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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

Moderate CoQ deficiency in Coq9Q95X mice leads to impaired mitochondrial bioenergetics functionA–C Mitochondrial CoQ9 levels from cerebrum (A), kidney (B) and skeletal muscle (C) of Coq9+/+ and Coq9Q95X males and females. n = 8 for each group.D–F CI+CIII activity in cerebrum (D), kidney (E) and skeletal muscle (F) of male and female Coq9+/+ and Coq9Q95X mice. n = 6 for each group.G–I CII+CIII activity in cerebrum (G), kidney (H) and skeletal muscle (I) of male and female Coq9+/+ and Coq9Q95X mice. n = 6 for each group.J–L Blue-native gel electrophoresis (BNGE) followed by immunoblotting analysis of mitochondrial supercomplexes from Coq9+/+ (n = 3) and Coq9Q95X mice (n = 4) at 3 months of age.Data information: (A–I) Data are expressed as mean ± SD. Statistical analyses were performed on Coq9+/+ male mice versus Coq9Q95X male mice and Coq9+/+ female mice versus Coq9Q95X female mice. **P < 0.01; ***P < 0.001. Student's t-test. Complex I+III, NADH-cytochrome c reductase; complex II+III, SDH-cytochrome c reductase.Source data are available online for this figure.
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fig06: Moderate CoQ deficiency in Coq9Q95X mice leads to impaired mitochondrial bioenergetics functionA–C Mitochondrial CoQ9 levels from cerebrum (A), kidney (B) and skeletal muscle (C) of Coq9+/+ and Coq9Q95X males and females. n = 8 for each group.D–F CI+CIII activity in cerebrum (D), kidney (E) and skeletal muscle (F) of male and female Coq9+/+ and Coq9Q95X mice. n = 6 for each group.G–I CII+CIII activity in cerebrum (G), kidney (H) and skeletal muscle (I) of male and female Coq9+/+ and Coq9Q95X mice. n = 6 for each group.J–L Blue-native gel electrophoresis (BNGE) followed by immunoblotting analysis of mitochondrial supercomplexes from Coq9+/+ (n = 3) and Coq9Q95X mice (n = 4) at 3 months of age.Data information: (A–I) Data are expressed as mean ± SD. Statistical analyses were performed on Coq9+/+ male mice versus Coq9Q95X male mice and Coq9+/+ female mice versus Coq9Q95X female mice. **P < 0.01; ***P < 0.001. Student's t-test. Complex I+III, NADH-cytochrome c reductase; complex II+III, SDH-cytochrome c reductase.Source data are available online for this figure.

Mentions: To assess whether there was a direct correlation between the tissue CoQ deficiency and the bioenergetics defect, we next evaluated CoQ levels and mitochondrial respiratory chain function in isolated mitochondria from cerebrum, kidney and muscle of Coq9Q95X and control mice at 6 months of age. Mitochondrial CoQ levels were significantly decreased in cerebrum, kidney and muscle of Coq9Q95X compared with Coq9+/+ mice (Fig6A–C), and the level of CoQ deficiency correlated with the CoQ levels measured in tissue homogenates.


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)

Moderate CoQ deficiency in Coq9Q95X mice leads to impaired mitochondrial bioenergetics functionA–C Mitochondrial CoQ9 levels from cerebrum (A), kidney (B) and skeletal muscle (C) of Coq9+/+ and Coq9Q95X males and females. n = 8 for each group.D–F CI+CIII activity in cerebrum (D), kidney (E) and skeletal muscle (F) of male and female Coq9+/+ and Coq9Q95X mice. n = 6 for each group.G–I CII+CIII activity in cerebrum (G), kidney (H) and skeletal muscle (I) of male and female Coq9+/+ and Coq9Q95X mice. n = 6 for each group.J–L Blue-native gel electrophoresis (BNGE) followed by immunoblotting analysis of mitochondrial supercomplexes from Coq9+/+ (n = 3) and Coq9Q95X mice (n = 4) at 3 months of age.Data information: (A–I) Data are expressed as mean ± SD. Statistical analyses were performed on Coq9+/+ male mice versus Coq9Q95X male mice and Coq9+/+ female mice versus Coq9Q95X female mice. **P < 0.01; ***P < 0.001. Student's t-test. Complex I+III, NADH-cytochrome c reductase; complex II+III, SDH-cytochrome c reductase.Source data are available online for this figure.
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fig06: Moderate CoQ deficiency in Coq9Q95X mice leads to impaired mitochondrial bioenergetics functionA–C Mitochondrial CoQ9 levels from cerebrum (A), kidney (B) and skeletal muscle (C) of Coq9+/+ and Coq9Q95X males and females. n = 8 for each group.D–F CI+CIII activity in cerebrum (D), kidney (E) and skeletal muscle (F) of male and female Coq9+/+ and Coq9Q95X mice. n = 6 for each group.G–I CII+CIII activity in cerebrum (G), kidney (H) and skeletal muscle (I) of male and female Coq9+/+ and Coq9Q95X mice. n = 6 for each group.J–L Blue-native gel electrophoresis (BNGE) followed by immunoblotting analysis of mitochondrial supercomplexes from Coq9+/+ (n = 3) and Coq9Q95X mice (n = 4) at 3 months of age.Data information: (A–I) Data are expressed as mean ± SD. Statistical analyses were performed on Coq9+/+ male mice versus Coq9Q95X male mice and Coq9+/+ female mice versus Coq9Q95X female mice. **P < 0.01; ***P < 0.001. Student's t-test. Complex I+III, NADH-cytochrome c reductase; complex II+III, SDH-cytochrome c reductase.Source data are available online for this figure.
Mentions: To assess whether there was a direct correlation between the tissue CoQ deficiency and the bioenergetics defect, we next evaluated CoQ levels and mitochondrial respiratory chain function in isolated mitochondria from cerebrum, kidney and muscle of Coq9Q95X and control mice at 6 months of age. Mitochondrial CoQ levels were significantly decreased in cerebrum, kidney and muscle of Coq9Q95X compared with Coq9+/+ mice (Fig6A–C), and the level of CoQ deficiency correlated with the CoQ levels measured in tissue homogenates.

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