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mtDNA-Depleted Mitochondria Form Sites of Contact with the Nucleus and Alter the Cellular Epigenome. mtdna缺失的线粒体形成与细胞核接触的位点并改变细胞表观基因组。
Contact (Thousand Oaks (Ventura County, Calif.)) Pub Date : 2026-03-16 eCollection Date: 2026-01-01 DOI: 10.1177/25152564261428840
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}
引用次数: 0
A Novel Phloem-Specific HVA22-Like Protein Facilitates Protein Movement via Plasmodesmata in Potato. 一种新的韧皮部特异性hva22样蛋白促进蛋白质通过马铃薯间连丝的运动。
Contact (Thousand Oaks (Ventura County, Calif.)) Pub Date : 2026-02-28 eCollection Date: 2026-01-01 DOI: 10.1177/25152564261418821
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":"https://doi.org/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}
引用次数: 0
Corrigendum to "Remodelling of Cellular Protein Homeostasis by Enhanced ER-Mitochondrial Tethering". “通过增强er -线粒体栓系重塑细胞蛋白质稳态”的勘误表。
Contact (Thousand Oaks (Ventura County, Calif.)) Pub Date : 2026-02-17 eCollection Date: 2026-01-01 DOI: 10.1177/25152564251410390
{"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}
引用次数: 0
What Peroxisomes (Don't) do to Mitochondria. 过氧化物酶体对线粒体有什么作用?
Contact (Thousand Oaks (Ventura County, Calif.)) Pub Date : 2026-01-29 eCollection Date: 2026-01-01 DOI: 10.1177/25152564251413010
Margret H Bülow, Sven Thoms
{"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}
引用次数: 0
Pseudomonas syringae HopN1 Binds Plant VAP12 and a Rho-GTPase, Suggesting a Role in Membrane-Associated Processes. 丁香假单胞菌HopN1结合植物VAP12和Rho-GTPase,提示在膜相关过程中起作用。
Contact (Thousand Oaks (Ventura County, Calif.)) Pub Date : 2025-09-04 eCollection Date: 2025-01-01 DOI: 10.1177/25152564251376890
Charlotte Brinkmann, Jennifer Bortlik, Frederik Börnke
{"title":"<i>Pseudomonas syringae</i> HopN1 Binds Plant VAP12 and a Rho-GTPase, Suggesting a Role in Membrane-Associated Processes.","authors":"Charlotte Brinkmann, Jennifer Bortlik, Frederik Börnke","doi":"10.1177/25152564251376890","DOIUrl":"10.1177/25152564251376890","url":null,"abstract":"<p><p>Many Gram-negative bacterial pathogens deploy type III effector proteins (T3Es) to manipulate host cellular processes and suppress immune responses. Increasing evidence suggests that certain T3Es mimic eukaryotic FFAT (two phenylalanines in an acidic tract) motifs, enabling interaction with vesicle-associated membrane protein (VAMP)-associated proteins (VAPs). These interactions likely help pathogens target and exploit host membrane contact sites. However, the significance and distribution of FFAT mimicry across different bacterial pathogens remain poorly understood, which is crucial to uncovering its role in pathogenic strategies. In this study, we analyzed the T3E repertoire of the model plant pathogenic bacterium <i>Pseudomonas syringae</i> pv. <i>tomato</i> (Pst) DC3000 to identify potential FFAT motifs. Our preliminary data reveal that HopN1, a Pst T3E belonging to the YopT/AvrPphB family of cysteine proteases, contains at least one functional FFAT motif. Yeast two-hybrid and <i>in planta</i> co-immunoprecipitation assays confirmed that HopN1 interacts with plant VAP proteins. This interaction suggests that VAP binding may facilitate its localization to specific membrane compartments. Furthermore, HopN1 was shown to interact with a plant RHO-GTPase, hinting at a functional parallel to YopT in mammals. Our findings demonstrate that HopN1 interacts with VAP12 and a plant RHO-GTPase, suggesting a potential role in membrane-associated processes. However, whether HopN1 actively exploits VAP proteins for subcellular localization remains to be determined. While FFAT motif mimicry may contribute to effector targeting in plant-pathogenic bacteria, further studies are required to establish its functional significance in HopN1 virulence.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251376890"},"PeriodicalIF":0.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017042","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}
引用次数: 0
