Selective autophagy of ubiquitinated proteins

Autophagy is a process occurring inside our cells that helps to keep them healthy. Autophagy functions by enclosing a part of the cell in small containers called autophagosomes. The autophagosomes later merge with cellular structures named lysosomes wherein the material that was enclosed in the autophagosomes is digested. Autophagosomes can enclose only damaged and dangerous material inside the cells very selectively and autophagy therefore serves to remove the cells waste. Numerous severe diseases including neurodegeneration and cancer can occur when the function of this process is perturbed. The ability of autophagosomes to select only damaged and dangerous material for digestion is conferred by receptor molecules, which link the material and the autophagosomes. Two particular receptor molecules are p62 and NBR1. Interestingly, in cells they are not only needed to link the damaged material and the autophagosomes but also for the initial assembly the material into larger structures, which are then enclosed by autophagosomes. Whether the p62 and NBR1 receptors are able to assemble the material on their own and if so, how precisely they function is unclear. We have discovered that the p62 receptor is indeed capable of assembling the material into particles and to recruit the machinery that is required to form autophagosomes without the help of other factors. This allows us to investigate how the p62 receptor acts together with NBR1 in this process. We will also follow the behaviour of the two receptors and the assembled material in cells using microscopy techniques. With these experiments we hope to gain important insights into this fascinating process, which helps to keep our cells functional.

Selective autophagy of ubiquitinated proteins: Self-assembly leading to membrane envelopment Autophagy is a process occurring inside our cells that helps to keep them healthy. Autophagy functions by enclosing a part of the cell in small containers called autophagosomes. The autophagosomes later merge with cellular structures named lysosomes wherein the material that was enclosed in the autophagosomes is digested. Autophagosomes can enclose only damaged and dangerous material inside the cells very selectively and autophagy therefore serves to remove the cells' waste. Numerous severe diseases including neurodegeneration and cancer can occur when the function of this process is perturbed. The ability of autophagosomes to select only damaged and dangerous material for digestion is conferred by receptor molecules, which link the material and the autophagosomes. Two particular receptor molecules are p62 and NBR1. Interestingly, in cells they are not only needed to link the damaged material and the autophagosomes but also for the initial assembly the material into larger structures, which are then enclosed by autophagosomes. Whether the p62 and NBR1 receptors are able to assemble the material on their own and if so, how precisely they function is unclear. We have discovered that the p62 receptor is indeed capable of assembling the material into particles and to recruit the machinery that is required to form autophagosomes without the help of other factors. This allows us to investigate how the p62 receptor acts together with NBR1 in this process. We will also follow the behaviour of the two receptors and the assembled material in cells using microscopy techniques. With these experiments we hope to gain important insights into this fascinating process, which helps to keep our cells functional.