Qualitative behavior analysis of a model underlying the Warburg effect

Abstract

The Warburg effect describes the preference of highly proliferating cells (like cancer cells) for aerobic glycolysis and lactate production despite oxygen availability. In a recent paper, Jaiswal and Singh (2024) proposed that this behavior arises from a negative feedback loop linking cytoplasmic NADH levels and cell proliferation. Their model integrates glycolysis, oxidative phosphorylation, and pyruvate-to-lactate conversion to explain how the NADH/NAD+ ratio governs proliferation and quiescence. Here, we propose the qualitative behavior analysis, showing how quiescent and non quiescent equilibria arise according to model parameters. The corresponding bifurcation diagrams provide new biological insights on cellular behavior and pave the way to further investigation on the cellular machinery leading to the Warburg effect.