{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:10:13Z","timestamp":1790975413825,"version":"4.1.0"},"reference-count":138,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitochondria, the energy factories of human organisms, can be the cause of a variety of genetic disorders called mitochondrial myopathies. Mitochondrial diseases arise from genetic alterations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) and can manifest with great heterogeneity, leading to multiorgan dysfunction. The purpose of this article is to concisely review the pathophysiology, genetics and main clinical features of mitochondrial myopathies, focusing mainly on the treatment and management of these disorders. Currently, a particular treatment for mitochondrial myopathies does not exist, while the available guidelines concerning management are based on experts\u2019 opinions. The therapeutic options currently applied largely aim at symptom relief and amelioration of patients\u2019 quality of life. The most commonly used regimens involve the administration of vitamins and cofactors, although hard evidence regarding their true benefit for patients is still lacking. Recent studies have demonstrated promising results for elamipretide; however, phase III clinical trials are still ongoing. Regarding patient management, a multidisciplinary approach with the collaboration of different specialties is required. Further clinical trials for the already applied treatment options, as well as on novel experimental therapies, are of utmost importance in order to improve patients\u2019 outcomes.<\/jats:p>","DOI":"10.3390\/ijms26115411","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T05:49:22Z","timestamp":1749102562000},"page":"5411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Advances in Management of Mitochondrial Myopathies"],"prefix":"10.3390","volume":"26","author":[{"given":"Athanasios","family":"Bangeas","sequence":"first","affiliation":[{"name":"Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41100 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0147-3948","authenticated-orcid":false,"given":"Vasiliki","family":"Poulidou","sequence":"additional","affiliation":[{"name":"First Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Stilponos Kyriakidi 1, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2958-5220","authenticated-orcid":false,"given":"Ioannis","family":"Liampas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41100 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5979-9916","authenticated-orcid":false,"given":"Chrysa","family":"Marogianni","sequence":"additional","affiliation":[{"name":"Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41100 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9354-774X","authenticated-orcid":false,"given":"Athina-Maria","family":"Aloizou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41100 Larissa, Greece"},{"name":"Neurology Department, St. Josef Hospital Bochum, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zisis","family":"Tsouris","sequence":"additional","affiliation":[{"name":"Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41100 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6337-4534","authenticated-orcid":false,"given":"Markos","family":"Sgantzos","sequence":"additional","affiliation":[{"name":"Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41100 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianthi","family":"Arnaoutoglou","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology, School of Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, Stilponos Kyriakidi 1, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9697-7902","authenticated-orcid":false,"given":"Dimitrios P.","family":"Bogdanos","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University General Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41100 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2957-641X","authenticated-orcid":false,"given":"Efthimios","family":"Dardiotis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41100 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios","family":"Siokas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41100 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/bmb\/ldt017","article-title":"Mitochondrial genetics","volume":"106","author":"Chinnery","year":"2013","journal-title":"Br. Med. Bull."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Parakatselaki, M.E., and Ladoukakis, E.D. (2021). mtDNA Heteroplasmy: Origin, Detection, Significance, and Evolutionary Consequences. Life, 11.","DOI":"10.3390\/life11070633"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1042\/bj20021594","article-title":"Mitochondrial threshold effects","volume":"370","author":"Rossignol","year":"2003","journal-title":"Biochem. J."