{"title":"Nitric oxide as a mechanistic link between metabolic dysfunction and cognitive decline in type 2 diabetes.","authors":"Ana L Marçal, João Laranjinha, Cátia F Lourenço","doi":"10.1042/BST20250325","DOIUrl":"10.1042/BST20250325","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is increasingly recognised as a driver of cerebrovascular dysfunction and cognitive decline, yet the molecular mechanisms underlying this association remain incompletely understood. Here, we review and support a key mechanistic role for nitric oxide (•NO), a pleiotropic diffusible messenger that integrates vascular, neuronal, and metabolic functions within the neurovascular unit (NVU). Under physiological conditions, •NO integrates vascular and metabolic responses by coupling blood supply to neuronal activity and fine-tuning cellular energy metabolism. In T2DM, chronic hyperglycemia and insulin resistance converge to reduce •NO bioavailability through multiple mechanisms: mitochondrial and NADPH oxidase-derived superoxide production, endothelial nitric oxide synthases (eNOS) uncoupling via BH4 oxidation, and impaired PI3K-Akt-dependent eNOS activation. The resulting redox imbalance shifts the cerebrovascular environment towards oxidant-mediated damage, compromising the functional and structural integrity of the NVU. This translates into impaired cerebral blood flow regulation and maladaptive remodelling of the cerebrovascular network, ultimately disrupting neurovascular coupling (NVC) and reducing regional cerebral perfusion. Together, impaired perfusion and disrupted NVC result in a sustained mismatch between energy supply and neuronal demand, particularly in metabolically vulnerable regions such as the hippocampus, ultimately leading to progressive cognitive impairment. In sum, the present review integrates current mechanistic evidence positioning •NO dysregulation as a central driver of neurovascular and metabolic dysfunction in T2DM, linking impaired cerebral perfusion, disrupted NVC, and structural vascular remodelling to cognitive decline.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 9","pages":"1239-1250"},"PeriodicalIF":4.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975640","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}
{"title":"Ubiquitin E3 ligase activity in TRIpartite Motif (TRIM) family proteins.","authors":"Jane Dudley-Fraser, Katrin Rittinger","doi":"10.1042/BST20260079","DOIUrl":"10.1042/BST20260079","url":null,"abstract":"<p><p>TRIpartite Motif (TRIM) family proteins are required for healthy development and homeostasis, while their dysregulation is observed in a wide range of diseases. Although diverse cellular roles are emerging for TRIMs, the majority function as ubiquitin E3 ligases by means of their RING (really interesting new gene) domain. Here, we delve into what is known about TRIM ubiquitin E3 ligase mechanisms, their ubiquitin chain specificities, and how they can be regulated through homo- and hetero-multimerisation and post-translational modifications.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 9","pages":"1251-1260"},"PeriodicalIF":4.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975729","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}
Giorgos Hiotis, Yoshitaka Nakayama, Swati Yadav, Thomas Walz
{"title":"The diverse gating mechanisms of bacterial MscS-like ion channels.","authors":"Giorgos Hiotis, Yoshitaka Nakayama, Swati Yadav, Thomas Walz","doi":"10.1042/BST20261105","DOIUrl":"10.1042/BST20261105","url":null,"abstract":"<p><p>Bacterial mechanosensitive (MS) channels protect cells against hypoosmotic shock by opening, in response to increased membrane tension, a transmembrane pore that allows rapid efflux of osmolytes. The MS channel of small conductance (MscS) in Escherichia coli has been extensively characterized both functionally and structurally, establishing its channel properties and revealing its architecture and the conformational changes that underlie channel gating. In particular, several lipids associated with MscS have been proposed to play a role in its mechanosensitivity. MscS is the founding member of the superfamily of MscS-like channels that share a structurally conserved core with MscS but feature additional structural elements that result in distinct functional properties. In addition to MscS, E. coli expresses five MscS-like channels. In the present review, we summarize recent advances in the structural characterization of E. coli MscS-like channels that revealed diverse gating mechanisms. Unlike the mechanosensation of MscS that appears to depend on its associated lipids, the mechanosensation of MscS-like channels seems to be the result of the deformation they cause on their surrounding membrane. Despite the diversity in observed gating mechanisms, we highlight unifying principles that dictate the properties of MscS-like channels and MS channels in general.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 9","pages":"1279-1288"},"PeriodicalIF":4.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988094","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}
Alexandre Almeida, Marta A Silva, Jorge M A Antunes, Mafalda V Fernandes, Leonor Morgado, Carlos A Salgueiro
