TARDBP and amyotrophic lateral sclerosis: Lastly, ALS-associated TDP-43 mutations were recently documented by provoking evident deregulation of autophagy up-stream regulators like the AMP-activated protein kinase (AMPK) pathway (Perera et al., 2014; Smith et al., 2019); while mutations related to optineurin disrupt the recruitment of the autophagic machinery to the outer mitochondrial membrane and suspend its incorporation into autophagosome structures (Wong and Holzbaur, 2014).