Functional alterations of the mitochondrially encoded ND4 subunit associated with Leber's hereditary optic neuropathy

Mauro Degli Esposti; Valerio Carelli; Anna Ghelli; Marina Ratta; Massimo Crimi; Simonetta Sangiorgi; Pasquale Montagna; Giorgio Lenaz; Elio Lugaresi; Pietro Cortelli

doi:10.1016/0014-5793(94)00971-6

Functional alterations of the mitochondrially encoded ND4 subunit associated with Leber's hereditary optic neuropathy

Mauro Degli Esposti, Valerio Carelli, Anna Ghelli, Marina Ratta, Massimo Crimi, Simonetta Sangiorgi, Pasquale Montagna, Giorgio Lenaz, Elio Lugaresi, Pietro Cortelli

Istituto Scienze Neurologiche

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	375-379
Number of pages	5
Journal	FEBS Letters
Volume	352
Issue number	3
DOIs	https://doi.org/10.1016/0014-5793(94)00971-6
Publication status	Published - Oct 3 1994

Keywords

LHON
Mitochondrial DNA
NADH: ubiquinone reductase
Ubiquinone

ASJC Scopus subject areas

Biochemistry
Biophysics
Molecular Biology

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10.1016/0014-5793(94)00971-6

Cite this

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title = "Functional alterations of the mitochondrially encoded ND4 subunit associated with Leber's hereditary optic neuropathy",

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.",

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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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Functional alterations of the mitochondrially encoded ND4 subunit associated with Leber's hereditary optic neuropathy

Abstract

Keywords

ASJC Scopus subject areas

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