Functional alterations of the mitochondrially encoded ND4 subunit associated with Leber's hereditary optic neuropathy
- 3 October 1994
- journal article
- case report
- Published by Wiley in FEBS Letters
- Vol. 352 (3) , 375-379
- https://doi.org/10.1016/0014-5793(94)00971-6
Abstract
Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease associated with point mutations in mitochondrial DNA. The most frequent of these mutations is the G-to-A substitution at nucleotide position 11,778 which changes an evolutionarily conserved arginine with a histidine at position 340 in subunit ND4 of NADH: ubiquinone reductase (respiratory complex I). We report that this amino acid substitution alters the affinity of complex I for the ubiquinone substrate and induces resistance towards its potent inhibitor rotenone in mitochondria of LHON patients. Such changes could reflect a substantial loss in the energy conserving function of NADH: ubiquinone reductase and thus explain the pathological effect of the ND4/11,778 mutation.Keywords
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