DFG SPP2306

Lipid metabolism contributes significantly to the regulation of ferroptosis and its execution. Cell fate decisions to undergo ferroptosis or to adapt to pro-ferroptotic stimuli are based on the cellular metabolic state, intercellular cross-talks and the overall microenvironment. Microenvironmental cues acting along the metabolic axis, including nutrient sensing, oxygen availability and pH, directly modulate lipid metabolism and thus ferroptosis sensitivity. However, our understanding of such metabolic networks remains limited.

Experiments performed during the first funding period, provided new insights into the metabolic remodelling of cells undergoing ferroptosis. In addition to oxidized lipids acting as an “end markers” of ferroptosis, we identified several metabolic features directly involved in cell death propagation or adaptation to pro-ferroptotic stimulation. Furthermore, we proposed an active role for lipid messengers in the ferroptosis-associated secretome, directing intercellular communication during ferroptosis execution. Building up on the molecular details of lipid metabolism regulation in pro-ferroptotic conditions obtained during the first funding period, we aim to broaden our view of ferroptosis regulation and execution by considering diverse cell metabolic environments and cell signalling via lipid messengers.