{"title":"S-acylation in apoptotic and non-apoptotic cell death: a central regulator of membrane dynamics and protein function.","authors":"Rojae Manhertz-Patterson, G Ekin Atilla-Gokcumen","doi":"10.1042/BST20253012","DOIUrl":"10.1042/BST20253012","url":null,"abstract":"<p><p>Protein lipidation is a collection of important post-translational modifications that modulate protein localization and stability. Protein lipidation affects protein function by facilitating interactions with cellular membranes, changing the local environment of protein interactions. Among these modifications, S-acylation has emerged as a key regulator of various cellular processes, including different forms of cell death. In this mini-review, we highlight the role of S-acylation in apoptosis and its emerging contributions to necroptosis and pyroptosis. While traditionally associated with the incorporation of palmitic acid (palmitoylation), recent findings indicate that other fatty acids can also participate in S-acylation, expanding its functional repertoire. In apoptosis, S-acylation influences the localization and function of key regulators such as Bcl-2-associated X protein and other proteins modulating their role in mitochondrial permeabilization and death receptor signaling. Similarly, in necroptosis, S-acylation of mixed lineage kinase domain-like protein (MLKL) with palmitic acid and very long-chain fatty acids enhances membrane binding and membrane permeabilization, contributing to cell death and inflammatory responses. Recent studies also highlight the role of S-acylation in pyroptosis, where S-acylated gasdermin D facilitates membrane localization and pore assembly upon inflammasome activation. Blocking palmitoylation has shown to suppress pyroptosis and cytokine release, reducing inflammatory activity and tissue damage in septic models. Collectively, these findings underscore S-acylation as a shared and important regulatory mechanism across cell death pathways affecting membrane association of key signaling proteins and membrane dynamics, and offer insights into the spatial and temporal control of protein function.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970451","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":"Functions and mechanisms of eukaryotic RNA-guided programmed DNA elimination.","authors":"Bozhidar-Adrian Stefanov, Mariusz Nowacki","doi":"10.1042/BST20253006","DOIUrl":"10.1042/BST20253006","url":null,"abstract":"<p><p>Many eukaryotic organisms, from ciliates to mammals, employ programmed DNA elimination during their postmeiotic reproduction. The process removes specific regions from the somatic DNA and has broad functions, including the irreversible silencing of genes, sex determination, and genome protection from transposable elements or integrating viruses. Multiple mechanisms have evolved that explain the sequence selectivity of the process. In some cases, the eliminated sequences lack centromeres and are flanked by conserved sequence motifs that are specifically recognized and cleaved by designated nucleases. Upon cleavage, all DNA fragments that lack centromeres are lost during the following mitosis. Alternatively, specific sequences can be destined for elimination by complementary small RNAs (sRNAs) as in some ciliates. These sRNAs enable a PIWI-mediated recruitment of chromatin remodelers, followed up by the precise positioning of a cleavage complex formed from a transposase like PiggyBac or Tc1. Here, we review the known molecular interplay of the cellular machinery that is involved in precise sRNA-guided DNA excision, and additionally, we highlight prominent knowledge gaps. We focus on the modes through which sRNAs enable the precise localization of the cleavage complex, and how the nuclease activity is controlled to prevent off-target cleavage. A mechanistic understanding of this process could enable the development of novel eukaryotic genome editing tools.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963913","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":"Correction: Exploring the influence of anionic lipids in the host cell membrane on viral fusion.","authors":"","doi":"10.1042/BST20240833_COR","DOIUrl":"10.1042/BST20240833_COR","url":null,"abstract":"","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975623","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}
Aurelio Lorico, Mark F Santos, Jana Karbanová, Denis Corbeil
{"title":"Extracellular membrane particles en route to the nucleus - exploring the VOR complex.","authors":"Aurelio Lorico, Mark F Santos, Jana Karbanová, Denis Corbeil","doi":"10.1042/BST20253005","DOIUrl":"https://doi.org/10.1042/BST20253005","url":null,"abstract":"<p><p>Intercellular communication is an essential hallmark of multicellular organisms for their development and adult tissue homeostasis. Over the past two decades, attention has been focused on communication mechanisms based on various membrane structures, as illustrated by the burst of scientific literature in the field of extracellular vesicles (EVs). These lipid bilayer-bound nano- or microparticles, as vehicle-like devices, act as regulators in various biological and physiological processes. When EVs are internalized by recipient