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AutoRecon SIGNED

Molecular mechanisms of autophagosome formation during selective autophagy

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EC-Contrib. €

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Partnership

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Project "AutoRecon" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAT WIEN 

Organization address
address: UNIVERSITATSRING 1
city: WIEN
postcode: 1010
website: www.univie.ac.at

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Austria [AT]
 Total cost 1˙999˙640 €
 EC max contribution 1˙999˙640 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-03-01   to  2021-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAT WIEN AT (WIEN) coordinator 1˙999˙640.00

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 Project objective

I propose to study how eukaryotic cells generate autophagosomes, organelles bounded by a double membrane. These are formed during autophagy and mediate the degradation of cytoplasmic substances within the lysosomal compartment. Autophagy thereby protects the organism from pathological conditions such as neurodegeneration, cancer and infections. Many core factors required for autophagosome formation have been identified but the order in which they act and their mode of action is still unclear. We will use a combination of biochemical and cell biological approaches to elucidate the choreography and mechanism of these core factors. In particular, we will focus on selective autophagy and determine how the autophagic machinery generates an autophagosome that selectively contains the cargo. To this end we will focus on the cytoplasm-to-vacuole-targeting pathway in S. cerevisiae that mediates the constitutive delivery of the prApe1 enzyme into the vacuole. We will use cargo mimetics or prApe1 complexes in combination with purified autophagy proteins and vesicles to reconstitute the process and so determine which factors are both necessary and sufficient for autophagosome formation, as well as elucidating their mechanism of action. In parallel we will study selective autophagosome formation in human cells. This will reveal common principles and special adaptations. In particular, we will use cell lysates from genome-edited cells in combination with purified autophagy proteins to reconstitute selective autophagosome formation around ubiquitin-positive cargo material. The insights and hypotheses obtained from these reconstituted systems will be validated using cell biological approaches. Taken together, our experiments will allow us to delineate the major steps of autophagosome formation during selective autophagy. Our results will yield detailed insights into how cells form and shape organelles in a de novo manner, which is major question in cell- and developmental biology.

 Publications

year authors and title journal last update
List of publications.
2016 Eleonora Turco, Sascha Martens
Insights into autophagosome biogenesis from in vitro reconstitutions
published pages: 29-36, ISSN: 1047-8477, DOI: 10.1016/j.jsb.2016.04.005
Journal of Structural Biology 196/1 2019-05-30
2016 Christine Abert, Georg Kontaxis, Sascha Martens
Accessory Interaction Motifs in the Atg19 Cargo Receptor Enable Strong Binding to the Clustered Ubiquitin-related Atg8 Protein
published pages: 18799-18808, ISSN: 0021-9258, DOI: 10.1074/jbc.M116.736892
Journal of Biological Chemistry 291/36 2019-05-30
2016 Sascha Martens, Shuhei Nakamura, Tamotsu Yoshimori
Phospholipids in Autophagosome Formation and Fusion
published pages: 4819-4827, ISSN: 0022-2836, DOI: 10.1016/j.jmb.2016.10.029
Journal of Molecular Biology 428/24 2019-05-30
2018 Gabriele Zaffagnini, Adriana Savova, Alberto Danieli, Julia Romanov, Shirley Tremel, Michael Ebner, Thomas Peterbauer, Martin Sztacho, Riccardo Trapannone, Abul K Tarafder, Carsten Sachse, Sascha Martens
p62 filaments capture and present ubiquitinated cargos for autophagy
published pages: e98308, ISSN: 0261-4189, DOI: 10.15252/embj.201798308
The EMBO Journal 37/5 2019-05-30
2016 Dorotea Fracchiolla, Justyna Sawa-Makarska, Bettina Zens, Anita de Ruiter, Gabriele Zaffagnini, Andrea Brezovich, Julia Romanov, Kathrin Runggatscher, Claudine Kraft, Bojan Zagrovic, Sascha Martens
Mechanism of cargo-directed Atg8 conjugation during selective autophagy
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.18544
eLife 5 2019-05-30
2019 Eleonora Turco, Marie Witt, Christine Abert, Tobias Bock-Bierbaum, Ming-Yuan Su, Riccardo Trapannone, Martin Sztacho, Alberto Danieli, Xiaoshan Shi, Gabriele Zaffagnini, Annamaria Gamper, Martina Schuschnig, Dorotea Fracchiolla, Daniel Bernklau, Julia Romanov, Markus Hartl, James H. Hurley, Oliver Daumke, Sascha Martens
FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates
published pages: , ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.01.035
Molecular Cell 2019-05-22
2019 Leo J Dudley, Ainara G Cabodevilla, Agata N Makar, Martin Sztacho, Tim Michelberger, Joseph A Marsh, Douglas R Houston, Sascha Martens, Xuejun Jiang, Noor Gammoh
Intrinsic lipid binding activity of ATG16L1 supports efficient membrane anchoring and autophagy
published pages: e100554, ISSN: 0261-4189, DOI: 10.15252/embj.2018100554
The EMBO Journal 2019-05-22
2018 Alberto Danieli, Sascha Martens
p62-mediated phase separation at the intersection of the ubiquitin-proteasome system and autophagy
published pages: jcs214304, ISSN: 0021-9533, DOI: 10.1242/jcs.214304
Journal of Cell Science 131/19 2019-05-22
2017 Jana Sánchez-Wandelmer, Franziska Kriegenburg, Sabrina Rohringer, Martina Schuschnig, Rubén Gómez-Sánchez, Bettina Zens, Susana Abreu, Ralph Hardenberg, David Hollenstein, Jieqiong Gao, Christian Ungermann, Sascha Martens, Claudine Kraft, Fulvio Reggiori
Atg4 proteolytic activity can be inhibited by Atg1 phosphorylation
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-00302-3
Nature Communications 8/1 2019-05-22
2017 Susana Abreu, Franziska Kriegenburg, Rubén Gómez‐Sánchez, Muriel Mari, Jana Sánchez‐Wandelmer, Mads Skytte Rasmussen, Rodrigo Soares Guimarães, Bettina Zens, Martina Schuschnig, Ralph Hardenberg, Matthias Peter, Terje Johansen, Claudine Kraft, Sascha Martens, Fulvio Reggiori
Conserved Atg8 recognition sites mediate Atg4 association with autophagosomal membranes and Atg8 deconjugation
published pages: 765-780, ISSN: 1469-221X, DOI: 10.15252/embr.201643146
EMBO reports 18/5 2019-05-07

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