Molecular Mechanisms of Autophagy
We are interested in the molecular mechanisms of autophagosome formation. In particular, we focus on the reconstitution of selective autophagy processes that enable cells to remove harmful material such as pathogens and protein aggregates.
* Tuco, E., Witt, M., Abert, C., Bock-Bierbaum, T., Su, M.-Y., Trapannone, R., Sztacho, M., Danieli, A., Shi, X., Zaffagnini, G., Gamper, A., Schuschnig, M., Fracchiolla, D., Bernklau, D., Romanov, J., Hartl, M., Hurley, J.H., Daumke, O., and Martens, S. (2019). FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates. Molecular Cell. in press
* Zaffagnini, G., Savova, A., Danieli, A., Romanov, J., Tremel, S., Ebner, M., Peterbauer, T., Sztacho, M., Trapannone, R., Tarafder, A.K., Sachse, C., and Martens, S. (2018). p62 filaments capture and present ubiquitinated cargos for autophagy. The EMBO Journal.
* Fracchiolla, D., Sawa-Makarska, J., Zens, B., de Ruiter, A., Zaffagnini, G., Brezovich, A., Romanov, J., Runggatscher, K., Kraft, C., Zagrovic, B., and Martens, S. (2016). Mechanism of cargo-directed Atg8 conjugation during selective autophagy. eLife 5, e18544.
Projects within VBC Ubiquitin Club
Ubiquitin and ubiquitin-related proteins play key roles during autophagy. First, ubiquitin modification renders intracellular material including damaged mitochondria, aggregated proteins and cytoplasmic pathogens targets for the autophagy machinery. Second, ubiquitin-like proteins of the ATG8 family (eg. LC3B) are conjugated to the nascent autophagosomal membrane and serve as docking factors for autophagy proteins.
We want to understand how the ubiquitin signal of the cellular autophagy targets are read out by receptor molecules and how this ultimately results in the formation of an autophagosomal membrane specifically around the cargo. To this end, we study autophagy and its role during protein quality control and defense against intracellular pathogens in mammalian cells. We also work on an autophagy–related pathway referred to as cytoplasm-to-vacuole targeting (Cvt) pathway in the yeast S. cerevisiae.