstract":"<p><p>Mammalian cells utilize over 1000 different lipid species to maintain cell and organelle membrane properties, control cell signaling and processes, and store energy. Lipid synthesis and metabolism are mediated by highly interconnected and spatiotemporally regulated networks of lipid-metabolizing enzymes and supported by vesicle trafficking and lipid-transfer at membrane contact sites. However, the regulatory mechanisms that achieve lipid homeostasis are largely unknown. Phosphatidic acid (PA) serves as the central hub for phospholipid biosynthesis, acting as a key intermediate in both the Kennedy pathway and the CDP-DAG pathway. Additionally, PA is a potent signaling molecule involved in various cellular processes. This dual role of PA, both as a critical intermediate in lipid biosynthesis and as a significant signaling molecule, suggests that it is tightly regulated within cells. This minireview will summarize the functional diversity of PA molecules based on their acyl tail structures and subcellular localization, highlighting recent tools and findings that shed light on how the physical, chemical, and spatial properties of PA species contribute to their differential metabolic fates and functions. Dysfunctional effects of altered PA metabolism as well as the strategies cells employ to maintain PA regulation and homeostasis will also be discussed. Furthermore, this review will explore the differential regulation of PA metabolism across distinct subcellular membranes. Our recent proximity labeling studies highlight the possibility that substrate cycling between PA and DAG may be location-dependent and have functional significance in cell signaling and lipid homeostasis.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2123-2132"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 mRNA dynamics underpinning translational control mechanisms of Drosophila melanogaster oogenesis. 黑腹果蝇卵子发生过程中翻译控制机制的 mRNA 动力学基础
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-30 DOI: 10.1042/BST20231293
Livia V Bayer, Samantha N Milano, Diana P Bratu

Advances in the study of mRNAs have yielded major new insights into post-transcriptional control of gene expression. Focus on the spatial regulation of mRNAs in highly polarized cells has demonstrated that mRNAs translocate through cells as mRNA:protein granules (mRNPs). These complex self-assemblies containing nuclear and cytoplasmic proteins are fundamental to the coordinated translation throughout cellular development. Initial studies on translational control necessitated fixed tissue, but the last 30 years have sparked innovative live-cell studies in several cell types to deliver a far more nuanced picture of how mRNA-protein dynamics exert translational control. In this review, we weave together the events that underpin mRNA processes and showcase the pivotal studies that revealed how a multitude of protein factors engage with a transcript. We highlight a mRNA's ability to act as a 'super scaffold' to facilitate molecular condensate formation and further moderate translational control. We focus on the Drosophila melanogaster germline due to the extensive post-transcriptional regulation occurring during early oogenesis. The complexity of the spatio-temporal expression of maternal transcripts in egg chambers allows for the exploration of a wide range of mechanisms that are crucial to the life cycle of mRNAs.