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Li, Z., Zhu, M., Du, J., Ma, H., Jin, G., and Dai, J. (2018). Genetic variants in nuclear DNA along with environmental factors modify mitochondrial DNA copy number: A population-based exome-wide association study. BMC Genom., 19.","DOI":"10.1186\/s12864-018-5142-7"},{"key":"ref_5","unstructured":"National Institute of Neurological Disorders and Stroke (NINDS) (2022, June 16). NINDS Mitochondrial Myopathy Information Page, Available online: http:\/\/www.ninds.nih.gov\/."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"32724","DOI":"10.1074\/jbc.M607135200","article-title":"Bovine complex I is a complex of 45 different subunits","volume":"281","author":"Carroll","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_7","first-page":"285","article-title":"Complex II deficiency--a case report and review of the literature","volume":"161a","author":"Cameron","year":"2013","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1146\/annurev.physiol.66.032102.150251","article-title":"The cytochrome bc1 complex: Function in the context of structure","volume":"66","author":"Crofts","year":"2004","journal-title":"Annu. Rev. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.bbamcr.2008.05.028","article-title":"Assembly of the oxidative phosphorylation system in humans: What we have learned by studying its defects","volume":"1793","author":"Tiranti","year":"2009","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_10","first-page":"S57","article-title":"Nuclear genetic defects of mitochondrial ATP synthase","volume":"63","author":"Pecina","year":"2014","journal-title":"Physiol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wallace, D.C., and Chalkia, D. (2013). Mitochondrial DNA genetics and the heteroplasmy conundrum in evolution and disease. Cold Spring Harb. Perspect. Biol., 5.","DOI":"10.1101\/cshperspect.a021220"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1038\/s41588-018-0264-z","article-title":"Mitochondrial genetic medicine","volume":"50","author":"Wallace","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_13","first-page":"227","article-title":"Neuromuscular and systemic presentations in adults: Diagnoses beyond MERRF and MELAS","volume":"10","author":"Cohen","year":"2013","journal-title":"J. Am. Soc. Exp. Neurother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"D1251","DOI":"10.1093\/nar\/gkv1003","article-title":"MitoCarta2.0: An updated inventory of mammalian mitochondrial proteins","volume":"44","author":"Calvo","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s40142-018-0137-x","article-title":"Mitochondrial Genomics: A complex field now coming of age","volume":"6","author":"McCormick","year":"2018","journal-title":"Curr. Genet. Med. Rep."},{"key":"ref_16","unstructured":"Muscular Dystrophy Association (MDA) (2025, May 29). Research. Available online: https:\/\/www.mda.org\/disease\/mitochondrial-myopathies\/research."},{"key":"ref_17","first-page":"943","article-title":"Diagnosis and Treatment of Mitochondrial Myopathies","volume":"15","author":"Ahmed","year":"2018","journal-title":"J. Am. Soc. Exp. Neurother."},{"key":"ref_18","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_19","unstructured":"Muscular Dystrophy Association (MDA) (2025, May 29). Causes\/Inheritance. Available online: https:\/\/www.mda.org\/disease\/mitochondrial-myopathies\/causes-inheritance."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.3390\/cimb44030074","article-title":"Use of Next-Generation Sequencing for Identifying Mitochondrial Disorders","volume":"44","author":"Mahmud","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.bbabio.2004.09.005","article-title":"The epidemiology of mitochondrial disorders--past, present and future","volume":"1659","author":"Schaefer","year":"2004","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.ajhg.2008.07.004","article-title":"Pathogenic mitochondrial DNA mutations are common in the general population","volume":"83","author":"Elliott","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_23","unstructured":"Powledge, T. (2022, June 16). Three Parent Baby Debate: FDA Ponders Mitochondrial Manipulation and, Perhaps, Germline Modification Too. Available online: https:\/\/geneticliteracyproject.org\/."