MCS Ultrastructural Analyses Using Electron Microscopy. 电子显微镜下MCS超微结构分析。
Contact (Thousand Oaks (Ventura County, Calif.)) Pub Date : 2025-09-01 eCollection Date: 2025-01-01 DOI: 10.1177/25152564251372668
Atsuki Nara
{"title":"MCS Ultrastructural Analyses Using Electron Microscopy.","authors":"Atsuki Nara","doi":"10.1177/25152564251372668","DOIUrl":"10.1177/25152564251372668","url":null,"abstract":"<p><p>Membrane contact sites (MCSs) are microdomains that exchange ions and lipids between the membranes of two organelles. They facilitate the exchange of metabolites and act as a site for intracellular communication through material transport. Because of the important physiological significance of MCSs in localizing the exchange of substances and metabolic regulation, they are considered to play an important role in cell biology. Understanding MCS structure is essential for analyzing how substances move to and from each organelle. Several methods have been developed to analyze MCS function, with electron microscopy (EM) being the predominant technique when structural detail is needed. In this review, we summarize the ultrastructure of MCSs and how EM can be used to determine their role in cell biology.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251372668"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994970","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}
引用次数: 0
Via Proteins and Lipids - Versatility of VAPs at Dynamic Membrane Contact Sites. 通过蛋白质和脂质- VAPs在动态膜接触部位的多功能性。
Contact (Thousand Oaks (Ventura County, Calif.)) Pub Date : 2025-08-26 eCollection Date: 2025-01-01 DOI: 10.1177/25152564251372673
Dan Zhang
{"title":"Via Proteins and Lipids - Versatility of VAPs at Dynamic Membrane Contact Sites.","authors":"Dan Zhang","doi":"10.1177/25152564251372673","DOIUrl":"10.1177/25152564251372673","url":null,"abstract":"<p><p>VAMP-associated proteins (VAPs) are highly conserved, endoplasmic reticulum (ER)-resident receptors that tether the ER to various membrane compartments in eukaryotic cells. Each VAP contains a transmembrane helix at its extreme C-terminus and a conserved N-terminal major sperm protein (MSP) domain that mediates various cytosolic interactions via both protein and lipid binding. Here, I question the fundamental difference between protein- and lipid-based associations in VAP-driven membrane contact site (MCS) formation and function - could the lipid affinity of VAPs be an overlooked factor in MCS dynamic regulation?</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251372673"},"PeriodicalIF":0.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985197","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}
引用次数: 0
Membrane Contact Sites in Proteostasis and ER Stress Response. 蛋白静止和内质网应激反应中的膜接触位点。
Contact (Thousand Oaks (Ventura County, Calif.)) Pub Date : 2025-07-28 eCollection Date: 2025-01-01 DOI: 10.1177/25152564251363050
Febe Vermue, Aysegul Sapmaz, Ilana Berlin
{"title":"Membrane Contact Sites in Proteostasis and ER Stress Response.","authors":"Febe Vermue, Aysegul Sapmaz, Ilana Berlin","doi":"10.1177/25152564251363050","DOIUrl":"10.1177/25152564251363050","url":null,"abstract":"<p><p>Execution of all cellular functions depends on a healthy proteome, whose maintenance requires multimodal oversight. Roughly a third of human proteins reside in membranes and thus present unique topological challenges with respect to biogenesis and degradation. To meet these challenges, eukaryotes have evolved organellar pathways of protein folding and quality control. Most transmembrane proteins originate in the endoplasmic reticulum (ER), where they are subject to surveillance and, if necessary, removal through either ER-associated proteasomal degradation (cytosolic pathway) or selective autophagy (ER-phagy; organellar pathway). In the latter case, ER cargoes are shuttled to (endo)lysosomes - the same organelles that degrade cell surface molecules via endocytosis. Here, we provide an overview of dynamic coordination between the ER and endolysosomes, with a focus on their engagement in specialized physical interfaces termed membrane contact sites (MCSs). We cover how cross-compartmental integration through MCSs allows biosynthetic and proteolytic organelles to fine-tune each other's membrane composition, organization, and dynamics and facilitates recovery from proteotoxic stress. Along the way, we highlight recent developments and open questions at the crossroads between organelle biology and protein quality control and cast them against the backdrop of factor-specific diseases associated with perturbed membrane homeostasis.