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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
Biochemical Society transactions Pub Date : 2024-10-30 DOI: 10.1042/BST20231519
Sneha S Varghese, Alessandro Giovanni Hernandez-De La Peña, Sangeeta Dhawan
{"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
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
Biochemical Society transactions Pub Date : 2024-10-30 DOI: 10.1042/BST20240015
Puck N Norell, Daniele Campisi, Jagan Mohan, Thomas Wollert
{"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
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
Biochemical Society transactions Pub Date : 2024-10-30 DOI: 10.1042/BST20231511
Reika Tei
{"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 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
Biochemical Society transactions Pub Date : 2024-10-30 DOI: 10.1042/BST20230375
Yannick Weyer, David Teis
{"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
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
Biochemical Society transactions Pub Date : 2024-10-30 DOI: 10.1042/BST20230027
Gabriel Torrens, Felipe Cava
{"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 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
Biochemical Society transactions Pub Date : 2024-10-30 DOI: 10.1042/BST20231293
Livia V Bayer, Samantha N Milano, Diana P Bratu
{"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
Biochemical Society transactions Pub Date : 2024-10-30 DOI: 10.1042/BST20231304
Cyril J Haller, Julia Acker, A Emilia Arguello, Alexander Borodavka
{"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
Biochemical Society transactions Pub Date : 2024-10-30 DOI: 10.1042/BST20240165
Eleonora Centonze, Stephan Kellenberger
{"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
Hetero-oligomeric interaction as a new regulatory mechanism for protein arginine methyltransferases. 异构体相互作用是蛋白质精氨酸甲基转移酶的一种新调控机制。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-10-30 DOI: 10.1042/BST20240242
Angela A Bae, Y George Zheng
{"title":"Hetero-oligomeric interaction as a new regulatory mechanism for protein arginine methyltransferases.","authors":"Angela A Bae, Y George Zheng","doi":"10.1042/BST20240242","DOIUrl":"10.1042/BST20240242","url":null,"abstract":"<p><p>Protein arginine methylation is a versatile post-translational protein modification that has notable cellular roles such as transcriptional activation or repression, cell signaling, cell cycle regulation, and DNA damage response. However, in spite of their extensive significance in the biological system, there is still a significant gap in understanding of the entire function of the protein arginine methyltransferases (PRMTs). It has been well-established that PRMTs form homo-oligomeric complexes to be catalytically active, but in recent years, several studies have showcased evidence that different members of PRMTs can have cross-talk with one another to form hetero-oligomeric complexes. Additionally, these heteromeric complexes have distinct roles separate from their homomeric counterparts. Here, we review and highlight the discovery of the heterodimerization of PRMTs and discuss the biological implications of these hetero-oligomeric interactions.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2193-2201"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340435","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
Coordinating BNIP3/NIX-mediated mitophagy in space and time. 在空间和时间上协调 BNIP3/NIX 介导的有丝分裂
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-10-30 DOI: 10.1042/BST20221364
Natalie M Niemi, Jonathan R Friedman
{"title":"Coordinating BNIP3/NIX-mediated mitophagy in space and time.","authors":"Natalie M Niemi, Jonathan R Friedman","doi":"10.1042/BST20221364","DOIUrl":"10.1042/BST20221364","url":null,"abstract":"<p><p>Mitochondria maintain organellar homeostasis through multiple quality control pathways, including the clearance of defective or unwanted mitochondria by selective autophagy. This removal of mitochondria, mitophagy, is controlled in large part by the outer mitochondrial membrane mitophagy receptors BNIP3 and NIX. While it has long been appreciated that BNIP3 and NIX mediate mitophagy by controlling the recruitment of autophagic machinery to the mitochondrial surface, the requirement for the carefully controlled spatiotemporal regulation of receptor-mediated mitophagy has only recently come to light. Several new factors that regulate the BNIP3/NIX-mediated mitophagy pathway have emerged, and various loss-of-function cell and animal models have revealed the dire consequences of their dysregulation. In this mini-review, we discuss new insights into the mechanisms and roles of the regulation of BNIP3 and NIX and highlight questions that have emerged from the identification of these new regulators.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1969-1979"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387604","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
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