Role of the MFN2650G>T/C217F mutation in CMT2A fibroblasts

This study investigated mitochondrial dynamics, respiratory capacity, and autophagy/mitophagy, to tackle the multifaceted MFN2 contribution to CMT2A pathogenesis. Transcriptomic analysis of mutated fibroblasts highlighted marked differentially expressed pathways related to cell population proliferation and extracellular matrix organization. The activation of mTORC2/AKT signaling andaccelerated proliferation was consistently found in the CMT2AMFN2 fibroblasts. The study provides the first evidence that CMT2AMFN2 fibroblasts harbor functionally impaired mitochondria that do not accumulate despite a defect of the initial steps of autophagy while performing an acceleration of cell division. So far, MFN2 is considered a tumor suppressor gene in various types of cancer, to our knowledge, this is the first report of increased proliferation of CMT2A patients' fibroblasts driven by MFN2 mutation.