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28 results on '"Delaunay‐Moisan, Agnès"'

1. Physiologically relevant reconstitution of iron-sulfur cluster biosynthesis uncovers persulfide-processing functions of ferredoxin-2 and frataxin

Author

Gervason, Sylvain, Larkem, Djabir, Mansour, Amir Ben, Botzanowski, Thomas, Müller, Christina S., Pecqueur, Ludovic, Le Pavec, Gwenaelle, Delaunay-Moisan, Agnès, Brun, Omar, Agramunt, Jordi, Grandas, Anna, Fontecave, Marc, Schünemann, Volker, Cianférani, Sarah, Sizun, Christina, Tolédano, Michel B., and D’Autréaux, Benoit

Published
2019
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2. Fast and Bioorthogonal Release of Isocyanates in Living Cells from Iminosydnones and Cycloalkynes

Author

Ribéraud, Maxime, primary, Porte, Karine, additional, Chevalier, Arnaud, additional, Madegard, Léa, additional, Rachet, Aurélie, additional, Delaunay-Moisan, Agnès, additional, Vinchon, Florian, additional, Thuéry, Pierre, additional, Chiappetta, Giovanni, additional, Champagne, Pier Alexandre, additional, Pieters, Grégory, additional, Audisio, Davide, additional, and Taran, Frédéric, additional

Published
2023
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3. Transit of H2O2 across the endoplasmic reticulum membrane is not sluggish

Author

Appenzeller-Herzog, Christian, Bánhegyi, Gabor, Bogeski, Ivan, Davies, Kelvin J.A., Delaunay-Moisan, Agnès, Forman, Henry Jay, Görlach, Agnes, Kietzmann, Thomas, Laurindo, Francisco, Margittai, Eva, Meyer, Andreas J., Riemer, Jan, Rützler, Michael, Simmen, Thomas, Sitia, Roberto, Toledano, Michel B., and Touw, Ivo P.

Published
2016
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6. Une infection antérieure par des coronavirus saisonniers n’empêche pas la COVID-19 chez les enfants

Author

Sermet-Gaudelus, Isabelle, Temmam, Sarah, Huon, Christèle, Behillil, Sylvie, Gajdos, Vincent, Bigot, Thomas, Lurier, Thibaut, Chrétien, Delphine, Backovic, Marija, Delaunay-Moisan, Agnès, Donati, Flora, Albert, Mélanie, Foucaud, Elsa, Mesplées, Bettina, Benoist, Grégoire, Faye, Albert, Duval-Arnould, Marc, Cretolle, Célia, Charbit, Marina, Aubart, Mélodie, Auriau, Johanne, Lorrot, Mathie, Kariyawasam, Dulanjalee, Fertitta, Laura, Orliaguet, Gilles, Pigneur, Bénédicte, Bader-Meunier, Brigitte, Briand, Coralie, Enouf, Vincent, Toubiana, Julie, Guilleminot, Tiffany, van Der Werf, Sylvie, Leruez-Ville, Marianne, Eloit, Marc, Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris] (IP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Département Plateforme (PF I2BC), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Hôpital Jean Verdier [AP-HP], Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Ambroise Paré [AP-HP], Hôpital Robert Debré, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de neurochirurgie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, École nationale vétérinaire - Alfort (ENVA), Institut Pasteur, ANR, Commission européenne, CRNS, Université Paris Cité, Santé publique France, and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)

