Compelling evidence has revealed that the disease-associated mutations of TARDBP increase TDP-43 mitochondrial localization and cause complex I disassembly [319], while inhibiting the mitochondrial localization of TDP-43 restores mitochondrial bioenergetic malfunctions, neuronal loss, and motor-coordinative and cognitive deficits in TDP-43M337V ALS mice [320]. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.