In a recent report, aggregated TDP-43 with ALS-associated mutations was shown to bind to and sequester a subset of nuclear encoded mitochondrial DNA, including ATP5B, while increasing expression of a different subset of mitochondrial DNA and thereby inducing a global imbalance in the mitochondria (Zuo et al., 2021). The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.