Prof. Rudolf Wiesner’s group investigates the mechanisms of mitochondrial loss of function. Mutations in mitochondrial DNA accumulate in the course of life and ultimately lead to functional defects in cells. The group’s work centers around deciphering this process to be able to slow it down and delay the resulting organ insufficiency.
Research: Mitochondria contain their own DNA molecules. The mutations that accumulate in many organs, such as the heart, brain and muscle, are mainly deletions, where a part of the DNA strand is missing. These deletions are not evenly distributed – few individual cells show massive accumulation, which leads to a loss of function of those cells. A mosaic of normal and heavily impaired cells develops. This process is accelerated in many aging-associated diseases, such as Parkinson’s disease or cardiac arrhythmia. The group investigates how these mutations arise, why they accumulate in individual cells, and how they influence tissue function.
Successes: In collaboration with other research teams, the scientists have uncovered new important aspects of mitochondrial dysfunction in liver and muscle in connection with diabetes. They have shown that in this setting mitochondrial dysfunction is not the cause, but rather a parallel development. The group was able to demonstrate the mutagenic effect of dopamine metabolism on mitochondrial DNA – an important pathomechanism in the development of aging-associated Parkinson’s disease. Now they are working on reconstructing the process that damages the mitochondrial DNA. The group was also the first to demonstrate that a very small number of heart muscle cells with mitochondrial dysfunction are sufficient to cause cardiac arrhythmia.
Goals: The group’s goal is to understand in detail how mitochondrial damage – in particular damage caused by mitochondrial DNA deletions – arises and how it leads to organ dysfunction by failure of single cells in a tissue. The aim is to develop therapeutic approaches to slow the process.
Methods/techniques: The scientists perform behavioral experiments with model organisms, measure organ function, and test mitochondrial DNA for mutations. The collaboration with the Imaging Facility allows mitochondrial function to be observed in situ and in vivo.