The mitochondrial unfolded protein response and mitophagy
This project follows the idea that the mitochondrial unfolded protein response (UPRmt) can activate mitophagy as a secondary response axis that leads to removal of mitochondria with perturbed proteostasis. We will analyze the underlying induction mechanism and determine the factors driving transition towards this degradative UPRmt. Finally, we will study additional factors important for flux through UPRmt-induced and canonical mitophagy.
Mitophagy induction upon mitochondrial protein misfolding. Protein misfolding in mitochondria leads to induction of the mitochondrial unfolded protein response (UPRmt) to restore folding. If this process fails (bottom), mitophagy becomes activated to remove dysfunctional mitochondria.