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1111\/j.1755-3768.2012.02506.x","article-title":"Prevalence of the primary LHON mutations in Northern Finland associated with bilateral optic atrophy and tobacco-alcohol amblyopia","volume":"91","author":"Kervinen","year":"2013","journal-title":"Acta Ophthalmol."},{"key":"ref_25","first-page":"1732","article-title":"Mitochondrial and Metabolic Myopathies","volume":"25","author":"Cohen","year":"2019","journal-title":"Continuum"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1097\/WCO.0000000000000126","article-title":"Mitochondrial myopathies in adults and children: Management and therapy development","volume":"27","author":"Pitceathly","year":"2014","journal-title":"Curr. Opin. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nrendo.2016.76","article-title":"The potential of endurance exercise-derived exosomes to treat metabolic diseases","volume":"12","author":"Safdar","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_28","unstructured":"Muscular Dystrophy Association (MDA) (2025, May 29). Signs and Symptoms. Available online: https:\/\/www.mda.org\/disease\/mitochondrial-myopathies\/signs-and-symptoms."},{"key":"ref_29","first-page":"934","article-title":"The mitochondrial tRNA(Leu(UUR)) mutation in mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS): Genetic, biochemical, and morphological correlations in skeletal muscle","volume":"50","author":"Moraes","year":"1992","journal-title":"Am. J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4612","DOI":"10.1093\/hmg\/ddu176","article-title":"Dissecting the mechanisms underlying the accumulation of mitochondrial DNA deletions in human skeletal muscle","volume":"23","author":"Campbell","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1055\/s-0032-1306387","article-title":"Mitochondrial syndromes with leukoencephalopathies","volume":"32","author":"Wong","year":"2012","journal-title":"Semin. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/0002-8703(90)90097-H","article-title":"Kearns-Sayre syndrome in the elderly: Mitochondrial myopathy with advanced heart block","volume":"120","author":"Kenny","year":"1990","journal-title":"Am. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1399-0004.1996.tb02732.x","article-title":"High incidence of pre-excitation syndrome in Japanese families with Leber\u2019s hereditary optic neuropathy","volume":"50","author":"Mashima","year":"1996","journal-title":"Clin. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ymeth.2010.05.008","article-title":"The clinical diagnosis of POLG disease and other mitochondrial DNA depletion disorders","volume":"51","author":"Cohen","year":"2010","journal-title":"Methods"},{"key":"ref_35","unstructured":"Saneto, R.P., Parikh, S., and Cohen, B.H. (2016). Chapter 20-MPV17-Related Hepatocerebral Mitochondrial DNA (mtDNA) Depletion Syndrome. Mitochondrial Case Studies, Academic Press."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/j.1478-3231.1999.tb00063.x","article-title":"Mitochondrial respiratory chain disorders and the liver","volume":"19","author":"Morris","year":"1999","journal-title":"Liver"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s00467-011-1926-6","article-title":"Renal involvement in mitochondrial cytopathies","volume":"27","author":"Emma","year":"2012","journal-title":"Pediatr. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bindoff, L. (2006). Mitochondrial gastroenterology. Mitochondrial Medicine, Informa Healthcare.","DOI":"10.1201\/b14623-8"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/pedi.12223","article-title":"The spectrum of clinical presentation, diagnosis, and management of mitochondrial forms of diabetes","volume":"16","author":"Karaa","year":"2015","journal-title":"Pediatr. Diabetes"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.mito.2014.07.008","article-title":"Glucose metabolism derangements in adults with the MELAS m.3243A>G mutation","volume":"18","author":"Emrick","year":"2014","journal-title":"Mitochondrion"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mazzaccara, C., Iafusco, D., Liguori, R., Ferrigno, M., Galderisi, A., Vitale, D., Simonelli, F., Landolfo, P., Prisco, F., and Masullo, M. (2012). Mitochondrial diabetes in children: Seek and you will find it. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034956"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.pediatrneurol.2007.12.001","article-title":"Presentation and Diagnosis of Mitochondrial Disorders in Children","volume":"38","author":"Koenig","year":"2008","journal-title":"Pediatr. Neurol."},{"key":"ref_43","unstructured":"Adam, M.P., Mirzaa, G.M., and Pagon, R.A. (2022, June 16). Mitochondrial DNA Deletion Syndromes, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1203\/."