The third one is gene therapy targeting complex I, such as the preclinical research and clinical trial for Leber’s hereditary optic neuropathy targeting ND4 gene [51, 52] and the gene therapy by AAV-Ndufs4 in Leigh syndrome mouse model of systemic Ndufs4-knockout [53]. Here, NDUFS4 is linked to Leber hereditary optic neuropathy.