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mTOR regula los canales lisosómicos de dos poros Na (((+) sensibles al ATP para adaptarse al estado metabólico
Chunlei Cang1, Yandong Zhou1, Betsy Navarro2
1Department of Biology, University of Pennsylvania, 415 S. University Ave., Philadelphia, Pennsylvania 19104, USA.
Cell
|February 12, 2013
Resumen
Los investigadores descubrieron un nuevo canal de sodio sensible al ATP en los lisosomas, llamado lisoNa(ATP), crucial para la detección de nutrientes y la resistencia física durante el ayuno.
Área de la Ciencia:
- Biología celular Biología celular.
- Fisiología Fisiología Fisiología.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Los endosomas y lisosomas son organelos vitales que vinculan la nutrición celular y el metabolismo con las respuestas celulares.
- Los mecanismos precisos por los cuales estos orgánulos perciben los niveles de ATP citosólico siguen siendo en gran medida desconocidos.
Objetivo del estudio:
- Identificar y caracterizar nuevos canales iónicos sensibles al ATP en los endolisosomas.
- Para aclarar el papel de estos canales en la detección de nutrientes y la adaptación metabólica.
Principales métodos:
- Electrofisiología para caracterizar la actividad de los canales iónicos.
- Ensayos bioquímicos para estudiar la formación y localización de complejos proteicos.
- Manipulación genética en ratones para evaluar la función in vivo.
Principales resultados:
- Identificación de un nuevo complejo endolisomal de canales Na ((+)) sensibles al ATP (lysoNa ((ATP)) compuesto por TPC1, TPC2 y mTOR.
- Demostración de que el lisoNa (((ATP) detecta el estado de los nutrientes, volviéndose constitutivamente abierto tras la privación de nutrientes.
- Evidencia de que el lisoNa (ATP) regula el potencial de la membrana lisosomal, el pH y la homeostasis de los aminoácidos.
Conclusiones:
- Las TPC forman una familia de canales iónicos que acoplan el estado metabólico celular con la función endolisosómica.
- LysoNa (ATP) es esencial para mantener la resistencia física durante los períodos de restricción de alimentos.
- Este descubrimiento proporciona nuevos conocimientos sobre la regulación del metabolismo celular y la adaptación del organismo a la disponibilidad de nutrientes.
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