{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:57:15Z","timestamp":1790837835045,"version":"4.1.0"},"reference-count":194,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":30,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Kelsey Wright Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Mitochondria are critical cellular organelles engaged in energy production, diverse intermediary metabolic functions and signaling. Inherited genetic disorders directly affecting mitochondrial structure and\/or function, known collectively as primary mitochondrial diseases, are among the most complex and heterogeneous inherited conditions, involving dual-genome origin, multisystem manifestations and widely variable clinical severity. These diseases can follow different inheritance patterns and are caused by pathogenic variants in nearly 400 genes encoded by either the mitochondrial or nuclear genome, which commonly impair proteins or RNAs in distinct molecular pathways, resulting in defective energy production by disrupting oxidative phosphorylation. Mitochondrial diseases are challenging to accurately diagnose because of their extensive clinical variability and common features with other metabolic and neuromuscular disorders, as well as limitations in existing diagnostic tools. However, advances in molecular genetics, imaging and systems biology have transformed the diagnostic landscape, enabling more comprehensive and integrative approaches. This Review provides an overview of mitochondrial physiology and outlines the current state of diagnostic strategies, ranging from conventional biochemical assessments and tissue-based analyses to next-generation genome-wide sequencing and the emerging omics technologies. We discuss how combining classical and modern methods can improve diagnostic accuracy and inform clinical decision making. Additionally, we highlight the need for continued refinement of diagnostic frameworks to better support personalized management and future therapeutic development in mitochondrial medicine.<\/jats:p>","DOI":"10.1242\/dmm.052804","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:17:46Z","timestamp":1790835466000},"source":"Crossref","is-referenced-by-count":0,"title":["Advances in diagnosis of mitochondrial dysfunction and primary mitochondrial disease"],"prefix":"10.1242","volume":"19","author":[{"given":"Melis","family":"Kose","sequence":"first","affiliation":[{"name":"Children's Hospital of Philadelphia 1 Mitochondrial Medicine Frontier Program, Division of Genetic and Genomic Medicine, Department of Pediatrics , , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"McCormick","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia 1 Mitochondrial Medicine Frontier Program, Division of Genetic and Genomic Medicine, Department of Pediatrics , , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia 1 Mitochondrial Medicine Frontier Program, Division of Genetic and Genomic Medicine, Department of Pediatrics , , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Muraresku","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia 1 Mitochondrial Medicine Frontier Program, Division of Genetic and Genomic Medicine, Department of Pediatrics , , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Viaene","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia 3 Department of Pathology and Laboratory Medicine , , Philadelphia, PA 19104 ,","place":["USA"]},{"name":"University of Pennsylvania Perelman School of Medicine 4 Department of Pathology and Laboratory Medicine , , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarazuela","family":"Zolkipli-Cunningham","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia 1 Mitochondrial Medicine Frontier Program, Division of Genetic and Genomic Medicine, Department of Pediatrics , , Philadelphia, PA 19104 ,","place":["USA"]},{"name":"University of Pennsylvania Perelman School of Medicine 2 Department of Pediatrics , , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1723-6728","authenticated-orcid":false,"given":"Marni J.","family":"Falk","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia 1 Mitochondrial Medicine Frontier Program, Division of Genetic and Genomic Medicine, Department of Pediatrics , , Philadelphia, PA 19104 ,","place":["USA"]},{"name":"University of Pennsylvania Perelman School of Medicine 2 Department of Pediatrics , , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"2026100102174285500_DMM052804C1","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.1515\/cclm-2015-0208","article-title":"Total folate and 5-methyltetrahydrofolate in the cerebrospinal fluid of children: correlation and reference values","volume":"53","author":"Akiyama","year":"2015","journal-title":"Clin. Chem. Lab. Med."},{"key":"2026100102174285500_DMM052804C2","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.ajhg.2019.12.001","article-title":"Pathogenic Bi-allelic mutations in NDUFAF8 cause Leigh syndrome with an isolated complex I deficiency","volume":"106","author":"Alston","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"2026100102174285500_DMM052804C3","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1002\/path.5641","article-title":"The genetics of mitochondrial disease: dissecting mitochondrial pathology using multi-omic pipelines","volume":"254","author":"Alston","year":"2021","journal-title":"J. Pathol."},{"key":"2026100102174285500_DMM052804C4","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.3174\/ajnr.A8670","article-title":"Single large-scale mitochondrial deletion syndromes: neuroimaging phenotypes and longitudinal progression in pediatric patients","volume":"46","author":"Alves","year":"2025","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"2026100102174285500_DMM052804C5","doi-asserted-by":"publisher","first-page":"e8124","DOI":"10.15252\/msb.20178124","article-title":"Multi-Omics Factor Analysis-a framework for unsupervised integration of multi-omics data sets","volume":"14","author":"Argelaguet","year":"2018","journal-title":"Mol. Syst. Biol."},{"key":"2026100102174285500_DMM052804C6","doi-asserted-by":"publisher","first-page":"5387","DOI":"10.1038\/s41467-024-49253-6","article-title":"Personalized and muscle-specific Oxphos measurement with integrated CrCEST MRI and proton MR spectroscopy","volume":"15","author":"Armbruster","year":"2024","journal-title":"Nat. Commun."},{"key":"2026100102174285500_DMM052804C7","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1016\/j.neuint.2013.10.002","article-title":"Levels of 5-methyltetrahydrofolate and ascorbic acid in cerebrospinal fluid are correlated: implications for the accelerated degradation of folate by reactive oxygen species","volume":"63","author":"Aylett","year":"2013","journal-title":"Neurochem. Int."},{"key":"2026100102174285500_DMM052804C8","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1093\/brain\/awt328","article-title":"Variant non ketotic hyperglycinemia is caused by mutations in Lias, BOLA3 and the novel gene GLRX5","volume":"137","author":"Baker","year":"2014","journal-title":"Brain"},{"key":"2026100102174285500_DMM052804C9","doi-asserted-by":"publisher","first-page":"e10575","DOI":"10.7554\/eLife.10575","article-title":"Mitochondrial dysfunction remodels one-carbon metabolism in human cells","volume":"5","author":"Bao","year":"2016","journal-title":"eLife"},{"key":"2026100102174285500_DMM052804C10","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1007\/s10545-018-0224-x","article-title":"Cerebrospinal fluid monoamines, pterins, and folate in patients with mitochondrial diseases: systematic review and hospital experience","volume":"41","author":"Batllori","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"2026100102174285500_DMM052804C11","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41525-024-00434-8","article-title":"Clinical genome sequencing in patients with suspected rare genetic disease in Peru","volume":"9","author":"Bazalar-Montoya","year":"2024","journal-title":"Npj Genom. Med."