Targeted Protein Degradation
Groups Bachmair Becker Beli Clausen Dagdas Haselbach Karagöz Köhler Loizou Martens Urbán Versteeg Winter

Group Martens

Degradation of nuclear proteins by autophagy

Group Leader, Scientific Coordinator

Sascha Martens

Sascha Martens obtained his Diploma and Doctoral degrees from the University of Cologne in Germany. For his postdoctoral training he moved to the MRC Laboratory of Molecular Biology in Cambridge, UK. In 2009 he established his independent laboratory at the Max Perutz Labs Vienna.

Projects within consortium

Autophagy is a conserved cytoplasmic degradation pathway for the degradation of harmful substances within lysosomes. This is achieved by the encapsulation of this cargo material by double membrane organelles – the autophagosomes. Among the many cargoes that are degraded by this pathway are damaged organelles, intercellular pathogens and aggregated proteins. Autophagy thereby protects us from various diseases including cancer and neurodegeneration.

In the cytoplasm autophagy acts together with the ubiquitin-proteasome system (UPS) in the degradation of ubiquitinated proteins. For autophagic degradation, these proteins are bound by cargo receptors, which facilitate the phase separation of these proteins into larger condensates. Subsequently, they recruit the autophagy machinery and link the condensates to the autophagosomal membrane. Finally, these autophagosomes fuse with lysosomes, wherein the ubiquitinated proteins are degraded.

While in the cytoplasm the process of protein degradation can rely on autophagy as backup system for the ubiquitin-proteasome system, it is unclear how the nucleoplasm copes with situations under which the UPS is overwhelmed. Since autophagosome formation and lysosomal degradation are confined to the cytoplasm, the entire process of autophagy cannot occur in the nucleoplasm. We aim to understand to which extent nuclear proteins are exported into the cytoplasm for autophagic degradation. We are particularly interested to study this process in long-lived postmitotic cells, in which the nuclear envelope does not periodically break down.

A neuron expressing an endogenously tagged cargo receptor.

Project members

  • PhD Student

    Alberto Danieli

    SFB Member

  • Postdoc

    Luca Ferrari

    SFB Member

  • Postdoc

    Justyna Sawa-Makarska

    Associated

  • PhD Student

    Bernd Bauer

    Associated

Targeted Protein Degradation related publications by Group Martens

  • 2022 Shuffled ATG8 interacting motifs form an ancestral bridge between UFMylation and C53-mediated autophagy bioRxiv Picchianti L, Sánchez de Medina Hernández V, Zhan N, Irwin NAT, Stephani M, Hornegger H, Beveridge R, Sawa-Makarska J, Lendl T, Grujic N, Martens S, Richards TA, Clausen T, Ramundo S, Karagöz E, Dagdas Y Go to publication →
  • 2021 Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation Nature Communications Turco E, Savova A, Gere F, Ferrari L, Romanov J, Schuschnig M, Martens S Go to publication →
  • 2020 Reconstitution of autophagosome nucleation defines Atg9 vesicles as seeds for membrane formation Science Sawa-Makarska J, Baumann V, Coudevylle N, von Bülow S, Nogellova V, Abert C, Schuschnig M, Graef M, Hummer G, Martens S Go to publication →
  • 2020 A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress eLife Stephani M, Picchianti L, Gajic A, Beveridge R, Skarwan R, Sanchez de Medina Hernandez V, Mohseni A, Clavel M, Zeng Y, Naumann C, Matuszkiewicz M, Turco E, Loefke C, Li B, Durnberger G, Schutzbier M, Chen HT, Abdrakhmanov A, Savova A, Chia KS, Djamei A, Schaffner I, Abel S, Jiang L, Mechtler K, Ikeda F, Martens S, Clausen T, Dagdas Y Go to publication →
  • 2020 A PI3K-WIPI2 positive feedback loop allosterically activates LC3 lipidation in autophagy Journal of Cell Biology Fracchiolla D, Chang C, Hurley JH, Martens S Go to publication →
  • 2019 FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates Molecular Cell Turco E, Witt M, Abert C, Bock-Bierbaum T, Su MY, Trapannone R, Sztacho M, Danieli A, Shi X, Zaffagnini G, Gamper A, Schuschnig M, Fracchiolla D, Bernklau D, Romanov J, Hartl M, Hurley JH, Daumke O, Martens S Go to publication →
  • 2018 p62 filaments capture and present ubiquitinated cargos for autophagy EMBO Journal Zaffagnini G, Savova A, Danieli A, Romanov J, Tremel S, Ebner M, Peterbauer T, Sztacho M, Trapannone R, Tarafder AK, Sachse C, Martens S Go to publication →
  • 2016 Mechanism of cargo-directed Atg8 conjugation during selective autophagy eLife Fracchiolla D, Sawa-Makarska J, Zens B, Ruiter A, Zaffagnini G, Brezovich A, Romanov J, Runggatscher K, Kraft C, Zagrovic B, Martens S Go to publication →
  • 2015 Oligomerization of p62 allows for selection of ubiquitinated cargo and isolation membrane during selective autophagy eLife Wurzer B, Zaffagnini G, Fracchiolla D, Turco E, Abert C, Romanov J, Martens S Go to publication →
  • 2014 Cargo binding to Atg19 unmasks additional Atg8 binding sites to mediate membrane–cargo apposition during selective autophagy Nat. Cell Biol. Sawa-Makarska J, Abert C, Romanov J, Zens B, Ibiricu I, Martens S Go to publication →