Molecular mechanisms and regulation of the import of hydrophobic transport proteins from the cytosol into the mitochondrial inner membrane

• Applicant: Professor Dr. Nikolaus Pfanner
• Subject Area: Biochemistry
• Term: from 2013 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 244743982

Mitochondria are essential cell organelles. They are of central importance for energy conversion and the metabolism of cells. Defects of mitochondria lead to severe diseases, in particular of the nervous system. The mitochondrial inner membrane contains a large number of hydrophobic transport proteins, which are crucial for the translocation of metabolites between mitochondria and the rest of the cell. The transport proteins are synthesized as precursors in the cytosol and are imported in a multistep process that involves translocases of mitochondrial outer and inner membranes and molecular chaperones in cytosol and intermembrane space. However, major questions of the mechanisms and regulation of the translocases of both mitochondrial membranes have not been addressed. We have established an experimental system to study the transport of hydrophobic precursor proteins and their interaction with import components by a combination of genetic, biochemical, molecular biological and cell biological approaches. This project pursues three main aims. (i) Characterization of the reaction cycle of precursor proteins, cytosolic chaperones and receptors of the mitochondrial outer membrane, as well as their regulation. (ii) Analysis of the molecular environment of hydrophobic precursor proteins during transport across the outer membrane and insertion into the inner membrane. The mechanism of recognition of precursor proteins at the inner membrane and the regulation of transport will be studied. (iii) Analysis of the assembly of the inner membrane translocase and function of new partner proteins. With these studies, we aim to characterize fundamental mechanisms of the import of hydrophobic transport proteins from the cytosol in the mitochondrial inner membrane, a process that is essential for cell viability.

• DFG Programme: Research Grants