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1056\/NEJM199509073331007","article-title":"Seminars in medicine of the Beth Israel Hospital, Boston. Mitochondrial DNA and disease","volume":"333","author":"Johns","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_45","unstructured":"Rosenberg, R.N., and Pascual, J.M. (2020). Chapter 27- Mitochondrial disorders due to mutations in the mitochondrial genome. Rosenberg\u2019s Molecular and Genetic Basis of Neurological and Psychiatric Disease, Academic Press. [6th ed.]."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/j.bbagen.2013.10.040","article-title":"The broadening spectrum of mitochondrial disease: Shifts in the diagnostic paradigm","volume":"1840","author":"Liang","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.2353\/ajpath.2008.080252","article-title":"Gastrointestinal dysmotility in mitochondrial neurogastrointestinal encephalomyopathy is caused by mitochondrial DNA depletion","volume":"173","author":"Giordano","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1002\/jimd.12300","article-title":"Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network","volume":"44","author":"Hirano","year":"2021","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/nrg1606","article-title":"Mitochondrial DNA mutations in human disease","volume":"6","author":"Taylor","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100113","DOI":"10.1016\/j.cellin.2023.100113","article-title":"Mitochondrial DNA-targeted therapy: A novel approach to combat cancer","volume":"2","author":"Lin","year":"2023","journal-title":"Cell Insight"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.mito.2010.01.003","article-title":"Extensive screening system using suspension array technology to detect mitochondrial DNA point mutations","volume":"10","author":"Nishigaki","year":"2010","journal-title":"Mitochondrion"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s10545-017-0027-5","article-title":"MtDNA-maintenance defects: Syndromes and genes","volume":"40","author":"Viscomi","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.mito.2019.09.002","article-title":"Genotypes of chronic progressive external ophthalmoplegia in a large adult-onset cohort","volume":"49","author":"Heighton","year":"2019","journal-title":"Mitochondrion"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3109\/07853890.2011.605389","article-title":"Diagnosis and treatment of mitochondrial myopathies","volume":"45","author":"Pfeffer","year":"2013","journal-title":"Ann. Med."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Peristeri, E., Aloizou, A.-M., Keramida, P., Tsouris, Z., Siokas, V., Mentis, A.F.A., and Dardiotis, E. (2020). Cognitive Deficits in Myopathies. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113795"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0960-8966(92)90045-8","article-title":"Melas: An original case and clinical criteria for diagnosis","volume":"2","author":"Hirano","year":"1992","journal-title":"Neuromuscul. Disord."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.bbagen.2011.03.015","article-title":"MELAS: A nationwide prospective cohort study of 96 patients in Japan","volume":"1820","author":"Yatsuga","year":"2012","journal-title":"Biochim. Et Biophys. Acta Gen. Subj."},{"key":"ref_58","unstructured":"Adam, M.P., Mirzaa, G.M., and Pagon, R.A. (2022, June 16). MELAS, GeneReviews\u00ae [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/sites\/books\/NBK1233\/."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"602","DOI":"10.3174\/ajnr.A7837","article-title":"MELAS: Phenotype Classification into Classic-versus-Atypical Presentations","volume":"44","author":"Alves","year":"2023","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"bcr2016216500","DOI":"10.1136\/bcr-2016-216500","article-title":"Classical triad of Kearns-Sayre syndrome","volume":"2016","author":"Sharma","year":"2016","journal-title":"BMJ Case Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1001\/archneur.62.5.730","article-title":"Severe impairment of complex I-driven adenosine triphosphate synthesis in leber hereditary optic neuropathy cybrids","volume":"62","author":"Baracca","year":"2005","journal-title":"Arch. Neurol."},{"key":"ref_62","first-page":"381","article-title":"Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage","volume":"60","author":"Brown","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref_63","unstructured":"Adam, M.P., Ardinger, H.H., and Pagon, R.A. (2022, June 16). MERRF, GeneReviews1 [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1520\/."