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ER-phagy mechanisms to maintain and restore endoplasmic reticulum homeostasis

English title ER-phagy mechanisms to maintain and restore endoplasmic reticulum homeostasis
Applicant Molinari Maurizio
Number 154421
Funding scheme Sinergia
Research institution Istituto di Ricerca in Biomedicina (IRB)
Institution of higher education Università della Svizzera italiana - USI
Main discipline Cellular Biology, Cytology
Start/End 01.10.2014 - 30.09.2017
Approved amount 1'545'988.00
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Keywords (6)

ER stress; Recovery from stress; Ubiquitin proteasome system; ER-phagy; Autophagy; Molecular chaperones

Lay Summary (Italian)

Lead
Il mantenimento della struttura e la funzionalità del reticolo endoplasmatico, un compartimento che ha un ruolo centrale nella fisiologia delle nostre cellule, necessita la degradazione di sue parti prodotte in eccesso o che non funzionano correttamente. Uno dei meccanismi implicati in questo processo di regolazione è l’autofagia. Come l’autofagia riconosce ed elimina specificamente le parti del reticolo endoplasmatico che devono essere eliminate dalla cellula, rimane sconosciuto. Questo progetto intende fornire delle risposte a questa domanda.
Lay summary

Soggetto e obiettivi

Il reticolo endoplasmatico (RE) è un compartimento cellulare dove circa un terzo delle proteine cellulari acquisiscono la loro struttura e funzione. La produzione di proteine è garantita da numerosi enzimi dedicati a questo scopo. Taluni riconoscono le proteine difettose e non funzionali e ne garantiscono la distruzione che viene operata dai proteasomi. Quando la produzione di proteine difettoe eccede la capacità degradativa della cellula, vengono attivati meccanismi di stress che comprendono anche l'attivazione dell'autofagia. L’autofagia che elimina porzioni di RE danneggiate o che contengono proteine difettose è chiamata RE-fagia (o autofagia dell'RE). IL RE difettoso viene sequestrato in vescicole chiamate autofagosomi che vengono in seguito trasportate all’interno dei lisosomi dove il RE viene distrutto. Come tutto questo avvenga, non è ancora stato chiarito.

Il principale obiettivo di questo progetto è di svelare i dettagli molecolari che permettono alla cellula di riprendersi da uno stress del RE eliminando parte di esso attraverso la RE-fagia. Tre laboratori esperti in questo campo, due in Svizzera e uno nei Paesi Bassi, collaboreranno combinando le loro competenze sperimentali e tecnologiche con lo scopo di identificare proteine e meccanismi che permettono al RE-fagia di degradare specificamente parte del RE.

 

Contesto socio-scientifico

Il progetto si occupa prettamente di ricerca fondamentale ma i risultati potrebbero avere un importante riscontro anche nell’ambito medico. Infatti, uno stress del RE che porta ad un’alterazione delle funzioni di questo compatimento subcellulare che si occupa della produzione di proteine si riscontra in varie malattie genetiche ed in taluni tumori. Conseguentemente una miglior conoscenza dei processi cellulari come quello del RE-fagia che portano ad un alleviamento dello stress del RE potrebbe permettere di sviluppare delle terapie per alleviare i sintomi patologici.

