Dynamic Analysis Of Gene Regulatory Networks For Autophagy And Apoptosis

Autophagy and apoptosis are two important processes in the life process of cells,and their mechanisms are regulated precisely.Researches have shown that there is an intertrack crosstalk between autophagy and apoptotic network pathways,and a complex regulatory effects between the two of them.The Bcl2 proteins family play major role in the regulation of them.However,when cells are subjected to external stresses such as nutrient starvation,DNA and organelle damage.Under these conditions,cells are forced to make destiny decisions that require further study.This study explains the mechanism problems by establishing a correct mathematical model.Firstly,the regulatory proteins Beclin1 and Caspases of autophagy and apoptosis respectively were introduced into the original model proposed by Kapuy et al..The regulation of autophagy and apoptosis were analyzed by endoplasmic reticulum stress and mTOR-related parameters.The results indicate that though mTOR inhibits autophagy,the stress of endoplasmic reticulum stimulates it as well.Once cells turn on apoptosis,both mTOR and endoplasmic reticulum stress speed up the death of cells.Further,Bcl2 bounds AMBRA1 in endoplasmic reticulum and mitochondria,which are added to the original model proposed by Kapuy et al.with two different stresses respectively.The new model focuses on how the feedback regulation affects and determines the fate of autophagy and apoptosis.AMBRA1 competes with Bcl2 for binding to Beclin1,which regulates autophagy.When the mitochondria is subjected to low stress,only endoplasmic reticulum undergoes stress stress to activate autophagy only;while,the mitochondria bears a large pressure,it initiates apoptosis.Due to the protein of AMBRA1,when endoplasmic reticulum is subjected to low-pressure stress and mitochondria are subjected to high-voltage stress,the duration of activation before activation of apoptosis is significantly shortened.Finally,apoptosis is prone to occur with the increasing activation rate of Caspases,inactivation rate of Beclin1-A and the Michaelis constant of Caspases.Our model provides a good sight for further mathematical models and experimental simulations of autophagy and apoptosis.