Garcia-Corzo 2013 Hum Mol Genet: Difference between revisions
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{{Publication | {{Publication | ||
|title= | |title=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. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/23255162 PMID: 23255162] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/23255162 PMID: 23255162 Open Access] | ||
|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 | |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 | ||
|year=2013 | |year=2013 | ||
|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 | |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<sup>X/X<sup>'') 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<sup>X/X<sup>'' 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 | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Genetic knockout;overexpression | |area=Respiration, Genetic knockout;overexpression, Pharmacology;toxicology | ||
|organism=Mouse | |organism=Mouse | ||
|tissues=Heart, Skeletal muscle, Nervous system, Kidney | |tissues=Heart, Skeletal muscle, Nervous system, Kidney | ||
|preparations=Isolated | |preparations=Isolated mitochondria | ||
|diseases=Myopathy, Neurodegenerative, Other | |diseases=Myopathy, Neurodegenerative, Other | ||
|couplingstates=OXPHOS | |couplingstates=OXPHOS | ||
| | |pathways=N, S | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=CoQ | |additional=CoQ | ||
}} | }} |
Latest revision as of 16:38, 7 November 2016
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. |
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