{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T16:38:06Z","timestamp":1764175086782,"version":"build-2065373602"},"reference-count":138,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:00:00Z","timestamp":1632268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018943","name":"Consejer\u00eda de Conocimiento, Investigaci\u00f3n y Universidad, Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["P18-RT-4572, UPO-126247, UPO-1265673 and BIO-177"],"award-info":[{"award-number":["P18-RT-4572, UPO-126247, UPO-1265673 and BIO-177"]}],"id":[{"id":"10.13039\/501100018943","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Instituto de Salud Carlos III","award":["FIS PI20\/00541"],"award-info":[{"award-number":["FIS PI20\/00541"]}]},{"name":"FEDER Funding Program from the European Union","award":["BBIO-177"],"award-info":[{"award-number":["BBIO-177"]}]},{"name":"CIBERER","award":["U729"],"award-info":[{"award-number":["U729"]}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RED2018-102576-T"],"award-info":[{"award-number":["RED2018-102576-T"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary coenzyme Q10 (CoQ) deficiency includes a heterogeneous group of mitochondrial diseases characterized by low mitochondrial levels of CoQ due to decreased endogenous biosynthesis rate. These diseases respond to CoQ treatment mainly at the early stages of the disease. The advances in the next generation sequencing (NGS) as whole-exome sequencing (WES) and whole-genome sequencing (WGS) have increased the discoveries of mutations in either gene already described to participate in CoQ biosynthesis or new genes also involved in this pathway. However, these technologies usually provide many mutations in genes whose pathogenic effect must be validated. To functionally validate the impact of gene variations in the disease\u2019s onset and progression, different cell models are commonly used. We review here the use of yeast strains for functional complementation of human genes, dermal skin fibroblasts from patients as an excellent tool to demonstrate the biochemical and genetic mechanisms of these diseases and the development of human-induced pluripotent stem cells (hiPSCs) and iPSC-derived organoids for the study of the pathogenesis and treatment approaches.<\/jats:p>","DOI":"10.3390\/ijms221910211","type":"journal-article","created":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T22:50:48Z","timestamp":1632351048000},"page":"10211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cellular Models for Primary CoQ Deficiency Pathogenesis Study"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2379-796X","authenticated-orcid":false,"given":"Carlos","family":"Santos-Oca\u00f1a","sequence":"first","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, and CIBERER, Instituto de Salud Carlos III, Universidad Pablo de Olavide-CSIC-JA, Carretera de Utrera km1, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda V.","family":"Cascajo","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, and CIBERER, Instituto de Salud Carlos III, Universidad Pablo de Olavide-CSIC-JA, Carretera de Utrera km1, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Alc\u00e1zar-Fabra","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Oncological Research (GENYO), Avenida de la Ilustraci\u00f3n 114, 18016 Granada, Spain"},{"name":"Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmine","family":"Staiano","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, and CIBERER, Instituto de Salud Carlos III, Universidad Pablo de Olavide-CSIC-JA, Carretera de Utrera km1, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9830-8502","authenticated-orcid":false,"given":"Guillermo","family":"L\u00f3pez-Lluch","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, and CIBERER, Instituto de Salud Carlos III, Universidad Pablo de Olavide-CSIC-JA, Carretera de Utrera km1, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5536-6868","authenticated-orcid":false,"given":"Gloria","family":"Brea-Calvo","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, and CIBERER, Instituto de Salud Carlos III, Universidad Pablo de Olavide-CSIC-JA, Carretera de Utrera km1, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4115-7966","authenticated-orcid":false,"given":"Pl\u00e1cido","family":"Navas","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, and CIBERER, Instituto de Salud Carlos III, Universidad Pablo de Olavide-CSIC-JA, Carretera de Utrera km1, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev-genom-091416-035426","article-title":"Recent advances in mitochondrial disease","volume":"18","author":"Craven","year":"2017","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nrneurol.2013.126","article-title":"The clinical maze of mitochondrial