Florian Wilfling – Mechanisms of Cellular Quality Control
How is cargo selected and packed into autophagosomes?
Proteins are the workhorses of cells and perform a vast array of functions. Often this requires the formation of large multi-protein complexes which act as a macromolecular machine for individual tasks. Recent technological advancements in structural biology have elucidated many aspects of the complex assembly and function of these machines. However, relatively little is known about how disused, damaged or misassembled macromolecular complexes are disposed of. Our aim is to systematically identify quality control signals and factors important for surveillance of the assembly and functional state of macromolecular assemblies. In particular, macroautophagy is well suited to degrade a wide variety of cytosolic cargo, ranging from macromolecular machines to protein aggregates, organelles and even invading pathogens. During macroautophagy, these diverse cargoes are engulfed in a double membrane compartment called “autophagosome”. How cargo is concentrated prior to uptake and how this process is synchronized with autophagosome biogenesis are the research focus of our group. To this end, we integrate a diverse set of techniques including biochemistry, advanced live-cell microscopy, correlative cryo-electron tomography, state-of-the-art quantitative mass spectrometry and unbiased system-wide approaches.
- Bieber, A.; Capitanio, C.; Erdmann, P. S.; Fiedler, F.; Beck, F.; Lee, C. W.; Li, D.; Hummer, G.; Schulman, B. A.; Baumeister, W. et al.: In situ structural analysis reveals membrane shape transitions during autophagosome formation. Proceeding of the National Academy of Sciences of the United States of America 119 (39), e2209823119 (2022)
- Wilfling, F.; Lee, C. W.; Erdmann, P. S.; Zheng, Y.; Jentsch, S.; Pfander, B.; Schulman, B. A.; Baumeister, W.: A selective autophagy pathway for phase separated endocytic protein deposits. Molecular Cell 80 (5), pp. 764-778 (2020)
- Allegretti, M.; Zimmerli, C. E.; Rantos, V.; Wilfling, F.; Ronchi, P.; Fung, H. K. H.; Lee, C.-W.; Hagen, W.; Turoňová, B.; Karius, K. et al.: In cell architecture of the nuclear pore complex and snapshots of its turnover. Nature 586 (7831), pp. 796-800 (2020)
- Lee, C.-W.; Wilfling, F.; Ronchi, P.; Allegretti, M.; Mosalaganti, S.; Jentsch, S.; Beck, M.; Pfander, B.: Selective autophagy degrades nuclear pore complexes. Nature Cell Biology 22 (2), pp. 159-166 (2020)