Pathophysiological characterization of MERRF patient-specific induced neurons generated by direct reprogramming

Publication date: Available online 22 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Marina Villanueva-Paz, Suleva Povea-Cabello, Irene Villalón-García, Juan M. Suárez-Rivero, Mónica Álvarez-Córdoba, Mario de la Mata, Marta Talaverón-Rey, Sandra Jackson, José A. Sánchez-AlcázarAbstractMitochondrial diseases are a group of rare heterogeneous genetic disorders caused by total or partial mitochondrial dysfunction. They can be caused by mutations in nuclear or mitochondrial DNA (mtDNA). MERRF (Myoclonic Epilepsy with Ragged-Red Fibers) syndrome is one of the most common mitochondrial disorders caused by point mutations in mtDNA. It is mainly caused by the m.8344A > G mutation in the tRNALys (UUR) gene of mtDNA (MT-TK gene). This mutation affects the translation of mtDNA encoded proteins; therefore, the assembly of the electron transport chain (ETC) complexes is disrupted, leading to a reduced mitochondrial respiratory function.However, the molecular pathogenesis of MERRF syndrome remains poorly understood due to the lack of appropriate cell models, particularly in those cell types most affected in the disease such as neurons. Patient-specific induced neurons (iNs) are originated from dermal fibroblasts derived from different individuals carrying the particular mutation causing the disease. Therefore, patient-specific iNs can be used as an excellent cell model to elucidate the mechanisms underlying MERRF syndrome. Here we...

Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - February 22, 2019 Category: Molecular Biology Source Type: research