{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:36:21Z","timestamp":1790811381006,"version":"4.1.0"},"reference-count":131,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["FPU"],"award-info":[{"award-number":["FPU"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Mitochondrial diseases are a heterogeneous group of rare genetic disorders that can be caused by mutations in nuclear (nDNA) or mitochondrial DNA (mtDNA). Mutations in mtDNA are associated with several maternally inherited genetic diseases, with mitochondrial dysfunction as a main pathological feature. These diseases, although frequently multisystemic, mainly affect organs that require large amounts of energy such as the brain and the skeletal muscle. In contrast to the difficulty of obtaining neuronal and muscle cell models, the development of induced pluripotent stem cells (iPSCs) has shed light on the study of mitochondrial diseases. However, it is still a challenge to obtain an appropriate cellular model in order to find new therapeutic options for people suffering from these diseases. In this review, we deepen the knowledge in the current models for the most studied mt-tRNA mutation-caused mitochondrial diseases, MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) and MERRF (myoclonic epilepsy with ragged red fibers) syndromes, and their therapeutic management. In particular, we will discuss the development of a novel model for mitochondrial disease research that consists of induced neurons (iNs) generated by direct reprogramming of fibroblasts derived from patients suffering from MERRF syndrome. We hypothesize that iNs will be helpful for mitochondrial disease modeling, since they could mimic patient\u2019s neuron pathophysiology and give us the opportunity to correct the alterations in one of the most affected cellular types in these disorders.<\/jats:p>","DOI":"10.3389\/fgene.2020.610764","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T09:28:57Z","timestamp":1610530137000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Advances in mt-tRNA Mutation-Caused Mitochondrial Disease Modeling: Patients\u2019 Brain in a Dish"],"prefix":"10.3389","volume":"11","author":[{"given":"Suleva","family":"Povea-Cabello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Villanueva-Paz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan M.","family":"Su\u00e1rez-Rivero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"\u00c1lvarez-C\u00f3rdoba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Villal\u00f3n-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Talaver\u00f3n-Rey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Su\u00e1rez-Carrillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Munuera-Cabeza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"S\u00e1nchez-Alc\u00e1zar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"B1","article-title":"The mitochondrion","author":"Alberts","year":"2002","journal-title":"Molecular Biology of the Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.neuron.2018.10.007","article-title":"Building models of brain disorders with three-dimensional organoids.","volume":"100","author":"Amin","year":"2018","journal-title":"Neuron"},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-07500-6","author":"Angelini","year":"2014","journal-title":"Genetic Neuromuscular Disorders: A Case-Based Approach."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1038\/s41591-018-0166-8","article-title":"MitoTALEN reduces mutant mtDNA load and restores tRNA(Ala) levels in a mouse model of heteroplasmic mtDNA mutation.","volume":"24","author":"Bacman","year":"2018","journal-title":"Nat. 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