Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosis
Summary: During infection, dengue virus (DENV) and Zika virus (ZIKV), two (ortho)flaviviruses of public health concern worldwide, induce alterations of mitochondria morphology to favor viral replication, suggesting a viral co-opting of mitochondria functions. Here, we performed an extensive transmis...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224028268 |
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| author | Wesley Freppel Viviana Andrea Barragan Torres Olus Uyar Anaïs Anton Zaynab Nouhi Mathilde Broquière Clément Mazeaud Aïssatou Aïcha Sow Alexanne Léveillé Claudia Gilbert Nicolas Tremblay Jonathan Eintrez Owen Cheyanne L. Bemis Xavier Laulhé Alain Lamarre Christopher J. Neufeldt Ian Gaël Rodrigue-Gervais Andreas Pichlmair Denis Girard Pietro Scaturro Laura Hulea Laurent Chatel-Chaix |
| author_facet | Wesley Freppel Viviana Andrea Barragan Torres Olus Uyar Anaïs Anton Zaynab Nouhi Mathilde Broquière Clément Mazeaud Aïssatou Aïcha Sow Alexanne Léveillé Claudia Gilbert Nicolas Tremblay Jonathan Eintrez Owen Cheyanne L. Bemis Xavier Laulhé Alain Lamarre Christopher J. Neufeldt Ian Gaël Rodrigue-Gervais Andreas Pichlmair Denis Girard Pietro Scaturro Laura Hulea Laurent Chatel-Chaix |
| author_sort | Wesley Freppel |
| collection | DOAJ |
| description | Summary: During infection, dengue virus (DENV) and Zika virus (ZIKV), two (ortho)flaviviruses of public health concern worldwide, induce alterations of mitochondria morphology to favor viral replication, suggesting a viral co-opting of mitochondria functions. Here, we performed an extensive transmission electron microscopy-based quantitative analysis to demonstrate that both DENV and ZIKV alter endoplasmic reticulum-mitochondria contact sites (ERMC). This correlated at the molecular level with an impairment of ERMC tethering protein complexes located at the surface of both organelles. Furthermore, virus infection modulated the mitochondrial oxygen consumption rate. Consistently, metabolomic and mitoproteomic analyses revealed a decrease in the abundance of several metabolites of the Krebs cycle and changes in the stoichiometry of the electron transport chain. Most importantly, ERMC destabilization by protein knockdown increased virus replication while dampening ZIKV-induced apoptosis. Overall, our results support the notion that flaviviruses hijack ERMCs to generate a cytoplasmic environment beneficial for sustained and efficient replication. |
| format | Article |
| id | doaj-art-a6e1d0fa45444f81a9d19c40cc1fead8 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-a6e1d0fa45444f81a9d19c40cc1fead82024-12-29T04:47:53ZengElsevieriScience2589-00422025-01-01281111599Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosisWesley Freppel0Viviana Andrea Barragan Torres1Olus Uyar2Anaïs Anton3Zaynab Nouhi4Mathilde Broquière5Clément Mazeaud6Aïssatou Aïcha Sow7Alexanne Léveillé8Claudia Gilbert9Nicolas Tremblay10Jonathan Eintrez Owen11Cheyanne L. Bemis12Xavier Laulhé13Alain Lamarre14Christopher J. Neufeldt15Ian Gaël Rodrigue-Gervais16Andreas Pichlmair17Denis Girard18Pietro Scaturro19Laura Hulea20Laurent Chatel-Chaix21Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaCentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaCentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaCentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaMaisonneuve-Rosemont Hospital Research Center, Montréal, Québec H1T 2M4, CanadaCentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaCentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaCentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaCentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaCentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaCentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USACentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaCentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USACentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaInstitute of Virology, Technical University of Munich, School of Medicine 81675 Munich, Germany; German Center of Infection Research (DZIF), Munich partner site, Munich, GermanyCentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, CanadaInstitute of Virology, Technical University of Munich, School of Medicine 81675 Munich, Germany; Leibniz Institute of Virology 20251 Hamburg, GermanyMaisonneuve-Rosemont Hospital Research Center, Montréal, Québec H1T 2M4, Canada; Department of Medicine, University of Montréal, Montréal, Québec H3C 3J7, CanadaCentre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, Canada; Center of Excellence in Orphan Diseases Research-Fondation Courtois, Québec, Canada; Regroupement Intersectoriel de Recherche en Santé de l’Université du Québec, Québec, Canada; Corresponding authorSummary: During infection, dengue virus (DENV) and Zika virus (ZIKV), two (ortho)flaviviruses of public health concern worldwide, induce alterations of mitochondria morphology to favor viral replication, suggesting a viral co-opting of mitochondria functions. Here, we performed an extensive transmission electron microscopy-based quantitative analysis to demonstrate that both DENV and ZIKV alter endoplasmic reticulum-mitochondria contact sites (ERMC). This correlated at the molecular level with an impairment of ERMC tethering protein complexes located at the surface of both organelles. Furthermore, virus infection modulated the mitochondrial oxygen consumption rate. Consistently, metabolomic and mitoproteomic analyses revealed a decrease in the abundance of several metabolites of the Krebs cycle and changes in the stoichiometry of the electron transport chain. Most importantly, ERMC destabilization by protein knockdown increased virus replication while dampening ZIKV-induced apoptosis. Overall, our results support the notion that flaviviruses hijack ERMCs to generate a cytoplasmic environment beneficial for sustained and efficient replication.http://www.sciencedirect.com/science/article/pii/S2589004224028268VirologyMembranesCell biologyProteomicsMetabolomics |
| spellingShingle | Wesley Freppel Viviana Andrea Barragan Torres Olus Uyar Anaïs Anton Zaynab Nouhi Mathilde Broquière Clément Mazeaud Aïssatou Aïcha Sow Alexanne Léveillé Claudia Gilbert Nicolas Tremblay Jonathan Eintrez Owen Cheyanne L. Bemis Xavier Laulhé Alain Lamarre Christopher J. Neufeldt Ian Gaël Rodrigue-Gervais Andreas Pichlmair Denis Girard Pietro Scaturro Laura Hulea Laurent Chatel-Chaix Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosis iScience Virology Membranes Cell biology Proteomics Metabolomics |
| title | Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosis |
| title_full | Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosis |
| title_fullStr | Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosis |
| title_full_unstemmed | Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosis |
| title_short | Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosis |
| title_sort | dengue virus and zika virus alter endoplasmic reticulum mitochondria contact sites to regulate respiration and apoptosis |
| topic | Virology Membranes Cell biology Proteomics Metabolomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224028268 |
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