Institute of Science and Technology (IST) Austria
Am Campus 1
”The dynamic machinery that imports proteins into mitochondria studied at the atomic level”
Mitochondria harbor 1000 (yeast) to 1500 (human) different proteins, that are involved in many cellular processes, including energy production, major metabolic pathways, and apoptosis. 99% of these proteins are not made in the mitochondria, but are nuclear-encoded and must be imported by a sophisticated machinery comprising chaperones ("proteins that transport/fold other proteins"), receptor domains, translocases and insertases. The function of this machinery is crucial for the cell, and while we know the identity of the components of the machinery fairly well, only little is known about the mechanisms at the atomic level. We aim to solve how the proteins that need to be imported are transported, recognised, sorted into the right sub-compartment and finally inserted.
By integrating structural biology techniques with import experiments in yeast, we have solved the mechanisms by which the central chaperone in the mitochondrial inter-membrane space binds and safely transports membrane proteins until their final destination in the membrane. We show that these complexes are highly dynamic on a molecular level. The dynamics of these molecules is a key requirement for the chaperones to bind at the same time with high affinity, while being able to release the “cargo” protein when arriving at the insertase machine. We have furthermore resolved the mechanism by which different chaperones achieve specificity for different “cargo” proteins.
Host: Thomas STOCKNER
Contact for questions: Helmut KUBISTA