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Un prión de levadura, Mod5, promueve la resistencia adquirida a los fármacos y la supervivencia celular bajo estrés
Genjiro Suzuki1, Naoyuki Shimazu, Motomasa Tanaka
1Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Science (New York, N.Y.)
|April 21, 2012
Resumen
Las células de levadura pueden adaptarse a los fármacos antifúngicos mediante la conversión de la proteína Mod5 en un prión. Esta formación de priones regula las vías celulares, mejorando la supervivencia bajo estrés ambiental y demostrando funciones activas de priones en la adaptación.
Área de la Ciencia:
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
- Genética de la levadura genética de la levadura.
Sus antecedentes:
- Las proteínas priónicas se convierten de estados solubles a estados agregados, ayudando potencialmente a la adaptación celular.
- No se comprende bien el papel de la conversión activa de priones en la concesión de ventajas físicas bajo estrés ambiental.
Objetivo del estudio:
- Investigar si las células de levadura utilizan activamente la conversión de priones para la adaptación ambiental.
- Identificar proteínas priónicas específicas involucradas en la respuesta al estrés y sus mecanismos.
Principales métodos:
- Identificación de Mod5, una isopenteniltransferasa de ARN de transferencia de levadura, como una proteína priónica.
- Análisis del efecto de la conversión de priones Mod5 en las vías celulares, específicamente la biosíntesis de esteroles.
- Exposición experimental de levadura a fármacos antifúngicos para observar la formación de priones y las tasas de supervivencia.
Principales resultados:
- Se descubrió que la conversión de priones Mod5 regula la vía biosintética del esterol.
- Esta regulación confirió la resistencia celular adquirida contra los agentes antifúngicos en la levadura.
- La presión selectiva del fármaco antifúngico promovió la aparición de novo de los estados priónicos Mod5, mejorando la supervivencia celular.
Conclusiones:
- La conversión activa de priones, ejemplificada por Mod5, puede contribuir activamente a la adaptación celular en respuesta a los desafíos ambientales.
- Los cambios fenotípicos impulsados por la formación de priones bajo presión selectiva son un mecanismo de supervivencia en los organismos.
- La regulación mediada por priones de las vías metabólicas ofrece una nueva perspectiva sobre la adaptación evolutiva.
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