},{"key":"2026100102174285500_DMM052804C12","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1212\/01.WNL.0000033795.17156.00","article-title":"Diagnostic criteria for respiratory chain disorders in adults and children","volume":"59","author":"Bernier","year":"2002","journal-title":"Neurology"},{"key":"2026100102174285500_DMM052804C13","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1002\/mus.27191","article-title":"A novel exercise testing algorithm to diagnose mitochondrial myopathy","volume":"63","author":"Bhatia","year":"2021","journal-title":"Muscle Nerve"},{"key":"2026100102174285500_DMM052804C14","doi-asserted-by":"publisher","first-page":"5058","DOI":"10.1038\/s41467-023-40797-7","article-title":"Apogee 2: multi-layer machine-learning model for the interpretable prediction of mitochondrial missense variants","volume":"14","author":"Bianco","year":"2023","journal-title":"Nat. Commun."},{"key":"2026100102174285500_DMM052804C15","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1042\/EBC20170111","article-title":"Biomarkers for mitochondrial energy metabolism diseases","volume":"62","author":"Boenzi","year":"2018","journal-title":"Essays Biochem."},{"key":"2026100102174285500_DMM052804C16","doi-asserted-by":"publisher","first-page":"103887","DOI":"10.1016\/j.mcn.2023.103887","article-title":"Glutamine metabolism in diseases associated with mitochondrial dysfunction","volume":"126","author":"Bornstein","year":"2023","journal-title":"Mol. Cell. Neurosci."},{"key":"2026100102174285500_DMM052804C17","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/ng1095-144","article-title":"Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency","volume":"11","author":"Bourgeron","year":"1995","journal-title":"Nat. Genet."},{"key":"2026100102174285500_DMM052804C18","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1093\/humupd\/dmaf004","article-title":"Genetic and reproductive strategies to prevent mitochondrial diseases","volume":"31","author":"Castelluccio","year":"2025","journal-title":"Hum. Reprod. Update"},{"key":"2026100102174285500_DMM052804C19","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1002\/jmri.29566","article-title":"Reliability of in vivo creatine-weighted chemical exchange saturation transfer (CrCEST) MRI in calf skeletal muscle of healthy volunteers at 3T","volume":"61","author":"Chakraborty","year":"2025","journal-title":"J. Magn. Reson. Imaging"},{"key":"2026100102174285500_DMM052804C20","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/S0021-9258(19)57191-5","article-title":"Respiratory enzymes in oxidative phosphorylation. III. The steady state","volume":"217","author":"Chance","year":"1955","journal-title":"J. Biol. Chem."},{"key":"2026100102174285500_DMM052804C21","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1684\/epd.2015.0779","article-title":"Cerebrospinal fluid findings after epileptic seizures","volume":"17","author":"Chatzikonstantinou","year":"2015","journal-title":"Epileptic Disord."},{"key":"2026100102174285500_DMM052804C22","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s12929-023-00967-7","article-title":"Induced pluripotent stem cells: ex vivo models for human diseases due to mitochondrial DNA mutations","volume":"30","author":"Chen","year":"2023","journal-title":"J. Biomed. Sci."},{"key":"2026100102174285500_DMM052804C23","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/s41586-023-06045-0","article-title":"A genomic mutational constraint map using variation in 76,156 human genomes","volume":"625","author":"Chen","year":"2024","journal-title":"Nature"},{"key":"2026100102174285500_DMM052804C24","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.ymgme.2013.07.011","article-title":"Mitochondrial respiratory chain disease discrimination by retrospective cohort analysis of blood metabolites","volume":"110","author":"Clarke","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"2026100102174285500_DMM052804C25","doi-asserted-by":"publisher","first-page":"16746","DOI":"10.3390\/ijms242316746","article-title":"Red flags in primary mitochondrial diseases: what should we recognize?","volume":"24","author":"Conti","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"2026100102174285500_DMM052804C26","doi-asserted-by":"publisher","first-page":"11624","DOI":"10.3390\/ijms241411624","article-title":"Neurofilament-light, a promising biomarker: analytical, metrological and clinical challenges","volume":"24","author":"Coppens","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"2026100102174285500_DMM052804C27","doi-asserted-by":"publisher","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. Genomics Hum. Genet."},{"key":"2026100102174285500_DMM052804C28","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1212\/WNL.0000000000002705","article-title":"A comparison of current serum biomarkers as diagnostic indicators of mitochondrial diseases","volume":"86","author":"Davis","year":"2016","journal-title":"Neurology"},{"key":"2026100102174285500_DMM052804C29","doi-asserted-by":"publisher","first-page":"e730","DOI":"10.1212\/WNL.0000000000200745","article-title":"Use of whole-genome sequencing for mitochondrial disease diagnosis","volume":"99","author":"Davis","year":"2022","journal-title":"Neurology"},{"key":"2026100102174285500_DMM052804C30","doi-asserted-by":"publisher","first-page":"933","DOI":"10.3390\/biomedicines12050933","article-title":"Cell-free nuclear and mitochondrial DNA as potential biomarkers for assessing sepsis severity","volume":"12","author":"De Miranda","year":"2024","journal-title":"Biomedicines"},{"key":"2026100102174285500_DMM052804C31","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1373\/clinchem.2006.081166","article-title":"Diagnostic accuracy of blood lactate-to-pyruvate molar ratio in the differential diagnosis of congenital lactic acidosis","volume":"53","author":"Debray","year":"2007","journal-title":"Clin. Chem."},{"key":"2026100102174285500_DMM052804C32","doi-asserted-by":"publisher","first-page":"e88207","DOI":"10.1172\/jci.insight.88207","article-title":"Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders","volume":"1","author":"Debrosse","year":"2016","journal-title":"JCI Insight"},{"key":"2026100102174285500_DMM052804C33","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1002\/ddrr.102","article-title":"Historical perspective on mitochondrial medicine","volume":"16","author":"Dimauro","year":"2010","journal-title":"Dev. Disabil. Res. Rev."},{"key":"2026100102174285500_DMM052804C34","doi-asserted-by":"publisher","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":"2026100102174285500_DMM052804C35","doi-asserted-by":"publisher","first-page":"54985","DOI":"10.3791\/54985","article-title":"High-resolution respirometry to assess mitochondrial function in permeabilized and intact cells","volume":"120","author":"Djafarzadeh","year":"2017","journal-title":"J. Vis. Exp"},{"key":"2026100102174285500_DMM052804C36","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/j.1460-9592.2006.02043.x","article-title":"Anesthesia-related morbidity and mortality after surgery for muscle biopsy in children with mitochondrial defects","volume":"17","author":"Driessen","year":"2007","journal-title":"Paediatr. Anaesth."},{"key":"2026100102174285500_DMM052804C37","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cmet.2016.08.009","article-title":"One-carbon metabolism in health and disease","volume":"25","author":"Ducker","year":"2017","journal-title":"Cell Metab."},{"key":"2026100102174285500_DMM052804C38","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1186\/s12887-021-02830-w","article-title":"The full spectrum of ethical issues in pediatric genome-wide sequencing: a systematic qualitative review","volume":"21","author":"Eichinger","year":"2021","journal-title":"BMC Pediatr."},{"key":"2026100102174285500_DMM052804C39","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1038\/s41588-025-02160-y","article-title":"Toward clinical long-read genome sequencing for rare diseases","volume":"57","author":"Eisfeldt","year":"2025","journal-title":"Nat. Genet."