Researchers from Cologne, Bochum, Padova and Angers have discovered a novel connection between mitochondrial function, protein quality control and cellular health, whose failure could be the leading cause in the currently incurable neurological disease Charcot-Marie-Tooth (CMT). The study led by Mafalda Escobar at the University of Cologne’s Institute of Genetics, CECAD Cluster of Excellence in Aging Research and Center for Molecular Medicine Cologne (CMMC), uncovered an unexpected function of the protein Mitofusin 2 (MFN2) in mitochondria. It could have far-reaching implications for the treatment of CMT and similar conditions. The work was published in Nature Communications under the title ‘Mitofusin 2 displays fusion-independent roles in proteostasis surveillance’.
Mitochondria are best known as the energy producers of the cell, but they also regulate metabolism, gene expression and cell survival, all essential for healthy aging. MFN2 has long been recognized for its role in mitochondrial fusion.
The researchers now uncovered an additional, unexpected function of MFN2 in maintaining protein quality within cells. The team found that MFN2 interacts with the proteasome and chaperones – cellular systems that prevent newly produced proteins from forming toxic aggregates, which can lead to neurodegeneration. Unexpectedly, MFN2 shares this protective function. Further analysis of skin cells from CMT patients confirmed that when MFN2 is mutated, this novel function is lost, leading to harmful protein clumping. This discovery opens new possibilities for treating diseases like CMT.
Although MFN2 is a leading causative gene in Charcot-Marie-Tooth, most other genes linked to the disease do not encode mitochondrial