{"title":"Bacterial AsmA Proteins Transfer Glycerophospholipids Between Membranes <i>in Vitro</i>.","authors":"Matthew A Schilling, Karin M Reinisch","doi":"10.1177/25152564261484576","DOIUrl":"10.1177/25152564261484576","url":null,"abstract":"<p><p>Gram-negative bacteria are surrounded by inner and outer membranes whose glycerophospholipid building blocks are synthesized in the inner membrane and redistributed to the outer membrane by poorly understood mechanisms. In eukaryotes, bridge-like lipid transfer proteins (BLTPs) transfer glycerophospholipids between membranes to support membrane homeostasis and biogenesis. Bacterial proteins in the AsmA family are related to BLTPs in structure and are proposed also to function in lipid transfer. Here we adapted a well-established in vitro lipid transfer assay to provide biochemical evidence that AsmA family proteins, TamB and YhdP, have the ability to transfer glycerophospholipids between membranes, supporting similar functions for AsmA proteins and BLTPs.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"9 ","pages":"25152564261484576"},"PeriodicalIF":0.0,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tomas Knedlik, Federica Dal Bello, Marta Giacomello
{"title":"Approaches to Organelle Spacing at Membrane Contact Sites.","authors":"Tomas Knedlik, Federica Dal Bello, Marta Giacomello","doi":"10.1177/25152564261473365","DOIUrl":"10.1177/25152564261473365","url":null,"abstract":"<p><p>Membrane contact sites (MCSs) are points where organelle surfaces are juxtaposed, without fusion of their membranes. Research in the MCS field has widely focused on the molecules and mechanisms that hold organelles together, known as \"tethers\", based on the correct presumption that processes mediated by MCSs depend on their spatial proximity. However, it has become clear that the distance between the membranes also have a biological role, particularly in processes such as Ca<sup>2+</sup> transfer, while its relevance for other functions, such as lipid exchange, remains less clear. This supports the idea that there may be molecules that keep membranes apart, referred to as \"spacers\". While some evidence supports this hypothesis, the mechanisms of spacing remain unclear. In this opinion article, we briefly describe three potential spacing mechanisms that we have hypothesised based on direct and indirect experimental evidence. Briefly, we propose the existence of different types of organelle spacing approaches (OSAs) that result in organelle distancing: first, the presence of rod-like spacing molecules; second, the removal of some tethers, achieved through their masking, dissociation from MCSs, or degradation, which could result either in complete untethering of the organelles or in variations in the distance between them due to changes in the composition of the MCSs; third, cytoskeleton-mediated pulling forces that can increase the distance between the two apposing membranes. Our aim is to stimulate discussion and initiate debate on the importance of maintaining the correct distance between organelles.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"9 ","pages":"25152564261473365"},"PeriodicalIF":0.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structural Organization of the Nvj3-Mdm1 Complex Reveals a Conserved Lipid-Compatible Contact Site Module.","authors":"Marwa Aboumourad, Hanaa Hariri","doi":"10.1177/25152564261471395","DOIUrl":"10.1177/25152564261471395","url":null,"abstract":"<p><p>Membrane contact sites are organized by protein assemblies that physically couple organelles and coordinate lipid metabolism, yet the structural principles that enable lipid exchange across these junctions remain poorly defined. At the nuclear-vacuolar junction (NVJ) in budding yeast, the tethering protein Mdm1 and its binding partner Nvj3 form a complex that regulates lipid metabolic pathways, but the structural features underlying their interaction have not been resolved. Here, we use AlphaFold-based complex prediction and comparative structural analysis to define the organization of Nvj3-Mdm1 complex assembly. We identify a high-confidence heterodimer in which conserved PXA and PXC domains generate an extended tunnel spanning both proteins. Tunnel analysis predicts a core hydrophobic conduit traversing the Nvj3-Mdm1 interface, consistent with a lipid-compatible architecture. Evolutionary conservation is enriched at the Nvj3-Mdm1 interface. The predicted conduit shares geometric and physicochemical properties with bridge-like lipid transfer proteins, including Atg2, Fmp27, and Hob2, suggesting that heteromeric tether assemblies may contribute directly to inter-organelle lipid transfer. Notably, this conduit is predicted to arise from a heteromeric α-helical assembly rather than the β-sheet-rich architecture characteristic of canonical bridge-like lipid transfer proteins. Comparative phylogenetic analyses showed that Nvj3 and Mdm1 share broadly congruent evolutionary patterns across Saccharomycetes, consistent with their conserved functional association. Together, these findings define Nvj3 as a structural partner of Mdm1 and support a conduit-based model of lipid transfer at the NVJ.