ER stress; Recovery from stress; Ubiquitin proteasome system; ER-phagy; Autophagy; Molecular chaperones
Sánchez-Wandelmer Jana, Kriegenburg Franziska, Rohringer Sabrina, Schuschnig Martina, Gómez-Sánchez Rubén, Zens Bettina, Abreu Susana, Hardenberg Ralph, Hollenstein David, Gao Jieqiong, Ungermann Christian, Martens Sascha, Kraft Claudine, Reggiori Fulvio (2017), Atg4 proteolytic activity can be inhibited by Atg1 phosphorylation, in Nature Communications
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Cong Yingying, Kriegenburg Franziska, de Haan Cornelis A. M., Reggiori Fulvio (2017), Coronavirus nucleocapsid proteins assemble constitutively in high molecular oligomers, in Scientific Reports
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Saad Shady, Cereghetti Gea, FengYuehan, Picotti Paola, Peter Matthias, Dechant Reinhard (2017), Reversible protein aggregation is a protective mechanism to ensure cell cycle restart after stress., in Nature Cell Biology
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Orhon Idil, Reggiori Fulvio (2017), Assays to Monitor Autophagy Progression in Cell Cultures, in Cells
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Gilberto Samuel, Peter Matthias (2017), Dynamic ubiquitin signaling in cell cycle regulation., in The Journal of cell biology
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Cong Yingying, Verlhac Pauline, Reggiori Fulvio (2017), The Interaction between Nidovirales and Autophagy Components, in Viruses
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Grumati Paolo, Morozzi Giulio, Hölper Soraya, Mari Muriel, Harwardt Marie-Lena IE, Yan Riqiang, Müller Stefan, Reggiori Fulvio, Heilemann Mike, Dikic Ivan (2017), Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy, in eLife
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Michel Agnès H., Hatakeyama Riko, Kimmig Philipp, Arter Meret, Peter Matthias, Matos Joao, De Virgilio Claudio, Kornmann Benoî T. (2017), Functional mapping of yeast genomes by saturated transposition, in eLife
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Abreu Susana, Kriegenburg Franziska, Gómez‐Sánchez Rubén, Mari Muriel, Sánchez‐Wandelmer Jana, Skytte Rasmussen Mads, Soares Guimarães Rodrigo, Zens Bettina, Schuschnig Martina, Hardenberg Ralph, Peter Matthias, Johansen Terje, Kraft Claudine, Martens Sascha, Reggiori Fulvio (2017), Conserved Atg8 recognition sites mediate Atg4 association with autophagosomal membranes and Atg8 deconjugation, in EMBO reports
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Reggiori Fulvio, Ungermann Christian (2017), Autophagosome Maturation and Fusion, in Journal of Molecular Biology
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Mauthe Mario, Reggiori Fulvio (2017), Using microbes as a key tool to unravel the mechanism of autophagy and the functions of the ATG proteins, in Microbial Cell
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Gómez-Sánchez R., Sánchez-Wandelmer J., Reggiori F. (2017), Monitoring the Formation of Autophagosomal Precursor Structures in Yeast Saccharomyces cerevisiae, in -, (ed.), Elsevier, -, 323-365.
