The removal of damaged cellular components is crucial for keeping our tissues and organs healthy. A global research team has discovered important mechanisms involved in the disposal of cellular waste, revealing that strength training triggers these processes. This research could lead to new treatments for conditions like heart failure and nerve diseases, and may also be beneficial for astronauts on space missions.
The removal of damaged cellular components is crucial for keeping our tissues and organs healthy. A global research team led by the University of Bonn has uncovered significant mechanisms involved in the disposal of cellular waste, demonstrating that strength training activates these processes. This research could pave the way for new treatments for heart failure and nerve diseases and may also benefit astronauts during space missions.
Muscles and nerves are long-lasting, high-performance tissues that undergo constant damage. The protein BAG3 is vital for eliminating these damaged components, as it identifies them and ensures they are encased in cellular membranes, forming a structure known as an “autophagosome.” Autophagosomes act like garbage bags, collecting 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 muscle tissues. This is crucial for the proper disposal of cellular waste, as BAG3 must be activated to effectively bind damaged components and promote their enclosure in membranes. Having a functioning waste disposal system is key for maintaining muscle health over the long term. “When the BAG3 system is impaired, it can lead to rapid muscle weakness in children and heart failure, a leading cause of death in industrialized countries,” explains Professor Höhfeld.
Significant implications for sports training and rehabilitation
This study involved contributions from sports physiologists at German Sport University Cologne and the University of Hildesheim. Professor Sebastian Gehlert from Hildesheim highlights the importance of these findings: “We now understand the level of intensity needed in strength training to activate the BAG3 system. This allows us to enhance training programs for elite athletes and assist in building muscle in physical therapy patients.” He also utilizes these insights to support members of the German Olympic team.
Crucial for muscles and beyond
The BAG3 system functions beyond just muscles. Mutations in BAG3 can lead to a condition called Charcot-Marie-Tooth syndrome, which affects the nerves in the arms and legs, causing loss of mobility. By analyzing cells from patients with this syndrome, the research team found that certain cases exhibit dysfunctional regulation of BAG3’s waste disposal processes. These discoveries underline the importance of the BAG3 system for maintaining tissue health.
Surprising regulation points to potential new treatments
Upon closer examination of BAG3 activation, the researchers were astonished by their findings. “Most cellular proteins are activated through the addition of phosphate groups in a process known as phosphorylation. In the case of BAG3, however, this process is reversed,” 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 when muscles are at rest, and the phosphate groups are removed during activation.” This leads to an increased interest in phosphatases, the enzymes responsible for removing these phosphate groups. To uncover which phosphatases activate BAG3, Höhfeld is collaborating with chemist and cell biologist Professor Maja Köhn at the University of Freiburg. “Determining the phosphatases involved is crucial,” she mentions, “as it will help us develop drugs that could influence BAG3 activation within the body.” This research may open new avenues for treating muscle weakness, heart failure, and nerve diseases.
Important for space exploration
Research on the BAG3 system is being supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) through a dedicated research unit led by Prof. Höhfeld. Additionally, funding from the German Space Agency highlights the relevance of this research for manned space missions. Professor Höhfeld raises an important question: “BAG3 is activated by mechanical force. But what happens when mechanical stimulation is absent? For instance, in astronauts in a weightless environment or in seriously ill patients on ventilators?” In these scenarios, the lack of mechanical stimulation can lead to muscle loss, and Höhfeld suggests that this issue may be partly due to inactivated BAG3. Developing medications to activate BAG3 could offer solutions for these challenges, prompting Höhfeld’s team to plan experiments on the International Space Station (ISS). Thus, BAG3 research may play a role in future missions to Mars.
Collaborating institutions and secured funding
The University of Bonn collaborates with the University of Freiburg, German Sport University, Forschungszentrum Jülich, the University of Antwerp, and the University of Hildesheim for this study. The work is co-funded by the German Research Foundation and the German Space Agency, which is a part of the German Aerospace Center.
