To date, LHON is the only human disease for which the influence of the mtDNA background (haplogroups) has been solidly documented [103], particularly on the m.14484T>C in MT-ND6 and m.11778G>A in MT-ND4 LHON mutations [104], whereas the association of LHON with a chromosome X locus is still a controversial, but interesting hypothesis since it could explain the male prevalence of this mitochondrial disorder [105]. Here, MT-ND4 is linked to Leber hereditary optic neuropathy.