Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - AutoRecon (Molecular mechanisms of autophagosome formation during selective autophagy)

Teaser

In order to stay healthy and functional, our cells must continuously degrade damaged and harmful parts and exchange these with new material. One of the main pathways our cells have to remove damaged parts is termed autophagy (self eating). During autophagy, cells encapsulate...

Summary

In order to stay healthy and functional, our cells must continuously degrade damaged and harmful parts and exchange these with new material. One of the main pathways our cells have to remove damaged parts is termed autophagy (self eating). During autophagy, cells encapsulate the damaged material in membrane bound organelles called autophagosomes. The autophagosomes deliver the material into the cellular incinerators, the lysosomes, wherein the material is degraded. Defects in autophagy can result in severe diseases including cancer, neurodegeneration or uncontrolled infection. Currently, we do not know how exactly our cells can identify the damaged cellular material and how this is linked to the formation of autophagosomes. Because, autophagy is linked to many devastating diseases it is important to find out how it works mechanistically, in order to be able to manipulate it in the future for the treatment or prevention of diseases. To obtain these mechanistic insight we aim to rebuild this process in vitro (i.e in a test tube) and thereby to understand what the individual parts of the autophagy machinery are doing during autophagy. Since autophagy is a very conserved process it occurs very similar in yeast and human cells. Therefore, we use both experimental systems for our reconstitution experiments.

Work performed

We have started the project by purifying the components we needed for the reconstitution of autophagy. We have already a large part of the autophagy machinery in our hands were able to rebuild individual reactions. These experiments have told us that the damaged material is recognized by special receptor molecules and that these receptors recruit the autophagy machinery that is responsible for the assembly of the autophagosome around the cargo material destined for degradation.

Final results

Our experiments represent the so far most comprehensive reconstitution of the selective autophagy of cellular material. Given the progress we have made, we are confident that a near complete reconstitution of selective autophagy using defined components is within reach in the framework of this action.