Figure 6: Mutations in superoxide dismutase (SOD1) and coiled-coil-helix-coiled-coil helix domain 10 (CHCHD10) cause mitochondrial dysfunction in familial cases of amyotrophic lateral sclerosis (ALS). SOD1 mutations cause a number of mitochondrial defects including mitochondrial fragmentation, impaired mitophagy, and impaired mitochondrial anterograde transport of mitochondria, mitochondrial vacuolation, and apoptosis. CHCHD10 is localized in the mitochondrial intermembrane space, and mutation of the gene encoding this protein leads to a defect in the formation of the respiratory complex, mtDNA instability, and fragmentation of the mitochondrial network. Overall, oxidative stress is a common feature in ALS pathology. This is potentially due to the disruption of the respiratory chain caused by mitochondrial dysfunction.