Garcia-Corzo 2013 Hum Mol Genet
| GarcĂa-Corzo L, Luna-SĂĄnchez M; Doerrier C; GarcĂa JA; GuarĂĄs A; AcĂn-PĂ©rez R; Bullejos-PeregrĂn J; LĂłpez A; Escames G; EnrĂquez JA; Acuña-Castroviejo D; LĂłpez LC (2012) Dysfunctional Coq9 protein causes predominant encephalomyopathy associated with CoQ deficiency.. Hum Mol Genet doi:10.1093/hmg/dds530. |
» http://www.ncbi.nlm.nih.gov/pubmed/23255162
GarcĂa-Corzo L, Luna-SĂĄnchez M, Doerrier C, GarcĂa JA, GuarĂĄs A, AcĂn-PĂ©rez R, Bullejos-PeregrĂn J, LĂłpez A, Escames G, EnrĂquez JA, Acuña-Castroviejo D, LĂłpez LC (2012) 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 (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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Stress:Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Genetic Defect; Knockdown; Overexpression"Genetic Defect; Knockdown; Overexpression" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Mouse Tissue;cell: Cardiac muscle"Cardiac muscle" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property., Skeletal muscle, Neurons; Brain"Neurons; Brain" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property., Kidney Preparation: Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.
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