Missense mutation of the COQ2 gene causes defects of bioenergetics and de novo pyrimidine synthesis

José M. López-Martín, Leonardo Salviati, Eva Trevisson, Giovanni Montini, Salvatore DiMauro, Catarina Quinzii, Michio Hirano, Angeles Rodriguez-Hernandez, Mario D. Cordero, José A. Sánchez-Alcázar, Carlos Santos-Ocaña, Plácido Navas

Research output: Contribution to journalArticlepeer-review


Coenzyme Q10 (CoQ10) deficiency has been associated with an increasing number of clinical phenotypes that respond to CoQ10 supplementation. In two siblings with encephalomyopathy, nephropathy and severe CoQ10 deficiency, a homozygous mutation was identified in the CoQ10 biosynthesis gene COQ2, encoding polyprenyl-pPB transferase. To confirm the pathogenicity of this mutation, we have demonstrated that human wild-type, but not mutant COQ2, functionally complements COQ2 defective yeast. In addition, an equivalent mutation introduced in the yeast COQ2 gene also decreases both CoQ6 concentration and growth in respiratory-chain dependent medium. Polyprenyl-pHB transferase activity was 33-45% of controls in COQ2 mutant fibroblasts. CoQ-dependent mitochondrial complexes activities were restored in deficient fibroblasts by CoQ10 supplementation, and growth rate was restored in these cells by either CoQ10 or uridine supplementation. This work is the first direct demonstration of the pathogenicity of a COQ2 mutation involved in human disease, and establishes yeast as a useful model to study human CoQ10 deficiency. Moreover, we demonstrate that CoQ10 deficiency in addition to the bioenergetics defect also impairs de novo pyrimidine synthesis, which may contribute to the pathogenesis of the disease.

Original languageEnglish
Pages (from-to)1091-1097
Number of pages7
JournalHuman Molecular Genetics
Issue number9
Publication statusPublished - May 2007

ASJC Scopus subject areas

  • Genetics


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