The removal of damaged cellular components is crucial for maintaining the body’s tissues and organs. A team of researchers from the University of Bonn and its international collaborators have made important discoveries about the processes involved in clearing cellular waste, revealing that strength training boosts these processes. These insights may pave the way for innovative treatments for heart failure and nerve disorders, along with potential advantages for human spaceflights.
The removal of damaged cellular components is crucial for maintaining the body’s tissues and organs. An international research team led by the University of Bonn has made important discoveries about the processes responsible for clearing cellular waste, revealing that strength training stimulates these processes. These insights may lead to new treatments for heart failure and nerve disorders, and they could also offer benefits for human space exploration. The corresponding research article is featured in the latest edition of the journal Current Biology.
Muscles and nerves, which are vital and long-lasting organs, experience continual wear and tear on their cellular components. The protein BAG3 is essential for the removal of damaged components; it identifies damaged parts and ensures they are encased by cellular membranes to create structures called “autophagosomes.” These autophagosomes function like garbage bags that collect cellular waste for later breakdown and recycling. The research team, led by Professor Jörg Höhfeld from the University of Bonn Institute of Cell Biology, discovered that strength training activates BAG3 in muscles. This revelation affects how cellular waste is managed since BAG3 must be activated to efficiently bind to damaged cell components and facilitate their encasement. A functional waste removal system is vital for the long-term health of muscle tissues. “Dysfunction of the BAG3 system can lead to rapidly progressing muscle weakness in children and heart failure, which is among the leading causes of death in industrialized Western countries,” explains Professor Höhfeld.
Significant implications for athletic training and rehabilitation
The study significantly involved sports scientists from the German Sport University Cologne and the University of Hildesheim. Professor Sebastian Gehlert of Hildesheim highlights the importance of these findings: “We now understand what intensity of strength training is required to activate the BAG3 system, allowing us to refine training programs for elite athletes and assist rehabilitation patients in building muscles more effectively.” He also applies this knowledge to support members of the German Olympic team.
Essential for muscles and more
The BAG3 system is not limited to muscles. Mutations in BAG3 can lead to a nerve condition known as Charcot-Marie-Tooth syndrome, which results in the degeneration of nerve fibers in the arms and legs, rendering individuals unable to move their hands or feet. By studying cells from affected individuals, the research team has discovered that some characteristics of the syndrome involve impaired regulation of BAG3’s elimination processes. These findings highlight the extensive importance of this system in preserving tissues.
Surprising regulatory mechanisms may inform new therapies
Upon a closer investigation of BAG3 activation, the researchers found unexpected results. “Many cell proteins are activated by the attaching of phosphate groups, a process known as phosphorylation. However, with BAG3, the opposite occurs,” explains Professor Jörg Höhfeld, who is also part of the Transdisciplinary Research Area (TRA) Life and Health at the University of Bonn. “BAG3 is phosphorylated in resting muscles, and the phosphate groups are removed when it becomes activated.” This points to phosphatases—enzymes that remove phosphate groups—as a critical area of focus. To identify which phosphatases activate BAG3, Höhfeld is collaborating with chemist and cell biologist Professor Maja Köhn from the University of Freiburg. “Finding these involved phosphatases is an essential step,” she states, “as it enables us to develop substances that may influence BAG3 activation within the body.” This research could lead to new treatment options for muscle weakness, heart failure, and nerve diseases.
Relevance for space missions
Research on the BAG3 system is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) through a unit led by Professor Höhfeld. Additionally, funding has been secured from the German Space Agency, emphasizing the research’s relevance for manned space missions. Professor Höhfeld raises an important question: “BAG3 is activated by mechanical forces, but what happens in the absence of such stimulation? For example, in astronauts living in a zero-gravity environment or intubated patients?” In these scenarios, the absence of mechanical stimulation leads to rapid muscle atrophy, which Höhfeld attributes partly to the non-activation of BAG3. He believes that drugs designed to activate BAG3 could be beneficial in these cases, which is why his team is preparing to conduct experiments aboard the International Space Station (ISS). Thus, BAG3 research may contribute to our ability to reach Mars in the future.
Collaborating institutions and secured funding
Institutions involved in this study alongside the University of Bonn include the University of Freiburg, German Sport University, Forschungszentrum Jülich, the University of Antwerp, and the University of Hildesheim. This work is co-funded by the German Research Foundation and the German Space Agency, part of the German Aerospace Center.
