Mitochondria are the power houses of the cell, as they generate the energy for cellular processes. In order to function, the power houses need molecular workers - more than 1,000 different proteins. These mitochondrial proteins are produced in the cytosol, the liquid component of the cell plasma, as so-called precursor proteins. They contain signals that mediate transport to mitochondria and recognition at their surface.
“It can happen that these proteins have to be degraded because their uptake into the mitochondria is disrupted,” explains Prof. Dr. Thomas Becker from the Institute of Biochemistry and Molecular Biology at the University of Bonn, coordinator of the new priority program. The accumulation of such non-imported precursor proteins can result in cell death. Factors outside the mitochondria are needed to prevent accumulation of these proteins. These include folding helpers called molecular chaperones or degraders like the proteasome, which are components of the proteostasis network. Disruptions in the cellular proteostasis network or mitochondria can cause neurodegenerative diseases and are involved in aging.
In the new priority program, Becker and his colleagues plan to investigate the mechanisms that transport the precursor proteins to the mitochondria and degrade the non-imported precursor proteins in the cell. “We will also investigate how these molecular mechanisms are coordinated to ensure mitochondrial function and formation,” Becker says. “Our studies will contribute to understanding molecular mechanisms that underlie aging and neurodegenerative diseases.”
Interdisciplinary cooperation
The priority program will bring together researchers with a range of expertise to find answers to the unresolved questions of transport and degradation of mitochondrial precursor proteins. For example, some of the researchers focus on mitochondrial biogenesis, while others focus on cellular proteostasis. “A comprehensive analysis is not possible without the expertise of both research fields,” emphasizes Thomas Becker, member of the Transdisciplinary Research Area “Life and Health” at the University of Bonn. “Together, we hope to gain new insights into the fundamental cell biology question of how cell organelles such as mitochondria are embedded in the cellular proteostasis network to control their function and formation.”
The initiative involves a number of institutes from several German universities - including the University of Bochum (Prof. Dr. Konstanze Winklhofer), the University of Kaiserslautern (Prof. Dr. Johannes Herrmann), the University of Konstanz (Prof. Dr. Elke Deuerling) and the University of Frankfurt (Dr. Christian Münch).
DFG priority programs
Priority programs are supra-regional research networks in which the scientific basis of particularly current or emerging research areas is to be investigated. The DFG has now established a total of six new priority programs, which are scheduled to start in 2024. The programs each examine one main topic - in this case, it is the “integration of mitochondria into the cellular proteostasis network.” To participate in a priority program, the DFG invites interested researchers to submit project proposals. The six new alliances, which were selected from 33 submitted initiatives, will initially receive a total of around 44 million euros for three years.