Subjects
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Abstract

International audience; Justification: Les enfants présentent un faible taux de COVID-19 et de syndrome inflammatoire multisystémique sévère apparenté à la maladie de Kawasaki (MIS) mais présentent une prévalence élevée d'infections aux coronavirus saisonniers.Objectif: Nous avons évalué par sérologie si une infection antérieure par les coronavirus saisonniers (NL63, HKU1, 229E, OC43) pouvait fournir une immunité croisée contre l'infection par le SARS-CoV-2 chez les enfants.Méthodes: Une étude observationnelle multicentrique transversale a été mise en place chez i) des enfants pauci- ou asymptomatiques hospitalisés à Paris lors de la première vague pour des raisons autres qu’une infection à SARS-CoV-2 (groupe HOS, n = 739) ; et ii) des enfants présentant un syndrome inflammatoire multisystémique (groupe MIS, n = 36). Un test LIPS d’immunoprécipitation a été utilisé afin de mesurer la présence d’anticorps anti-SARS-CoV-2 dirigés contre les domaines C-terminal de la nucléoprotéine N et les domaines S1 et S2 de la protéine de spicule S. Un total de 69 patients séropositifs pour SARS-CoV-2, dont 15 MIS, et de 115 patients séronégatifs (CTL) appariés en fonction de l’âge et du sexe ont été sélectionnés afin de mesurer le niveau d’anticorps dirigés contre le SARS-CoV-2 et les coronavirus saisonniers (HCoV). La séroprévalence et le niveau de réponse anticorps dirigés contre les différents virus ont servi à évaluer si l’infection à SARS-CoV-2 chez les enfants est influencée par une infection antérieure par des coronavirus saisonniers. Principaux résultats: La prévalence des infections à HCoV était très élevée et similaire dans les trois groupes HOS, MIS et CTL. De même, les niveaux de réponse anticorps dirigés contre les HCoV n'étaient pas significativement différents dans les trois groupes et n'étaient pas corrélés au niveau de réponse anticorps anti-SARS-CoV-2 dans les groupes HOS et MIS. Les profils d'anticorps anti-SARS-CoV-2 étaient différents chez les enfants des groupes HOS et MIS, avec un niveau de réponse anti-S1 et –N significativement plus élevés chez les enfants atteints de syndrome inflammatoire multisystémique.Conclusion: Une infection antérieure par les coronavirus saisonniers (évaluée par sérologie) n'interfère pas avec le risque d’être infecté par le SARS-CoV-2 ni avec celui de développer un MIS chez les enfants.

Published
2021

9. Prior infection by seasonal coronaviruses, as assessed by serology, does not prevent SARS-CoV-2 infection and disease in children, France, April to June 2020

Author

Sermet-Gaudelus, Isabelle, primary, Temmam, Sarah, additional, Huon, Christèle, additional, Behillil, Sylvie, additional, Gajdos, Vincent, additional, Bigot, Thomas, additional, Lurier, Thibaut, additional, Chrétien, Delphine, additional, Backovic, Marija, additional, Delaunay-Moisan, Agnès, additional, Donati, Flora, additional, Albert, Mélanie, additional, Foucaud, Elsa, additional, Mesplées, Bettina, additional, Benoist, Grégoire, additional, Faye, Albert, additional, Duval-Arnould, Marc, additional, Cretolle, Célia, additional, Charbit, Marina, additional, Aubart, Mélodie, additional, Auriau, Johanne, additional, Lorrot, Mathie, additional, Kariyawasam, Dulanjalee, additional, Fertitta, Laura, additional, Orliaguet, Gilles, additional, Pigneur, Bénédicte, additional, Bader-Meunier, Brigitte, additional, Briand, Coralie, additional, Enouf, Vincent, additional, Toubiana, Julie, additional, Guilleminot, Tiffany, additional, van der Werf, Sylvie, additional, Leruez-Ville, Marianne, additional, and Eloit, Marc, additional

Published
2021
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11. The importance of naturally attenuated SARS‐CoV ‐2 in the fight against COVID ‐19