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1212\/WNL.0b013e318294b44c","article-title":"Phenotypic heterogeneity of the 8344A>G mtDNA \u201cMERRF\u201d mutation","volume":"80","author":"Mancuso","year":"2013","journal-title":"Neurology"},{"key":"ref_65","unstructured":"Adam, M.P., Ardinger, H.H., and Pagon, R.A. (2022, June 16). TK2-related mitochondrial DNA maintenance defect, myopathic form, GeneReviews1 [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK114628\/."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1136\/jmedgenet-2017-105012","article-title":"Retrospective natural history of thymidine kinase 2 deficiency","volume":"55","author":"Garone","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1159\/000362826","article-title":"Genetics of coenzyme q10 deficiency","volume":"5","author":"Doimo","year":"2014","journal-title":"Mol. Syndromol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Mantle, D., Millichap, L., Castro-Marrero, J., and Hargreaves, I.P. (2023). Primary Coenzyme Q10 Deficiency: An Update. Antioxidants, 12.","DOI":"10.3390\/antiox12081652"},{"key":"ref_69","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (1993). Primary Coenzyme Q(10) Deficiency Overview. GeneReviews(\u00ae), University of Washington. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.: Seattle (WA)."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.cmet.2019.08.019","article-title":"Fibroblast Growth Factor 21 Drives Dynamics of Local and Systemic Stress Responses in Mitochondrial Myopathy with mtDNA Deletions","volume":"30","author":"Jackson","year":"2019","journal-title":"Cell Metab."},{"key":"ref_71","first-page":"Cd004426","article-title":"Treatment for mitochondrial disorders","volume":"2012","author":"Pfeffer","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1007\/s11940-009-0046-0","article-title":"A modern approach to the treatment of mitochondrial disease","volume":"11","author":"Parikh","year":"2009","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.cmet.2012.04.022","article-title":"The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity","volume":"15","author":"Houtkooper","year":"2012","journal-title":"Cell Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1080\/02713683.2020.1736307","article-title":"Therapeutic Effects of Idebenone on Leber Hereditary Optic Neuropathy","volume":"45","author":"Zhao","year":"2020","journal-title":"Curr. Eye Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"101437","DOI":"10.1016\/j.xcrm.2024.101437","article-title":"Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial","volume":"5","author":"Carelli","year":"2024","journal-title":"Cell Rep. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/WNO.0b013e318272c643","article-title":"Effects of idebenone on color vision in patients with leber hereditary optic neuropathy","volume":"33","author":"Rudolph","year":"2013","journal-title":"J. Neuro Ophthalmol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.2337\/db14-0667","article-title":"Evidence for a direct effect of the NAD+ precursor acipimox on muscle mitochondrial function in humans","volume":"64","author":"Phielix","year":"2015","journal-title":"Diabetes"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e11589","DOI":"10.15252\/emmm.201911589","article-title":"Metabolic effects of bezafibrate in mitochondrial disease","volume":"12","author":"Steele","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e687","DOI":"10.1212\/WNL.0000000000008861","article-title":"Safety and efficacy of omaveloxolone in patients with mitochondrial myopathy: MOTOR trial","volume":"94","author":"Madsen","year":"2020","journal-title":"Neurology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1136\/jnnp-2018-317964","article-title":"Taurine supplementation for prevention of stroke-like episodes in MELAS: A multicentre, open-label, 52-week phase III trial","volume":"90","author":"Ohsawa","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.ymgme.2012.09.007","article-title":"EPI-743 reverses the progression of the pediatric mitochondrial disease--genetically defined Leigh Syndrome","volume":"107","author":"Martinelli","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1001\/archneurol.2011.2972","article-title":"Effect of EPI-743 on the clinical course of the mitochondrial disease Leber hereditary optic neuropathy","volume":"69","author":"Sadun","year":"2012","journal-title":"Arch. Neurol."},{"key":"ref_83","first-page":"307","article-title":"Review of clinical trials for mitochondrial disorders: 1997\u20132012","volume":"10","author":"Kerr","year":"2013","journal-title":"J. Am. Soc. Exp. Neurother."