Direct link to Lay Summary Last update: 05.09.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
Atg4 proteolytic activity can be inhibited by Atg1 phosphorylation
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, 8(1), 295-295.
Coronavirus nucleocapsid proteins assemble constitutively in high molecular oligomers
Cong Yingying, Kriegenburg Franziska, de Haan Cornelis A. M., Reggiori Fulvio (2017), Coronavirus nucleocapsid proteins assemble constitutively in high molecular oligomers, in Scientific Reports, 7(1), 5740-5740.
Reversible protein aggregation is a protective mechanism to ensure cell cycle restart after stress.
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, Oct;19(10):1202-1213, 1202-1213.
Assays to Monitor Autophagy Progression in Cell Cultures
Orhon Idil, Reggiori Fulvio (2017), Assays to Monitor Autophagy Progression in Cell Cultures, in Cells, 6(3), 20-20.
Dynamic ubiquitin signaling in cell cycle regulation.
Gilberto Samuel, Peter Matthias (2017), Dynamic ubiquitin signaling in cell cycle regulation., in The Journal of cell biology, 216(8), 2259-2271.
The Interaction between Nidovirales and Autophagy Components
Cong Yingying, Verlhac Pauline, Reggiori Fulvio (2017), The Interaction between Nidovirales and Autophagy Components, in Viruses, 9(7), 182-182.
Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy
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, 6, e25555.
Functional mapping of yeast genomes by saturated transposition
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, 6, 1-1.
Conserved Atg8 recognition sites mediate Atg4 association with autophagosomal membranes and Atg8 deconjugation
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, 18(5), 765-780.
Autophagosome Maturation and Fusion
Reggiori Fulvio, Ungermann Christian (2017), Autophagosome Maturation and Fusion, in Journal of Molecular Biology, 429(4), 486-496.
Using microbes as a key tool to unravel the mechanism of autophagy and the functions of the ATG proteins
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, 4(1), 1-5.
Monitoring the Formation of Autophagosomal Precursor Structures in Yeast Saccharomyces cerevisiae
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.
Role of Sec62 in ER maintenance: a link with ER stress tolerance in SEC62 overexpressing-tumors?
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, 4(2), e1264351.
The MMS22L-TONSL heterodimer directly promotes RAD51-dependent recombination upon replication stress.
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, 35(23), 2584-2601.
An evidence based hypothesis on the existence of two pathways of mitochondrial crista formation
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, 5, e18853.
ATG proteins: Are we always looking at autophagy?
Mauthe Mario, Reggiori Fulvio (2016), ATG proteins: Are we always looking at autophagy?, in Autophagy, 12(12), 2502-2503.
CRL4(WDR23)-Mediated SLBP Ubiquitylation Ensures Histone Supply during DNA Replication.
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, 62(4), 627-35.
A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes.
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, 5, 13841-13841.
An siRNA screen for ATG depletion reveals the extent of unconventional functions of the autophagy proteome in virus replication
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, 214, 619-635.
Five Questions (with their Answers) on ER-Associated Degradation
Pisoni Giorgia Brambilla, Molinari Maurizio (2016), Five Questions (with their Answers) on ER-Associated Degradation, in TRAFFIC, 17(4), 341-350.
Genetic coding variant in GPR65 alters lysosomal pH and links lysosomal dysfunction with colitis ris
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, 44, 1392-1405.
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
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, 12(1), 1-222.
Post ER quality control: a role for UDP-glucose:glycoprotein glucosyl transferase and p97
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 , 1, 40-42.
Quality control mechanisms of protein biogenesis: Proteostasis dies hard
Bergmann T.J., Pisoni G.B., Molinari M. (2016), Quality control mechanisms of protein biogenesis: Proteostasis dies hard, in AIMS Biophysics, 3(4), 456-478.
Structural and kinetic analysis of the COP9-Signalosome activation and the cullin-RING ubiquitin ligase deneddylation cycle.
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, 5, 5pii.
The Replisome-Coupled E3 Ubiquitin Ligase Rtt101Mms22 Counteracts Mrc1 Function to Tolerate Genotoxic Stress.
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, 12(2), 1005843-1005843.
Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery
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, 18, 1173-1184.
Assessing the progression of autophagy pathways in different organisms and tissues
Reggiori F, Codogno P (2015), Assessing the progression of autophagy pathways in different organisms and tissues, in Methods, 75, 1-2.
Autophagy competes for a common phosphatidylethanolamine pool with major cellular PE-consuming pathways in Saccharomyces cerevisiae.
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, 199(2), 475-85.
Electron microscopy methods for the ultrastructural analysis and protein localization at the nanoscale level of yeast Saccharomyces cerevisiae
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, 2, 412-428.
Lipid partitioning at the nuclear envelope controls membrane biogenesis
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, 26, 3641-3657.
Assays for the biochemical and ultrastructural measurement of selective and nonselective types of autophagy in the yeast Saccharomyces cerevisiae
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, 75, 141-150.
Autophagy competes for a common phosphatidylethanolamine pool with major cellular pe-consuming pathways in saccharomyces cerevisiae
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, 199(2), 475-485.
The yeast Saccharomyces cerevisiae: An overview of methods to study autophagy progression
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, 75, 3-12.