neurology","volume":"9","author":"DiMauro","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16080","DOI":"10.1038\/nrdp.2016.80","article-title":"Mitochondrial diseases","volume":"2","author":"Gorman","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3389\/fendo.2017.00296","article-title":"Functional mitochondria in health and disease","volume":"8","author":"Herst","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ajhg.2014.12.023","article-title":"COQ4 mutations cause a broad spectrum of mitochondrial disorders associated with CoQ10 Deficiency","volume":"96","author":"Calvo","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.bbabio.2016.03.010","article-title":"Coenzyme Q biosynthesis and its role in the respiratory chain structure","volume":"1857","author":"Navas","year":"2016","journal-title":"Biochim. Biophys. Acta BBA -Bioenergy"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Banerjee, R., Purhonen, J., and Kallij\u00e4rvi, J. (2021). The mitochondrial coenzyme Q junction and complex III: Biochemistry and pathophysiology. FEBS J.","DOI":"10.1111\/febs.16164"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.celrep.2016.03.009","article-title":"The CoQH2\/CoQ ratio serves as a sensor of respiratory chain efficiency","volume":"15","author":"Calvo","year":"2016","journal-title":"Cell Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1126\/science.1230381","article-title":"Supercomplex assembly determines electron flux in the mitochondrial electron transport chain","volume":"340","author":"Balsa","year":"2013","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1073\/pnas.1811938116","article-title":"PARL deficiency in mouse causes complex III defects, coenzyme Q depletion, and Leigh-like syndrome","volume":"116","author":"Spinazzi","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1042\/EBC20170107","article-title":"Clinical syndromes associated with coenzyme Q10 deficiency","volume":"62","author":"Trevisson","year":"2018","journal-title":"Essays Biochem."},{"key":"ref_12","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Mirzaa, G., and Amemiya, A. (2017). Primary coenzyme Q10 deficiency. GeneReviews\u00ae, University of Washington."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"17744","DOI":"10.1038\/s41598-017-17564-y","article-title":"Estimating the occurrence of primary ubiquinone deficiency by analysis of large-scale sequencing data","volume":"7","author":"Hughes","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1373\/clinchem.2004.043653","article-title":"Biological variation of coenzyme Q10","volume":"51","author":"Molyneux","year":"2005","journal-title":"Clin. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1373\/clinchem.2005.054643","article-title":"Determination of coenzyme Q10 status in blood Mononuclear cells, skeletal muscle, and plasma by HPLC with Di-propoxy-coenzyme Q10 as an internal standard","volume":"51","author":"Duncan","year":"2005","journal-title":"Clin. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"659","DOI":"10.2165\/00002018-200528080-00002","article-title":"The effect of HMG-CoA reductase inhibitors on coenzyme Q10: Possible biochemical\/clinical implications","volume":"28","author":"Hargreaves","year":"2005","journal-title":"Drug Saf."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s10522-013-9491-y","article-title":"Physical activity affects plasma coenzyme Q10 levels differently in young and old humans","volume":"15","author":"Tung","year":"2014","journal-title":"Biogerontology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/gerona\/glu002","article-title":"Age-dependent effect of every-other-day feeding and aerobic exercise in ubiquinone levels and related antioxidant activities in mice muscle","volume":"70","author":"Navas","year":"2015","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Paredes-Fuentes, A.J., Montero, R., Codina, A., Jou, C., Fern\u00e1ndez, G., Maynou, J., Santos-Oca\u00f1a, C., Riera, J., Navas, P., and Drobnic, F. (2020). Coenzyme Q10 treatment monitoring in different human biological samples. Antioxidants, 9.","DOI":"10.3390\/antiox9100979"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/ana.410420221","article-title":"Coenzyme Q10 levels correlate with the activities of complexes I and II\/III in mitochondria from parkinsonian and nonparkinsonian subjects","volume":"42","author":"Shults","year":"1997","journal-title":"Ann. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.ajhg.2007.12.024","article-title":"ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency","volume":"82","author":"Tazir","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Aguilera, J.C., Cort\u00e9s, A.B., Fern\u00e1ndez-Ayala, D.J.M., and Navas, P. (2017). Biochemical assessment of coenzyme Q10 deficiency. J. Clin. Med., 6.","DOI":"10.3390\/jcm6030027"},{"key":"ref_23","first-page":"22","article-title":"Redefining infantile-onset multisystem phenotypes of coenzyme Q10-deficiency in the next-generation sequencing era","volume":"4","author":"Berardo","year":"2020","journal-title":"J. Transl. Genet. Genom."