Piñero-Pérez, R.; López-Cabrera, A.; Álvarez-Córdoba, M.; Cilleros-Holgado, P.; Talaverón-Rey, M.; Suárez-Carrillo, A.; Munuera-Cabeza, M.; Gómez-Fernández, D.; Reche-López, D.; Romero-González, A.; Romero-Domínguez, J.M.; de Pablos, R.M.; Sánchez-Alcázar, J.A. Actin Polymerization Defects Induce Mitochondrial Dysfunction in Cellular Models of Nemaline Myopathies. Antioxidants2023, 12, 2023.
Piñero-Pérez, R.; López-Cabrera, A.; Álvarez-Córdoba, M.; Cilleros-Holgado, P.; Talaverón-Rey, M.; Suárez-Carrillo, A.; Munuera-Cabeza, M.; Gómez-Fernández, D.; Reche-López, D.; Romero-González, A.; Romero-Domínguez, J.M.; de Pablos, R.M.; Sánchez-Alcázar, J.A. Actin Polymerization Defects Induce Mitochondrial Dysfunction in Cellular Models of Nemaline Myopathies. Antioxidants 2023, 12, 2023.
Piñero-Pérez, R.; López-Cabrera, A.; Álvarez-Córdoba, M.; Cilleros-Holgado, P.; Talaverón-Rey, M.; Suárez-Carrillo, A.; Munuera-Cabeza, M.; Gómez-Fernández, D.; Reche-López, D.; Romero-González, A.; Romero-Domínguez, J.M.; de Pablos, R.M.; Sánchez-Alcázar, J.A. Actin Polymerization Defects Induce Mitochondrial Dysfunction in Cellular Models of Nemaline Myopathies. Antioxidants2023, 12, 2023.
Piñero-Pérez, R.; López-Cabrera, A.; Álvarez-Córdoba, M.; Cilleros-Holgado, P.; Talaverón-Rey, M.; Suárez-Carrillo, A.; Munuera-Cabeza, M.; Gómez-Fernández, D.; Reche-López, D.; Romero-González, A.; Romero-Domínguez, J.M.; de Pablos, R.M.; Sánchez-Alcázar, J.A. Actin Polymerization Defects Induce Mitochondrial Dysfunction in Cellular Models of Nemaline Myopathies. Antioxidants 2023, 12, 2023.
Abstract
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 exam-ination. The most common forms of NM are caused by mutations in the ACTA1 (Actin Alpha 1) and NEB (Nebulin) genes. Clinical features include hypotonia and muscle weakness. Unfortunate-ly, there is no curative treatment and the pathogenetic mechanisms remains unclear. In this man-uscript, 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 microsco-py. We found that patients' fibroblasts showed incorrect actin filament polymerization compared to control fibroblasts. Actin filament polymerization defects was 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 fibro-blasts 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.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
