Quantitative modeling of triacylglycerol homeostasis in yeast – metabolic requirement for lipolysis to promote membrane lipid synthesis and cellular growth

TLDR

Triacylglycerol metabolism in yeast was quantitatively studied using a systems biology approach. The authors built a dynamic flux‑balance model trained on time‑course measurements of growth, glucose uptake, and ethanol secretion, integrating mass balances of key metabolites to simulate triacylglycerol degradation and its coupling to fatty‑acid and membrane‑lipid synthesis. The model accurately reproduced metabolite dynamics and revealed that TAG lipolysis drives membrane‑lipid synthesis and cell‑size increase during early growth, whereas de novo fatty‑acid synthesis plays a minor role.

Abstract

Triacylglycerol metabolism in Saccharomyces cerevisiae was analyzed quantitatively using a systems biological approach. Cellular growth, glucose uptake and ethanol secretion were measured as a function of time and used as input for a dynamic flux-balance model. By combining dynamic mass balances for key metabolites with a detailed steady-state analysis, we trained a model network and simulated the time-dependent degradation of cellular triacylglycerol and its interaction with fatty acid and membrane lipid synthesis. This approach described precisely, both qualitatively and quantitatively, the time evolution of various key metabolites in a consistent and self-contained manner, and the predictions were found to be in excellent agreement with experimental data. We showed that, during pre-logarithmic growth, lipolysis of triacylglycerol allows for the rapid synthesis of membrane lipids, whereas de novo fatty acid synthesis plays only a minor role during this growth phase. Progress in triacylglycerol hydrolysis directly correlates with an increase in cell size, demonstrating the importance of lipolysis for supporting efficient growth initiation.