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1097\/WCO.0000000000000126","article-title":"Mitochondrial myopathies in adults and children","volume":"27","author":"Pitceathly","year":"2014","journal-title":"Curr. Opin. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nrm.2017.66","article-title":"Mitochondrial diseases: The contribution of organelle stress responses to pathology","volume":"19","author":"Battersby","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nature11707","article-title":"Mitochondrial disorders as windows into an ancient organelle","volume":"491","author":"Vafai","year":"2012","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s10545-018-0146-7","article-title":"The functional genomics laboratory: Functional validation of genetic variants","volume":"41","author":"Rodenburg","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1042\/EBC20170106","article-title":"Coenzyme Q10 deficiencies: Pathways in yeast and humans","volume":"62","author":"Awad","year":"2018","journal-title":"Essays Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.freeradbiomed.2021.02.046","article-title":"Primary coenzyme Q deficiencies: A literature review and online platform of clinical features to uncover genotype-phenotype correlations","volume":"167","author":"Trevisson","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/nbt.3683","article-title":"Mitochondrial protein functions elucidated by multi-omic mass spectrometry profiling","volume":"34","author":"Stefely","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.tibs.2017.06.008","article-title":"Biochemistry of Mitochondrial Coenzyme Q Biosynthesis","volume":"42","author":"Stefely","year":"2017","journal-title":"Trends Biochem. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.freeradbiomed.2021.01.055","article-title":"Regulation of coenzyme Q biosynthesis pathway in eukaryotes","volume":"165","author":"Villalba","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/3904905","article-title":"Vanillic acid restores coenzyme q biosynthesis and ATP production in human cells lackingcoq6","volume":"2019","author":"Lopez","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/09168451.2015.1065172","article-title":"Biosynthesis of coenzyme Q in eukaryotes","volume":"80","author":"Kawamukai","year":"2016","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13157","DOI":"10.1016\/S0021-9258(19)38280-8","article-title":"Elucidation of the deficiency in two yeast coenzyme Q mutants. Characterization of the structural gene encoding hexaprenyl pyrophosphate synthetase","volume":"265","author":"Ashby","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1042\/BJ20040261","article-title":"Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ","volume":"382","author":"Forsgren","year":"2004","journal-title":"Biochem. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12381","DOI":"10.1074\/jbc.275.17.12381","article-title":"Isolation and functional expression of human COQ3, a gene encoding a methyltransferase required for ubiquinone biosynthesis","volume":"275","author":"Jonassen","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ymgme.2017.05.012","article-title":"Detection of 6-demethoxyubiquinone in CoQ 10 deficiency disorders: Insights into enzyme interactions and identification of potential therapeutics","volume":"121","author":"Herebian","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_39","first-page":"1628","article-title":"Molecular characterization of the human COQ5 C-methyltransferase in coenzyme Q10 biosynthesis","volume":"1841","author":"Nguyen","year":"2014","journal-title":"Biochim. Biophys. Acta BBA -Mol. Cell Biol. Lipids"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/j.chembiol.2011.07.008","article-title":"Coenzyme Q biosynthesis: Coq6 is required for the C5-hydroxylation reaction and substrate analogs rescue Coq6 deficiency","volume":"18","author":"Ozeir","year":"2011","journal-title":"Chem. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"16401","DOI":"10.1074\/jbc.M513267200","article-title":"Complementation of saccharomyces cerevisiae coq7 mutants by mitochondrial targeting of the escherichia coli UbiF polypeptide: Two functions of yeast Coq7 polypeptide in coenzyme Q biosynthesis","volume":"281","author":"Tran","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.molcel.2014.11.002","article-title":"Mitochondrial ADCK3 Employs an Atypical Protein Kinase-like Fold to Enable Coenzyme Q Biosynthesis","volume":"57","author":"Stefely","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1681\/ASN.2019070756","article-title":"ADCK4 Deficiency destabilizes the coenzyme Q complex, which is rescued by 2,4-dihydroxybenzoic acid