Autophagy is an evolutionarily conserved “self‐degradation” process through which cytosolic compartments and organelles are delivered to the lysosome for degradation. Normally, autophagy is selectively activated to eliminate cell damage. Under stress conditions, autophagy will be non-selectively activated to provide energy and maintain the vitality of cells/organisms.
There are three forms of autophagy:
The use of ordinary differential equations (ODE) to clearly describe component interactions and cellular processes is the most commonly used approach to modeling systems biology. Based on the interaction between protein and second messenger, ODE modeling has been used to predict the dynamic changes of autophagy activity state under various autophagy activity states and the response to apoptotic stimuli, and make model predictions based on experimental measurement results.
However, ODE modeling assumes a "mixed bag" environment and cannot consider the non-uniform distribution of model components. Studies have shown that an agent-based model (ABM) can be used to represent the autophagy pathway, thereby providing a framework for studying the temporal and spatial aspects of autophagy regulation and dynamic behavior. The rules of ABM come from the literature and high-resolution images of autophagy markers under basic and activation conditions. Use genetic algorithms and predefined fitness functions to iteratively fit key model parameters. Through this method, the functional integration of autophagy and cellular nutritional status can be achieved, and accurate prediction of spatiotemporal behavior requires increasing the complexity of the model. Under basic and activated autophagy conditions, the generated model can reproduce short-term autophagic flux measurements and can measure the degree of cell-to-cell variation.
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