期刊
MITOCHONDRION
卷 26, 期 -, 页码 72-80出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.mito.2015.12.004
关键词
NFU1; Lipoic acid; Iron-sulfur cluster; Mitochondrial disease; Mitochondrial cofactor; Metabolic disorder
资金
- Instituto de Salud Carlos III [FIS PI12/01138]
- Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), an initiative of Instituto de Salud Carlos III (Ministerio de Ciencia e Innovacion, Spain)
- Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) [SGR393]
- Wellcome Trust Centre for Mitochondrial Research [096919Z/11/Z]
- Medical Research Council (UK) Centre for Translational Muscle Disease Research [G0601943]
- Lily Foundation
- UK NHS
- National Institute for Health Research (NIHR) doctoral fellowship [NIHR-HCS-D12-03-04]
- Medical Research Council [G0601943, MR/K000608/1] Funding Source: researchfish
- National Institute for Health Research [NIHR-HCS-D12-03-04] Funding Source: researchfish
- MRC [G0601943, MR/K000608/1] Funding Source: UKRI
Mutations in NFU1 were recently identified in patients with fatal encephalopathy. NFU1 is an iron-sulfur cluster protein necessary for the activity of the mitochondrial respiratory chain complexes I-II and the synthesis of lipoic acid. We report two NFU1 compound heterozygous individuals with normal complex I and lipoic acid-dependent enzymatic activities and low, but detectable, levels of lipoylated proteins. We demonstrated a leaky splicing regulation due to a splice site mutation (c545 + 5G > A) that produces small amounts of wild type NFU1 mRNA that might result in enough protein to partially lipoylate and restore the activity of lipoic add-dependent enzymes and the assembly and activity of complex I. These results allowed us to gain insights into the molecular basis underlying this disease and should be considered for the diagnosis of NFU1 patients. (C) 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
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