Current research
The focus of the scientific work in my laboratory is on researching the molecular mechanisms underlying mitochondrial protein homeostasis. We are primarily interested in applying these biochemical findings to elucidate the pathological processes in neurodegenerative diseases such as Parkinson's disease or Alzheimer's disease. The particular focus of our research are the degradative processes that are responsible for maintenance of mitochondrial function and integrity.
Mitochondria – important for essential processes
Mitochondria are essential components of a eukaryotic cell. In addition to generating the majority of cellular ATP, mitochondria are required for many essential biosynthetic processes and are also involved in important signaling processes such as apoptosis. Maintaining mitochondrial protein functions under normal and pathological conditions ("protein homeostasis") is therefore essential for the survival of the eukaryotic cell. In addition to having a decisive influence on aging processes, defects in mitochondrial processes play an important role in many diseases, particularly neurodegenerative and tumor diseases.
Defective mitochondria
Primarily, protective and repair functions for damaged proteins are taken over by a functional network of folding helper proteins (chaperones) and ATP-dependent proteases. The mitochondrial chaperones of the Hsp70 and Hsp60 families have a high affinity for unfolded and predominantly hydrophobic polypeptide segments in an ATP-regulated reaction.Binding stabilizes such substrate proteins and allows them to be folded back into the active form. Terminally damaged or completely denatured proteins must be recognized and removed by special proteases in the matrix compartment and the inner membrane before they can contribute to cellular damage through aggregation. If protein aggregation does occur due to overloading of the chaperone/protease system, the latest results show that these aggregates are deposited and neutralized in special mitochondrial compartments, named IMiQ for "intramitochondrial quality control compartment".Neurodegenerative diseases often show an accumulation of defective mitochondria. In addition to the processes described above, novel mechanisms of quality control are postulated that are still largely not understood at the molecular level and are actively studied in the lab.
The role of mitochondria in human pathological processes
To elucidate these mechanisms, a wide range of biochemical and cell biological methods are used on the model organism Saccharomyces cerevisiae (brewer's yeast) and in human cell culture systems. For this purpose, specific techniques have been established to characterize mitochondrial degradation and aggregation reactions. In addition, the qualitative and quantitative protein throughput through the protein quality control system is determined by applying proteomic analysis techniques. The primary aim is to identify the natural substrate spectrum of mitochondrial chaperones and proteases and to define their substrate selectivity, which in the case of mitochondria - in contrast to the ubiquitin-proteasome system of the cytosol - is not based on a special labeling of substrate proteins. The findings will form the basis for characterizing the role of mitochondria in human pathological processes.
Open positions
Due to the interdisciplinary approach of the laboratory, graduates in biochemistry, biology, biomedicine and medicine are welcome to join the team. The scientific work is funded by the German Research Foundation.