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The clinical heterogeneity of coenzyme Q10 deficiency results from genotypic differences in the Coq9 gene.

Luna-Sánchez M, Díaz-Casado E, Barca E, Tejada MÁ, Montilla-García Á, Cobos EJ, Escames G, Acuña-Castroviejo D, Quinzii CM, López LC - EMBO Mol Med (2015)

Bottom Line: Primary coenzyme Q10 (CoQ10) deficiency is due to mutations in genes involved in CoQ biosynthesis.The disease has been associated with five major phenotypes, but a genotype-phenotype correlation is unclear.Our study points out the importance of the multiprotein complex for CoQ biosynthesis in mammals, which may provide new insights to understand the genotype-phenotype heterogeneity associated with human CoQ deficiency and may have a potential impact on the treatment of this mitochondrial disorder.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain Centro de Investigación Biomédica, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Granada, Spain.

No MeSH data available.


Related in: MedlinePlus

Mitochondrial respiration of Coq9+/+, Coq9Q95X and Coq9R239X miceA–D Measurement of phosphorylating respiration (represented as State 3o, in the presence of ADP and substrates) in kidney (A) and skeletal muscle (C) from male and female Coq9+/+, Coq9Q95X and Coq9R239X mice at 3 months of age. Representative O2 consumption graphic in kidney (B) and skeletal muscle (D) from female Coq9+/+, Coq9Q95X and Coq9R239X mice. Data information: All values are presented as mean ± SD. (A, C) *P < 0.05; **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+ mice. #P < 0.05; Coq9Q95X versus Coq9R239X mice. One-way ANOVA with a Tukey's post hoc test. Numbers above columns indicate P-values of the one-way ANOVA test (n = 3 for each group).
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fig07: Mitochondrial respiration of Coq9+/+, Coq9Q95X and Coq9R239X miceA–D Measurement of phosphorylating respiration (represented as State 3o, in the presence of ADP and substrates) in kidney (A) and skeletal muscle (C) from male and female Coq9+/+, Coq9Q95X and Coq9R239X mice at 3 months of age. Representative O2 consumption graphic in kidney (B) and skeletal muscle (D) from female Coq9+/+, Coq9Q95X and Coq9R239X mice. Data information: All values are presented as mean ± SD. (A, C) *P < 0.05; **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+ mice. #P < 0.05; Coq9Q95X versus Coq9R239X mice. One-way ANOVA with a Tukey's post hoc test. Numbers above columns indicate P-values of the one-way ANOVA test (n = 3 for each group).

Mentions: The bioenergetics defect in kidney and muscle of Coq9Q95X mice was confirmed by measurement of mitochondrial O2 consumption using isolated mitochondria in the XFe24 Extracellular Flux Analyzer (Seahorse Bioscience). In kidney, the phosphorylating respiration (State 3o, in the presence of ADP and substrates) showed a significant decrease in Coq9Q95X females (82 ± 6%), and Coq9R239X males and females (56 ± 13 and 57 ± 1%, respectively) compared with wild-type controls (Fig7A and B and Supplementary Fig S7A). In muscle, State 3o was significantly decreased in Coq9Q95X (62 ± 7% in males and 73 ± 6% in females) and Coq9R239X mice (58 ± 10% in males and 44 ± 4% in females) (Fig7C and D and Supplementary Fig S7B). In both mutant models, the percentage of decrease in the ADP-stimulated respiration was higher in muscle than in kidney (Fig7A and C). Similar data were obtained in other respiratory states, for example, basal respiration (State 2), resting respiration (State 4, after the addition of oligomycin) and maximal uncoupler-stimulated respiration (State 3u, after the addition of FCCP) (Supplementary Figs S6A–F and S7A and B and Fig7B and D).


The clinical heterogeneity of coenzyme Q10 deficiency results from genotypic differences in the Coq9 gene.

Luna-Sánchez M, Díaz-Casado E, Barca E, Tejada MÁ, Montilla-García Á, Cobos EJ, Escames G, Acuña-Castroviejo D, Quinzii CM, López LC - EMBO Mol Med (2015)

Mitochondrial respiration of Coq9+/+, Coq9Q95X and Coq9R239X miceA–D Measurement of phosphorylating respiration (represented as State 3o, in the presence of ADP and substrates) in kidney (A) and skeletal muscle (C) from male and female Coq9+/+, Coq9Q95X and Coq9R239X mice at 3 months of age. Representative O2 consumption graphic in kidney (B) and skeletal muscle (D) from female Coq9+/+, Coq9Q95X and Coq9R239X mice. Data information: All values are presented as mean ± SD. (A, C) *P < 0.05; **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+ mice. #P < 0.05; Coq9Q95X versus Coq9R239X mice. One-way ANOVA with a Tukey's post hoc test. Numbers above columns indicate P-values of the one-way ANOVA test (n = 3 for each group).
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Related In: Results  -  Collection

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fig07: Mitochondrial respiration of Coq9+/+, Coq9Q95X and Coq9R239X miceA–D Measurement of phosphorylating respiration (represented as State 3o, in the presence of ADP and substrates) in kidney (A) and skeletal muscle (C) from male and female Coq9+/+, Coq9Q95X and Coq9R239X mice at 3 months of age. Representative O2 consumption graphic in kidney (B) and skeletal muscle (D) from female Coq9+/+, Coq9Q95X and Coq9R239X mice. Data information: All values are presented as mean ± SD. (A, C) *P < 0.05; **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+ mice. #P < 0.05; Coq9Q95X versus Coq9R239X mice. One-way ANOVA with a Tukey's post hoc test. Numbers above columns indicate P-values of the one-way ANOVA test (n = 3 for each group).
Mentions: The bioenergetics defect in kidney and muscle of Coq9Q95X mice was confirmed by measurement of mitochondrial O2 consumption using isolated mitochondria in the XFe24 Extracellular Flux Analyzer (Seahorse Bioscience). In kidney, the phosphorylating respiration (State 3o, in the presence of ADP and substrates) showed a significant decrease in Coq9Q95X females (82 ± 6%), and Coq9R239X males and females (56 ± 13 and 57 ± 1%, respectively) compared with wild-type controls (Fig7A and B and Supplementary Fig S7A). In muscle, State 3o was significantly decreased in Coq9Q95X (62 ± 7% in males and 73 ± 6% in females) and Coq9R239X mice (58 ± 10% in males and 44 ± 4% in females) (Fig7C and D and Supplementary Fig S7B). In both mutant models, the percentage of decrease in the ADP-stimulated respiration was higher in muscle than in kidney (Fig7A and C). Similar data were obtained in other respiratory states, for example, basal respiration (State 2), resting respiration (State 4, after the addition of oligomycin) and maximal uncoupler-stimulated respiration (State 3u, after the addition of FCCP) (Supplementary Figs S6A–F and S7A and B and Fig7B and D).

Bottom Line: Primary coenzyme Q10 (CoQ10) deficiency is due to mutations in genes involved in CoQ biosynthesis.The disease has been associated with five major phenotypes, but a genotype-phenotype correlation is unclear.Our study points out the importance of the multiprotein complex for CoQ biosynthesis in mammals, which may provide new insights to understand the genotype-phenotype heterogeneity associated with human CoQ deficiency and may have a potential impact on the treatment of this mitochondrial disorder.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain Centro de Investigación Biomédica, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Granada, Spain.

No MeSH data available.


Related in: MedlinePlus