Collaboration

Group / person Country
Types of collaboration
Prof. Paola Picotti Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Carmine Settembre, TIGEM, Pozzuoli Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Eelco Van Anken, San Raffaele, Milan Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Richard Zimmermann, Universität des Saarlandes Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Dr. Kay Hofmann/University of Cologne Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Andrea Raimondi, San Raffaele Scientific Institute DIBIT Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Ruedi Aebersold, ETH Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
International symposium to celebrate scientific career of Prof. Gustav Ammerer Talk given at a conference Regulation of cell growth and division 29.09.2017 IMP Vienna, Austria Peter Matthias;
9th ÖGMBT Annual Meeting Talk given at a conference Function and regulation of CRL complexes 26.09.2017 Innsbruck, Austria Peter Matthias;
Ubiquitin and SUMO: From molecular mechanisms to system-wide responses Talk given at a conference Regulation of autophagy by the atg1 kinase 15.09.2017 Cavtat, Croatia Schreiber Anne;
Talk at Institute of Biochemistry II, University of Frankfurt Individual talk Regulation of autophagy by the atg1 kinase 15.08.2017 Frankfurt, France Schreiber Anne;
Regulation Mechanisms of Proteins and Signaling Pathways in Humans, Animals and Plants Talk given at a conference Ubiquitin-Dependent Regulation of Cell Growth and Division 13.08.2017 The Hong Kong University of Science and Technology, Hongkong Peter Matthias;
ZMBH Heidelberg Individual talk Regulation of autophagy by the atg1 kinase 25.07.2017 Heidelberg, Germany Schreiber Anne;
EMBL Heidelberg Talk given at a conference Regulation of autophagy by the atg1 kinase 13.07.2017 Heidelberg, Germany Schreiber Anne;
Sticking together: Protein aggregation in health and disease Talk given at a conference Function and regulation of reversible aggregation in stress response 20.06.2017 ETH Zürich , Switzerland Peter Matthias;
FASEB meeting “From Unfolded Proteins in the ER to Disease” Individual talk Role of ER-resident LC3-binding proteins in maintenance of ER homeostasis 18.06.2017 Saxton's River, United States of America Molinari Maurizio;
8th International Symposium on Autophagy (ISA) Talk given at a conference Regulation of the last steps of autophagosome biogenesis 28.05.2017 Nara, Japan Reggiori Fulvio;
Twelfth International Calreticulin Workshop Talk given at a conference Lysosomal-associated degradation of proteasome-resistant protein polymers from the ER 26.05.2017 Delphi, Greece Galli Molinari Carmela; Molinari Maurizio;
Department of Biochemistry, University of Fribourg Individual talk Evolutionary conserved Atg8-recognition sites mediate Atg4 association to autophagosomal membranes and Atg8 deconjugation from phosphatidylethanolamine 15.05.2017 Fribourg, Switzerland Reggiori Fulvio;
Seminar invitation Jaques-Monod Paris Individual talk Regulation of cell growth and division 28.04.2017 Institut Jacques Monod, Paris , France Peter Matthias;
Multidisciplinar meeting for clinicians Individual talk Ricerca fondamentale su malattie rare: una visita in clinica 03.04.2017 Ospedale San Giovanni, Bellinzona, Switzerland Molinari Maurizio;
Stazione Zoologica Anton Dohrn Individual talk Autophagy proteins: Autophagy and beyond 30.03.2017 Naples, Italy Reggiori Fulvio;
Symposium in Autophagy, Phagocytosis and Innate Immunity Talk given at a conference Autophagy, ATG proteins and viral infections 23.01.2017 Salvador Bahia, Brazil Reggiori Fulvio;
Department of Molecular Biology, University of Tuebingen Individual talk Autophagy, ATG proteins and viral infections 14.12.2016 Tuebingen, Germany Reggiori Fulvio;
Transautophagy COST meeting Talk given at a conference Spatial Atg8 deconjugation depends on the regulation of Atg4 function by Atg1 phosphorylation 06.10.2016 Warsaw, Poland Reggiori Fulvio;
EMBO Workshop New approaches to study ubiquitin and ubiquitin-like modifications Talk given at a conference Regulation of Cullin-RING-Ligases 18.09.2016 Alghero, Italy Enchev Radoslav Ivanov;
Instituto Goncalo Moniz - FIOCRUZ Bahia Individual talk Spatial Atg8 deconjugation depends on the regulation of Atg4 function by Atg1 phosphorylation 16.09.2016 Salvador Bahia, Brazil Reggiori Fulvio;
Unfolded proteins: from basic to bedside Poster Revealing mechanisms involved in recovery from transient ER stress in mammalian cells 04.09.2016 Stockholm, Sweden Fumagalli Fiorenza;
