Autophagy and mitochondrial fission are intricately linked as excessive fission leads to damaged mitochondria, which lowers the available ATP pool for autophagy to occur. Recent studies have demonstrated that autophagic alteration may be involved in ALS (An et al, 2014; Rudnick et al, 2017). Accumulation of p62 plays a role in protein aggregation in multiple neurodegenerative diseases, including ALS (Gal et al, 2007; Lee et al, 2015; Madill et al, 2017). Furthermore, p62 serves as a shuttling factor for polyubiquitinated proteins to the proteasome and p62 actually interacts with the proteasome (Seibenhener et al, 2004; Babu et al, 2005). A deficiency in autophagy may compromise the ubiquitin–proteasome system, since overabundant p62 would impair delivery of the proteasomal substrates to the proteasome. Furthermore, as shown also here, the proteasomal activity in ALS is decreased (Cheroni et al, 2009; Kabashi et al, 2012), thereby further increasing the oxidative stress.