Por motivos de mantenimiento se ha deshabilitado el inicio de sesión temporalmente. Rogamos disculpen las molestias.
Artículo
Actin Polymerization Defects Induce Mitochondrial Dysfunction in Cellular Models of Nemaline Myopathies
Autor/es | Piñero Pérez, Rocío
López Cabrera, Alejandra Álvarez Córdoba, Mónica Cilleros Holgado, Paula Talaverón Rey, Marta Suárez Carrillo, Alejandra Munuera Cabeza, Manuel Gómez Fernández, David Reche López, Diana Romero González, Ana Belén Romero Domínguez, José Manuel Martínez de Pablos, Rocío Sánchez Alcázar, José Antonio |
Departamento | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular |
Fecha de publicación | 2023-12 |
Fecha de depósito | 2024-02-12 |
Publicado en |
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Resumen | Nemaline myopathy (NM) is one of the most common forms of congenital myopathy and it is identified by the presence of “nemaline bodies” (rods) in muscle fibers by histopathological examination. The most common forms of NM ... Nemaline myopathy (NM) is one of the most common forms of congenital myopathy and it is identified by the presence of “nemaline bodies” (rods) in muscle fibers by histopathological examination. The most common forms of NM are caused by mutations in the Actin Alpha 1 (ACTA1) and Nebulin (NEB) genes. Clinical features include hypotonia and muscle weakness. Unfortunately, there is no curative treatment and the pathogenetic mechanisms remain unclear. In this manuscript, we examined the pathophysiological alterations in NM using dermal fibroblasts derived from patients with mutations in ACTA1 and NEB genes. Patients’ fibroblasts were stained with rhodamine–phalloidin to analyze the polymerization of actin filaments by fluorescence microscopy. We found that patients’ fibroblasts showed incorrect actin filament polymerization compared to control fibroblasts. Actin filament polymerization defects were associated with mitochondrial dysfunction. Furthermore, we identified two mitochondrial-boosting compounds, linoleic acid (LA) and L-carnitine (LCAR), that improved the formation of actin filaments in mutant fibroblasts and corrected mitochondrial bioenergetics. Our results indicate that cellular models can be useful to study the pathophysiological mechanisms involved in NM and to find new potential therapies. Furthermore, targeting mitochondrial dysfunction with LA and LCAR can revert the pathological alterations in NM cellular models. |
Agencias financiadoras | Instituto de Salud Carlos III Junta de Andalucía |
Identificador del proyecto | FIS PI19/00377
FIS PI22/00142 CTS-5725 PY18-850 UPO-1380614 |
Cita | Piñero Pérez, R., López Cabrera, A., Álvarez Córdoba, M., Cilleros Holgado, P., Talaverón Rey, M., Suárez Carrillo, A.,...,Sánchez Alcázar, J.A. (2023). Actin Polymerization Defects Induce Mitochondrial Dysfunction in Cellular Models of Nemaline Myopathies. Antioxidants, 12 (12), 2023. https://doi.org/10.3390/antiox12122023. |
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Actin Polymerization.pdf | 9.028Mb | [PDF] | Ver/ | Versión publicada |