mRNA 研究的进展为基因表达的转录后控制提供了重要的新见解。对高度极化细胞中 mRNA 空间调控的关注表明,mRNA 在细胞中以 mRNA:蛋白质颗粒(mRNPs)的形式进行转运。这些包含核蛋白和细胞质蛋白的复杂自组装是整个细胞发育过程中协调翻译的基础。最初的翻译控制研究必须使用固定组织,但过去 30 年来,在多种细胞类型中开展了创新性活细胞研究,对 mRNA 蛋白动态如何发挥翻译控制作用有了更细致入微的了解。在这篇综述中,我们将 mRNA 过程的基本事件编织在一起,并展示了揭示多种蛋白因子如何与转录本相互作用的关键研究。我们强调了 mRNA 作为 "超级支架 "的能力,以促进分子凝聚物的形成并进一步缓和翻译控制。我们的研究重点是黑腹果蝇生殖系,因为在早期卵子发生过程中会出现大量转录后调控。卵室中母体转录本的时空表达非常复杂,因此可以探索对 mRNA 生命周期至关重要的各种机制。
{"title":"The mRNA dynamics underpinning translational control mechanisms of Drosophila melanogaster oogenesis.","authors":"Livia V Bayer, Samantha N Milano, Diana P Bratu","doi":"10.1042/BST20231293","DOIUrl":"10.1042/BST20231293","url":null,"abstract":"<p><p>Advances in the study of mRNAs have yielded major new insights into post-transcriptional control of gene expression. Focus on the spatial regulation of mRNAs in highly polarized cells has demonstrated that mRNAs translocate through cells as mRNA:protein granules (mRNPs). These complex self-assemblies containing nuclear and cytoplasmic proteins are fundamental to the coordinated translation throughout cellular development. Initial studies on translational control necessitated fixed tissue, but the last 30 years have sparked innovative live-cell studies in several cell types to deliver a far more nuanced picture of how mRNA-protein dynamics exert translational control. In this review, we weave together the events that underpin mRNA processes and showcase the pivotal studies that revealed how a multitude of protein factors engage with a transcript. We highlight a mRNA's ability to act as a 'super scaffold' to facilitate molecular condensate formation and further moderate translational control. We focus on the Drosophila melanogaster germline due to the extensive post-transcriptional regulation occurring during early oogenesis. The complexity of the spatio-temporal expression of maternal transcripts in egg chambers allows for the exploration of a wide range of mechanisms that are crucial to the life cycle of mRNAs.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2087-2099"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Phase separation and viral factories: unveiling the physical processes supporting RNA packaging in dsRNA viruses. 相分离和病毒工厂:揭示支持 dsRNA 病毒中 RNA 包装的物理过程。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-30 DOI: 10.1042/BST20231304
Cyril J Haller, Julia Acker, A Emilia Arguello, Alexander Borodavka

Understanding of the physicochemical properties and functions of biomolecular condensates has rapidly advanced over the past decade. More recently, many RNA viruses have been shown to form cytoplasmic replication factories, or viroplasms, via phase separation of their components, akin to numerous cellular membraneless organelles. Notably, diverse viruses from the Reoviridae family containing 10-12 segmented double-stranded RNA genomes induce the formation of viroplasms in infected cells. Little is known about the inner workings of these membraneless cytoplasmic inclusions and how they may support stoichiometric RNA assembly in viruses with segmented RNA genomes, raising questions about the roles of phase separation in coordinating viral genome packaging. Here, we discuss how the molecular composition of viroplasms determines their properties, highlighting the interplay between RNA structure, RNA remodelling, and condensate self-organisation. Advancements in RNA structural probing and theoretical modelling of condensates can reveal the mechanisms through which these ribonucleoprotein complexes support the selective enrichment and stoichiometric assembly of distinct viral RNAs.

在过去的十年中,人们对生物分子凝聚体的理化性质和功能的认识有了飞速的发展。最近的研究表明,许多 RNA 病毒通过其成分的相分离形成细胞质复制工厂或病毒体,类似于许多细胞膜无细胞器。值得注意的是,Reoviridae 家族的多种病毒含有 10-12 段双链 RNA 基因组,能诱导受感染细胞形成病毒浆。人们对这些无膜细胞质包涵体的内部运作以及它们如何支持具有分段 RNA 基因组的病毒中的 RNA 按比例组装知之甚少,这就提出了关于相分离在协调病毒基因组包装中的作用的问题。在这里,我们将讨论病毒增殖体的分子组成如何决定它们的特性,突出 RNA 结构、RNA 重塑和凝聚体自组织之间的相互作用。RNA 结构探测和凝集物理论建模的进步可以揭示这些核糖核蛋白复合物支持不同病毒 RNA 选择性富集和按比例组装的机制。
{"title":"Phase separation and viral factories: unveiling the physical processes supporting RNA packaging in dsRNA viruses.","authors":"Cyril J Haller, Julia Acker, A Emilia Arguello, Alexander Borodavka","doi":"10.1042/BST20231304","DOIUrl":"10.1042/BST20231304","url":null,"abstract":"<p><p>Understanding of the physicochemical properties and functions of biomolecular condensates has rapidly advanced over the past decade. More recently, many RNA viruses have been shown to form cytoplasmic replication factories, or viroplasms, via phase separation of their components, akin to numerous cellular membraneless organelles. Notably, diverse viruses from the Reoviridae family containing 10-12 segmented double-stranded RNA genomes induce the formation of viroplasms in infected cells. Little is known about the inner workings of these membraneless cytoplasmic inclusions and how they may support stoichiometric RNA assembly in viruses with segmented RNA genomes, raising questions about the roles of phase separation in coordinating viral genome packaging. Here, we discuss how the molecular composition of viroplasms determines their properties, highlighting the interplay between RNA structure, RNA remodelling, and condensate self-organisation. Advancements in RNA structural probing and theoretical modelling of condensates can reveal the mechanisms through which these ribonucleoprotein complexes support the selective enrichment and stoichiometric assembly of distinct viral RNAs.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2101-2112"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Voltage-clamp fluorometry for advancing mechanistic understanding of ion channel mechanisms with a focus on acid-sensing ion channels. 电压钳荧光测定法促进对离子通道机制的机理认识,重点关注酸感应离子通道。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-30 DOI: 10.1042/BST20240165
Eleonora Centonze, Stephan Kellenberger

