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Dysfunctional Coq9 protein causes predominant encephalomyopathy associated with CoQ deficiency.

Authors: 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 
Citation: Garcia-Corzo L, etal., Hum Mol Genet. 2013 Mar 15;22(6):1233-48. doi: 10.1093/hmg/dds530. Epub 2012 Dec 18.
Pubmed: (View Article at PubMed) PMID:23255162
DOI: Full-text: DOI:10.1093/hmg/dds530

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 (Coq9(X/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 Coq9(X/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.

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RGD ID: 10402107
Created: 2015-10-15
Species: All species
Last Modified: 2015-10-15
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.