Disease Causing-Mfn2 Mutations Alter Mitochondrial Fusion and Fission Dynamics in Mouse Embryonic Fibroblast

Abstract

Part of the mitochondrial dynamics is the fusion-fission balance. Although, the key proteins that regulate the individual processes are known, the mechanism that maintains the balance between fusion and fusion it is poorly understood. Mutations in mitochondrial fusion protein Mfn2 cause Charcot Marie-Tooth 2A, a motor-neuron degenerative disease. Some, but not all MFN2 mutants alter mitochondrial morphology. Whether Mfn2 mutations alters mitochondrial fission is unknown. In this work, we evaluate the effect of Mfn2 disease-causing mutants in fusion and fission balance.Patient-derived fibroblasts carrying MFN2-L248H or MFN2-M376V, or WT MEF acutely expressing each mutant were co-transfected with mitochondria-targeting mtDsRed and mtPAGFP.