Bergmann T.J., Fumagalli F., Loi M., Molinari M. (2017), Role of Sec62 in ER maintenance: a link with ER stress tolerance in SEC62 overexpressing-tumors?, in Molecular and Cellular Oncology
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Piwko Wojciech, Mlejnkova Lucie J, Mutreja Karun, Ranjha Lepakshi, Stafa Diana, Smirnov Alexander, Brodersen Mia Ml, Zellweger Ralph, Sturzenegger Andreas, Janscak Pavel, Lopes Massimo, Peter Matthias, Cejka Petr (2016), The MMS22L-TONSL heterodimer directly promotes RAD51-dependent recombination upon replication stress., in The EMBO journal
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Harner Max E, Unger Ann-Katrin, Geerts Willie JC, Mari Muriel, Izawa Toshiaki, Stenger Maria, Geimer Stefan, Reggiori Fulvio, Westermann Benedikt, Neupert Walter (2016), An evidence based hypothesis on the existence of two pathways of mitochondrial crista formation, in eLife
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Mauthe Mario, Reggiori Fulvio (2016), ATG proteins: Are we always looking at autophagy?, in Autophagy
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Brodersen Mia M L, Lampert Fabienne, Barnes Christopher A, Soste Martin, Piwko Wojciech, Peter Matthias (2016), CRL4(WDR23)-Mediated SLBP Ubiquitylation Ensures Histone Supply during DNA Replication., in Molecular cell
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Gschweitl Michaela, Ulbricht Anna, Barnes Christopher A, Enchev Radoslav I, Stoffel-Studer Ingrid, Meyer-Schaller Nathalie, Huotari Jatta, Yamauchi Yohei, Greber Urs F, Helenius Ari, Peter Matthias (2016), A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes., in eLife
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Mauthe M, Langereis M, Jung J, Zhou X, Jones A, Omta W, Tooze SA, Stork B, Paludan SR, Ahola T, Egan D, Behrends C, Mokry M, de Haan C, van Kupperveld F, Reggiori F (2016), An siRNA screen for ATG depletion reveals the extent of unconventional functions of the autophagy proteome in virus replication, in Journal of Cell Biology
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Pisoni Giorgia Brambilla, Molinari Maurizio (2016), Five Questions (with their Answers) on ER-Associated Degradation, in TRAFFIC
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Lassen KG, McKenzie CI, Mari M, Murano T, Begun J, Baxt LA, Goel G, Villablanca EJ, Kuo S-Y, Huang H, Macia L, Bhan A, Batten M, Daly MJ, Reggiori F, Mackay CR, Xavier RK (2016), Genetic coding variant in GPR65 alters lysosomal pH and links lysosomal dysfunction with colitis ris, in Immunity
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Klionsky Daniel J., Abdelmohsen Kotb, Abe Akihisa, Abedin Md Joynal, Abeliovich Hagai, Arozena Abraham Acevedo, Adachi Hiroaki, Adams Christopher M., Adams Peter D., Adeli Khosrow, Adhihetty Peter J., Adler Sharon G., Agam Galila, Agarwal Rajesh, Aghi Manish K., Agnello Maria, Agostinis Patrizia, Aguilar Patricia V., Aguirre-Ghiso Julio, Airoldi Edoardo M., Ait-Si-Ali Slimane, Akematsu Takahiko, Akporiaye Emmanuel T., Al-Rubeai Mohamed, Albaiceta Guillermo M. (2016), Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition), in AUTOPHAGY
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Fregno I., Molinari M. (2016), Post ER quality control: a role for UDP-glucose:glycoprotein glucosyl transferase and p97, in Journal of Clinical Research on Rare Diseases
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Bergmann T.J., Pisoni G.B., Molinari M. (2016), Quality control mechanisms of protein biogenesis: Proteostasis dies hard, in AIMS Biophysics
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Mosadeghi Ruzbeh, Reichermeier Kurt M, Winkler Martin, Schreiber Anne, Reitsma Justin M, Zhang Yaru, Stengel Florian, Cao Junyue, Kim Minsoo, Sweredoski Michael J, Hess Sonja, Leitner Alexander, Aebersold Ruedi, Peter Matthias, Deshaies Raymond J, Enchev Radoslav I (2016), Structural and kinetic analysis of the COP9-Signalosome activation and the cullin-RING ubiquitin ligase deneddylation cycle., in eLife
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Buser Raymond, Kellner Vanessa, Melnik Andre, Wilson-Zbinden Caroline, Schellhaas René, Kastner Lisa, Piwko Wojciech, Dees Martina, Picotti Paola, Maric Marija, Labib Karim, Luke Brian, Peter Matthias (2016), The Replisome-Coupled E3 Ubiquitin Ligase Rtt101Mms22 Counteracts Mrc1 Function to Tolerate Genotoxic Stress., in PLoS genetics
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Fumagalli F., Noack J., Bergmann T.J., Cebollero E., Brambilla Pisoni G., Fasana E., Fregno I., Galli C., Loi M., Soldà T., D’Antuono R., Raimondi A., Jung M., Melnyk A., Schorr S., Schreiber A., Simonelli L., Varani L., Wilson-Zbinden C., Zerbe O., Hofmann K., Peter M., Quadroni M., Zimmermann R., Molinari M. (2016), Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery, in Nature Cell Biology
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Wilson-Zbinden Caroline, dos Santos Aline Xavier da Silveira, Stoffel-Studer Ingrid, van der Vaart Aniek, Hofmann Kay, Reggiori Fulvio, Riezman Howard, Kraft Claudine, Peter Matthias (2015), Autophagy competes for a common phosphatidylethanolamine pool with major cellular PE-consuming pathways in Saccharomyces cerevisiae., in Genetics
