Looking for traces: when proteins meet

Two cells exchange compounds, respectively entire mitochondria via so-called tunnelling nanotubes (TNTs) in dependence on the energy demand of the cells.
© K. Psathaki/K. Busch

Project title: Tunneling nanotubes and mitochondria: Intracellular interactions and intercellular trafficking investigated with new intein-based techniques
Principal investigators: Karin Busch, Henning Mootz
Project time: 11/2017 - 12/2018
Project code: FF-2017-07

How do cells produce the energy necessary for our bodily functions? Which proteins are involved? And what are the precise processes which take place in the production of this energy on the cellular level? These are the questions that cell biologist Prof. Karin Busch is investigating. She does research into mitochondria, which are present in every cell in the human body and are the ‘power plants’ for the body’s own energy. Mitochondria also perform a variety of functions in the body and therefore play a central role in cellular health. As a result, researchers suspect that any damage to, or malfunction in, mitochondria can increase the risk of diseases of the nervous system such as Alzheimer’s or Parkinson’s disease.

The focus of this research project is the spatio-temporal behaviour of proteins within mitochondria. Specifically, the questions being looked at are: Do certain proteins in active mitochondria form more complexes than usual? And does any exchange of mitochondria or mitochondria proteins take place between two cells? In order to provide answers to these questions, Prof. Henning Mootz, a biochemist, and Prof. Karin Busch aim to develop and establish a new labelling method. The idea of such a technology would be to enable researchers to visualize the interaction between proteins using living cell microscopy. This would become possible by using various fluorescence stains which go beyond already established methods such as resonance energy transfer. The technology would also enable researchers to distinguish between whether a protein is present individually or in interaction in a complex. It is possible to do this because the two forms of the protein move in different ways and the patterns of their movement can be recorded.

In a second sub-project the researchers want to put their new staining method into practice in order to provide an answer to another unsolved question: What happens when mitochondria age or become damaged and, as a result, no longer work as actively as before? Researchers currently assume that cells pass on certain compounds to one another, even entire mitochondria, in order to support weaker cells. Their hypothesis is that cells exchange important proteins via so-called tunnelling nanotubes (TNTs). These are supply lines with a diameter ten times smaller than a human hair. So far, the problem in proving this has been that researchers have only stained the mitochondria with a soluble dye. However, this dye can become separated from the mitochondria and, as a result, can migrate independently from one cell to another. Karin Busch and Henning Mootz now want to use the new method they will develop to find an unequivocal answer to the question of whether only soluble molecules can be exchanged among cells or whether entire mitochondria can, too.

The aim of the new method is to provide exact information in future on how cells rush to help one another in cases of stress or deficiency and stabilize the energy balance. In the long term, the researchers also want to find an answer to the question of whether, in the case of an undersupplied protein, it is enough to replace certain proteins, or whether ‘assembly instructions’ for proteins have to be exchanged to improve the energy supply.