title: Survival transcriptome in the coenzyme Q10 deficiency syndrome is acquired by epigenetic modifications: a modelling study for human coenzyme Q10 deficiencies.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Four hospitals and medical centres from Spain, Italy and the USA, and two research laboratories from Spain and the USA.
  
  
  METHODS
  Primary cells were collected from patients in the above centres.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  CoQ10 deficiency induces a specific transcriptomic profile that promotes cell survival, which is only partially rescued by CoQ10 supplementation.
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD-CSIC), Universidad Pablo Olavide, Seville, Spain.
authors.forename: Daniel J M
authors.initials: DJ
authors.lastname: Fernández-Ayala
authors.forename: Ignacio
authors.initials: I
authors.lastname: Guerra
authors.forename: Sandra
authors.initials: S
authors.lastname: Jiménez-Gancedo
authors.forename: Maria V
authors.initials: MV
authors.lastname: Cascajo
authors.forename: Angela
authors.initials: A
authors.lastname: Gavilán
authors.forename: Salvatore
authors.initials: S
authors.lastname: Dimauro
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Paz
authors.initials: P
authors.lastname: Briones
authors.forename: Rafael
authors.initials: R
authors.lastname: Artuch
authors.forename: Rafael
authors.initials: R
authors.lastname: De Cabo
authors.forename: Leonardo
authors.initials: L
authors.lastname: Salviati
authors.forename: Plácido
authors.initials: P
authors.lastname: Navas