Why do cells age? Kaiserslautern professor receives 2.35 million euros in EU funding

The European Research Council (ERC) has awarded Professor Dr. Johannes Herrmann an ERC Advanced Grant, one of the most prestigious research grants worldwide. The cell biologist from Kaiserslautern will receive around 2.35 million euros for five years to study how cells remain functional over a long period of time. The focus is on the molecular mechanisms of cellular quality control and the communication pathways through which the various parts of the cells can communicate problems to the cell nucleus. Disruptions in these processes lead to premature aging and the development of neurodegenerative diseases such as Parkinson's disease.

Just as organs perform different functions in our body, organelles do so at the cellular level. Particularly important cell organelles are the nucleus and the mitochondria. "The cell nucleus is perhaps best compared to our brain, because that's where the important decisions are made," says Professor Dr. Johannes Herrmann, who heads the Department of Cell Biology at the Technische Universität Kaiserslautern (TUK). "The mitochondria, on the other hand, produce the energy for the cell and are as important as the heart is for our body. Without the energy production of the mitochondria, our cells could not survive for long. Thus, the nucleus and mitochondria are essential organelles, just as the brain and heart are essential organs."

Mitochondria are made of proteins. "In our model organism, baker's yeast, 902 different proteins are needed to form fully functional mitochondria. Only when all these proteins function correctly mitochondria can also properly fulfill their tasks in energy production and metabolism," Herrmann explains. "In aging cells, problems accumulate, so that proteins increasingly have to be newly formed and replaced. It's similar to an aging car. Then repair mechanisms become crucial."

Herrmann's research project focuses on the processes by which mitochondria can report disorders to the cell nucleus. Herrmann's research group at the TU Kaiserslautern recently discovered how this communication works. Mitochondrial proteins are formed in the cytosol, i.e. outside the mitochondria, and then taken up by the mitochondria. If the mitochondria are healthy, this uptake occurs very quickly and efficiently. However, if there are defects, uptake occurs slowly and inefficient, so thatmitochondrial proteins accumulate outside of the mitochondria. "Most of these proteins are rapidly degraded. However, my research group has recently discovered that some of these proteins are stable and actively transported to different locations of the cell, even into the nucleus," the professor continues. "These proteins then have signaling effects and trigger a series of actions that cells can use to specifically repair the problems." These actions are crucial for the functionality of the mitochondria and thus the entire cell.

These repair measures are particularly important for long-lived cells. Nerve cells in the brain grow as old as we humans do. This means that an 80-year-old person has 80-year-old nerve cells in the brain. This highlights the importance of keeping these cells functional, because nerve cells in the brain do not regenerate as we age. Maintaining the quality of mitochondria is therefore crucial for healthy aging and for preventing neurodegenerative diseases. "In Parkinson's disease, more and more functionally compromised mitochondria accumulate. Energy production in the nerve cells keeps going down, like in an old cell phone with a bad battery," explains Herrmann. "We now want to find out how the cells can identify and repair such 'bad' mitochondria." As part of the ERC-funded project "Mitochondrial Precursor Proteins in the Cytosol as Major Determinants of Cellular Health" (MitoCyto), he and an interdisciplinary team want to investigate which processes take place here.

Various modern methods are used to carry out the experiments. These include high-throughput approaches, which can analyze thousands of molecules simultaneously, and microfluidics-based microscopy, which can be used to observe molecular processes in the cytosol. "Especially the environment of a technical university with many engineers and computer scientists in the neighborhood is ideal for this," Herrmann says. The findings from the project will help to understand how cells manage to maintain a proteome, i.e. the totality of their proteins, over their entire lifespan despite fluctuating metabolic conditions.

Professor Herrmann is already the spokesman for the STRESSistance Research Training Group, which has been funded by the German Research Foundation since January in an initial funding period of four and a half years with around 3.9 million euros. Here, too, the aim is to better investigate cellular reactions to stress. The college is affiliated with the profile area "BioComp - Complex Data Analysis in Life Sciences and Biotechnology", which is funded at the TUK as part of the state's research initiative. This has facilitated essential preparatory research in recent years.

Contact:
Professor Dr. Johannes Herrmann
Department of
Cell Biology / TU Kaiserslautern
Tel.: 0631 205-2406
E-Mail: hannes.herrmann[at]biologie.uni-kl.de