{"title":"Overview of pathways and dynamic interactions of c-type cytochromes in Geobacter sulfurreducens.","authors":"Alexandre Almeida, Marta A Silva, Jorge M A Antunes, Mafalda V Fernandes, Leonor Morgado, Carlos A Salgueiro","doi":"10.1042/BST20260147","DOIUrl":"10.1042/BST20260147","url":null,"abstract":"<p><p>Extracellular electron transfer (EET) is a central process in the respiratory metabolism of electrogenic bacteria, enabling cells to exchange electrons with extracellular acceptors and donors. This capability has opened opportunities to exploit these bacteria in diverse practical applications, many of which would benefit from a precise understanding of the electron transfer (ET) events occurring within their respiratory chains. These chains rely on highly populated networks of c-type cytochromes that mediate electron flow across cellular compartments toward terminal electron acceptors. Although genomic, proteomic, biochemical, and structural studies have identified many ET components, defining their physiological redox partners and the directionality of electron flow remains challenging. This difficulty arises from the similar spectroscopic properties of key cytochromes, their transient interactions, and the complex overlap of their redox potential windows. In the present review, we examine how recently developed NMR-based strategies have been used to identify redox complexes established between cytochromes located in the inner membrane, periplasm, outer membrane, and extracellular conductive structures in the bacterium Geobacter sulfurreducens. These strategies exploited the distinct redox-dependent NMR fingerprints of individual heme groups, allowing direct detection of electron exchange, redox equilibria, and transient protein-protein interactions. Collectively, these studies reveal that ET pathways are not organized as single linear chains, but rather as dynamic and highly interconnected redox networks characterized by weak transient redox complexes and extensive promiscuity. This organization provides bacterial electron-buffering capacity, functional flexibility, and adaptability to changing environmental redox conditions.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 9","pages":"1289-1308"},"PeriodicalIF":4.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988107","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}
{"title":"Building peroxisomes: perspectives on plant peroxins.","authors":"Gabrielle C Buck, Bonnie Bartel","doi":"10.1042/BST20230940","DOIUrl":"10.1042/BST20230940","url":null,"abstract":"<p><p>Peroxisomes are dynamic organelles with diverse metabolic functions that are essential for life in plants and mammals. In humans, peroxisomal defects underlie peroxisome biogenesis disorders, which are often fatal. In plants, peroxisomes contribute to photorespiration and phytohormone production during plant development and are the sole site of fatty acid β-oxidation, which is critical for fat mobilization during germination. Despite their functional diversity, much of the machinery involved in building and maintaining peroxisomes is conserved across most eukaryotes. The model plant Arabidopsis thaliana is ideal for peroxisome studies due to its large peroxisomes, whole-organism and molecular assays for peroxisome function, and facile genetics. New applications of microscopy, computational modeling, and biochemistry have advanced the understanding of peroxisome biogenesis across eukaryotic life. These advances have generated insights into the functions of the proteins involved in peroxisome biogenesis, known as peroxins. Here, we review knowledge of Arabidopsis thaliana peroxins and discuss how new perspectives on peroxin functions across kingdoms inform future research on plant peroxisomes.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 9","pages":"1261-1278"},"PeriodicalIF":4.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988120","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}
{"title":"NINJ1: implications for plasma membrane rupture and disease.","authors":"Elliott M Bernard, Ella Hartenian","doi":"10.1042/BST20260711","DOIUrl":"10.1042/BST20260711","url":null,"abstract":"<p><p>Cell death pathways are ancient strategies that maintain homeostasis and protect organisms from infection and injury. Lytic cell death culminates in the rupture of the plasma membrane, which was recently revealed to be driven by Ninjurin-1 (NINJ1), a plasma membrane protein that oligomerizes during cell death. NINJ1 oligomerization creates lesions in the plasma membrane that facilitate the release of cytosolic contents. In the present review, we discuss what is currently known about NINJ1 biology, focusing on the most current research into potential mechanisms of activation. We then highlight how NINJ1 has been implicated in specific disease contexts and discuss potential ways NINJ1 may contribute to disease. We conclude with the remaining open questions relating to NINJ1 biology.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 9","pages":"1309-1318"},"PeriodicalIF":4.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988139","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}
Lilia Colina-Tenorio, Martina Bohuslavová, Alexander W Bruce, Hassan Hashimi
{"title":"Correction: The molecular mechanisms of crista formation: how mitochondria give themselves breathing room.","authors":"Lilia Colina-Tenorio, Martina Bohuslavová, Alexander W Bruce, Hassan Hashimi","doi":"10.1042/BST20260167_COR","DOIUrl":"10.1042/BST20260167_COR","url":null,"abstract":"","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 9","pages":"1221"},"PeriodicalIF":4.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905052","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}