},{"key":"2026100102174285500_DMM052804C40","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1016\/j.bbadis.2017.02.017","article-title":"Mitochondrial DNA maintenance defects","volume":"1863","author":"El-Hattab","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis. Dis."},{"key":"2026100102174285500_DMM052804C41","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1001\/archneurol.2012.206","article-title":"Heterogeneity of coenzyme Q10 deficiency: patient study and literature review","volume":"69","author":"Emmanuele","year":"2012","journal-title":"Arch. Neurol."},{"key":"2026100102174285500_DMM052804C42","volume-title":"Mitochondrial Disease Genes Compendium from Genes to Clinical Manifestations","author":"Falk","year":"2020"},{"key":"2026100102174285500_DMM052804C43","doi-asserted-by":"publisher","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":"2026100102174285500_DMM052804C44","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1016\/j.cell.2025.02.019","article-title":"Small-molecule hypoxia therapy in mitochondrial disease","volume":"188","author":"Falk","year":"2025","journal-title":"Cell"},{"key":"2026100102174285500_DMM052804C45","first-page":"389","article-title":"Mitochondrial disease genetic diagnostics: optimized whole-exome analysis for all MitoCarta nuclear genes and the mitochondrial genome","volume":"14","author":"Falk","year":"2012","journal-title":"Discov. Med."},{"key":"2026100102174285500_DMM052804C46","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.ymgme.2014.11.016","article-title":"Mitochondrial Disease Sequence Data Resource (MSeqDR): a global grass-roots consortium to facilitate deposition, curation, annotation, and integrated analysis of genomic data for the mitochondrial disease clinical and research communities","volume":"114","author":"Falk","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"2026100102174285500_DMM052804C47","doi-asserted-by":"publisher","first-page":"e12821","DOI":"10.1002\/jimd.12821","article-title":"The clinical utility in hospital-wide use of growth differentiation factor 15 as a biomarker for mitochondrial DNA-related disorders","volume":"48","author":"Fern\u00e1ndez","year":"2025","journal-title":"J. Inherit. Metab. Dis."},{"key":"2026100102174285500_DMM052804C48","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1002\/1873-3468.14021","article-title":"Mitochondrial DNA copy number in human disease: the more the better?","volume":"595","author":"Filograna","year":"2021","journal-title":"FEBS Lett."},{"key":"2026100102174285500_DMM052804C49","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1002\/crt2.41","article-title":"Development of a mitochondrial myopathy-composite assessment tool","volume":"6","author":"Flickinger","year":"2021","journal-title":"JCSM. Clin. Rep."},{"key":"2026100102174285500_DMM052804C50","doi-asserted-by":"publisher","first-page":"e597","DOI":"10.1212\/NXG.0000000000000597","article-title":"Diagnosing mitochondrial disorders remains challenging in the omics era","volume":"7","author":"Forny","year":"2021","journal-title":"Neurol. Genet."},{"key":"2026100102174285500_DMM052804C51","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1093\/hmg\/ddw431","article-title":"Mutations in the accessory subunit NDUFB10 result in isolated complex I deficiency and illustrate the critical role of intermembrane space import for complex I holoenzyme assembly","volume":"26","author":"Friederich","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"2026100102174285500_DMM052804C52","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.ymgme.2021.06.001","article-title":"Pathogenic variants in MRPL44 cause infantile cardiomyopathy due to a mitochondrial translation defect","volume":"133","author":"Friederich","year":"2021","journal-title":"Mol. Genet. Metab."},{"key":"2026100102174285500_DMM052804C53","doi-asserted-by":"publisher","first-page":"101386","DOI":"10.1016\/j.gim.2025.101386","article-title":"Recognizing the evolution of clinical syndrome spectrum progression in individuals with single large-scale mitochondrial DNA deletion syndromes (Slsmds)","volume":"27","author":"Ganetzky","year":"2025","journal-title":"Genet. Med."},{"key":"2026100102174285500_DMM052804C54","doi-asserted-by":"publisher","first-page":"2493","DOI":"10.1093\/hmg\/ddx144","article-title":"Respiratory chain enzyme deficiency induces mitochondrial location of actin-binding gelsolin to modulate the oligomerization of VDAC complexes and cell survival","volume":"26","author":"Garc\u00eda-Bartolom\u00e9","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"2026100102174285500_DMM052804C55","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.3390\/cells9091922","article-title":"Altered expression ratio of actin-binding gelsolin isoforms is a novel hallmark of mitochondrial OXPHOS dysfunction","volume":"9","author":"Garc\u00eda-Bartolom\u00e9","year":"2020","journal-title":"Cells"},{"key":"2026100102174285500_DMM052804C56","doi-asserted-by":"publisher","first-page":"ooae134","DOI":"10.1093\/jamiaopen\/ooae134","article-title":"MMFP-Tableau: enabling precision mitochondrial medicine through integration, visualization, and analytics of clinical and research health system electronic data","volume":"7","author":"George-Sankoh","year":"2024","journal-title":"JAMIA Open"},{"key":"2026100102174285500_DMM052804C57","doi-asserted-by":"publisher","first-page":"4855","DOI":"10.3390\/ijms25094855","article-title":"Mitochondrial biomarkers in the omics era: a clinical-pathophysiological perspective","volume":"25","author":"Gervasoni","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"2026100102174285500_DMM052804C58","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1093\/clinchem\/hvad037","article-title":"Methodologies in mitochondrial testing: diagnosing a primary mitochondrial respiratory chain disorder","volume":"69","author":"Gill","year":"2023","journal-title":"Clin. Chem."},{"key":"2026100102174285500_DMM052804C59","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1136\/jmg-2024-110330","article-title":"Canadian College of Medical Geneticists: clinical practice advisory document - responsibility to recontact for reinterpretation of clinical genetic testing","volume":"61","author":"Goh","year":"2024","journal-title":"J. Med. Genet."},{"key":"2026100102174285500_DMM052804C60","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.ymgme.2011.11.193","article-title":"Non-invasive evaluation of buccal respiratory chain enzyme dysfunction in mitochondrial disease: comparison with studies in muscle biopsy","volume":"105","author":"Goldenthal","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"2026100102174285500_DMM052804C61","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/jimd.12320","article-title":"Seeking impact: global perspectives on outcome measure selection for translational and clinical research for primary mitochondrial disorders","volume":"44","author":"Goldstein","year":"2021","journal-title":"J. Inherit. Metab. Dis."},{"key":"2026100102174285500_DMM052804C62","doi-asserted-by":"publisher","first-page":"e8262","DOI":"10.15252\/emmm.201708262","article-title":"mtDNA heteroplasmy level and copy number indicate disease burden in m.3243A&gt;G mitochondrial disease","volume":"10","author":"Grady","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"2026100102174285500_DMM052804C63","doi-asserted-by":"publisher","first-page":"e00311","DOI":"10.1016\/j.neurot.2023.e00311","article-title":"Challenges and opportunities to bridge translational to clinical research for personalized mitochondrial medicine","volume":"21","author":"Gropman","year":"2024","journal-title":"Neurotherapeutics"},{"key":"2026100102174285500_DMM052804C64","doi-asserted-by":"publisher","first-page":"e17163","DOI":"10.7554\/eLife.17163","article-title":"QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease","volume":"5","author":"Guarani","year":"2016","journal-title":"eLife"},{"key":"2026100102174285500_DMM052804C65","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.1161\/CIR.0b013e31826fb946","article-title":"EACPR\/AHA scientific statement. Clinical recommendations for cardiopulmonary exercise testing data assessment in specific patient populations","volume":"126","author":"Guazzi","year":"2012","journal-title":"Circulation"},{"key":"2026100102174285500_DMM052804C66","doi-asserted-by":"publisher","first-page":"e145158","DOI":"10.1172\/JCI145158","article-title":"Proteomic and metabolomic advances uncover biomarkers of mitochondrial disease pathophysiology and severity","volume":"131","author":"Gucek","year":"2021","journal-title":"J. Clin. Invest."