Reduction in cytochrome c oxidase (Complex IV: COX) activity is a pathological marker for mitochondrial diseases of mtDNA derivation, because COX contains three mtDNA-coded subunits, COI, COII, and COIII (see Figure 1A), and the loss of these subunits by mutated mtDNAs can lead to mitochondrial respiration deficiencies and disease phenotypes [1]. The gene discussed is MT-CO1; the disease is inborn mitochondrial metabolism disorder.