Voltage-clamp fluorometry (VCF) has revolutionized the study of ion channels by combining electrophysiology with fluorescence spectroscopy. VCF allows ion channel researchers to link dynamic structural changes, measured in real time, to function. Acid-sensing ion channels (ASICs) are Na+-permeable non-voltage-gated ion channels of the central and peripheral nervous system. They function as pH sensors, triggering neuronal excitation when pH decreases. Animal studies have shown the importance of ASICs for pain and fear sensation, learning, and neurodegeneration following ischaemic stroke. This review explores the technical bases and various developments of VCF, including fluorescence resonance energy transfer and the use of unnatural fluorescent amino acids. We provide an overview of VCF applications with a focus on ASICs, detailing how VCF has unveiled proton-induced conformational changes in key regions such as the acid pocket, wrist, and pore, crucial for understanding transitions between closed, open, and desensitized states.

电压钳荧光测定法(VCF)将电生理学与荧光光谱学相结合,彻底改变了离子通道研究。VCF 使离子通道研究人员能够将实时测量到的动态结构变化与功能联系起来。酸感应离子通道(ASIC)是中枢和外周神经系统中的Na+渗透性非电压门控离子通道。它们具有 pH 值传感器的功能,当 pH 值降低时会触发神经元兴奋。动物研究表明,ASIC 对缺血性中风后的疼痛和恐惧感觉、学习和神经变性具有重要作用。本综述探讨了 VCF 的技术基础和各种发展,包括荧光共振能量转移和非天然荧光氨基酸的使用。我们概述了 VCF 在 ASIC 上的应用,详细介绍了 VCF 如何揭示酸袋、腕和孔等关键区域中质子诱导的构象变化,这对于理解封闭、开放和脱敏状态之间的转变至关重要。
{"title":"Voltage-clamp fluorometry for advancing mechanistic understanding of ion channel mechanisms with a focus on acid-sensing ion channels.","authors":"Eleonora Centonze, Stephan Kellenberger","doi":"10.1042/BST20240165","DOIUrl":"10.1042/BST20240165","url":null,"abstract":"<p><p>Voltage-clamp fluorometry (VCF) has revolutionized the study of ion channels by combining electrophysiology with fluorescence spectroscopy. VCF allows ion channel researchers to link dynamic structural changes, measured in real time, to function. Acid-sensing ion channels (ASICs) are Na+-permeable non-voltage-gated ion channels of the central and peripheral nervous system. They function as pH sensors, triggering neuronal excitation when pH decreases. Animal studies have shown the importance of ASICs for pain and fear sensation, learning, and neurodegeneration following ischaemic stroke. This review explores the technical bases and various developments of VCF, including fluorescence resonance energy transfer and the use of unnatural fluorescent amino acids. We provide an overview of VCF applications with a focus on ASICs, detailing how VCF has unveiled proton-induced conformational changes in key regions such as the acid pocket, wrist, and pore, crucial for understanding transitions between closed, open, and desensitized states.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2167-2177"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
期刊
Biochemical Society transactions
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1