},{"key":"2026100102174285500_DMM052804C67","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1542\/peds.2007-0391","article-title":"Mitochondrial disease: a practical approach for primary care physicians","volume":"120","author":"Haas","year":"2007","journal-title":"Pediatrics"},{"key":"2026100102174285500_DMM052804C68","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.ymgme.2007.11.018","article-title":"The in-depth evaluation of suspected mitochondrial disease","volume":"94","author":"Haas","year":"2008","journal-title":"Mol. Genet. Metab."},{"key":"2026100102174285500_DMM052804C69","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/BF00692217","article-title":"The occurrence of paracrystalline mitochondrial inclusions in normal human skeletal muscle","volume":"49","author":"Hammersen","year":"1980","journal-title":"Acta Neuropathol."},{"key":"2026100102174285500_DMM052804C70","doi-asserted-by":"publisher","first-page":"6695","DOI":"10.3390\/ijms21186695","article-title":"Disorders of human coenzyme Q10 metabolism: an overview","volume":"21","author":"Hargreaves","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2026100102174285500_DMM052804C71","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.ejpn.2024.10.009","article-title":"Mitochondrial disorder diagnosis and management- what the pediatric neurologist wants to know","volume":"54","author":"Heath","year":"2025","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"2026100102174285500_DMM052804C72","doi-asserted-by":"publisher","first-page":"106822","DOI":"10.1016\/j.nbd.2025.106822","article-title":"iPSC models of mitochondrial diseases","volume":"207","author":"Heiduschka","year":"2025","journal-title":"Neurobiol. Dis."},{"key":"2026100102174285500_DMM052804C73","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.jns.2006.03.017","article-title":"Restoring balance to ataxia with coenzyme Q10 deficiency","volume":"246","author":"Hirano","year":"2006","journal-title":"J. Neurol. Sci."},{"key":"2026100102174285500_DMM052804C74","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s13073-025-01467-z","article-title":"Untargeted proteomics enables ultra-rapid variant prioritisation in mitochondrial and other rare diseases","volume":"17","author":"Hock","year":"2025","journal-title":"Genome Med."},{"key":"2026100102174285500_DMM052804C75","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/331717a0","article-title":"Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies","volume":"331","author":"Holt","year":"1988","journal-title":"Nature"},{"key":"2026100102174285500_DMM052804C76","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.mito.2021.10.008","article-title":"Blood biomarkers for assessment of mitochondrial dysfunction: an expert review","volume":"62","author":"Hubens","year":"2022","journal-title":"Mitochondrion"},{"key":"2026100102174285500_DMM052804C77","doi-asserted-by":"publisher","first-page":"945","DOI":"10.18632\/aging.100950","article-title":"Study of mitochondrial respiratory defects on reprogramming to human induced pluripotent stem cells","volume":"8","author":"Hung","year":"2016","journal-title":"Aging"},{"key":"2026100102174285500_DMM052804C78","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1007\/s10545-010-9159-6","article-title":"Cerebral folate deficiency","volume":"33","author":"Hyland","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"2026100102174285500_DMM052804C79","doi-asserted-by":"publisher","first-page":"795838","DOI":"10.3389\/fcell.2021.795838","article-title":"Regulation of mitochondrial function by the actin cytoskeleton","volume":"9","author":"Illescas","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"2026100102174285500_DMM052804C80","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.3390\/jcm10081796","article-title":"Exercise testing, physical training and fatigue in patients with mitochondrial myopathy related to mtDNA mutations","volume":"10","author":"Jeppesen","year":"2021","journal-title":"J. Clin. Med."},{"key":"2026100102174285500_DMM052804C81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/9780470942390.mo150182","article-title":"Analysis of mitochondrial respiratory chain supercomplexes using blue native polyacrylamide gel electrophoresis (BN-PAGE)","volume":"6","author":"Jha","year":"2016","journal-title":"Curr. Protoc. Mouse Biol."},{"key":"2026100102174285500_DMM052804C82","doi-asserted-by":"publisher","first-page":"4913","DOI":"10.3390\/molecules26164913","article-title":"The role of taurine in mitochondria health: more than just an antioxidant","volume":"26","author":"Jong","year":"2021","journal-title":"Molecules"},{"key":"2026100102174285500_DMM052804C83","doi-asserted-by":"publisher","first-page":"e22","DOI":"10.15420\/usc.2024.37","article-title":"Cardiopulmonary exercise testing: methodology, interpretation, and role in exercise prescription for cardiac rehabilitation","volume":"18","author":"Kabbadj","year":"2024","journal-title":"US Cardiol."},{"key":"2026100102174285500_DMM052804C84","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s10545-017-0081-z","article-title":"Erratum to: common data elements for clinical research in mitochondrial disease: a National Institute for Neurological Disorders and Stroke project","volume":"41","author":"Karaa","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"2026100102174285500_DMM052804C85","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/s41576-023-00683-w","article-title":"The expanding diagnostic toolbox for rare genetic diseases","volume":"25","author":"Kernohan","year":"2024","journal-title":"Nat. Rev. Genet."},{"key":"2026100102174285500_DMM052804C86","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1042\/EBC20170108","article-title":"Natural history of mitochondrial disorders: a systematic review","volume":"62","author":"Keshavan","year":"2018","journal-title":"Essays Biochem."},{"key":"2026100102174285500_DMM052804C87","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S0091-679X(06)80004-X","article-title":"Biochemical assays of respiratory chain complex activity","volume":"80","author":"Kirby","year":"2007","journal-title":"Methods Cell Biol."},{"key":"2026100102174285500_DMM052804C88","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1002\/jmri.24412","article-title":"In vivo chemical exchange saturation transfer imaging of creatine (CrCEST) in skeletal muscle at 3T","volume":"40","author":"Kogan","year":"2014","journal-title":"J. Magn. Reson. Imaging"},{"key":"2026100102174285500_DMM052804C89","doi-asserted-by":"publisher","first-page":"15824","DOI":"10.1038\/ncomms15824","article-title":"Genetic diagnosis of Mendelian disorders via RNA sequencing","volume":"8","author":"Kremer","year":"2017","journal-title":"Nat. Commun."