scholarly journals Food derived respiratory complex I inhibitors modify the effect of Leber hereditary optic neuropathy mutations

2018 ◽  
Vol 120 ◽  
pp. 89-97 ◽  
Author(s):  
Ester López-Gallardo ◽  
Sonia Emperador ◽  
Carmen Hernández-Ainsa ◽  
Julio Montoya ◽  
M. Pilar Bayona-Bafaluy ◽  
...  
Keyword(s):  
Optic Neuropathy ◽  
Complex I ◽  
Leber Hereditary Optic Neuropathy ◽  
Respiratory Complex ◽  
Respiratory Complex I ◽  
Hereditary Optic Neuropathy

scholarly journals Case Report: A Novel Mutation in the Mitochondrial MT-ND5 Gene Is Associated With Leber Hereditary Optic Neuropathy (LHON)

2021 ◽  
Vol 12 ◽  
Author(s):  
Martin Engvall ◽  
Aki Kawasaki ◽  
Valerio Carelli ◽  
Rolf Wibom ◽  
Helene Bruhn ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Respiratory Chain ◽  
Optic Neuropathy ◽  
Complex I ◽  
Novel Mutation ◽  
Mitochondrial Respiratory Chain ◽  
Leber Hereditary Optic Neuropathy ◽  
Mild Defect ◽  
Hereditary Optic Neuropathy ◽  
Mitochondrial Respiratory

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease causing severe bilateral visual loss, typically in young adults. The disorder is commonly caused by one of three primary point mutations in mitochondrial DNA, but a number of other rare mutations causing or associated with the clinical syndrome of LHON have been reported. The mutations in LHON are almost exclusively located in genes encoding subunits of complex I in the mitochondrial respiratory chain. Here we report two patients, a mother and her son, with the typical LHON phenotype. Genetic investigations for the three common mutations were negative, instead we found a new and previously unreported mutation in mitochondrial DNA. This homoplasmic mutation, m.13345G>A, is located in the MT-ND5 gene, encoding a core subunit in complex I in the mitochondrial respiratory chain. Investigation of the patients mitochondrial respiratory chain in muscle found a mild defect in the combined activity of complex I+III. In the literature six other mutations in the MT-ND5 gene have been associated with LHON and by this report a new putative mutation in the MT-ND5 can be added.

scholarly journals Severe Impairment of Complex I–Driven Adenosine Triphosphate Synthesis in Leber Hereditary Optic Neuropathy Cybrids

2005 ◽  
Vol 62 (5) ◽  
pp. 730 ◽  
Author(s):  
Alessandra Baracca ◽  
Giancarlo Solaini ◽  
Gianluca Sgarbi ◽  
Giorgio Lenaz ◽  
Agostino Baruzzi ◽  
...  
Keyword(s):  
Adenosine Triphosphate ◽  
Optic Neuropathy ◽  
Complex I ◽  
Leber Hereditary Optic Neuropathy ◽  
Severe Impairment ◽  
Hereditary Optic Neuropathy

Leber hereditary optic neuropathy mutations in the ND6 subunit of mitochondrial complex I affect ubiquinone reduction kinetics in a bacterial model of the enzyme

2007 ◽  
Vol 409 (1) ◽  
pp. 129-137 ◽  
Author(s):  
Jukka Pätsi ◽  
Marko Kervinen ◽  
Moshe Finel ◽  
Ilmo E. Hassinen
Keyword(s):  
Optic Neuropathy ◽  
Complex I ◽  
Reductase Activity ◽  
Substrate Inhibition ◽  
Reduction Rate ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Leber Hereditary Optic Neuropathy ◽  
Nadh:Quinone Oxidoreductase ◽  
Hereditary Optic Neuropathy

LHON (Leber hereditary optic neuropathy) is a maternally inherited disease that leads to sudden loss of central vision at a young age. There are three common primary LHON mutations, occurring at positions 3460, 11778 and 14484 in the human mtDNA (mitochondrial DNA), leading to amino acid substitutions in mitochondrial complex I subunits ND1, ND4 and ND6 respectively. We have now examined the effects of ND6 mutations on the function of complex I using the homologous NuoJ subunit of Escherichia coli NDH-1 (NADH:quinone oxidoreductase) as a model system. The assembly level of the NDH-1 mutants was assessed using electron transfer from deamino-NADH to the ‘shortcut’ electron acceptor HAR (hexammine ruthenium), whereas ubiquinone reductase activity was determined using DB (decylubiquinone) as a substrate. Mutant growth in minimal medium with malate as the main carbon source was used for initial screening of the efficiency of energy conservation by NDH-1. The results indicated that NuoJ-M64V, the equivalent of the common LHON mutation in ND6, had a mild effect on E. coli NDH-1 activity, while nearby mutations, particularly NuoJ-Y59F, NuoJ-V65G and NuoJ-M72V, severely impaired the DB reduction rate and cell growth on malate. NuoJ-Met64 and NuoJ-Met72 position mutants lowered the affinity of NDH-1 for DB and explicit C-type inhibitors, whereas NuoJ-Y59C displayed substrate inhibition by oxidized DB. The results are compatible with the notion that the ND6 subunit delineates the binding cavity of ubiquinone substrate, but does not directly take part in the catalytic reaction. How these changes in the enzyme's catalytic properties contribute to LHON pathogenesis is discussed.

Clinical features of vision improvement in patients with Leber hereditary optic neuropathy

2020 ◽  
pp. 47-49
Author(s):  
N.L. Sheremet ◽  
◽  
N.A. Andreeva ◽  
N.V. Zhorzholadze ◽  
M.S. Shmelkova ◽  
...  
Keyword(s):  
Clinical Features ◽  
Optic Neuropathy ◽  
Leber Hereditary Optic Neuropathy ◽  
Hereditary Optic Neuropathy
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