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La inactivación transitorio de APC/C por mTOR aumenta la glucólisis durante la entrada en el ciclo celular

Debasish Paul¹, Derek L Bolhuis^2,3, Hualong Yan¹

¹Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

|July 31, 2025

Resumen

Las células de mamíferos que entran en el ciclo celular inactivan transitoriamente el complejo/ciclosoma promotor de la anafase (APC/C) para estimular la glucólisis. Este cambio metabólico apoya la rápida acumulación de biomasa para la división celular.

Área de la Ciencia:

Biología celular
El metabolismo
La bioquímica

Sus antecedentes:

La entrada en el ciclo celular requiere ATP y biosíntesis rápidas, favoreciendo la glucólisis.
El complejo promotor de anafase / ciclosoma (APC / C) regula la división celular pero paradójicamente inhibe la glucólisis.
La regulación coordinada del ciclo celular y el metabolismo es crucial para la división celular.

Objetivo del estudio:

Investigar cómo las células de mamíferos coordinan la entrada en el ciclo celular con las demandas metabólicas.
Esclarecer el mecanismo por el cual se favorece la glucólisis durante la progresión del ciclo celular a pesar de la actividad APC/C.

Principales métodos:

Se investigó el papel de la actividad de APC/C^CDH1 en la regulación de la glucólisis durante la entrada en el ciclo celular.
Se utilizaron modelos de células de mamíferos para estudiar los efectos de la estimulación mitogénica en los niveles de APC/C y de enzimas glicolíticas.
Se examinó el impacto de la fosforilación de CDH1 mediada por mTOR en la función APC/C y la acumulación de PFKFB3.

Principales resultados:

La inactivación transitoria de APC/C durante la entrada en el ciclo celular permite un cambio metabólico hacia la glucólisis.
La estimulación mitogénica desencadena la fosforilación de CDH1 mediada por mTOR, lo que lleva a una inactivación parcial de APC/C.
Esta inactivación estabiliza PFKFB3, una enzima glicolítica clave, mejorando la glucólisis para la producción de biomasa.

Conclusiones:

Las células emplean un bucle de alimentación incoherente que implica una inhibición transitorio de APC / C para generar un pulso glicolítico para la entrada en el ciclo celular.
Este mecanismo asegura suficiente ATP y productos intermedios biosintéticos para una rápida proliferación celular.
El estudio revela una nueva estrategia de coordinación entre la progresión del ciclo celular y el metabolismo celular.

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