},{"key":"2026100102174285500_DMM052804C90","doi-asserted-by":"publisher","first-page":"102061","DOI":"10.1016\/j.mito.2025.102061","article-title":"Machine learning to predict mitochondrial diseases by phenotypes","volume":"84","author":"Kuo","year":"2025","journal-title":"Mitochondrion"},{"key":"2026100102174285500_DMM052804C91","doi-asserted-by":"publisher","first-page":"590842","DOI":"10.3389\/fmolb.2020.590842","article-title":"Multi-omics approaches to improve mitochondrial disease diagnosis: challenges, advances, and perspectives","volume":"7","author":"Labory","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"2026100102174285500_DMM052804C92","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.ajhg.2017.07.005","article-title":"Biallelic mutations in mrps34 lead to instability of the small mitoribosomal subunit and Leigh syndrome","volume":"101","author":"Lake","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"2026100102174285500_DMM052804C93","doi-asserted-by":"publisher","first-page":"2967","DOI":"10.1093\/bioinformatics\/btac216","article-title":"MitoVisualize: a resource for analysis of variants in human mitochondrial RNAs and DNA","volume":"38","author":"Lake","year":"2022","journal-title":"Bioinformatics"},{"key":"2026100102174285500_DMM052804C94","doi-asserted-by":"publisher","first-page":"17923","DOI":"10.18632\/oncotarget.4235","article-title":"Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice","volume":"6","author":"Leduc-Gaudet","year":"2015","journal-title":"Oncotarget"},{"key":"2026100102174285500_DMM052804C95","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1002\/jimd.12307","article-title":"Diagnostic value of serum biomarkers FGF21 and GDF15 compared to muscle sample in mitochondrial disease","volume":"44","author":"Lehtonen","year":"2021","journal-title":"J. Inherit. Metab. Dis."},{"key":"2026100102174285500_DMM052804C96","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1007\/s12031-025-02440-6","article-title":"Hypocitrullinemia as an early diagnostic biomarker for MT-ATP6 mitochondrial diseases","volume":"75","author":"Li","year":"2025","journal-title":"J. Mol. Neurosci."},{"key":"2026100102174285500_DMM052804C97","doi-asserted-by":"publisher","first-page":"106556","DOI":"10.1016\/j.biocel.2024.106556","article-title":"The application of brain organoid for drug discovery in mitochondrial diseases","volume":"170","author":"Liang","year":"2024","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2026100102174285500_DMM052804C98","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1002\/acn3.51104","article-title":"Accuracy of FGF-21 and GDF-15 for the diagnosis of mitochondrial disorders: a meta-analysis","volume":"7","author":"Lin","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"2026100102174285500_DMM052804C99","doi-asserted-by":"publisher","first-page":"1.23.1","DOI":"10.1002\/0471250953.bi0123s44","article-title":"mtDNA variation and analysis using mitomap and mitomaster","volume":"44","author":"Lott","year":"2013","journal-title":"Curr. Protoc. Bioinformatics"},{"key":"2026100102174285500_DMM052804C100","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1080\/14737159.2023.2241365","article-title":"Enhanced mitochondrial genome analysis: bioinformatic and long-read sequencing advances and their diagnostic implications","volume":"23","author":"Macken","year":"2023","journal-title":"Expert Rev. Mol. Diagn."},{"key":"2026100102174285500_DMM052804C101","doi-asserted-by":"publisher","first-page":"108348","DOI":"10.1016\/j.ymgme.2024.108348","article-title":"Bridging the clinical-research gap: harnessing an electronic data capture, integration, and visualization platform to systematically assess prospective patient-reported outcomes in mitochondrial medicine","volume":"142","author":"MacMullen","year":"2024","journal-title":"Mol. Genet. Metab."},{"key":"2026100102174285500_DMM052804C102","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1186\/s13023-025-03632-4","article-title":"Single large-scale mitochondrial DNA deletion syndromes: scientific and family conference optimizes the collection of rare disease research outcomes","volume":"20","author":"MacMullen","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"2026100102174285500_DMM052804C103","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.3390\/antiox12081652","article-title":"Primary coenzyme Q10 deficiency: an update","volume":"12","author":"Mantle","year":"2023","journal-title":"Antioxidants"},{"key":"2026100102174285500_DMM052804C104","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1007\/s00109-020-01967-y","article-title":"Expanding and validating the biomarkers for mitochondrial diseases","volume":"98","author":"Maresca","year":"2020","journal-title":"J. Mol. Med."},{"key":"2026100102174285500_DMM052804C105","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41431-022-01249-w","article-title":"Genetic testing for mitochondrial disease: the United Kingdom best practice guidelines","volume":"31","author":"Mavraki","year":"2023","journal-title":"Eur. J. Hum. Genet."},{"key":"2026100102174285500_DMM052804C106","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.ajhg.2011.11.011","article-title":"Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation","volume":"89","author":"Mayr","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"2026100102174285500_DMM052804C107","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/s13311-012-0174-1","article-title":"Molecular genetic testing for mitochondrial disease: from one generation to the next","volume":"10","author":"McCormick","year":"2013","journal-title":"Neurotherapeutics"},{"key":"2026100102174285500_DMM052804C108","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1097\/MOP.0000000000000686","article-title":"Mitochondrial disease genetics update: recent insights into the molecular diagnosis and expanding phenotype of primary mitochondrial disease","volume":"30","author":"McCormick","year":"2018","journal-title":"Curr. Opin. Pediatr."},{"key":"2026100102174285500_DMM052804C109","doi-asserted-by":"publisher","first-page":"2028","DOI":"10.1002\/humu.24107","article-title":"Specifications of the ACMG\/AMP standards and guidelines for mitochondrial DNA variant interpretation","volume":"41","author":"McCormick","year":"2020","journal-title":"Hum. Mutat."},{"key":"2026100102174285500_DMM052804C110","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1002\/ana.26716","article-title":"Expert panel curation of 113 primary mitochondrial disease genes for the Leigh syndrome spectrum","volume":"94","author":"McCormick","year":"2023","journal-title":"Ann. Neurol."},{"key":"2026100102174285500_DMM052804C111","doi-asserted-by":"publisher","first-page":"20406223251344763","DOI":"10.1177\/20406223251344763","article-title":"The profound implications of mitochondrial myopathy on activities of daily living: an observational qualitative study of standardized structured and semi-structured patient interviews","volume":"16","author":"McCormick","year":"2025","journal-title":"Ther. Adv. Chronic Dis."},{"key":"2026100102174285500_DMM052804C112","doi-asserted-by":"publisher","first-page":"7730","DOI":"10.3390\/ijms22147730","article-title":"Modelling mitochondrial disease in human pluripotent stem cells: what have we learned?","volume":"22","author":"McKnight","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2026100102174285500_DMM052804C113","doi-asserted-by":"publisher","first-page":"e70036","DOI":"10.1002\/jmd2.70036","article-title":"Mitochondrial DNA pathogenic variant prevalence in primary mitochondrial disease patients with African (L) mitochondrial genome haplogroups","volume":"66","author":"Meldau","year":"2025","journal-title":"JIMD Rep."},{"key":"2026100102174285500_DMM052804C114","doi-asserted-by":"publisher","first-page":"109704","DOI":"10.1016\/j.ymgme.2025.109704","article-title":"Clinical and biochemical footprints of primary mitochondrial disorders: proposed nosology","volume":"147","author":"Messina","year":"2026","journal-title":"Mol. Genet. Metab."},{"key":"2026100102174285500_DMM052804C115","doi-asserted-by":"publisher","first-page":"100866","DOI":"10.1016\/j.gim.2023.100866","article-title":"ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG)","volume":"25","author":"Miller","year":"2023","journal-title":"Genet. Med."},{"key":"2026100102174285500_DMM052804C116","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3892\/mmr.2025.13443","article-title":"Mitochondrial DNA copy number alterations: key players in the complexity of glioblastoma (review)","volume":"31","author":"Mohamed Yusoff","year":"2025","journal-title":"Mol. Med. Rep."