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251363050"},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746724","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}
引用次数: 0
Endoplasmic reticulum-Mitochondria Coupling in Alzheimer's Disease. 阿尔茨海默病的内质网-线粒体偶联。
Contact (Thousand Oaks (Ventura County, Calif.)) Pub Date : 2025-07-17 eCollection Date: 2025-01-01 DOI: 10.1177/25152564251330069
Michela Rossini, Tânia Fernandes, Irene D'Arsiè, Riccardo Filadi
{"title":"Endoplasmic reticulum-Mitochondria Coupling in Alzheimer's Disease.","authors":"Michela Rossini, Tânia Fernandes, Irene D'Arsiè, Riccardo Filadi","doi":"10.1177/25152564251330069","DOIUrl":"10.1177/25152564251330069","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common neurodegenerative disorder of the elderly and no cure is currently available, as the mechanisms leading to neuronal damage and cognitive impairments remain elusive. In the last years, accumulating evidence highlighted early perturbations of the communication between mitochondria and endoplasmic reticulum (ER) in AD models. In this short review, we summarize recent findings linking alterations of ER-mitochondria coupling with typical AD hallmarks.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251330069"},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677129","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}
引用次数: 0
Identification of ER:Melanosome Membrane Contact Sites in the Retinal Pigment Epithelium. 视网膜色素上皮内黑素小体膜接触部位的鉴定。
Contact (Thousand Oaks (Ventura County, Calif.)) Pub Date : 2025-06-02 eCollection Date: 2025-01-01 DOI: 10.1177/25152564251340949
T Burgoyne, D Doncheva, E R Eden
{"title":"Identification of ER:Melanosome Membrane Contact Sites in the Retinal Pigment Epithelium.","authors":"T Burgoyne, D Doncheva, E R Eden","doi":"10.1177/25152564251340949","DOIUrl":"10.1177/25152564251340949","url":null,"abstract":"<p><p>The retinal pigment epithelium (RPE) forms a monolayer of cells at the blood:retina interface that plays important roles for photoreceptor renewal and function and is central to retinal health. RPE pigment is provided by melanin-containing melanosomes which offer protection against light and oxidative stress. Melanosome migration into the apical processes of the RPE following light onset is thought to contribute to preventing retinal degeneration with age, though the mechanism is not yet clear. Melanosomes are transported along microtubules to the apical surface where they are transferred to actin filaments within the apical processes. Melanosomes are lysosome-related organelles derived from endosomes and endosome transport along microtubules is heavily influenced by the endoplasmic reticulum (ER) through ER:endosome contact sites. Here we describe extensive connection between the ER and melanosomes in the RPE. We further show, in skin melanocytes, that the ER forms contact sites with all stages of melanosome maturation, but ER contact is reduced as melanosomes mature. Finally, we identify tripartite contact sites between the ER, melanosomes and mitochondria in both RPE tissue and cellular models, suggesting that the ER may influence melanosome biogenesis, maturation and interaction with mitochondria.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251340949"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218095","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}
引用次数: 0
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