All these results confirm that mtDNA amount largely determines the OXPHOS function and could explain why risk factors for LHON have been associated with lesser mtDNA amount [7], and why higher mtDNA levels protect against LHON mutations, as reported in healthy homoplasmic LHON mutation carriers [6, 34]. The gene discussed is MT-ND4; the disease is Leber hereditary optic neuropathy.