Difference between revisions of "Garcia-Corzo 2013 Hum Mol Genet"
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|journal=Hum Mol Genet | |journal=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. | |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. | ||
|keywords=Coenzyme Q10, Mitochondrial encephalomyopathy | |keywords=Coenzyme Q10, Mitochondrial encephalomyopathy | ||
|mipnetlab=ES Granada Acuna-Castroviejo D | |mipnetlab=ES Granada Acuna-Castroviejo D | ||
}} | }} | ||
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|tissues=Heart, Skeletal muscle, Nervous system, Kidney | |tissues=Heart, Skeletal muscle, Nervous system, Kidney | ||
|preparations=Isolated Mitochondria | |preparations=Isolated Mitochondria | ||
|diseases= | |diseases=Myopathy, Neurodegenerative, Other | ||
|couplingstates=OXPHOS | |couplingstates=OXPHOS | ||
|substratestates=CI, CII | |substratestates=CI, CII | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=CoQ | |||
}} | }} |
Revision as of 16:23, 17 August 2013
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) Dysfunctional Coq9 protein causes predominant encephalomyopathy associated with CoQ deficiency. Hum Mol Genet 22: 1233-1248 |
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 (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. β’ Keywords: Coenzyme Q10, Mitochondrial encephalomyopathy
β’ O2k-Network Lab: ES Granada Acuna-Castroviejo D
Labels: MiParea: Genetic knockout;overexpression
Pathology: Myopathy, Neurodegenerative, Other
Organism: Mouse Tissue;cell: Heart, Skeletal muscle, Nervous system, 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.
Coupling state: OXPHOS
HRR: Oxygraph-2k
CoQ