Lopez 2015 Abstract MiP2015

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Unraveling the causes of the clinical heterogeneity of coenzyme Q10 deficiency due to different molecular defects in Coq9 gene.


Luna-Sanchez M, Diaz-Casado E, Barca E, Hidalgo-Gutierrez A, Barriocanal-Casado E, Quinzii CM, Lopez LC (2015)

Event: MiP2015

Primary coenzyme Q10 (CoQ10) deficiency is due to mutations in genes involved in CoQ biosynthesis. The disease has been associated with five major phenotypes, but a genotype-phenotype correlation is unclear [1]. Here, we compare two mouse models with a genetic modification in Coq9 gene (Coq9Q95X and Coq9R239X). The comparison was done by biochemical, molecular, genetics, histopathological and phenotypic analyses. Coq9R239X mice manifest severe widespread CoQ deficiency associated with fatal encephalomyopathy [2]. In contrast, Coq9Q95X mice exhibit mild CoQ deficiency manifesting with reduction in CI&III activity and mitochondrial respiration in skeletal muscle, and late-onset mild mitochondrial myopathy. We show that these differences are due to the levels of COQ biosynthetic proteins, suggesting that the presence of a truncated version of COQ9 protein in Coq9R239X mice destabilizes the CoQ multiprotein complex [3]. Our study points out the importance of the multiprotein complex for CoQ biosynthesis in mammals, which may provide new insights to understand the genotype-phenotype heterogeneity associated with human CoQ deficiency and may have a potential impact on the treatment of this mitochondrial disorder.

Labels: MiParea: Respiration, nDNA;cell genetics  Pathology: Other  Stress:Mitochondrial disease  Organism: Mouse  Tissue;cell: Skeletal muscle 

Pathway: Other combinations 

Event: A1, Oral  MiP2015 


1-Dept Fisiología, Fac Medicina, Univ Granada, Spain; 2-Centro Investigación Biomédica, Inst Biotecnología, Parque Tecnológico Ciencias de la Salud, Granada, Spain; 3-Dept Neurology, Columbia Univ Med Center, New York, NY, USA. - luisca@ugr.es

References and acknowledgements

  1. Emmanuele V, López LC, Berardo A, Naini A, Tadesse S, Wen B, D’Agostino E, Salomon M, DiMauro S, Quinzii CM, Hirano M (2012) Heterogeneity of coenzyme Q10 deficiency: Patient Study and Literature Review. Arch Neurol 69:978-83.
  2. García-Corzo L, Luna-Sánchez M, Doerrier C, Ortiz F, Escames G, Acuña-Castroviejo D, López LC (2014) Ubiquinol-10 amelioratesmitochondrial encephalopathy associated with CoQ deficiency. Biochimica et Biophysica Acta 1842:893–901.
  3. Luna-Sanchez M, Diaz-Casado E, Barca E, Tejada MA, Montilla-Garcia A, Cobos EJ, Escames G, Acuña-Castroviejo D, Quinzii CM, López LC (2015) The clinical heterogeneity of coenzyme Q10 deficiency results from genotypic differences in the Coq9 gene. EMBO Mol Med 7:670-87.