To ascertain if the toxicity caused by TDP-43 cytoplasmic foci—often occurring under pathological conditions—alters the physical interaction between ER and mitochondria, we also monitored ER–mitochondria networks in HeLa cells transfected with either wild-type (WT) TDP-43 or the ALS-related Q331K TDP-43 mutant. Here, TARDBP is linked to amyotrophic lateral sclerosis.