Sequence homology of NADH CoQ reductase subunit IV with nucleotide-requiring enzymes

The amino acid sequence of NADH CoQ reductase subunit IV is highly homologous with those of enzymes such as ATPase, argininosuccinate synthetase and adenylate kinase. Replacement of arginine by histidine in three enzymes was shown to result in loss of enzyme activity, causing pathologies including citrullinemia. As an analogy, we submit the hypothesis that replacement of arginine by histidine in NADH CoQ reductase subunit IV leads to its activity change, and ultimately results in Leber's hereditary optic neuropathy.