treatment","volume":"31","author":"Widmeier","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.molcel.2018.11.033","article-title":"An isoprene lipid-binding protein promotes eukaryotic coenzyme Q biosynthesis","volume":"73","author":"Lohman","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"V\u00e1zquez-Fonseca, L., Sch\u00e4efer, J., Navas-Enamorado, I., Santos-Oca\u00f1a, C., Hern\u00e1ndez-Camacho, J.D., Guerra, I., Cascajo, M.V., S\u00e1nchez-Cuesta, A., Horvath, Z., and Siendones, E. (2019). ADCK2 Haploinsufficiency Reduces Mitochondrial Lipid Oxidation and Causes Myopathy Associated with CoQ Deficiency. J. Clin. Med., 8.","DOI":"10.20944\/preprints201908.0069.v1"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s12311-019-01011-x","article-title":"COQ4 Mutation leads to childhood-onset ataxia improved by CoQ10 administration","volume":"18","author":"Caglayan","year":"2019","journal-title":"Cerebellum"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5179","DOI":"10.1172\/JCI69000","article-title":"ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption","volume":"123","author":"Ashraf","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.chembiol.2017.11.001","article-title":"Conserved lipid and small-molecule modulation of COQ8 reveals regulation of the ancient kinase-like UbiB family","volume":"25","author":"Reidenbach","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1194\/jlr.M093534","article-title":"Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function","volume":"60","author":"Tsui","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/j.1442-200X.2012.03644.x","article-title":"Next-generation sequencing for mitochondrial diseases: A wide diagnostic spectrum","volume":"54","author":"Vasta","year":"2012","journal-title":"Pediatr. Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1172\/JCI29089","article-title":"Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders","volume":"117","author":"Mollet","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1086\/510023","article-title":"Leigh Syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) Mutations","volume":"79","author":"Schuelke","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1038\/ejhg.2014.277","article-title":"Primary coenzyme Q10 deficiency presenting as fatal neonatal multiorgan failure","volume":"23","author":"Desbats","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4256","DOI":"10.1093\/hmg\/ddw257","article-title":"TheCOQ2genotype predicts the severity of coenzyme Q10deficiency","volume":"25","author":"Desbats","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jns.2013.01.004","article-title":"A novel mutation in COQ2 leading to fatal infantile multisystem disease","volume":"326","author":"Jakobs","year":"2013","journal-title":"J. Neurol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ygeno.2013.04.013","article-title":"Diagnosis of mitochondrial disorders by concomitant next-generation sequencing of the exome and mitochondrial genome","volume":"102","author":"Dinwiddie","year":"2013","journal-title":"Genomics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ajhg.2007.12.022","article-title":"CABC1 Gene Mutations Cause Ubiquinone Deficiency with Cerebellar Ataxia and Seizures","volume":"82","author":"Mollet","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1681\/ASN.2006080833","article-title":"COQ2 nephropathy: A newly described inherited mitochondriopathy with primary renal involvement","volume":"18","author":"Santorelli","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.ejpn.2013.05.013","article-title":"Early myoclonic epilepsy, hypertrophic cardiomyopathy and subsequently a nephrotic syndrome in a patient with CoQ10 deficiency caused by mutations in para-hydroxybenzoate-polyprenyl transferase (COQ2)","volume":"17","author":"Scalais","year":"2013","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1086\/500092","article-title":"A mutation in Para-hydroxybenzoate-Polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency","volume":"78","author":"Quinzii","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1212\/01.wnl.0000172859.55579.a7","article-title":"Infantile encephalomyopathy and nephropathy with CoQ10 deficiency: A CoQ10-responsive condition","volume":"65","author":"Salviati","year":"2005","journal-title":"Neurology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"637","DOI":"10.2215\/CJN.07200712","article-title":"Simultaneous sequencing of 24 genes associated with steroid-resistant nephrotic syndrome","volume":"8","author":"McCarthy","year":"2013","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/cge.12960","article-title":"Further phenotypic heterogeneity of CoQ10 deficiency associated with steroid resistant nephrotic syndrome and novel COQ2 and COQ6 variants","volume":"92","author":"Gigante","year":"2017","journal-title":"Clin. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ijcard.2019.01.017","article-title":"Cardiomyopathy in children with mitochondrial disease: Prognosis and genetic background","volume":"279","author":"Kishita","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1136\/jmedgenet-2015-103140","article-title":"Mutations inCOQ4, an essential component of coenzyme Q biosynthesis, cause lethal neonatal mitochondrial encephalomyopathy","volume":"52","author":"Chung","year":"2015","journal-title":"J. Med. Genet."},{"key":"ref_66","first-page":"23","article-title":"Novel recessive mutations in COQ4 cause severe infantile cardiomyopathy and encephalopathy associated with CoQ 10 deficiency","volume":"12","author":"Sondheimer","year":"2017","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41525-019-0091-x","article-title":"Primary coenzyme Q10 deficiency-7: Expanded phenotypic spectrum and a founder mutation in southern Chinese","volume":"4","author":"Yu","year":"2019","journal-title":"NPJ Genom. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/s10038-019-0563-y","article-title":"Clinical phenotype, in silico and biomedical analyses, and intervention for an East Asian population-specific c.370G>A (p.G124S) COQ4 mutation in a Chinese family with CoQ10 deficiency-associated Leigh syndrome","volume":"64","author":"Lu","year":"2019","journal-title":"J. Hum. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1136\/jmedgenet-2011-100394","article-title":"Haploinsufficiency of COQ4causes coenzyme Q10deficiency","volume":"49","author":"Salviati","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.cca.2019.07.016","article-title":"Clinical whole-exome sequencing reveals a common pathogenic variant in patients with CoQ10 deficiency: An underdiagnosed cause of mitochondriopathy","volume":"497","author":"Ling","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"ref_71","first-page":"88","article-title":"New pathogenic variants in COQ4 cause ataxia and neurodevelopmental disorder without detectable CoQ10 deficiency in muscle or skin fibroblasts","volume":"497","author":"Mero","year":"2019","journal-title":"J. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/humu.23345","article-title":"A novel inborn error of the coenzyme Q10 biosynthesis pathway: Cerebellar ataxia and static encephalomyopathy due to COQ5 C-methyltransferase deficiency","volume":"39","author":"Malicdan","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbadis.2013.10.007","article-title":"Effect of vanillic acid on COQ6 mutants identified in patients with coenzyme Q10 deficiency","volume":"1842","author":"Doimo","year":"2014","journal-title":"Biochim. Biophys. Acta BBA -Mol. Basis Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1172\/JCI45693","article-title":"COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness","volume":"121","author":"Heeringa","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00467-018-4150-9","article-title":"CoenzymeQ10 therapy in two sisters with CoQ6 mutations with long-term follow-up","volume":"34","author":"Koyun","year":"2018","journal-title":"Pediatr. Nephrol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1053\/j.ajkd.2016.10.040","article-title":"COQ6 mutations in children with steroid-resistant focal segmental glomerulosclerosis and sensorineural hearing loss","volume":"70","author":"Park","year":"2017","journal-title":"Am. J. Kidney Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/jmd2.12032","article-title":"A fatal case of COQ7-associated primary coenzyme Q 10 deficiency","volume":"47","author":"Kwong","year":"2019","journal-title":"JIMD Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1136\/jmedgenet-2015-102986","article-title":"Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4\u2013dihydroxybensoic acid","volume":"52","author":"Freyer","year":"2015","journal-title":"J. Med Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1111\/jcmm.13154","article-title":"Pathogenicity of two COQ7 mutations and responses to 2,4-dihydroxybenzoate bypass treatment","volume":"21","author":"Wang","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.mito.2010.05.008","article-title":"Nonsense mutations in CABC1\/ADCK3 cause progressive cerebellar ataxia and atrophy","volume":"10","author":"Gerards","year":"2010","journal-title":"Mitochondrion"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1136\/jnnp-2011-301258","article-title":"Adult-onset cerebellar ataxia due to mutations inCABC1\/ADCK3","volume":"83","author":"Horvath","year":"2011","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/1750-1172-8-173","article-title":"Phenotypic variability in ARCA2 and identification of a core ataxic phenotype with slow progression","volume":"8","author":"Mignot","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10048-009-0196-y","article-title":"Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: