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Title

Survival transcriptome in the coenzyme Q10 deficiency syndrome is acquired by epigenetic modifications: a modelling study for human coenzyme Q10 deficiencies

AuthorsFernández-Ayala, Daniel J. M.; Guerra, Ignacio; Jiménez-Gancedo, Sandra; Cascajo Almenara, M. V. ; Gavilán, Angela; DiMauro, Salvatore; Hirano, Michio; Briones, Paz; Artuch, Rafael; Cabo, Rafael de; Salviati, Leonardo; Navas, Plácido
KeywordsBasic sciences
Genetics
Issue Date2013
PublisherBMJ Publishing Group
CitationBMJ Open 3(3): e002524 (2013)
Abstract[Objectives]: Coenzyme Q10 (CoQ10) deficiency syndrome is a rare condition that causes mitochondrial dysfunction and includes a variety of clinical presentations as encephalomyopathy, ataxia and renal failure. First, we sought to set up what all have in common, and then investigate why CoQ10 supplementation reverses the bioenergetics alterations in cultured cells but not all the cellular phenotypes. [Design Modelling study]: This work models the transcriptome of human CoQ10 deficiency syndrome in primary fibroblast from patients and study the genetic response to CoQ10 treatment in these cells. [Setting]: Four hospitals and medical centres from Spain, Italy and the USA, and two research laboratories from Spain and the USA. [Participants]: Primary cells were collected from patients in the above centres. [Measurements]: We characterised by microarray analysis the expression profile of fibroblasts from seven CoQ10-deficient patients (three had primary deficiency and four had a secondary form) and aged-matched controls, before and after CoQ10 supplementation. Results were validated by Q-RT-PCR. The profile of DNA (CpG) methylation was evaluated for a subset of gene with displayed altered expression. [Results]: CoQ10-deficient fibroblasts (independently from the aetiology) showed a common transcriptomic profile that promotes cell survival by activating cell cycle and growth, cell stress responses and inhibiting cell death and immune responses. Energy production was supported mainly by glycolysis while CoQ10 supplementation restored oxidative phosphorylation. Expression of genes involved in cell death pathways was partially restored by treatment, while genes involved in differentiation, cell cycle and growth were not affected. Stably demethylated genes were unaffected by treatment whereas we observed restored gene expression in either non-methylated genes or those with an unchanged methylation pattern.
DescriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License.
Publisher version (URL)http://dx.doi.org/10.1136/bmjopen-2012-002524
URIhttp://hdl.handle.net/10261/129137
DOI10.1136/bmjopen-2012-002524
ISSN2044-6055
Appears in Collections:(CABD) Artículos
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