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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

Histopathology of muscle from female Coq9+/+ and Coq9Q95X mice at 6 and 18 months of ageA–H Complex II (SDH) and complex IV (COX) histochemistry of triceps surae showing a decreased stain in 18-month-old Coq9Q95X female mice (D, H) in contrast to normal SDH and COX activity in 6- and 18-month-old Coq9+/+ (A, C, E, G), as well as 6-month-old Coq9Q95X female mice (B, F).I–L Gomori trichrome stain (TGM) of triceps surae showed no differences between 6- and 18-month-old Coq9+/+ and Coq9Q95X female mice.M–P Hematoxylin and eosin (H&E) stains of triceps surae did not reveal any structural abnormality.Data information: Scale bars: 100 μm. n = 3 for each group. Complex IV, cytochrome c oxidase (COX); complex II, succinate dehydrogenase (SDH).
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fig08: Histopathology of muscle from female Coq9+/+ and Coq9Q95X mice at 6 and 18 months of ageA–H Complex II (SDH) and complex IV (COX) histochemistry of triceps surae showing a decreased stain in 18-month-old Coq9Q95X female mice (D, H) in contrast to normal SDH and COX activity in 6- and 18-month-old Coq9+/+ (A, C, E, G), as well as 6-month-old Coq9Q95X female mice (B, F).I–L Gomori trichrome stain (TGM) of triceps surae showed no differences between 6- and 18-month-old Coq9+/+ and Coq9Q95X female mice.M–P Hematoxylin and eosin (H&E) stains of triceps surae did not reveal any structural abnormality.Data information: Scale bars: 100 μm. n = 3 for each group. Complex IV, cytochrome c oxidase (COX); complex II, succinate dehydrogenase (SDH).

Mentions: In triceps surae muscle, we observed round-shaped muscle fibers with central nuclei in one Coq9Q95X female sample (out of six) (Supplementary Fig S8G–J). To check whether this was an isolated event or it was a sign of muscle pathology, we next performed a histochemical examination of triceps surae in controls and homozygous mutant mice at 3, 6, 12 and 18 months of age. In younger Coq9Q95X mice (3–12 months old), cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) activity did not differ compared to Coq9+/+ littermates (Fig8A, B, E and F and Supplementary Fig S9A–H). Nevertheless, at 18 months, Coq9Q95X females showed a higher number of COX- and SDH-negative fibers (Fig8C, D, G and H), suggesting that there was a shift from type I fibers (slow-twitch) to type II fibers (fast-twitch). The Gomori trichrome stain did not show signs of mitochondrial proliferation and scattered ragged red fibers (RRF) (Fig8I–L and Supplementary Fig S9I–L). No changes in the overall architecture and general morphology were detected by H&E stain (Fig8M–P and Supplementary Fig S9M–P).


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)

Histopathology of muscle from female Coq9+/+ and Coq9Q95X mice at 6 and 18 months of ageA–H Complex II (SDH) and complex IV (COX) histochemistry of triceps surae showing a decreased stain in 18-month-old Coq9Q95X female mice (D, H) in contrast to normal SDH and COX activity in 6- and 18-month-old Coq9+/+ (A, C, E, G), as well as 6-month-old Coq9Q95X female mice (B, F).I–L Gomori trichrome stain (TGM) of triceps surae showed no differences between 6- and 18-month-old Coq9+/+ and Coq9Q95X female mice.M–P Hematoxylin and eosin (H&E) stains of triceps surae did not reveal any structural abnormality.Data information: Scale bars: 100 μm. n = 3 for each group. Complex IV, cytochrome c oxidase (COX); complex II, succinate dehydrogenase (SDH).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4492823&req=5

fig08: Histopathology of muscle from female Coq9+/+ and Coq9Q95X mice at 6 and 18 months of ageA–H Complex II (SDH) and complex IV (COX) histochemistry of triceps surae showing a decreased stain in 18-month-old Coq9Q95X female mice (D, H) in contrast to normal SDH and COX activity in 6- and 18-month-old Coq9+/+ (A, C, E, G), as well as 6-month-old Coq9Q95X female mice (B, F).I–L Gomori trichrome stain (TGM) of triceps surae showed no differences between 6- and 18-month-old Coq9+/+ and Coq9Q95X female mice.M–P Hematoxylin and eosin (H&E) stains of triceps surae did not reveal any structural abnormality.Data information: Scale bars: 100 μm. n = 3 for each group. Complex IV, cytochrome c oxidase (COX); complex II, succinate dehydrogenase (SDH).
Mentions: In triceps surae muscle, we observed round-shaped muscle fibers with central nuclei in one Coq9Q95X female sample (out of six) (Supplementary Fig S8G–J). To check whether this was an isolated event or it was a sign of muscle pathology, we next performed a histochemical examination of triceps surae in controls and homozygous mutant mice at 3, 6, 12 and 18 months of age. In younger Coq9Q95X mice (3–12 months old), cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) activity did not differ compared to Coq9+/+ littermates (Fig8A, B, E and F and Supplementary Fig S9A–H). Nevertheless, at 18 months, Coq9Q95X females showed a higher number of COX- and SDH-negative fibers (Fig8C, D, G and H), suggesting that there was a shift from type I fibers (slow-twitch) to type II fibers (fast-twitch). The Gomori trichrome stain did not show signs of mitochondrial proliferation and scattered ragged red fibers (RRF) (Fig8I–L and Supplementary Fig S9I–L). No changes in the overall architecture and general morphology were detected by H&E stain (Fig8M–P and Supplementary Fig S9M–P).

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