},{"key":"2026100102174285500_DMM052804C117","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.clinbiochem.2008.03.007","article-title":"Analysis of coenzyme Q10 in muscle and fibroblasts for the diagnosis of CoQ10 deficiency syndromes","volume":"41","author":"Montero","year":"2008","journal-title":"Clin. Biochem."},{"key":"2026100102174285500_DMM052804C118","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1007\/s40142-018-0138-9","article-title":"Mitochondrial disease: advances in clinical diagnosis, management, therapeutic development, and preventative strategies","volume":"6","author":"Muraresku","year":"2018","journal-title":"Curr. Genet. Med. Rep."},{"key":"2026100102174285500_DMM052804C119","doi-asserted-by":"publisher","first-page":"100469","DOI":"10.1016\/j.xhgg.2025.100469","article-title":"Identification of technically challenging variants: whole-genome sequencing improves diagnostic yield in patients with high clinical suspicion of rare diseases","volume":"6","author":"Ng","year":"2025","journal-title":"HGG Adv."},{"key":"2026100102174285500_DMM052804C120","doi-asserted-by":"publisher","first-page":"101103","DOI":"10.1016\/j.gim.2024.101103","article-title":"Additional findings from the 100,000 genomes project: a qualitative study of recipient perspectives","volume":"26","author":"Nolan","year":"2024","journal-title":"Genet. Med."},{"key":"2026100102174285500_DMM052804C121","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.bbacli.2017.04.001","article-title":"Pathogenicity in POLG syndromes: DNA polymerase gamma pathogenicity prediction server and database","volume":"7","author":"Nurminen","year":"2017","journal-title":"BBA Clin."},{"key":"2026100102174285500_DMM052804C122","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.pediatrneurol.2006.05.007","article-title":"Normal muscle respiratory chain enzymes can complicate mitochondrial disease diagnosis","volume":"35","author":"Oglesbee","year":"2006","journal-title":"Pediatr. Neurol."},{"key":"2026100102174285500_DMM052804C123","doi-asserted-by":"publisher","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":"2026100102174285500_DMM052804C124","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.pcl.2023.05.011","article-title":"Ethical aspects of pediatric genetic care: testing and treatment","volume":"70","author":"Ormond","year":"2023","journal-title":"Pediatr. Clin. North Am."},{"key":"2026100102174285500_DMM052804C125","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.mehy.2018.02.022","article-title":"Plasma creatine as a marker of mitochondrial dysfunction","volume":"113","author":"Ostojic","year":"2018","journal-title":"Med. Hypotheses"},{"key":"2026100102174285500_DMM052804C126","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/gim.2014.177","article-title":"Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society","volume":"17","author":"Parikh","year":"2015","journal-title":"Genet. Med."},{"key":"2026100102174285500_DMM052804C127","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1136\/jmedgenet-2018-105800","article-title":"Diagnosis of \u2018possible\u2019 mitochondrial disease: an existential crisis","volume":"56","author":"Parikh","year":"2019","journal-title":"J. Med. Genet."},{"key":"2026100102174285500_DMM052804C128","doi-asserted-by":"publisher","first-page":"6396","DOI":"10.3390\/ijms22126396","article-title":"Plasma gelsolin reinforces the diagnostic value of FGF-21 and GDF-15 for mitochondrial disorders","volume":"22","author":"Pe\u00f1as","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2026100102174285500_DMM052804C129","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.ymgme.2021.06.007","article-title":"Prospective diagnosis of MT-ATP6-related mitochondrial disease by newborn screening","volume":"134","author":"Peretz","year":"2021","journal-title":"Mol. Genet. Metab."},{"key":"2026100102174285500_DMM052804C130","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1093\/hmg\/3.3.449","article-title":"Extremely high levels of mutant mtDNAs co-localize with cytochrome c oxidase-negative ragged-red fibers in patients harboring a point mutation at NT 3243","volume":"3","author":"Petruzzella","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"2026100102174285500_DMM052804C131","doi-asserted-by":"publisher","first-page":"64","DOI":"10.3390\/jcm6070064","article-title":"Myopathology of adult and paediatric mitochondrial diseases","volume":"6","author":"Phadke","year":"2017","journal-title":"J. Clin. Med."},{"key":"2026100102174285500_DMM052804C132","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.gim.2021.08.009","article-title":"Us private payers\u2019 perspectives on insurance coverage for genome sequencing versus exome sequencing: a study by the Clinical Sequencing Evidence-Generating Research Consortium (CSER)","volume":"24","author":"Phillips","year":"2022","journal-title":"Genet. Med."},{"key":"2026100102174285500_DMM052804C133","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1002\/acn3.532","article-title":"Phenotypic heterogeneity in m.3243A&gt;G mitochondrial disease: the role of nuclear factors","volume":"5","author":"Pickett","year":"2018","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"2026100102174285500_DMM052804C134","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1111\/joim.13054","article-title":"Mitochondrial disease in children","volume":"287","author":"Rahman","year":"2020","journal-title":"J. Intern. Med."},{"key":"2026100102174285500_DMM052804C135","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41582-018-0101-0","article-title":"POLG-related disorders and their neurological manifestations","volume":"15","author":"Rahman","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"2026100102174285500_DMM052804C136","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1016\/S0140-6736(18)30727-X","article-title":"Mitochondrial medicine in the omics era","volume":"391","author":"Rahman","year":"2018","journal-title":"Lancet"},{"key":"2026100102174285500_DMM052804C137","doi-asserted-by":"publisher","first-page":"D1541","DOI":"10.1093\/nar\/gkaa1011","article-title":"MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations","volume":"49","author":"Rath","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2026100102174285500_DMM052804C138","doi-asserted-by":"publisher","first-page":"9686","DOI":"10.1093\/nar\/gkab726","article-title":"MitoPhen database: a human phenotype ontology-based approach to identify mitochondrial DNA diseases","volume":"49","author":"Ratnaike","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2026100102174285500_DMM052804C139","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"2026100102174285500_DMM052804C140","doi-asserted-by":"publisher","first-page":"15037","DOI":"10.1038\/srep15037","article-title":"A novel immunofluorescent assay to investigate oxidative phosphorylation deficiency in mitochondrial myopathy: understanding mechanisms and improving diagnosis","volume":"5","author":"Rocha","year":"2015","journal-title":"Sci. Rep."},{"key":"2026100102174285500_DMM052804C141","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.cell.2020.02.051","article-title":"Mitochondrial diseases: hope for the future","volume":"181","author":"Russell","year":"2020","journal-title":"Cell"},{"key":"2026100102174285500_DMM052804C142","article-title":"Primary Coenzyme Q(10) Deficiency Overview","volume-title":"GeneReviews(\u00ae)","author":"Salviati","year":"1993"},{"key":"2026100102174285500_DMM052804C143","doi-asserted-by":"publisher","first-page":"e066288","DOI":"10.1136\/bmj-2021-066288","article-title":"Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study","volume":"375","author":"Schon","year":"2021","journal-title":"BMJ"},{"key":"2026100102174285500_DMM052804C144","doi-asserted-by":"publisher","first-page":"2527","DOI":"10.1007\/s00415-021-10821-1","article-title":"In vivo assessment of Oxphos capacity using 3 T CrCEST Mri in Friedreich's ataxia","volume":"269","author":"Schur","year":"2022","journal-title":"J. Neurol."