Figueroa-Martínez FJ, González-Halphen D

Idioma: Español
Referencias bibliográficas: 68
Paginas: 106-119
Archivo PDF: 259.96 Kb.

RESUMEN

La expresión alotópica es la relocalización funcional de genes de un compartimento celular a otro. En este trabajo, se refiere a la expresión de genes mitocondriales desde el núcleo o desde un vector citosólico. Se considera que esta estrategia es una de las más prometedoras para desarrollar terapias génicas para el eventual tratamiento de enfermedades ocasionadas por mutaciones en el genoma mitocondrial. Actualmente, existen herramientas para introducir material genético en los cromosomas nucleares, se tiene un conocimiento razonable de los mecanismos de importación de proteínas a la mitocondria y en teoría, una sola copia del gen por célula es suficiente para que se sintetice la proteína necesaria y se distribuya en todas las mitocondrias afectadas. Durante los últimos 20 años se ha intentado la expresión alotópica de diversos genes mitocondriales en levaduras, plantas y células de mamífero, así como en animales con enfermedades mitocondriales. Muchos trabajos publicados en los últimos 10 años apuntaban a que la expresión alotópica era una estrategia exitosa, al grado de que han autorizado los primeros estudios clínicos para tratar mediante terapia génica a pacientes con enfermedades mitocondriales. Sin embargo, también se han reportado evidencias que cuestionan la viabilidad de la expresión alotópica y que proponen nuevos criterios para asegurar que las proteínas expresadas alotópicamente verdaderamente se integraron al complejo mitocondrial al cual pertenecen. En este trabajo, presentamos una breve introducción de lo que es la expresión alotópica, hacemos una revisión de los resultados más relevantes en el campo de la expresión de genes mitocondriales desde el núcleo y discutimos las dificultades que consideramos que hay que sortear antes de proponer terapias génicas para combatir con éxito las enfermedades mitocondriales.

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