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"9 ","pages":"25152564261471395"},"PeriodicalIF":0.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148595456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Annexin A6 Is a Novel Cytosolic Regulator of Multiple Inter-organelle Contact Sites.","authors":"Carlos Enrich, Carles Rentero, Thomas Grewal","doi":"10.1177/25152564261466547","DOIUrl":"10.1177/25152564261466547","url":null,"abstract":"<p><p>Annexins are a widely expressed family of multifunctional cytosolic proteins with diverse cellular roles. Recent advances have uncovered new avenues for the involvement of several annexins in membrane dynamics, suggesting a potential link to the coordination of membrane contact site (MCS) formation. Up to date, Annexin A1 (ANXA1), ANXA6 and ANXA11 have been defined as MCS-associated annexins. In a recent study, we demonstrated that ANXA6 critically influences the formation of multiple inter-organelle contact sites. Using electron microscopy, proximity-labelling and proteomic assays, ANXA6 deficiency was shown to substantially reduce the extent and number of MCS between several organelles in a number of cell lines. This correlated with ANXA6 interacting with various tethers and bona fide MCS proteins that can modulate multi-organelle contacts, indicating that the loss of ANXA6-related protein-protein interactions reduced the ability to develop contacts between organelles. Importantly, restoration of ANXA6 expression in ANXA6-deficient cells re-established MCS numbers, suggesting that transient changes in ANXA6 expression levels significantly impact on MCS dynamics. These findings identify ANXA6 as the first example of a cytosolic protein whose expression levels directly modulate the cellular organization of MCS.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"9 ","pages":"25152564261466547"},"PeriodicalIF":0.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148392973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetically Encoded Tools to Monitor and Interrogate Membrane Contact Sites.","authors":"Yuepeng Ke, Tien-Hung Lan, Thomas Ahn, Yubin Zhou","doi":"10.1177/25152564261451667","DOIUrl":"10.1177/25152564261451667","url":null,"abstract":"<p><p>Membrane contact sites (MCSs) are dynamic subcellular compartments formed between organelles that coordinate diverse aspects of cellular communication, including signaling, metabolism, and membrane organization. Tools capable of monitoring and controlling the spatially localized and dynamic properties of MCSs are needed to dissect their regulatory mechanisms and physiological roles. Recent advances in protein engineering have begun to address this need. Proximity-based reporters, chemogenetic approaches, and optogenetic systems have been developed to enable the visualization, interrogation, and manipulation of inter-organelle contacts with improved spatial and temporal precision. This minireview highlights key developments in these molecular toolkits and their representative applications in studying MCS biology. These approaches provide new insights into organelle crosstalk and may inform future therapeutic strategies targeting MCSs.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"9 ","pages":"25152564261451667"},"PeriodicalIF":0.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13180065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147978195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juliane Da Graça, Dobrawa Amiri Czajkowski, Etienne Morel
{"title":"ER-driven Contact Sites in Autophagosome Biogenesis Sequence.","authors":"Juliane Da Graça, Dobrawa Amiri Czajkowski, Etienne Morel","doi":"10.1177/25152564261451671","DOIUrl":"10.1177/25152564261451671","url":null,"abstract":"<p><p>Autophagosome biogenesis is a highly coordinated membrane remodeling process that relies on the <i>de novo</i> formation and expansion of the phagophore, yet the cellular principles governing its spatial and temporal organization remain incompletely understood. Accumulating evidence now places the endoplasmic reticulum (ER) at the center of this process, not merely as a membrane source, but as a dynamic scaffold that organizes phagophore assembly through extensive membrane contact sites with multiple organelles. ER-mediated contacts with endosomes, mitochondria, the plasma membrane, and ER-Golgi intermediates create specialized microenvironments that integrate signaling, lipid transfer, vesicle formation and trafficking, and biophysical constraints to drive phagophore nucleation and growth. These contact sites enable the coordinated mobilization of diverse membrane carriers and autophagy regulators in a stress- and context-dependent manner. In this review, we discuss how ER-driven membrane contact sites orchestrate autophagosome biogenesis, highlight emerging mechanistic and biophysical concepts, and consider their broader implications for cellular stress adaptation and disease.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"9 ","pages":"25152564261451671"},"PeriodicalIF":0.0,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13168723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Richard Boulton-McDonald, Eva Sidlauskaite, Jiri Neuzil, Michelangelo Campanella
