Advances in mt-tRNA Mutation-Caused Mitochondrial Disease Modeling: Patients’ Brain in a Dish
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 featu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2020.610764/full |
| _version_ | 1818736171329519616 |
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| author | Suleva Povea-Cabello Marina Villanueva-Paz Juan M. Suárez-Rivero Mónica Álvarez-Córdoba Irene Villalón-García Marta Talaverón-Rey Alejandra Suárez-Carrillo Manuel Munuera-Cabeza José A. Sánchez-Alcázar |
| author_facet | Suleva Povea-Cabello Marina Villanueva-Paz Juan M. Suárez-Rivero Mónica Álvarez-Córdoba Irene Villalón-García Marta Talaverón-Rey Alejandra Suárez-Carrillo Manuel Munuera-Cabeza José A. Sánchez-Alcázar |
| author_sort | Suleva Povea-Cabello |
| collection | DOAJ |
| description | 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’s neuron pathophysiology and give us the opportunity to correct the alterations in one of the most affected cellular types in these disorders. |
| first_indexed | 2024-12-18T00:32:54Z |
| format | Article |
| id | doaj.art-268f8afa474c4a08b7566ae38cb2c542 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-18T00:32:54Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-268f8afa474c4a08b7566ae38cb2c5422022-12-21T21:27:06ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-01-011110.3389/fgene.2020.610764610764Advances in mt-tRNA Mutation-Caused Mitochondrial Disease Modeling: Patients’ Brain in a DishSuleva Povea-Cabello0Marina Villanueva-Paz1Juan M. Suárez-Rivero2Mónica Álvarez-Córdoba3Irene Villalón-García4Marta Talaverón-Rey5Alejandra Suárez-Carrillo6Manuel Munuera-Cabeza7José A. Sánchez-Alcázar8Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III, Seville, SpainInstituto de Investigación Biomédica de Málaga, Departamento de Farmacología y Pediatría, Facultad de Medicina, Universidad de Málaga, Málaga, SpainCentro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III, Seville, SpainCentro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III, Seville, SpainCentro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III, Seville, SpainCentro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III, Seville, SpainCentro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III, Seville, SpainCentro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III, Seville, SpainCentro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III, Seville, SpainMitochondrial 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’s neuron pathophysiology and give us the opportunity to correct the alterations in one of the most affected cellular types in these disorders.https://www.frontiersin.org/articles/10.3389/fgene.2020.610764/fullmitochondrial diseasesmtDNAdisease modelingdirect reprogramminginduced neurons |
| spellingShingle | Suleva Povea-Cabello Marina Villanueva-Paz Juan M. Suárez-Rivero Mónica Álvarez-Córdoba Irene Villalón-García Marta Talaverón-Rey Alejandra Suárez-Carrillo Manuel Munuera-Cabeza José A. Sánchez-Alcázar Advances in mt-tRNA Mutation-Caused Mitochondrial Disease Modeling: Patients’ Brain in a Dish Frontiers in Genetics mitochondrial diseases mtDNA disease modeling direct reprogramming induced neurons |
| title | Advances in mt-tRNA Mutation-Caused Mitochondrial Disease Modeling: Patients’ Brain in a Dish |
| title_full | Advances in mt-tRNA Mutation-Caused Mitochondrial Disease Modeling: Patients’ Brain in a Dish |
| title_fullStr | Advances in mt-tRNA Mutation-Caused Mitochondrial Disease Modeling: Patients’ Brain in a Dish |
| title_full_unstemmed | Advances in mt-tRNA Mutation-Caused Mitochondrial Disease Modeling: Patients’ Brain in a Dish |
| title_short | Advances in mt-tRNA Mutation-Caused Mitochondrial Disease Modeling: Patients’ Brain in a Dish |
| title_sort | advances in mt trna mutation caused mitochondrial disease modeling patients brain in a dish |
| topic | mitochondrial diseases mtDNA disease modeling direct reprogramming induced neurons |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2020.610764/full |
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