Author

Armengaud, Jean, Delaunay‐Moisan, Agnès, Thuret, Jean‐Yves, Anken, Eelco, Acosta‐Alvear, Diego, Aragón, Tomás, Arias, Carolina, Blondel, Marc, Braakman, Ineke, Collet, Jean‐François, Courcol, René, Danchin, Antoine, Deleuze, Jean‐François, Lavigne, Jean‐Philippe, Lucas, Sophie, Michiels, Thomas, Moore, Edward R. B., Nixon‐Abell, Jonathon, Rossello‐Mora, Ramon, Shi, Zheng‐Li, Siccardi, Antonio G., Sitia, Roberto, Tillett, Daniel, Timmis, Kenneth N., Toledano, Michel B., Sluijs, Peter, Vicenzi, Elisa, Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Stress Oxydatif et Cancer (SOC), Département Biologie Cellulaire (BioCell), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Sénescence et stabilité génomique (SEN), Département Biologie des Génomes (DBG), San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, University of California [Santa Barbara] (UC Santa Barbara), University of California (UC), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé (UBO UFR MSS), Utrecht University [Utrecht], Université Catholique de Louvain = Catholic University of Louvain (UCL), Walloon Excellence in Life sciences and BIOtechnology [Liège] (WELBIO), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Gothenburg (GU), Sahlgrenska University Hospital [Gothenburg], University of Cambridge [UK] (CAM), Institut Mediterrani d'Estudis Avancats (IMEDEA), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universidad de las Islas Baleares (UIB), Wuhan Institute of Virology [Wuhan, China], Chinese Academy of Sciences [Wuhan Branch], Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig], ANR-17-CE18-0023,Phylopeptidomics,Identification rapide de bactéries pathogènes et résistances aux antibiotiques(2017), Armengaud, Jean [0000-0003-1589-445X], Thuret, Jean-Yves [0000-0001-5385-7620], Anken, Eelco van [0000-0001-9529-2701], Acosta-Alvear, Diego [0000-0002-1139-8486], Aragón, Tomás [0000-0002-1700-2729], Arias, Carolina [0000-0002-4445-0826], Blondel, Marc [0000-0003-4897-2995], Braakman, Ineke [0000-0003-1592-4364], Collet, Jean-François [0000-0001-8069-7036], Courcol, René [0000-0003-2324-5687], Danchin, Antoine [0000-0002-6350-5001], Deleuze, Jean-François [0000-0002-5358-4463], Lavigne, Jean-Philippe [0000-0002-9484-0304], Lucas, Sophie [0000-0003-1287-7996], Michiels, Thomas [0000-0001-9615-8053], Moore, Edward R.B. [0000-0001-7693-924X], Nixon-Abell, Jonathon [0000-0003-4169-0012], Rosselló-Mora, Ramón [0000-0001-8253-3107], Shi, Zheng-Li [0000-0001-8089-163X], Siccardi, Antonio G. [0000-0002-1654-5545], Sitia, Roberto [0000-0001-7086-4152], Tillett, Daniel [0000-0003-1061-0489], Timmis, Kenneth N. [0000-0002-0066-4670], Toledano, Michel B. [0000-0002-3079-1179], Sluijs, Peter van der [0000-0002-4485-3342], Vicenzi, Elisa [0000-0003-0051-3968], University of California [Santa Barbara] (UCSB), University of California, Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Technical University Braunschweig, Armengaud, Jean, Thuret, Jean-Yves, Anken, Eelco van, Acosta-Alvear, Diego, Aragón, Tomás, Arias, Carolina, Blondel, Marc, Braakman, Ineke, Collet, Jean-François, Courcol, René, Danchin, Antoine, Deleuze, Jean-François, Lavigne, Jean-Philippe, Lucas, Sophie, Michiels, Thomas, Moore, Edward R.B., Nixon-Abell, Jonathon, Rosselló-Mora, Ramón, Shi, Zheng-Li, Siccardi, Antonio G., Sitia, Roberto, Tillett, Daniel, Timmis, Kenneth N., Toledano, Michel B., Sluijs, Peter van der, Vicenzi, Elisa, Armengaud, J., Delaunay-Moisan, A., Thuret, J. -Y., van Anken, E., Acosta-Alvear, D., Aragon, T., Arias, C., Blondel, M., Braakman, I., Collet, J. -F., Courcol, R., Danchin, A., Deleuze, J. -F., Lavigne, J. -P., Lucas, S., Michiels, T., Moore, E. R. B., Nixon-Abell, J., Rossello-Mora, R., Shi, Z., Siccardi, A. G., Sitia, R., Tillett, D., Timmis, K. N., Toledano, M. B., van der Sluijs, P., Vicenzi, E., and UCL - SSS/DDUV - Institut de Duve

Subjects
Opinion, viruses, Pneumonia, Viral, Gene Expression, Microbiology, Disease Outbreaks, Evolution, Molecular, Betacoronavirus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Animals, Humans, Health emergency, Selection, Genetic, Pandemics, Ecology, Evolution, Behavior and Systematics, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Virulence, SARS-CoV-2, fungi, COVID-19, SARS Virus, Adaptation, Physiological, Severe acute respiratory syndrome-related coronavirus, Host-Pathogen Interactions, Mutation, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Coronavirus Infections
Abstract

The current SARS‐CoV‐2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID‐19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS‐CoV‐2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS‐CoV‐2 would offer significant relief, although vaccine developers have warned that design, testing and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (i), but the earliest vaccines were based on the live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS‐CoV‐2 will mutate and may naturally attenuate over time (ii). What makes the current pandemic unique is that, thanks to state‐of‐the‐art nucleic acid sequencing technologies, we can follow in detail how SARS‐CoV‐2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS‐CoV‐2 variants across the globe should be of key interest in our fight against the pandemic.

