ODE-based models of signaling networks in autophagy

Abstract

Aberrant metabolism and nutrient processing are hallmarks of cancer. Autophagy is a catabolic process, clearing macromolecules and providing metabolite intermediates for anabolism. Autophagy safeguards healthy cells from tumorigenesis while mobilizing metabolites promoting tumor growth. Autophagy is controlled by the mTOR signaling network in conjunction with AMPK and ULK1. This kinase triad features highly intertwined feedback and feedforward mechanisms, complicating predictions on nutrient and drug response. ODE-based models offer a deterministic approach frequently used for the exploration of signaling dynamics. Recent ODE models of the mTOR-AMPK-ULK1 network revealed non-linear behaviors, bistable switches, and oscillatory patterns, shedding light on the robustness and adaptability of autophagy control. We highlight emerging perspectives on AMPK in mTORC1-ULK1 crosstalk and mechanisms for integration into future models.