{"title":"Insights into the synchronization between DNA replication and parental histone recycling.","authors":"Xiaorong Tang, Yuan Yao, Gang Li, Haiyun Gan","doi":"10.1042/BST20253014","DOIUrl":"10.1042/BST20253014","url":null,"abstract":"<p><p>Accurate parental histone recycling is of pivotal importance in epigenetic inheritance. Its proper functioning hinges on the precise co-ordination among a diverse array of proteins. During DNA replication, any aberration in the distribution of parental histones can potentially result in the loss of epigenetic memory. To date, although several key proteins involved in parental histone recycling have been identified, the detailed molecular mechanisms underlying their functions remain elusive. This mini-review focuses on summarizing the synchrony between DNA replication and parental histone recycling, along with the key participants in parental histone recycling. In the end, we provide an overview of the inherent connection between parental histone recycling and epigenetic inheritance, shedding light on the fundamental role of histone recycling in maintaining epigenetic information across cell divisions.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"547-554"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085611","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}
Ankanahalli N Nanjaraj Urs, Lucas Kim, Hani S Zaher
{"title":"Insights into the role of collided ribosomes during the activation of the integrated stress response.","authors":"Ankanahalli N Nanjaraj Urs, Lucas Kim, Hani S Zaher","doi":"10.1042/BST20253034","DOIUrl":"10.1042/BST20253034","url":null,"abstract":"<p><p>Mechanisms that regulate and reprogram gene expression are particularly important under stress conditions. The integrated stress response (ISR) signaling pathway is one such pro-survival and adaptive mechanism conserved in eukaryotes. The ISR is characterized by the activation of protein kinases that phosphorylate the eukaryotic initiation factor 2α (eIF2α) in response to several stress conditions, including nutrient deprivation, viral infection, and protein misfolding. Phosphorylation of eIF2α results in global inhibition of translation, while promoting the translation of a few pro-survival genes. Here, we focus on the mechanism of activation of the eIF2α kinase general control nonderepressible 2 (Gcn2). The protein was initially discovered in yeast more than four decades ago, and it was proposed to respond to amino acid starvation through the accumulation of deacylated tRNAs. However, more recent studies have changed our understanding of its activation and suggest a direct role for ribosome stalling and collisions in the process. In this review, we discuss the classical model for the tRNA-mediated activation of GCN2 and the recent shift in this model to accommodate the observations that wide-ranging translational stresses trigger its activation.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"615-626"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172493","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}
Saieeda Fabia Ali, Adrianna E White, Amy Medlock, Oleh Khalimonchuk
{"title":"Mechanisms of heme transport in the mitochondria.","authors":"Saieeda Fabia Ali, Adrianna E White, Amy Medlock, Oleh Khalimonchuk","doi":"10.1042/BST20253013","DOIUrl":"10.1042/BST20253013","url":null,"abstract":"<p><p>Heme is a vital but highly reactive compound that is synthesized in mitochondria and subsequently distributed to a variety of subcellular compartments for utilization. The transport of heme is essential for normal cellular metabolism, growth, and development. Despite the vital importance of heme transport within the cell, data are lacking about how newly synthesized heme is shuttled within the mitochondrion or exported from the organelle. Here, we briefly summarize current knowledge about the process of mitochondrial heme distribution and discuss the current unresolved questions pertinent to this process.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"603-614"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172496","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}
{"title":"Emerging tools and methods to study cell signalling mediated by branched ubiquitin chains.","authors":"Matthew R McFarland, Yogesh Kulathu","doi":"10.1042/BST20253015","DOIUrl":"10.1042/BST20253015","url":null,"abstract":"<p><p>Branched ubiquitin chains are complex molecular structures in which two or more ubiquitin moieties are attached to distinct lysine residues of a single ubiquitin molecule within a polyubiquitin chain. These bifurcated architectures significantly expand the signalling capacity of the ubiquitin system. Although branched chains constitute a substantial fraction of cellular polyubiquitin, their biological functions largely remain enigmatic due to their complex nature and the associated technical challenges of studying them. Recent technological innovations have enabled the identification of key molecular players and revealed essential roles for branched chains in diverse cellular processes. In this review, we discuss the bespoke strategies that have driven these discoveries, as well as the technologies needed to advance this rapidly evolving field.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"579-592"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085603","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}