cells, their membrane and cytoplasmic cargoes can interfere with cellular activities, affecting pathways that regulate cell proliferation, differentiation, and migration. In cancer, EVs can transfer oncogenic factors, stimulate neo-angiogenesis and immunosuppression, reprogram stromal cells, and confer drug resistance traits, thereby remodeling the surrounding microenvironment. Although the mechanisms underlying EV biogenesis and uptake are now better understood, little is known about the spatiotemporal mechanism(s) of their actions after internalization. In this respect, we have shown that a fraction of endocytosed EVs reaches the nuclear compartment via the VOR (VAP-A-ORP3-Rab7) complex-mediated docking of late endosomes to the outer nuclear membrane in the nucleoplasmic reticulum, positioning and facilitating the transfer of EV cargoes into the nucleoplasm via nuclear pores. Here, we highlight the EV heterogeneity, the cellular pathways governing EV release and uptake by donor and recipient cells, respectively, and focus on a novel intracellular pathway leading to the nuclear transfer of EV cargoes. We will discuss how to intercept it, which could open up new avenues for clinical applications in which EVs and other small extracellular particles (e.g., retroviruses) are implicated.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970426","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 spherical bacteria regulate cell division?","authors":"Félix Ramos-León, Kumaran S Ramamurthi","doi":"10.1042/BST20240956","DOIUrl":"10.1042/BST20240956","url":null,"abstract":"<p><p>Many bacteria divide by binary fission, producing two identical daughter cells, which requires proper placement of the division machinery at mid-cell. Spherical bacteria (cocci) face unique challenges due to their lack of natural polarity. In this review, we compile current knowledge on how cocci regulate cell division, how they select the proper division plane, and ensure accurate Z-ring positioning at mid-cell. While Streptococcus pneumoniae and Staphylococcus aureus are the most well-studied models for cell division in cocci, we also cover other less-characterized cocci across different bacterial groups and discuss the conservation of known Z-ring positioning mechanisms in these understudied bacteria.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975539","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":"Manipulation of targeted protein degradation in plant biology.","authors":"Marcela Rojas-Pierce, Sebastian Y Bednarek","doi":"10.1042/BST20230939","DOIUrl":"10.1042/BST20230939","url":null,"abstract":"<p><p>Inducible protein degradation systems are an important but untapped resource for the study of protein function in plant cells. Unlike mutagenesis or transcriptional control, regulated degradation of proteins of interest allows the study of the biological mechanisms of highly dynamic cellular processes involving essential proteins. While systems for targeted protein degradation are available for research and therapeutics in animals, there are currently limited options in plant biology. Targeted protein degradation systems rely on target ubiquitination by E3 ubiquitin ligases. Systems that are available or being developed in plants can be distinguished primarily by the type of E3 ubiquitin ligase involved, including those that utilize Cullin-RING ligases, bacterial novel E3 ligases, and N-end rule pathway E3 ligases, or they can be controlled by proteolysis targeting chimeras. Target protein ubiquitination leads to degradation by the proteasome or targeting to the vacuole, with both pathways being ubiquitous and important for the endogenous control of protein abundance in plants. Targeted proteolysis approaches for plants will likely be an important tool for basic research and to yield novel traits for crop biotechnology.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953262","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":"Insights into non-proteinaceous ubiquitination.","authors":"Emily L Dearlove, Danny T Huang","doi":"10.1042/BST20253029","DOIUrl":"10.1042/BST20253029","url":null,"abstract":"<p><p>Ubiquitination plays a key role in the regulation of numerous diverse cellular functions. This process involves the covalent attachment of ubiquitin to protein substrates by a cascade of enzymes. In recent years, various non-proteinaceous substrates of ubiquitination have been discovered, expanding the potential for the functions of ubiquitination beyond its conventional role as a post-translational modification. Here, we profile the non-proteinaceous substrates of ubiquitination reported to date, the enzymes that regulate these activities, and the mechanistic details of substrate modification. The biological functions linked to these modifications are discussed, and finally, we highlight the challenges hindering further progress in the identification and functional characterization of non-proteinaceous substrates of ubiquitination within cellular contexts.