Electron microscopy was performed to quantify the degree mitochondrial ultrastructure abnormalities in perikarya of motor neurons in the ventral horn of SOD1G93A mice. This analysis showed lower density of normal mitochondria as well as increased circular mitochondria with damaged cristae (Fig 5A) similar to previously reported observation (Milanese et al, 2014). Balancing the mitochondrial fission with P110 significantly reduced the number of mitochondria with damaged cristae (P = 0.0086). mtDNA content has been previously used to assess the mitochondrial number in various diseases, including ALS, where a significant decrease was observed in the spinal cord of patients (Wiedemann et al, 2002; Kim et al, 2010; Disatnik et al, 2016). We measured the levels of the transcript of the mitochondrial gene, mtND2 (mitochondria‐encoded NADH dehydrogenase 2; a subunit of complex 1 located at the inner mitochondrial membrane) as a surrogate measure for mitochondrial number in the spinal cord and found a significant decrease in mtND2 levels in spinal cords from SOD1 G93A mice as compared to WT mice, which was improved by sustained P110 treatment (Fig 5A; P = 0.0271).