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/mus.20688","article-title":"Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders","volume":"35","author":"Rodriguez","year":"2007","journal-title":"Muscle Nerve"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0092-8674(04)00416-7","article-title":"Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans","volume":"117","author":"Bieganowski","year":"2004","journal-title":"Cell"},{"key":"ref_86","unstructured":"Muscular Dystrophy Association (MDA) (2025, May 29). Medical Management. Available online: https:\/\/www.mda.org\/disease\/mitochondrial-myopathies\/medical-management."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1002\/emmm.201403943","article-title":"Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3","volume":"6","author":"Khan","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1007\/s00415-018-9057-7","article-title":"Therapeutic regimen of L-arginine for MELAS: 9-year, prospective, multicenter, clinical research","volume":"265","author":"Koga","year":"2018","journal-title":"J. Neurol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e2318","DOI":"10.1212\/WNL.0000000000200299","article-title":"l-Arginine in Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes: A Systematic Review","volume":"98","author":"Stefanetti","year":"2022","journal-title":"Neurology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/ana.1050","article-title":"Aerobic conditioning in patients with mitochondrial myopathies: Physiological, biochemical, and genetic effects","volume":"50","author":"Taivassalo","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3402","DOI":"10.1093\/brain\/awl149","article-title":"Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy","volume":"129","author":"Jeppesen","year":"2006","journal-title":"Brain A J. Neurol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.1093\/brain\/awl282","article-title":"Endurance training and detraining in mitochondrial myopathies due to single large-scale mtDNA deletions","volume":"129","author":"Taivassalo","year":"2006","journal-title":"Brain A J. Neurol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1093\/brain\/awg028","article-title":"The spectrum of exercise tolerance in mitochondrial myopathies: A study of 40 patients","volume":"126","author":"Taivassalo","year":"2003","journal-title":"Brain A J. Neurol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/mus.20368","article-title":"Exercise training in mitochondrial myopathy: A randomized controlled trial","volume":"32","author":"Cejudo","year":"2005","journal-title":"Muscle Nerve"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1093\/brain\/awn252","article-title":"Resistance training in patients with single, large-scale deletions of mitochondrial DNA","volume":"131","author":"Murphy","year":"2008","journal-title":"Brain A J. Neurol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1016\/j.ijcard.2013.05.062","article-title":"Defining cardiac adaptations and safety of endurance training in patients with m.3243A>G-related mitochondrial disease","volume":"168","author":"Bates","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1093\/brain\/awn264","article-title":"Train, train, train! No pain, just gain","volume":"131","author":"Zeviani","year":"2008","journal-title":"Brain A J. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1093\/hmg\/ddq076","article-title":"Ketogenic diet slows down mitochondrial myopathy progression in mice","volume":"19","author":"Carroll","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.15252\/emmm.201606592","article-title":"Modified Atkins diet induces subacute selective ragged-red-fiber lysis in mitochondrial myopathy patients","volume":"8","author":"Ahola","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1186\/s13023-021-01927-w","article-title":"Ketogenic diet for mitochondrial disease: A systematic review on efficacy and safety","volume":"16","author":"Zweers","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1093\/brain\/awr170","article-title":"A randomized placebo-controlled trial of idebenone in Leber\u2019s hereditary optic neuropathy","volume":"134","author":"Klopstock","year":"2011","journal-title":"Brain A J. Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1358\/dot.2016.52.3.2463564","article-title":"Idebenone for Leber\u2019s hereditary optic neuropathy","volume":"52","author":"Gueven","year":"2016","journal-title":"Drugs Today"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1007\/s00417-019-04444-6","article-title":"Visual function in chronic Leber\u2019s hereditary optic neuropathy during idebenone treatment initiated 5 to 50 years after onset","volume":"257","author":"Pemp","year":"2019","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s10384-020-00789-2","article-title":"Characteristics of Japanese patients with Leber\u2019s hereditary optic neuropathy and idebenone trial: A prospective, interventional, non-comparative study","volume":"65","author":"Ishikawa","year":"2021","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Esmaeil, A., Ali, A., and Behbehani, R. (2022). Leber\u2019s hereditary optic neuropathy: Update on current diagnosis and treatment. Front. Ophthalmol., 2.","DOI":"10.3389\/fopht.2022.1077395"},{"key":"ref_106","first-page":"320","article-title":"The Progress of Gene Therapy for Leber\u2019s Optic Hereditary Neuropathy","volume":"17","author":"Zhang","year":"2017","journal-title":"Curr. Gene. Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.ophtha.2020.12.012","article-title":"Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset","volume":"128","author":"Newman","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"eaaz7423","DOI":"10.1126\/scitranslmed.aaz7423","article-title":"Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy","volume":"12","author":"Newman","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1212\/WNL.98.18_supplement.928","article-title":"The Phase III REFLECT Trial: Efficacy and Safety of Bilateral Gene Therapy for Leber Hereditary Optic Neuropathy (LHON) (P17-12.002)","volume":"98","author":"Newman","year":"2022","journal-title":"Neurology"},{"key":"ref_110","first-page":"1","article-title":"Mitochondrial neurogastrointestinal encephalomyopathy: Approaches to diagnosis and treatment","volume":"4","author":"Bax","year":"2020","journal-title":"J. Transl. Genet. Genom."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1212\/WNL.0b013e3182a6cb4b","article-title":"Clinical and biochemical improvements in a patient with MNGIE following enzyme replacement","volume":"81","author":"Bax","year":"2013","journal-title":"Neurology"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Levene, M., Bain, M.D., Moran, N.F., Nirmalananthan, N., Poulton, J., Scarpelli, M., Filosto, M., Mandel, H., MacKinnon, A.D., and Fairbanks, L. (2019). Safety and Efficacy of Erythrocyte Encapsulated Thymidine Phosphorylase in Mitochondrial Neurogastrointestinal Encephalomyopathy. J. Clin. Med., 8.","DOI":"10.3390\/jcm8040457"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.15252\/emmm.201404092","article-title":"Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency","volume":"6","author":"Garone","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1093\/hmg\/ddn143","article-title":"Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance","volume":"17","author":"Akman","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/ana.25506","article-title":"Deoxynucleoside Therapy for Thymidine Kinase 2-Deficient Myopathy","volume":"86","author":"Mavillard","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1002\/ana.26185","article-title":"Synergistic Deoxynucleoside and Gene Therapies for Thymidine Kinase 2 Deficiency","volume":"90","author":"Lee","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e1212","DOI":"10.1212\/WNL.0000000000005255","article-title":"Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy","volume":"90","author":"Karaa","year":"2018","journal-title":"Neurology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e238","DOI":"10.1212\/WNL.0000000000207402","article-title":"Efficacy and Safety of Elamipretide in Individuals with Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial","volume":"101","author":"Karaa","year":"2023","journal-title":"Neurology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-physiol-021115-105339","article-title":"Understanding the Physiology of FGF21","volume":"78","author":"Fisher","year":"2016","journal-title":"Annu. Rev. Physiol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Kim, K.H., and Lee, M.S. (2021). GDF15 as a central mediator for integrated stress response and a promising therapeutic molecule for metabolic disorders and NASH. Biochim. Et Biophys. Acta. Gen. Subj., 1865.","DOI":"10.1016\/j.bbagen.2020.129834"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Foo, A.S.C., Soong, T.W., Yeo, T.T., and Lim, K.L. (2020). Mitochondrial Dysfunction and Parkinson\u2019s Disease-Near-Infrared Photobiomodulation as a Potential Therapeutic Strategy. Front. Aging Neurosci., 12.","DOI":"10.3389\/fnagi.2020.00089"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"6601","DOI":"10.1007\/s12035-017-0852-4","article-title":"Brain Photobiomodulation Therapy: A Narrative Review","volume":"55","author":"Salehpour","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nrm.2017.110","article-title":"The mitochondrial UPR: Mechanisms, physiological functions and implications in ageing","volume":"19","author":"Shpilka","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Torres, A.K., Fleischhart, V., and Inestrosa, N.C. (2024). Mitochondrial unfolded protein response (UPR(mt)): What we know thus far. