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La retroalimentación mediada por HIF-1α previene que la señalización TOR agote el suministro de oxígeno y desencadene

Yifan Zhao¹, Cyrille Alexandre¹, Gavin Kelly¹

¹The Francis Crick Institute, London, UK.

Nature communications

|December 21, 2025

Resumen

Durante el desarrollo, los discos alares de Drosophila ralentizan el crecimiento cambiando el metabolismo y volviéndose hipóxicos. Esta hipoxia, regulada por HIF-1α, crea un bucle de retroalimentación para prevenir el agotamiento de oxígeno por crecimiento excesivo.

Área de la Ciencia:

Biología del Desarrollo
Metabolismo Celular
Señalización de Hipoxia

Sus antecedentes:

La desaceleración del crecimiento precede a la terminación del crecimiento en organismos en desarrollo.
Los cambios metabólicos y los niveles de oxígeno son factores críticos que influyen en las tasas de crecimiento del desarrollo.

Objetivo del estudio:

Investigar los mecanismos que subyacen a la desaceleración del crecimiento en los discos imaginales de Drosophila.
Elucidar el papel de la hipoxia y HIF-1α en la regulación del crecimiento y los cambios metabólicos durante el desarrollo.

Principales métodos:

Análisis de transcriptómica para estudiar los cambios metabólicos durante la desaceleración del crecimiento.
Utilización de reporteros ultrasensibles para la estabilidad y actividad de HIF-1α.
Investigación de la interacción entre la señalización TOR, la hipoxia y HIF-1α.

Principales resultados:

Los discos alares de Drosophila exhiben un cambio metabólico de la fosforilación oxidativa a la glucólisis durante la desaceleración del crecimiento.
Se desarrolla hipoxia progresiva en los discos imaginales durante el desarrollo normal, lo que se correlaciona con la ralentización del crecimiento.
Existe un bucle de retroalimentación negativa donde la señalización TOR induce hipoxia (a través de HIF-1α), lo que a su vez atenúa la señalización TOR.

Conclusiones:

HIF-1α desempeña un papel crucial en la mediación de un bucle de retroalimentación que equilibra el crecimiento impulsado por TOR con la disponibilidad de oxígeno.
Este mecanismo de retroalimentación previene que el crecimiento excesivo agote las reservas de oxígeno locales durante el desarrollo de Drosophila.
Sima/HIF-1α actúa como un factor protector contra el estrés celular causado por el desequilibrio de oxígeno durante el desarrollo.

Palabras clave:

desaceleración del crecimiento disco alar de Drosophila hipoxia HIF-1α señalización TOR metabolismo desarrollo

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