Implications for clinical management","volume":"11","author":"Anheim","year":"2009","journal-title":"Neurogenetics"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/8904_2017_73","article-title":"Compound heterozygous inheritance of mutations in coenzyme Q8A results in autosomal recessive cerebellar ataxia and coenzyme q10 deficiency in a female Sib-Pair","volume":"42","author":"Jacobsen","year":"2017","journal-title":"JIMD Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1111\/ene.13003","article-title":"ADCK3 mutations with epilepsy, stroke-like episodes and ataxia: A POLG mimic?","volume":"23","author":"Hikmat","year":"2016","journal-title":"Eur. J. Neurol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1002\/mdc3.12667","article-title":"ADCK3-related Coenzyme Q10 Deficiency: A Potentially Treatable Genetic Disease","volume":"5","author":"Chang","year":"2018","journal-title":"Mov. Disord. Clin. Pract."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ejpn.2011.07.016","article-title":"The use of muscle biopsy in the diagnosis of undefined ataxia with cerebellar atrophy in children","volume":"16","author":"Terracciano","year":"2012","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1136\/jnnp-2013-306483","article-title":"Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: Clinical, genetic and biochemical characterisation","volume":"85","author":"Liu","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.parkreldis.2019.09.015","article-title":"Dystonia-Ataxia with early handwriting deterioration in COQ8A mutation carriers: A case series and literature review","volume":"68","author":"Galosi","year":"2019","journal-title":"Park. Relat. Disord."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/cge.12742","article-title":"Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3","volume":"90","author":"Barca","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1007\/s00467-017-3634-3","article-title":"Follow-up results of patients with ADCK4 mutations and the efficacy of CoQ10 treatment","volume":"32","author":"Atmaca","year":"2017","journal-title":"Pediatr. Nephrol."},{"key":"ref_92","first-page":"406","article-title":"Mutations in COQ8B (ADCK4) found in patients with steroid-resistant nephrotic syndrome alter COQ8B function","volume":"39","author":"Doimo","year":"2017","journal-title":"Hum. Mutat."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1681\/ASN.2014121240","article-title":"ADCK4-Associated Glomerulopathy Causes Adolescence-Onset FSGS","volume":"27","author":"Korkmaz","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s10545-017-0122-7","article-title":"A family segregating lethal neonatal coenzyme Q10 deficiency caused by mutations in COQ9","volume":"41","author":"Smith","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/ejhg.2015.133","article-title":"Fatal neonatal encephalopathy and lactic acidosis caused by a homozygous loss-of-function variant in COQ9","volume":"24","author":"Danhauser","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.ajhg.2009.03.018","article-title":"A Nonsense Mutation in COQ9 Causes Autosomal-Recessive Neonatal-Onset Primary Coenzyme Q10 Deficiency: A Potentially Treatable Form of Mitochondrial Disease","volume":"84","author":"Duncan","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1067\/mpd.2001.117575","article-title":"Neonatal presentation of coenzyme Q10 deficiency","volume":"139","author":"Rahman","year":"2001","journal-title":"J. Pediatr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1128\/mr.54.3.211-225.1990","article-title":"PET genes of Saccharomyces cerevisiae","volume":"54","author":"Tzagoloff","year":"1990","journal-title":"Microbiol. Rev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.1016\/j.mito.2007.03.007","article-title":"Endogenous synthesis of coenzyme Q in eukaryotes","volume":"7","author":"Tran","year":"2007","journal-title":"Mitochondrion"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5606","DOI":"10.1111\/j.1742-4658.2005.04956.x","article-title":"Characterization of solanesyl and decaprenyl diphosphate synthases in mice and humans","volume":"272","author":"Saiki","year":"2005","journal-title":"FEBS J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1101\/gr.8.10.1038","article-title":"Novel Families of Putative Protein Kinases in Bacteria and Archaea: Evolution of the \u201cEukaryotic\u201d Protein Kinase Superfamily","volume":"8","author":"Leonard","year":"1998","journal-title":"Genome Res."