Project Details
Projekt
Role of cells and tissues microenvironment in lipid metabolism and signaling in ferroptosis
Applicant
Professorin Dr. Maria Fedorova
Subject Area
Cell Biology
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 549677318
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 remodeling 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 signaling via lipid messengers. Using innovative technologies developed in our laboratory, we will use our epilipidomics platform to address the diversity of oxidized bioactive lipids as well as click chemistry approach to monitor lipid fluxes in cells undergoing ferroptosis. Finally, we will validate the results obtained in cell culture experiments by multimodal imaging of animal tissues by combining immunofluorescence detection of cell types with mass spectrometry imaging of their lipotypes. Taken together, the proposed project will provide a time- and space-resolved map of ferroptosis regulation and execution at the molecular level, covering different aspects of lipid metabolism with unprecedented cell type specificity, reflecting a range of metabolic and histological microenvironments.
DFG Programme
Priority Programmes
