POLG and amyotrophic lateral sclerosis: In this study, we used prematurely aging mtDNA-mutator mice and control littermates with a wild-type nuclear genome derived from heterozygous PolgAwt/mut mice to elucidate whether mitochondrial dysfunction per se, caused by being homozygous for the PolgA mutation, is sufficient to impair the UPS and ALS in cells and lead to the generalized perturbation of protein homeostasis typically observed in aging [10,33].