Research Group "Molecular Membrane and Organelle Biology" (Thomas Wollert)
The reaction compartments of the cell (organelles) are permanently exposed to harmful environmental influences. In order to maintain their specific functions, organelles are continuously regenerated and damaged organelles are removed. The catabolic pathway that mediates degradation of organelles is highly conserved from yeast to humans and has been termed autophagy, which means ‘self-digestion’. During autophagy, a membrane is formed that captures the damaged organelles to separate them from the cytoplasm. Eventually the autophagic membrane surrounds the cargo entirely. The organelle containing structure, termed autophagosome, is transported to recycling stations within the cell where its content is being degraded. Impaired autophagy is involved in developing neurodegenerative disorders, such as Alzheimers and Parkinsons disease as well as cancer.
The team of Thomas Wollert aims to decipher the molecular mechanisms that drive autophagosome biogenesis using a highly innovative approach. They reconstitute autophagy in a test tube by combining artificial model membranes with components of the autophagic machine. Recently, the team succeeded in elucidating the mechanism how the autophagic membrane captures damaged organelles. Similar to garbage bags made of plastic-foils, membranes are flexible but can be shaped by stiff scaffolds. During autophagy, such a scaffold, made of proteins that form part of the autophagic machine, is assembled on membranes to allow them to wrap around the cargo. The picture shows an alienated ‘artistic’ depiction of the reconstituted scaffold on a spherical model membrane. The membrane is shown in red and yellow, the scaffold proteins in black and grey. The researchers hope that their insights into the function of this disposal system will identify new therapeutic targets to develop specific drugs to treat neurodegenerative diseases or cancer.