Structure and mechanism of the mitochondrial MIM insertase

Mitochondria are organelles within each cell of eukaryotic organisms, from yeast to humans. Mitochondria are known as the powerhouse of the cell, because they produce energy, in form of ATP, for the cell. Moreover, mitochondria are involved in many other functions, and play an important role in controlled cell death, ageing and cancer. There are more than 1000 different proteins in mitochondria, but only a handful of them are made inside the mitochondrion. 99% of the proteins that work in mitochondria are made elsewhere in the cell, and they have to be imported and placed in their right location within the mitochondrion. The mechanisms of this controlled protein import has been intensely studied by biochemical methods over the last decades, and increasingly also at the atomic level, by determining the structures of the involved machineries. In this project, we want to decipher the early stages of the protein import into mitochondria. We are particularly interested in the mechanisms by which proteins which eventually get inserted into the mitochondrial outer membrane are handled by the machineries at the outer membrane. We will combine structural methods, in particular nuclear magnetic resonance spectroscopy, with biochemical and biophysical methods and cellular experiments. We foresee that our project will tell us at the molecular detail how proteins that play important roles in the mitochondrial outer membrane get there.