Disease-associated mt-tRNAMet point mutations that impair Nsun3-mediated methylation have pathological consequences (Nakano et al. 2016), and loss of function mutations in NSUN3 are reported to cause severe multisystem mitochondrial disease associated with combined OXPHOS deficiency (Van Haute et al. 2016). Here, NSUN3 is linked to inborn mitochondrial metabolism disorder.