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Fraenkl A, Mari M, Reggiori F (2015), Electron microscopy methods for the ultrastructural analysis and protein localization at the nanoscale level of yeast Saccharomyces cerevisiae, in Microbial Cell
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Barbosa AD, Sembongi H, Su W-M, Abreu S, Reggiori F, Carman GM, Siniossoglou S (2015), Lipid partitioning at the nuclear envelope controls membrane biogenesis, in Molecular Biology of the Cell
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Guimaraes Rodrigo Soares, Guimaraes Rodrigo Soares, Delorme-Axford Elizabeth, Klionsky Daniel J., Reggiori Fulvio, Reggiori Fulvio (2014), Assays for the biochemical and ultrastructural measurement of selective and nonselective types of autophagy in the yeast Saccharomyces cerevisiae, in Methods
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Wilson-Zbinden Caroline, Dos Da Silveira Santos Aline Xavier, Stoffel-Studer Ingrid, Van Der Vaart Aniek, Hofmann Kay, Reggiori Fulvio, Riezman Howard, Kraft Claudine, Kraft Claudine, Peter Matthias (2014), Autophagy competes for a common phosphatidylethanolamine pool with major cellular pe-consuming pathways in saccharomyces cerevisiae, in Genetics
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Delorme-Axford Elizabeth, Guimaraes Rodrigo Soares, Guimaraes Rodrigo Soares, Reggiori Fulvio, Reggiori Fulvio, Klionsky Daniel J. (2014), The yeast Saccharomyces cerevisiae: An overview of methods to study autophagy progression, in Methods
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The endoplasmic reticulum (ER) is the site of folding and assembly for about a third of the eukaryote proteome. This membrane-bound organelle contains high concentrations of molecular chaperones and enzymes that 1) prevent aggregation of non-native newly synthesized polypeptides, 2) catalyze rate-limiting reactions of the protein folding process, and 3) insure that only native and fully-assembled proteins can leave the compartment to be transported to their intra- or extracellular functional site. The ER also contains molecular chaperones and enzymes that recognize terminally misfolded polypeptides and orphan subunits of oligomeric complexes, extract them from the folding environment and regulate their transport across the ER membrane for delivery into the cytosol where they are degraded by proteasomes. This process is known as ER-associated degradation (ERAD). Balanced activity of the ER folding and ERAD machineries is instrumental to maintain cellular homeostasis. A substantial increase in the ER cargo load, accumulation of misfolded polypeptides and environmental changes elicit an adaptation program known as the unfolded protein response (UPR). The UPR is triggered by ER stress sensors embedded in the ER membrane, and involves the activation of transcriptional/translational programs resulting in expansion of the ER volume, attenuated synthesis of ER cargo proteins and increased production of ER-resident chaperones and enzymes. Emerging evidence shows that the specific engulfment of part of the ER into autophagosomes through a selective type of autophagy, which has been named ER-phagy or reticulophagy, plays a key role in the maintenance of ER homeostasis in two important aspects of the cell response to ER stress. First, ER-phagy teams up with the ERAD machinery to clear accumulated protein aggregates from the ER. Second, it counteracts the uncontrolled expansion of the ER that occurs during ER stress. If UPR activation does not alleviate the ER stress or does not allow adaptation to it, cell death programs are activated. In contrast, if the cellular response relieves the stress condition, a recovery phase starts whereby the volume of the ER and the content of ER-resident proteins return to pre-stress levels. Our preliminary data lead us to propose a third role for ER-phagy in reducing the ER size and content during the recovery phase initiated upon termination of ER stress.The major goal of this collaborative project is to identify the components and regulatory mechanisms underlying ER-phagy during cell recovery from ER stresses, which, to our knowledge, has remained totally unexplored until now. We will closely collaborate among 3 leading research groups, two in Switzerland and one in the Netherlands, to exploit our complementary experimental expertise and model systems (budding yeast and mammalian cells). Identified factors and principles will also be tested in the context of the two documented types of ER-phagy, i.e. clearance of ER aggregates and buffering ER expansion, to also shed light onto these poorly characterized processes and to determine whether ER-phagy operates through similar mechanisms under different stimulus conditions. Our studies will reveal important aspects of the coordinated cross talk between ER quality control, ER stress, ERAD and ER-phagy, which is crucial to maintain cell and organism homeostasis. The importance of these studies is highlighted by the growing interest and clinical use of proteostasis-modifying substances and autophagy modulators to contrast the onset and progression of several diseases caused by protein misfolding that leads to the accumulation of toxic aggregates.