},{"key":"2026100102174285500_DMM052804C145","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1093\/hmg\/3.1.13","article-title":"Distribution of wild-type and common deletion forms of mtDNA in normal and respiration-deficient muscle fibers from patients with mitochondrial myopathy","volume":"3","author":"Sciacco","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"2026100102174285500_DMM052804C146","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1007\/s11064-019-02786-5","article-title":"Primary coenzyme Q deficiency due to novel ADCK3 variants, studies in fibroblasts and review of literature","volume":"44","author":"Shalata","year":"2019","journal-title":"Neurochem. Res."},{"key":"2026100102174285500_DMM052804C147","doi-asserted-by":"publisher","first-page":"e136055","DOI":"10.1172\/JCI136055","article-title":"Circulating markers of NADH-reductive stress correlate with mitochondrial disease severity","volume":"131","author":"Sharma","year":"2021","journal-title":"J. Clin. Invest."},{"key":"2026100102174285500_DMM052804C148","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1016\/j.pediatrneurol.2014.08.009","article-title":"Role of plasma amino acids and urinary organic acids in diagnosis of mitochondrial diseases in children","volume":"51","author":"Shatla","year":"2014","journal-title":"Pediatr. Neurol."},{"key":"2026100102174285500_DMM052804C149","doi-asserted-by":"publisher","first-page":"e00325","DOI":"10.1016\/j.neurot.2024.e00325","article-title":"Biomarkers of mitochondrial disorders","volume":"21","author":"Shayota","year":"2024","journal-title":"Neurotherapeutics"},{"key":"2026100102174285500_DMM052804C150","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.cll.2020.02.002","article-title":"Clinical bioinformatics in precise diagnosis of mitochondrial disease","volume":"40","author":"Shen","year":"2020","journal-title":"Clin. Lab. Med."},{"key":"2026100102174285500_DMM052804C151","doi-asserted-by":"publisher","first-page":"e955","DOI":"10.1002\/cpz1.955","article-title":"MSeqDR Quick-Mitome (Qm): combining phenotype-guided variant interpretation and machine learning classifiers to aid primary mitochondrial disease genetic diagnosis","volume":"4","author":"Shen","year":"2024","journal-title":"Curr. Protoc."},{"key":"2026100102174285500_DMM052804C152","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1007\/978-1-0716-2309-1_25","article-title":"Analysis of organization and activity of mitochondrial respiratory chain complexes in primary fibroblasts using blue native page","volume":"2497","author":"Singh","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"2026100102174285500_DMM052804C153","doi-asserted-by":"publisher","first-page":"26778","DOI":"10.1038\/s41598-024-78270-0","article-title":"The quality and detection limits of mitochondrial heteroplasmy by long read nanopore sequencing","volume":"14","author":"Slapnik","year":"2024","journal-title":"Sci. Rep."},{"key":"2026100102174285500_DMM052804C154","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1002\/humu.22844","article-title":"GeneMatcher: a matching tool for connecting investigators with an interest in the same gene","volume":"36","author":"Sobreira","year":"2015","journal-title":"Hum. Mutat."},{"key":"2026100102174285500_DMM052804C155","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.mito.2018.07.002","article-title":"Cerebrospinal fluid neurofilament light is associated with survival in mitochondrial disease patients","volume":"46","author":"Sofou","year":"2019","journal-title":"Mitochondrion"},{"key":"2026100102174285500_DMM052804C156","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.ajhg.2018.11.014","article-title":"Integrating genomics into healthcare: a global responsibility","volume":"104","author":"Stark","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"2026100102174285500_DMM052804C157","doi-asserted-by":"publisher","first-page":"102784","DOI":"10.1016\/j.ebiom.2020.102784","article-title":"Genetics of mitochondrial diseases: identifying mutations to help diagnosis","volume":"56","author":"Stenton","year":"2020","journal-title":"EBioMedicine"},{"key":"2026100102174285500_DMM052804C158","doi-asserted-by":"publisher","first-page":"100441","DOI":"10.1016\/j.xhgg.2025.100441","article-title":"Mitochondrial DNA variant detection in over 6,500 rare disease families by the systematic analysis of exome and genome sequencing data resolves undiagnosed cases","volume":"6","author":"Stenton","year":"2025","journal-title":"HGG Adv."},{"key":"2026100102174285500_DMM052804C159","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/nrg3966","article-title":"The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease","volume":"16","author":"Stewart","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"2026100102174285500_DMM052804C160","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.ajhg.2017.04.015","article-title":"Evaluating the clinical validity of gene-disease associations: an evidence-based framework developed by the clinical genome resource","volume":"100","author":"Strande","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"2026100102174285500_DMM052804C161","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s13073-021-00855-5","article-title":"Integration of whole genome sequencing into a healthcare setting: high diagnostic rates across multiple clinical entities in 3219 rare disease patients","volume":"13","author":"Stranneheim","year":"2021","journal-title":"Genome Med."},{"key":"2026100102174285500_DMM052804C162","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1016\/S1474-4422(11)70155-7","article-title":"FGF-21 as a biomarker for muscle-manifesting mitochondrial respiratory chain deficiencies: a diagnostic study","volume":"10","author":"Suomalainen","year":"2011","journal-title":"Lancet Neurol."},{"key":"2026100102174285500_DMM052804C163","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0022-510X(00)00354-3","article-title":"Kearns-Sayre syndrome: oncocytic transformation of choroid plexus epithelium","volume":"178","author":"Tanji","year":"2000","journal-title":"J. Neurol. Sci."},{"key":"2026100102174285500_DMM052804C164","doi-asserted-by":"publisher","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":"2026100102174285500_DMM052804C165","doi-asserted-by":"publisher","first-page":"101867","DOI":"10.1016\/j.gimo.2024.101867","article-title":"Variant reclassification and recontact research: a scoping review","volume":"2","author":"Thummala","year":"2024","journal-title":"Genet. Med. Open"},{"key":"2026100102174285500_DMM052804C166","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1002\/ajmg.a.63159","article-title":"MT-ATP6 mitochondrial disease identified by newborn screening reveals a distinct biochemical phenotype","volume":"191","author":"Tise","year":"2023","journal-title":"Am. J. Med. Genet. A"},{"key":"2026100102174285500_DMM052804C167","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.4049\/jimmunol.2001016","article-title":"Loss of mitochondrial protease CLPP activates Type I IFN Responses through the mitochondrial DNA-cGAS-sting signaling axis","volume":"206","author":"Torres-Odio","year":"2021","journal-title":"J. Immunol."},{"key":"2026100102174285500_DMM052804C168","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1093\/clinchem\/hvab091","article-title":"Circulating cell-free mitochondrial DNA in cerebrospinal fluid as a biomarker for mitochondrial diseases","volume":"67","author":"Trifunov","year":"2021","journal-title":"Clin. Chem."},{"key":"2026100102174285500_DMM052804C169","doi-asserted-by":"publisher","first-page":"7487","DOI":"10.3390\/ijms23137487","article-title":"The biochemical assessment of mitochondrial respiratory chain disorders","volume":"23","author":"Turton","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2026100102174285500_DMM052804C170","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1203\/00006450-200111000-00020","article-title":"Blue native polyacrylamide gel electrophoresis: a powerful tool in diagnosis of oxidative phosphorylation defects","volume":"50","author":"Van Coster","year":"2001","journal-title":"Pediatr. Res."