Contact (Thousand Oaks (Ventura County, Calif.))最新文献

{"title":"Plant NETWORKED and VAP27 Proteins Work in Complexes to Regulate Membrane-Based Functions.","authors":"Patrick J Duckney, Pengwei Wang, Patrick J Hussey","doi":"10.1177/25152564251342533","DOIUrl":"10.1177/25152564251342533","url":null,"abstract":"<p><p>Eukaryotic cells are subdivided into specialised organelle compartments, each with unique physiological environments and functions. Interaction and cross-talk between organelles is inherent to Eukaryotic life, and each organelle is physically interconnected to their surrounding subcellular components including the cytoskeleton and adjacent membrane compartments. In animals and yeast, the mechanisms of organelle interaction have been well characterised and are known to have fundamental importance to life. In contrast, we are only beginning to understand the mechanisms and functions of such interactions in plants. The discovery and ongoing characterisation of the NETWORKED (NET) protein family of plant actin-membrane adaptors has greatly advanced our understanding of the mechanisms of organelle-cytoskeletal interaction. Furthermore, unfolding investigation into the NET proteins has revealed their binding partner, VAMP-ASSOCIATED PROTEIN-27 (VAP27), to be a regulator of organelle tethering and interaction with previously unknown, specialised roles in plants. Research on NET and VAP27 proteins has rapidly increased our knowledge of the mechanisms regulating membrane interaction in plants, their functions in regulating cell structure and organisation, as well as their importance to plant growth, development and stress-response. Here, we discuss the discovery and characterisation of the NET and VAP27 proteins, their regulation of organelle interaction and their functions in plants.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251342533"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210655","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":"Artificial ER-Mitochondrion Tethering Restores Erg6 Localization and Lipid Droplet Formation in <i>Hansenula polymorpha Δpex23</i> and <i>Δpex29</i> Cells.","authors":"Haiqiong Chen, Rinse de Boer, David C Lamb, Steven L Kelly, Ida J van der Klei","doi":"10.1177/25152564251336908","DOIUrl":"https://doi.org/10.1177/25152564251336908","url":null,"abstract":"<p><p>Pex23 proteins are a family of fungal endoplasmic reticulum proteins. <i>Hansenula polymorpha</i> contains four members, two of which, Pex24 and Pex32, function in endoplasmic reticulum-peroxisome membrane contact sites. In the absence of the other two members, Pex23 and Pex29, mitochondria are fragmented and lipid droplet numbers are reduced. We here show that in <i>Δpex23</i> and <i>Δpex29</i> cells an increased portion of the lipid droplet protein Erg6 (C24-methyltransferase), an enzyme involved in ergosterol biosynthesis, localizes to mitochondria. Erg6 relocalization and the reduction in lipid droplet numbers are suppressed by an artificial endoplasmic reticulum-mitochondrion tether protein. Sterol measurements showed that the presence of Erg6 at mitochondria did not cause major changes in the overall sterol composition. Our findings suggest that Pex23 and Pex29 play a role in endoplasmic reticulum-mitochondrion contact sites which prevent mitochondrial mislocalization of Erg6.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251336908"},"PeriodicalIF":0.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056738","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":"Profiling the LAM Family of Contact Site Tethers Provides Insights into Their Regulation and Function.","authors":"Emma J Fenech, Meital Kupervaser, Angela Boshnakovska, Shani Ravid, Inês Gomes Castro, Yeynit Asraf, Sylvie Callegari, Christof Lenz, Henning Urlaub, Peter Rehling, Maya Schuldiner","doi":"10.1177/25152564251321770","DOIUrl":"https://doi.org/10.1177/25152564251321770","url":null,"abstract":"<p><p>Membrane contact sites are molecular bridges between organelles that are sustained by tethering proteins and enable organelle communication. The endoplasmic reticulum (ER) membrane harbors many distinct families of tether proteins that enable the formation of contacts with all other organelles. One such example is the LAM (Lipid transfer protein Anchored at Membrane contact sites) family in yeast, which is composed of six members, each containing a putative lipid binding and transfer domain and an ER-embedded transmembrane segment. The family is divided into three homologous pairs each unique in their molecular architecture and localization to different ER subdomains. However, what determines the distinct localization of the different LAMs and which specific roles they carry out in each contact are still open questions. To address these, we utilized a labeling approach to profile the proximal protein landscape of the entire family. Focusing on unique, candidate interactors we could support that Lam5 resides at the ER-mitochondria contact site and demonstrate a role for it in sustaining mitochondrial activity. Capturing shared, putative interactors of multiple LAMs, we show how the Lam1/3 and Lam2/4 paralogous pairs could be associated specifically with the plasma membrane. Overall, our work provides new insights into the regulation and function of the LAM family members. More globally it demonstrates how proximity labeling can help identify the shared or unique functions of paralogous proteins.