Possible crucial connection of TDP-43, mtDNA and inflammation in pathogenesis of ALS has been demonstrated recently in a remarkable study by Yu at al. Using motor neurons derived from induced pluripotent stem cell (iPSC) of patients with ALS, authors proved previous findings that TDP-43 enters mitochondria via TIM22, the mitochondrial import inner membrane translocase, and destabilizes homeostasis. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.