},{"key":"2026100102174285500_DMM052804C171","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.mito.2004.07.005","article-title":"Biochemical examination of fibroblasts in the diagnosis and research of oxidative phosphorylation (Oxphos) defects","volume":"4","author":"van den Heuvel","year":"2004","journal-title":"Mitochondrion"},{"key":"2026100102174285500_DMM052804C172","doi-asserted-by":"publisher","DOI":"10.64898\/2026.06.12.26355546","article-title":"The clinical utility of functional testing in fibroblasts to diagnose primary mitochondrial disease","author":"Van Hove","year":"2026","journal-title":"medRxiv"},{"key":"2026100102174285500_DMM052804C173","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/s41387-022-00213-3","article-title":"Role of branched-chain amino acid metabolism in the pathogenesis of obesity and type 2 diabetes-related metabolic disturbances Bcaa metabolism in type 2 diabetes","volume":"12","author":"Vanweert","year":"2022","journal-title":"Nutr. Diabetes"},{"key":"2026100102174285500_DMM052804C174","doi-asserted-by":"publisher","first-page":"fcaa222","DOI":"10.1093\/braincomms\/fcaa222","article-title":"Serum biomarkers in primary mitochondrial disorders","volume":"3","author":"Varhaug","year":"2021","journal-title":"Brain Commun."},{"key":"2026100102174285500_DMM052804C175","doi-asserted-by":"publisher","first-page":"30610","DOI":"10.1038\/srep30610","article-title":"The spectrum of mitochondrial ultrastructural defects in mitochondrial myopathy","volume":"6","author":"Vincent","year":"2016","journal-title":"Sci. Rep."},{"key":"2026100102174285500_DMM052804C176","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1093\/jnen\/60.3.217","article-title":"Mitochondrial myopathies and the role of the pathologist in the molecular era","volume":"60","author":"Vogel","year":"2001","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"2026100102174285500_DMM052804C177","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1126\/science.3201231","article-title":"Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy","volume":"242","author":"Wallace","year":"1988","journal-title":"Science"},{"key":"2026100102174285500_DMM052804C178","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/0092-8674(88)90218-8","article-title":"Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease","volume":"55","author":"Wallace","year":"1988","journal-title":"Cell"},{"key":"2026100102174285500_DMM052804C179","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.ymgme.2021.12.006","article-title":"Advanced approach for comprehensive mtDNA genome testing in mitochondrial disease","volume":"135","author":"Wang","year":"2022","journal-title":"Mol. Genet. Metab."},{"key":"2026100102174285500_DMM052804C180","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.3390\/genes14061222","article-title":"MitoTrace: a computational framework for analyzing mitochondrial variation in single-cell RNA sequencing data","volume":"14","author":"Wang","year":"2023","journal-title":"Genes"},{"key":"2026100102174285500_DMM052804C181","doi-asserted-by":"publisher","first-page":"1507493","DOI":"10.3389\/fphar.2025.1507493","article-title":"Interpreting the clinical significance of multiple large-scale mitochondrial DNA deletions (MLSMD) in skeletal muscle tissue in the diagnostic evaluation of primary mitochondrial disease","volume":"16","author":"Wang","year":"2025","journal-title":"Front. Pharmacol."},{"key":"2026100102174285500_DMM052804C182","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41392-024-02044-3","article-title":"Mitochondrial diseases: from molecular mechanisms to therapeutic advances","volume":"10","author":"Wen","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"2026100102174285500_DMM052804C183","doi-asserted-by":"publisher","first-page":"781","DOI":"10.33549\/physiolres.930391","article-title":"Polarographic evaluation of mitochondrial enzymes activity in isolated mitochondria and in permeabilized human muscle cells with inherited mitochondrial defects","volume":"52","author":"Wenchich","year":"2003","journal-title":"Physiol. Res."},{"key":"2026100102174285500_DMM052804C184","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1038\/nprot.2006.62","article-title":"Blue native page","volume":"1","author":"Wittig","year":"2006","journal-title":"Nat. Protoc."},{"key":"2026100102174285500_DMM052804C185","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1186\/s13023-021-01916-z","article-title":"PhenoDB, GeneMatcher and VariantMatcher, tools for analysis and sharing of sequence data","volume":"16","author":"Wohler","year":"2021","journal-title":"Orphanet J. Rare. Dis."},{"key":"2026100102174285500_DMM052804C186","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1111\/cen.12095","article-title":"Fibroblast growth factor 21 as an emerging metabolic regulator: clinical perspectives","volume":"78","author":"Woo","year":"2013","journal-title":"Clin. Endocrinol."},{"key":"2026100102174285500_DMM052804C187","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s10545-010-9210-7","article-title":"The 3-methylglutaconic acidurias: what's new?","volume":"35","author":"Wortmann","year":"2012","journal-title":"J. Inherit. Metab. Dis."},{"key":"2026100102174285500_DMM052804C188","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1007\/s10545-012-9580-0","article-title":"Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature","volume":"36","author":"Wortmann","year":"2013","journal-title":"J. Inherit. Metab. Dis."},{"key":"2026100102174285500_DMM052804C189","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s10545-015-9823-y","article-title":"Whole exome sequencing of suspected mitochondrial patients in clinical practice","volume":"38","author":"Wortmann","year":"2015","journal-title":"J. Inherit. Metab. Dis."},{"key":"2026100102174285500_DMM052804C190","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1055\/s-0037-1603776","article-title":"A guideline for the diagnosis of pediatric mitochondrial disease: the value of muscle and skin biopsies in the genetics era","volume":"48","author":"Wortmann","year":"2017","journal-title":"Neuropediatrics"},{"key":"2026100102174285500_DMM052804C191","doi-asserted-by":"publisher","first-page":"776807","DOI":"10.3389\/fgene.2021.776807","article-title":"Primary coenzyme Q10 deficiency-7 and pathogenic COQ4 variants: clinical presentation, biochemical analyses, and treatment","volume":"12","author":"Xie","year":"2021","journal-title":"Front. Genet."},{"key":"2026100102174285500_DMM052804C192","doi-asserted-by":"publisher","first-page":"18","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":"2026100102174285500_DMM052804C193","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.1038\/s41598-021-81721-7","article-title":"Neurofilament light is a novel biomarker for mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes","volume":"11","author":"Zheng","year":"2021","journal-title":"Sci. Rep."},{"key":"2026100102174285500_DMM052804C194","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.bbamcr.2008.06.013","article-title":"Cristae formation-linking ultrastructure and function of mitochondria","volume":"1793","author":"Zick","year":"2009","journal-title":"Biochim. Biophys. Acta"}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052804\/3719990\/dmm052804.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052804\/3719990\/dmm052804.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:17:48Z","timestamp":1790835468000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/19\/9\/dmm052804\/373065\/Advances-in-diagnosis-of-mitochondrial-dysfunction"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":194,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.052804","relation":{},"ISSN":["1754-8403","1754-8411"],"issn-type":[{"value":"1754-8403","type":"print"},{"value":"1754-8411","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"article-number":"dmm052804"}}