Garcia-Corzo 2013 Hum Mol Genet

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García-Corzo L, Luna-Sánchez M, Doerrier C, García JA, Guarás A, Acín-Pérez R, Bullejos-Peregrín J, López A, Escames G, Enríquez JA, Acuña-Castroviejo D, López LC (2013) Dysfunctional Coq9 protein causes predominant encephalomyopathy associated with CoQ deficiency. Hum Mol Genet 22:1233-48.

» PMID: 23255162 Open Access

Garcia-Corzo L, Luna-Sanchez M, Doerrier C, Garcia JA, Guaras A, Acin-Perez R, Bullejos-Peregrin J, Lopez A, Escames G, Enriquez JA, Acuna-Castroviejo D, Lopez LC (2013) Hum Mol Genet

Abstract: Coenzyme Q10 (CoQ(10)) or ubiquinone is a well-known component of the mitochondrial respiratory chain. In humans, CoQ(10) deficiency causes a mitochondrial syndrome with an unexplained variability in the clinical presentations. To try to understand this heterogeneity in the clinical phenotypes, we have generated a Coq9 Knockin (R239X) mouse model. The lack of a functional Coq9 protein in homozygous Coq9 mutant (Coq9X/X) mice causes a severe reduction in the Coq7 protein and, as consequence, a widespread CoQ deficiency and accumulation of demethoxyubiquinone. The deficit in CoQ induces a brain-specific impairment of mitochondrial bioenergetics performance, a reduction in respiratory control ratio, ATP levels and ATP/ADP ratio and specific loss of respiratory complex I. These effects lead to neuronal death and demyelinization with severe vacuolization and astrogliosis in the brain of Coq9X/X mice that consequently die between 3 and 6 months of age. These results suggest that the instability of mitochondrial complex I in the brain, as a primary event, triggers the development of mitochondrial encephalomyopathy associated with CoQ deficiency.

Keywords: Coenzyme Q10, Mitochondrial encephalomyopathy

O2k-Network Lab: ES Granada Acuna-Castroviejo D


Labels: MiParea: Respiration, Genetic knockout;overexpression, Pharmacology;toxicology  Pathology: Myopathy, Neurodegenerative, Other 

Organism: Mouse  Tissue;cell: Heart, Skeletal muscle, Nervous system, Kidney  Preparation: Isolated mitochondria 


Coupling state: OXPHOS  Pathway: N, S  HRR: Oxygraph-2k 

CoQ