Oxidative phosphorylation differences between mitochondrial DNA haplogroups modify the risk of Leber's hereditary optic neuropathy

Biochim Biophys Acta. 2012 Aug;1822(8):1216-22. doi: 10.1016/j.bbadis.2012.04.014. Epub 2012 Apr 26.


Leber's hereditary optic neuropathy is a maternally inherited optic atrophy caused by mitochondrial DNA point mutations. Previous epidemiological studies have shown that individuals from mitochondrial genetic backgrounds (haplogroups) J/Uk and H have a higher and a lower risk, respectively, of suffering this disorder. To analyze the bases of these associations at cellular and molecular levels, functional studies with cybrids provide high quality evidence. Cybrids from haplogroup J contain less mitochondrial deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) and synthesize a smaller amount of mitochondrial DNA-encoded polypeptides than those from haplogroup H. Haplogroup J cybrids also display lower oxygen consumption, mitochondrial inner membrane potential and total adenosine-5'-triphosphate (ATP) levels. Moreover, mitochondrial DNA levels correlate with many parameters of the oxidative phosphorylation system. These results suggest that the mitochondrial DNA amount determines oxidative phosphorylation capacity and, along with other recently published observations, support the possibility that mitochondrial DNA levels may be responsible for the bias of the disorder toward males, for the incomplete penetrance of mutations causing Leber's hereditary optic neuropathy and for the association of the disease with particular mitochondrial DNA haplogroups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Cell Line, Tumor
  • DNA, Mitochondrial / blood
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism*
  • Haplotypes
  • Humans
  • Membrane Potential, Mitochondrial
  • Mitochondrial Proteins / biosynthesis
  • Optic Atrophy, Hereditary, Leber / blood
  • Optic Atrophy, Hereditary, Leber / genetics
  • Optic Atrophy, Hereditary, Leber / metabolism*
  • Oxidative Phosphorylation
  • Oxygen Consumption
  • Point Mutation
  • RNA / metabolism
  • RNA, Mitochondrial
  • Risk Factors


  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • RNA, Mitochondrial
  • RNA
  • Adenosine Triphosphate