bers expressing mt-SOD1G93A-Dendra had visible aggregated fluorescent protein inside mitochondria and fragmented mitochondria. In contrast, not a single fiber expressing wild type mt-SOD1-Dendra displayed this phenotype. Protein aggregates and fragmented mitochondria have been reported in cultured motor neurons that were transfected with mitochondria-targeted mutant SOD1. Our similar MedChemExpress Vorapaxar results in muscle demonstrate that mitochondria in skeletal muscle are also directly subject to pathological actions of the ALS-causing mutant SOD1. Expression of wild type SOD1 inside mitochondria did not alter normal mitochondrial dynamics. The migration rate of mtSOD1-Dendra in normal muscle fibers was almost the same as that of mt-PAGFP in normal muscle fibers. However, the expression of mutant mtSOD1G93A-Dendra inside mitochondrial resulted in a 2.4-fold reduction in the migration rate in normal muscle fibers. This is similar to that observed 
in G93A muscle. These results provide strong evidence that accumulation of mutant SOD1G93A inside mitochondria is able to disrupt the homeostasis of mitochondrial fission and fusion dynamics in skeletal muscle. Further, these results show that the disruption occurs in the absence of motor neuron degeneration. The migration rate in fibers expressing mtSOD1G93A-Dendra was reduced 1.6-fold, which is identical to that observed in the 7884917 G93A muscle. This indicates that accumulation of mutant SOD1G93A inside mitochondria also leads to discontinuity in mitochondrial network. Overall, these results suggest that normal muscle fibers expressing mutant mt-SOD1G93A-Dendra protein reasonably reproduce the phonotype of G93A muscle. G93A mouse model has systematic overexpression of mutant SOD1G93A protein. It is possible that the SOD1 mutation also causes impaired mitochondrial dynamics in motor neurons before onset of ALS. To our best knowledge, there are no reports on mitochondrial dynamics in live motor neurons derived from adult ALS mice with SOD1 mutations, because it is difficult to isolate live motor neurons from the spinal cord of adult mice to apply advanced gene transfection and live cell imaging methods. However, SOD1 mutation reduced mitochondrial 22451932 dynamics in cultured motor neuron cell lines and primary motor neuron cultures derived from rodent embryos. Here, by examining mitochondrial dynamics in skeletal muscle we provide new evidence supporting that impaired mitochondrial dynamics is likely a common pathologic defect caused by ALS-linked SOD1 mutations in both muscle and motor neuron during the disease progression. Normal mitochondrial dynamics rely on the balance between fusion and fission processes. Accumulating evidence has shown that abnormal mitochondrial fission mediated by Drp1 induces excessive mitochondrial fragmentation. This is a common pathway that leads to abnormal mitochondrial function critical to neuronal cell death. We applied Mdivi-1, a specific inhibitor of mitochondrial fission protein Drp1, to normal mice whose skeletal muscle was transfected with mutant SOD1G93A. Remarkably, inhibition of Drp1 restored mitochondrial network and the migration rate of the fluorescent protein. The results indicate that mutant SOD1G93A promotes Drp1-based mitochondrial fission in skeletal muscle. We also examined expression levels of Drp1 and the mitochondrial fusion promoters in skeletal muscle of G93A mice at the age showing reduced mitochondrial dynamics. Expression of Mfn1/2 slightly decreased and Drp1 expressi