Mitofusin 2 Regulates Axonal Transport of Calpastatin to Prevent Neuromuscular Synaptic Elimination in Skeletal Muscles.

Cell Metabolism
Luwen WangXinglong Wang

Abstract

Skeletal muscles undergo atrophy in response to diseases and aging. Here we report that mitofusin 2 (Mfn2) acts as a dominant suppressor of neuromuscular synaptic loss to preserve skeletal muscles. Mfn2 is reduced in spinal cords of transgenic SOD1G93A and aged mice. Through preserving neuromuscular synapses, increasing neuronal Mfn2 prevents skeletal muscle wasting in both SOD1G93A and aged mice, whereas deletion of neuronal Mfn2 produces neuromuscular synaptic dysfunction and skeletal muscle atrophy. Neuromuscular synaptic loss after sciatic nerve transection can also be alleviated by Mfn2. Mfn2 coexists with calpastatin largely in mitochondria-associated membranes (MAMs) to regulate its axonal transport. Genetic inactivation of calpastatin abolishes Mfn2-mediated protection of neuromuscular synapses. Our results suggest that, as a potential key component of a novel and heretofore unrecognized mechanism of cytoplasmic protein transport, Mfn2 may play a general role in preserving neuromuscular synapses and serve as a common therapeutic target for skeletal muscle atrophy.

Citations

Jun 4, 2019·Journal of Alzheimer's Disease : JAD·Mengyu LiuXinglong Wang
Dec 5, 2019·Journal of Biochemistry·Daisuke MurataHiromi Sesaki
Jun 10, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Robert H Baloh
Jul 11, 2020·Cells·Ana Paula Magalhães RebeloMarta Giacomello
Mar 3, 2020·Frontiers in Neuroscience·Zeynep ÖztürkJuan José Pérez-Moreno
Jan 20, 2019·Proceedings of the National Academy of Sciences of the United States of America·Nathalie Bernard-MarissalRoman Chrast
Mar 19, 2019·The Journal of Clinical Investigation·Yueqin ZhouRobert H Baloh
Apr 10, 2020·Frontiers in Neuroscience·Naoki SuzukiMasashi Aoki
Mar 4, 2021·Antioxidants·Paulo H C MesquitaMichael D Roberts
Jun 12, 2021·Disease Models & Mechanisms·Marlies P RossmannLeonard I Zon
Aug 25, 2019·Molecular and Cellular Neurosciences·Ju GaoXinglong Wang

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