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251321770"},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051866","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":"Mitochondria-Plasma Membrane Contact Sites: Emerging Regulators of Mitochondrial Form and Function.","authors":"Jason C Casler, Matilde V Neto, Thomas Burgoyne, Laura L Lackner","doi":"10.1177/25152564251332141","DOIUrl":"10.1177/25152564251332141","url":null,"abstract":"<p><p>Sites of close apposition between organelles, known as membrane contact sites (MCSs), are critical regulators of organelle function. Mitochondria form elaborate reticular networks that perform essential metabolic and signaling functions. Many mitochondrial functions are regulated by MCSs formed between mitochondria and other organelles. In this review, we aim to bring attention to an understudied, but physiologically important, MCS between mitochondria and the plasma membrane (PM). We first describe the molecular mechanism of mitochondria-PM tethering in budding yeast and discuss its role in regulating multiple biological processes, including mitochondrial dynamics and lipid metabolism. Next, we discuss the evidence for mitochondria-PM tethering in higher eukaryotes, with a specific emphasis on mitochondria-PM contacts in retinal cells, and speculate on their functions. Finally, we discuss unanswered questions to guide future research into the function of mitochondria-PM contact sites.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251332141"},"PeriodicalIF":0.0,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061829","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":"Remodelling of Cellular Protein Homeostasis by Enhanced ER-Mitochondrial Tethering.","authors":"Elisa Tonelli, Justyna Malecka, Elettra Barberis, Camilla Romano, Emanuela Pessolano, Maria Talmon, Armando A Genazzani, Claudio Casali, Marco Biggiogera, Marcello Manfredi, Laura Tapella, Dmitry Lim, Giulia Dematteis","doi":"10.1177/25152564251329704","DOIUrl":"10.1177/25152564251329704","url":null,"abstract":"<p><p>Alterations of endoplasmic reticulum (ER)-mitochondrial interaction have been associated with different pathological conditions, including neurodegenerative diseases, characterized by dysregulation of protein homeostasis. However, little is known about how enhanced ER-mitochondrial tethering affects cellular proteostatic machinery. Here, we transiently overexpressed synthetic ER-mitochondrial linkers (EMLs), stabilizing the ER-mitochondrial distance at ≤5 nm (denominated as 5 nm-EML) and ∼10 nm (10 nm-EML), in HeLa cells. No alterations were found in cell growth, although metabolic activity and total ATP were significantly reduced. In EML-expressing cells, global protein synthesis was significantly reduced, accompanied by a reduction of total PERK and eIF2α protein levels, but increased p-eIF2α. Unfolded protein response (UPR) markers ATF4 and ATF6 were upregulated, suggesting that enhanced ER-mitochondrial tethering deranges protein synthesis and induces a low-grade ER stress/UPR. To further investigate ER-mitochondrial tethering-induced protein dyshomeostasis, we performed shotgun mass spectrometry proteomics followed by bioinformatic analysis. Analysis of highly changed proteins and the most significantly overrepresented gene ontology (GO) terms revealed that ≤5 nm tethering preferentially affected the expression of proteins involved in RNA processing and splicing and proteasomal protein degradation, while ∼10 nm tethering preferentially affected protein translation. Both EMLs affected expression of proteins involved in mitochondrial bioenergetics and metabolism, defense against oxidative stress, ER protein homeostasis, signaling and secretion. Finally, lipidomic analysis suggests that 5 nm-EML and 10 nm-EML differentially affect lipid homeostasis. Altogether, our results suggest that enhanced ER-mitochondrial tethering leads to a profound remodeling of cellular protein homeostasis, which may play a key role in pathogenesis of Alzheimer's and other neurodegenerative diseases.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251329704"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775189","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":"Comparative Analysis of SPLICS and MCS-DETECT for Detecting Mitochondria-ER Contact Sites (MERCs).","authors":"Jieyi Zheng, Ben Cardoen, Milene Ortiz-Silva, Ghassan Hamarneh, Ivan R Nabi","doi":"10.1177/25152564251313721","DOIUrl":"10.1177/25152564251313721","url":null,"abstract":"<p><p>Detection of mitochondria-ER contacts (MERCs) from diffraction limited confocal images commonly uses fluorescence colocalization analysis of mitochondria and endoplasmic reticulum (ER) as well as split fluorescent probes, such as the split-GFP-based contact site sensor (SPLICS). However, inter-organelle distances (∼10-60 nm) for MERCs are lower than the 200-250 nm diffraction limited resolution obtained by standard confocal microscopy. Super-resolution microscopy of 3D volume analysis provides a two-fold resolution improvement (∼120 nm XY; 250 nm Z), which remains unable to resolve MERCs. MCS-DETECT, a membrane contact site (MCS) detection algorithm faithfully detects elongated ribosome-studded riboMERCs when applied to 3D STED super-resolution image volumes. Here, we expressed the SPLICS_L reporter in HeLa cells co-transfected with the ER reporter RFP-KDEL and label fixed cells with antibodies to RFP and the mitochondrial protein TOM20. MCS-DETECT analysis of 3D STED volumes was compared to contacts determined by co-occurrence colocalization analysis of mitochondria and ER or the SPLICS_L probe. Percent mitochondria coverage by MCS-DETECT derived contacts was significantly smaller than those obtained for colocalization analysis or SPLICS_L, and more closely matched contact site metrics obtained by 3D electron microscopy. Further, STED analysis localized a subset of the SPLICS_L label to mitochondria with some SPLICS_L puncta observed to be completely enveloped by mitochondria in 3D views. These data suggest that MCS-DETECT reports on a limited set of MERCs that more closely corresponds to those observed by EM.