New hope for CMT patients: Mitofusin 2 as a cell protection discoverer!

New hope for CMT patients: Mitofusin 2 as a cell protection discoverer!

On March 9, 2025, researchers from Cologne, Bochum, Padua and Angers will report on the newly discovered role of the mitochondrial protein mitofusin 2 (MFN2) in protein quality control. These results could potentially enable new therapeutic approaches to treat Charcot-Marie-Tooth (CMT) disease, a currently incurable neurological disease. The study was published in the renowned journal Nature Communications published and shows a significant connection between mitochondrial function, protein quality and general cell health.

Led by Dr. Mafalda Escobar from the Institute of Genetics, the research team identified that MFN2 is not only known for mitochondrial fusion, but also plays a protective role against the clumping of proteins in cells. The results show that a mutation in MFN2 leads to harmful protein aggregates in the skin cells of CMT patients. The protein specifically interacts with the proteasome and chaperones to prevent the formation of toxic proteins.

The influence of MFN2 on cell health

The research group also found that comparison of MFN2 with the related protein MFN1 shows that only MFN2 interacts with the proteasome, underscoring its central role in maintaining protein quality. This work shows how important MFN2 is for the balance between the synthesis and breakdown of proteins within the cell. Failure in this mechanism could lead to the development and worsening of diseases such as CMT and obesity.

In addition to identifying MFN2 as a critical player in protein quality control, the scientists used cutting-edge techniques in proteomics, microscopy and biochemistry to investigate their hypotheses. They looked at specific aspects such as the crystallization of MFN2 and its interactions with chaperones and the proteasome. This detailed variety of methods, which ranges from recombination to assays such as the FRET test, illustrates the in-depth analysis of protein structures and their functions.

Research environment and future perspectives

The project received extensive support from institutions such as the German Research Foundation and the Fritz Thyssen Foundation. Doctoral students from the Cologne Graduate School of Aging Research (CGA) were also actively involved in the investigations and thus contributed to the depth of the study.

The results of this research could not only be important for CMT treatment, but also open up new avenues for therapeutic approaches in the fight against other diseases such as obesity. Dr. Escobar sees the work with MFN2 and its role in cellular health as a crucial step forward in protecting neuronal functions and developing advanced treatments.