2026-06-14T03:52:27Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/104952025-04-29T10:18:01Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Romero-Moya, Damià
author
Santos-Ocaña, Carlos
author
Castaño, Julio
author
Garrabou, Gloria
author
Rodríguez-Gómez, José A
author
Ruiz-Bonilla, Vanesa
author
Bueno, Clara
author
González-Rodríguez, Patricia
author
Giorgetti, Alessandra
author
Perdiguero, Eusebio
author
Prieto, Cristina
author
Moren-Nuñez, Constanza
author
Fernández-Ayala, Daniel J
author
Cascajo, Maria Victoria
author
Velasco, Iván
author
Canals, Josep Maria
author
Montero, Raquel
author
Yubero, Delia
author
Jou, Cristina
author
López-Barneo, José
author
Cardellach, Francesc
author
Munoz-Canoves, Pura
author
Artuch, Rafael
author
Navas, Placido
author
Menéndez, Pablo
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Fundación La Caixa
funder
Fundación Josep Carreras Contra la Leucemia
funder
Government of Catalonia (España)
2020-06-18T13:53:58Z
2020-06-18T13:53:58Z
2017-07
Stem Cells. 2017; 35(7):1687-1703
10.1002/stem.2634
1549-4918
Stem cells (Dayton, Ohio)
28472853
http://hdl.handle.net/20.500.12105/10495
Coenzyme Q10 (CoQ10 ) plays a crucial role in mitochondria as an electron carrier within the mitochondrial respiratory chain (MRC) and is an essential antioxidant. Mutations in genes responsible for CoQ10 biosynthesis (COQ genes) cause primary CoQ10 deficiency, a rare and heterogeneous mitochondrial disorder with no clear genotype-phenotype association, mainly affecting tissues with high-energy demand including brain and skeletal muscle (SkM). Here, we report a four-year-old girl diagnosed with minor mental retardation and lethal rhabdomyolysis harboring a heterozygous mutation (c.483G > C (E161D)) in COQ4. The patient's fibroblasts showed a decrease in [CoQ10 ], CoQ10 biosynthesis, MRC activity affecting complexes I/II + III, and respiration defects. Bona fide induced pluripotent stem cell (iPSCs) lines carrying the COQ4 mutation (CQ4-iPSCs) were generated, characterized and genetically edited using the CRISPR-Cas9 system (CQ4ed -iPSCs). Extensive differentiation and metabolic assays of control-iPSCs, CQ4-iPSCs and CQ4ed -iPSCs demonstrated a genotype association, reproducing the disease phenotype. The COQ4 mutation in iPSC was associated with CoQ10 deficiency, metabolic dysfunction, and respiration defects. iPSC differentiation into SkM was compromised, and the resulting SkM also displayed respiration defects. Remarkably, iPSC differentiation in dopaminergic or motor neurons was unaffected. This study offers an unprecedented iPSC model recapitulating CoQ10 deficiency-associated functional and metabolic phenotypes caused by COQ4 mutation. Stem Cells 2017;35:1687-1703.
eng
Genetic Rescue of Mitochondrial and Skeletal Muscle Impairment in an Induced Pluripotent Stem Cells Model of Coenzyme Q10 Deficiency.
journal article
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URL
https://repisalud.isciii.es/bitstreams/9066862b-0f39-44f2-a578-854b2a2332be/download
File
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application/pdf
GeneticRescueMitochondrialSkeletal _2017.pdf
URL
https://repisalud.isciii.es/bitstreams/e07625f7-dd0a-4434-959c-65fb9df1dfd7/download
File
MD5
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text/plain
GeneticRescueMitochondrialSkeletal _2017.pdf.txt