{"title":"mtDNA-Depleted Mitochondria Form Sites of Contact with the Nucleus and Alter the Cellular Epigenome.","authors":"Richard Boulton-McDonald, Eva Sidlauskaite, Jiri Neuzil, Michelangelo Campanella","doi":"10.1177/25152564261428840","DOIUrl":"10.1177/25152564261428840","url":null,"abstract":"<p><p>Mitochondrial sites of contact with the nucleus, hereafter referred to as Nucleus-Associated Mitochondria (NAM), are specialised domains that enable communication, influencing cellular function. Previous studies have shown that these contacts can be stabilised by protein scaffolds acting as tethers to promote retrograde signalling, particularly during apoptotic stress. This is facilitated via the mitochondrial protein TSPO. In this study, we have investigated a mitochondrial DNA (mtDNA)-depleted (ρ<sup>0</sup>) 4T1 cell model to further inform the role of NAM in retrograde communication between corrupted mitochondria and the nucleus. Our data report an increase in NAM frequency in mtDNA-depleted cells compared to the mtDNA-retaining parental 4T1 line. Using a combination of cellular assays, transmission electron microscopy, and epigenetic profiling, we have found that under conditions of mtDNA loss, mitochondria become enriched in TSPO, evading mitophagic clearance and are prone to forming stable contacts with the nucleus. This coincides with an extreme reduction in DNA methylation, as well as histone modifications associated with chromatin decondensation.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"9 ","pages":"25152564261428840"},"PeriodicalIF":0.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lara Lansky, Fabienne Drescher, Katarina Sugic, Karoline Diesing, Aleksandra Hackel, Vanessa Wahl, Jens Tilsner, Christina Kühn
{"title":"A Novel Phloem-Specific HVA22-Like Protein Facilitates Protein Movement via Plasmodesmata in Potato.","authors":"Lara Lansky, Fabienne Drescher, Katarina Sugic, Karoline Diesing, Aleksandra Hackel, Vanessa Wahl, Jens Tilsner, Christina Kühn","doi":"10.1177/25152564261418821","DOIUrl":"10.1177/25152564261418821","url":null,"abstract":"<p><p>Subcellular targeting and functionality of plant sucrose transporters (SUTs) are affected at the post-translational level by protein-protein interactions. A systematic screening for SUT-interacting proteins identified a novel plasmodesma (PD)-localized membrane protein belonging to the HVA22 family of stress-induced ER proteins. It carries three transmembrane domains and three zinc-finger domains, interacts with all three sucrose transporters from potato, and co-localizes with PD callose and PD marker proteins. Detailed analyses of transgenic potato plants with decreased expression of this PD protein displaying phenotypic alterations regarding trichome length, leaf expansion, root length, flowering time and tuberization helped to determine its physiological function. These effects are partially graft-transmissible indicating the participation of phloem-mobile signals. Changes in the levels of callose in RNAi plants suggested effects on PD permeability. Co-infiltration experiments revealed enhanced mobility of sucrose transporter-GFP fusion proteins via plasmodesmata in the presence of the HVA22-like protein. The analysis of transgenic plants further suggests that HVA22 protein is a general regulator of PD permeability in potato. Taken together, the HVA22-like protein is an ER protein localized close to phloem plasmodesmata and enhances mobility of GFP proteins of different sizes.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"9 ","pages":"25152564261418821"},"PeriodicalIF":0.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147358337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to \"Remodelling of Cellular Protein Homeostasis by Enhanced ER-Mitochondrial Tethering\".","authors":"","doi":"10.1177/25152564251410390","DOIUrl":"https://doi.org/10.1177/25152564251410390","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1177/25152564251329704.].</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"9 ","pages":"25152564251410390"},"PeriodicalIF":0.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12914067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"What Peroxisomes (Don't) do to Mitochondria.","authors":"Margret H Bülow, Sven Thoms","doi":"10.1177/25152564251413010","DOIUrl":"10.1177/25152564251413010","url":null,"abstract":"<p><p>Mitochondria and peroxisomes have long been recognized as interconnected. More than half a century ago it was observed that both types of cell organelles exhibit defects in peroxisome biogenesis disorders. Remarkably, until today, the molecular basis of this connection remains elusive. This Short Review aims to highlight some of the functional links between peroxisomes and mitochondria, and how genetic defects in peroxisomes may impact mitochondria.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"9 ","pages":"25152564251413010"},"PeriodicalIF":0.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12855727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}