EMBO Meeting 2016, Structure and Function of the Endoplasmic Reticulum Talk given at a conference Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery 23.08.2016 Girona, Spain Molinari Maurizio;
FASEB - Ubiquitin and Cellular Regulation Talk given at a conference Function and regulation of CRL complexes 12.06.2016 Big Sky, Montana, United States of America Peter Matthias;
Keystone Symposium on Autophagy Talk given at a conference Spatial Atg8 deconjugation depends on the regulation of Atg4 function by Atg1 phosphorylation 05.06.2016 Whistler, Canada Reggiori Fulvio;
Meet the expert Individual talk Rare Diseases: Alport’s syndrome 04.05.2016 Lugano, Switzerland Molinari Maurizio;
Institute of Biology, University of Leiden Individual talk Viral infections reveal the extend of unconventional functions of the autophagy proteome 21.04.2016 Leiden, Netherlands Reggiori Fulvio;
IRB Student Retreat Talk given at a conference Revealing mechanisms involved in recovery from transient ER stress in mammalian cells 06.04.2016 Grindelwald, Switzerland Fumagalli Fiorenza;
Sanford-Burnham-Prebys Medical Discovery Institute Individual talk Viral infections reveal the extend of unconventional functions of the autophagy proteome 18.03.2016 La Jolla, United States of America Reggiori Fulvio;
LS2 Annual Meeting, Lausanne, Interdisciplinary Sciences Poster Revealing mechanisms involved in recovery from transient ER stress in mammalian cells 15.02.2016 Lausanne, Switzerland Fumagalli Fiorenza;
GCB Symposium Poster Revealing mechanisms involved in recovery from transient ER stress in mammalian cells 04.02.2016 Bern, Switzerland Fumagalli Fiorenza;
Departments of Cellular Biology and Virology, I2BC - CNRS Individual talk Viral infections reveal the extend of unconventional functions of the autophagy proteome 22.01.2016 Gif-sur-Yvette, France Reggiori Fulvio;
Walter and Eliza Hall Institute of Medical Research Individual talk Function and regulation of Cullin-based ubiquitin ligases 24.11.2015 Melbourne, Australia Peter Matthias;
Trinity College Individual talk Spatial Atg8 deconjugation depends on the regulation of Atg4 function by Atg1 phosphorylation 28.10.2015 Dublin, Ireland Reggiori Fulvio;
Japan Australia Meeting on Cell Death Talk given at a conference Ubiquitin-dependent regulation of selective autophagy 21.10.2015 Melbourne, Australia Peter Matthias;
The WEHI Individual talk Selective degradation by ubiquitin-dependent mechanisms and autophagy 20.10.2015 Melbourne, Australia Peter Matthias;
Apoptosis in yeast meeting Talk given at a conference Selective degradation by ubiquitin-dependent mechanisms and autophagy 29.09.2015 Porto, Portugal Reggiori Fulvio;
Autophagy signaling and progression in health and disease Poster Revealing mechanisms involved in recovery from transient ER stress in mammalian cells 09.09.2015 Chia, Italy Fumagalli Fiorenza; Reggiori Fulvio;
The Telethon Institute of Genetics and Medicine (TIGEM) Individual talk Viral infections and the unconventional roles of the autophagy machinery 22.06.2015 Naples, Italy Reggiori Fulvio;
European Research Institute for the Biology of Ageing (ERIBA) Individual talk Roles of phosphatidylinositol-3-phosphate in autophagy 05.06.2015 Groningen, Netherlands Reggiori Fulvio;
11th International Calreticulin Workshop Talk given at a conference A novel UGGT1 and p97-dependent checkpoint 15.05.2015 New York, United States of America Molinari Maurizio;
Fondation des Treilles meeting on Mitochondrial quality control and neurodegenerative diseases Talk given at a conference Unconventional roles of ATG proteins in viral infections 04.05.2015 Tourtour, France Reggiori Fulvio;
IRB Student Retreat Talk given at a conference Revealing mechanisms involved in recovery from transient ER stress in mammalian cells 04.05.2015 Weggis, Switzerland Fumagalli Fiorenza;
7th International Symposium on Autophagy (ISA) Talk given at a conference Unconventional roles of ATG proteins in viral infections 19.03.2015 Huangshan, China Reggiori Fulvio; Mari Muriel;
Institute of Biological Chemistry, Academia Sinica Individual talk Roles of phosphatidylinositol-3-phosphate in autophagy 14.03.2015 Taipei, Taiwan Mari Muriel; Reggiori Fulvio;
Institute of Life Sciences, University of Louvain Individual talk Roles of phosphatidylinositol-3-phosphate in autophagy 26.02.2015 Louvain-la-Neuve, Belgium Reggiori Fulvio;
LS2 Annual Meeting, Zurich: Light: from the basis of life to life science technologies Poster Revealing mechanisms involved in recovery from transient ER stress in mammalian cells 29.01.2015 Zurich, Switzerland Fumagalli Fiorenza;