Published
2020
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12. The importance of naturally attenuated SARS‐CoV‐2in the fight against COVID‐19

Author

Armengaud, Jean, primary, Delaunay‐Moisan, Agnès, additional, Thuret, Jean‐Yves, additional, van Anken, Eelco, additional, Acosta‐Alvear, Diego, additional, Aragón, Tomás, additional, Arias, Carolina, additional, Blondel, Marc, additional, Braakman, Ineke, additional, Collet, Jean‐François, additional, Courcol, René, additional, Danchin, Antoine, additional, Deleuze, Jean‐François, additional, Lavigne, Jean‐Philippe, additional, Lucas, Sophie, additional, Michiels, Thomas, additional, Moore, Edward R. B., additional, Nixon‐Abell, Jonathon, additional, Rossello‐Mora, Ramon, additional, Shi, Zheng‐Li, additional, Siccardi, Antonio G., additional, Sitia, Roberto, additional, Tillett, Daniel, additional, Timmis, Kenneth N., additional, Toledano, Michel B., additional, van der Sluijs, Peter, additional, and Vicenzi, Elisa, additional

Published
2020
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14. Ouabain and chloroquine trigger senolysis of BRAF‐V600E‐induced senescent cells by targeting autophagy.

Author

L'Hôte, Valentin, Courbeyrette, Régis, Pinna, Guillaume, Cintrat, Jean‐Christophe, Le Pavec, Gwenaëlle, Delaunay‐Moisan, Agnès, Mann, Carl, and Thuret, Jean‐Yves

Subjects
OUABAIN, CHLOROQUINE, AUTOPHAGY, ION transport (Biology), CELLULAR aging, CELL death
Abstract

The expression of BRAF‐V600E triggers oncogene‐induced senescence in normal cells and is implicated in the development of several cancers including melanoma. Here, we report that cardioglycosides such as ouabain are potent senolytics in BRAF senescence. Sensitization by ATP1A1 knockdown and protection by supplemental potassium showed that senolysis by ouabain was mediated by the Na,K‐ATPase pump. Both ion transport inhibition and signal transduction result from cardioglycosides binding to Na,K‐ATPase. An inhibitor of the pump that does not trigger signaling was not senolytic despite blocking ion transport, demonstrating that signal transduction is required for senolysis. Ouabain triggered the activation of Src, p38, Akt, and Erk in BRAF‐senescent cells, and signaling inhibitors prevented cell death. The expression of BRAF‐V600E increased ER stress and autophagy in BRAF‐senescent cells and sensitized the cell to senolysis by ouabain. Ouabain inhibited autophagy flux, which was restored by signaling inhibitors. Consequently, we identified autophagy inhibitor chloroquine as a novel senolytic in BRAF senescence based on the mode of action of cardioglycosides. Our work underlies the interest of characterizing the mechanisms of senolytics to discover novel compounds and identifies the endoplasmic reticulum stress‐autophagy tandem as a new vulnerability in BRAF senescence that can be exploited for the development of further senolytic strategies. [ABSTRACT FROM AUTHOR]

Published
2021
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15. A guide to assessing endoplasmic reticulum homeostasis and stress in mammalian systems.

Author

Sicari, Daria, Delaunay‐Moisan, Agnès, Combettes, Laurent, Chevet, Eric, and Igbaria, Aeid

Subjects
*ENDOPLASMIC reticulum, *HOMEOSTASIS, *INTRACELLULAR calcium, *MEMBRANE proteins, *LIPID synthesis, *PROTEIN folding
Abstract

