TY - JOUR
T1 - Functional alterations of the mitochondrially encoded ND4 subunit associated with Leber's hereditary optic neuropathy
AU - Esposti, Mauro Degli
AU - Carelli, Valerio
AU - Ghelli, Anna
AU - Ratta, Marina
AU - Crimi, Massimo
AU - Sangiorgi, Simonetta
AU - Montagna, Pasquale
AU - Lenaz, Giorgio
AU - Lugaresi, Elio
AU - Cortelli, Pietro
PY - 1994/10/3
Y1 - 1994/10/3
N2 - 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.
AB - 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.
KW - LHON
KW - Mitochondrial DNA
KW - NADH: ubiquinone reductase
KW - Ubiquinone
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U2 - 10.1016/0014-5793(94)00971-6
DO - 10.1016/0014-5793(94)00971-6
M3 - Article
C2 - 7926004
AN - SCOPUS:0027964504
VL - 352
SP - 375
EP - 379
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 3
ER -