The origin of increased ROS production and the mechanisms underlying redox imbalances remain elusive, but most likely involve physical interactions of protein aggregates with mitochondria, leading to impaired mitochondrial metabolism [309, 330, 331, 333], and/or aggregation of mutant superoxide dismutase SOD1, as observed in some ALS cases, resulting in nuclear depletion of wild type SOD1 [334]. Here, SOD1 is linked to amyotrophic lateral sclerosis.