scholarly journals NDUFS8-related Complex I Deficiency Extends Phenotype from “PEO Plus” to Leigh Syndrome

2012 ◽  
pp. 17-22 ◽  
Author(s):  
Adela Della Marina ◽  
Ulrike Schara ◽  
Angela Pyle ◽  
Claudia Möller-Hartmann ◽  
Elke Holinski-Feder ◽  
...  
Keyword(s):  
Complex I ◽  
Leigh Syndrome ◽  
Complex I Deficiency ◽  
Related Complex

P180 – 1827 NDFUS8-related Complex I Deficiency – “PEO-Plus” and mild Leigh syndrome

2013 ◽  
Vol 17 ◽  
pp. S103
Author(s):  
A Della Marina ◽  
U Schara ◽  
A Pyle ◽  
C Möller-Hartmann ◽  
E Holinski-Feder ◽  
...  
Keyword(s):  
Complex I ◽  
Leigh Syndrome ◽  
Complex I Deficiency ◽  
Related Complex

scholarly journals TAT-Conjugated NDUFS8 Can Be Transduced into Mitochondria in a Membrane-Potential-Independent Manner and Rescue Complex I Deficiency

2021 ◽  
Vol 22 (12) ◽  
pp. 6524
Author(s):  
Bo-Yu Lin ◽  
Gui-Teng Zheng ◽  
Kai-Wen Teng ◽  
Juan-Yu Chang ◽  
Chao-Chang Lee ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Fusion Proteins ◽  
Complex I ◽  
Nadh Dehydrogenase ◽  
Leigh Syndrome ◽  
Protein Transduction ◽  
Independent Manner ◽  
Complex I Deficiency ◽  
Transactivator Of Transcription ◽  
Hiv 1

NADH dehydrogenase (ubiquinone) Fe-S protein 8 (NDUFS8) is a nuclear-encoded core subunit of human mitochondrial complex I. Defects in NDUFS8 are associated with Leigh syndrome and encephalomyopathy. Cell-penetrating peptide derived from the HIV-1 transactivator of transcription protein (TAT) has been successfully applied as a carrier to bring fusion proteins into cells without compromising the biological function of the cargoes. In this study, we developed a TAT-mediated protein transduction system to rescue complex I deficiency caused by NDUFS8 defects. Two fusion proteins (TAT-NDUFS8 and NDUFS8-TAT) were exogenously expressed and purified from Escherichia coli for transduction of human cells. In addition, similar constructs were generated and used in transfection studies for comparison. The results showed that both exogenous TAT-NDUFS8 and NDUFS8-TAT were delivered into mitochondria and correctly processed. Interestingly, the mitochondrial import of TAT-containing NDUFS8 was independent of mitochondrial membrane potential. Treatment with TAT-NDUFS8 not only significantly improved the assembly of complex I in an NDUFS8-deficient cell line, but also partially rescued complex I functions both in the in-gel activity assay and the oxygen consumption assay. Our current findings suggest the considerable potential of applying the TAT-mediated protein transduction system for treatment of complex I deficiency.

A novel recurrent mitochondrial DNA mutation inND3 gene is associated with isolated complex I deficiency causing Leigh syndrome and dystonia

2007 ◽  
Vol 143A (1) ◽  
pp. 33-41 ◽  
Author(s):  
Emmanuelle Sarzi ◽  
Michael D. Brown ◽  
Sophie Lebon ◽  
Dominique Chretien ◽  
Arnold Munnich ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Complex I ◽  
Leigh Syndrome ◽  
Mitochondrial Dna Mutation ◽  
Dna Mutation ◽  
Complex I Deficiency

scholarly journals Phenotype-genotype correlations in Leigh syndrome: new insights from a multicentre study of 96 patients

2017 ◽  
Vol 55 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Kalliopi Sofou ◽  
Irenaeus F M de Coo ◽  
Elsebet Ostergaard ◽  
Pirjo Isohanni ◽  
Karin Naess ◽  
...  
Keyword(s):  
Complex I ◽  
Mitochondrial Disorder ◽  
Mitochondrial Diseases ◽  
Leigh Syndrome ◽  
Central Nervous System Disease ◽  
Genetic Defects ◽  
System Disease ◽  
Ocular Manifestations ◽  
Complex I Deficiency ◽  
Mitochondrial Atp Synthase

BackgroundLeigh syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. While some genetic defects are associated with well-described phenotypes, phenotype-genotype correlations in Leigh syndrome are not fully explored.ObjectiveWe aimed to identify phenotype-genotype correlations in Leigh syndrome in a large cohort of systematically evaluated patients.MethodsWe studied 96 patients with genetically confirmed Leigh syndrome diagnosed and followed in eight European centres specialising in mitochondrial diseases.ResultsWe found that ataxia, ophthalmoplegia and cardiomyopathy were more prevalent among patients with mitochondrial DNA defects. Patients with mutations in MT-ND and NDUF genes with complex I deficiency shared common phenotypic features, such as early development of central nervous system disease, followed by high occurrence of cardiac and ocular manifestations. The cerebral cortex was affected in patients with NDUF mutations significantly more often than the rest of the cohort. Patients with the m.8993T>G mutation in MT-ATP6 gene had more severe clinical and radiological manifestations and poorer disease outcome compared with patients with the m.8993T>C mutation.ConclusionOur study provides new insights into phenotype-genotype correlations in Leigh syndrome and particularly in patients with complex I deficiency and with defects in the mitochondrial ATP synthase.

scholarly journals Leigh Syndrome Associated With Mitochondrial Complex I Deficiency Due to a Novel Mutation in the NDUFS1 Gene

2005 ◽  
Vol 62 (4) ◽  
pp. 659 ◽  
Author(s):  
Miguel A. Martín ◽  
Alberto Blázquez ◽  
Luis G. Gutierrez-Solana ◽  
Daniel Fernández-Moreira ◽  
Paz Briones ◽  
...  
Keyword(s):  
Complex I ◽  
Novel Mutation ◽  
Leigh Syndrome ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Complex I Deficiency

scholarly journals Exogenous NAD+ prevents galactose-induced death of Leigh Syndrome patient fibroblasts with isolated complex I deficiency

2018 ◽  
Vol 1859 ◽  
pp. e28-e29
Author(s):  
Werner J.H. Koopman ◽  
Eligio F. Iannetti ◽  
Jan A.M. Smeitink ◽  
Peter H.G.M. Willems ◽  
Julien Beyrath
Keyword(s):  
Complex I ◽  
Leigh Syndrome ◽  
Syndrome Patient ◽  
Complex I Deficiency

Biochemical and genetic analysis of Leigh syndrome with complex I deficiency

Mitochondrion ◽  
2011 ◽  
Vol 11 (4) ◽  
pp. 650-651
Author(s):  
Dina A. Mehaney⁎ ◽  
Fayza A. Hassan ◽  
Laila A. Selim ◽  
Sawsn A. Hassan ◽  
Enrico Bertini ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Complex I ◽  
Leigh Syndrome ◽  
Complex I Deficiency
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