Self-organised

Title Date Place

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Ricerche non redditizie per l’industria dei farmaci Corriere del Ticino Italian-speaking Switzerland 2017
Media relations: print media, online media Ticino at the forefront of medical research Ticino Wellcome Rhaeto-Romanic Switzerland Western Switzerland German-speaking Switzerland Italian-speaking Switzerland 2017
Media relations: print media, online media Hohe Auszeichnung für die Hefeforschung ETH-Life International 2016
Media relations: radio, television Interviews mit Prof. Peter in Zus. mit Nobelpreisvergabe Medizin (Yoshinori Ohsumi - Authophagie) SRF 1 Radio, SRF Tagesschau, ETH Life International 2016
Media relations: print media, online media Le Proteine impazzite che ci fanno ammalare Il Caffè Italian-speaking Switzerland 2016
Media relations: print media, online media Tutte le Malattie rare ancora da sconfiggere Il Caffè Italian-speaking Switzerland 2016

Associated projects

Number Title Start Funding scheme
163063 Protein folding, quality control and degradation in the endoplasmic reticulum 01.01.2016 Project funding (Div. I-III)
164092 Upgrade of a Titan Krios electron cryo-microscope for single particle analysis and tomography 01.12.2015 R'EQUIP
184827 Protein folding, quality control and degradation in the endoplasmic reticulum 01.05.2019 Project funding (Div. I-III)

Abstract

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.
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