2026-06-14T03:56:04Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/104952025-04-29T10:18:01Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 author 2017-07 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. 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 Genetic Rescue of Mitochondrial and Skeletal Muscle Impairment in an Induced Pluripotent Stem Cells Model of Coenzyme Q10 Deficiency.