David J Williamson, Cecilia Zaza, Irene Carlon-Andres, Tobias Starling, Alessia Gentili, Joseph W Thrush, Audrey Le Bas, Ravi Teja Ravi, Stuart Neil, Ray J Owens, Maud Dumoux, Sabrina Simoncelli, Sergi Padilla-Parra
{"title":"Single-molecule localisation microscopy approaches reveal envelope glycoprotein clusters in single-enveloped viruses: a potential functional role?","authors":"David J Williamson, Cecilia Zaza, Irene Carlon-Andres, Tobias Starling, Alessia Gentili, Joseph W Thrush, Audrey Le Bas, Ravi Teja Ravi, Stuart Neil, Ray J Owens, Maud Dumoux, Sabrina Simoncelli, Sergi Padilla-Parra","doi":"10.1042/BST20240769","DOIUrl":"10.1042/BST20240769","url":null,"abstract":"<p><p>Understanding how viruses enter and fuse with host cells is crucial for developing effective antiviral therapies. The process of viral entry and fusion involves a series of complex steps that allow the virus to breach the host cell membrane and deliver its genetic material inside, with viral fusogens often co-operating to attain the required energy for successful membrane fusion. This co-operative clustering of fusogens in viral envelopes is similar to receptor clustering in cellular systems, where receptors aggregate to initiate signalling cascades. Single-molecule localisation microscopy (SMLM) approaches have emerged as powerful tools to study these intricate mechanisms, allowing the observation of proteins with unprecedented levels of detail. These technologies provide unparalleled insights into the dynamics of viral entry and fusion at a molecular level, revealing how the co-ordinated action of fusogens facilitates membrane fusion. By employing the newest advances in SMLM techniques, such as DNA-PAINT and MINFLUX, we anticipate that precise information on the key steps of viral fusion can be revealed with high spatial and temporal resolutions, identifying critical points in the process that can be targeted by antiviral strategies.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"643-652"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265187","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}
{"title":"Is the SPLUNC1-Orai1 axis a critical determinant of lung health?","authors":"Robert Tarran","doi":"10.1042/BST20241029","DOIUrl":"https://doi.org/10.1042/BST20241029","url":null,"abstract":"<p><p>Short palate lung and nasal epithelial clone 1 (SPLUNC1; gene name BPIFA1) is a secreted protein that is highly expressed in the nasopharyngeal and pulmonary systems. By data mining, we found that SPLUNC1 is also expressed in other organs, including the kidneys and the pituitary gland. SPLUNC1 is an asthma and cystic fibrosis gene modifier that also inversely correlates with the severity of bronchiectasis. Orai1 is a plasma membrane Ca2+ channel that is an essential regulator of the immune system. We previously found that SPLUNC1 binds to Orai1, causing it to be ubiquitinated, internalized and trafficked to the lysosome for degradation, thus reducing Ca2+ signaling. Here, we discuss how dysregulation of SPLUNC1-Orai1 interactions may contribute to hyperinflammation in multiple pulmonary diseases. We, and others, have also targeted Orai1 therapeutically, and we will also discuss how Orai1 inhibition may overcome SPLUNC1 deficiency and be beneficial for the treatment of chronic lung disease.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 3","pages":"709-721"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526345","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}
{"title":"Exploring the interaction dynamics of eukaryotic translation initiation factor 2.","authors":"Assen Marintchev","doi":"10.1042/BST20253022","DOIUrl":"10.1042/BST20253022","url":null,"abstract":"<p><p>Eukaryotic translation initiation typically involves recruitment of the 43S ribosomal pre-initiation complex (PIC) to the 5'-end of the mRNA to form the 48S PIC, followed by scanning in search of a start codon in a favorable nucleotide complex. The start codon is recognized through base-pairing with the anticodon of the initiator Met-tRNAi. The stringency of start codon selection controls the probability of initiation from a start codon in a suboptimal nucleotide context. Met-tRNAi itself is recruited to the 43S PIC by the eukaryotic translation initiation factor 2 (eIF2), in the form of the eIF2-GTP•Met-tRNAi ternary complex (TC). GTP hydrolysis by eIF2, promoted by its GTPase-activating protein eIF5, leads to the release of eIF2-GDP from the PIC. Recycling of eIF2-GDP to TC is promoted by the guanine nucleotide exchange factor eIF2B. Its inhibition by a number of stress factors triggers the integrated stress response (ISR). This review describes the recent advances in elucidating the interactions of eIF2 and its partners, with an emphasis on the timing and dynamics of their binding to, and release from the PIC. Special attention is given to the regulation of the stringency of start codon selection and the ISR. The discussion is mostly limited to translation initiation in mammals and budding yeast.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"593-602"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135997","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}
