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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

Levels of COQ biosynthetic proteinsA–D Representative Western blot and quantitation of Western blot bands of COQ7 (A), ADCK3 (B), COQ5 (C) and COQ6 (D), and VDAC1 as a loading control in the kidneys of 3-month-old mice. *P < 0.05; **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+ mice. ##P < 0.01; ###P < 0.001; Coq9Q95X versus Coq9R239X mice. One-way ANOVA with a Tukey's post hoc test.E–H Representative Western blot and quantitation of Western blot bands of COQ7 (E), ADCK3 (F), COQ5 (G) and COQ6 (H), and VDAC1 as a loading control in skeletal muscle of 3-month-old mice. **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+ mice. #P < 0.05; ##P < 0.01; Coq9Q95X versus Coq9R239X mice.Data information: All values are presented as mean ± SD. One-way ANOVA with a Tukey's post hoc test. Numbers above columns indicate P-values of the one-way ANOVA test. Coq9+/+ mice n = 4; Coq9Q95X and Coq9R239X mice n = 5.Source data are available online for this figure.
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fig05: Levels of COQ biosynthetic proteinsA–D Representative Western blot and quantitation of Western blot bands of COQ7 (A), ADCK3 (B), COQ5 (C) and COQ6 (D), and VDAC1 as a loading control in the kidneys of 3-month-old mice. *P < 0.05; **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+ mice. ##P < 0.01; ###P < 0.001; Coq9Q95X versus Coq9R239X mice. One-way ANOVA with a Tukey's post hoc test.E–H Representative Western blot and quantitation of Western blot bands of COQ7 (E), ADCK3 (F), COQ5 (G) and COQ6 (H), and VDAC1 as a loading control in skeletal muscle of 3-month-old mice. **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+ mice. #P < 0.05; ##P < 0.01; Coq9Q95X versus Coq9R239X mice.Data information: All values are presented as mean ± SD. One-way ANOVA with a Tukey's post hoc test. Numbers above columns indicate P-values of the one-way ANOVA test. Coq9+/+ mice n = 4; Coq9Q95X and Coq9R239X mice n = 5.Source data are available online for this figure.

Mentions: Secondly, we measured the levels of the CoQ biosynthetic proteins encoded by these genes. In Coq9Q95X mice, steady-state levels of COQ7 and COQ5 were significantly decreased in cerebrum (19 ± 9 and 41 ± 13%), kidney (9 ± 6 and 50 ± 9%) and muscle (16 ± 3 and 17 ± 6%) compared with Coq9+/+ mice. Coq9R239X mice showed extremely reduced levels of COQ5 and COQ7 in cerebrum (0.1 ± 0.1 and 35 ± 11%), kidney (0.1 ± 0.1 and 38 ± 14%), and muscle (undetectable, and 17 ± 6%) compared to Coq9+/+ mice (Supplementary Fig S4A and C; Fig5A, C, E and G).


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)

Levels of COQ biosynthetic proteinsA–D Representative Western blot and quantitation of Western blot bands of COQ7 (A), ADCK3 (B), COQ5 (C) and COQ6 (D), and VDAC1 as a loading control in the kidneys of 3-month-old mice. *P < 0.05; **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+ mice. ##P < 0.01; ###P < 0.001; Coq9Q95X versus Coq9R239X mice. One-way ANOVA with a Tukey's post hoc test.E–H Representative Western blot and quantitation of Western blot bands of COQ7 (E), ADCK3 (F), COQ5 (G) and COQ6 (H), and VDAC1 as a loading control in skeletal muscle of 3-month-old mice. **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+ mice. #P < 0.05; ##P < 0.01; Coq9Q95X versus Coq9R239X mice.Data information: All values are presented as mean ± SD. One-way ANOVA with a Tukey's post hoc test. Numbers above columns indicate P-values of the one-way ANOVA test. Coq9+/+ mice n = 4; Coq9Q95X and Coq9R239X mice n = 5.Source data are available online for this figure.
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Related In: Results  -  Collection

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fig05: Levels of COQ biosynthetic proteinsA–D Representative Western blot and quantitation of Western blot bands of COQ7 (A), ADCK3 (B), COQ5 (C) and COQ6 (D), and VDAC1 as a loading control in the kidneys of 3-month-old mice. *P < 0.05; **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+ mice. ##P < 0.01; ###P < 0.001; Coq9Q95X versus Coq9R239X mice. One-way ANOVA with a Tukey's post hoc test.E–H Representative Western blot and quantitation of Western blot bands of COQ7 (E), ADCK3 (F), COQ5 (G) and COQ6 (H), and VDAC1 as a loading control in skeletal muscle of 3-month-old mice. **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+ mice. #P < 0.05; ##P < 0.01; Coq9Q95X versus Coq9R239X mice.Data information: All values are presented as mean ± SD. One-way ANOVA with a Tukey's post hoc test. Numbers above columns indicate P-values of the one-way ANOVA test. Coq9+/+ mice n = 4; Coq9Q95X and Coq9R239X mice n = 5.Source data are available online for this figure.
Mentions: Secondly, we measured the levels of the CoQ biosynthetic proteins encoded by these genes. In Coq9Q95X mice, steady-state levels of COQ7 and COQ5 were significantly decreased in cerebrum (19 ± 9 and 41 ± 13%), kidney (9 ± 6 and 50 ± 9%) and muscle (16 ± 3 and 17 ± 6%) compared with Coq9+/+ mice. Coq9R239X mice showed extremely reduced levels of COQ5 and COQ7 in cerebrum (0.1 ± 0.1 and 35 ± 11%), kidney (0.1 ± 0.1 and 38 ± 14%), and muscle (undetectable, and 17 ± 6%) compared to Coq9+/+ mice (Supplementary Fig S4A and C; Fig5A, C, E and G).

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