TARDBP and mitochondrial disease: Though the pathogenesis of ALS is different from the metabolic myopathy, such as mitochondrial disease, dysfunction of mitochondria has been linked to muscle weakness in ALS: (1) the deposition of pathological protein of ALS such as TAR DNA-binding protein 43 (TDP-43) impairs the mitochondrial structure, which further induces death of muscular cells through devastating mitophagy, excitotoxicity, and oxidative stress (Kodavati et al., 2020).