{"id":286597,"date":"2024-10-25T10:00:15","date_gmt":"2024-10-25T08:00:15","guid":{"rendered":"https:\/\/www.cbm.uam.es\/index.php\/2024\/10\/25\/descubren-las-bases-moleculares-del-fallo-mitocondrial-en-el-cerebro\/"},"modified":"2024-11-04T11:56:38","modified_gmt":"2024-11-04T10:56:38","slug":"descubren-las-bases-moleculares-del-fallo-mitocondrial-en-el-cerebro","status":"publish","type":"post","link":"https:\/\/www.cbm.uam.es\/index.php\/2024\/10\/25\/descubren-las-bases-moleculares-del-fallo-mitocondrial-en-el-cerebro\/","title":{"rendered":"Descubren las bases moleculares del fallo mitocondrial en el cerebro"},"content":{"rendered":"<p>Las enfermedades mitocondriales son un grupo heterog\u00e9neo de trastornos hereditarios que carecen de cura. Estas enfermedades est\u00e1n provocadas por deficiencias en el metabolismo mitocondrial, que produce la energ\u00eda que permite funcionar a nuestras c\u00e9lulas.<\/p>\n<p>Estos trastornos son causados por mutaciones gen\u00e9ticas que est\u00e1n presentes en todas las c\u00e9lulas del individuo afectado por la enfermedad. Sin embargo, no todos los tipos celulares o tejidos son igual de sensibles, y los mecanismos moleculares que causan esta diferente sensibilidad son poco conocidos. Se sabe que los fallos del metabolismo mitocondrial ocurren en particular en la cadena de transporte de electrones.<\/p>\n<p>En este nuevo estudio, investigadores del Centro de Biolog\u00eda Molecular Severo Ochoa (CSIC-UAM), han descubierto que cuando se interrumpe la cadena de transporte de electrones, se activa una v\u00eda alternativa del ciclo del \u00e1cido tricarbox\u00edlico. Con esto se consigue mantener los niveles de malato y producir NADPH, una mol\u00e9cula clave que ayuda a las c\u00e9lulas a hacer frente al estr\u00e9s oxidativo.<\/p>\n<p><img decoding=\"async\" class=\"alignnone wp-image-286574\" src=\"https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2024\/10\/Captura-de-pantalla-2024-10-24-a-las-16.26.38.png\" alt=\"\" width=\"895\" height=\"477\" \/><\/p>\n<p>El estudio muestra que las dos enzimas que median en esta reprogramaci\u00f3n metab\u00f3lica son la piruvato carboxilasa y la enzima m\u00e1lica 1. Dichas enzimas son esenciales para mantener la funci\u00f3n mitocondrial y el equilibrio redox en las c\u00e9lulas con disfunci\u00f3n mitocondrial. En el tejido cerebral, estas dos enzimas con m\u00e1s activas en los astrocitos, las c\u00e9lulas que dan soporte al cerebro, que en las neuronas. Este hecho revela por qu\u00e9 los astrocitos con m\u00e1s resistentes a los fallos en la cadena de transporte de electrones que las neuronas. Adem\u00e1s, se observ\u00f3 que el fenotipo perjudicial en las c\u00e9lulas cerebrales est\u00e1 vinculado a un descenso del antioxidante NADPH, y no a la p\u00e9rdida de producci\u00f3n de energ\u00eda en forma de ATP.<\/p>\n<p>Adem\u00e1s, los investigadores lograron reducir la neuroinflamaci\u00f3n y mejorar la funci\u00f3n motora en un modelo de rat\u00f3n de deficiencia de la cadena de transporte de electrones, al aumentar los niveles de enzima m\u00e1lica 1 en el cerebro.<\/p>\n<p>Estos hallazgos aportan datos fundamentales sobre los factores moleculares y metab\u00f3licos que explican por qu\u00e9 algunas c\u00e9lulas cerebrales son m\u00e1s vulnerables al da\u00f1o mitocondrial. El estudio ofrece as\u00ed nuevas perspectivas para el tratamiento de las enfermedades mitocondriales. En particular, los investigadores sugieres que aumentar los niveles de enzima m\u00e1lica 1 en el cerebro puede ser una posible estrategia terap\u00e9utica para mitigar los s\u00edntomas neurol\u00f3gicos de las enfermedades mitocondriales.<\/p>\n<p>&nbsp;<\/p>\n<h3>Art\u00edculo:<\/h3>\n<p>del Prado, L., Jara\u00edz-Rodr\u00edguez, M., Agro, M.\u00a0<em>et al.<\/em>\u00a0Compensatory activity of the PC-ME1 metabolic axis underlies differential sensitivity to mitochondrial complex I inhibition.\u00a0<em>Nat Commun<\/em>\u00a0<strong>15<\/strong>, 8682 (2024). <a href=\"https:\/\/doi.org\/10.1038\/s41467-024-52968-1\">https:\/\/doi.org\/10.1038\/s41467-024-52968-1<\/a><\/p>\n<p>&nbsp;<\/p>\n<h3>Contacto:<\/h3>\n<p>CBM Comunicaci\u00f3n &#8211; <a href=\"mailto:Comunicacion@cbm.csic.es\">Comunicacion@cbm.csic.es<\/a><\/p>\n<p>Eduardo Balsa &#8211; <a href=\"mailto:ebalsa@cbm.csic.es\">ebalsa@cbm.csic.es<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Las enfermedades mitocondriales son un grupo heterog\u00e9neo de trastornos hereditarios que carecen de cura. Estas enfermedades est\u00e1n provocadas por deficiencias en el metabolismo mitocondrial, que produce la energ\u00eda que permite [&hellip;]<\/p>\n","protected":false},"author":5,"featured_media":286577,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[114,115],"tags":[],"class_list":["post-286597","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news-2-2","category-scientific-article-2-2"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Descubren las bases moleculares del fallo mitocondrial en el cerebro - Centro de Biolog\u00eda Molecular Severo Ochoa<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.cbm.uam.es\/index.php\/2024\/10\/25\/descubren-las-bases-moleculares-del-fallo-mitocondrial-en-el-cerebro\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Descubren las bases moleculares del fallo mitocondrial en el cerebro - Centro de Biolog\u00eda Molecular Severo Ochoa\" \/>\n<meta property=\"og:description\" content=\"Las enfermedades mitocondriales son un grupo heterog\u00e9neo de trastornos hereditarios que carecen de cura. 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