| First Author | García-Corzo L | Year | 2013 |
| Journal | Hum Mol Genet | Volume | 22 |
| Issue | 6 | Pages | 1233-48 |
| PubMed ID | 23255162 | Mgi Jnum | J:193288 |
| Mgi Id | MGI:5468078 | Doi | 10.1093/hmg/dds530 |
| Citation | Garcia-Corzo L, et al. (2013) Dysfunctional Coq9 protein causes predominant encephalomyopathy associated with CoQ deficiency. Hum Mol Genet 22(6):1233-48 |
| abstractText | 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. |