{"title":"Communication is key: combinatorial phosphorylation and functional cross-talk in the RNA polymerase II CTD code.","authors":"Y Jessie Zhang, Erin Ramsey","doi":"10.1042/BST20250032","DOIUrl":"10.1042/BST20250032","url":null,"abstract":"<p><p>The C-terminal domain (CTD) of the largest subunit of RNA polymerase II serves as a dynamic platform coordinating transcription and RNA processing. Recent advances in mass spectrometry, structural biology, and sequencing approaches have revealed a far more complex, combinatorial CTD code than previously appreciated. The present review examines the CTD as an integrative signaling hub that translates diverse environmental signals into genomic outputs. We explore the hierarchical transitions between phosphorylation states, highlighting how combinatorial marks rather than isolated modifications shape transcriptional progression and prevent cryptic initiation through cross-talk with the histone code. Special focus is given to the roles of 'enigmatic' marks such as pTyr1 and pThr4, whose functional significance has been complicated by biochemical masking effects and species-specific regulatory nodes. We also discuss emerging evidence that CTD remodeling contributes to stress-responsive transcription, including oxidative stress, heat shock, and DNA damage. Together, these observations support a dynamic model of the CTD in which combinatorial phosphorylation states coordinate transcriptional progression, genome stability, and stress-responsive gene regulation.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 8","pages":"1065-1077"},"PeriodicalIF":4.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683173","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}
{"title":"Evolution of self-reactive B cells: lessons from a lupus model.","authors":"Kristine Oleinika, Michael C Carroll","doi":"10.1042/BST20250392","DOIUrl":"10.1042/BST20250392","url":null,"abstract":"<p><p>Systemic lupus erythematosus develops when autoreactive B cells escape tolerance and enter differentiation pathways that sustain pathogenic autoantibody responses. A defining feature of lupus is the evolving autoantibody repertoire, in which initially focused autoreactivity broadens over time through recruitment of additional self-reactive B cell clones as well as continued mutation and selection of B cells engaged in the response. Here, we review insights from the 564Igi lupus model, in which a defined autoreactive B cell clone creates an autoimmune environment that permits a previously tolerant polyclonal wild-type (WT) B cell repertoire to enter the response. Studies using mixed bone marrow chimera and adoptive transfer approaches show that WT-derived B cells can be recruited into established autoreactive niches, participate in germinal center and extrafollicular pathways, and contribute to epitope-spread autoantibody responses. We discuss how studies in the present model have reframed epitope spreading as a dynamic process of self-reactive B cell evolution, in which otherwise restrained B cells are incorporated into an ongoing autoimmune response and shaped by the niches that support their activation, differentiation, persistence, and diversification.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 8","pages":"1011-1020"},"PeriodicalIF":4.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629318","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}
{"title":"Genetically encoded tools for tracking metabolites in live cells.","authors":"Austin H Ablicki, Katharine L Diehl","doi":"10.1042/BST20250115","DOIUrl":"10.1042/BST20250115","url":null,"abstract":"<p><p>Biosensors enable the in situ measurement of metabolites in living systems over time and space. Fully genetically encoded metabolite biosensors (fGEMBs) use fluorescent proteins (FPs) linked to ligand binding domains (LBDs) to transduce the ligand binding event to a measurable change in the fluorescence behavior of the FP. Because these sensors are genetically encoded, they can be expressed in cells using standard protein expression approaches, and the fluorescence changes are quantified using fluorimetry, fluorescence microscopy, and/or flow cytometry. While there are general sensor design principles to follow, an fGEMB must be engineered for each metabolite based on a particular LBD. This development process can be slow, but there are strategies emerging to increase testing throughput and improve structure-guided design. While genetically-encoded FPs remain popular, there are now numerous chemigenetic and nucleic acid-based metabolite sensors (cGEMBs) that incorporate small molecule fluorophores. De novo design of LBDs is rapidly advancing as well, and the field may soon exhibit a shift away from relying on nature's catalog of LBDs. Despite the engineering challenges, the metabolite biosensor field has expanded significantly in recent years to meet the demand for new and better-performing sensors that visualize metabolites within their cellular environments.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 8","pages":"973-983"},"PeriodicalIF":4.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577068","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}