SOD1 and amyotrophic lateral sclerosis: Interestingly, a sequestration pathological mechanism has been proposed in transgenic models of SOD1 as well, as mutant SOD1 builds up in the intermembrane space and forms aggregates which impair the activity of the ETC, especially complexes I and IV.120,121 Moreover, previous research on SOD1 models described decreased calcium homeostasis122 and an abnormal interaction between mitochondria and the ER,123 but a causal link between these two features of ALS pathology is still to be confirmed in SOD1 mutants.