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1405393"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"R91","DOI":"10.1530\/JME-18-0005","article-title":"The mitochondrial unfolded protein response and mitohormesis: A perspective on metabolic diseases","volume":"61","author":"Yi","year":"2018","journal-title":"J. Mol. Endocrinol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Cilleros-Holgado, P., G\u00f3mez-Fern\u00e1ndez, D., Pi\u00f1ero-P\u00e9rez, R., Reche-L\u00f3pez, D., \u00c1lvarez-C\u00f3rdoba, M., Munuera-Cabeza, M., Talaver\u00f3n-Rey, M., Povea-Cabello, S., Su\u00e1rez-Carrillo, A., and Romero-Gonz\u00e1lez, A. (2023). mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021482"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s42255-020-00334-y","article-title":"Tetracyclines promote survival and fitness in mitochondrial disease models","volume":"3","author":"Perry","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/s13023-022-02331-8","article-title":"UPR(mt) activation improves pathological alterations in cellular models of mitochondrial diseases","volume":"17","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Su\u00e1rez-Rivero, J.M., Pastor-Maldonado, C.J., Romero-Gonz\u00e1lez, A., G\u00f3mez-Fernandez, D., Povea-Cabello, S., \u00c1lvarez-C\u00f3rdoba, M., Villal\u00f3n-Garc\u00eda, I., Talaver\u00f3n-Rey, M., Su\u00e1rez-Carrillo, A., and Munuera-Cabeza, M. (2022). Pterostilbene in Combination with Mitochondrial Cofactors Improve Mitochondrial Function in Cellular Models of Mitochondrial Diseases. Front. Pharmacol, 13.","DOI":"10.3389\/fphar.2022.862085"},{"key":"ref_130","first-page":"1380","article-title":"Patient care standards for primary mitochondrial disease: A consensus statement from the Mitochondrial Medicine Society","volume":"19","author":"Parikh","year":"2017","journal-title":"Anesth. Analg."},{"key":"ref_131","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. Prim."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s10545-015-9855-3","article-title":"Emerging aspects of treatment in mitochondrial disorders","volume":"38","author":"Rahman","year":"2015","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_133","first-page":"186","article-title":"Mitochondrial DNA depletion syndromes: Review and updates of genetic basis, manifestations, and therapeutic options","volume":"10","author":"Scaglia","year":"2013","journal-title":"J. Am. Soc. Exp. Neurother."},{"key":"ref_134","unstructured":"Millhouse-Flourie, T. (2016). MITO 101\u2000Therapies for Mitochondrial Disease Symptoms, United Mitochondrial Disease Foundation. Available online: https:\/\/www.umdf.org\/wp-content\/uploads\/2017\/11\/mito101_Therapies_Millhouse-Flourie.pdf."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.mito.2004.07.013","article-title":"Physical, occupational, respiratory, speech, equine and pet therapies for mitochondrial disease","volume":"4","year":"2004","journal-title":"Mitochondrion"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ymgme.2016.09.002","article-title":"Nutritional interventions in primary mitochondrial disorders: Developing an evidence base","volume":"119","author":"Camp","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.mito.2013.09.003","article-title":"Practice patterns of mitochondrial disease physicians in North America. Part 2: Treatment, care and management","volume":"13","author":"Parikh","year":"2013","journal-title":"Mitochondrion"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/stem.2221","article-title":"Research into Policy: A Brief History of Mitochondrial Donation","volume":"34","author":"Craven","year":"2016","journal-title":"Stem Cells"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5411\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:46:54Z","timestamp":1760032014000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,5]]},"references-count":138,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26115411"],"URL":"https:\/\/doi.org\/10.3390\/ijms26115411","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,5]]}}}