Nghiem Dinh Nguyen, Loraine M Rourke, Alexandra Cleaver, Joseph Brock, Benedict M Long, Dean G Price
{"title":"Understanding carboxysomes to enhance carbon fixation in crops.","authors":"Nghiem Dinh Nguyen, Loraine M Rourke, Alexandra Cleaver, Joseph Brock, Benedict M Long, Dean G Price","doi":"10.1042/BST20253072","DOIUrl":"10.1042/BST20253072","url":null,"abstract":"<p><p>Carboxysomes are bacterial microcompartments that enhance photosynthetic CO2 fixation by encapsulating ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) within a high-CO2 environment. Their modular, self-assembling nature makes them attractive for synthetic biology applications, particularly their transplantation alongside functional bicarbonate (HCO3-) transporters into plant chloroplasts to achieve improved photosynthetic efficiency. Recent advances have deepened our understanding of carboxysome biogenesis, Rubisco organisation and shell function. However, key questions remain, including the precise shell mechanistic action, which is critical for functional integration into new hosts. Addressing these questions, as well as identifying suitable bicarbonate transporters and fine-tuning expression levels, will be essential to utilising carboxysomes and the cyanobacterial CO2-concentrating mechanism for enhanced photosynthetic efficiency in crops.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"671-685"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504759","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}
{"title":"How do different cell populations orchestrate myelin regeneration?","authors":"Sara Grassi, Alessandro Prinetti","doi":"10.1042/BST20231085","DOIUrl":"10.1042/BST20231085","url":null,"abstract":"<p><p>Approximately 35 in 100,000 people are affected by diseases associated with loss of myelin, generally described as demyelinating diseases. Demyelinating diseases encompass many different pathological conditions characterized by heterogeneous and sometimes disease-specific etiopathological mechanisms. While several approaches aimed at ameliorating the symptoms and the progression of some of these diseases exist, the most effective cure for all demyelinating diseases would be regeneration of lost myelin. Myelin regeneration occurs spontaneously in the central nervous system in response to myelin damage but is inefficient for a variety of reasons, especially in human patients. In this review, we will discuss the contributions of different cell populations to the creation of conditions permissive for effective remyelination and to the formation of new myelin after injury. Moreover, we would like to highlight the importance of sphingolipids in the network of interactions between these cell populations. Mutations in genes encoding sphingolipid metabolic enzymes (such as GALC) represent a major risk factor for multiple sclerosis, and alterations in sphingolipid metabolism in specific cell types contribute to myelin damage. On the other hand, sphingolipid signaling, in particular through sphingosine 1 phosphate, directly affects the process of myelin regeneration, with distinct effects on different cellular populations.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"653-669"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473878","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}
{"title":"Connecting tubules: mechanisms of endoplasmic reticulum membrane fusion.","authors":"Eunhong Jang, Youngsoo Jun","doi":"10.1042/BST20253043","DOIUrl":"https://doi.org/10.1042/BST20253043","url":null,"abstract":"<p><p>Atlastins (ATLs) are integral dynamin-like GTPases that are critical for the formation and maintenance of the endoplasmic reticulum (ER) network, one of the most complex and essential organelles in eukaryotic cells. The ER, which is composed of interconnected tubules and sheets, serves vital functions, including calcium storage, protein and lipid synthesis, and inter-organelle communication. Homotypic membrane fusion, mediated by ATLs, ensures the tubular structure of the ER by generating and stabilizing three-way junctions. Humans express three ATL paralogs, called ATL1, ATL2, and ATL3, which have distinct expression patterns and regulatory mechanisms. Mutations in these proteins are linked to hereditary sensory neuropathies and hereditary spastic paraplegia, highlighting their critical importance in cellular and neuronal health. Here, we review recent studies providing insights into how ATLs are regulated by their N- and C-terminal extensions, as well as how extrinsic factors potentially regulate the activities of ATLs to establish and maintain the normal ER structure.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 3","pages":"699-707"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526344","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}