The endoplasmic reticulum (ER) is a multifunctional organelle that constitutes the entry into the secretory pathway. The ER contributes to the maintenance of cellular calcium homeostasis, lipid synthesis and productive secretory, and transmembrane protein folding. Physiological, chemical, and pathological factors that compromise ER homeostasis lead to endoplasmic reticulum stress (ER stress). To cope with this situation, cells activate an adaptive signaling pathway termed the unfolded protein response (UPR) that aims at restoring ER homeostasis. The UPR is transduced through post‐translational, translational, post‐transcriptional, and transcriptional mechanisms initiated by three ER‐resident sensors, inositol‐requiring protein 1α, activating transcription factor 6α, and PRKR‐like endoplasmic reticulum kinase. Determining the in and out of ER homeostasis control and UPR activation still represents a challenge for the community. Hence, standardized criteria and methodologies need to be proposed for monitoring ER homeostasis and ER stress in different model systems. Here, we summarize the pathways that are activated during ER stress and provide approaches aimed at assess ER homeostasis and stress in vitro and in vivo mammalian systems that can be used by researchers to plan and interpret experiments. We recommend the use of multiple assays to verify ER stress because no individual assay is guaranteed to be the most appropriate one. [ABSTRACT FROM AUTHOR]

Published
2020
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17. Endoplasmic reticulum transport of glutathione by Sec61 is regulated by Ero1 and Bip

Author

Ponsero, Alise J., Igbaria, Aeid, Darch, Maxwell A., Miled, Samia, Outten, Caryn E., Winther, Jakob R., Palais, Gael, D'Autréaux, Benoit, Delaunay-Moisan, Agnès, Toledano, Michel B., Ponsero, Alise J., Igbaria, Aeid, Darch, Maxwell A., Miled, Samia, Outten, Caryn E., Winther, Jakob R., Palais, Gael, D'Autréaux, Benoit, Delaunay-Moisan, Agnès, and Toledano, Michel B.

Abstract

In the endoplasmic reticulum (ER), Ero1 catalyzes disulfide bond formation and promotes glutathione (GSH) oxidation to GSSG. Since GSSG cannot be reduced in the ER, maintenance of the ER glutathione redox state and levels likely depends on ER glutathione import and GSSG export. We used quantitative GSH and GSSG biosensors to monitor glutathione import into the ER of yeast cells. We found that glutathione enters the ER by facilitated diffusion through the Sec61 protein-conducting channel, while oxidized Bip (Kar2) inhibits transport. Increased ER glutathione import triggers H2O2-dependent Bip oxidation through Ero1 reductive activation, which inhibits glutathione import in a negative regulatory loop. During ER stress, transport is activated by UPR-dependent Ero1 induction, and cytosolic glutathione levels increase. Thus, the ER redox poise is tuned by reciprocal control of glutathione import and Ero1 activation. The ER protein-conducting channel is permeable to small molecules, provided the driving force of a concentration gradient. Ponsero et al. show that cytosol-to-ER transport of glutathione proceeds via facilitated diffusion through Sec61. Upon import, glutathione activates Ero1 by reduction, causing Bip oxidation and inhibition of glutathione transport. Coupling of glutathione ER import to Ero1 activation provides a basis for glutathione ER redox poise maintenance.

Published
2017

28. A scaffold protein that chaperones a cysteine-sulfenic acid in H 2 O 2 signaling.

Author

Bersweiler A, D'Autréaux B, Mazon H, Kriznik A, Belli G, Delaunay-Moisan A, Toledano MB, and Rahuel-Clermont S

Subjects
Cysteine metabolism, Hydrogen Peroxide metabolism, Molecular Chaperones metabolism, Saccharomyces cerevisiae Proteins metabolism, Signal Transduction, Sulfenic Acids metabolism, Transcription Factors metabolism
Abstract

In Saccharomyces cerevisiae, Yap1 regulates an H 2 O 2 -inducible transcriptional response that controls cellular H 2 O 2 homeostasis. H 2 O 2 activates Yap1 by oxidation through the intermediary of the thiol peroxidase Orp1. Upon reacting with H 2 O 2 , Orp1 catalytic cysteine oxidizes to a sulfenic acid, which then engages into either an intermolecular disulfide with Yap1, leading to Yap1 activation, or an intramolecular disulfide that commits the enzyme into its peroxidatic cycle. How the first of these two competing reactions, which is kinetically unfavorable, occurs was previously unknown. We show that the Yap1-binding protein Ybp1 brings together Orp1 and Yap1 into a ternary complex that selectively activates condensation of the Orp1 sulfenylated cysteine with one of the six Yap1 cysteines while inhibiting Orp1 intramolecular disulfide formation. We propose that Ybp1 operates as a scaffold protein and as a sulfenic acid chaperone to provide specificity in the transfer of oxidizing equivalents by a reactive sulfenic acid species.

Published
2017
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