Mutations in the mitochondrial membrane protein mitofusin 2 (MFN2) cause the neurodegenerative disorder Charcot-Marie Tooth disease type 2A. MFN2 is a GTPase that participates in the dynamic process of mitochondrial tethering and fusion, but a complete understanding its mechanism of action has been lacking. A paper published October 24 in Nature online provides the first description of structural changes MFN2 undergoes as it transitions between conformations that either promote or restrict mitochondrial fusion. The researchers designed minipeptides to stabilize the active state of MFN2, and successfully enhanced mitochondrial fusion in cellular models of CMT2A. These findings open the doors to novel therapeutic approaches to repair mitochondrial abnormalities in CMT patients.
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Franco A, Kitsis RN, Fleischer JA, Gavathiotis E, Kornfeld OS, Gong G, Biris N, Benz A, Qvit N, Donnelly SK, Chen Y, Mennerick S, Hodgson L, Mochly-Rosen D, Dorn GW 2nd. Correcting mitochondrial fusion by manipulating mitofusin conformations. Nature. 2016 Oct 24. Epub ahead of print. [Pubmed].