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778848","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":"Spo11: from topoisomerase VI to meiotic recombination initiator.","authors":"Jon A Harper, George G B Brown, Matthew J Neale","doi":"10.1042/BST20253019","DOIUrl":"10.1042/BST20253019","url":null,"abstract":"<p><p>Meiotic recombination is required to break up gene linkage and facilitate faithful chromosome segregation during gamete formation. By inducing DNA double-strand breaks, Spo11, a protein that is conserved in all meiotic organisms, initiates the process of recombination. Here, we chart the evolutionary history of Spo11 and compare the protein to its ancestors. Evolving from the A subunit of archaeal topoisomerase VI (Topo VI), a heterotetrameric type II topoisomerase, Spo11 appears to have evolved alongside meiosis and been present in the last eukaryotic common ancestor. There are many differences between Spo11 and TopVIA, particularly in regulation, despite similarities in structure and mechanism of action. Critical to its function as an inducer of recombination, Spo11 has an apparently amputated activity that, unlike topoisomerases, does not re-seal the DNA breaks it creates. We discuss how and why Spo11 has taken its path down the tree of life, considering its regulation and its roles compared with those of its progenitor Topo VI, in both meiotic and non-meiotic species. We find some commonality between different forms and orthologs of Spo11 in different species and touch upon how recent biochemical advances are beginning to finally unlock the molecular secrets hidden within this fundamental yet enigmatic protein.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778850","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}
Natalie Koh, Zhengyu Ma, Abhishek Sarup, Amy Claire Kristl, Mark Agrios, Margaret Young, Andrew Miri
{"title":"Selective direct motor cortical influence during naturalistic climbing in mice.","authors":"Natalie Koh, Zhengyu Ma, Abhishek Sarup, Amy Claire Kristl, Mark Agrios, Margaret Young, Andrew Miri","doi":"10.1101/2023.06.18.545509","DOIUrl":"10.1101/2023.06.18.545509","url":null,"abstract":"<p><p>It remains poorly resolved when and how motor cortical output directly influences limb muscle activity through descending projections, which impedes mechanistic understanding of motor control. Here we addressed this in mice performing an ethologically inspired climbing behavior. We quantified the direct influence of forelimb primary motor cortex (caudal forelimb area, CFA) on muscles across the muscle activity states expressed during climbing. We found that CFA instructs muscle activity pattern by selectively activating certain muscles, while less frequently activating or suppressing their antagonists. From Neuropixels recordings, we identified linear combinations (components) of motor cortical activity that covary with these effects. These components differ partially from those that covary with muscle activity and differ almost completely from those that covary with kinematics. Collectively, our results reveal an instructive direct motor cortical influence on limb muscles that is selective within a motor behavior and reliant on a distinct neural activity subspace.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"17 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80178576","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}
Eric Rubinstein, Clotilde Théry, Pascale Zimmermann
{"title":"Tetraspanins affect membrane structures and the trafficking of molecular partners: what impact on extracellular vesicles?","authors":"Eric Rubinstein, Clotilde Théry, Pascale Zimmermann","doi":"10.1042/BST20240523","DOIUrl":"10.1042/BST20240523","url":null,"abstract":"<p><p>Tetraspanins are a family of 33 proteins in mammals believed to play a crucial role in the compartmentalization of various associated proteins within cells and membranes. Recent studies have elucidated the structure of several tetraspanin members, revealing that while the four transmembrane domains typically adopt a cone-shaped configuration in crystals, other conformations are also possible. This cone-shaped structure may explain why tetraspanins are often enriched in curved and tubular cellular structures, such as microvilli, tunneling nanotubes, retraction fibers, or at the site of virus budding, and may contribute to the formation or maintenance of these structures. Tetraspanins have also been detected on midbody remnants and migrasomes, as well as on extracellular vesicles (EVs), for which CD9, CD81, and CD63 are widely used as markers. Although their impact on certain membrane structures and their ability to regulate the function and trafficking of associated proteins would suggest a potential role of tetraspanins either in EV formation or in regulating their protein composition, or both, efforts to characterize these roles have been complicated by conflicting results. In line with the interaction of certain tetraspanins with cholesterol, two recent studies have suggested that the presence or organization of oxysterols and cholesterol in EVs may be regulated by Tspan6 and CD63, respectively, paving the way for further research on the influence of tetraspanins on the lipid composition of EVs.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"0 0","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708349","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}