},{"key":"ref_102","first-page":"630","article-title":"Coenzyme Q supplementation or over-expression of the yeast Coq8 putative kinase stabilizes multi-subunit Coq polypeptide complexes in yeast coq null mutants","volume":"1841","author":"He","year":"2014","journal-title":"Biochim. Biophys. Acta BBA -Mol. Cell Biol. Lipids"},{"key":"ref_103","first-page":"348","article-title":"Expression of the human atypical kinase ADCK3 rescues coenzyme Q biosynthesis and phosphorylation of Coq polypeptides in yeast coq8 mutants","volume":"1811","author":"Xie","year":"2011","journal-title":"Biochim. Biophys. Acta BBA -Mol. Cell Biol. Lipids"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/hmg\/ddm058","article-title":"Missense mutation of the COQ2 gene causes defects of bioenergetics and de novo pyrimidine synthesis","volume":"16","author":"Salviati","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"9797","DOI":"10.1021\/bi9602932","article-title":"Complementation of coq3 Mutant Yeast by Mitochondrial Targeting of the Escherichia coli UbiG Polypeptide: Evidence That UbiG Catalyzes Both O-Methylation Steps in Ubiquinone Biosynthesis","volume":"35","author":"Hsu","year":"1996","journal-title":"Biochemistry"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1074\/jbc.271.6.2995","article-title":"The COQ7 gene encodes a protein in saccharomyces cerevisiae necessary for ubiquinone biosynthesis","volume":"271","author":"Marbois","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"35104","DOI":"10.1074\/jbc.M704891200","article-title":"Substitutions of potentially phosphorylatable serine residues of bax reveal how they may regulate its interaction with mitochondria","volume":"282","author":"Arokium","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"25995","DOI":"10.1074\/jbc.M400001200","article-title":"Demethoxy-Q, An Intermediate of coenzyme Q biosynthesis, fails to support respiration in saccharomyces cerevisiae and lacks antioxidant activity","volume":"279","author":"Padilla","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"12341","DOI":"10.1016\/S0021-9258(19)49845-1","article-title":"Functional expression of plant plasma membrane H (+)-ATPase in yeast endoplasmic reticulum","volume":"267","author":"Villalba","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"17443","DOI":"10.1074\/jbc.M311853200","article-title":"Mechanism of genetic complementation of ammonium transport in yeast by human erythrocyte Rh-associated glycoprotein","volume":"279","author":"Westhoff","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1080\/14737159.2018.1478290","article-title":"Molecular diagnosis of coenzyme Q10 deficiency: An update","volume":"18","author":"Yubero","year":"2018","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.molcel.2016.06.030","article-title":"Cerebellar ataxia and coenzyme q deficiency through loss of unorthodox kinase activity","volume":"63","author":"Stefely","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1111\/febs.15561","article-title":"Coenzyme Q biosynthesis inhibition induces HIF-1\u03b1 stabilization and metabolic switch toward glycolysis","volume":"288","author":"Liparulo","year":"2021","journal-title":"FEBS J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/nature24049","article-title":"RNA targeting with CRISPR\u2013Cas13","volume":"550","author":"Abudayyeh","year":"2017","journal-title":"Nature"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1002\/jimd.12319","article-title":"The pursuit of precision mitochondrial medicine: Harnessing preclinical cellular and animal models to optimize mitochondrial disease therapeutic discovery","volume":"44","author":"Falk","year":"2021","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1681\/ASN.2016050517","article-title":"Modeling Monogenic Human Nephrotic Syndrome in the Drosophila Garland Cell Nephrocyte","volume":"28","author":"Hermle","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_117","first-page":"1","article-title":"Chemical modifications of adenine base editor mRNA and guide RNA expand its application scope","volume":"11","author":"Jiang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s12015-019-09935-x","article-title":"Advances in pluripotent stem cells: History, mechanisms, technologies, and applications","volume":"16","author":"Liu","year":"2020","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"McKnight, C., Low, Y., Elliott, D., Thorburn, D., and Frazier, A. (2021). Modelling mitochondrial disease in human pluripotent stem cells: What have we learned?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147730"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.bbagen.2016.01.009","article-title":"Mitochondrial resetting and metabolic reprogramming in induced pluripotent stem cells and mitochondrial disease modeling","volume":"1860","author":"Hsu","year":"2016","journal-title":"Biochim. Biophys. Acta BBA -Gen. Subj."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1002\/stem.2292","article-title":"Concise Review: Heteroplasmic Mitochondrial DNA Mutations and Mitochondrial Diseases: Toward iPSC-Based Disease Modeling, Drug Discovery, and Regenerative Therapeutics","volume":"34","author":"Hatakeyama","year":"2016","journal-title":"Stem Cells"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1631\/jzus.B1900196","article-title":"Cell models and drug discovery for mitochondrial diseases","volume":"20","author":"Hu","year":"2019","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Hargreaves, I., Heaton, R.A., and Mantle, D. (2020). Disorders of Human Coenzyme Q10 Metabolism: An Overview. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186695"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Galera-Monge, T., Zurita-D\u00edaz, F., Canals, I., Hansen, M.G., Rufi\u00e1n-V\u00e1zquez, L., Ehinger, J.K., Elm\u00e9r, E., Martin, M.A., Garesse, R., and Ahlenius, H. (2020). Mitochondrial Dysfunction and Calcium Dysregulation in Leigh Syndrome Induced Pluripotent Stem Cell Derived Neurons. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093191"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.cell.2018.09.010","article-title":"Stem Cells, Genome Editing, and the Path to Translational Medicine","volume":"175","author":"Soldner","year":"2018","journal-title":"Cell"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"165431","DOI":"10.1016\/j.bbadis.2019.03.004","article-title":"Using induced pluripotent stem cell neuronal models to study neurodegenerative diseases","volume":"1866","author":"Zhang","year":"2020","journal-title":"Biochim. Biophys. Acta BBA -Mol. Basis Dis."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.scr.2016.09.007","article-title":"Generation, genome edition and characterization of iPSC lines from a patient with coenzyme Q 10 deficiency harboring a heterozygous mutation in COQ4 gene","volume":"24","author":"Navas","year":"2017","journal-title":"Stem Cell Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1002\/stem.2634","article-title":"Genetic Rescue of Mitochondrial and Skeletal Muscle Impairment in an Induced Pluripotent Stem Cells Model of Coenzyme Q10 Deficiency","volume":"35","author":"Garrabou","year":"2017","journal-title":"Stem Cells"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3389\/fphys.2018.00044","article-title":"Coenzyme Q10 supplementation in aging and disease","volume":"9","author":"Bernier","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Chang, C.-Y., Ting, H.-C., Liu, C.-A., Su, H.-L., Chiou, T.-W., Lin, S.-Z., Harn, H.-J., and Ho, T.-J. (2020). Induced pluripotent stem cell (iPSC)-based neurodegenerative disease models for phenotype recapitulation and drug screening. Molecules, 25.","DOI":"10.3390\/molecules25082000"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"14215","DOI":"10.1038\/s41598-018-32573-1","article-title":"The pathogenesis linked to coenzyme Q10 insufficiency in iPSC-derived neurons from patients with multiple-system atrophy","volume":"8","author":"Nakamoto","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Bonaventura, G., Iemmolo, R., Attaguile, G., La Cognata, V., Pistone, B., Raudino, G., D\u2019Agata, V., Cantarella, G., Barcellona, M., and Cavallaro, S. (2021). iPSCs: A preclinical drug research tool for neurological disorders. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094596"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1126\/science.aaf1502","article-title":"Conversion of human fibroblasts into functional cardiomyocytes by small molecules","volume":"352","author":"Cao","year":"2016","journal-title":"Science"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13036-019-0144-9","article-title":"Direct cell reprogramming for tissue engineering and regenerative medicine","volume":"13","author":"Grath","year":"2019","journal-title":"J. Biol. Eng."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.pneurobio.2013.11.001","article-title":"Induced neural stem cells: Methods of reprogramming and potential therapeutic applications","volume":"114","author":"Ruggieri","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41418-020-00680-0","article-title":"Engineering organoids: A promising platform to understand biology and treat diseases","volume":"28","author":"Aqeilan","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"4523","DOI":"10.1038\/s41598-021-84071-6","article-title":"Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells","volume":"11","author":"Duong","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/dneu.22818","article-title":"Tools and approaches for analyzing the role of mitochondria in health, development and disease using human cerebral organoids","volume":"81","author":"Liput","year":"2021","journal-title":"Dev. Neurobiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10211\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:03:27Z","timestamp":1760166207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,22]]},"references-count":138,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms221910211"],"URL":"https:\/\/doi.org\/10.3390\/ijms221910211","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,9,22]]}}}