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251313721"},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672165","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":"Mitochondria-Lysosome Contact Sites: Emerging Players in Cellular Homeostasis and Disease.","authors":"Francesca Rizzollo, Patrizia Agostinis","doi":"10.1177/25152564251329250","DOIUrl":"10.1177/25152564251329250","url":null,"abstract":"<p><p>Mitochondria and lysosomes regulate a multitude of biological processes that are essential for the maintenance of nutrient and metabolic homeostasis and overall cell viability. Recent evidence reveals that these pivotal organelles, similarly to others previously studied, communicate through specialized membrane contact sites (MCSs), hereafter referred to as mitochondria-lysosome contacts (or MLCs), which promote their dynamic interaction without involving membrane fusion. Signal integration through MLCs is implicated in key processes, including mitochondrial fission and dynamics, and the exchange of calcium, cholesterol, and amino acids. Impairments in the formation and function of MLCs are increasingly associated with age-related diseases, specifically neurodegenerative disorders and lysosomal storage diseases. However, MLCs may play roles in other pathological contexts where lysosomes and mitochondria are crucial. In this review, we introduce the methodologies used to study MLCs and discuss known molecular players and key factors involved in their regulation in mammalian cells. We also argue other potential regulatory mechanisms depending on the acidic lysosomal pH and their impact on MLC's function. Finally, we explore the emerging implications of dysfunctional mitochondria-lysosome interactions in disease, highlighting their potential as therapeutic targets in cancer.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251329250"},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665795","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":"Editorial on Special Collection in <i>Contact</i>: Lipid Transfer Proteins: From Molecular Mechanisms to Functional Validation.","authors":"Bruno Mesmin","doi":"10.1177/25152564251322628","DOIUrl":"10.1177/25152564251322628","url":null,"abstract":"","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251322628"},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485345","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":"Mitochondrial-ER Contact Sites and Tethers Influence the Biosynthesis and Function of Coenzyme Q.","authors":"Noelle Alexa Novales, Hadar Meyer, Yeynit Asraf, Maya Schuldiner, Catherine F Clarke","doi":"10.1177/25152564251316350","DOIUrl":"10.1177/25152564251316350","url":null,"abstract":"<p><p>Coenzyme Q (CoQ) is an essential redox-active lipid that plays a major role in the electron transport chain, driving mitochondrial ATP synthesis. In <i>Saccharomyces cerevisiae</i> (yeast), CoQ biosynthesis occurs exclusively in the mitochondrial matrix via a large protein-lipid complex, the CoQ synthome, comprised of CoQ itself, late-stage CoQ-intermediates, and the polypeptides Coq3-Coq9 and Coq11. Coq11 is suggested to act as a negative modulator of CoQ synthome assembly and CoQ synthesis, as its deletion enhances Coq polypeptide content, produces an enlarged CoQ synthome, and restores respiration in mutants lacking the CoQ chaperone polypeptide, Coq10. The CoQ synthome resides in specific niches within the inner mitochondrial membrane, termed CoQ domains, that are often located adjacent to the endoplasmic reticulum-mitochondria encounter structure (ERMES). Loss of ERMES destabilizes the CoQ synthome and renders CoQ biosynthesis less efficient. Here we show that deletion of <i>COQ11</i> suppresses the respiratory deficient phenotype of select <i>ERMES</i> mutants, results in repair and reorganization of the CoQ synthome, and enhances mitochondrial CoQ domains. Given that ER-mitochondrial contact sites coordinate CoQ biosynthesis, we used a Split-MAM (Mitochondrial Associated Membrane) artificial tether consisting of an ER-mitochondrial contact site reporter, to evaluate the effects of artificial membrane tethers on CoQ biosynthesis in both wild-type and <i>ERMES</i> mutant yeast strains. Overall, this work identifies the deletion of <i>COQ11</i> as a novel suppressor of phenotypes associated with <i>ERMES</i> deletion mutants and indicates that ER-mitochondria tethers influence CoQ content and turnover, highlighting the role of membrane contact sites in regulating mitochondrial respiratory homeostasis.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564251316350"},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191653","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":"Remodeling of ER Membrane Contact Sites During Cell Division.","authors":"Fang Yu, Khaled Machaca","doi":"10.1177/25152564241309207","DOIUrl":"https://doi.org/10.1177/25152564241309207","url":null,"abstract":"<p><p>Membrane contact sites (MCS) provide specialized conduits for inter-organelle communications to maintain cellular homeostasis. Most organelles are interconnected, which supports their coordination and function. M-phase (mitosis or meiosis) is associated with dramatic cellular remodeling to support cell division, including the equal distribution of organelles to the two daughter cells. However, the fate of MCS in M-phase is poorly understood. Here we review recent advances arguing for differential remodeling of endoplasmic reticulum (ER) MCS with the plasma membrane (PM, ERPMCS) and the mitochondria (MERCS) during cell division.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"8 ","pages":"25152564241309207"},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070547","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}